Appropriateness of early management of newly diagnosed Crohn's disease in a European population-based cohort.

PubMed

Juillerat, Pascal; Pittet, Valérie; Mottet, Christian; Felley, Christian; Gonvers, Jean-Jacques; Vader, John-Paul; Burnand, Bernard; Froehlich, Florian; Wolters, Frank L; Stockbrügger, Reinhold W; Michetti, Pierre

2010-12-01

The European Panel on the Appropriateness of Crohn's disease Therapy (EPACT) has developed appropriateness criteria. We have applied these criteria retrospectively to the population-based inception cohort of Crohn's disease (CD) patients of the European Collaborative Study Group on Inflammatory Bowel Disease (EC-IBD). A total of 426 diagnosed CD patients from 13 European centers were enrolled at the time of diagnosis (first flare, naive patients). We used the EPACT definitions to identify 247 patients with active luminal CD. We then assessed the appropriateness of the initial drug prescription according to the EPACT criteria. Among the cohort patients 163 suffered from mild-to-moderate CD and 84 from severe CD. Among the mild-to-moderate disease group, 96 patients (59%) received an appropriate treatment, whereas for 66 patients (40%) the treatment was uncertain and in one case (1%) inappropriate. Among the severe disease group, 86% were treated medically and 14% required surgery. 59 (70%) were appropriately treated, whereas for one patient (1%) the procedure was considered uncertain and for 24 patients (29%) inappropriate. Initial treatment was appropriate in the majority of cases for non-complicated luminal CD. Inappropriate or uncertain treatment was given in a significant minority of patients, with an increased potential risk of adverse events.

[Use of Cone Beam Computed Tomography in endodontics: rational case selection criteria].

PubMed

Rosen, E; Tsesis, I

2016-01-01

To present rational case selection criteria for the use of CBCT (Cone Beam Computed Tomography) in endodontics. This article reviews the literature concerning the benefits of CBCT in endodontics, alongside its radiation risks, and present case selection criteria for referral of endodontic patients to CBCT. Up to date, the expected ultimate benefit of CBCT to the endodontic patient is yet uncertain, and the current literature is mainly restricted to its technical efficacy. In addition, the potential radiation risks of CBCT scan are stochastic in nature and uncertain, and are worrying especially in pediatric patients. Both the efficacy of CBCT in supporting the endodontic practitioner decision making and in affecting treatment outcomes, and its long term potential radiation risks are yet uncertain. Therefore, a cautious rational decision making is essential when a CBCT scan is considered in endodontics. Risk-benefit considerations are presented.

Reasons for non-recruitment of eligible patients to a randomised controlled trial of secondary prevention after intracerebral haemorrhage: observational study.

PubMed

Maxwell, Amy E; MacLeod, Mary Joan; Joyson, Anu; Johnson, Sharon; Ramadan, Hawraman; Bellfield, Ruth; Byrne, Anthony; McGhee, Caroline; Rudd, Anthony; Price, Fiona; Vasileiadis, Evangelos; Holden, Melinda; Hewitt, Jonathan; Carpenter, Michael; Needle, Ann; Valentine, Stacey; Patel, Farzana; Harrington, Frances; Mudd, Paul; Emsley, Hedley; Gregary, Bindu; Kane, Ingrid; Muir, Keith; Tiwari, Divya; Owusu-Agyei, Peter; Temple, Natalie; Sekaran, Lakshmanan; Ragab, Suzanne; England, Timothy; Hedstrom, Amanda; Jones, Phil; Jones, Sarah; Doherty, Mandy; McCarron, Mark O; Cohen, David L; Tysoe, Sharon; Al-Shahi Salman, Rustam

2017-04-05

Recruitment to randomised prevention trials is challenging, not least for intracerebral haemorrhage (ICH) associated with antithrombotic drug use. We investigated reasons for not recruiting apparently eligible patients at hospital sites that keep screening logs in the ongoing REstart or STop Antithrombotics Randomised Trial (RESTART), which seeks to determine whether to start antiplatelet drugs after ICH. By the end of May 2015, 158 participants had been recruited at 108 active sites in RESTART. The trial coordinating centre invited all sites that kept screening logs to submit screening log data, followed by one reminder. We checked the integrity of data, focused on the completeness of data about potentially eligible patients and categorised the reasons they were not randomised. Of 108 active sites, 39 (36%) provided usable screening log data over a median of ten (interquartile range = 5-13) months of recruitment per site. During this time, sites screened 633 potentially eligible patients and randomised 53 (8%) of them. The main reasons why 580 patients were not randomised were: 43 (7%) patients started anticoagulation, 51 (9%) patients declined, 148 (26%) patients' stroke physicians were not uncertain about using antiplatelet drugs, 162 (28%) patients were too unwell and 176 (30%) patients were not randomised due to other reasons. RESTART recruited ~8% of eligible patients. If more physicians were uncertain about the therapeutic dilemma that RESTART is addressing, RESTART could have recruited up to four times as many participants. The trial coordinating centre continues to engage with physicians about their uncertainty. EU Clinical Trials, EudraCT 2012-003190-26 . Registered on 3 July 2012.

Broad Ligament Perivascular Epithelioid Cell Tumor (PEComa) of Uncertain Malignant Potential.

PubMed

Mathew, Mary; Nayal, Bhavna; Rao, Lakshmi; Nagel, Bhawna

2016-01-01

PEComas are uncommon mesenchymal tumors often involving the pelvic organs. They have an unpredictable behavior. Accurate diagnosis and long-term follow-up is therefore essential in these patients. We report this case of PEComa of uncertain malignant potential in an unusual location with excellent prognosis.

Shared Decision Making in Cancer Care

ERIC Educational Resources Information Center

Butow, Phyllis; Tattersall, Martin

2005-01-01

Cancer treatment outcomes have improved over the past 20 years, but treatment decision making in this context remains complex. There are often a number of reasonable treatment alternatives, including no treatment in some circumstances. Patients and doctors often have to weigh up uncertain benefits against uncertain costs. Shared decision making…

Diagnostic accuracy of the vegetative and minimally conscious state: Clinical consensus versus standardized neurobehavioral assessment

PubMed Central

Schnakers, Caroline; Vanhaudenhuyse, Audrey; Giacino, Joseph; Ventura, Manfredi; Boly, Melanie; Majerus, Steve; Moonen, Gustave; Laureys, Steven

2009-01-01

Background Previously published studies have reported that up to 43% of patients with disorders of consciousness are erroneously assigned a diagnosis of vegetative state (VS). However, no recent studies have investigated the accuracy of this grave clinical diagnosis. In this study, we compared consensus-based diagnoses of VS and MCS to those based on a well-established standardized neurobehavioral rating scale, the JFK Coma Recovery Scale-Revised (CRS-R). Methods We prospectively followed 103 patients (55 ± 19 years) with mixed etiologies and compared the clinical consensus diagnosis provided by the physician on the basis of the medical staff's daily observations to diagnoses derived from CRS-R assessments performed by research staff. All patients were assigned a diagnosis of 'VS', 'MCS' or 'uncertain diagnosis.' Results Of the 44 patients diagnosed with VS based on the clinical consensus of the medical team, 18 (41%) were found to be in MCS following standardized assessment with the CRS-R. In the 41 patients with a consensus diagnosis of MCS, 4 (10%) had emerged from MCS, according to the CRS-R. We also found that the majority of patients assigned an uncertain diagnosis by clinical consensus (89%) were in MCS based on CRS-R findings. Conclusion Despite the importance of diagnostic accuracy, the rate of misdiagnosis of VS has not substantially changed in the past 15 years. Standardized neurobehavioral assessment is a more sensitive means of establishing differential diagnosis in patients with disorders of consciousness when compared to diagnoses determined by clinical consensus. PMID:19622138

Patent Foramen Ovale in Patients with Cerebral Infarction: A Transesophageal Echocradigraphy Study

NASA Technical Reports Server (NTRS)

Petty, George W.; Khandheria, Bijoy K.; Chu, Chu-Pin; Sicks, JoRean D.; Whisnant, Jack P.

1997-01-01

Patent foramen ovale was detected in 37 patients (32%). Mean age was similar in those with (60 years) and those without (64 years) PFO. Patent foramen ovale was more frequent among men (39%) than women (20%, P=.03). Patients with PFO had a lower frequency of atrial fibrillation, diabetes me!litus, hypertension, and peripheral vascular disease compared with those without PFO. There was no difference in frequency of the following characteristics in patients with PFO compared with those without PFO: pulmonary embolus, chronic obstructive pulmonary disease, pulmonary hypertension, peripheral embolism, prior cerebral infarction, nosocomial cerebral infarction, Valsalva maneuver at the time of cerebral infarction, recent surgery, or hemorrhagic transformation of cerebral infarction. Patent foramen ovale was found in 22 (40%) of 55 patients with infarcts of uncertain cause and in 15 (25%) of 61 with infarcts of known cause (cardioembolic, 21%; large vessel atherostenosis, 25%; lacune, 40%) (P=.08). When the analysis was restricted to patients who underwent Valsalva maneuver, PFO with right to left or bidirectional shunt was found in 19 (50%) of 38 patients with infarcts of uncertain cause and in 6 (20%) of 30 with infarcts of known cause (P=.Ol). Conclusion: Although PFO was over-represented in patients with infarcts of uncertain cause in our and other studies, it has a high frequency among patients with cerebral infarction of all types. The relation between PFO and stroke requires further study.

Application of 2011 American College of Cardiology Foundation/American Society of Echocardiography appropriateness use criteria in hospitalized patients referred for transthoracic echocardiography in a community setting.

PubMed

Ballo, Piercarlo; Bandini, Fabrizio; Capecchi, Irene; Chiodi, Leandro; Ferro, Giuseppe; Fortini, Alberto; Giuliani, Gabriele; Landini, Giancarlo; Laureano, Raffaele; Milli, Massimo; Nenci, Gabriele; Pizzarelli, Francesco; Santoro, Giovanni Maria; Vannelli, Pasquale; Cappelletti, Carlo; Zuppiroli, Alfredo

2012-06-01

A recent American College of Cardiology Foundation and American Society of Echocardiography document updated previous appropriate use criteria (AUC) for echocardiography. The aim of this study was to explore the application of the new AUC, and the resulting appropriateness rate, in hospitalized patients referred for transthoracic echocardiography (TTE) in a community setting. A total of 931 consecutive inpatients referred for TTE were prospectively recruited in five community hospitals. Patients were categorized as having appropriate, uncertain, or inappropriate indications for TTE according to the AUC. An additional group of 259 inpatients, discharged without having been referred for TTE, was also considered. In the group referred for TTE, the large majority of indications (98.8%) were classifiable according to the AUC with good interobserver reproducibility. Indications were appropriate in 739 patients (80.3%), of uncertain appropriateness in 46 (5.0%), and inappropriate in 135 (14.7%). Compared with patients with appropriate or uncertain indications, those with inappropriate indications were younger and more often referred by noncardiologists. Most common causes of inappropriate indications were related to the lack of changes in clinical status or to the absence of cardiovascular symptoms and signs. Examinations with appropriate or uncertain indications had an impact on clinical decision making more often than those with inappropriate indications (86.7% vs 14.1%, P < .0001). In the group discharged without having been referred for TTE, TTE might have been appropriate in 16.2% of cases. Clinical application of the new AUC was highly feasible in a community setting. Although inpatient referral for TTE was appropriate in most patients, strategies aimed at implementing these criteria in clinical practice are desirable. Copyright © 2012 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.

Epidemiology of chronic kidney disease, with special emphasis on chronic kidney disease of uncertain etiology, in the north central region of Sri Lanka.

PubMed

Jayasekara, Kithsiri Bandara; Dissanayake, Dhammika Menike; Sivakanesan, Ramiah; Ranasinghe, Asanga; Karunarathna, Ranawaka Hewage; Priyantha Kumara, Gardiye Waligamage Gamini

2015-01-01

The aim of the study was to identify the epidemiology of chronic kidney disease of uncertain etiology in Sri Lanka. A cross-sectional study was carried out by analyzing health statistics, and three cohort studies were conducted (n = 15 630, 3996, and 2809) to analyze the demographic information, age-specific prevalence, etiology, and stage of presentation. We screened 7604 individuals for chronic kidney disease of uncertain etiology. The results showed that the male:female ratio was 2.4:1, the mean age of patients was 54.7 ± 8 years, 92% of the patients were farmers, and 93% consumed water from shallow dug wells. Familial occurrence was common (36%). The prevalence of chronic kidney disease in different age groups was 3% in those aged 30-40 years; 7% in those aged 41-50 years, 20% in those aged 51-60 years, and 29% in those older than 60 years. Chronic kidney disease of uncertain etiology was diagnosed in 70.2% of patients, while 15.7% and 9.6% were due to hypertension and diabetic mellitus, respectively. The majority of patients were stage 4 (40%) at first presentation, while 31.8% were stage 3 and 24.5% were stage 5. Stage 1 and 2 presentation accounted for only 3.4%. Low prevalence of CKDU was noticed (1.5%) among those who consumed water from natural springs. Prevalence was highest among males, rice farming communities, and those presenting at later disease stages.

Parkinson's Disease Diagnostic Observations (PADDO): study rationale and design of a prospective cohort study for early differentiation of parkinsonism.

PubMed

van Rumund, Anouke; Aerts, Marjolein B; Esselink, Rianne A J; Meijer, Frederick J A; Verbeek, Marcel M; Bloem, Bastiaan R

2018-05-16

Differentiation of Parkinson's disease (PD) from the various types of atypical parkinsonism (AP) such as multiple system atrophy (MSA), progressive supranuclear palsy (PSP), dementia with Lewy bodies (DLB), corticobasal syndrome (CBS) and vascular parkinsonism (VP), can be challenging, especially early in the disease course when symptoms overlap. A major unmet need in the diagnostic workup of these disorders is a diagnostic tool that differentiates the various disorders, preferably in the earliest disease stages when the clinical presentation is similar. Many diagnostic tests have been evaluated, but their added value was studied mostly in retrospective case-control studies that included patients with a straightforward clinical diagnosis. Here, we describe the design of a prospective cohort study in patients with parkinsonism in an early disease stage who have an uncertain clinical diagnosis. Our aim is to evaluate the diagnostic accuracy of (1) detailed clinical examination by a movement disorder specialist, (2) magnetic resonance imaging (MRI) techniques and (3) cerebrospinal fluid (CSF) biomarkers. Patients with parkinsonism with an uncertain clinical diagnosis and a disease course less than three years will be recruited. Patients will undergo extensive neurological examination, brain MRI including conventional and advanced sequences, and a lumbar puncture. The diagnosis (including level of certainty) will be defined by a movement disorders expert, neuroradiologist and neurochemist based on clinical data, MRI results and CSF results, respectively. The clinical diagnosis after three years' follow-up will serve as the "gold standard" reference diagnosis, based on consensus criteria and as established by two movement disorder specialists (blinded to the test results). Diagnostic accuracy of individual instruments and added value of brain MRI and CSF analysis after evaluation by a movement disorder expert will be calculated, expressed as the change in percentage of individuals that are correctly diagnosed with PD or AP. This study will yield new insights into the diagnostic value of clinical evaluation by a movement disorder specialist, brain MRI and CSF analysis in discriminating PD from AP in early disease stages. The outcome has the potential to help clinicians in choosing the optimal diagnostic strategy for patients with an uncertain clinical diagnosis. NCT01249768, registered November 26 2010.

Adaptive output feedback control of uncertain nonlinear systems using single-hidden-layer neural networks.

PubMed

Hovakimyan, N; Nardi, F; Calise, A; Kim, Nakwan

2002-01-01

We consider adaptive output feedback control of uncertain nonlinear systems, in which both the dynamics and the dimension of the regulated system may be unknown. However, the relative degree of the regulated output is assumed to be known. Given a smooth reference trajectory, the problem is to design a controller that forces the system measurement to track it with bounded errors. The classical approach requires a state observer. Finding a good observer for an uncertain nonlinear system is not an obvious task. We argue that it is sufficient to build an observer for the output tracking error. Ultimate boundedness of the error signals is shown through Lyapunov's direct method. The theoretical results are illustrated in the design of a controller for a fourth-order nonlinear system of relative degree two and a high-bandwidth attitude command system for a model R-50 helicopter.

Community resources for frail older patients.

PubMed Central

Borgenicht, K; Carty, E; Feigenbaum, L Z

1997-01-01

The goal of community-based services for frail older patients is to help them achieve the greatest degree of functional ability and independence. The services available include case management, geriatric assessment, adult day health care, home health services, and the Program for All-inclusive Care for the Elderly (PACE). Definitive criteria for referral have not been established, but without some targeting, the efficacy of these services remains uncertain. Targeting criteria identified include dependency in 2 or more activities of daily living, no family support, dementia, many long-term illnesses, and many hospital stays. Although efficacy and cost-effectiveness remain uncertain, patients, families, and physicians generally report these services to be helpful. PMID:9348762

Inferring extinction risks from sighting records.

PubMed

Thompson, C J; Lee, T E; Stone, L; McCarthy, M A; Burgman, M A

2013-12-07

Estimating the probability that a species is extinct based on historical sighting records is important when deciding how much effort and money to invest in conservation policies. The framework we offer is more general than others in the literature to date. Our formulation allows for definite and uncertain observations, and thus better accommodates the realities of sighting record quality. Typically, the probability of observing a species given it is extant/extinct is challenging to define, especially when the possibility of a false observation is included. As such, we assume that observation probabilities derive from a representative probability density function. We incorporate this randomness in two different ways ("quenched" versus "annealed") using a framework that is equivalent to a Bayes formulation. The two methods can lead to significantly different estimates for extinction. In the case of definite sightings only, we provide an explicit deterministic calculation (in which observation probabilities are point estimates). Furthermore, our formulation replicates previous work in certain limiting cases. In the case of uncertain sightings, we allow for the possibility of several independent observational types (specimen, photographs, etc.). The method is applied to the Caribbean monk seal, Monachus tropicalis (which has only definite sightings), and synthetic data, with uncertain sightings. © 2013 Elsevier Ltd. All rights reserved.

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

Grantham, K; Santanam, L; Goddu, S

Purpose: We retrospectively evaluate the dosimetric impact of a 3.5% range uncertainty on CTV coverage and normal organ toxicity for a cohort of brain patients. Methods: Twenty treatment plans involving 20 brain cancer patients treated with Mevions S250 were reviewed. Forty uncertain plans were made by changing the ranges in original plans by ±3.5% while keeping all devices unchanged. Fidelity to the original plans was evaluated with gamma index. Changes in generalized equivalent uniform dose (gEUD) were reported for the following structures: CTV coverage, brainstem, optic chiasm, and optic nerves. Comparisons were made by plotting the relevant endpoints from themore » uncertain plans as a function of the same endpoints from the original clinical plan. Results: Gamma-index analysis resulted in a 50% pass rate of the uncertain plans using a 90% passing rate and 3%/3mm criterion. A 9.5% decrease in the slope of gEUD plot for the CTV was observed for the 3.5% downward range shift. However, the change in slope did not result in a gEUD change greater than 1.1% for the CTV. The slopes of the gEUD plots for normal structures increased by 3.1% 3.9% 2.4% and 0.2% for the chiasm, brainstem, left optic nerve and right optic nerve respectively. The maximum deviation from the gEUD of the clinical plan for normal structures was: 64% in the chiasm, 31% for the brainstem, and 19% for both optic nerves. Conclusion: A retrospective review shows moderate radiobiological impact of range uncertainty in passively scattered proton therapy with sporadic catastrophe. The linear regression analysis on the statistical data indicates a systematic deviation of gEUD from treatment planning in the light of range uncertainty.« less

Epidemiology of Chronic Kidney Disease, With Special Emphasis on Chronic Kidney Disease of Uncertain Etiology, in the North Central Region of Sri Lanka

PubMed Central

Jayasekara, Kithsiri Bandara; Dissanayake, Dhammika Menike; Sivakanesan, Ramiah; Ranasinghe, Asanga; Karunarathna, Ranawaka Hewage; Priyantha Kumara, Gardiye Waligamage Gamini

2015-01-01

Background The aim of the study was to identify the epidemiology of chronic kidney disease of uncertain etiology in Sri Lanka. Methods A cross-sectional study was carried out by analyzing health statistics, and three cohort studies were conducted (n = 15 630, 3996, and 2809) to analyze the demographic information, age-specific prevalence, etiology, and stage of presentation. We screened 7604 individuals for chronic kidney disease of uncertain etiology. Results The results showed that the male:female ratio was 2.4:1, the mean age of patients was 54.7 ± 8 years, 92% of the patients were farmers, and 93% consumed water from shallow dug wells. Familial occurrence was common (36%). The prevalence of chronic kidney disease in different age groups was 3% in those aged 30–40 years; 7% in those aged 41–50 years, 20% in those aged 51–60 years, and 29% in those older than 60 years. Chronic kidney disease of uncertain etiology was diagnosed in 70.2% of patients, while 15.7% and 9.6% were due to hypertension and diabetic mellitus, respectively. The majority of patients were stage 4 (40%) at first presentation, while 31.8% were stage 3 and 24.5% were stage 5. Stage 1 and 2 presentation accounted for only 3.4%. Conclusions Low prevalence of CKDU was noticed (1.5%) among those who consumed water from natural springs. Prevalence was highest among males, rice farming communities, and those presenting at later disease stages. PMID:25787679

Feature-Based versus Category-Based Induction with Uncertain Categories

ERIC Educational Resources Information Center

Griffiths, Oren; Hayes, Brett K.; Newell, Ben R.

2012-01-01

Previous research has suggested that when feature inferences have to be made about an instance whose category membership is uncertain, feature-based inductive reasoning is used to the exclusion of category-based induction. These results contrast with the observation that people can and do use category-based induction when category membership is…

Adaptive Fault-Tolerant Control of Uncertain Nonlinear Large-Scale Systems With Unknown Dead Zone.

PubMed

Chen, Mou; Tao, Gang

2016-08-01

In this paper, an adaptive neural fault-tolerant control scheme is proposed and analyzed for a class of uncertain nonlinear large-scale systems with unknown dead zone and external disturbances. To tackle the unknown nonlinear interaction functions in the large-scale system, the radial basis function neural network (RBFNN) is employed to approximate them. To further handle the unknown approximation errors and the effects of the unknown dead zone and external disturbances, integrated as the compounded disturbances, the corresponding disturbance observers are developed for their estimations. Based on the outputs of the RBFNN and the disturbance observer, the adaptive neural fault-tolerant control scheme is designed for uncertain nonlinear large-scale systems by using a decentralized backstepping technique. The closed-loop stability of the adaptive control system is rigorously proved via Lyapunov analysis and the satisfactory tracking performance is achieved under the integrated effects of unknown dead zone, actuator fault, and unknown external disturbances. Simulation results of a mass-spring-damper system are given to illustrate the effectiveness of the proposed adaptive neural fault-tolerant control scheme for uncertain nonlinear large-scale systems.

Effect of estrogen replacement therapy on bone and cardiovascular outcomes in women with turner syndrome: a systematic review and meta-analysis.

PubMed

Cintron, Dahima; Rodriguez-Gutierrez, Rene; Serrano, Valentina; Latortue-Albino, Paula; Erwin, Patricia J; Murad, Mohammad Hassan

2017-02-01

Patients with Turner syndrome have adverse bone and cardiovascular outcomes from chronic estrogen deficiency. Hence, long-term estrogen replacement therapy is the cornerstone treatment. The estimates of its effect and optimal use, however, remain uncertain. We aimed to summarize the benefits and harms of estrogen replacement therapy on bone, cardiovascular, vasomotor and quality of life outcomes in patients with Turner syndrome. A comprehensive search of four databases was performed from inception through January 2016. Randomized clinical trials and observational cohort studies studying the effect of estrogen replacement therapy in patients with Turner syndrome under the age of 40 were included. Independently and in duplicate reviewers selected studies, extracted data and assessed risk of bias. Subgroup analyses were based on route of administration and type of estrogen formulation. Twenty-five studies at moderate to high risk of bias (12 randomized trials, 13 cohort studies) with 771 patients were included. Using random-effects models, estrogen replacement therapy showed an increase in bone mineral density [weighted mean change from baseline 0.09 g/cm2 (0.04-0.14)] that differed by type of estrogen but not route of administration. Oral estrogen replacement therapy showed a higher increase in high density lipoprotein cholesterol levels when compared to transdermal [weighted mean difference 9.33 mg/dl (4.82-13.85)] with no significant effect on other lipid fractions. The current evidence suggests possible benefit of estrogen replacement therapy on bone mineral density and high density lipoprotein cholesterol. Whether this improvement translates into changes in patient important outcomes (cardiovascular events or fractures) remains uncertain. Larger randomized clinical trials with direct comparisons on patient important outcomes are necessary.

Assimilating uncertain, dynamic and intermittent streamflow observations in hydrological models

NASA Astrophysics Data System (ADS)

Mazzoleni, Maurizio; Alfonso, Leonardo; Chacon-Hurtado, Juan; Solomatine, Dimitri

2015-09-01

Catastrophic floods cause significant socio-economical losses. Non-structural measures, such as real-time flood forecasting, can potentially reduce flood risk. To this end, data assimilation methods have been used to improve flood forecasts by integrating static ground observations, and in some cases also remote sensing observations, within water models. Current hydrologic and hydraulic research works consider assimilation of observations coming from traditional, static sensors. At the same time, low-cost, mobile sensors and mobile communication devices are becoming also increasingly available. The main goal and innovation of this study is to demonstrate the usefulness of assimilating uncertain streamflow observations that are dynamic in space and intermittent in time in the context of two different semi-distributed hydrological model structures. The developed method is applied to the Brue basin, where the dynamic observations are imitated by the synthetic observations of discharge. The results of this study show how model structures and sensors locations affect in different ways the assimilation of streamflow observations. In addition, it proves how assimilation of such uncertain observations from dynamic sensors can provide model improvements similar to those of streamflow observations coming from a non-optimal network of static physical sensors. This can be a potential application of recent efforts to build citizen observatories of water, which can make the citizens an active part in information capturing, evaluation and communication, helping simultaneously to improvement of model-based flood forecasting.

Non-fragile observer-based output feedback control for polytopic uncertain system under distributed model predictive control approach

NASA Astrophysics Data System (ADS)

Zhu, Kaiqun; Song, Yan; Zhang, Sunjie; Zhong, Zhaozhun

2017-07-01

In this paper, a non-fragile observer-based output feedback control problem for the polytopic uncertain system under distributed model predictive control (MPC) approach is discussed. By decomposing the global system into some subsystems, the computation complexity is reduced, so it follows that the online designing time can be saved.Moreover, an observer-based output feedback control algorithm is proposed in the framework of distributed MPC to deal with the difficulties in obtaining the states measurements. In this way, the presented observer-based output-feedback MPC strategy is more flexible and applicable in practice than the traditional state-feedback one. What is more, the non-fragility of the controller has been taken into consideration in favour of increasing the robustness of the polytopic uncertain system. After that, a sufficient stability criterion is presented by using Lyapunov-like functional approach, meanwhile, the corresponding control law and the upper bound of the quadratic cost function are derived by solving an optimisation subject to convex constraints. Finally, some simulation examples are employed to show the effectiveness of the method.

Robust decentralized hybrid adaptive output feedback fuzzy control for a class of large-scale MIMO nonlinear systems and its application to AHS.

PubMed

Huang, Yi-Shao; Liu, Wel-Ping; Wu, Min; Wang, Zheng-Wu

2014-09-01

This paper presents a novel observer-based decentralized hybrid adaptive fuzzy control scheme for a class of large-scale continuous-time multiple-input multiple-output (MIMO) uncertain nonlinear systems whose state variables are unmeasurable. The scheme integrates fuzzy logic systems, state observers, and strictly positive real conditions to deal with three issues in the control of a large-scale MIMO uncertain nonlinear system: algorithm design, controller singularity, and transient response. Then, the design of the hybrid adaptive fuzzy controller is extended to address a general large-scale uncertain nonlinear system. It is shown that the resultant closed-loop large-scale system keeps asymptotically stable and the tracking error converges to zero. The better characteristics of our scheme are demonstrated by simulations. Copyright © 2014. Published by Elsevier Ltd.

Immunomodulatory drugs and the risk of serious infection in multiple myeloma: systematic review and meta-analysis of randomized and observational studies.

PubMed

Chen, Min; Zhao, Yongfeng; Xu, Chuanxin; Wang, Xian; Zhang, Xianping; Mao, Benyu

2018-06-01

The effect of immunomodulatory drugs (IMiDs) on serious infection remains uncertain. We therefore conducted a systematic review and meta-analysis to assess the possible impact of IMiDs on serious infection in patients with multiple myeloma (MM). We searched randomized controlled trials (RCTs) and observational studies from databases that addressed the effect of IMiDs on serious infection in patients with MM. We pooled data from RCTs and observational studies separately and used the GRADE approach to rate the quality of evidence. Rates in patients with individual IMiDs at different treatment status ranged from 7.00 to 23.00%. The use of thalidomide- or lenalidomide-based regimen induction therapy for autologous stem cell transplantation (ASCT)-ineligible patients suggests increase in serious infection (RR = 1.59, 95% CI 1.31-1.93, p < 0.01). Compared to conventional therapy, IMiDs' induction in ASCT-eligible patients significantly decreases the risk of serious infection (RR = 0.82, 95% CI 0.72-0.94, p < 0.01). Lenalidomide-based therapy was associated with a significant increase in risk of serious infection in patients treated compared with conventional therapy (RR = 2.45, 95% CI 1.57-3.83, p < 0.01). The current evidence suggests that patients with MM treated with IMiDs are at a high risk of serious infection.

Design of sliding-mode observer for a class of uncertain neutral stochastic systems

NASA Astrophysics Data System (ADS)

Liu, Zhen; Zhao, Lin; Zhu, Quanmin; Gao, Cunchen

2017-05-01

The problem of robust ? control for a class of uncertain neutral stochastic systems (NSS) is investigated by utilising the sliding-mode observer (SMO) technique. This paper presents a novel observer and integral-type sliding-surface design, based on which a new sufficient condition guaranteeing the resultant sliding-mode dynamics (SMDs) to be mean-square exponentially stable with a prescribed level of ? performance is derived. Then, an adaptive reaching motion controller is synthesised to lead the system to the predesigned sliding surface in finite-time almost surely. Finally, two illustrative examples are exhibited to verify the validity and superiority of the developed scheme.

Germline BRCA1/BRCA2 mutations among high risk breast cancer patients in Jordan.

PubMed

Abdel-Razeq, Hikmat; Al-Omari, Amal; Zahran, Farah; Arun, Banu

2018-02-06

Breast cancer is the most common malignancy and the leading cause of cancer-related deaths among Jordanian women. With a median age of 50 years at diagnosis, a higher prevalence of hereditary breast cancer may be expected. The objective of this pilot study is to evaluate, for the first time, the contribution of germline mutations in BRCA1/2 to breast cancer among Jordanian patients. Jordanian breast cancer women with a selected high risk profile were invited to participate. Peripheral blood samples were obtained for DNA extraction. A detailed 3-generation family history was also collected. BRCA sequencing was performed at a reference laboratory. Mutations were classified as deleterious, suspected deleterious, variant of uncertain significance or favor polymorphisms. Patients' medical records were reviewed for extraction of clinical and tumor pathology data. One hundred patients were enrolled to the study. Median age was 40 (22-75) years. In total, 20 patients had deleterious and 7 suspected deleterious mutations in BRCA1 or BRCA2 genes. Seven variants of uncertain significance were also detected. After excluding patients tested subsequent to the index case in their families, highest mutation rates were observed among triple negatives (9/16, 56.3%) especially among those with positive family history of breast and/or ovarian cancer (9/13, 69.2%), patients with bilateral or second primary breast cancer (10/15, 66.7%) and those with family history of male breast cancer (2/5, 40.0%). BRCA1/2 mutations are not uncommon among selected Jordanian females with breast cancer. The contribution of these findings to much younger age at diagnosis is debatable. Although small, our selected patient cohort shows an important incidence of deleterious and suspected deleterious BRCA1/2 mutations suggesting that genetic testing should be offered to patients with certain high risk features.

The clinical significance of occult gynecologic primary tumours in metastatic cancer.

PubMed

Hannouf, M B; Winquist, E; Mahmud, S M; Brackstone, M; Sarma, S; Rodrigues, G; Rogan, P K; Hoch, J S; Zaric, G S

2017-10-01

We estimated the frequency of occult gynecologic primary tumours (gpts) in patients with metastatic cancer from an uncertain primary and evaluated the effect on disease management and overall survival (os). We used Manitoba administrative health databases to identify all patients initially diagnosed with metastatic cancer during 2002-2011. We defined patients as having an "occult" primary tumour if the primary was classified at least 6 months after the initial diagnosis. Otherwise, we considered patients to have "obvious" primaries. We then compared clinicopathologic and treatment characteristics and 2-year os for women with occult and with obvious gpts. We used Cox regression adjustment and propensity score methods to assess the effect on os of having an occult gpt. Among the 5953 patients diagnosed with metastatic cancer, occult primary tumours were more common in women ( n = 285 of 2552, 11.2%) than in men ( n = 244 of 3401, 7.2%). In women, gpts were the most frequent occult primary tumours ( n = 55 of 285, 19.3%). Compared with their counterparts having obvious gpts, women with occult gpts ( n = 55) presented with similar histologic and metastatic patterns but received fewer gynecologic diagnostic examinations during diagnostic work-up. Women with occult gpts were less likely to undergo surgery, waited longer for radiotherapy, and received a lesser variety of chemotherapeutic agents. Having an occult compared with an obvious gpt was associated with decreased os (hazard ratio: 1.62; 95% confidence interval: 1.2 to 2.35). Similar results were observed in adjusted analyses. In women with metastatic cancer from an uncertain primary, gpts constitute the largest clinical entity. Accurate diagnosis of occult gpts early in the course of metastatic cancer might lead to more effective treatment decisions and improved survival outcomes.

The clinical significance of occult gynecologic primary tumours in metastatic cancer

PubMed Central

Hannouf, M.B.; Winquist, E.; Mahmud, S.M.; Brackstone, M.; Sarma, S.; Rodrigues, G.; Rogan, P.K.; Hoch, J.S.; Zaric, G.S.

2017-01-01

Objective We estimated the frequency of occult gynecologic primary tumours (gpts) in patients with metastatic cancer from an uncertain primary and evaluated the effect on disease management and overall survival (os). Methods We used Manitoba administrative health databases to identify all patients initially diagnosed with metastatic cancer during 2002–2011. We defined patients as having an “occult” primary tumour if the primary was classified at least 6 months after the initial diagnosis. Otherwise, we considered patients to have “obvious” primaries. We then compared clinicopathologic and treatment characteristics and 2-year os for women with occult and with obvious gpts. We used Cox regression adjustment and propensity score methods to assess the effect on os of having an occult gpt. Results Among the 5953 patients diagnosed with metastatic cancer, occult primary tumours were more common in women (n = 285 of 2552, 11.2%) than in men (n = 244 of 3401, 7.2%). In women, gpts were the most frequent occult primary tumours (n = 55 of 285, 19.3%). Compared with their counterparts having obvious gpts, women with occult gpts (n = 55) presented with similar histologic and metastatic patterns but received fewer gynecologic diagnostic examinations during diagnostic work-up. Women with occult gpts were less likely to undergo surgery, waited longer for radiotherapy, and received a lesser variety of chemotherapeutic agents. Having an occult compared with an obvious gpt was associated with decreased os (hazard ratio: 1.62; 95% confidence interval: 1.2 to 2.35). Similar results were observed in adjusted analyses. Conclusions In women with metastatic cancer from an uncertain primary, gpts constitute the largest clinical entity. Accurate diagnosis of occult gpts early in the course of metastatic cancer might lead to more effective treatment decisions and improved survival outcomes. PMID:29089807

Burning mouth syndrome: an enigmatic disorder.

PubMed

Javali, M A

2013-01-01

Burning mouth syndrome (BMS) is a chronic oral pain or burning sensation affecting the oral mucosa, often unaccompanied by mucosal lesions or other evident clinical signs. It is observed principally in middle-aged patients and postmenopausal women and may be accompanied by xerostomia and altered taste. Burning mouth syndrome is characterized by an intense burning or stinging sensation, preferably on the tongue or in other areas of mouth. This disorder is one of the most common, encountered in the clinical practice. This condition is probably of multifactorial origin; however the exact underlying etiology remains uncertain. This article discusses several aspects of BMS, updates current knowledge about the etiopathogenesis and describes the clinical features as well as the diagnosis and management of BMS patients.

Intratemporal facial nerve ultrastructure in patients with idiopathic facial paralysis: viral infection evidence study.

PubMed

Florez, Rosangela Aló Maluza; Lang, Raquel; Veridiano, Adriano Mora; Zanini, Renato de Oliveira; Calió, Pedro Luiz; Simões, Ricardo Dos Santos; Testa, José Ricardo Gurgel

2010-01-01

The etiology of idiopathic peripheral facial palsy (IPFP) is still uncertain; however, some authors suggest the possibility of a viral infection. to analyze the ultrastructure of the facial nerve seeking viral evidences that might provide etiological data. We studied 20 patients with peripheral facial palsy (PFP), with moderate to severe FP, of both genders, between 18-60 years of age, from the Clinic of Facial Nerve Disorders. The patients were broken down into two groups - Study: eleven patients with IPFP and Control: nine patients with trauma or tumor-related PFP. The fragments were obtained from the facial nerve sheath or from fragments of its stumps - which would be discarded or sent to pathology exam during the facial nerve repair surgery. The removed tissue was fixed in 2% glutaraldehyde, and studied under Electronic Transmission Microscopy. In the study group we observed an intense repair cellular activity by increased collagen fibers, fibroblasts containing developed organelles, free of viral particles. In the control group this repair activity was not evident, but no viral particles were observed. There were no viral particles, and there were evidences of intense activity of repair or viral infection.

High resolution manometry findings in patients with esophageal epiphrenic diverticula.

PubMed

Vicentine, Fernando P P; Herbella, Fernando A M; Silva, Luciana C; Patti, Marco G

2011-12-01

The pathophysiology of esophageal epiphrenic diverticula is still uncertain even though a concomitant motility disorder is found in the majority of patients in different series. High resolution manometry may allow detection of motor abnormalities in a higher number of patients with esophageal epiphrenic diverticula compared with conventional manometry. This study aims to evaluate the high resolution manometry findings in patients with esophageal epiphrenic diverticula. Nine individuals (mean age 63 ± 10 years, 4 females) with esophageal epiphrenic diverticula underwent high resolution manometry. A single diverticulum was observed in eight patients and multiple diverticula in one. Visual analysis of conventional tracings and color pressure plots for identification of segmental abnormalities was performed by two researchers experienced in high resolution manometry. Upper esophageal sphincter was normal in all patients. Esophageal body was abnormal in eight patients; lower esophageal sphincter was abnormal in seven patients. Named esophageal motility disorders were found in seven patients: achalasia in six, diffuse esophageal spasm in one. In one patient, a segmental hypercontractile zone was noticed with pressure of 196 mm Hg. High resolution manometry demonstrated motor abnormalities in all patients with esophageal epiphrenic diverticula.

Intracranial hemorrhage in anticoagulated patients with mild traumatic brain injury: significant differences between direct oral anticoagulants and vitamin K antagonists.

PubMed

Cipriano, Alessandro; Pecori, Alessio; Bionda, Alessandra Eugenia; Bardini, Michele; Frassi, Francesca; Leoli, Francesco; Lami, Valentina; Ghiadoni, Lorenzo; Santini, Massimo

2018-03-08

Prognosis after mild traumatic brain injury (MTBI) on oral anticoagulant therapy (OAT) is uncertain. We evaluated the rate of immediate and delayed traumatic intracranial hemorrhage (ICH) comparing vitamin K antagonists (VKAs) to direct oral anticoagulants (DOACs) and the safety of a clinical management protocol. In this single-center prospective observational study, we enrolled 220 patients on OAT with MTBI. After a first negative CT scan, asymptomatic patients underwent a close neurological observation; if neurologically stable, they were discharged without a second CT scan and followed up for 1 month. Out of the 220 patients, 206 met the inclusion criteria. 23 of them (11.2%) had a positive first CT scan for ICH. Only 1 (0.5%, 95% CI 0.0-1.4%) died because of ICH; no one required neurosurgical intervention. The observed prevalence rate of immediate ICH resulted statistically higher in VKAs-treated patients compared to those treated with DOACs (15.7 vs. 4.7%, RR 3.34, 95% CI 1.18-9.46, P < 0.05). In the 1-month follow-up, 5 out of the 183 patients with a negative CT scan were lost. Out of the remaining 178 patients, only 3 showed a delayed ICH (1.7%, 95% CI 0.0-3.6%), 1 of them died (0.6%, 95% CI 0.5-1.7%) and the others did not require neurosurgical intervention. DOACs resulted safer than VKAs also in the setting of MTBI. In our observation, the rate of delayed hemorrhage was relatively low. Patients presenting with a negative first CT scan and without neurological deterioration could be safely discharged after a short period of in-ward observation with a low rate of complications and without a second CT scan.

Neuropsychiatric lupus and auto-antibodies against ionotropic glutamate receptor (NMDAR)

PubMed Central

Cohen-Solal, J.F.G.; Diamond, B.

2010-01-01

Almost half of lupus patients will experience neuropsychiatric symptoms during the course of their disease. The etiology of the neuronal damages are still uncertain and probably multiple. Auto-antibodies reactive with brain have been postulated to play a role. The observation of pathogenic auto-antibodies binding the NR2A and NR2B subunits of the ionotropic glutamate receptor (NMDAR) illustrates this hypothesis. First studies showed that 40% of lupus patients possess serum titers of anti-NR2A/B antibody, but the presence of these auto-antibodies is not always associated with the occurrence of neuronal damages or neuropsychiatric symptoms. Nevertheless, their presence is observed in the cerebro-spinal fluid (CSF) of one half of the patients suffering from neurolupus. The presence in the serum of these auto-antibodies anti-NR2A/B of the NMDAR is preliminary to their presence in the CSF where their deleterious effect is observable. Their entry into the brain is dependent on a breach of the blood brain barrier (BBB). In conclusion, the serum titer of auto-antibodies against NR2A/B subunits is an indication of the potential for neuro-psychiatric manifestations during the course of the disease. PMID:20605660

Secure estimation, control and optimization of uncertain cyber-physical systems with applications to power networks

NASA Astrophysics Data System (ADS)

Taha, Ahmad Fayez

Transportation networks, wearable devices, energy systems, and the book you are reading now are all ubiquitous cyber-physical systems (CPS). These inherently uncertain systems combine physical phenomena with communication, data processing, control and optimization. Many CPSs are controlled and monitored by real-time control systems that use communication networks to transmit and receive data from systems modeled by physical processes. Existing studies have addressed a breadth of challenges related to the design of CPSs. However, there is a lack of studies on uncertain CPSs subject to dynamic unknown inputs and cyber-attacks---an artifact of the insertion of communication networks and the growing complexity of CPSs. The objective of this dissertation is to create secure, computational foundations for uncertain CPSs by establishing a framework to control, estimate and optimize the operation of these systems. With major emphasis on power networks, the dissertation deals with the design of secure computational methods for uncertain CPSs, focusing on three crucial issues---(1) cyber-security and risk-mitigation, (2) network-induced time-delays and perturbations and (3) the encompassed extreme time-scales. The dissertation consists of four parts. In the first part, we investigate dynamic state estimation (DSE) methods and rigorously examine the strengths and weaknesses of the proposed routines under dynamic attack-vectors and unknown inputs. In the second part, and utilizing high-frequency measurements in smart grids and the developed DSE methods in the first part, we present a risk mitigation strategy that minimizes the encountered threat levels, while ensuring the continual observability of the system through available, safe measurements. The developed methods in the first two parts rely on the assumption that the uncertain CPS is not experiencing time-delays, an assumption that might fail under certain conditions. To overcome this challenge, networked unknown input observers---observers/estimators for uncertain CPSs---are designed such that the effect of time-delays and cyber-induced perturbations are minimized, enabling secure DSE and risk mitigation in the first two parts. The final part deals with the extreme time-scales encompassed in CPSs, generally, and smart grids, specifically. Operational decisions for long time-scales can adversely affect the security of CPSs for faster time-scales. We present a model that jointly describes steady-state operation and transient stability by combining convex optimal power flow with semidefinite programming formulations of an optimal control problem. This approach can be jointly utilized with the aforementioned parts of the dissertation work, considering time-delays and DSE. The research contributions of this dissertation furnish CPS stakeholders with insights on the design and operation of uncertain CPSs, whilst guaranteeing the system's real-time safety. Finally, although many of the results of this dissertation are tailored to power systems, the results are general enough to be applied for a variety of uncertain CPSs.

Uncertain behaviours of integrated circuits improve computational performance.

PubMed

Yoshimura, Chihiro; Yamaoka, Masanao; Hayashi, Masato; Okuyama, Takuya; Aoki, Hidetaka; Kawarabayashi, Ken-ichi; Mizuno, Hiroyuki

2015-11-20

Improvements to the performance of conventional computers have mainly been achieved through semiconductor scaling; however, scaling is reaching its limitations. Natural phenomena, such as quantum superposition and stochastic resonance, have been introduced into new computing paradigms to improve performance beyond these limitations. Here, we explain that the uncertain behaviours of devices due to semiconductor scaling can improve the performance of computers. We prototyped an integrated circuit by performing a ground-state search of the Ising model. The bit errors of memory cell devices holding the current state of search occur probabilistically by inserting fluctuations into dynamic device characteristics, which will be actualised in the future to the chip. As a result, we observed more improvements in solution accuracy than that without fluctuations. Although the uncertain behaviours of devices had been intended to be eliminated in conventional devices, we demonstrate that uncertain behaviours has become the key to improving computational performance.

Physicians’ Perspectives on the Uncertainties and Implications of Chromosomal Microarray Testing of Children and Families

PubMed Central

Reiff, Marian; Ross, Kathryn; Mulchandani, Surabhi; Propert, Kathleen Joy; Pyeritz, Reed E.; Spinner, Nancy B.; Bernhardt, Barbara A.

2012-01-01

Chromosomal microarray analysis (CMA) has improved the diagnostic rate of genomic disorders in pediatric populations, but can produce uncertain and unexpected findings. This paper explores clinicians’ perspectives and identifies challenges in effectively interpreting results and communicating with families about CMA. Responses to an online survey were obtained from 40 clinicians who had ordered CMA. Content included practice characteristics and perceptions, and queries about a hypothetical case involving uncertain and incidental findings. Data were analyzed using non-parametric statistical tests. Clinicians’ comfort levels differed significantly for explaining uncertain, abnormal, and normal CMA results, with lowest levels for uncertain results. Despite clinical guidelines recommending informed consent, many clinicians did not consider it pertinent to discuss the potential for CMA to reveal information concerning biological parentage or predisposition to late-onset disease, in a hypothetical case. Many non-genetics professionals ordering CMA did not feel equipped to interpret the results for patients, and articulated needs for education and access to genetics professionals. This exploratory study highlights key challenges in the practice of genomic medicine, and identifies needs for education, disseminated practice guidelines, and access to genetics professionals, especially when dealing with uncertain or unexpected findings. PMID:22989118

Déjà vu experiences in schizophrenia: relations with psychopathology and antipsychotic medication.

PubMed

Adachi, Naoto; Adachi, Takuya; Akanuma, Nozomi; Matsubara, Ryouji; Ito, Masumi; Takekawa, Yoshikazu; Ikeda, Hiroshi; Arai, Heii

2007-01-01

To clarify why patients with schizophrenia show déjà vu experiences less frequently, we studied déjà vu experiences in 113 schizophrenic patients in relation to psychopathologies and antipsychotic medication. Déjà vu experiences were observed in 53.1% of the schizophrenic patients. Patients with increased negative symptoms (blunted affect, motor retardation, emotional withdrawal, conceptual disorganization, and mannerisms) had déjà vu experiences less frequently. The other psychopathologies were not significantly associated with presence of déjà vu experiences. The dosage of antipsychotic drugs was significantly correlated with the frequency of déjà vu experiences. This correlation was not affected by their psychopathologies at the time of examination. The decreased frequency of déjà vu experiences in patients with schizophrenia may be mainly due to the negative symptoms. The positive relation between frequency of déjà vu experiences and the dosage of neuroleptics remains uncertain.

Potential Cost-Effectiveness of Ambulatory Cardiac Rhythm Monitoring After Cryptogenic Stroke.

PubMed

Yong, Jean Hai Ein; Thavorn, Kednapa; Hoch, Jeffrey S; Mamdani, Muhammad; Thorpe, Kevin E; Dorian, Paul; Sharma, Mike; Laupacis, Andreas; Gladstone, David J

2016-09-01

Prolonged ambulatory ECG monitoring after cryptogenic stroke improves detection of covert atrial fibrillation, but its long-term cost-effectiveness is uncertain. We estimated the cost-effectiveness of noninvasive ECG monitoring in patients aged ≥55 years after a recent cryptogenic stroke and negative 24-hour ECG. A Markov model used observed rates of atrial fibrillation detection and anticoagulation from a randomized controlled trial (EMBRACE) and the published literature to predict lifetime costs and effectiveness (ischemic strokes, hemorrhages, life-years, and quality-adjusted life-years [QALYs]) for 30-day ECG (primary analysis) and 7-day or 14-day ECG (secondary analysis), when compared with a repeat 24-hour ECG. Prolonged ECG monitoring (7, 14, or 30 days) was predicted to prevent more ischemic strokes, decrease mortality, and improve QALYs. If anticoagulation reduced stroke risk by 50%, 30-day ECG (at a cost of USD $447) would be highly cost-effective ($2000 per QALY gained) for patients with a 4.5% annual ischemic stroke recurrence risk. Cost-effectiveness was sensitive to stroke recurrence risk and anticoagulant effectiveness, which remain uncertain, especially at higher costs of monitoring. Shorter duration (7 or 14 days) monitoring was cost saving and more effective than an additional 24-hour ECG; its cost-effectiveness was less sensitive to changes in ischemic stroke risk and treatment effect. After a cryptogenic stroke, 30-day ECG monitoring is likely cost-effective for preventing recurrent strokes; 14-day monitoring is an attractive value alternative, especially for lower risk patients. These results strengthen emerging recommendations for prolonged ECG monitoring in secondary stroke prevention. Cost-effectiveness in practice will depend on careful patient selection. © 2016 American Heart Association, Inc.

A case of non-arteritic anterior ischemic optic neuropathy after completion of Harvoni therapy.

PubMed

Manoharan, Niranjan; Subramanian, Prem Sagar

2017-06-01

To report the first reported case of non-arteritic anterior ischemic optic neuropathy (NAION) associated with the use of Harvoni (Gilead Sciences, Foster City, CA, USA), a newly approved treatment for Hepatitis C. We report a case of NAION in a hepatitis C patient who completed Harvoni therapy just prior to presentation. Harvoni was suspected to be the causative agent given a lack of NAION risk factors in an otherwise healthy young patient. NAION is an acute, painless vision loss that typically affects adults over 50. The mechanism of NAION remains uncertain although numerous associations have been identified including certain medications. Harvoni, a combination drug of ledipasvir/sofosbuvir, is a recently FDA-approved treatment for Hepatitis C. To date, however, no ophthalmological side effects have been reported with its use. Continued surveillance of patients treated with Harvoni will be needed to determine if additional events are observed in the future.

Chronic kidney disease of uncertain etiology in Sri Lanka: Are leptospirosis and Hantaviral infection likely causes?

PubMed

Gamage, Chandika Damesh; Sarathkumara, Yomani Dilukshi

2016-06-01

Chronic kidney disease of uncertain etiology (CKDu) has been a severe burden and a public health crisis in Sri Lanka over the past two decades. Many studies have established hypotheses to identify potential risk factors although causative agents, risk factors and etiology of this disease are still uncertain. Several studies have postulated that fungal and bacterial nephrotoxins are a possible etiological factor; however, the precise link between hypothesized risk factors and the pathogenesis of chronic kidney disease has yet to be proven in prior studies. Leptospirosis and Hantavirus infections are important zoonotic diseases that are naturally maintained and transmitted via infected rodent populations and which present similar clinical and epidemiological features. Both infections are known to be a cause of acute kidney damage that can proceed into chronic renal failure. Several studies have reported presence of both infections in Sri Lanka. Therefore, we hypothesized that pathogenic Leptospira or Hantavirus are possible causative agents of acute kidney damage which eventually progresses to chronic kidney disease in Sri Lanka. The proposed hypothesis will be evaluated by means of an observational study design. Past infection will be assessed by a cross-sectional study to detect the presence of IgG antibodies with further confirmatory testing among chronic kidney disease patients and individuals from the community in selected endemic areas compared to low prevalence areas. Identification of possible risk factors for these infections will be followed by a case-control study and causality will be further determined with a cohort study. If the current hypothesis is true, affected communities will be subjected for medical interventions related to the disease for patient management while considering supportive therapies. Furthermore and possibly enhance their preventive and control measures to improve vector control to decrease the risk of infection. Copyright © 2016 Elsevier Ltd. All rights reserved.

Primary bone marrow oedema syndromes.

PubMed

Patel, Sanjeev

2014-05-01

MRI scanning in patients with rheumatological conditions often shows bone marrow oedema, which can be secondary to inflammatory, degenerative, infective or malignant conditions but can also be primary. The latter condition is of uncertain aetiology and it is also uncertain whether it represents a stage in the progression to osteonecrosis in some patients. Patients with primary bone marrow oedema usually have lower limb pain, commonly the hip, knee, ankle or feet. The diagnosis is one of exclusion with the presence of typical MRI findings. Treatment is usually conservative and includes analgesics and staying off the affected limb. The natural history is that of gradual resolution of symptoms over a number of months. Evidence for medical treatment is limited, but open-label studies suggest bisphosphonates may help in the resolution of pain and improve radiological findings. Surgical decompression is usually used as a last resort.

Resolving structural uncertainty in natural resources management using POMDP approaches

USGS Publications Warehouse

Williams, B.K.

2011-01-01

In recent years there has been a growing focus on the uncertainties of natural resources management, and the importance of accounting for uncertainty in assessing management effectiveness. This paper focuses on uncertainty in resource management in terms of discrete-state Markov decision processes (MDP) under structural uncertainty and partial observability. It describes the treatment of structural uncertainty with approaches developed for partially observable resource systems. In particular, I show how value iteration for partially observable MDPs (POMDP) can be extended to structurally uncertain MDPs. A key difference between these process classes is that structurally uncertain MDPs require the tracking of system state as well as a probability structure for the structure uncertainty, whereas with POMDPs require only a probability structure for the observation uncertainty. The added complexity of the optimization problem under structural uncertainty is compensated by reduced dimensionality in the search for optimal strategy. A solution algorithm for structurally uncertain processes is outlined for a simple example in conservation biology. By building on the conceptual framework developed for POMDPs, natural resource analysts and decision makers who confront structural uncertainties in natural resources can take advantage of the rapid growth in POMDP methods and approaches, and thereby produce better conservation strategies over a larger class of resource problems. ?? 2011.

BRCA1 and BRCA2 genetic testing—pitfalls and recommendations for managing variants of uncertain clinical significance

PubMed Central

Eccles, D. M.; Mitchell, G.; Monteiro, A. N. A.; Schmutzler, R.; Couch, F. J.; Spurdle, A. B.; Gómez-García, E. B.

2015-01-01

Background Increasing use of BRCA1/2 testing for tailoring cancer treatment and extension of testing to tumour tissue for somatic mutation is moving BRCA1/2 mutation screening from a primarily prevention arena delivered by specialist genetic services into mainstream oncology practice. A considerable number of gene tests will identify rare variants where clinical significance cannot be inferred from sequence information alone. The proportion of variants of uncertain clinical significance (VUS) is likely to grow with lower thresholds for testing and laboratory providers with less experience of BRCA. Most VUS will not be associated with a high risk of cancer but a misinterpreted VUS has the potential to lead to mismanagement of both the patient and their relatives. Design Members of the Clinical Working Group of ENIGMA (Evidence-based Network for the Interpretation of Germline Mutant Alleles) global consortium (www.enigmaconsortium.org) observed wide variation in practices in reporting, disclosure and clinical management of patients with a VUS. Examples from current clinical practice are presented and discussed to illustrate potential pitfalls, explore factors contributing to misinterpretation, and propose approaches to improving clarity. Results and conclusion Clinicians, patients and their relatives would all benefit from an improved level of genetic literacy. Genetic laboratories working with clinical geneticists need to agree on a clinically clear and uniform format for reporting BRCA test results to non-geneticists. An international consortium of experts, collecting and integrating all available lines of evidence and classifying variants according to an internationally recognized system, will facilitate reclassification of variants for clinical use. PMID:26153499

A risk score for in-hospital death in patients admitted with ischemic or hemorrhagic stroke.

PubMed

Smith, Eric E; Shobha, Nandavar; Dai, David; Olson, DaiWai M; Reeves, Mathew J; Saver, Jeffrey L; Hernandez, Adrian F; Peterson, Eric D; Fonarow, Gregg C; Schwamm, Lee H

2013-01-28

We aimed to derive and validate a single risk score for predicting death from ischemic stroke (IS), intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH). Data from 333 865 stroke patients (IS, 82.4%; ICH, 11.2%; SAH, 2.6%; uncertain type, 3.8%) in the Get With The Guidelines-Stroke database were used. In-hospital mortality varied greatly according to stroke type (IS, 5.5%; ICH, 27.2%; SAH, 25.1%; unknown type, 6.0%; P<0.001). The patients were randomly divided into derivation (60%) and validation (40%) samples. Logistic regression was used to determine the independent predictors of mortality and to assign point scores for a prediction model in the overall population and in the subset with the National Institutes of Health Stroke Scale (NIHSS) recorded (37.1%). The c statistic, a measure of how well the models discriminate the risk of death, was 0.78 in the overall validation sample and 0.86 in the model including NIHSS. The model with NIHSS performed nearly as well in each stroke type as in the overall model including all types (c statistics for IS alone, 0.85; for ICH alone, 0.83; for SAH alone, 0.83; uncertain type alone, 0.86). The calibration of the model was excellent, as demonstrated by plots of observed versus predicted mortality. A single prediction score for all stroke types can be used to predict risk of in-hospital death following stroke admission. Incorporation of NIHSS information substantially improves this predictive accuracy.

Epidemiology of primary brain tumors in the Middle Eastern population in California, USA 2001-2005.

PubMed

Nasseri, Kiumarss; Mills, John R

2009-01-01

The fast growing Middle Eastern (ME) population has rarely been studied in the U.S.. The purpose of this study was to compare the epidemiology of primary brain tumors in this ethnic population with the non-Hispanic, non-Middle Eastern White (NHNMW) in California. ME cases were identified by surname in the California cancer registry and ME population estimates were based on ancestry. Data for 683 cases of primary brain tumors (429 benign, 238 malignant, 16 uncertain) in the ME and 15,589 cases (8352 benign, 6812 malignant, 425 uncertain) in the NHNMW were available for this study. ME patients were significantly (p < 0.05) younger and their age-adjusted incidence rates per 100,000 for benign tumors of 10.0 in men and 17.6 in women were higher than similar rates of 7.3 and 10.6 in the NHNMW group (p < 0.05). Rates for malignant tumors were similar. Meningioma was the main histology responsible for the observed increase in patients over 40 years of age. Also increased were benign tumors of the pituitary and pineal glands. The overall mortality in patients with benign tumors was significantly lower than malignant tumors. This study presents a significantly high incidence of benign meningioma in the ME population in California. This may be due to higher susceptibility or exposure of this ethnic group to the risk factor(s) for this neoplasm. Considering the reported causal association of benign meningioma with childhood radiation exposure from Israel, exposure to this risk factor in this ethnic group needs to be evaluated in future studies.

Financial arrangements for health systems in low-income countries: an overview of systematic reviews.

PubMed

Wiysonge, Charles S; Paulsen, Elizabeth; Lewin, Simon; Ciapponi, Agustín; Herrera, Cristian A; Opiyo, Newton; Pantoja, Tomas; Rada, Gabriel; Oxman, Andrew D

2017-09-11

One target of the Sustainable Development Goals is to achieve "universal health coverage, including financial risk protection, access to quality essential health-care services and access to safe, effective, quality and affordable essential medicines and vaccines for all". A fundamental concern of governments in striving for this goal is how to finance such a health system. This concern is very relevant for low-income countries. To provide an overview of the evidence from up-to-date systematic reviews about the effects of financial arrangements for health systems in low-income countries. Secondary objectives include identifying needs and priorities for future evaluations and systematic reviews on financial arrangements, and informing refinements in the framework for financial arrangements presented in the overview. We searched Health Systems Evidence in November 2010 and PDQ-Evidence up to 17 December 2016 for systematic reviews. We did not apply any date, language, or publication status limitations in the searches. We included well-conducted systematic reviews of studies that assessed the effects of financial arrangements on patient outcomes (health and health behaviours), the quality or utilisation of healthcare services, resource use, healthcare provider outcomes (such as sick leave), or social outcomes (such as poverty, employment, or financial burden of patients, e.g. out-of-pocket payment, catastrophic disease expenditure) and that were published after April 2005. We excluded reviews with limitations important enough to compromise the reliability of the findings. Two overview authors independently screened reviews, extracted data, and assessed the certainty of evidence using GRADE. We prepared SUPPORT Summaries for eligible reviews, including key messages, 'Summary of findings' tables (using GRADE to assess the certainty of the evidence), and assessments of the relevance of findings to low-income countries. We identified 7272 reviews and included 15 in this overview, on: collection of funds (2 reviews), insurance schemes (1 review), purchasing of services (1 review), recipient incentives (6 reviews), and provider incentives (5 reviews). The reviews were published between 2008 and 2015; focused on 13 subcategories; and reported results from 276 studies: 115 (42%) randomised trials, 11 (4%) non-randomised trials, 23 (8%) controlled before-after studies, 51 (19%) interrupted time series, 9 (3%) repeated measures, and 67 (24%) other non-randomised studies. Forty-three per cent (119/276) of the studies included in the reviews took place in low- and middle-income countries. Collection of funds: the effects of changes in user fees on utilisation and equity are uncertain (very low-certainty evidence). It is also uncertain whether aid delivered under the Paris Principles (ownership, alignment, harmonisation, managing for results, and mutual accountability) improves health outcomes compared to aid delivered without conforming to those principles (very low-certainty evidence). Insurance schemes: community-based health insurance may increase service utilisation (low-certainty evidence), but the effects on health outcomes are uncertain (very low-certainty evidence). It is uncertain whether social health insurance improves utilisation of health services or health outcomes (very low-certainty evidence). Purchasing of services: it is uncertain whether increasing salaries of public sector healthcare workers improves the quantity or quality of their work (very low-certainty evidence). Recipient incentives: recipient incentives may improve adherence to long-term treatments (low-certainty evidence), but it is uncertain whether they improve patient outcomes. One-time recipient incentives probably improve patient return for start or continuation of treatment (moderate-certainty evidence) and may improve return for tuberculosis test readings (low-certainty evidence). However, incentives may not improve completion of tuberculosis prophylaxis, and it is uncertain whether they improve completion of treatment for active tuberculosis. Conditional cash transfer programmes probably lead to an increase in service utilisation (moderate-certainty evidence), but their effects on health outcomes are uncertain. Vouchers may improve health service utilisation (low-certainty evidence), but the effects on health outcomes are uncertain (very low-certainty evidence). Introducing a restrictive cap may decrease use of medicines for symptomatic conditions and overall use of medicines, may decrease insurers' expenditures on medicines (low-certainty evidence), and has uncertain effects on emergency department use, hospitalisations, and use of outpatient care (very low-certainty evidence). Reference pricing, maximum pricing, and index pricing for drugs have mixed effects on drug expenditures by patients and insurers as well as the use of brand and generic drugs. Provider incentives: the effects of provider incentives are uncertain (very low-certainty evidence), including: the effects of provider incentives on the quality of care provided by primary care physicians or outpatient referrals from primary to secondary care, incentives for recruiting and retaining health professionals to serve in remote areas, and the effects of pay-for-performance on provider performance, the utilisation of services, patient outcomes, or resource use in low-income countries. Research based on sound systematic review methods has evaluated numerous financial arrangements relevant to low-income countries, targeting different levels of the health systems and assessing diverse outcomes. However, included reviews rarely reported social outcomes, resource use, equity impacts, or undesirable effects. We also identified gaps in primary research because of uncertainty about applicability of the evidence to low-income countries. Financial arrangements for which the effects are uncertain include external funding (aid), caps and co-payments, pay-for-performance, and provider incentives. Further studies evaluating the effects of these arrangements are needed in low-income countries. Systematic reviews should include all outcomes that are relevant to decision-makers and to people affected by changes in financial arrangements.

The doctor-patient relationship as a toolkit for uncertain clinical decisions.

PubMed

Diamond-Brown, Lauren

2016-06-01

Medical uncertainty is a well-recognized problem in healthcare, yet how doctors make decisions in the face of uncertainty remains to be understood. This article draws on interdisciplinary literature on uncertainty and physician decision-making to examine a specific physician response to uncertainty: using the doctor-patient relationship as a toolkit. Additionally, I ask what happens to this process when the doctor-patient relationship becomes fragmented. I answer these questions by examining obstetrician-gynecologists' narratives regarding how they make decisions when faced with uncertainty in childbirth. Between 2013 and 2014, I performed 21 semi-structured interviews with obstetricians in the United States. Obstetricians were selected to maximize variation in relevant physician, hospital, and practice characteristics. I began with grounded theory and moved to analytical coding of themes in relation to relevant literature. My analysis renders it evident that some physicians use the doctor-patient relationship as a toolkit for dealing with uncertainty. I analyze how this process varies for physicians in different models of care by comparing doctors' experiences in models with continuous versus fragmented doctor-patient relationships. My key findings are that obstetricians in both models appealed to the ideal of patient-centered decision-making to cope with uncertain decisions, but in practice physicians in fragmented care faced a number of challenges to using the doctor-patient relationship as a toolkit for decision-making. These challenges led to additional uncertainties and in some cases to poor outcomes for doctors and/or patients; they also raised concerns about the reproduction of inequality. Thus organization of care delivery mitigates the efficacy of doctors' use of the doctor-patient relationship toolkit for uncertain decisions. These findings have implications for theorizing about decision-making under conditions of medical uncertainty, for understanding how the doctor-patient relationship and model of care affect physician decision-making, and for forming policy on the optimal structure of medical work. Copyright © 2016 Elsevier Ltd. All rights reserved.

Results of the 2017 Mexican Asteroid Photometry Campaign - Part 1

NASA Astrophysics Data System (ADS)

Sada, Pedro; Loera-Gonzalez, Pablo; Olguin, Lorenzo; Saucedo-Morales, Julio C.; Ayala-Gómez, Sandra A.; Garza, Jaime R.

2018-04-01

We report the results for the first semester of the 2017 Mexican Asteroid Photometry Campaign. Asteroid 1218 Aster (synodic period of 3.1581 ± 0.0002 h and amplitude of 0.35 mag) was well observed and showed slight variations of its lightcurve at the end of the seven week observing window. An uncertain, but long, period of 93.23 ± 0.02 h and amplitude of 0.36 mag were estimated for 2733 Hamina from sparse data. Asteroid 8443 Svecica was also well observed and yielded a period of 20.9905 ± 0.0015 h and amplitude of 0.65 mag. Observations of NEA (143404) 2003 BD44 also resulted in an uncertain and long period of 78.617 ± 0.009 h and amplitude of 0.66 mag with a sparsely covered lightcurve.

Urologist characteristics predict use of androgen deprivation therapy for prostate cancer

PubMed Central

Shahinian, Vahakn B.; Kuo, Yong-fang; Freeman, Jean L.; Orihuela, Eduardo; Goodwin, James S.

2007-01-01

Purpose We have previously reported wide variations among urologists in use of androgen deprivation for prostate cancer. Using Surveillance, Epidemiology and End-Results (SEER)-Medicare linked data we examined how individual urologist characteristics influenced use of androgen deprivation therapy. Methods Participants included 82,375 men with prostate cancer diagnosed from January 1, 1992, through December 31, 2002, and 2,080 urologists providing care to them. Multi-level analyses were used to estimate likelihood of androgen deprivation use within six months of diagnosis in the overall cohort, a subgroup where use would be of uncertain benefit (primary therapy for localized prostate cancer), and a subgroup where use would be evidence-based (adjuvant therapy with radiation for locally advanced disease). Results In the overall cohort of patients, a multi-level model adjusted for patient, tumor and urologist characteristics (board certification, academic affiliation, patient panel size, years since medical school graduation) showed that the likelihood of androgen deprivation use was significantly higher for patients who saw urologists without an academic affiliation. This pattern was also noted when the analysis was limited to settings where androgen deprivation would have been of uncertain benefit. Odds ratios for use in that context were 1.66 (95%CI: 1.27-2.16) for no academic affiliation and 1.45 (95%CI:1.13-1.85) for minor versus major academic affiliation. Conclusion Use of androgen deprivation for prostate cancer varies by the characteristics of the urologist. Patients of non-academically affiliated urologists were significantly more likely to receive primary androgen deprivation therapy for localized prostate cancer, a setting where the benefits are uncertain. PMID:18048816

Electromagnetic hypersensitivity: The opinion of an observer neurologist

NASA Astrophysics Data System (ADS)

Marc-Vergnes, Jean-Pierre

2010-11-01

Electromagnetic hypersensitivity (EHS) is a recent, uncertain and somehow confusing concept. It is now widely agreed that people claiming to be EHS really experience symptoms. However, no evidence for a causal link between the symptoms and electromagnetic fields (EMF) has been reported. Thus, we have to wonder whether EHS constitutes truly a relevant entity. Most of the previous studies suffer from methodological flaws. Owing to the quantification of symptoms, the interdisciplinary assessment of patients, and the use of personal exposimeters, the recent studies are of better quality. A set of convergent associated signs suggests that individual neuropsychic factors take a prominent, but maybe not unique, part in this condition.

Prolonged Follow-Up of Patients in the U.S. Multicenter Trial of Ursodeoxycholic Acid for Primary Biliary Cirrhosis

PubMed Central

Combes, Burton; Luketic, Velimir A.; Peters, Marion G.; Zetterman, Rowen K.; Garcia-Tsao, Guadalupe; Munoz, Santiago J.; Lin, Danyu; Flye, Nancy; Carithers, Robert L.

2013-01-01

OBJECTIVE Randomized, double-blind, placebo-controlled trials of ursodeoxycholic acid (UDCA) in patients with primary biliary cirrhosis (PBC) have not demonstrated improvement in survival during the placebo-controlled phases of these trials. Analyses purporting to demonstrate a survival advantage of UDCA are largely dependent on data obtained after the placebo phases were terminated, and placebo-treated patients were offered open-label UDCA. After completion of our 2-yr placebo-controlled trial of UDCA in which we observed no survival benefit for UDCA, we provided the patients with open-label UDCA to see if delay in providing UDCA for 2 yr had any effect on subsequent liver transplantation or death without liver transplantation. METHODS In our previously reported 2-yr placebo-controlled trial, 151 patients with PBC were randomized to receive either UDCA (n = 77) or placebo (n = 74). The number of patients who progressed to liver transplantation or death without transplantation were similar in both the groups, 12 (16%) in the UDCA-treated and 11 (15%) in placebo-treated patients. All the patients were then offered open-label UDCA, with 61 original UDCA and 56 original placebo-treated patients now taking UDCA in an extended open-label phase of the trial. RESULTS No significant differences were observed in the number of patients who underwent liver transplantation or died without liver transplantation in the open-label phase of the trial. Moreover, no difference in the time to these endpoints was seen over the period of observation of as long as 6 yr from the time of initial randomization. CONCLUSIONS Results of open-label extensions of previous conducted placebo-controlled trials of UDCA in PBC leave uncertain whether UDCA impacts significantly on liver transplantation and death without liver transplantation in patients with PBC. PMID:15046215

Use of the Coronary Artery Calcium Score in Discussion of Initiation of Statin Therapy in Primary Prevention.

PubMed

Michos, Erin D; Blaha, Michael J; Blumenthal, Roger S

2017-12-01

Clinical guidelines for instituting pharmacotherapy for the primary prevention of atherosclerotic cardiovascular disease (ASCVD), specifically lipid management and aspirin, have long been based on absolute risk. However, lipid management in the current era remains challenging to both patients and clinicians in the setting of somewhat discordant recommendations from various organizations. All guidelines endorse the use of statins for primary prevention for those at sufficient absolute risk, and treatment recommendations are generally "risk-based" rather than exclusively targeting specific low-density lipoprotein cholesterol levels. Nonetheless, guidelines differ in relation to the risk threshold for initiation and the intensity of statin treatment. The key concept of the clinician-patient risk discussion introduced in the 2013 American College of Cardiology/American Heart Association cholesterol guidelines is a process that addresses the potential for ASCVD risk reduction with statin treatment, potential for adverse treatment effects, patient preferences, encouragement of heart-healthy lifestyle, and management of other risk factors. However, operationalizing the clinician-patient risk discussion requires effective communication of the most accurate and personalized risk information. In this article, we review our treatment approach for the appropriate use of coronary artery calcium testing in the intermediate-risk patient to guide shared decision making. The decision to initiate or intensify statin therapy may be uncertain across a broad range of estimated 10-year ASCVD risk of 5% to 20%, and coronary artery calcium testing can reclassify risk upward or downward in approximately 50% of this group to inform the risk discussion. We conclude with 2 case-based examples of uncertain risk and uncertain statin therapeutic benefit to illustrate execution of the clinician-patient risk discussion. Copyright © 2017 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Interpreting null results from measurements with uncertain correlations: an info-gap approach.

PubMed

Ben-Haim, Yakov

2011-01-01

Null events—not detecting a pernicious agent—are the basis for declaring the agent is absent. Repeated nulls strengthen confidence in the declaration. However, correlations between observations are difficult to assess in many situations and introduce uncertainty in interpreting repeated nulls. We quantify uncertain correlations using an info-gap model, which is an unbounded family of nested sets of possible probabilities. An info-gap model is nonprobabilistic and entails no assumption about a worst case. We then evaluate the robustness, to uncertain correlations, of estimates of the probability of a null event. This is then the basis for evaluating a nonprobabilistic robustness-based confidence interval for the probability of a null. © 2010 Society for Risk Analysis.

Formation Learning Control of Multiple Autonomous Underwater Vehicles With Heterogeneous Nonlinear Uncertain Dynamics.

PubMed

Yuan, Chengzhi; Licht, Stephen; He, Haibo

2017-09-26

In this paper, a new concept of formation learning control is introduced to the field of formation control of multiple autonomous underwater vehicles (AUVs), which specifies a joint objective of distributed formation tracking control and learning/identification of nonlinear uncertain AUV dynamics. A novel two-layer distributed formation learning control scheme is proposed, which consists of an upper-layer distributed adaptive observer and a lower-layer decentralized deterministic learning controller. This new formation learning control scheme advances existing techniques in three important ways: 1) the multi-AUV system under consideration has heterogeneous nonlinear uncertain dynamics; 2) the formation learning control protocol can be designed and implemented by each local AUV agent in a fully distributed fashion without using any global information; and 3) in addition to the formation control performance, the distributed control protocol is also capable of accurately identifying the AUVs' heterogeneous nonlinear uncertain dynamics and utilizing experiences to improve formation control performance. Extensive simulations have been conducted to demonstrate the effectiveness of the proposed results.

No improvement in serological response among serofast latent patients retreated with benzathine penicillin.

PubMed

Ren, Rong-Xin; Wang, Lin-Na; Zheng, He-Yi; Li, Jun

2016-01-01

Persistent non-treponemal titres after treatment are common among patients with latent syphilis. Although retreatment is often done in clinical practice, optimal management remains uncertain due to the paucity of data regarding serological response to retreatment and long-term outcomes. We compared the serological responses of serofast latent syphilis patients retreated with 7.2 million units of benzathine penicillin with the responses of patients who did not receive retreatment (control group). We retrospectively analysed the serological response to therapy following retreatment of 35 serofast latent syphilis patients at 12 months with benzathine penicillin 2.4 million units weekly for 3 weeks. In all, 74.3% (26/35) of the cases with latent syphilis who failed to achieve serological cure at 12 months after initial therapy achieved serological cure after retreatment and after an additional 12 months of follow-up. However, statistically similar serological cure rate was observed in 80.0% (28/35) of the control group (p > .05). Our findings illustrate no improvement in serological response among serofast latent patients retreated with three doses of benzathine penicillin. © The Author(s) 2015.

Helicobacter pylori infection and chronic immune thrombocytopenic purpura: long-term results of bacterium eradication and association with bacterium virulence profiles.

PubMed

Emilia, Giovanni; Luppi, Mario; Zucchini, Patrizia; Morselli, Monica; Potenza, Leonardo; Forghieri, Fabio; Volzone, Francesco; Jovic, Gordana; Leonardi, Giovanna; Donelli, Amedea; Torelli, Giuseppe

2007-12-01

Eradication of Helicobacter pylori may lead to improvement of chronic immune thrombocytopenic purpura (ITP), although its efficacy over time is uncertain. We report the results of H pylori screening and eradication in 75 consecutive adult patients with ITP. We also used molecular methods to investigate lymphocyte clonality and H pylori genotypes in the gastric biopsies from 10 H pylori-positive patients with ITP and 19 H pylori-positive patients without ITP with chronic gastritis. Active H pylori infection was documented in 38 (51%) patients and successfully eradicated in 34 (89%) patients. After a median follow-up of 60 months, a persistent platelet response in 23 (68%) of patients with eradicated infection was observed; 1 relapse occurred. No differences in mucosal B- or T-cell clonalities were observed between patients with ITP and control participants. Of note, the frequency of the H pylori cagA gene (P = .02) and the frequency of concomitant H pylori cagA, vacAs1, and iceA genes (triple-positive strains; P = .015) resulted statistically higher in patients with ITP than in control participants. All asymptomatic H pylori-positive patients with ITP were suffering from chronic gastritis. Our data suggest a sustained platelet recovery in a proportion of patients with ITP by H pylori eradication alone. Overrepresentation of specific H pylori genotypes in ITP suggests a possible role for bacterium-related factors in the disease pathogenesis.

High-order sliding-mode control for blood glucose regulation in the presence of uncertain dynamics.

PubMed

Hernández, Ana Gabriela Gallardo; Fridman, Leonid; Leder, Ron; Andrade, Sergio Islas; Monsalve, Cristina Revilla; Shtessel, Yuri; Levant, Arie

2011-01-01

The success of blood glucose automatic regulation depends on the robustness of the control algorithm used. It is a difficult task to perform due to the complexity of the glucose-insulin regulation system. The variety of model existing reflects the great amount of phenomena involved in the process, and the inter-patient variability of the parameters represent another challenge. In this research a High-Order Sliding-Mode Control is proposed. It is applied to two well known models, Bergman Minimal Model, and Sorensen Model, to test its robustness with respect to uncertain dynamics, and patients' parameter variability. The controller designed based on the simulations is tested with the specific Bergman Minimal Model of a diabetic patient whose parameters were identified from an in vivo assay. To minimize the insulin infusion rate, and avoid the hypoglycemia risk, the glucose target is a dynamical profile.

Communicating Uncertain News in Cancer Consultations.

PubMed

Alby, Francesca; Zucchermaglio, Cristina; Fatigante, Marilena

2017-12-01

In cancer communication, most of the literature is in the realm of delivering bad news while much less attention has been given to the communication of uncertain news around the diagnosis and the possible outcomes of the illness. Drawing on video-recorded cancer consultations collected in two Italian hospitals, this article analyzes three communication practices used by oncologists to interactionally manage the uncertainty during the visit: alternating between uncertain bad news and certain good news, anticipating scenarios, and guessing test results. Both diagnostic and personal uncertainties are not hidden to the patient, yet they are reduced through these practices. Such communication practices are present in 32 % of the visits in the data set, indicating that the interactional management of uncertainty is a relevant phenomenon in oncological encounters. Further studies are needed to improve both its understanding and its teaching.

[Disease perception in patients with wet age-related macular degeneration].

PubMed

Kostadinov, F; Valmaggia, C

2015-04-01

The disease perception of the patients treated with intravitreal injections of anti-vascular endothelial growth factor due to wet age-related macular degeneration was investigated. 177 questionnaires focusing on the development of the perceived visual acuity and the quality of life were evaluated. The subgroup 1 included 125 patients (70.6%) with a unilateral wet age-related macular degeneration. The subgroup 2 included 52 patients (29.4%) with a bilateral wet age-related macular degeneration. Patients would almost always recommend the therapy to a friend (97.2%). The critical remarks are related to the uncertain course of the disease (22.8%) and the uncertain duration of the treatment (19%). There was a discrepancy between the measured visual outcome and the perceived one in 5.6% in the subgroup 1, and in 38.5% in the subgroup 2. This difference was statistically significant (chi-square test with p<0.01). The treatment of wet age-related macular degeneration with intravitreal injections of anti-vascular endothelial growth factor is judged positively. Binocular affected patients have a higher disease perception and therefore a poorer self-assessment of their visual acuity and their quality of life compared with monocular affected patients. Georg Thieme Verlag KG Stuttgart · New York.

Polyclonal and monoclonal antibodies for induction therapy in kidney transplant recipients.

PubMed

Hill, Penny; Cross, Nicholas B; Barnett, A Nicholas R; Palmer, Suetonia C; Webster, Angela C

2017-01-11

Prolonging kidney transplant survival is an important clinical priority. Induction immunosuppression with antibody therapy is recommended at transplantation and non-depleting interleukin-2 receptor monoclonal antibodies (IL2Ra) are considered first line. It is suggested that recipients at high risk of rejection should receive lymphocyte-depleting antibodies but the relative benefits and harms of the available agents are uncertain. We aimed to: evaluate the relative and absolute effects of different antibody preparations (except IL2Ra) when used as induction therapy in kidney transplant recipients; determine how the benefits and adverse events vary for each antibody preparation; determine how the benefits and harms vary for different formulations of antibody preparation; and determine whether the benefits and harms vary in specific subgroups of recipients (e.g. children and sensitised recipients). Randomised controlled trials (RCTs) comparing monoclonal or polyclonal antibodies with placebo, no treatment, or other antibody therapy in adults and children who had received a kidney transplant. Randomised controlled trials (RCTs) comparing monoclonal or polyclonal antibodies with placebo, no treatment, or other antibody therapy in adults and children who had received a kidney transplant. Two authors independently extracted data and assessed risk of bias. Dichotomous outcomes are reported as relative risk (RR) and continuous outcomes as mean difference (MD) together with their 95% confidence intervals (CI). We included 99 studies (269 records; 8956 participants; 33 with contemporary agents). Methodology was incompletely reported in most studies leading to lower confidence in the treatment estimates.Antithymocyte globulin (ATG) prevented acute graft rejection (17 studies: RR 0.63, 95% CI 0.51 to 0.78). The benefits of ATG on graft rejection were similar when used with (12 studies: RR 0.61, 0.49 to 0.76) or without (5 studies: RR 0.65, 0.43 to 0.98) calcineurin inhibitor (CNI) treatment. ATG (with CNI therapy) had uncertain effects on death (3 to 6 months, 3 studies: RR 0.41, 0.13 to 1.22; 1 to 2 years, 5 studies: RR 0.75, 0.27 to 2.06; 5 years, 2 studies: RR 0.94, 0.11 to 7.81) and graft loss (3 to 6 months, 4 studies: RR 0.60, 0.34 to 1.05; 1 to 2 years, 3 studies: RR 0.65, 0.36 to 1.19). The effect of ATG on death-censored graft loss was uncertain at 1 to 2 years and 5 years. In non-CNI studies, ATG had uncertain effects on death but reduced death-censored graft loss (6 studies: RR 0.55, 0.38 to 0.78). When CNI and older non-CNI studies were combined, a benefit was seen with ATG at 1 to 2 years for both all-cause graft loss (7 studies: RR 0.71, 0.53 to 0.95) and death-censored graft loss (8 studies: RR 0.55, 0.39 to 0.77) but not sustained longer term. ATG increased cytomegalovirus (CMV) infection (6 studies: RR 1.55, 1.24 to 1.95), leucopenia (4 studies: RR 3.86, 2.79 to 5.34) and thrombocytopenia (4 studies: RR 2.41, 1.61 to 3.61) but had uncertain effects on delayed graft function, malignancy, post-transplant lymphoproliferative disorder (PTLD), and new onset diabetes after transplantation (NODAT).Alemtuzumab was compared to ATG in six studies (446 patients) with early steroid withdrawal (ESW) or steroid minimisation. Alemtuzumab plus steroid minimisation reduced acute rejection compared to ATG at one year (4 studies: RR 0.57, 0.35 to 0.93). In the two studies with ESW only in the alemtuzumab arm, the effect of alemtuzumab on acute rejection at 1 year was uncertain compared to ATG (RR 1.27, 0.50 to 3.19). Alemtuzumab had uncertain effects on death (1 year, 2 studies: RR 0.39, 0.06 to 2.42; 2 to 3 years, 3 studies: RR 0.67, 95% CI 0.15 to 2.95), graft loss (1 year, 2 studies: RR 0.39, 0.13 to 1.30; 2 to 3 years, 3 studies: RR 0.98, 95% CI 0.47 to 2.06), and death-censored graft loss (1 year, 2 studies: RR 0.38, 0.08 to 1.81; 2 to 3 years, 3 studies: RR 2.45, 95% CI 0.67 to 8.97) compared to ATG. Creatinine clearance was lower with alemtuzumab plus ESW at 6 months (2 studies: MD -13.35 mL/min, -23.91 to -2.80) and 2 years (2 studies: MD -12.86 mL/min, -23.73 to -2.00) compared to ATG plus triple maintenance. Across all 6 studies, the effect of alemtuzumab versus ATG was uncertain on all-cause infection, CMV infection, BK virus infection, malignancy, and PTLD. The effect of alemtuzumab with steroid minimisation on NODAT was uncertain, compared to ATG with steroid maintenance.Alemtuzumab plus ESW compared with triple maintenance without induction therapy had uncertain effects on death and all-cause graft loss at 1 year, acute rejection at 6 months and 1 year. CMV infection was increased (2 studies: RR 2.28, 1.18 to 4.40). Treatment effects were uncertain for NODAT, thrombocytopenia, and malignancy or PTLD.Rituximab had uncertain effects on death, graft loss, acute rejection and all other adverse outcomes compared to placebo. ATG reduces acute rejection but has uncertain effects on death, graft survival, malignancy and NODAT, and increases CMV infection, thrombocytopenia and leucopenia. Given a 45% acute rejection risk without ATG induction, seven patients would need treatment to prevent one having rejection, while incurring an additional patient experiencing CMV disease for every 12 treated. Excluding non-CNI studies, the risk of rejection was 37% without induction with six patients needing treatment to prevent one having rejection.In the context of steroid minimisation, alemtuzumab prevents acute rejection at 1 year compared to ATG. Eleven patients would require treatment with alemtuzumab to prevent 1 having rejection, assuming a 21% rejection risk with ATG.Triple maintenance without induction therapy compared to alemtuzumab combined with ESW had similar rates of acute rejection but adverse effects including NODAT were poorly documented. Alemtuzumab plus steroid withdrawal would cause one additional patient experiencing CMV disease for every six patients treated compared to no induction and triple maintenance, in the absence of any clinical benefit. Overall, ATG and alemtuzumab decrease acute rejection at a cost of increased CMV disease while patient-centred outcomes (reduced death or lower toxicity) do not appear to be improved.

The impact of personalized probabilistic wall thickness models on peak wall stress in abdominal aortic aneurysms.

PubMed

Biehler, J; Wall, W A

2018-02-01

If computational models are ever to be used in high-stakes decision making in clinical practice, the use of personalized models and predictive simulation techniques is a must. This entails rigorous quantification of uncertainties as well as harnessing available patient-specific data to the greatest extent possible. Although researchers are beginning to realize that taking uncertainty in model input parameters into account is a necessity, the predominantly used probabilistic description for these uncertain parameters is based on elementary random variable models. In this work, we set out for a comparison of different probabilistic models for uncertain input parameters using the example of an uncertain wall thickness in finite element models of abdominal aortic aneurysms. We provide the first comparison between a random variable and a random field model for the aortic wall and investigate the impact on the probability distribution of the computed peak wall stress. Moreover, we show that the uncertainty about the prevailing peak wall stress can be reduced if noninvasively available, patient-specific data are harnessed for the construction of the probabilistic wall thickness model. Copyright © 2017 John Wiley & Sons, Ltd.

Output Feedback-Based Boundary Control of Uncertain Coupled Semilinear Parabolic PDE Using Neurodynamic Programming.

PubMed

Talaei, Behzad; Jagannathan, Sarangapani; Singler, John

2018-04-01

In this paper, neurodynamic programming-based output feedback boundary control of distributed parameter systems governed by uncertain coupled semilinear parabolic partial differential equations (PDEs) under Neumann or Dirichlet boundary control conditions is introduced. First, Hamilton-Jacobi-Bellman (HJB) equation is formulated in the original PDE domain and the optimal control policy is derived using the value functional as the solution of the HJB equation. Subsequently, a novel observer is developed to estimate the system states given the uncertain nonlinearity in PDE dynamics and measured outputs. Consequently, the suboptimal boundary control policy is obtained by forward-in-time estimation of the value functional using a neural network (NN)-based online approximator and estimated state vector obtained from the NN observer. Novel adaptive tuning laws in continuous time are proposed for learning the value functional online to satisfy the HJB equation along system trajectories while ensuring the closed-loop stability. Local uniformly ultimate boundedness of the closed-loop system is verified by using Lyapunov theory. The performance of the proposed controller is verified via simulation on an unstable coupled diffusion reaction process.

Overcoming barriers to implementing patient-reported outcomes in an electronic health record: a case report.

PubMed

Harle, Christopher A; Listhaus, Alyson; Covarrubias, Constanza M; Schmidt, Siegfried Of; Mackey, Sean; Carek, Peter J; Fillingim, Roger B; Hurley, Robert W

2016-01-01

In this case report, the authors describe the implementation of a system for collecting patient-reported outcomes and integrating results in an electronic health record. The objective was to identify lessons learned in overcoming barriers to collecting and integrating patient-reported outcomes in an electronic health record. The authors analyzed qualitative data in 42 documents collected from system development meetings, written feedback from users, and clinical observations with practice staff, providers, and patients. Guided by the Unified Theory on the Adoption and Use of Information Technology, 5 emergent themes were identified. Two barriers emerged: (i) uncertain clinical benefit and (ii) time, work flow, and effort constraints. Three facilitators emerged: (iii) process automation, (iv) usable system interfaces, and (v) collecting patient-reported outcomes for the right patient at the right time. For electronic health record-integrated patient-reported outcomes to succeed as useful clinical tools, system designers must ensure the clinical relevance of the information being collected while minimizing provider, staff, and patient burden. © The Author 2015. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The uncertain response in humans and animals

NASA Technical Reports Server (NTRS)

Smith, J. D.; Shields, W. E.; Schull, J.; Washburn, D. A.; Rumbaugh, D. M. (Principal Investigator)

1997-01-01

There has been no comparative psychological study of uncertainty processes. Accordingly, the present experiments asked whether animals, like humans, escape adaptively when they are uncertain. Human and animal observers were given two primary responses in a visual discrimination task, and the opportunity to escape from some trials into easier ones. In one psychophysical task (using a threshold paradigm), humans escaped selectively the difficult trials that left them uncertain of the stimulus. Two rhesus monkeys (Macaca mulatta) also showed this pattern. In a second psychophysical task (using the method of constant stimuli), some humans showed this pattern but one escaped infrequently and nonoptimally. Monkeys showed equivalent individual differences. The data suggest that escapes by humans and monkeys are interesting cognitive analogs and may reflect controlled decisional processes prompted by the perceptual ambiguity at threshold.

Self-expanding stent for spontaneous coronary artery dissection: a rational choice.

PubMed

Mele, Marco; Langialonga, Tommaso; Maggi, Alessandro; Villella, Massimo; Villella, Alessandro

2016-12-01

: Spontaneous coronary artery dissection (SCAD) is a rare and poorly understood cause of acute coronary syndrome in relatively young patients. Nowadays, the optimal treatment of SCAD is uncertain. A conservative approach seems to be preferable, but in particular conditions, an invasive strategy is necessary. The poor rate of procedural success, the high risk of procedural complications and the uncertain long and mid-term results make the interventional treatment of SCAD a challenge. We report a case of a young male patient presenting with SCAD successfully treated with a sirolimus-eluting self-expanding coronary stent. To our knowledge, the use of self-expanding coronary stent for SCAD has never been described yet and we discuss about the rationale of a possible larger use in clinical practice.

Morphological analysis of circulating tumour cells in patients undergoing surgery for non-small cell lung carcinoma using the isolation by size of epithelial tumour cell (ISET) method.

PubMed

Hofman, V; Long, E; Ilie, M; Bonnetaud, C; Vignaud, J M; Fléjou, J F; Lantuejoul, S; Piaton, E; Mourad, N; Butori, C; Selva, E; Marquette, C H; Poudenx, M; Sibon, S; Kelhef, S; Vénissac, N; Jais, J P; Mouroux, J; Molina, T J; Vielh, P; Hofman, P

2012-02-01

Recurrence rates after surgery for non-small cell lung cancer (NSCLC) range from 25 to 50% and 5-year survival is only 60-70%. Because no biomarkers are predictive of recurrence or the onset of metastasis, pathological TNM (pTNM) staging is currently the best prognostic factor. Consequently, the preoperative detection of circulating tumour cells (CTCs) might be useful in tailoring therapy. The aim of this study was to characterize morphologically any circulating non-haematological cells (CNHCs) in patients undergoing surgery for NSCLC using the isolation by size of epithelial tumour cell (ISET) method. Of 299 blood samples tested, 250 were from patients with resectable NSCLC and 59 from healthy controls. The presence of CNHCs was assessed blindly and independently by 10 cytopathologists on May-Grünwald-Giemsa stained filters and the cells classified into three groups: (i) malignant cells, (ii) uncertain malignant cells, and (iii) benign cells. We assessed interobserver agreement using Kappa (κ) analysis as the measure of agreement. A total of 123 out of 250 (49%) patients showed CNHCs corresponding to malignant, uncertain malignant and benign cells, in 102/250 (41%), 15/250 (6%) and 6/250 (2%) cases, respectively. No CNHCs were detected in the blood of healthy subjects. Interobserver diagnostic variability was absent for CNHCs, low for malignant cells and limited for uncertain malignant and benign cells. Identification of CTCs in resectable NSCLC patients, using ISET technology and according to cytopathological criteria of malignancy, appears to be a new and promising field of cytopathology with potential relevance to lung oncology. © 2011 Blackwell Publishing Ltd.

BRCA1 and BRCA2 genetic testing-pitfalls and recommendations for managing variants of uncertain clinical significance.

PubMed

Eccles, D M; Mitchell, G; Monteiro, A N A; Schmutzler, R; Couch, F J; Spurdle, A B; Gómez-García, E B

2015-10-01

Increasing use of BRCA1/2 testing for tailoring cancer treatment and extension of testing to tumour tissue for somatic mutation is moving BRCA1/2 mutation screening from a primarily prevention arena delivered by specialist genetic services into mainstream oncology practice. A considerable number of gene tests will identify rare variants where clinical significance cannot be inferred from sequence information alone. The proportion of variants of uncertain clinical significance (VUS) is likely to grow with lower thresholds for testing and laboratory providers with less experience of BRCA. Most VUS will not be associated with a high risk of cancer but a misinterpreted VUS has the potential to lead to mismanagement of both the patient and their relatives. Members of the Clinical Working Group of ENIGMA (Evidence-based Network for the Interpretation of Germline Mutant Alleles) global consortium (www.enigmaconsortium.org) observed wide variation in practices in reporting, disclosure and clinical management of patients with a VUS. Examples from current clinical practice are presented and discussed to illustrate potential pitfalls, explore factors contributing to misinterpretation, and propose approaches to improving clarity. Clinicians, patients and their relatives would all benefit from an improved level of genetic literacy. Genetic laboratories working with clinical geneticists need to agree on a clinically clear and uniform format for reporting BRCA test results to non-geneticists. An international consortium of experts, collecting and integrating all available lines of evidence and classifying variants according to an internationally recognized system, will facilitate reclassification of variants for clinical use. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Composite Robust $$H_\\infty$$ Control for Uncertain Stochastic Nonlinear Systems with State Delay via Disturbance Observer

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

Liu, Yunlong; Wang, Hong; Guo, Lei

Here in this note, the robust stochastic stabilization and robust H_infinity control problems are investigated for uncertain stochastic time-delay systems with nonlinearity and multiple disturbances. By estimating the disturbance, which can be described by an exogenous model, a composite hierarchical control scheme is proposed that integrates the output of the disturbance observer with state feedback control law. Sufficient conditions for the existence of the disturbance observer and composite hierarchical controller are established in terms of linear matrix inequalities, which ensure the mean-square asymptotic stability of the resulting closed-loop system and the disturbance attenuation. It has been shown that the disturbancemore » rejection performance can also be achieved. A numerical example is provided to show the potential of the proposed techniques and encouraging results have been obtained.« less

Composite Robust $$H_\\infty$$ Control for Uncertain Stochastic Nonlinear Systems with State Delay via Disturbance Observer

DOE PAGES

Liu, Yunlong; Wang, Hong; Guo, Lei

2018-03-26

Here in this note, the robust stochastic stabilization and robust H_infinity control problems are investigated for uncertain stochastic time-delay systems with nonlinearity and multiple disturbances. By estimating the disturbance, which can be described by an exogenous model, a composite hierarchical control scheme is proposed that integrates the output of the disturbance observer with state feedback control law. Sufficient conditions for the existence of the disturbance observer and composite hierarchical controller are established in terms of linear matrix inequalities, which ensure the mean-square asymptotic stability of the resulting closed-loop system and the disturbance attenuation. It has been shown that the disturbancemore » rejection performance can also be achieved. A numerical example is provided to show the potential of the proposed techniques and encouraging results have been obtained.« less

Managment of thoracic empyema.

PubMed

Sherman, M M; Subramanian, V; Berger, R L

1977-04-01

Over a ten year period, 102 patients with thoracic empyemata were treated at Boston City Hospital. Only three patients died from the pleural infection while twenty-six succumbed to the associated diseases. Priniciples of management include: (1) thoracentesis; (2) antibiotics; (3) closed-tube thoracostomy; (4) sinogram; (5) open drainage; (6) empyemectomy and decortication in selected patients; and (7) bronchoscopy and barium swallow when the etiology is uncertain.

Initial Results of Multigene Panel Testing for Hereditary Breast and Ovarian Cancer and Lynch Syndrome.

PubMed

Howarth, Dt R; Lum, Sharon S; Esquivel, Pamela; Garberoglio, Carlos A; Senthil, Maheswari; Solomon, Naveenraj L

2015-10-01

Multigene panel testing for hereditary cancer risk has recently become commercially available; however, the impact of its use on patient care is undefined. We sought to evaluate results from implementation of panel testing in a multidisciplinary cancer center. We performed a retrospective review of consecutive patients undergoing genetic testing after initiating use of multigene panel testing at Loma Linda University Medical Center. From February 13 to August 25, 2014, 92 patients were referred for genetic testing based on National Comprehensive Cancer Network guidelines. Testing was completed in 90 patients. Overall, nine (10%) pathogenic mutations were identified: five BRCA1/2, and four in non-BRCA loci. Single-site testing identified one BRCA1 and one BRCA2 mutation. The remaining mutations were identified by use of panel testing for hereditary breast and ovarian cancer. There were 40 variants of uncertain significance identified in 34 patients. The use of panel testing more than doubled the identification rate of clinically significant pathogenic mutations that would have been missed with BRCA testing alone. The large number of variants of uncertain significance identified will require long-term follow-up for potential reclassification. Multigene panel testing provides additional information that may improve patient outcomes.

Morcellation worsens survival outcomes in patients with undiagnosed uterine leiomyosarcomas: A retrospective MITO group study.

PubMed

Raspagliesi, Francesco; Maltese, Giuseppa; Bogani, Giorgio; Fucà, Giovanni; Lepori, Stefano; De Iaco, Pierandrea; Perrone, Myriam; Scambia, Giovanni; Cormio, Gennaro; Bogliolo, Stefano; Bergamini, Alice; Bifulco, Giuseppe; Casali, Paolo Giovanni; Lorusso, Domenica

2017-01-01

To investigate the impact of morcellation on survival outcomes of patients affected by undiagnosed uterine sarcoma. This is a retrospective study performed in 8 referral centers of MITO group. Data of women undergoing morcellation for apparent benign uterine myomas who were ultimately diagnosed with stage I uterine sarcoma on final pathology were compared with data of women who did not undergo morcellation. Uterine sarcoma included: leiomyosarcomas (LMS), smooth muscle tumors of uncertain malignant potential (STUMP), low-grade endometrial stromal sarcomas (LG-ESS) and undifferentiated uterine sarcomas (UUS). Two-year survival outcomes were evaluated using Kaplan-Meir and Cox models. Overall 125 patients were identified: 31(24.8%), 21(16.8%) and 73(58.4%) patients had power morcellation during laparoscopy, non power morcellation during open surgery and non morcellation during open procedures, respectively. Considering patients affected by LMS, morcellation did not correlated with disease-free survival. However, patients undergoing either morcellation or power morcellation experienced a 3-fold increase risk of death in comparison to patients who had not morcellation (p=0.02). A trend towards an increase of recurrence was observed for patients undergoing morcellation for STUMP (HR 7.7, p=0.09); while no differences in survival outcomes were observed for patients with LG-ESS and UUS. Our data suggest that morcellation increase the risk of death in patients affected by undiagnosed LMS. Further prospective studies are warranted in order to assess the risk to benefit ratio of power morcellator utilization in patients with apparent benign uterine myomas. Copyright © 2016 Elsevier Inc. All rights reserved.

An optimization approach for observation association with systemic uncertainty applied to electro-optical systems

NASA Astrophysics Data System (ADS)

Worthy, Johnny L.; Holzinger, Marcus J.; Scheeres, Daniel J.

2018-06-01

The observation to observation measurement association problem for dynamical systems can be addressed by determining if the uncertain admissible regions produced from each observation have one or more points of intersection in state space. An observation association method is developed which uses an optimization based approach to identify local Mahalanobis distance minima in state space between two uncertain admissible regions. A binary hypothesis test with a selected false alarm rate is used to assess the probability that an intersection exists at the point(s) of minimum distance. The systemic uncertainties, such as measurement uncertainties, timing errors, and other parameter errors, define a distribution about a state estimate located at the local Mahalanobis distance minima. If local minima do not exist, then the observations are not associated. The proposed method utilizes an optimization approach defined on a reduced dimension state space to reduce the computational load of the algorithm. The efficacy and efficiency of the proposed method is demonstrated on observation data collected from the Georgia Tech Space Object Research Telescope.

Pathophysiology and implications of intradialytic hypertension.

PubMed

Van Buren, Peter Noel

2017-07-01

Intradialytic hypertension occurs regularly in 10--15% of hemodialysis patients. A large observational study recently showed that intradialytic hypertension of any magnitude increased mortality risk comparable to the most severe degrees of intradialytic hypotension. The present review review discusses the most recent evidence underlying the pathophysiology of intradialytic hypertension and implications for its management. Patients with intradialytic hypertension typically have small interdialytic weight gains, but bioimpedance spectroscopy shows these patients have significant chronic extracellular volume excess. Intradialytic hypertension patients have lower albumin and predialysis urea nitrogen levels, which may contribute to small reductions in osmolarity that prevents blood pressure decreases. Intradialytic vascular resistance surges remain implicated as the driving force for blood pressure increases, but mediators other than endothelin-1 may be responsible. Beyond dry weight reduction, the only controlled intervention shown to interrupt the blood pressure increase is lowering dialysate sodium. Patients with recurrent intradialytic hypertension should be identified as high-risk patients. Dry weight should be re-evaluated, even if patients do not clinically appear volume overloaded. Antihypertensive drugs should be prescribed because of the persistently elevated ambulatory blood pressure. Dialysate sodium reduction should be considered, although the long term effects of this intervention are uncertain.

Variational Assimilation of Sparse and Uncertain Satellite Data For 1D Saint-Venant River Models

NASA Astrophysics Data System (ADS)

Garambois, P. A.; Brisset, P.; Monnier, J.; Roux, H.

2016-12-01

Profusion of satellites are providing increasingly accurate measurements of continental water cyle, and water bodies variations while in situ observability is declining. The future Surface Water and Ocean Topography (SWOT) mission will provide maps of river surface elevations widths and slopes with an almost global coverage and temporal revisits. This will offer the possibility to address a larger variety of inverse problems in surface hydrology. Data assimilation techniques, that are broadly used in several scientific fields, aim to optimally combine models, system observations and prior information. Variational assimilation consists in iterative minimization of a discrepency measure between model outputs and observations, here for retrieving boundary conditions and parameters of a 1D Saint Venant model. Nevertheless, inferring river discharge and hydraulic parameters thanks to the observation of river surface is not straightforward. This is particularly true in the case of sparse and uncertain observations of flow state variables since they are governed by nonlinear physical processes. This paper investigates the identifiability of hydraulic controls given sparse and uncertain satellite observations of a river. The identifiability of river discharge alone and with roughness is tested for several spatio temporal patterns of river observations, including SWOT like observations. A new 1D Shallow water model with variational data assimilation, within the DassFlow chain is presented as well as postprocessing and observation operator dedicated to the future SWOT and SWOT simulator data. In view to decrease inverse problem dimensionality discharge is represented in a reduced basis. Moreover we introduce an original and reduced parametrization of the flow resistance that can account for various flow regimes along with a cross section design dedicated to remote sensing. We show which discharge temporal frequencies can be identified w.r.t observation ones and at which accuracy. Eventually the important question of the discharge identifiability potential between observation times and depending on the spatio-temporal sampling is adressed with respect to the wave lengths of the hydrological signals.

Cesarean scar ectopic pregnancy in a patient with multiple prior cesarean sections: a case report.

PubMed

Kiley, Jessica; Shulman, Lee P

2009-04-01

Cesarean scar pregnancy, an abnormal gestation implanted in the hysterotomy site of a previous cesarean section, is a unique type of ectopic pregnancy. Once uncommon, these life-threatening gestations are increasing in frequency. Outcomes depend on a high index of suspicion and early diagnosis. A 39-year-old, gravida 9, para 5-0-3-5, with a history of 5 cesarean deliveries, presented with vaginal bleeding secondary to cesarean scar pregnancy at 8 weeks' gestation. The patient, who desired future fertillty, was successfully treated conservatively with methotrexate and uterine artery embolization. Reports of cesarean scar pregnancies are rising in the literature, and we describe a scar pregnancy in a woman with multiple prior cesareans. Although the relationship between cesarean scar pregnancy and the number of previous cesarean deliveries is unclear, rising cesarean section rates worldwide will further increase overall incidence. The optimal treatment modality remains uncertain, but conservative management is appropriate when desired by the patient and administered under close observation.

[The scombroid syndrome, a potentially serious ichthyotoxicosis of uncertain pathogenesis: personal experience].

PubMed

Di Grande, A; Giuffrida, C; Gatta, C; Condorelli, B

1999-01-01

The aim of this report is to point out the potential seriousness of the scombroid syndrome which, on the basis of our experience, can be characterized by extremely serious symptoms. We describe 12 cases of scombroid syndrome: two-thirds of the patients presented with rapid worsening of their clinical condition and hypotension severe enough to require use of plasma-expanders and hospitalization in an Internal Medicine Department. In the youngest patient, hypotension and symptoms were so marked that intravenous administration of epinephrine, and hospitalization in the Intensive Care Unit were required. Thus, in contrast to reports in the literature, the scombroid syndrome should be considered as a potentially serious ichthyotoxicosis. The pathogenetic role played by histamine, poorly absorbed by the intestine and rapidly metabolized by the liver, should be reevaluated. The potential onset of serious clinical symptoms warrants prolonged observation of the patient in an environment equipped to deal with the not infrequent emergencies that can arise, even in young and healthy subjects.

A robust H∞-tracking design for uncertain Takagi-Sugeno fuzzy systems with unknown premise variables using descriptor redundancy approach

NASA Astrophysics Data System (ADS)

Hassan Asemani, Mohammad; Johari Majd, Vahid

2015-12-01

This paper addresses a robust H∞ fuzzy observer-based tracking design problem for uncertain Takagi-Sugeno fuzzy systems with external disturbances. To have a practical observer-based controller, the premise variables of the system are assumed to be not measurable in general, which leads to a more complex design process. The tracker is synthesised based on a fuzzy Lyapunov function approach and non-parallel distributed compensation (non-PDC) scheme. Using the descriptor redundancy approach, the robust stability conditions are derived in the form of strict linear matrix inequalities (LMIs) even in the presence of uncertainties in the system, input, and output matrices simultaneously. Numerical simulations are provided to show the effectiveness of the proposed method.

Guaranteed estimation of solutions to Helmholtz transmission problems with uncertain data from their indirect noisy observations

NASA Astrophysics Data System (ADS)

Podlipenko, Yu. K.; Shestopalov, Yu. V.

2017-09-01

We investigate the guaranteed estimation problem of linear functionals from solutions to transmission problems for the Helmholtz equation with inexact data. The right-hand sides of equations entering the statements of transmission problems and the statistical characteristics of observation errors are supposed to be unknown and belonging to certain sets. It is shown that the optimal linear mean square estimates of the above mentioned functionals and estimation errors are expressed via solutions to the systems of transmission problems of the special type. The results and techniques can be applied in the analysis and estimation of solution to forward and inverse electromagnetic and acoustic problems with uncertain data that arise in mathematical models of the wave diffraction on transparent bodies.

Rivals in the dark: how competition influences search in decisions under uncertainty.

PubMed

Phillips, Nathaniel D; Hertwig, Ralph; Kareev, Yaakov; Avrahami, Judith

2014-10-01

In choices between uncertain options, information search can increase the chances of distinguishing good from bad options. However, many choices are made in the presence of other choosers who may seize the better option while one is still engaged in search. How long do (and should) people search before choosing between uncertain options in the presence of such competition? To address this question, we introduce a new experimental paradigm called the competitive sampling game. We use both simulation and empirical data to compare search and choice between competitive and solitary environments. Simulation results show that minimal search is adaptive when one expects competitors to choose quickly or is uncertain about how long competitors will search. Descriptively, we observe that competition drastically reduces information search prior to choice. Copyright © 2014 Elsevier B.V. All rights reserved.

Contribution of MRI to clinically equivocal penile fracture cases.

PubMed

Türkay, Rüştü; Yenice, Mustafa Gürkan; Aksoy, Sema; Şeker, Gökhan; Şahin, Selçuk; İnci, Ercan; Tuğcu, Volkan; Taşcı, Ali İhsan

2016-11-01

Penile fracture is a surgical emergency defined as rupture of the tunica albuginea. Although most cases can be diagnosed with clinical evaluation, it has been stated in the literature that diagnosis in as many as 15% of cases can be challenging. In uncertain cases, imaging can help determine diagnosis. Present study included 20 cases where diagnosis could not be made with certainty and magnetic resonance imaging (MRI) was performed. MR images were examined for tunical rupture and accompanying pathologies. When rupture was observed, localization and length of rupture were noted. All patients underwent degloving surgery. All imaging findings were compared to surgical findings. MRI revealed 19 tunical ruptures. In 1 case, hematoma was seen with no sign of penile fracture. No urethral injuries were found. All MRI findings were confirmed during surgery. Performing MRI in clinically equivocal cases can provide crucial data to make precise diagnosis and improve patient management.

Radiotherapy Dose Fractionation under Parameter Uncertainty

NASA Astrophysics Data System (ADS)

Davison, Matt; Kim, Daero; Keller, Harald

2011-11-01

In radiotherapy, radiation is directed to damage a tumor while avoiding surrounding healthy tissue. Tradeoffs ensue because dose cannot be exactly shaped to the tumor. It is particularly important to ensure that sensitive biological structures near the tumor are not damaged more than a certain amount. Biological tissue is known to have a nonlinear response to incident radiation. The linear quadratic dose response model, which requires the specification of two clinically and experimentally observed response coefficients, is commonly used to model this effect. This model yields an optimization problem giving two different types of optimal dose sequences (fractionation schedules). Which fractionation schedule is preferred depends on the response coefficients. These coefficients are uncertainly known and may differ from patient to patient. Because of this not only the expected outcomes but also the uncertainty around these outcomes are important, and it might not be prudent to select the strategy with the best expected outcome.

An Audit on the Appropriateness of Coronary Computed Tomography Angiography Referrals in a Tertiary Cardiac Center.

PubMed

Alderazi, Ahmed Ali; Lynch, Mary

2017-01-01

In response to growing concerns regarding the overuse of coronary computed tomography angiography (CCTA) in the clinical setting, multiple societies, including the American College of Cardiology Foundation, have jointly published revised criteria regarding the appropriate use of this imaging modality. However, previous research indicates significant discrepancies in the rate of adherence to these guidelines. To assess the appropriateness of CCTA referrals in a tertiary cardiac center in Bahrain. This retrospective clinical audit examined the records of patients referred to CCTA between the April 1, 2015 and December 31, 2015 in Mohammed bin Khalifa Cardiac Center. Using information from medical records, each case was meticulously audited against guidelines to categorize it as appropriate, inappropriate, or uncertain. Of the 234 records examined, 176 (75.2%) were appropriate, 47 (20.1%) were uncertain, and 11 (4.7%) were inappropriate. About 74.4% of all referrals were to investigate coronary artery disease (CAD). The most common indication that was deemed appropriate was the detection of CAD in the setting of suspected ischemic equivalent in patients with an intermediate pretest probability of CAD (65.9%). Most referrals deemed inappropriate were requested to detect CAD in asymptomatic patients at low or intermediate risk of CAD (63.6%). This audit demonstrates a relatively low rate of inappropriate CCTA referrals, indicating the appropriate and efficient use of this resource in the Mohammed bin Khalifa Cardiac Center. Agreement on and reclassification of "uncertain" cases by guideline authorities would facilitate a deeper understanding of referral appropriateness.

Distributed neural network control for adaptive synchronization of uncertain dynamical multiagent systems.

PubMed

Peng, Zhouhua; Wang, Dan; Zhang, Hongwei; Sun, Gang

2014-08-01

This paper addresses the leader-follower synchronization problem of uncertain dynamical multiagent systems with nonlinear dynamics. Distributed adaptive synchronization controllers are proposed based on the state information of neighboring agents. The control design is developed for both undirected and directed communication topologies without requiring the accurate model of each agent. This result is further extended to the output feedback case where a neighborhood observer is proposed based on relative output information of neighboring agents. Then, distributed observer-based synchronization controllers are derived and a parameter-dependent Riccati inequality is employed to prove the stability. This design has a favorable decouple property between the observer and the controller designs for nonlinear multiagent systems. For both cases, the developed controllers guarantee that the state of each agent synchronizes to that of the leader with bounded residual errors. Two illustrative examples validate the efficacy of the proposed methods.

An imprecise probability approach for squeal instability analysis based on evidence theory

NASA Astrophysics Data System (ADS)

Lü, Hui; Shangguan, Wen-Bin; Yu, Dejie

2017-01-01

An imprecise probability approach based on evidence theory is proposed for squeal instability analysis of uncertain disc brakes in this paper. First, the squeal instability of the finite element (FE) model of a disc brake is investigated and its dominant unstable eigenvalue is detected by running two typical numerical simulations, i.e., complex eigenvalue analysis (CEA) and transient dynamical analysis. Next, the uncertainty mainly caused by contact and friction is taken into account and some key parameters of the brake are described as uncertain parameters. All these uncertain parameters are usually involved with imprecise data such as incomplete information and conflict information. Finally, a squeal instability analysis model considering imprecise uncertainty is established by integrating evidence theory, Taylor expansion, subinterval analysis and surrogate model. In the proposed analysis model, the uncertain parameters with imprecise data are treated as evidence variables, and the belief measure and plausibility measure are employed to evaluate system squeal instability. The effectiveness of the proposed approach is demonstrated by numerical examples and some interesting observations and conclusions are summarized from the analyses and discussions. The proposed approach is generally limited to the squeal problems without too many investigated parameters. It can be considered as a potential method for squeal instability analysis, which will act as the first step to reduce squeal noise of uncertain brakes with imprecise information.

Estimation for the Linear Model With Uncertain Covariance Matrices

NASA Astrophysics Data System (ADS)

Zachariah, Dave; Shariati, Nafiseh; Bengtsson, Mats; Jansson, Magnus; Chatterjee, Saikat

2014-03-01

We derive a maximum a posteriori estimator for the linear observation model, where the signal and noise covariance matrices are both uncertain. The uncertainties are treated probabilistically by modeling the covariance matrices with prior inverse-Wishart distributions. The nonconvex problem of jointly estimating the signal of interest and the covariance matrices is tackled by a computationally efficient fixed-point iteration as well as an approximate variational Bayes solution. The statistical performance of estimators is compared numerically to state-of-the-art estimators from the literature and shown to perform favorably.

Prediction-based control for LTI systems with uncertain time-varying delays and partial state knowledge

NASA Astrophysics Data System (ADS)

Léchappé, V.; Moulay, E.; Plestan, F.

2018-06-01

The stability of a prediction-based controller for linear time-invariant (LTI) systems is studied in the presence of time-varying input and output delays. The uncertain delay case is treated as well as the partial state knowledge case. The reduction method is used in order to prove the convergence of the closed-loop system including the state observer, the predictor and the plant. Explicit conditions that guarantee the closed-loop stability are given, thanks to a Lyapunov-Razumikhin analysis. Simulations illustrate the theoretical results.

Tea and Cardiovascular Disease

PubMed Central

Deka, Apranta; Vita, Joseph A.

2011-01-01

There is increasing evidence for a protective effect of tea consumption against cardiovascular disease. This review summarizes the available epidemiological data providing evidence for and against such an effect. We also review observational and intervention studies that investigated an effect of tea and tea extracts on cardiovascular risk factors, including blood pressure, serum lipids, diabetes mellitus, and obesity. Finally, we review potential mechanisms of benefit, including anti-inflammatory, anti-oxidant, and anti-proliferative effects, as well as favorable effects on endothelial function. Overall, the observational data suggest a benefit, but results are mixed and likely confounded by lifestyle and background dietary factors. The weight of evidence indicates favorable effects on risk factors and a number of plausible mechanisms have been elucidated in experimental and translational human studies. Despite the growing body evidence, it remains uncertain whether tea consumption should be recommended to the general population or to patients as a strategy to reduce cardiovascular risk. PMID:21477653

A robust adaptive observer for a class of singular nonlinear uncertain systems

NASA Astrophysics Data System (ADS)

Arefinia, Elaheh; Talebi, Heidar Ali; Doustmohammadi, Ali

2017-05-01

This paper proposes a robust adaptive observer for a class of singular nonlinear non-autonomous uncertain systems with unstructured unknown system and derivative matrices, and unknown bounded nonlinearities. Unlike many existing observers, no strong assumption such as Lipschitz condition is imposed on the recommended system. An augmented system is constructed, and the unknown bounds are calculated online using adaptive bounding technique. Considering the continuous nonlinear gain removes the chattering which may appear in practical applications such as analysis of electrical circuits and estimation of interaction force in beating heart robotic-assisted surgery. Moreover, a simple yet precise structure is attained which is easy to implement in many systems with significant uncertainties. The existence conditions of the standard form observer are obtained in terms of linear matrix inequality and the constrained generalised Sylvester's equations, and global stability is ensured. Finally, simulation results are obtained to evaluate the performance of the proposed estimator and demonstrate the effectiveness of the developed scheme.

Value of sentinel lymph node biopsy and adjuvant interferon treatment in thick (>4 mm) cutaneous melanoma: an observational study.

PubMed

Morera-Sendra, Natalia; Tejera-Vaquerizo, Antonio; Traves, Víctor; Requena, Celia; Bolumar, Isidro; Pla, Angel; Vázquez, Carlos; Soriano, Virtudes; Nagore, Eduardo

2016-01-01

The role of sentinel lymph node biopsy and the benefit of immunotherapy with interferon in thick (>4 mm) melanomas remain uncertain. Our aim was to assess the value of both sentinel lymph node (SLN) biopsy and immunotherapy in the prognosis of thick melanomas. A retrospective study based on a computerized patient database in which patients have been prospectively collected since 2005 was performed. Age, sex, location, Breslow thickness, tumor ulceration, regression, Clark level, tumor infiltrating lymphocytes, tumor mitotic rate, microscopic satellite and vascular invasion were included in the analysis. Disease-free (DFS), disease-specific (DSS) and overall (OS) survivals were evaluated by the Kaplan-Meier method and Cox regression analysis. A series of 141 patients with melanomas thicker than 4 mm were included. Multivariate regression showed a worse prognosis in SLN-positive patients with respect to SLN biopsy-negative patients (DFS, hazard ratio [HR] 2, p = 0.04; DSS, HR 2.2, p = 0.002; OS, HR 2.4, p = 0.02). The observational group was shown to have a worse prognosis than the SLN-positive group but was very similar to the clinically positive group. Immunotherapy with high-dose interferon showed a protective effect (DFS, HR 0.5, p = 0.02; DSS, HR 0.3, p = 0.001; OS, HR 0.3, p = 0.001). Our data indicate that SLN biopsy and adjuvant interferon should be considered for patients with thick melanomas.

Randomized comparison of Zotarolimus-Eluting Endeavor Sprint versus bare-metal stent implantation in uncertain drug-eluting stent candidates: rationale, design, and characterization of the patient population for the Zotarolimus-eluting Endeavor Sprint stent in uncertain DES candidates study.

PubMed

Valgimigli, Marco; Patialiakas, Athanasios; Thury, Attila; Colangelo, Salvatore; Campo, Gianluca; Tebaldi, Matteo; Ungi, Imre; Tondi, Stefano; Roffi, Marco; Menozzi, Alberto; de Cesare, Nicoletta; Garbo, Roberto; Meliga, Emanuele; Testa, Luca; Gabriel, Henrique M; Airoldi, Flavio; Ferlini, Marco; Liistro, Francesco; Dellavalle, Antonio; Vranckx, Pascal; Briguori, Carlo

2013-11-01

The use of drug-eluting stent (DES) instead of bare-metal stent (BMS) in patients at high stent thrombosis or bleeding risk as well as in those at low restenosis risk (ie, uncertain DES candidates) remains a matter of debate. Zotarolimus-Eluting Endeavor Sprint stent (E-ZES) (Santa Rosa, CA) is a hydrophilic polymer-based second-generation device with unique drug fast-release profile, which may allow for a shorter dual antiplatelet therapy (DAPT) duration without safety concerns. The primary objective is to assess whether E-ZES implantation followed by a shorter than currently recommended course of DAPT will decrease the incidence of 12-month major adverse cardiovascular events as compared with BMS in undefined DES recipients. Actual duration of DAPT regimen will be dictated by patients' characteristics and not by stent type and, as such, can be as short as 30 days after intervention in both stent groups. The ZEUS study is an open-label randomized clinical trial conducted at 20 clinical sites in Italy, Switzerland, Portugal, and Hungary. With 1,600 individuals, this study will have 85% power to detect a 33% difference in the primary end point consisting of the composite of death, nonfatal myocardial infarction, or target vessel revascularization. The ZEUS trial aims to assess whether the use of E-ZES, followed by a DAPT duration regimen based on patients' characteristics and not by stent type, is superior to conventional BMS implantation in undefined DES recipients who qualify for the presence of high thrombosis, bleeding, or low restenosis risk criteria. © 2013.

Glycated hemoglobin level is an independent predictor of major adverse cardiac events after nonfatal acute myocardial infarction in nondiabetic patients: A retrospective observational study.

PubMed

Chen, Chin-Lan; Yen, David H-T; Lin, Chin-Sheng; Tsai, Shih-Hung; Chen, Sy-Jou; Sheu, Wayne H-H; Hsu, Chin-Wang

2017-05-01

The effect of glycemic control on the prognosis of nondiabetic patients after acute myocardial infarction (AMI) remains uncertain. We investigated whether glycated hemoglobin (HbA1c) is associated with adverse outcomes after AMI in nondiabetic patients. In this observational study, we enrolled nondiabetic patients with AMI in the emergency department of 2 medical centers from January 2011 to September 2014. All patients received primary percutaneous coronary intervention and were divided into 4 groups according to the interquartile range of average HbA1c level (Group I, ≤5.6%; Group II, 5.6%-5.8%; Group III, 5.8%-6.0%; and Group IV, >6.0%). Multivariate logistic analysis was performed to estimate the correlation of HbA1c with major adverse cardiac events (MACEs) after AMI. In total, 267 eligible patients were enrolled; 48 patients (18%) developed MACEs within a median follow-up of 178 days. Univariate analysis showed HbA1c > 6.0%, with a higher risk of MACEs in Group IV than in Group I (odds ratio [OR]: 2.733; 95% confidence interval [CI]: 1.123-6.651 vs OR: 1.511; 95% CI: 0.595-3.835). Multivariate analysis revealed an approximately 3.8 times higher risk of MACEs in Group IV than in Group I (OR: 3.769; 95% CI: 1.30-10.86). The HbA1 level is a significant predictor of MACEs after AMI in nondiabetic patients.

Multiobjective optimization in structural design with uncertain parameters and stochastic processes

NASA Technical Reports Server (NTRS)

Rao, S. S.

1984-01-01

The application of multiobjective optimization techniques to structural design problems involving uncertain parameters and random processes is studied. The design of a cantilever beam with a tip mass subjected to a stochastic base excitation is considered for illustration. Several of the problem parameters are assumed to be random variables and the structural mass, fatigue damage, and negative of natural frequency of vibration are considered for minimization. The solution of this three-criteria design problem is found by using global criterion, utility function, game theory, goal programming, goal attainment, bounded objective function, and lexicographic methods. It is observed that the game theory approach is superior in finding a better optimum solution, assuming the proper balance of the various objective functions. The procedures used in the present investigation are expected to be useful in the design of general dynamic systems involving uncertain parameters, stochastic process, and multiple objectives.

Stabilization of a Quadrotor With Uncertain Suspended Load Using Sliding Mode Control

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

Zhou, Xu; Liu, Rui; Zhang, Jiucai

2016-08-21

The stability and trajectory control of a quadrotor carrying a suspended load with a fixed known mass has been extensively studied in recent years. However, the load mass is not always known beforehand in practical applications. This mass uncertainty brings uncertain disturbances to the quadrotor system, causing existing controllers to have a worse performance or to be collapsed. To improve the quadrotor's stability in this situation, we investigate the impacts of the uncertain load mass on the quadrotor. By comparing the simulation results of two controllers -- the proportional-derivative (PD) controller and the sliding mode controller (SMC) driven by amore » sliding mode disturbance of observer (SMDO), the quadrotor's performance is verified to be worse as the uncertainty increases. The simulation results also show a controller with stronger robustness against disturbances is better for practical applications.« less

Robust passive control for a class of uncertain neutral systems based on sliding mode observer.

PubMed

Liu, Zhen; Zhao, Lin; Kao, Yonggui; Gao, Cunchen

2017-01-01

The passivity-based sliding mode control (SMC) problem for a class of uncertain neutral systems with unmeasured states is investigated. Firstly, a particular non-fragile state observer is designed to generate the estimations of the system states, based upon which a novel integral-type sliding surface function is established for the control process. Secondly, a new sufficient condition for robust asymptotic stability and passivity of the resultant sliding mode dynamics (SMDs) is obtained in terms of linear matrix inequalities (LMIs). Thirdly, the finite-time reachability of the predesigned sliding surface is ensured by resorting to a novel adaptive SMC law. Finally, the validity and superiority of the scheme are justified via several examples. Copyright © 2016 ISA. Published by Elsevier Ltd. All rights reserved.

The stories they tell: How third year medical students portray patients, family members, physicians, and themselves in difficult encounters.

PubMed

Shapiro, Johanna; Rakhra, Pavandeep; Wong, Adrianne

2016-10-01

Physicians have long had patients whom they have labeled "difficult", but little is known about how medical students perceive difficult encounters with patients. In this study, we analyzed 134 third year medical students' reflective essays written over an 18-month period about difficult student-patient encounters. We used a qualitative computerized software program, Atlas.ti to analyze students' observations and reflections. Main findings include that students described patients who were angry and upset; noncompliant with treatment plans; discussed "nonmedical" problems; fearful, worried, withdrawn, or "disinterested" in their health. Students often described themselves as anxious, uncertain, confused, and frustrated. Nevertheless, they saw themselves behaving in empathic and patient-centered ways while also taking refuge in "standard" behaviors not necessarily appropriate to the circumstances. Students rarely mentioned receiving guidance from attendings regarding how to manage these challenging interactions. These third-year medical students recognized the importance of behaving empathically in difficult situations and often did so. However, they often felt overwhelmed and frustrated, resorting to more reductive behaviors that did not match the needs of the patient. Students need more guidance from attending physicians in order to approach difficult interactions with specific problem-solving skills while maintaining an empathic, patient-centered context.

Electroconvulsive therapy--efficacy and side-effects.

PubMed

Moksnes, Kjell Martin; Ilner, Stein Opjordsmoen

2010-12-16

Efficacy of electroconvulsive therapy (ECT) and duration of associated side effects is uncertain. We wanted to study indications, efficacy, time to response and side effects. ECT-protocols and medical records (from the period 1960-95) in three psychiatric wards of Dikemark Mental Hospital, Norway were systematically assessed. 141 persons underwent 241 ECT series comprising 1960 treatment sessions. Major depressive disorder was the main diagnosis in most patients 124 [88 %]. Before ECT, 129 (91 %) patients had been treated with at least one antidepressant, 107 (76 %) with at least two and 67 (48 %) with two different classes of antidepressants without sufficient clinical recovery from the incident. 31 (22 %) had received lithium before ECT. Within four weeks after the first ECT, 120 (85 %) patients had recovered. 61 of these achieved remission and were discharged within four weeks. After the first ECT series, 92 patients showed signs of improvement. 71 (77 %) had signs of improvement within 6 days. Side effects were noted after 123 of totally 241 series (51 %). Five patients experienced serious complications. Interpretation. The immediate effect of ECT was good and signs of recovery were observed in most patients during the first week. Depressed psychotic patients and the elderly seemed to respond best. Considering these patients' serious and long-lasting disorders ECT was fairly safe and well tolerated.

Heightened aversion to risk and loss in depressed patients with a suicide attempt history.

PubMed

Baek, Kwangyeol; Kwon, JaeHyung; Chae, Jeong-Ho; Chung, Yong An; Kralik, Jerald D; Min, Jung-Ah; Huh, HyuJung; Choi, Kyung Mook; Jang, Kuk-In; Lee, Na-Bin; Kim, Sunyoung; Peterson, Bradley S; Jeong, Jaeseung

2017-09-11

Suicide attempters have been found to be impaired in decision-making; however, their specific biases in evaluating uncertain outcomes remain unclear. Here we tested the hypothesis that suicidal behavior is associated with heightened aversion to risk and loss, which might produce negative predictions about uncertain future events. Forty-five depressed patients with a suicide attempt history, 47 nonsuicidal depressed patients, and 75 healthy controls participated in monetary decision-making tasks assessing risk and loss aversion. Suicide attempters compared with the other groups exhibited greater aversion to both risk and loss during gambles involving potential loss. Risk and loss aversion correlated with each other in the depressed patients, suggesting that a common pathophysiological mechanism underlies these biases. In addition, emotion regulation via suppression, a detrimental emotional control strategy, was positively correlated with loss aversion in the depressed patients, also implicating impairment in regulatory processes. A preliminary fMRI study also found disrupted neural responses to potential gains and losses in the subgenual anterior cingulate cortex, insula cortex, and left amygdala, brain regions involved in valuation, emotion reactivity, and emotion regulation. The findings thus implicate heightened negative valuation in decision-making under risk, and impaired emotion regulation in depressed patients with a history of suicide attempts.

Differences in omega-3 and omega-6 polyunsaturated fatty acid consumption in people at ultra-high risk of psychosis, first-episode schizophrenia, and in healthy controls.

PubMed

Pawełczyk, Tomasz; Trafalska, Elżbieta; Pawełczyk, Agnieszka; Kotlicka-Antczak, Magdalena

2017-12-01

Supplementation with omega-3 PUFA showed efficacy in reducing the risk of transition into psychosis in UHR individuals. It is uncertain whether dietary patterns can be partly responsible for n-3 deficiencies observed in susceptible participants before the diagnosis of schizophrenia. The study was designed to assess differences in omega-3 and omega-6 PUFA consumption in healthy controls (HC), UHR participants and FES patients as well as to verify the hypothesis that dietary changes in PUFA consumption are present before active psychosis develops, that is, in UHR individuals. Dietary habits during the previous year were assessed in 34 patients at UHR of psychosis, 33 patients diagnosed with FES and 33 HC participants using a validated Food-Frequency Questionnaire and the Polish Food Composition Tables. Significant differences in omega-3 and omega-6 PUFA intake were observed between study groups. UHR and FES groups reported significantly higher consumption of omega-6 PUFA in comparison with HC. FES patients also reported a higher consumption of alpha-linolenic acid (omega-3) in comparison with HC. No significant differences were seen in consumption of long-chain marine PUFA. Differences in omega-6 and omega-3 PUFA consumption exist before development of psychotic symptoms, fulfilling the criteria of schizophrenia. © 2015 Wiley Publishing Asia Pty Ltd.

Two-stage revisions for culture-negative infected total knee arthroplasties: A five-year outcome in comparison with one-stage and two-stage revisions for culture-positive cases.

PubMed

Li, Heng; Ni, Ming; Li, Xiang; Zhang, Qingmeng; Li, Xin; Chen, Jiying

2017-03-01

Culture-negative periprosthetic joint infection (PJI) is very intractable when dealing with an infected total knee arthroplasty (TKA) patient. Two-stage revision has been proved to be a reliable solution for PJI patients. Whether it is still credible for culture-negative infected patients remains uncertain. Our group retrospectively reviewed all total knee revision patients from January 2003 to January 2014, 145 PJI patients were diagnosed as infection with the PJI diagnostic criteria and 129 patients were successfully followed. As different treating strategies were utilized, these patients were divided into culture-negative (18 cases, CN) group, culture-positive with one-stage revision group (CP1, 21 cases) and culture-positive with two-stage revision group (CP2, 87 cases) groups. The CN group and CP2 group underwent two-stage revision with antibiotic loaded cement spacers and intravenous antibiotics, CP1 group received one-stage revision. All the culture results and relevant medical records were thoroughly reviewed. The mean follow-up time was 59.5 ± 32.3 months (range 12-158 months). The culture-negative rate was 14.2%. The overall infection control rate was 92.12%. Infection recurrence was observed in two cases in CP1 group (9.09%), six cases in CP2 group (6.90%) and two cases in CN group (11.1%). The reinfection rate of culture-negative patients and culture-positive patients was 7.34% and 11.1% with no significant difference (p = 0.94). No statistically difference was observed between CP2 group and CN group (p = 0.90). No Spacer fracture or dislocation was observed. With combined or broad spectrum antibiotics, two-stage revision showed comparable outcome when treating culture-negative infected TKA patients at five-year follow-up. Copyright © 2016. Published by Elsevier B.V.

Asthma caused by potassium aluminium tetrafluoride: a case series.

PubMed

Laštovková, Andrea; Klusáčková, Pavlina; Fenclová, Zdenka; Bonneterre, Vincent; Pelclová, Daniela

2015-01-01

The objective of this study is to describe a case-series of potassium aluminium tetrafluoride (KAlF(4))-induced occupational asthma (OA) and/or occupational rhinitis (OR). The study involves five patients from a heat-exchanger production line who were examined (including specific inhalation challenge tests) for suspected OA and/or OR caused by a flux containing almost 100% KAlF(4) - with fluorides' workplace air concentrations ranging between 1.7 and 2.8 mg/m(3). No subject had a previous history of asthma. All five patients had a positive specific challenge test (three patients were diagnosed with OA alone, one with OR and one with both OR and OA). At the follow-up visit, after three years on average, all patients needed permanent corticosteroid therapy (four topical, one oral). After elimination from the exposure, only one of the observed subjects gave an indication of an improvement, two subjects stabilized and two worsened. Our case series focuses on the correlation between patients' exposure to fluorides in air-conditioner production and the subsequent occurrence of OR/OA. Currently, it is uncertain whether these OR/OA were caused by hypersensitivity or irritation.

[Prostatic Stromal Tumors of Uncertain Malignant Potential (STUMP): definition, pathology, prognosis and management].

PubMed

Michaud, S; Moreau, A; Braud, G; Renaudin, K; Branchereau, J; Bouchot, O; Rigaud, J

2012-10-01

Prostatic Stromal Tumors of Uncertain Malignant Potential (STUMP) are rare tumor of the prostate of mesenchymal origin, accounting, with sarcoma for 0.1-0.2% of all malignant prostatic tumours. They however require to be individualized, to differentiate it from a benign prostatic hyperplasia or a sarcoma of the prostate. The therapeutic management should be made keeping in mind the risk of degeneration towards a malignant shape. Although the appropriate treatment is unknown, radical prostatectomy seem to be the treatment of reference, especially for young patient or for extensive lesion. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Children's Causal Inferences from Conflicting Testimony and Observations

ERIC Educational Resources Information Center

Bridgers, Sophie; Buchsbaum, Daphna; Seiver, Elizabeth; Griffiths, Thomas L.; Gopnik, Alison

2016-01-01

Preschoolers use both direct observation of statistical data and informant testimony to learn causal relationships. Can children integrate information from these sources, especially when source reliability is uncertain? We investigate how children handle a conflict between what they hear and what they see. In Experiment 1, 4-year-olds were…

Financial arrangements for health systems in low-income countries: an overview of systematic reviews

PubMed Central

Wiysonge, Charles S; Paulsen, Elizabeth; Lewin, Simon; Ciapponi, Agustín; Herrera, Cristian A; Opiyo, Newton; Pantoja, Tomas; Rada, Gabriel; Oxman, Andrew D

2017-01-01

Background One target of the Sustainable Development Goals is to achieve "universal health coverage, including financial risk protection, access to quality essential health-care services and access to safe, effective, quality and affordable essential medicines and vaccines for all". A fundamental concern of governments in striving for this goal is how to finance such a health system. This concern is very relevant for low-income countries. Objectives To provide an overview of the evidence from up-to-date systematic reviews about the effects of financial arrangements for health systems in low-income countries. Secondary objectives include identifying needs and priorities for future evaluations and systematic reviews on financial arrangements, and informing refinements in the framework for financial arrangements presented in the overview. Methods We searched Health Systems Evidence in November 2010 and PDQ-Evidence up to 17 December 2016 for systematic reviews. We did not apply any date, language, or publication status limitations in the searches. We included well-conducted systematic reviews of studies that assessed the effects of financial arrangements on patient outcomes (health and health behaviours), the quality or utilisation of healthcare services, resource use, healthcare provider outcomes (such as sick leave), or social outcomes (such as poverty, employment, or financial burden of patients, e.g. out-of-pocket payment, catastrophic disease expenditure) and that were published after April 2005. We excluded reviews with limitations important enough to compromise the reliability of the findings. Two overview authors independently screened reviews, extracted data, and assessed the certainty of evidence using GRADE. We prepared SUPPORT Summaries for eligible reviews, including key messages, 'Summary of findings' tables (using GRADE to assess the certainty of the evidence), and assessments of the relevance of findings to low-income countries. Main results We identified 7272 reviews and included 15 in this overview, on: collection of funds (2 reviews), insurance schemes (1 review), purchasing of services (1 review), recipient incentives (6 reviews), and provider incentives (5 reviews). The reviews were published between 2008 and 2015; focused on 13 subcategories; and reported results from 276 studies: 115 (42%) randomised trials, 11 (4%) non-randomised trials, 23 (8%) controlled before-after studies, 51 (19%) interrupted time series, 9 (3%) repeated measures, and 67 (24%) other non-randomised studies. Forty-three per cent (119/276) of the studies included in the reviews took place in low- and middle-income countries. Collection of funds: the effects of changes in user fees on utilisation and equity are uncertain (very low-certainty evidence). It is also uncertain whether aid delivered under the Paris Principles (ownership, alignment, harmonisation, managing for results, and mutual accountability) improves health outcomes compared to aid delivered without conforming to those principles (very low-certainty evidence). Insurance schemes: community-based health insurance may increase service utilisation (low-certainty evidence), but the effects on health outcomes are uncertain (very low-certainty evidence). It is uncertain whether social health insurance improves utilisation of health services or health outcomes (very low-certainty evidence). Purchasing of services: it is uncertain whether increasing salaries of public sector healthcare workers improves the quantity or quality of their work (very low-certainty evidence). Recipient incentives: recipient incentives may improve adherence to long-term treatments (low-certainty evidence), but it is uncertain whether they improve patient outcomes. One-time recipient incentives probably improve patient return for start or continuation of treatment (moderate-certainty evidence) and may improve return for tuberculosis test readings (low-certainty evidence). However, incentives may not improve completion of tuberculosis prophylaxis, and it is uncertain whether they improve completion of treatment for active tuberculosis. Conditional cash transfer programmes probably lead to an increase in service utilisation (moderate-certainty evidence), but their effects on health outcomes are uncertain. Vouchers may improve health service utilisation (low-certainty evidence), but the effects on health outcomes are uncertain (very low-certainty evidence). Introducing a restrictive cap may decrease use of medicines for symptomatic conditions and overall use of medicines, may decrease insurers' expenditures on medicines (low-certainty evidence), and has uncertain effects on emergency department use, hospitalisations, and use of outpatient care (very low-certainty evidence). Reference pricing, maximum pricing, and index pricing for drugs have mixed effects on drug expenditures by patients and insurers as well as the use of brand and generic drugs. Provider incentives: the effects of provider incentives are uncertain (very low-certainty evidence), including: the effects of provider incentives on the quality of care provided by primary care physicians or outpatient referrals from primary to secondary care, incentives for recruiting and retaining health professionals to serve in remote areas, and the effects of pay-for-performance on provider performance, the utilisation of services, patient outcomes, or resource use in low-income countries. Authors' conclusions Research based on sound systematic review methods has evaluated numerous financial arrangements relevant to low-income countries, targeting different levels of the health systems and assessing diverse outcomes. However, included reviews rarely reported social outcomes, resource use, equity impacts, or undesirable effects. We also identified gaps in primary research because of uncertainty about applicability of the evidence to low-income countries. Financial arrangements for which the effects are uncertain include external funding (aid), caps and co-payments, pay-for-performance, and provider incentives. Further studies evaluating the effects of these arrangements are needed in low-income countries. Systematic reviews should include all outcomes that are relevant to decision-makers and to people affected by changes in financial arrangements. Financial arrangements for health systems in low-income countries What is the aim of this overview? The aim of this Cochrane Overview is to provide a broad summary of what is known about the effects of financial arrangements for health systems in low-income countries. This overview is based on 15 systematic reviews. Each of these systematic reviews searched for studies that evaluated different types of financial arrangements within the scope of the review question. The reviews included a total of 276 studies. This overview is one of a series of four Cochrane Overviews that evaluate different health system arrangements. Main results What are the effects of different ways of collecting funds to pay for health services? Two reviews looked for studies that addressed this question and found the following. - The effects of changes in user fees on utilisation and equity are uncertain (very low-certainty evidence). - It is uncertain whether aid delivered under Paris Principles (ownership, alignment, harmonisation, managing for results, and mutual accountability) improves health compared to aid delivered without conforming to those principles (very low-certainty evidence). What are the effects of different types of insurance schemes? One systematic review looked for studies that addressed this question and found the following. - Community-based health insurance may increase people's use of services (low-certainty evidence), but the effects on people's health are uncertain. It is uncertain whether social health insurance increases people's use of services (very low-certainty evidence). What are the effects of different ways of paying for health services? One systematic review looked for studies that addressed this question and found the following. - It is uncertain whether increasing salaries of public sector healthcare workers improves the quantity or quality of their work. What are the effects of different types of financial incentives for recipients of care? Six systematic reviews looked for studies that addressed this question and found the following. - Giving healthcare recipients incentives may improve their adherence to long-term treatments (low-certainty evidence), but it is uncertain whether they improve people's health. - Giving healthcare recipients one-time incentives probably leads more people to return to start or continue treatment for tuberculosis (moderate-certainty evidence). The certainty of the evidence for other types of recipient incentives for tuberculosis is low or very low. - Conditional cash transfer programmes (giving money to recipients of care on the condition that they take a specified action to improve their health) probably increase people's use of services (moderate-certainty evidence), but have mixed effect on people's health. - Vouchers may improve people's use of health services (low-certainty evidence) but have mixed effects on people's health (low-certainty evidence). - A combination of a ceiling and co-insurance probably slightly decreases the overall use of medicines (moderate-certainty evidence) and may increase health service utilisation (low-certainty evidence). The certainty of the evidence for the effects of other combinations of caps, co-insurance, co-payments, and ceilings is low or very low. - Limits on how much insurers pay for different groups of drugs (reference pricing, maximum pricing, and index pricing) have mixed effects on drug expenditures by patients and insurers as well as the use of brand and generic drugs. What are the effects of different types of financial incentives for health workers? Five systematic reviews looked for studies that addressed this question and found the following. - We are uncertain whether pay-for-performance improves health worker performance, people's use of services, people's health, or resource use in low-income countries (very low-certainty evidence). - We are uncertain whether financial incentives for health workers improve the quality of care provided by primary care physicians or outpatient referrals from primary to secondary care (very low-certainty evidence). - There is no rigorous research evaluating incentives (e.g. bursaries or scholarships linked to future practice location, rural allowances) for recruiting health workers to serve in remote areas. It is uncertain whether giving health workers incentives lead more of them to stay in underserved areas (very low-certainty evidence). - No studies assessed the effects of financial interventions on the movement of health workers between public and private organisations in low- and middle-income countries. How up to date is this overview? The overview authors searched for systematic reviews published up to 17 December 2016. PMID:28891235

Trimethoprim/sulfamethoxazole-induced phenytoin toxicity in the elderly: a population-based study

PubMed Central

Antoniou, Tony; Gomes, Tara; Mamdani, Muhammad M; Juurlink, David N

2011-01-01

AIMS Pharmacokinetic studies suggest that trimethoprim (TMP) can inhibit the hepatic metabolism of phenytoin, but the clinical relevance of this is uncertain. We studied the risk of phenytoin toxicity following the prescription of trimethoprim/sulfamethoxazole (TMP/SMX), a commonly used antibiotic, among elderly patients receiving phenytoin. METHODS We conducted a population-based, nested case–control study of a cohort of Ontario residents aged 66 years of age or older treated with phenytoin over a 17-year period (April 1 1992 to March 31 2009). Within this group, case patients were those hospitalized with phenytoin toxicity. For each case, we identified up to four control patients from the same cohort, matched for age and sex, and determined the odds ratio (OR) for the association between phenytoin toxicity and receipt of TMP/SMX in the preceding 30 days. RESULTS Among 58 429 elderly patients receiving phenytoin during the study period, we identified 796 case patients hospitalized for phenytoin toxicity and 3148 matched controls. Following multivariable adjustment for potential confounders, we observed a more than doubling of the risk of phenytoin toxicity following the receipt of TMP/SMX [adjusted OR 2.11, 95% confidence interval (CI) 1.24, 3.60]. In contrast, we observed no such risk with amoxicillin, an antibiotic with similar indications but not expected to interact with phenytoin (adjusted OR 1.12, 95% CI 0.64, 1.98). CONCLUSION Among older patients receiving phenytoin, treatment with TMP/SMX is associated with a more than twofold increase in the risk of phenytoin toxicity. When clinically appropriate, alternate antibiotics should be considered for these patients. PMID:21395647

Sudden cardiac death in adults with congenital heart disease.

PubMed

Yap, Sing-Chien; Harris, Louise

2009-12-01

Sudden cardiac death is one of the leading causes of death in patients with congenital heart disease, especially in patients with repaired cyanotic and left heart obstructive lesions. While the overall annual incidence of sudden cardiac death is relatively low, estimated at 0.09% per year, this nonetheless represents a many-fold increase over that of comparable age-matched control populations. The most frequent cause of sudden cardiac death is believed to be arrhythmic, usually ventricular arrhythmia. Most studies investigating risk factors for ventricular arrhythmia and/or sudden cardiac death have focused on patients with repaired tetralogy of Fallot and patients with Mustard/Senning repair for complete transposition of the great arteries. Despite a multitude of risk factors, their predictive value for the occurrence of sudden cardiac death is relatively low. Current experience with implantable cardioverter defibrillators in this patient population is limited to observational studies and the selection of patients for prophylactic implantable cardioverter defibrillator implantation is impeded both by the absence of randomized trials and weak predictors. Catheter ablation of ventricular tachycardia has emerged as a promising therapy for abolishing or reducing the burden of arrhythmia but experience is still limited and the impact on long-term outcome uncertain. Future studies will have to focus on improving risk stratification of patients with congenital heart disease.

Patients' experiences with continuum of care across hospitals. A multilevel analysis of Consumer Quality Index Continuum of Care.

PubMed

Kollen, Boudewijn J; Groenier, Klaas H; Berendsen, Annette J

2011-05-01

Communication between professionals is essential because it contributes to an optimal continuum of care. Whether patients experience adequate continuum of care is uncertain. To address this, a questionnaire was developed to elucidate this care process from a patients' perspective. In this study, the instrument's ability to measure differences in "Consumer Quality Index Continuum of Care" scores between hospitals was investigated. The questionnaire was mailed to a random sample of 2159 patients and comprised of 22 items divided over four domains, GP approach, GP referral, specialist and collaboration. Multilevel analysis was conducted to identify case-mix and determine this questionnaire's ability to measure differences in domain scores between hospitals. Based on a 65% response rate, 1404 questionnaires were available for analysis. Case-mix of patient characteristics across hospitals could not be demonstrated. Some differences in scores between hospitals were observed. At most two in eight hospitals showed different domain scores. The ability of this questionnaire to measure differences in continuum of care scores between hospitals is limited. The outcome of this survey suggests that hospitals provide a similar level of continuum of care from a patient's perspective. This questionnaire is especially useful for measuring differences between patients. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Commentary on "Prognostic effect of carcinoma in situ in muscle-invasive urothelial carcinoma patients receiving neoadjuvant chemotherapy."

PubMed

Thomas, D E; Kaimakliotis, H Z; Rice, K R; Pereira, J A; Johnston, P; Moore, M L; Reed, A; Cregar, D M; Franklin, C; Loman, R L; Koch, M O; Bihrle, R; Foster, R S; Masterson, T A; Gardner, T A; Sundaram, C P; Powell, C R; Beck, Sdw; Grignon, D J; Cheng, L; Albany, C; Hahn, N M

2018-07-01

Carcinoma in situ (CIS) is a poor prognostic finding in urothelial carcinoma. However, its significance in muscle-invasive urothelial carcinoma (MIUC) treated with neoadjuvant chemotherapy (NAC) is uncertain. We assessed the effect of CIS found in pretreatment transurethral resection of bladder tumor (TURBT) biopsies on the pathologic and clinical outcomes. Subjects with MIUC treated with NAC before cystectomy were identified. The pathologic complete response (pCR) rates stratified by TURBT CIS status were compared. The secondary analyses included tumor response, progression-free survival (PFS), overall survival (OS), and an exploratory post hoc analysis of patients with pathologic CIS only (pTisN0) at cystectomy. A total of 137 patients with MIUC were identified. TURBT CIS was noted in 30.7% of the patients. The absence of TURBT CIS was associated with a significantly increased pCR rate (23.2% vs. 9.5%; odds ratio = 4.08; 95% CI: 1.19-13.98; P = 0.025). Stage pTisN0 disease was observed in 19.0% of the TURBT CIS patients. TURBT CIS status did not significantly affect the PFS or OS outcomes. Post hoc analysis of the pTisN0 patients revealed prolonged median PFS (104.5 vs. 139.9 months; P = 0.055) and OS (104.5 vs. 152.3 months; P = 0.091) outcomes similar to those for the pCR patients. The absence of CIS on pretreatment TURBT in patients with MIUC undergoing NAC was associated with increased pCR rates, with no observed differences in PFS or OS. Isolated CIS at cystectomy was frequently observed, with lengthy PFS and OS durations similar to those for pCR patients. Further studies aimed at understanding the biology and clinical effect of CIS in MIUC are warranted. Copyright © 2018 Elsevier Inc. All rights reserved.

Prognostic Effect of Carcinoma In Situ in Muscle-invasive Urothelial Carcinoma Patients Receiving Neoadjuvant Chemotherapy.

PubMed

Thomas, Derek E; Kaimakliotis, Hristos Z; Rice, Kevin R; Pereira, Jose A; Johnston, Paul; Moore, Marietta L; Reed, Angela; Cregar, Dylan M; Franklin, Cindy; Loman, Rhoda L; Koch, Michael O; Bihrle, Richard; Foster, Richard S; Masterson, Timothy A; Gardner, Thomas A; Sundaram, Chandru P; Powell, Charles R; Beck, Stephen D W; Grignon, David J; Cheng, Liang; Albany, Costantine; Hahn, Noah M

2017-08-01

Carcinoma in situ (CIS) is a poor prognostic finding in urothelial carcinoma. However, its significance in muscle-invasive urothelial carcinoma (MIUC) treated with neoadjuvant chemotherapy (NAC) is uncertain. We assessed the effect of CIS found in pretreatment transurethral resection of bladder tumor (TURBT) biopsies on the pathologic and clinical outcomes. Subjects with MIUC treated with NAC before cystectomy were identified. The pathologic complete response (pCR) rates stratified by TURBT CIS status were compared. The secondary analyses included tumor response, progression-free survival (PFS), overall survival (OS), and an exploratory post hoc analysis of patients with pathologic CIS only (pTisN0) at cystectomy. A total of 137 patients with MIUC were identified. TURBT CIS was noted in 30.7% of the patients. The absence of TURBT CIS was associated with a significantly increased pCR rate (23.2% vs. 9.5%; odds ratio, 4.08; 95% confidence interval, 1.19-13.98; P = .025). Stage pTisN0 disease was observed in 19.0% of the TURBT CIS patients. TURBT CIS status did not significantly affect the PFS or OS outcomes. Post hoc analysis of the pTisN0 patients revealed prolonged median PFS (104.5 vs. 139.9 months; P = .055) and OS (104.5 vs. 152.3 months; P = .091) outcomes similar to those for the pCR patients. The absence of CIS on pretreatment TURBT in patients with MIUC undergoing NAC was associated with increased pCR rates, with no observed differences in PFS or OS. Isolated CIS at cystectomy was frequently observed, with lengthy PFS and OS durations similar to those for pCR patients. Further studies aimed at understanding the biology and clinical effect of CIS in MIUC are warranted. Copyright © 2016 Elsevier Inc. All rights reserved.

Climate science: Clouds unfazed by haze

NASA Astrophysics Data System (ADS)

Stevens, Bjorn

2017-06-01

The extent to which aerosols affect climate is highly uncertain. Observations of clouds interacting with aerosols from a volcanic eruption suggest that the effect is much smaller than was once feared. See Article p.485

Observer-Based Adaptive NN Control for a Class of Uncertain Nonlinear Systems With Nonsymmetric Input Saturation.

PubMed

Yong-Feng Gao; Xi-Ming Sun; Changyun Wen; Wei Wang

2017-07-01

This paper is concerned with the problem of adaptive tracking control for a class of uncertain nonlinear systems with nonsymmetric input saturation and immeasurable states. The radial basis function of neural network (NN) is employed to approximate unknown functions, and an NN state observer is designed to estimate the immeasurable states. To analyze the effect of input saturation, an auxiliary system is employed. By the aid of adaptive backstepping technique, an adaptive tracking control approach is developed. Under the proposed adaptive tracking controller, the boundedness of all the signals in the closed-loop system is achieved. Moreover, distinct from most of the existing references, the tracking error can be bounded by an explicit function of design parameters and saturation input error. Finally, an example is given to show the effectiveness of the proposed method.

Reduced head steadiness in whiplash compared with non-traumatic neck pain.

PubMed

Woodhouse, Astrid; Liljebäck, Pål; Vasseljen, Ottar

2010-01-01

While sensorimotor alterations have been observed in patients with neck pain, it is uncertain whether such changes distinguish whiplash-associated disorders from chronic neck pain without trauma. The aim of this study was to investigate head steadiness during isometric neck flexion in subjects with chronic whiplash-associated disorders (WAD), those with chronic non-traumatic neck pain and healthy subjects. Associations with fatigue and effects of pain and dizziness were also investigated. Head steadiness in terms of head motion velocity was compared in subjects with whiplash (n=59), non-traumatic neck pain (n=57) and healthy controls (n=57) during 2 40-s isometric neck flexion tests; a high load test and a low load test. Increased velocity was expected to reflect decreased head steadiness. The whiplash group showed significantly decreased head steadiness in the low load task compared with the other 2 groups. The difference was explained largely by severe levels of neck pain and dizziness. No group differences in head steadiness were found in the high load task. Reduced head steadiness during an isometric holding test was observed in a group of patients with whiplash-associated disorders. Decreased head steadiness was related to severe pain and dizziness.

The Role of Intelligence in Social Learning.

PubMed

Vostroknutov, Alexander; Polonio, Luca; Coricelli, Giorgio

2018-05-02

Studies in cultural evolution have uncovered many types of social learning strategies that are adaptive in certain environments. The efficiency of these strategies also depends on the individual characteristics of both the observer and the demonstrator. We investigate the relationship between intelligence and the ways social and individual information is utilised to make decisions in an uncertain environment. We measure fluid intelligence and study experimentally how individuals learn from observing the choices of a demonstrator in a 2-armed bandit problem with changing probabilities of a reward. Participants observe a demonstrator with high or low fluid intelligence. In some treatments they are aware of the intelligence score of the demonstrator and in others they are not. Low fluid intelligence individuals imitate the demonstrator more when her fluid intelligence is known than when it is not. Conversely, individuals with high fluid intelligence adjust their use of social information, as the observed behaviour changes, independently of the knowledge of the intelligence of the demonstrator. We provide evidence that intelligence determines how social and individual information is integrated in order to make choices in a changing uncertain environment.

Adjuvant Anti-HER2 Therapy, Treatment-Related Amenorrhea, and Survival in Premenopausal HER2-Positive Early Breast Cancer Patients.

PubMed

Lambertini, Matteo; Campbell, Christine; Bines, José; Korde, Larissa A; Izquierdo, Miguel; Fumagalli, Debora; Del Mastro, Lucia; Ignatiadis, Michail; Pritchard, Kathleen; Wolff, Antonio C; Jackisch, Christian; Lang, Istvan; Untch, Michael; Smith, Ian; Boyle, Frances; Xu, Binghe; Barrios, Carlos H; Baselga, José; Moreno-Aspitia, Alvaro; Piccart, Martine; Gelber, Richard D; de Azambuja, Evandro

2018-06-05

In premenopausal patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer, the gonadotoxicity of trastuzumab and lapatinib remains largely uncertain, and the prognostic effect of treatment-related amenorrhea (TRA) is unknown. In the Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization (BIG 2-06) phase III trial, HER2-positive early breast cancer patients were randomized (1:1:1:1) to receive one year of trastuzumab, lapatinib, their sequence, or their combination. As per study protocol, menopausal status was collected in all patients at random assignment and at week 37 visit. We investigated TRA rates and whether TRA in patients with hormone receptor-positive and -negative tumors would impact disease-free survival (DFS) and overall survival (OS). Landmark and time-dependent modeling were used to account for guarantee-time bias. All statistical tests were two-sided. A total of 2862 premenopausal women were included, of whom 1679 (58.7%) had hormone receptor-positive disease. Median age was 43 (interquartile range = 38-47) years. Similar TRA rates were observed in the trastuzumab (72.6%), lapatinib (74.0%), trastuzumab→lapatinib (72.1%), and trastuzumab+lapatinib (74.8%) arms (P = .64). The association between TRA and survival outcomes differed according to hormone-receptor status (Pinteraction for DFS = .007; Pinteraction for OS = .003). For hormone receptor-positive patients, the TRA cohort had statistically significantly better DFS (adjusted hazard ratio [aHR] = 0.58, 95% confidence interval [CI] = 0.45 to 0.76) and OS (aHR = 0.63, 95% CI = 0.40 to 0.99) than the no TRA cohort. No difference was observed in hormone receptor-negative patients. In this unplanned analysis, no association between TRA rate and type of anti-HER2 treatment was observed. TRA was associated with statistically significant survival benefits in premenopausal hormone receptor-positive/HER2-positive early breast cancer patients.

Rethinking AASM guideline for split-night polysomnography in Asian patients with obstructive sleep apnea.

PubMed

Kim, Dong-Kyu; Choi, Jihye; Kim, Kyung Rae; Hwang, Kyung-Gyun; Ryu, Seungho; Cho, Seok Hyun

2015-12-01

Split-night polysomnography (SN-PSG) provides both a diagnosis and titration of continuous positive airway pressure over a single night in patients with suspected obstructive sleep apnea (OSA). However, in Asian patients, the diagnostic validity of American Academy of Sleep Medicine (AASM) guidelines for SN-PSG remains uncertain. Therefore, we examined whether the current criteria for SN-PSG are pertinent for Asian patients. We investigated 134 consecutive patients who were diagnosed with OSA (apnea-hypopnea index (AHI) ≥ 5). We divided the raw data (full-night study) into two parts and compared the first 2 h of sleep with the full night of sleep to evaluate the diagnostic precision and accuracy of the first 2 h of sleep. No difference in AHI was observed between the first 2 h and the full night of sleep. A significant correlation of AHI was observed between the first 2 h and the full night of sleep for severe OSA patients (AHI ≥ 30). A correlation coefficient of AHI was higher by the criterion of AHI ≥ 30 than by the criterion of AHI ≥ 40 (r = 0.831 and r = 0.778, respectively), which is the current AASM criterion for SN-PSG. Moreover, the criterion AHI ≥ 30 showed better diagnostic accuracy than the criterion AHI ≥ 40 (89.3 and 88.7 %, respectively). This study found possible evidence supporting different diagnostic criteria for SN-PSG in Asian population. We suggest further studies in other Asian populations to confirm these findings.

Combined ultrasound-guided cutting-needle biopsy and standard pleural biopsy for diagnosis of malignant pleural effusions.

PubMed

Wang, Jinlin; Zhou, Xinghua; Xie, Xiaohong; Tang, Qing; Shen, Panxiao; Zeng, Yunxiang

2016-11-17

The most efficient approach to diagnose malignant pleural effusions (MPEs) is still controversial and uncertain. This study aimed to evaluate the utility of a combined approach using ultrasound (US)-guided cutting-needle biopsy (CNB) and standard pleural biopsy (SPB) for diagnosing MPE. Pleural effusions were collected from 172 patients for biochemical and microbiological analyses. US-guided CNB and SPB were performed in the same operation sequentially to obtain specimens for histological analysis. US-guided CNB and SPB procedures provided adequate material for histological analysis in 90.7 and 93.0% of cases, respectively, while a combination of the 2 techniques was in 96.5% of cases. The sensitivity, specificity, positive-predictive value (PPV), negative-predictive value (NPV) and diagnostic accuracy of US-guided CNB versus SPB were: 51.2 vs 63.4%, 100 vs 100%, 100 vs 100%, 64.9 vs 72.2% and 74.4 vs 81.3%, respectively. When CNB was combined with SPB, the corresponding values were 88.6, 100, 100, 88.6 and 93.9%, respectively. Whereas sensitivity, NPV and diagnostic accuracy were not significantly different between CNB and SPB, the combination of CNB and SPB significantly improved the sensitivity, NPV and diagnostic accuracy versus each technique alone (p < 0.05). Significant pain (eight patients), moderate haemoptysis (two patients) and chest wall haematomas (two patients) were observed following CNB, while syncope (four patients) and a slight pneumothorax (four patients) were observed following SPB. Use of a combination of US-guided CNB and SPB afforded a high sensitivity to diagnose MPEs, it is a convenient and safe approach.

Predischarge screening for chronic obstructive pulmonary disease in patients with acute coronary syndrome and smoking history.

PubMed

Campo, Gianluca; Pavasini, Rita; Barbetta, Carlo; Maietti, Elisa; Mascetti, Susanna; Biscaglia, Simone; Zaraket, Fatima; Spitaleri, Giosafat; Gallo, Francesco; Tonet, Elisabetta; Papi, Alberto; Ferrari, Roberto; Contoli, Marco

2016-11-01

Several studies suggested that chronic obstructive pulmonary disease (COPD) is largely underdiagnosed in patients with acute coronary syndrome (ACS) contributing to further affect clinical outcome. Our aim was to validate a screening procedure to identify, in ACS patients, those with negligible risk of undiagnosed COPD. From December 2014 to August 2015, 169 ACS patients with smoking history underwent screening procedure. Screening procedure combined peak expiratory flow rate (PEFR, defined as positive if <80% of predicted) and respiratory health status questionnaire (RHSQ, defined as positive if >19.5 points). The screening was considered negative if both tests provided negative results, positive if both were positive, uncertain in presence of discrepancy. Spirometry was planned after 2months to identify or not the presence of irreversible airflow obstruction (undiagnosed COPD). The primary endpoint was the negative predictive value of screening for undiagnosed COPD. Overall, 137 (81%) patients received spirometry (final study population). Screening was negative, uncertain and positive in 58 (42%), 46 (34%) and 33 (24%) patients, respectively. We found undiagnosed COPD in 39 (29%) patients. Only 3 patients with negative screening showed undiagnosed COPD. Negative screening showed the best ability to discriminate patients without COPD (negative predictive value 95%). Two-month health status in patients with undiagnosed COPD was significantly poor. Undiagnosed COPD is relatively frequent in ACS patients with smoking history and a simple screening procedure including PEFR and RHSQ can be administered before hospital discharge to discriminate those at negligible risk of undiagnosed COPD (ClinicalTrials.gov, NCT02324660). Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Surgery for constipation: systematic review and practice recommendations: Results I: Colonic resection.

PubMed

Knowles, C H; Grossi, U; Chapman, M; Mason, J

2017-09-01

To assess the outcomes of colectomy in adults with chronic constipation (CC). Standardised methods and reporting of benefits and harms were used for all CapaCiTY reviews that closely adhered to PRISMA 2016 guidance. Main conclusions were presented as summary evidence statements (SES) with a summative Oxford Centre for Evidence-Based Medicine (2009) level. Forty articles were identified, providing data on outcomes in 2045 patients. Evidence was derived almost exclusively from observational studies, the majority of which concerned colectomy and ileorectal anastomosis (CIRA) rather than other procedural variations. Average length of stay (LOS) ranged between 7-15 days. Although inconsistent, laparoscopic surgery may be associated with longer mean operating times (210 vs 167 min) and modest decreases in LOS (10-8 days). Complications occurred in approximately 24% of patients. Six (0.4%) procedure-related deaths were observed. Recurrent episodes of small bowel obstruction occurred in about 15% (95%CI: 10-21%) of patients in the long-term, with significant burden of re-hospitalisation and frequent recourse to surgery. Most patients reported a satisfactory or good outcome after colectomy but negative long-term functional outcomes persist in a minority of patients. The influence of resection extent, anastomotic configuration and method of access on complication rates remains uncertain. Available evidence weakly supports selection of patients with an isolated slow-transit phenotype. Colectomy for CC may benefit some patients but at the cost of substantial short- and long-term morbidity. Current evidence is insufficient to guide patient or procedural selection. © 2017 The Authors. Colorectal Disease published by John Wiley & Sons Ltd on behalf of Association of Coloproctology of Great Britain and Ireland.

[Cancer screening in clinical practice: the value of shared decision-making].

PubMed

Cornuz, Jacques; Junod, Noëlle; Pasche, Olivier; Guessous, Idris

2010-07-14

Shared decision-making approach to uncertain clinical situations such as cancer screening seems more appropriate than ever. Shared decision making can be defined as an interactive process where physician and patient share all the stages of the decision making process. For patients who wish to be implicated in the management of their health conditions, physicians might express difficulty to do so. Use of patient decision aids appears to improve such process of shared decision making.

Mild cognitive impairment: coping with an uncertain label.

PubMed

Joosten-Weyn Banningh, Liesbeth; Vernooij-Dassen, Myrra; Rikkert, Marcel Olde; Teunisse, Jan-Pieter

2008-02-01

The recently introduced diagnostic label of Mild Cognitive Impairment (MCI) identifies patients with a cognitive decline that is more pronounced than is usual for a person's age and educational level but does not notably interfere with activities of daily living (ADL). The natural course of the syndrome is uncertain although MCI sufferers have a higher risk of developing dementia. To investigate how patients fulfilling MCI criteria experience and cope with their cognitive decline with the secondary aim to derive key themes for a prospective MCI support-group programme. The grounded theory approach. Analysis of guided interviews with eight MCI patients revealed four common themes. Changes related to cognitive abilities, mobility, affect, vitality and somatic complaints. Attributions were numerous and concerned aetiologies such as personality traits and overload of information. Consequences were all negative and concerned the patients themselves such as anxiety and loss of self-confidence, others such as feelings of irritation and anger towards others or activities like abandoning leisure activities. Patients applied emotion-oriented, problem-focused and avoidant coping strategies. MCI patients encounter stress-inducing practical, social and psychological difficulties. Based on the current preliminary findings, the key themes for an MCI support-group programme should include the provision of information about the syndrome's causes, course, concomitant symptoms, attributions, social consequences, and available treatments. The impact of receiving an MCI label warrants further investigation. Copyright (c) 2007 John Wiley & Sons, Ltd.

Inability to determine tissue health is main indication of allograft use in intermediate extent burns.

PubMed

Fletcher, John L; Cancio, Leopoldo C; Sinha, Indranil; Leung, Kai P; Renz, Evan M; Chan, Rodney K

2015-12-01

Cutaneous allograft is commonly used in the early coverage of excised burns when autograft is unavailable. However, allograft is also applied in intermediate-extent burns (25-50%), during cases in which it is possible to autograft. In this population, there is a paucity of data on the indications for allograft use. This study explores the indications for allograft usage in moderate size burns. Under an IRB-approved protocol, patients admitted to our burn unit between March 2003 and December 2010 were identified through a review of the burn registry. Data on allograft use, total burn surface area, operation performed, operative intent, number of operations, intensive care unit length of stay, and overall length of stay were collected and analyzed. Data are presented as means±standard deviations, except where noted. In the study period, 146 patients received allograft during their acute hospitalization. Twenty-five percent of allograft recipients sustained intermediate-extent burns. Patients with intermediate-extent burns received allograft later in their hospitalization than those with large-extent (50-75% TBSA) burns (6.8 days vs. 3.4 days, p=0.01). Allografted patients with intermediate-extent burns underwent more operations (10.8 vs. 6.1, p=0.002) and had longer hospitalizations (78.3 days vs. 40.9 days, p<0.001) than non-allografted patients, when controlled for TBSA. Clinical rationale for placement of allograft in this population included autograft failure, uncertain depth of excision, lack of autograft donor site, and wound complexity. When uncertain depth of excision was the indication, allograft was universally applied onto the face. In half of allografted intermediate-extent burn patients the inability to identify a viable recipient bed was the ultimate reason for allograft use. Unlike large body surface area burns, allograft skin use in intermediate-extent injury occurs later in the hospitalization and is driven by the inability to determine wound bed suitability for autograft application. Allograft application can be utilized to test recipient site viability in cases of autograft failure or uncertain depth of excision. Published by Elsevier Ltd.

Asthma caused by potassium aluminium tetrafluoride: a case series

PubMed Central

LAŠTOVKOVÁ, Andrea; KLUSÁČKOVÁ, Pavlina; FENCLOVÁ, Zdenka; BONNETERRE, Vincent; PELCLOVÁ, Daniela

2015-01-01

The objective of this study is to describe a case-series of potassium aluminium tetrafluoride (KAlF4)-induced occupational asthma (OA) and/or occupational rhinitis (OR). The study involves five patients from a heat-exchanger production line who were examined (including specific inhalation challenge tests) for suspected OA and/or OR caused by a flux containing almost 100% KAlF4 − with fluorides’ workplace air concentrations ranging between 1.7 and 2.8 mg/m3. No subject had a previous history of asthma. All five patients had a positive specific challenge test (three patients were diagnosed with OA alone, one with OR and one with both OR and OA). At the follow-up visit, after three years on average, all patients needed permanent corticosteroid therapy (four topical, one oral). After elimination from the exposure, only one of the observed subjects gave an indication of an improvement, two subjects stabilized and two worsened. Our case series focuses on the correlation between patients’ exposure to fluorides in air-conditioner production and the subsequent occurrence of OR/OA. Currently, it is uncertain whether these OR/OA were caused by hypersensitivity or irritation. PMID:26212411

Communicative practices in talking about death and dying in the context of Thai cancer care.

PubMed

Wilainuch, Pairote

2013-01-01

This article explores communicative practices surrounding how nurses, patients and family members engage when talking about death and dying, based on study conducted in a province in northern Thailand. Data were collected from three environments: a district hospital (nine cases), district public health centres (four cases), and in patients' homes (27 cases). Fourteen nurses, 40 patients and 24 family members gave written consent for participation. Direct observation and in-depth interviews were used for supplementary data collection, and 40 counselling sessions were recorded on video. The raw data were analysed using Conversation Analysis. The study found that Thai counselling is asymmetrical. Nurses initiated the topic of death by referring to the death of a third person--a dead patient--with the use of clues and via list-construction. As most Thai people are oriented to Buddhism, religious support is selected for discussing this sensitive topic, and nurses also use Buddhism and list-construction to help their clients confront uncertain futures. However, Buddhism is not brought into discussion on its own, but combined with other techniques such as the use of euphemisms or concern and care for others.

A Hierarchical Multi-Model Approach for Uncertainty Segregation, Prioritization and Comparative Evaluation of Competing Modeling Propositions

NASA Astrophysics Data System (ADS)

Tsai, F. T.; Elshall, A. S.; Hanor, J. S.

2012-12-01

Subsurface modeling is challenging because of many possible competing propositions for each uncertain model component. How can we judge that we are selecting the correct proposition for an uncertain model component out of numerous competing propositions? How can we bridge the gap between synthetic mental principles such as mathematical expressions on one hand, and empirical observation such as observation data on the other hand when uncertainty exists on both sides? In this study, we introduce hierarchical Bayesian model averaging (HBMA) as a multi-model (multi-proposition) framework to represent our current state of knowledge and decision for hydrogeological structure modeling. The HBMA framework allows for segregating and prioritizing different sources of uncertainty, and for comparative evaluation of competing propositions for each source of uncertainty. We applied the HBMA to a study of hydrostratigraphy and uncertainty propagation of the Southern Hills aquifer system in the Baton Rouge area, Louisiana. We used geophysical data for hydrogeological structure construction through indictor hydrostratigraphy method and used lithologic data from drillers' logs for model structure calibration. However, due to uncertainty in model data, structure and parameters, multiple possible hydrostratigraphic models were produced and calibrated. The study considered four sources of uncertainties. To evaluate mathematical structure uncertainty, the study considered three different variogram models and two geological stationarity assumptions. With respect to geological structure uncertainty, the study considered two geological structures with respect to the Denham Springs-Scotlandville fault. With respect to data uncertainty, the study considered two calibration data sets. These four sources of uncertainty with their corresponding competing modeling propositions resulted in 24 calibrated models. The results showed that by segregating different sources of uncertainty, HBMA analysis provided insights on uncertainty priorities and propagation. In addition, it assisted in evaluating the relative importance of competing modeling propositions for each uncertain model component. By being able to dissect the uncertain model components and provide weighted representation of the competing propositions for each uncertain model component based on the background knowledge, the HBMA functions as an epistemic framework for advancing knowledge about the system under study.

Adapting environmental management to uncertain but inevitable change.

PubMed

Nicol, Sam; Fuller, Richard A; Iwamura, Takuya; Chadès, Iadine

2015-06-07

Implementation of adaptation actions to protect biodiversity is limited by uncertainty about the future. One reason for this is the fear of making the wrong decisions caused by the myriad future scenarios presented to decision-makers. We propose an adaptive management (AM) method for optimally managing a population under uncertain and changing habitat conditions. Our approach incorporates multiple future scenarios and continually learns the best management strategy from observations, even as conditions change. We demonstrate the performance of our AM approach by applying it to the spatial management of migratory shorebird habitats on the East Asian-Australasian flyway, predicted to be severely impacted by future sea-level rise. By accounting for non-stationary dynamics, our solution protects 25,000 more birds per year than the current best stationary approach. Our approach can be applied to many ecological systems that require efficient adaptation strategies for an uncertain future. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Using Direct Policy Search to Identify Robust Strategies in Adapting to Uncertain Sea Level Rise and Storm Surge

NASA Astrophysics Data System (ADS)

Garner, G. G.; Keller, K.

2017-12-01

Sea-level rise poses considerable risks to coastal communities, ecosystems, and infrastructure. Decision makers are faced with deeply uncertain sea-level projections when designing a strategy for coastal adaptation. The traditional methods have provided tremendous insight into this decision problem, but are often silent on tradeoffs as well as the effects of tail-area events and of potential future learning. Here we reformulate a simple sea-level rise adaptation model to address these concerns. We show that Direct Policy Search yields improved solution quality, with respect to Pareto-dominance in the objectives, over the traditional approach under uncertain sea-level rise projections and storm surge. Additionally, the new formulation produces high quality solutions with less computational demands than the traditional approach. Our results illustrate the utility of multi-objective adaptive formulations for the example of coastal adaptation, the value of information provided by observations, and point to wider-ranging application in climate change adaptation decision problems.

Morton's metatarsalgia: sonographic findings and correlated histopathology.

PubMed

Read, J W; Noakes, J B; Kerr, D; Crichton, K J; Slater, H K; Bonar, F

1999-03-01

The results of 79 high resolution ultrasound examinations of the forefoot that were performed for suspected Morton's metatarsalgia were retrospectively assessed. Scans were only obtained if the pain was poorly localized or if there were atypical features that made the clinical diagnosis uncertain. Ultrasound detected 92 hypoechoic intermetatarsal web space masses in 63 patients. Surgery was performed on 23 web spaces in 22 patients where the response to nonsurgical management had been poor. The surgical specimens were retrieved and reviewed by a pathologist in 21 cases. The histopathology in 20 of 21 operated cases was that of Morton's neuroma; however, prominent mucoid degeneration was also found to involve the adjacent loose fibroadipose tissues in 19 of 20 neuroma specimens. Ultrasound was sensitive in the detection of web space abnormality (sensitivity, 0.95), but could not clearly separate Morton's neuroma from associated mass-like mucoid degeneration in the adjacent loose connective tissues. The implications of these observations for both diagnosis and treatment are discussed.

Stronger steerability criterion for more uncertain continuous-variable systems

NASA Astrophysics Data System (ADS)

Chowdhury, Priyanka; Pramanik, Tanumoy; Majumdar, A. S.

2015-10-01

We derive a fine-grained uncertainty relation for the measurement of two incompatible observables on a single quantum system of continuous variables, and show that continuous-variable systems are more uncertain than discrete-variable systems. Using the derived fine-grained uncertainty relation, we formulate a stronger steering criterion that is able to reveal the steerability of NOON states that has hitherto not been possible using other criteria. We further obtain a monogamy relation for our steering inequality which leads to an, in principle, improved lower bound on the secret key rate of a one-sided device independent quantum key distribution protocol for continuous variables.

Chronic kidney diseases of uncertain etiology (CKDue) in Sri Lanka: geographic distribution and environmental implications.

PubMed

Chandrajith, Rohana; Nanayakkara, Shanika; Itai, Kozuyoshi; Aturaliya, T N C; Dissanayake, C B; Abeysekera, Thilak; Harada, Kouji; Watanabe, Takao; Koizumi, Akio

2011-06-01

The increase in the number of chronic kidney disease (CKD) patients from the north central region of Sri Lanka has become a environmental health issue of national concern. Unlike in other countries where long-standing diabetes and hypertension are the leading causes of renal diseases, the majority of CKD patients from this part of Sri Lanka do not show any identifiable cause. As the disease is restricted to a remarkably specific geographical terrain, particularly in the north central dry zone of the country, multidisciplinary in-depth research studies are required to identify possible etiologies and risk factors. During this study, population screening in the prevalent region and outside the region, analysis of geoenvironmental and biochemical samples were carried out. Population screening that was carried out using a multistage sampling technique indicated that the point prevalence of CKD with uncertain etiology is about 2-3% among those above 18 years of age. Drinking water collected from high-prevalent and non-endemic regions was analyzed for their trace and ultratrace element contents, including the nephrotoxic heavy metals Cd and U using ICP-MS. The results indicate that the affected regions contain moderate to high levels of fluoride. The Cd contents in drinking water, rice from affected regions and urine from symptomatic and non-symptomatic patients were much lower indicating that Cd is not a contributing factor for CKD with uncertain etiology in Sri Lanka. Although no single geochemical parameter could be clearly and directly related to the CKD etiology on the basis of the elements determined during this study, it is very likely that the unique hydrogeochemistry of the drinking water is closely associated with the incidence of the disease. © Springer Science+Business Media B.V. 2010

Applied estimation for hybrid dynamical systems using perceptional information

NASA Astrophysics Data System (ADS)

Plotnik, Aaron M.

This dissertation uses the motivating example of robotic tracking of mobile deep ocean animals to present innovations in robotic perception and estimation for hybrid dynamical systems. An approach to estimation for hybrid systems is presented that utilizes uncertain perceptional information about the system's mode to improve tracking of its mode and continuous states. This results in significant improvements in situations where previously reported methods of estimation for hybrid systems perform poorly due to poor distinguishability of the modes. The specific application that motivates this research is an automatic underwater robotic observation system that follows and films individual deep ocean animals. A first version of such a system has been developed jointly by the Stanford Aerospace Robotics Laboratory and Monterey Bay Aquarium Research Institute (MBARI). This robotic observation system is successfully fielded on MBARI's ROVs, but agile specimens often evade the system. When a human ROV pilot performs this task, one advantage that he has over the robotic observation system in these situations is the ability to use visual perceptional information about the target, immediately recognizing any changes in the specimen's behavior mode. With the approach of the human pilot in mind, a new version of the robotic observation system is proposed which is extended to (a) derive perceptional information (visual cues) about the behavior mode of the tracked specimen, and (b) merge this dissimilar, discrete and uncertain information with more traditional continuous noisy sensor data by extending existing algorithms for hybrid estimation. These performance enhancements are enabled by integrating techniques in hybrid estimation, computer vision and machine learning. First, real-time computer vision and classification algorithms extract a visual observation of the target's behavior mode. Existing hybrid estimation algorithms are extended to admit this uncertain but discrete observation, complementing the information available from more traditional sensors. State tracking is achieved using a new form of Rao-Blackwellized particle filter called the mode-observed Gaussian Particle Filter. Performance is demonstrated using data from simulation and data collected on actual specimens in the ocean. The framework for estimation using both traditional and perceptional information is easily extensible to other stochastic hybrid systems with mode-related perceptional observations available.

Giant pseudoaneurysm from Vieussens' arterial ring.

PubMed

Kocica, Mladen J; Vranes, Mile R; Djukic, Petar L; Mikic, Aleksandar Dj; Velinovic, Milos M; Havelka, Marija; Kanjuh, Vladimir I

2004-11-01

A giant coronary pseudoaneurysm of uncertain cause, arising from Vieussens' arterial ring, was preoperatively diagnosed in an oligosymptomatic female patient. Successful off-pump surgical excision without additional bypass grafting was performed. Difficulties in diagnostic algorithm, as well as possible cause and extremely rare localization were discussed.

Patient Populations, Clinical Associations, and System Efficiency in Healthcare Delivery System

NASA Astrophysics Data System (ADS)

Liu, Yazhuo

The efforts to improve health care delivery usually involve studies and analysis of patient populations and healthcare systems. In this dissertation, I present the research conducted in the following areas: identifying patient groups, improving treatments for specific conditions by using statistical as well as data mining techniques, and developing new operation research models to increase system efficiency from the health institutes' perspective. The results provide better understanding of high risk patient groups, more accuracy in detecting disease' correlations and practical scheduling tools that consider uncertain operation durations and real-life constraints.

BRCA1 and BRCA2 mutations in ethnic Lebanese Arab women with high hereditary risk breast cancer.

PubMed

El Saghir, Nagi S; Zgheib, Nathalie K; Assi, Hussein A; Khoury, Katia E; Bidet, Yannick; Jaber, Sara M; Charara, Raghid N; Farhat, Rania A; Kreidieh, Firas Y; Decousus, Stephanie; Romero, Pierre; Nemer, Georges M; Salem, Ziad; Shamseddine, Ali; Tfayli, Arafat; Abbas, Jaber; Jamali, Faek; Seoud, Muhieddine; Armstrong, Deborah K; Bignon, Yves-Jean; Uhrhammer, Nancy

2015-04-01

Breast cancer is the most common malignancy among women in Lebanon and in Arab countries, with 50% of cases presenting before the age of 50 years. Between 2009 and 2012, 250 Lebanese women with breast cancer who were considered to be at high risk of carrying BRCA1 or BRCA2 mutations because of presentation at young age and/or positive family history (FH) of breast or ovarian cancer were recruited. Clinical data were analyzed statistically. Coding exons and intron-exon boundaries of BRCA1 and BRCA2 were sequenced from peripheral blood DNA. All patients were tested for BRCA1 rearrangements using multiplex ligation-dependent probe amplification (MLPA). BRCA2 MLPA was done in selected cases. Overall, 14 of 250 patients (5.6%) carried a deleterious BRCA mutation (7 BRCA1, 7 BRCA2) and 31 (12.4%) carried a variant of uncertain significance. Eight of 74 patients (10.8%) aged ≤40 years with positive FH and only 1 of 74 patients (1.4%) aged ≤40 years without FH had a mutated BRCA. Four of 75 patients (5.3%) aged 41-50 years with FH had a deleterious mutation. Only 1 of 27 patients aged >50 years at diagnosis had a BRCA mutation. All seven patients with BRCA1 mutations had grade 3 infiltrating ductal carcinoma and triple-negative breast cancer. Nine BRCA1 and 17 BRCA2 common haplotypes were observed. Prevalence of deleterious BRCA mutations is lower than expected and does not support the hypothesis that BRCA mutations alone cause the observed high percentage of breast cancer in young women of Lebanese and Arab descent. Studies to search for other genetic mutations are recommended. ©AlphaMed Press.

Outcome by mode of anaesthesia for hip fracture surgery. An observational audit of 65 535 patients in a national dataset.

PubMed

White, S M; Moppett, I K; Griffiths, R

2014-03-01

Large observational studies of accurate data can provide similar results to more arduous and expensive randomised controlled trials. In 2012, the National Hip Fracture Database extended its dataset to include 'type of anaesthesia' data fields. We analysed 65 535 patient record sets to determine differences in outcome. Type of anaesthesia was recorded in 59 191 (90%) patients. Omitting patients who received both general and spinal anaesthesia or in whom an uncertain type of anaesthesia was recorded, there was no significant difference in either cumulative five-day (2.8% vs 2.8%, p = 0.991) or 30-day (7.0% vs 7.5%, p = 0.053) mortality between 30 130 patients receiving general anaesthesia and 22 999 patients receiving spinal anaesthesia, even when 30-day mortality was adjusted for age and ASA physical status (p = 0.226). Mortality within 24 hours after surgery was significantly higher among patients receiving cemented compared with uncemented hemiarthroplasty (1.6% vs 1.2%, p = 0.030), suggesting excess early mortality related to bone cement implantation syndrome. If these data are accurate, then either there is no difference in 30-day mortality between general and spinal anaesthesia after hip fracture surgery per se, and therefore future research should focus on how to make both types of anaesthesia safer, or there is a difference, but mortality is not the correct outcome to measure after anaesthesia, and therefore future research should focus on differences between general and spinal anaesthesia. These could include more anaesthesia-sensitive outcomes, such as hypotension, pain, postoperative confusion, respiratory infection and mobilisation. © 2014 The Association of Anaesthetists of Great Britain and Ireland.

Risk factors associated with disease progression and mortality in chronic kidney disease of uncertain etiology: a cohort study in Medawachchiya, Sri Lanka.

PubMed

Senevirathna, Lalantha; Abeysekera, Tilak; Nanayakkara, Shanika; Chandrajith, Rohana; Ratnatunga, Neelakanthi; Harada, Kouji H; Hitomi, Toshiaki; Komiya, Toshiyuki; Muso, Eri; Koizumi, Akio

2012-05-01

The alarming rise in the prevalence of chronic kidney disease of uncertain etiology (CKDu) among the low socioeconomic farming community in the North Central Province of Sri Lanka has been recognized as an emerging public health issue in the country. This study sought to determine the possible factors associated with the progression and mortality of CKDu. The study utilized a single-center cohort registered in 2003 and followed up until 2009 in a regional clinic in the endemic region, and used a Cox proportional hazards model. We repeatedly found an association between disease progression and hypertension. Men were at higher risk of CKDu than women. A significant proportion of the patients in this cohort were underweight, which emphasized the need for future studies on the nutritional status of these patients. Compared with findings in western countries and other regions of Asia, we identified hypertension as a major risk factor for progression of CKDu in this cohort.

The Effects of the Previous Outcome on Probabilistic Choice in Rats

PubMed Central

Marshall, Andrew T.; Kirkpatrick, Kimberly

2014-01-01

This study examined the effects of previous outcomes on subsequent choices in a probabilistic-choice task. Twenty-four rats were trained to choose between a certain outcome (1 or 3 pellets) versus an uncertain outcome (3 or 9 pellets), delivered with a probability of .1, .33, .67, and .9 in different phases. Uncertain outcome choices increased with the probability of uncertain food. Additionally, uncertain choices increased with the probability of uncertain food following both certain-choice outcomes and unrewarded uncertain choices. However, following uncertain-choice food outcomes, there was a tendency to choose the uncertain outcome in all cases, indicating that the rats continued to “gamble” after successful uncertain choices, regardless of the overall probability or magnitude of food. A subsequent manipulation, in which the probability of uncertain food varied within each session as a function of the previous uncertain outcome, examined how the previous outcome and probability of uncertain food affected choice in a dynamic environment. Uncertain-choice behavior increased with the probability of uncertain food. The rats exhibited increased sensitivity to probability changes and a greater degree of win–stay/lose–shift behavior than in the static phase. Simulations of two sequential choice models were performed to explore the possible mechanisms of reward value computations. The simulation results supported an exponentially decaying value function that updated as a function of trial (rather than time). These results emphasize the importance of analyzing global and local factors in choice behavior and suggest avenues for the future development of sequential-choice models. PMID:23205915

The Clinical Significance of Occult Gastrointestinal Primary Tumours in Metastatic Cancer: A Population Retrospective Cohort Study.

PubMed

Hannouf, Malek B; Winquist, Eric; Mahmud, Salaheddin M; Brackstone, Muriel; Sarma, Sisira; Rodrigues, George; Rogan, Peter K; Hoch, Jeffrey S; Zaric, Gregory S

2018-01-01

The purpose of this study was to estimate the incidence of occult gastrointestinal (GI) primary tumours in patients with metastatic cancer of uncertain primary origin and evaluate their influence on treatments and overall survival (OS). We used population heath data from Manitoba, Canada to identify all patients initially diagnosed with metastatic cancer between 2002 and 2011. We defined patients to have "occult" primary tumour if the primary was found at least 6 months after initial diagnosis. Otherwise, we considered primary tumours as "obvious." We used propensity-score methods to match each patient with occult GI tumour to four patients with obvious GI tumour on all known clinicopathologic features. We compared treatments and 2-year survival data between the two patient groups and assessed treatment effect on OS using Cox regression adjustment. Eighty-three patients had occult GI primary tumours, accounting for 17.6% of men and 14% of women with metastatic cancer of uncertain primary. A 1:4 matching created a matched group of 332 patients with obvious GI primary tumour. Occult cases compared to the matched group were less likely to receive surgical interventions and targeted biological therapy, and more likely to receive cytotoxic empiric chemotherapeutic agents. Having an occult GI tumour was associated with reduced OS and appeared to be a nonsignificant independent predictor of OS when adjusting for treatment differences. GI tumours are the most common occult primary tumours in men and the second most common in women. Patients with occult GI primary tumours are potentially being undertreated with available GI site-specific and targeted therapies.

Heterozygous RTEL1 variants in bone marrow failure and myeloid neoplasms

PubMed Central

Marsh, Judith C. W.; Gutierrez-Rodrigues, Fernanda; Cooper, James; Jiang, Jie; Gandhi, Shreyans; Kajigaya, Sachiko; Feng, Xingmin; Ibanez, Maria del Pilar F.; Donaires, Flávia S.; Lopes da Silva, João P.; Li, Zejuan; Das, Soma; Ibanez, Maria; Smith, Alexander E.; Lea, Nicholas; Best, Steven; Ireland, Robin; Kulasekararaj, Austin G.; McLornan, Donal P.; Pagliuca, Anthony; Callebaut, Isabelle; Young, Neal S.; Calado, Rodrigo T.; Townsley, Danielle M.

2018-01-01

Biallelic germline mutations in RTEL1 (regulator of telomere elongation helicase 1) result in pathologic telomere erosion and cause dyskeratosis congenita. However, the role of RTEL1 mutations in other bone marrow failure (BMF) syndromes and myeloid neoplasms, and the contribution of monoallelic RTEL1 mutations to disease development are not well defined. We screened 516 patients for germline mutations in telomere-associated genes by next-generation sequencing in 2 independent cohorts; one constituting unselected patients with idiopathic BMF, unexplained cytopenia, or myeloid neoplasms (n = 457) and a second cohort comprising selected patients on the basis of the suspicion of constitutional/familial BMF (n = 59). Twenty-three RTEL1 variants were identified in 27 unrelated patients from both cohorts: 7 variants were likely pathogenic, 13 were of uncertain significance, and 3 were likely benign. Likely pathogenic RTEL1 variants were identified in 9 unrelated patients (7 heterozygous and 2 biallelic). Most patients were suspected to have constitutional BMF, which included aplastic anemia (AA), unexplained cytopenia, hypoplastic myelodysplastic syndrome, and macrocytosis with hypocellular bone marrow. In the other 18 patients, RTEL1 variants were likely benign or of uncertain significance. Telomeres were short in 21 patients (78%), and 3′ telomeric overhangs were significantly eroded in 4. In summary, heterozygous RTEL1 variants were associated with marrow failure, and telomere length measurement alone may not identify patients with telomere dysfunction carrying RTEL1 variants. Pathogenicity assessment of heterozygous RTEL1 variants relied on a combination of clinical, computational, and functional data required to avoid misinterpretation of common variants. PMID:29344583

Heterozygous RTEL1 variants in bone marrow failure and myeloid neoplasms.

PubMed

Marsh, Judith C W; Gutierrez-Rodrigues, Fernanda; Cooper, James; Jiang, Jie; Gandhi, Shreyans; Kajigaya, Sachiko; Feng, Xingmin; Ibanez, Maria Del Pilar F; Donaires, Flávia S; Lopes da Silva, João P; Li, Zejuan; Das, Soma; Ibanez, Maria; Smith, Alexander E; Lea, Nicholas; Best, Steven; Ireland, Robin; Kulasekararaj, Austin G; McLornan, Donal P; Pagliuca, Anthony; Callebaut, Isabelle; Young, Neal S; Calado, Rodrigo T; Townsley, Danielle M; Mufti, Ghulam J

2018-01-09

Biallelic germline mutations in RTEL1 (regulator of telomere elongation helicase 1) result in pathologic telomere erosion and cause dyskeratosis congenita. However, the role of RTEL1 mutations in other bone marrow failure (BMF) syndromes and myeloid neoplasms, and the contribution of monoallelic RTEL1 mutations to disease development are not well defined. We screened 516 patients for germline mutations in telomere-associated genes by next-generation sequencing in 2 independent cohorts; one constituting unselected patients with idiopathic BMF, unexplained cytopenia, or myeloid neoplasms (n = 457) and a second cohort comprising selected patients on the basis of the suspicion of constitutional/familial BMF (n = 59). Twenty-three RTEL1 variants were identified in 27 unrelated patients from both cohorts: 7 variants were likely pathogenic, 13 were of uncertain significance, and 3 were likely benign. Likely pathogenic RTEL1 variants were identified in 9 unrelated patients (7 heterozygous and 2 biallelic). Most patients were suspected to have constitutional BMF, which included aplastic anemia (AA), unexplained cytopenia, hypoplastic myelodysplastic syndrome, and macrocytosis with hypocellular bone marrow. In the other 18 patients, RTEL1 variants were likely benign or of uncertain significance. Telomeres were short in 21 patients (78%), and 3' telomeric overhangs were significantly eroded in 4. In summary, heterozygous RTEL1 variants were associated with marrow failure, and telomere length measurement alone may not identify patients with telomere dysfunction carrying RTEL1 variants. Pathogenicity assessment of heterozygous RTEL1 variants relied on a combination of clinical, computational, and functional data required to avoid misinterpretation of common variants.

Strong correlation of elastin deletions, detected by FISH, with Williams syndrome: Evaluation of 235 patients

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

Lowery, M.C.; Brothman, L.J.; Leonard, C.O.

1995-07-01

Williams syndrome (WS) is generally characterized by mental deficiency, gregarious personality, dysmorphic facies, supravalvular aortic stenosis, and idiopathic infantile hypercalcemia. Patients with WS show allelic loss of elastin (ELN), exhibiting a submicroscopic deletion, at 7q11.23, detectable by FISH. Hemizygosity is likely the cause of vascular abnormalities in WS patients. A series of 235 patients was studied, and molecular cytogenetic deletions were seen in 96% of patients with classic WS. Patients included 195 solicited through the Williams Syndrome Association (WSA), plus 40 clinical cytogenetics cases referred by primary-care physicians. Photographs and medical records of most WSA subjects were reviewed, and patientsmore » were identified as {open_quotes}classic{open_quotes} (n = 114) or{open_quotes}uncertain{close_quotes} (n = 39). An additional 42 WSA patients were evaluated without clinical information. FISH was performed with biotinylated ELN cosmids on metaphase cells from immortalized lymphoblastoid lines from WSA patients and after high-resolution banding analysis on clinical referral patients. An alpha-satellite probe for chromosome 7 was included in hybridizations, as an internal control. Ninety-six percent of the patients with classic WS showed a deletion in one ELN allele; four of these did not show a deletion. Of the uncertain WS patients, only 3 of 39 showed a deletion. Of the 42 who were not classified phenotypically, because of lack of clinical information, 25 patients (60%) showed a deletion. Thirty-eight percent (15/40) of clinical cytogenetics cases showed an ELN deletion and no cytogenetic deletion by banded analysis. These results support the usefulness of FISH for the detection of elastin deletions as an initial diagnostic assay for WS. 14 refs., 2 figs., 4 tabs.« less

Multivariate analysis of matrix-assisted laser desorption/ionization mass spectrometric data related to glycoxidation products of human globins in nephropathic patients.

PubMed

Lapolla, Annunziata; Ragazzi, Eugenio; Andretta, Barbara; Fedele, Domenico; Tubaro, Michela; Seraglia, Roberta; Molin, Laura; Traldi, Pietro

2007-06-01

To clarify the possible pathogenetic role of oxidation products originated from the glycation of proteins, human globins from nephropathic patients have been studied by matrix-assisted laser desorption/ionization mass spectrometry (MALDI), revealing not only unglycated and monoglycated globins, but also a series of different species. For the last ones, structural assignments were tentatively done on the basis of observed masses and expectations for the Maillard reaction pattern. Consequently, they must be considered only propositive, and the discussion which will follow must be considered in this view. In our opinion this approach does not seem to compromise the intended diagnostic use of the data because distinctions are valid even if the assignments are uncertain. We studied nine healthy subjects and 19 nephropathic patients and processed the data obtained from the MALDI spectra using a multivariate analysis. Our results showed that multivariate analytical techniques enable differential aspects of the profile of molecular species to be identified in the blood of end stage nephropathic patients. A correct grouping can be achieved by principal component analysis (PCA) and the results suggest that several products involved in carbonyl stress exist in nephropathic patients. These compounds may have a relevant role as specific markers of the pathological state.

An error of self-diagnosis--but what was the real diagnosis?

PubMed

de Carvalho, Mamede; Swash, Michael

2009-10-01

The availability of information on the internet encourages people to explore their own diagnosis. Although more knowledge is usually a good thing, self-diagnosis in this way may not always be correct, and it can even adversely influence the medical diagnosis, as in this patient, where the underlying disorder is still uncertain. The patient illustrates the confusion and difficulty in categorising an usual clinical syndrome.

Cognitive-Behavioral Therapy, Behavioral Weight Loss, and Sequential Treatment for Obese Patients with Binge-Eating Disorder: A Randomized Controlled Trial

ERIC Educational Resources Information Center

Grilo, Carlos M.; Masheb, Robin M.; Wilson, G. Terence; Gueorguieva, Ralitza; White, Marney A.

2011-01-01

Objective: Cognitive-behavioral therapy (CBT) is the best established treatment for binge-eating disorder (BED) but does not produce weight loss. The efficacy of behavioral weight loss (BWL) in obese patients with BED is uncertain. This study compared CBT, BWL, and a sequential approach in which CBT is delivered first, followed by BWL (CBT + BWL).…

Deadly intracranial bleed in patients with dengue fever: A series of nine patients and review of literature

PubMed Central

Sam, Jo Ee; Gee, Teak Sheng; Nasser, Abdul Wahab

2016-01-01

Introduction: Dengue fever is a global pandemic threat with increasing incidence. To date, there are no cures and the effectiveness of dengue vaccines is still uncertain. World Heath Organization introduced expanded dengue syndrome to include unusual presentations of dengue fever including severe neurologic complications. One of the deadly complications is intracranial hemorrhage (ICH). Methodology: We collected data of patients with ICH diagnosed via a plain computed tomography of the brain (CT brain) with thrombocytopenia and positive Dengue virus type 1 nonstructural protein (NS1) antigen test or positive dengue serology IgM from January 2014 till June 2015 at our center. Nine patients were included and all 20 other remaining patients reported in literature so far are discussed. Discussion: We found that all patients in our center requiring neurosurgical intervention died. Another interesting observation is that detection of Dengue IgG usually meant more severe ICH and poorer outcomes. From our series, platelet levels did not seem to influence the outcome. Conclusion: We recommend that for early detection of ICH, Dengue IgG should be routinely screened and a high index of suspicion be maintained. Future research should be focused on determining predictors of ICH in patients with dengue fever so that preventive steps can be taken as mortality is high and no treatment seems beneficial at the moment once severe ICH occurs. PMID:27365962

Long-Term Effects of Spironolactone in Peritoneal Dialysis Patients

PubMed Central

Mizuno, Masashi; Suzuki, Yasuhiro; Tamai, Hirofumi; Hiramatsu, Takeyuki; Ohashi, Hiroshige; Ito, Isao; Kasuga, Hirotake; Horie, Masanobu; Maruyama, Shoichi; Yuzawa, Yukio; Matsubara, Tatsuaki; Matsuo, Seiichi

2014-01-01

ESRD treated with dialysis is associated with increased left ventricular hypertrophy, which, in turn, is related to high mortality. Mineralocorticoid receptor antagonists improve survival in patients with chronic heart failure; however, the effects in patients undergoing dialysis remain uncertain. We conducted a multicenter, open-label, prospective, randomized trial with 158 patients receiving angiotensin-converting enzyme inhibitor or angiotensin type 1 receptor antagonist and undergoing peritoneal dialysis with and without (control group) spironolactone for 2 years. As a primary endpoint, rate of change in left ventricular mass index assessed by echocardiography improved significantly at 6 (P=0.03), 18 (P=0.004), and 24 (P=0.01) months in patients taking spironolactone compared with the control group. Rate of change in left ventricular ejection fraction improved significantly at 24 weeks with spironolactone compared with nontreatment (P=0.02). The benefits of spironolactone were clear in patients with reduced residual renal function. As secondary endpoints, renal Kt/V and dialysate-to-plasma creatinine ratio did not differ significantly between groups during the observation period. No serious adverse effects, such as hyperkalemia, occurred. In this trial, spironolactone prevented cardiac hypertrophy and decreases in left ventricular ejection fraction in patients undergoing peritoneal dialysis, without significant adverse effects. Further studies, including those to determine relative effectiveness in women and men and to evaluate additional secondary endpoints, should confirm these data in a larger cohort. PMID:24335969

Deciphering Variability of PKD1 and PKD2 in an Italian Cohort of 643 Patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD)

PubMed Central

Carrera, Paola; Calzavara, Silvia; Magistroni, Riccardo; den Dunnen, Johan T.; Rigo, Francesca; Stenirri, Stefania; Testa, Francesca; Messa, Piergiorgio; Cerutti, Roberta; Scolari, Francesco; Izzi, Claudia; Edefonti, Alberto; Negrisolo, Susanna; Benetti, Elisa; Alibrandi, Maria Teresa Sciarrone; Manunta, Paolo; Boletta, Alessandra; Ferrari, Maurizio

2016-01-01

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common hereditary kidney disease. We analysed PKD1 and PKD2, in a large cohort of 440 unrelated Italian patients with ADPKD and 203 relatives by direct sequencing and MLPA. Molecular and detailed phenotypic data have been collected and submitted to the PKD1/PKD2 LOVD database. This is the first large retrospective study in Italian patients, describing 701 variants, 249 (35.5%) already associated with ADPKD and 452 (64.5%) novel. According to the criteria adopted, the overall detection rate was 80% (352/440). Novel variants with uncertain significance were found in 14% of patients. Among patients with pathogenic variants, in 301 (85.5%) the disease is associated with PKD1, 196 (55.7%) truncating, 81 (23%) non truncating, 24 (6.8%) IF indels, and in 51 (14.5%) with PKD2. Our results outline the high allelic heterogeneity of variants, complicated by the presence of variants of uncertain significance as well as of multiple variants in the same subject. Classification of novel variants may be particularly cumbersome having an important impact on the genetic counselling. Our study confirms the importance to improve the assessment of variant pathogenicity for ADPKD; to this point databasing of both clinical and molecular data is crucial. PMID:27499327

Specifying the effects of physician's communication on patients' outcomes: A randomised controlled trial.

PubMed

van Osch, Mara; van Dulmen, Sandra; van Vliet, Liesbeth; Bensing, Jozien

2017-08-01

To experimentally test the effects of physician's affect-oriented communication and inducing expectations on outcomes in patients with menstrual pain. Using a 2×2 RCT design, four videotaped simulated medical consultations were used, depicting a physician and a patient with menstrual pain. In the videos, two elements of physician's communication were manipulated: (1) affect-oriented communication (positive: warm, emphatic; versus negative: cold, formal), and (2) outcome expectation induction (positive versus uncertain). Participants (293 women with menstrual pain), acting as analogue patients, viewed one of the four videos. Pre- and post video participants' outcomes (anxiety, mood, self-efficacy, outcome expectations, and satisfaction) were assessed. Positive affect-oriented communication reduced anxiety (p<0.001), negative mood (p=0.001), and increased satisfaction (p<0.001) compared to negative affect-oriented communication. Positive expectations increased feelings of self-efficacy (p<0.001) and outcome expectancies (p<0.001), compared to uncertain expectations, but did not reduce anxiety. The combination of positive affect-oriented communication and a positive expectation reduced anxiety (p=0.02), increased outcome expectancies (p=0.01) and satisfaction (p=0.001). Being empathic and inducing positive expectations have distinct and combined effects, demonstrating that both are needed to influence patients' outcomes for the best. Continued medical training is needed to harness placebo-effects of medical communication into practice. Copyright © 2017 Elsevier B.V. All rights reserved.

OPTICAL SPECTROSCOPIC OBSERVATIONS OF GAMMA-RAY BLAZAR CANDIDATES. V. TNG, KPNO, AND OAN OBSERVATIONS OF BLAZAR CANDIDATES OF UNCERTAIN TYPE IN THE NORTHERN HEMISPHERE

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

Álvarez Crespo, N.; Massaro, F.; Masetti, N.

The extragalactic γ-ray sky is dominated by emission from blazars, a peculiar class of active galactic nuclei. Many of the γ-ray sources included in the Fermi-Large Area Telescope Third Source catalog (3FGL) are classified as blazar candidates of uncertain type (BCUs) because there are no optical spectra available in the literature to confirm their nature. In 2013, we started a spectroscopic campaign to look for the optical counterparts of the BCUs and of the unidentified γ-ray sources to confirm their blazar nature. Whenever possible we also determine their redshifts. Here, we present the results of the observations carried out inmore » the northern hemisphere in 2013 and 2014 at the Telescopio Nazionale Galileo, Kitt Peak National Observatory, and Observatorio Astronómico Nacional in San Pedro Mártir. In this paper, we describe the optical spectra of 25 sources. We confirmed that all of the 15 BCUs observed in our campaign and included in our sample are blazars and we estimated the redshifts for three of them. In addition, we present the spectra for three sources classified as BL Lacs in the literature but with no optical spectra available to date. We found that one of them is a quasar (QSO) at a redshift of z = 0.208 and the other two are BL Lacs. Moreover, we also present seven new spectra for known blazars listed in the Roma-BZCAT that have an uncertain redshift or are classified as BL Lac candidates. We found that one of them, 5BZB J0724+2621, is a “changing look” blazar. According to the spectrum available in the literature, it was classified as a BL Lac, but in our observation we clearly detected a broad emission line that led us to classify this source as a QSO at z = 1.17.« less

Gauging Metallicity of Diffuse Gas under an Uncertain Ionizing Radiation Field

NASA Astrophysics Data System (ADS)

Chen, Hsiao-Wen; Johnson, Sean D.; Zahedy, Fakhri S.; Rauch, Michael; Mulchaey, John S.

2017-06-01

Gas metallicity is a key quantity used to determine the physical conditions of gaseous clouds in a wide range of astronomical environments, including interstellar and intergalactic space. In particular, considerable effort in circumgalactic medium (CGM) studies focuses on metallicity measurements because gas metallicity serves as a critical discriminator for whether the observed heavy ions in the CGM originate in chemically enriched outflows or in more chemically pristine gas accreted from the intergalactic medium. However, because the gas is ionized, a necessary first step in determining CGM metallicity is to constrain the ionization state of the gas which, in addition to gas density, depends on the ultraviolet background radiation field (UVB). While it is generally acknowledged that both the intensity and spectral slope of the UVB are uncertain, the impact of an uncertain spectral slope has not been properly addressed in the literature. This Letter shows that adopting a different spectral slope can result in an order of magnitude difference in the inferred CGM metallicity. Specifically, a harder UVB spectrum leads to a higher estimated gas metallicity for a given set of observed ionic column densities. Therefore, such systematic uncertainties must be folded into the error budget for metallicity estimates of ionized gas. An initial study shows that empirical diagnostics are available for discriminating between hard and soft ionizing spectra. Applying these diagnostics helps reduce the systematic uncertainties in CGM metallicity estimates.

Gauging Metallicity of Diffuse Gas under an Uncertain Ionizing Radiation Field

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

Chen, Hsiao-Wen; Zahedy, Fakhri S.; Johnson, Sean D.

Gas metallicity is a key quantity used to determine the physical conditions of gaseous clouds in a wide range of astronomical environments, including interstellar and intergalactic space. In particular, considerable effort in circumgalactic medium (CGM) studies focuses on metallicity measurements because gas metallicity serves as a critical discriminator for whether the observed heavy ions in the CGM originate in chemically enriched outflows or in more chemically pristine gas accreted from the intergalactic medium. However, because the gas is ionized, a necessary first step in determining CGM metallicity is to constrain the ionization state of the gas which, in addition tomore » gas density, depends on the ultraviolet background radiation field (UVB). While it is generally acknowledged that both the intensity and spectral slope of the UVB are uncertain, the impact of an uncertain spectral slope has not been properly addressed in the literature. This Letter shows that adopting a different spectral slope can result in an order of magnitude difference in the inferred CGM metallicity. Specifically, a harder UVB spectrum leads to a higher estimated gas metallicity for a given set of observed ionic column densities. Therefore, such systematic uncertainties must be folded into the error budget for metallicity estimates of ionized gas. An initial study shows that empirical diagnostics are available for discriminating between hard and soft ionizing spectra. Applying these diagnostics helps reduce the systematic uncertainties in CGM metallicity estimates.« less

Uncertainty increases neural indices of attention in obsessive-compulsive disorder.

PubMed

Dieterich, Raoul; Endrass, Tanja; Kathmann, Norbert

2017-11-01

Patients with obsessive-compulsive disorder (OCD) experience abnormally high levels of uncertainty, and unpredictability is evaluated negatively and not well tolerated. The current study examined neural correlates of attentional processing in response to experimentally induced uncertainty in OCD. Twenty-four OCD patients and 24 healthy controls performed a task where neutral and negative pictures were preceded by a cue, either being predictive (certain condition) or nonpredictive (uncertain condition) of subsequent picture valence. We examined prepicture anticipatory attention through α (∼8-12 Hz) suppression, and attentional allocation during picture presentation with the P1, N1, P2, N2, and late positive potential (LPP) of the event-related potential. Additionally, we tested how clinical measures related to these attentional markers. Subjectively, patients overestimated the frequency of negative pictures after nonpredictive cues. Patients, but not controls, showed upper α(10-12 Hz) suppression after nonpredictive and predictive negative cues relative to predictive neutral cues. Only patients showed increased P2 and decreased N2 amplitudes for pictures after nonpredictive cues, and, whereas both groups showed increased LPP amplitudes for pictures after nonpredictive cues, this modulation was more pronounced in OCD during the early LPP (<1,000 ms). In patients, P2 and LPP amplitudes for negative pictures were associated positively with anxiety and negatively with depression. These results suggest that OCD patients process anticipation of inevitable and potential threat similarly and highlight the substantial motivational impact of uncertain events to OCD patients. Finally, the correlation with anxiety implies that anxiety represents the source of hypervigilance during uncertainty resolution. © 2017 Wiley Periodicals, Inc.

Compete, coordinate, and cooperate: How to exploit uncertain environments with social interaction.

PubMed

Schulze, Christin; Newell, Ben R

2015-10-01

Countless decisions, from the trivial to the crucial, are made in complex social contexts while facing uncertain consequences. Yet a large portion of decision making research focuses on either the effects of social interaction or the effects of environmental uncertainty by examining strategic games against others or individual games against nature. Drawing a connection between these approaches, the authors extend a standard individual choice paradigm to include social interaction with 1 other person. In this paradigm, 2 competing decision makers repeatedly select among 2 options, each offering a particular probability of a fixed payoff. When both players choose the same, correct option, the payoff is evenly split; when they choose different options, the player choosing the correct option receives the full payoff. The addition of this social dimension gives players an opportunity to fully exploit an uncertain environment via cooperation: By consistently choosing opposite options, two players can exploit the uncertain environment more effectively than a single player could. We present 2 experiments that manipulate environmental (Experiment 1) and social (Experiment 2) aspects of the paradigm. In Experiment 1, the outcome probabilities were either known or unknown to participants; in Experiment 2, participants' attention was drawn to individual or group gains by introducing either within- or between-group competition. Efficient cooperation did not emerge spontaneously in Experiment 1. Instead, most people probability maximized, mirroring the behavior observed in individual choice. By contrast, between--group competition in Experiment 2 facilitated efficient-but not always equitable--exploitation of uncertain environments. This work links the concepts of individual risky choice and strategic decision making under both environmental and social uncertainty. (c) 2015 APA, all rights reserved).

Cued uncertainty modulates later recognition of emotional pictures: An ERP study.

PubMed

Lin, Huiyan; Xiang, Jing; Li, Saili; Liang, Jiafeng; Zhao, Dongmei; Yin, Desheng; Jin, Hua

2017-06-01

Previous studies have shown that uncertainty about the emotional content of an upcoming event modulates event-related potentials (ERPs) during the encoding of the event, and this modulation is affected by whether there are cues (i.e., cued uncertainty) or not (i.e., uncued uncertainty) prior to the encoding of the uncertain event. Recently, we showed that uncued uncertainty affected ERPs in later recognition of the emotional event. However, it is as yet unknown how the ERP effects of recognition are modulated by cued uncertainty. To address this issue, participants were asked to view emotional (negative and neutral) pictures that were presented after cues. The cues either indicated the emotional content of the pictures (the certain condition) or not (the cued uncertain condition). Subsequently, participants had to perform an unexpected old/new task in which old and novel pictures were shown without any cues. ERP data in the old/new task showed smaller P2 amplitudes for neutral pictures in the cued uncertain condition compared to the certain condition, but this uncertainty effect was not observed for negative pictures. Additionally, P3 amplitudes were generally enlarged for pictures in the cued uncertain condition. Taken together, the present findings indicate that cued uncertainty alters later recognition of emotional events in relevance to feature processing and attention allocation. Copyright © 2017. Published by Elsevier B.V.

Association of the average rate of change in HbA1c with severe adverse events: a longitudinal evaluation of audit data from the Bavarian Disease Management Program for patients with type 2 diabetes mellitus.

PubMed

Bonke, Florian C; Donnachie, Ewan; Schneider, Antonius; Mehring, Michael

2016-02-01

In patients with type 2 diabetes mellitus, the effects of HbA1c variability on macrovascular events remain uncertain. The present investigation evaluates the association of HbA1c variability with non-fatal cardiovascular events, emergency admissions and episodes of severe hypoglycaemia in a cohort of patients newly started on insulin therapy. HbA1c variability was defined as the rate of change in values between observations. The medical records of 406,356 patients enrolled in a disease management programme for type 2 diabetes mellitus were analysed to identify a cohort of 13,777 patients with observed transition to insulin therapy. The cohort was observed for a period of at least 5 years. Cox regression models were applied to quantify the association of HbA1c variability with the events of interest. The models reveal a significant non-linear association between HbA1c variability and the risk of experiencing myocardial infarction, stroke and hypoglycaemia. The lowest risk is seen with a variability of approximately 0.5% (5.5 mmol/mol) per quarter. Using Cox models to predict survival curves for the cohort with hypothetical HbA1c variability of 0.5% (5.5 mmol/mol) and 1.5% (16.4 mmol/mol) per quarter, the proportion experiencing myocardial infarction within 2 years increases significantly from 1% to 10%. The proportion experiencing stroke increases from 1% to 29%, hypoglycaemia from 2% to 24% and the risk of emergency admission from 2% to 21%. In patients newly started on insulin therapy, rapid and higher HbA1c variability is associated with an increased risk of myocardial infarction, stroke, severe hypoglycaemia and emergency admission.

Pancreatic head excavation for tissue diagnosis may reduce unnecessary pancreaticoduodenectomies in the setting of chronic pancreatitis.

PubMed

Fancellu, Alessandro; Ginesu, Giorgio C; Feo, Claudio F; Cossu, Maria L; Puledda, Marco; Pinna, Antonio; Porcu, Alberto

2017-06-01

The necessity to obtain a tissue diagnosis of cancer prior to pancreatic surgery still remains an open debate. In fact, a non-negligible percentage of patients undergoing pancreaticoduodenectomy (PD) for suspected cancer has a benign lesion at final histology. We describe an approach for patients with diagnostic uncertainty between cancer and chronic pancreatitis, with the aim of minimizing the incidence of PD for suspicious malignancy finally diagnosed as benign disease. Eighty-eight patients (85.4%) with a clinicoradiological picture highly suggestive for malignancy received formal PD (group 1). Fifteen patients (14.6%) in whom preoperative diagnosis was uncertain between pancreatic cancer and chronic pancreatitis underwent pancreatic head excavation (PHEX) for intraoperative tissue diagnosis (group 2): those diagnosed as having cancer received PD, whereas those with chronic pancreatitis received pancreaticojejunostomy (PJ). No patient received PD for benign disease. All patients in group 1 had adenocarcinoma on final histology. Eight patients of group 2 (53.3%) received PD after intraoperative diagnosis of cancer, whereas 7 (46.7%) received PJ because no malignancy was found at introperative frozen sections. No signs of cancer were encountered in patients receiving PHEX and PJ after a median follow-up of 42 months. Overall survival did not differ between patients receiving PD for cancer in the group 1 and those receiving PD for cancer after PHEX in the group 2 (P=0.509). Although the described technique has been used in a very selected group of patients, our results suggest that PHEX for tissue diagnosis may reduce rates of unnecessary PD, when the preoperative diagnosis is uncertain between cancer and chronic pancreatitis.

Multiple sclerosis and human T-cell lymphotropic retroviruses

NASA Astrophysics Data System (ADS)

Koprowski, Hilary; Defreitas, Elaine C.; Harper, Mary E.; Sandberg-Wollheim, Magnhild; Sheremata, William A.; Robert-Guroff, Marjorie; Saxinger, Carl W.; Feinberg, Mark B.; Wong-Staal, Flossie; Gallo, Robert C.

1985-11-01

A combination of different types of data suggests that some multiple sclerosis patients respond immunologically to, and have cerebrospinal T cells containing, a retrovirus that is related to, but distinct from, the three types of human T-cell lymphotropic viruses. The role of this virus in multiple sclerosis is uncertain.

Treatment outcome of intravenous artesunate in patients with severe malaria in the Netherlands and Belgium.

PubMed

Kreeftmeijer-Vegter, Annemarie R; van Genderen, Perry J; Visser, Leo G; Bierman, Wouter F W; Clerinx, Jan; van Veldhuizen, Cees K W; de Vries, Peter J

2012-03-31

Intravenous (IV) artesunate is the treatment of choice for severe malaria. In Europe, however, no GMP-manufactured product is available and treatment data in European travellers are scarce. Fortunately, artesunate became available in the Netherlands and Belgium through a named patient programme. This is the largest case series of artesunate treated patients with severe malaria in Europe. Hospitalized patients treated with IV artesunate between November 2007 and December 2010 in the Netherlands and Belgium were retrospectively evaluated. Patient characteristics, treatment and clinical outcome were recorded on a standardized form and mortality, parasite clearance times and the occurrence of adverse events were evaluated. Of the 68 treated patients, including 55 with severe malaria, two patients died (2/55 = 3.6%). The mean time to 50% parasite clearance (PCT50), 90% and 99% were 4.4 hours (3.9 - 5.2), 14.8 hours (13.0 - 17.2), and 29.5 hours (25.9 - 34.4) respectively. Artesunate was well tolerated. However, an unusual form of haemolytic anaemia was observed in seven patients. The relationship with artesunate remains uncertain. Data from the named patient programme demonstrate that IV artesunate is effective and well-tolerated in European travellers lacking immunity. However, increased attention needs to be paid to the possible development of haemolytic anaemia 2-3 weeks after start of treatment.Treatment of IV artesunate should be limited to the period that IV treatment is required and should be followed by a full oral course of an appropriate anti-malarial drug.

Ibrutinib (Imbruvica). Relapsed chronic lymphocytic leukaemia and mantle cell lymphoma: uncertain impact on survival.

PubMed

January

2016-04-01

codynamic interactions are also likely in view of its adverse effect profile. There is no consensus on the treatment of patients with refractory or relapsed mantle cell lymphoma, or for patients with relapsed or possibly refractory chronic lymphocytic leukaemia. Ibrutinib inhibits an enzyme involved in regulating B lymphocyte activity. It has been authorised in the European Union for these conditions. Clinical evaluation of ibrutinib in mantle cell lymphoma is based on a single non-comparative trial in 111 patients, in which the median overall survival time was 22.5 months. Clinical evaluation of ibrutinib in chronic lymphocytic leukaemia is based on two randomised trials. One unblinded trial compared ibrutinib versus ofatumumab and involved 391 patients, most of whom were sufficiently fit to receive anticancer combination therapy. Ibrutinib was more effective than ofatumumab, but the choice of this comparator might not have been appropriate for most of the patients who received it. The other double-blind, placebo-controlled trial involved 578 patients with relapsed or refractory chronic lymphocytic leukaemia. Ibrutinib was added to the bendamustine + rituximab combination. No significant difference in mortality was observed between the two groups. The main adverse effects of ibrutinib were: gastrointestinal disorders such as diarrhoea; life-threatening infections and bleeding disorders; and cardiac disorders, including atrial fibrillation. Ibrutinib carries a risk of multiple pharmacokinetic interactions. Pharmacodynamic interactions are also likely in view of its adverse effect profile.

Characteristics of anemia in subclinical and overt hypothyroid patients.

PubMed

Erdogan, Mehmet; Mehmet, Erdogan; Kösenli, Aybike; Aybike, Kosenli; Ganidagli, Sencer; Kulaksizoglu, Mustafa; Mustafa, Kulaksizoglu

2012-01-01

Thyroid hormones stimulate directly or indirectly growth of erythroid colonies through erythropoietin. Anemia is often the first sign of hypothyroidism. Hypothyroidism can cause a wide variety of anemic disorders. Numerous mechanisms are involved in the pathogenesis of these anemias that can be microcytic, macrocytic and normocytic. We designed this study to investigate the anemia frequency and if present, etiology of anemia in hypothyroid patients. 100 patients with overt hypothyroid, 100 patients with subclinical hypothyroid, and 200 healthy controls were enrolled in this study. Overt hypothyroidism diagnosis is done when elevated TSH and low levels of free T4 and/or free T3 have been observed. Subclinical hypothyroidism is defined as elevated serum TSH with normal free T(4) and free T(3) levels. Peripheral smears of the anemic patients were examined. Anemia prevalence was 43% in the overt hypothyroid group, 39% in the subclinical hypothyroid group, and 26% in the control group (p=0.0003 and p=0.021 respectively related to controls). Thus, the frequency of anemia in subclinical hypothyroidism is as high as that in overt hypothyroidism. There was no difference between the hypothyroid groups in terms of anemia. Vitamin B12, Fe, and folic acid were similar between these groups. According to our findings, anemia of chronic disease is the most common type of anemia in hypothyroid patients. Suspicion of hypothyroidism should be considered in anemias with uncertain etiology.

Clinical germline diagnostic exome sequencing for hereditary cancer: Findings within novel candidate genes are prevalent.

PubMed

Powis, Zöe; Espenschied, Carin R; LaDuca, Holly; Hagman, Kelly D; Paudyal, Tripti; Li, Shuwei; Inaba, Hiroto; Mauer, Ann; Nathanson, Katherine L; Knost, James; Chao, Elizabeth C; Tang, Sha

2018-08-01

Clinical diagnostic exome sequencing (DES) has been effective in diagnosing individuals with suspected genetic conditions; nevertheless little has been described regarding its clinical utility in individuals with a personal and family history of cancer. This study aimed to assess diagnostic yield and clinical characteristics of pediatric and adult patients undergoing germline DES for hereditary cancer. We retrospectively reviewed 2171 patients referred for DES; cases with a personal and/or family history of cancer were further studied. Of 39 cancer patients, relevant alterations were found in eight individuals (21%), including one (3%) positive pathogenic alteration within a characterized gene, two (5%) uncertain findings in characterized genes, and five (13%) alterations in novel candidate genes. Two of the 5 pediatric patients, undergoing testing, (40%) had findings in novel candidate genes, with the remainder being negative. We include brief case studies to illustrate the variety of challenging issues related to these patients. Our observations demonstrate utility of family-based exome sequencing in patients for suspected hereditary cancer, including familial co-segregation analysis, and comprehensive medical review. DES may be particularly useful when traditional approaches do not result in a diagnosis or in families with unique phenotypes. This work also highlights the importance and complexity of analysis of uncharacterized genes in exome sequencing for hereditary cancer. Copyright © 2018 Elsevier Inc. All rights reserved.

Carvedilol case history: the discovery and development of the first β-blocker for the treatment of congestive heart failure.

PubMed

Ruffolo, Robert R; Feuerstein, Giora Z

2006-06-01

Carvedilol is a multiple action drug that blocks β1-, β2- and α1- adrenoceptors, and has potent antioxidant properties. Carvedilol is the first drug of its kind to be approved for the treatment of congestive heart failure, and is now the standard of care for this devastating disease. The discovery and development of carvedilol encountered an adverse regulatory climate, skepticism by the cardiology community and hesitance by the company, and in the early 1990s, the fate of the drug was uncertain. Nonetheless, in the largest heart failure study conducted up until that point, carvedilol produced marked reductions in morbidity and mortality, and has given new hope to patients afflicted with congestive heart failure. The story behind carvedilol contains important observations and lessons for scientists, regulators and physicians.

Neural-network-based online HJB solution for optimal robust guaranteed cost control of continuous-time uncertain nonlinear systems.

PubMed

Liu, Derong; Wang, Ding; Wang, Fei-Yue; Li, Hongliang; Yang, Xiong

2014-12-01

In this paper, the infinite horizon optimal robust guaranteed cost control of continuous-time uncertain nonlinear systems is investigated using neural-network-based online solution of Hamilton-Jacobi-Bellman (HJB) equation. By establishing an appropriate bounded function and defining a modified cost function, the optimal robust guaranteed cost control problem is transformed into an optimal control problem. It can be observed that the optimal cost function of the nominal system is nothing but the optimal guaranteed cost of the original uncertain system. A critic neural network is constructed to facilitate the solution of the modified HJB equation corresponding to the nominal system. More importantly, an additional stabilizing term is introduced for helping to verify the stability, which reinforces the updating process of the weight vector and reduces the requirement of an initial stabilizing control. The uniform ultimate boundedness of the closed-loop system is analyzed by using the Lyapunov approach as well. Two simulation examples are provided to verify the effectiveness of the present control approach.

Why shared decision making is not good enough: lessons from patients.

PubMed

Olthuis, Gert; Leget, Carlo; Grypdonck, Mieke

2014-07-01

A closer look at the lived illness experiences of medical professionals themselves shows that shared decision making is in need of a logic of care. This paper underlines that medical decision making inevitably takes place in a messy and uncertain context in which sharing responsibilities may impose a considerable burden on patients. A better understanding of patients' lived experiences enables healthcare professionals to attune to what individual patients deem important in their lives.This will contribute to making medical decisions in a good and caring manner, taking into account the lived experience of being ill.

QUANTIFYING AN UNCERTAIN FUTURE: HYDROLOGIC MODEL PERFORMANCE FOR A SERIES OF REALIZED "/FUTURE" CONDITIONS

EPA Science Inventory

A systematic analysis of model performance during simulations based on observed landcover/use change is used to quantify errors associated with simulations of known "future" conditions. Calibrated and uncalibrated assessments of relative change over different lengths of...

An approach to quantifying the efficiency of a Bayesian filter

USDA-ARS?s Scientific Manuscript database

Data assimilation is defined as the Bayesian conditioning of uncertain model simulations on observations for the purpose of reducing uncertainty about model states. Practical data assimilation applications require that simplifying assumptions be made about the prior and posterior state distributions...

Communicating Uncertain Experimental Evidence

ERIC Educational Resources Information Center

Davis, Alexander L.; Fischhoff, Baruch

2014-01-01

Four experiments examined when laypeople attribute unexpected experimental outcomes to error, in foresight and in hindsight, along with their judgments of whether the data should be published. Participants read vignettes describing hypothetical experiments, along with the result of the initial observation, considered as either a possibility…

Chronic kidney disease of uncertain etiology in Sri Lanka is a possible sequel of interstitial nephritis!

PubMed

Badurdeen, Zeid; Nanayakkara, Nishantha; Ratnatunga, Neelakanthi V I; Wazil, Abdul W M; Abeysekera, Tilak D J; Rajakrishna, Premil N; Thinnarachchi, Jalitha P; Kumarasiri, Ranjith; Welagedera, Dulani D; Rajapaksha, Needika; Alwis, Adambarage P D

The majority of published data on chronic kidney disease of uncertain etiology (CKDu) is on asymptomatic patients who were detected in screening programs. The clinicopathological profile of a group of patients presenting with acute symptoms and renal dysfunction from CKDu endemic regions in Sri Lanka was studied. 59 patients > 10 years of age with backache, feverish fatigue feeling, dysuria, joint pain, or dyspepsia, singly or in combination with elevated serum creatinine (> 116 and > 98 µmol/L for male and females, respectively) were included in the study. Those patients who had normal-sized kidneys were biopsied after excluding clinically detectable causes for renal dysfunction. Histology was scored with activity and chronicity indices. These patients' urinary sediment and inflammatory markers were checked. Patients were stratified into three groups based on duration of symptom onset to the time of biopsy. The natural course of the disease was described using serial mean serum creatinine and histological activity as well as chronicity indices in these 3 groups. These patients' mean age, occupation, and sex ratio were 44 (9) years, 57 farmers, and male : female 55 : 4, respectively. Mean serum creatinine at biopsy was 143.8 (47.9) µmol/L. Elevated inflammatory markers and active urine sediment were reported. Histology was compatible with an interstitial nephritis with a mixture of acute and chronic tubulointerstitial lesions and glomerular scarring. In the natural course of an acute episode of CKDu, serum creatinine and histological activity were reduced while histological chronicity increased. CKDu may be preceded by an acute episode of tubulointerstitial nephritis (TIN).

Patterns of Novel Alleles and Genotype/Phenotype Correlations Resulting from the Analysis of 108 Previously Undetected Mutations in Patients Affected by Neurofibromatosis Type I

PubMed Central

Bonatti, Francesco; Adorni, Alessia; Matichecchia, Annalisa; Mozzoni, Paola; Uliana, Vera; Pisani, Francesco; Garavelli, Livia; Graziano, Claudio; Gnoli, Maria; Bigoni, Stefania; Boschi, Elena; Martorana, Davide; Percesepe, Antonio

2017-01-01

Neurofibromatosis type I, a genetic disorder due to mutations in the NF1 gene, is characterized by a high mutation rate (about 50% of the cases are de novo) but, with the exception of whole gene deletions associated with a more severe phenotype, no specific hotspots and few solid genotype/phenotype correlations. After retrospectively re-evaluating all NF1 gene variants found in the diagnostic activity, we studied 108 patients affected by neurofibromatosis type I who harbored mutations that had not been previously reported in the international databases, with the aim of analyzing their type and distribution along the gene and of correlating them with the phenotypic features of the affected patients. Out of the 108 previously unreported variants, 14 were inherited by one of the affected parents and 94 were de novo. Twenty-nine (26.9%) mutations were of uncertain significance, whereas 79 (73.2%) were predicted as pathogenic or probably pathogenic. No differential distribution in the exons or in the protein domains was observed and no statistically significant genotype/phenotype correlation was found, confirming previous evidences. PMID:28961165

Slowness in Movement Initiation is Associated with Proactive Inhibitory Network Dysfunction in Parkinson's Disease.

PubMed

Criaud, Marion; Poisson, Alice; Thobois, Stéphane; Metereau, Elise; Redouté, Jérôme; Ibarrola, Danièle; Baraduc, Pierre; Broussolle, Emmanuel; Strafella, Antonio P; Ballanger, Bénédicte; Boulinguez, Philippe

2016-04-02

Impairment in initiating movements in PD might be related to executive dysfunction associated with abnormal proactive inhibitory control, a pivotal mechanism consisting in gating movement initiation in uncertain contexts. Testing this hypothesis on the basis of direct neural-based evidence. Twelve PD patients on antiparkinsonian medication and fifteen matched healthy controls performed a simple reaction time task during event-related functional MRI scanning. For all subjects, the level of activation of SMA was found to predict RT on a trial-by-trial basis. The increase in movement initiation latency observed in PD patients with regard to controls was associated with pre-stimulus BOLD increases within several nodes of the proactive inhibitory network (caudate nucleus, precuneus, thalamus). These results provide physiological data consistent with impaired control of proactive inhibition over motor initiation in PD. Patients would be locked into a mode of control maintaining anticipated inhibition over willed movements even when the situation does not require action restraint. The functional and neurochemical bases of brain activity associated with executive settings need to be addressed thoroughly in future studies to better understand disabling symptoms that have few therapeutic options like akinesia.

Electronic health records to facilitate clinical research.

PubMed

Cowie, Martin R; Blomster, Juuso I; Curtis, Lesley H; Duclaux, Sylvie; Ford, Ian; Fritz, Fleur; Goldman, Samantha; Janmohamed, Salim; Kreuzer, Jörg; Leenay, Mark; Michel, Alexander; Ong, Seleen; Pell, Jill P; Southworth, Mary Ross; Stough, Wendy Gattis; Thoenes, Martin; Zannad, Faiez; Zalewski, Andrew

2017-01-01

Electronic health records (EHRs) provide opportunities to enhance patient care, embed performance measures in clinical practice, and facilitate clinical research. Concerns have been raised about the increasing recruitment challenges in trials, burdensome and obtrusive data collection, and uncertain generalizability of the results. Leveraging electronic health records to counterbalance these trends is an area of intense interest. The initial applications of electronic health records, as the primary data source is envisioned for observational studies, embedded pragmatic or post-marketing registry-based randomized studies, or comparative effectiveness studies. Advancing this approach to randomized clinical trials, electronic health records may potentially be used to assess study feasibility, to facilitate patient recruitment, and streamline data collection at baseline and follow-up. Ensuring data security and privacy, overcoming the challenges associated with linking diverse systems and maintaining infrastructure for repeat use of high quality data, are some of the challenges associated with using electronic health records in clinical research. Collaboration between academia, industry, regulatory bodies, policy makers, patients, and electronic health record vendors is critical for the greater use of electronic health records in clinical research. This manuscript identifies the key steps required to advance the role of electronic health records in cardiovascular clinical research.

Influence of Double-J Catheters on Urinary Infections After Kidney Transplantation.

PubMed

Jonas, M; Jóźwik, A; Kawecki, D; Durlik, M; Pączek, L; Młynarczyk, G; Chmura, A

2016-06-01

One of the most important problem in kidney transplantation is risk of the urinary anastomosis stricture. In uncertain cases the use of a double-J (or JJ) catheter is a standard solution. In case of urinary leak or fistula after the reanastomosis operation, transuretheral JJ implantation is used. A number of patients after JJ use present urinary infection. Between 2012 and 2014, 283 kidney transplantations were performed in our center. In 77 cases (27.2%), a JJ was used at the time of operation, in 10 other cases (3.5%) during postoperative period. Urinary infection was observed in 95 patients (33.6%), with Proteus, Klebsiella, Enterobacter, Escherichia, Enterococcus, Pseudomonas, Morganella, and Staphylococcus cultures. In the group of patients without JJ catheters, infections were found in 27.6% of cases and in group with JJ, in 47.1% (46.8% in intraoperative use of catheters and 50% in postoperative curse). The analysis shows that use of JJ catheters gives urinary infections almost twice more frequent (47.1% vs 27.6%; P = .001) with no difference if the implantation took place during or after the operation. Copyright © 2016. Published by Elsevier Inc.

Mathematical Modelling of the Infusion Test

NASA Astrophysics Data System (ADS)

Cieslicki, Krzysztof

2007-01-01

The objective of this paper was to improve the well established in clinical practice Marmarou model for intracranial volume-pressure compensation by adding the pulsatile components. It was demonstrated that complicated pulsation and growth in intracranial pressure during infusion test could be successfully modeled by the relatively simple analytical expression derived in this paper. The CSF dynamics were tested in 25 patients with clinical symptoms of hydrocephalus. Basing on the frequency spectrum of the patient's baseline pressure and identified parameters of CSF dynamic, for each patient an "ideal" infusion test curve free from artefacts and slow waves was simulated. The degree of correlation between simulated and real curves obtained from clinical observations gave insight into the adequacy of assumptions of Marmarou model. The proposed method of infusion tests analysis designates more exactly the value of the reference pressure, which is usually treated as a secondary and of uncertain significance. The properly identified value of the reference pressure decides on the degree of pulsation amplitude growth during IT, as well as on the value of elastance coefficient. The artificially generated tests with various pulsation components were also applied to examine the correctness of the used algorithm of identification of the original Marmarou model parameters.

Transfusional iron burden and liver toxicity after bone marrow transplantation for acute myelogenous leukemia and hemoglobinopathies.

PubMed

Jastaniah, Wasil; Harmatz, Paul; Pakbaz, Zahra; Fischer, Roland; Vichinsky, Elliott; Walters, Mark C

2008-02-01

While it is appropriate to treat transfusional iron overload to limit end-organ injury after bone marrow transplantation (BMT) for beta-thalassemia major (TM), this approach after BMT for sickle cell disease (SCD) and hematological malignancies has not been studied. Fifteen children with SCD (n = 4), TM (n = 6), or acute myelogenous leukemia (AML, n = 5) underwent HLA-identical sibling BMT between 2000 and 2003. Prospective evaluations of iron biomarkers were performed and the three groups were compared. The pre-BMT duration and volume of RBC transfusions varied among the three groups, but baseline ferritin and liver iron concentration (LIC) were similar. In contrast, liver histology differed. Liver inflammation was present in four TM patients and portal fibrosis was observed in five TM and one SCD patient. Hepatic veno-occlusive disease (VOD) developed in 5 of 15 patients. VOD was not associated with age, ferritin, ALT, or transfusions, but an association with liver inflammation and elevated LIC was suggested. Phlebotomy was performed in five patients after BMT. Changes in LIC were minimal in non-phlebotomized patients (P = 0.02). Iron biomarkers demonstrated significant iron overload before BMT in patients with malignant and non-malignant disorders. However, iron overload was associated with liver inflammation and VOD primarily in TM patients. The clinical significance of iron overload in patients after BMT remains uncertain, but this is the first study to suggest that VOD may be associated with transfusional iron burden. (c) 2007 Wiley-Liss, Inc.

Impact of low skeletal muscle mass and density on short and long-term outcome after resection of stage I-III colorectal cancer.

PubMed

van Vugt, Jeroen L A; Coebergh van den Braak, Robert R J; Lalmahomed, Zarina S; Vrijland, Wietske W; Dekker, Jan W T; Zimmerman, David D E; Vles, Wouter J; Coene, Peter-Paul L O; IJzermans, Jan N M

2018-06-06

Preoperative low skeletal muscle mass and density are associated with increased postoperative morbidity in patients undergoing curative colorectal cancer (CRC) surgery. However, the long-term effects of low skeletal muscle mass and density remain uncertain. Patients with stage I-III CRC undergoing surgery, enrolled in a prospective observational cohort study, were included. Skeletal muscle mass and density were measured on CT. Patients with high and low skeletal muscle mass and density were compared regarding postoperative complications, disease-free survival (DFS), overall survival (OS), and cancer-specific survival (CSS). In total, 816 patients (53.9% males, median age 70) were included; 50.4% had low skeletal muscle mass and 64.1% low density. The severe postoperative complication rate was significantly higher in patients with low versus high skeletal muscle and density (20.9% versus 13.6%, p = 0.006; 20.0% versus 11.8%, p = 0.003). Low skeletal muscle mass (OR 1.91, p = 0.018) and density (OR 1.87, p = 0.045) were independently associated with severe postoperative complications. Ninety-day mortality was higher in patients with low skeletal muscle mass and density compared with patients with high skeletal muscle mass and density (3.6% versus 1.7%, p = 0.091; 3.4% versus 1.0%, p = 0.038). No differences in DFS were observed. After adjustment for covariates such as age and comorbidity, univariate differences in OS and CSS diminished. Low skeletal muscle mass and density are associated with short-term, but not long-term, outcome in patients undergoing CRC surgery. These findings recommend putting more emphasis on preoperative management of patients at risk for surgical complications, but do not support benefit for long-term outcome. Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

An observational study: associations between nurse-reported hospital characteristics and estimated 30-day survival probabilities

PubMed Central

Tvedt, Christine; Sjetne, Ingeborg Strømseng; Helgeland, Jon; Bukholm, Geir

2014-01-01

Background There is a growing body of evidence for associations between the work environment and patient outcomes. A good work environment may maximise healthcare workers’ efforts to avoid failures and to facilitate quality care that is focused on patient safety. Several studies use nurse-reported quality measures, but it is uncertain whether these outcomes are correlated with clinical outcomes. The aim of this study was to determine the correlations between hospital-aggregated, nurse-assessed quality and safety, and estimated probabilities for 30-day survival in and out of hospital. Methods In a multicentre study involving almost all Norwegian hospitals with more than 85 beds (sample size=30, information about nurses’ perceptions of organisational characteristics were collected. Subscales from this survey were used to describe properties of the organisations: quality system, patient safety management, nurse–physician relationship, staffing adequacy, quality of nursing and patient safety. The average scores for these organisational characteristics were aggregated to hospital level, and merged with estimated probabilities for 30-day survival in and out of hospital (survival probabilities) from a national database. In this observational, ecological study, the relationships between the organisational characteristics (independent variables) and clinical outcomes (survival probabilities) were examined. Results Survival probabilities were correlated with nurse-assessed quality of nursing. Furthermore, the subjective perception of staffing adequacy was correlated with overall survival. Conclusions This study showed that perceived staffing adequacy and nurses’ assessments of quality of nursing were correlated with survival probabilities. It is suggested that the way nurses characterise the microsystems they belong to, also reflects the general performance of hospitals. PMID:24728887

Criteria for the validity of clinical trials of treatments of cohorts of cancer patients based on the Hardin Jones principle.

PubMed Central

Pauling, L; Herman, Z S

1989-01-01

With the assumption of the validity of the Hardin Jones principle that the death rate of members of a homogeneous cohort of cancer patients is constant, three criteria for the validity of clinical trials of cancer treatments are formulated. These criteria are satisfied by most published clinical trials, but one trial was found to violate all three, rendering the validity of its reported results uncertain. PMID:2780542

Lipid-laden macrophage infiltration of human adenocarcinoma in vivo associated with taxol and GCSF treatment.

PubMed

Abramson, N; Castro, S; Goldstein, J D

1997-01-01

This brief report illustrates the presence of lipid-laden macrophages in proximity to metastatic adenocarcinoma cells within the bone marrow of a patient receiving taxol and GCSF therapy. The pathophysiological mechanism is uncertain. Taxol, which is associated with macrophage function in vitro, may have been responsible for the recruitment of macrophages in this patient. GCSF could have contributed as well; however, GCSF usually has little effect on monocytes and macrophages.

Communicating microarray results of uncertain clinical significance in consultation summary letters and implications for practice.

PubMed

Paul, Jean Lillian; Pope-Couston, Rachel; Wake, Samantha; Burgess, Trent; Tan, Tiong Yang

2016-01-01

Letter-writing is an integral practice for genetic health professionals. In Victoria, Australia, patients with a chromosomal variant of uncertain clinical significance (VUS) referred to a clinical geneticist (CG) for evaluation receive consultation summary letters. While communication of uncertainty has been explored in research to some extent, little has focused on how uncertainty is communicated within consultation letters. We aimed to develop a multi-layered understanding of the ways in which CGs communicate diagnostic uncertainty in consultation summary letters. We used theme-oriented discourse analysis of 49 consultation summary letters and thematic analysis of a focus group involving eight CGs. Results showed that CGs have become more confident in their description of VUS as 'contributing factors' to patients' clinical features, but remain hesitant to assign definitive causality. CGs displayed strong epistemic stance when discussing future technological improvements to provide hope and minimise potentially disappointing outcomes for patients and families. CGs reported feeling overwhelmed by their workload associated with increasing numbers of patients with VUS, and this has led to a reduction in the number of review appointments offered over time. This study provides a rich description of the content and process of summary letters discussing VUS. Our findings have implications for letter-writing and workforce management. Furthermore, these findings may be of relevance to VUS identified by genomic sequencing in clinical practice.

Quantum uncertainty switches on or off the error-disturbance tradeoff

NASA Astrophysics Data System (ADS)

Zhang, Yu-Xiang; Su, Zu-En; Zhu, Xuanmin; Wu, Shengjun; Chen, Zeng-Bing

2016-06-01

The indeterminacy of quantum mechanics was originally presented by Heisenberg through the tradeoff between the measuring error of the observable A and the consequential disturbance to the value of another observable B. This tradeoff now has become a popular interpretation of the uncertainty principle. However, the historic idea has never been exactly formulated previously and is recently called into question. A theory built upon operational and state-relevant definitions of error and disturbance is called for to rigorously reexamine the relationship. Here by putting forward such natural definitions, we demonstrate both theoretically and experimentally that there is no tradeoff if the outcome of measuring B is more uncertain than that of A. Otherwise, the tradeoff will be switched on and well characterized by the Jensen-Shannon divergence. Our results reveal the hidden effect of the uncertain nature possessed by the measured state, and conclude that the state-relevant relation between error and disturbance is not almosteverywhere a tradeoff as people usually believe.

The frequency of CSF oligoclonal banding in multiple sclerosis increases with latitude.

PubMed

Lechner-Scott, J; Spencer, B; de Malmanche, T; Attia, J; Fitzgerald, M; Trojano, M; Grand'Maison, F; Gomez, J Antonio C; Izquierdo, G; Duquette, P; Girard, M; Grammond, P; Oreja-Guevara, C; Hupperts, R; Bergamaschi, R; Boz, C; Giuliani, G; van Pesch, V; Iuliano, G; Fiol, M; Cristiano, E; Verheul, F; Saladino, M Laura; Slee, M; Barnett, M; Deri, N; Flechter, S; Vella, N; Shaw, C; Herbert, J; Moore, F; Petkovska-Boskova, T; Jokubaitis, V; Butzkueven, H

2012-07-01

With the advent of MRI scanning, the value of lumbar puncture to assess oligoclonal band (OCB) status-for the diagnosis of multiple sclerosis (MS) is increasingly uncertain. One major issue is that the reported frequency of cerebrospinal fluid (CSF)-restricted oligoclonal banding for the diagnosis of MS varies considerably in different studies. In addition, the relationship between OCB positivity and disease outcome remains uncertain, as reported studies are generally too small to assess comparative disability outcomes with sufficient power. In order to further investigate variation of OCB positivity in patients with MS, we utilized MSBase, a longitudinal, Web-based collaborative MS outcomes registry following clinical cohorts in several continents and latitudes. We also assessed whether OCB positivity affects long-term disability outcome. A total of 13,242 patient records were obtained from 37 MS specialist centres in 19 different countries. OCB status was documented in 4481 (34%) patients and 80% of these were OCB positive. The presence of OCB was associated with degree of latitude (p = 0.02). Furthermore, the outcome of patients negative for CSF-specific OCB was significantly better in comparison to the OCB positive patients, as assessed by Expanded Disability Status Scale change (p < 0.001). The results of this study indicate that latitude could explain some of the inconsistencies in OCB status reported in different populations. The study confirms that OCB positivity in MS is associated with a worse long-term prognosis.

Teaching Evidence-Based Medicine Skills through a Residency-Developed Guideline.

ERIC Educational Resources Information Center

Epling, John; Smucny, John; Patil, Anita; Tudiver, Fred

2002-01-01

Describes a curriculum intended to culminate in a resident-produced, evidence-based guideline for the care of patients with diabetes. Evaluation of the curriculum showed that learners appreciated the skills and knowledge gained in devising guidelines in an evidence-based manner but were uncertain that their searches were complete. Clinical…

Survey of Botulinum Toxin Injections in Anticoagulated Patients: Korean Physiatrists' Preference in Controlling Anticoagulation Profile Prior to Intramuscular Injection.

PubMed

Jang, Yongjun; Park, Geun-Young; Park, Jihye; Choi, Asayeon; Kim, Soo Yeon; Boulias, Chris; Phadke, Chetan P; Ismail, Farooq; Im, Sun

2016-04-01

To evaluate Korean physiatrists' practice of performing intramuscular botulinum toxin injection in anticoagulated patients and to assess their preference in controlling the bleeding risk before injection. As part of an international collaboration survey study, a questionnaire survey was administered to 100 Korean physiatrists. Physiatrists were asked about their level of experience with botulinum toxin injection, the safe international normalized ratio range in anticoagulated patients undergoing injection, their tendency for injecting into deep muscles, and their experience of bleeding complications. International normalized ratio <2.0 was perceived as an ideal range for performing Botulinum toxin injection by 41% of the respondents. Thirty-six respondents replied that the international normalized ratio should be lowered to sub-therapeutic levels before injection, and 18% of the respondents reported that anticoagulants should be intentionally withheld and discontinued prior to injection. In addition, 20%-30% of the respondents answered that they were uncertain whether they should perform the injection regardless of the international normalized ratio values. About 69% of the respondents replied that they did have any standardized protocols for performing botulinum toxin injection in patients using anticoagulants. Only 1 physiatrist replied that he had encountered a case of compartment syndrome. In accordance with the lack of consensus in performing intramuscular botulinum toxin injection in anticoagulated patients, our survey shows a wide range of practices among many Korean physiatrists; they tend to avoid botulinum toxin injection in anticoagulated patients and are uncertain about how to approach these patients. The results of this study emphasize the need for formulating a proper international consensus on botulinum toxin injection management in anticoagulated patients.

Longing for existential recognition: a qualitative study of everyday concerns for people with somatoform disorders.

PubMed

Lind, Annemette Bondo; Risoer, Mette Bech; Nielsen, Klaus; Delmar, Charlotte; Christensen, Morten Bondo; Lomborg, Kirsten

2014-02-01

Patients with somatoform disorders could be vulnerable to stressors and have difficulties coping with stress. The aim was to explore what the patients experience as stressful and how they resolve stress in everyday life. A cross-sectional retrospective design using 24 semi-structured individual life history interviews. Data-analysis was based on grounded theory. A major concern in patients was a longing for existential recognition. This influenced the patients' self-confidence, stress appraisals, symptom perceptions, and coping attitudes. Generally, patients had difficulties with self-confidence and self-recognition of bodily sensations, feelings, vulnerability, and needs, which negatively framed their attempts to obtain recognition in social interactions. Experiences of recognition appeared in three different modalities: 1) "existential misrecognition" covered the experience of being met with distrust and disrespect, 2) "uncertain existential recognition" covered experiences of unclear communication and a perception of not being totally recognized, and 3) "successful existential recognition" covered experiences of total respect and understanding. "Misrecognition" and "uncertain recognition" related to decreased self-confidence, avoidant coping behaviours, increased stress, and symptom appraisal; whereas "successful recognition" related to higher self-confidence, active coping behaviours, decreased stress, and symptom appraisal. Different modalities of existential recognition influenced self-identity and social identity affecting patients' daily stress and symptom appraisals, self-confidence, self-recognition, and coping attitudes. Clinically it seems crucial to improve the patients' ability to communicate concerns, feelings, and needs in social interactions. Better communicative skills and more active coping could reduce the harm the patients experienced by not being recognized and increase the healing potential of successful recognition. Copyright © 2013 Elsevier Inc. All rights reserved.

Gaps in Incorporating Germline Genetic Testing Into Treatment Decision-Making for Early-Stage Breast Cancer.

PubMed

Kurian, Allison W; Li, Yun; Hamilton, Ann S; Ward, Kevin C; Hawley, Sarah T; Morrow, Monica; McLeod, M Chandler; Jagsi, Reshma; Katz, Steven J

2017-07-10

Purpose Genetic testing for breast cancer risk is evolving rapidly, with growing use of multiple-gene panels that can yield uncertain results. However, little is known about the context of such testing or its impact on treatment. Methods A population-based sample of patients with breast cancer diagnosed in 2014 to 2015 and identified by two SEER registries (Georgia and Los Angeles) were surveyed about genetic testing experiences (N = 3,672; response rate, 68%). Responses were merged with SEER data. A patient subgroup at higher pretest risk of pathogenic mutation carriage was defined according to genetic testing guidelines. Patients' attending surgeons were surveyed about genetic testing and results management. We examined patterns and correlates of genetic counseling and testing and the impact of results on bilateral mastectomy (BLM) use. Results Six hundred sixty-six patients reported genetic testing. Although two thirds of patients were tested before surgical treatment, patients without private insurance more often experienced delays. Approximately half of patients (57% at higher pretest risk, 42% at average risk) discussed results with a genetic counselor. Patients with pathogenic mutations in BRCA1/2 or another gene had the highest rates of BLM (higher risk, 80%; average risk, 85%); however, BLM was also common among patients with genetic variants of uncertain significance (VUS; higher risk, 43%; average risk, 51%). Surgeons' confidence in discussing testing increased with volume of patients with breast cancer, but many surgeons (higher volume, 24%; lower volume, 50%) managed patients with BRCA1/2 VUS the same as patients with BRCA1/2 pathogenic mutations. Conclusion Many patients with breast cancer are tested without ever seeing a genetic counselor. Half of average-risk patients with VUS undergo BLM, suggesting a limited understanding of results that some surgeons share. These findings emphasize the need to address challenges in personalized communication about genetic testing.

Physicians' Religious Topic Avoidance during Clinical Interactions.

PubMed

Villagran, Melinda M; MacArthur, Brenda L; Lee, Lauren E; Ledford, Christy J W; Canzona, Mollie R

2017-05-08

Religious and spiritual (R/S) conversations at the end-of-life function to help patients and their families find comfort in difficult circumstances. Physicians who feel uncertain about how to discuss topics related to religious beliefs may seek to avoid R/S conversations with their patients. This study utilized a two-group objective structured clinical examination with a standardized patient to explore differences in physicians' use of R/S topic avoidance tactics during a clinical interaction. Results indicated that physicians used more topic avoidance tactics in response to patients' R/S inquiries than patients' R/S disclosures; however, the use of topic avoidance tactics did not eliminate the need to engage in patient-initiated R/S interactions.

Prevalence of Analgesic Prescriptions among Patients with Cancer in Japan: An Analysis of Health Insurance Claims Data

PubMed Central

Higashi, Takahiro; Yoshimoto, Tetsusuke; Matoba, Motohiro

2012-01-01

Objectives: To promote effective management of cancer pain as a nationwide health policy, it is necessary to monitor the performance of health care providers in managing pain in their patients. To plan a system that monitors the performance of pain management, the exact methods of measurement, including the range of target patients, and estimate the resources must be defined. Performance in pain management can be evaluated either in all patients with cancer or restricted to patients with cancer who are already taking analgesics. Restricting the target patient group to patients on analgesics may be more efficient but the extent of that efficiency remains uncertain. Methods: Using insurance claims from eight employer-sponsored insurance companies, we analyzed data from patients (N = 2858) who had received anti-cancer treatment (ie, surgery, chemotherapy, and radiation therapy) for the five major cancers in Japan (ie, breast, colorectal, liver, lung, and stomach cancers). Results: Overall, 22.9% of patients received some kind of analgesic prescription in the course of a month. Lung cancer patients were more likely to be prescribed analgesic prescriptions (any analgesics 34.8%; opioids 18.2%) than patients with the other four cancers. The observed percentage of patients who received analgesic prescriptions over the study period (ie, January 2005 to November 2009) decreased. Conclusion: If we limit the target patient group to patients with cancer already on analgesics, we can reduce the number of persons to be contacted by about three-fourths, compared to assessing pain in all patients with cancer. Although we do not wish to ignore the problem of undetected pain among patients with cancer, beginning our systematic evaluation with patients with cancer already on analgesics may be a realistic option. PMID:23121757

Functional MRI examination of empathy for pain in people with schizophrenia reveals abnormal activation related to cognitive perspective-taking but typical activation linked to affective sharing

PubMed Central

Vistoli, Damien; Lavoie, Marie-Audrey; Sutliff, Stephanie; Jackson, Philip L.; Achim, Amélie M.

2017-01-01

Background Schizophrenia is associated with important disturbances in empathy that are related to everyday functioning. Empathy is classically defined as including affective (sharing others’ emotions) and cognitive (taking others’ cognitive perspectives) processes. In healthy individuals, studies on empathy for pain revealed specific brain systems associated with these sets of processes, notably the anterior middle cingulate (aMCC) and anterior insula (AI) for affective sharing and the bilateral temporoparietal junction (TPJ) for the cognitive processes, but the integrity of these systems in patients with schizophrenia remains uncertain. Methods Patients with schizophrenia and healthy controls performed a pain empathy task while undergoing fMRI scanning. Participants observed pictures of hands in either painful or nonpainful situations and rated the level of pain while imagining either themselves (self) or an unknown person (other) in these situations. Results We included 27 patients with schizophrenia and 21 healthy controls in our analyses. For the pain versus no pain contrast, patients showed overall typical activation patterns in the aMCC and AI, with only a small part of the aMCC showing reduced activation compared with controls. For the other versus self contrast, patients showed an abnormal modulation of activation in the TPJ bilaterally (extending to the posterior superior temporal sulcus, referred to as the TPJ/pSTS). Limitations The design included an unnecessary manipulation of the visual perspective that reduced the number of trials for analysis. The sample size may not account for the heterogeneity of schizophrenia. Conclusion People with schizophrenia showed relatively intact brain activation when observing others’ pain, but showed abnormalities when asked to take the cognitive perspectives of others. PMID:28556774

Increase in hospital admission rates for heart failure in The Netherlands, 1980-1993.

PubMed Central

Reitsma, J. B.; Mosterd, A.; de Craen, A. J.; Koster, R. W.; van Capelle, F. J.; Grobbee, D. E.; Tijssen, J. G.

1996-01-01

OBJECTIVE: To study the trend in hospital admission rates for heart failure in the Netherlands from 1980 to 1993. DESIGN: All hospital admissions in the Netherlands with a principal discharge diagnosis of heart failure were analysed. In addition, individual records of heart failure patients from a subset of 7 hospitals were analysed to estimate the frequency and timing of readmissions. RESULTS: The total number of discharges for men increased from 7377 in 1980 to 13 022 in 1993, and for women from 7064 to 12 944. From 1980 through 1993 age adjusted discharge rates rose 48% for men and 40% for women. Age adjusted in-hospital mortality for heart failure decreased from 19% in 1980 to 15% in 1993. For all age groups in-hospital mortality for men was higher than for women. The mean length of hospital admissions in 1993 was 14.0 days for men and 16.4 days for women. A review of individual patient records from a 6.3% sample of all hospital admissions in the Netherlands indicated that within a 2 year period 18% of the heart failure patients were admitted more than once and 5% more than twice. CONCLUSIONS: For both men and women a pronounced increase in age adjusted discharge rates for heart failure was observed in the Netherlands from 1980 to 1993. Readmissions were a prominent feature among heart failure patients. Higher survival rates after acute myocardial infarction and the longer survival of patients with heart disease, including heart failure may have contributed to the observed increase. The importance of advances in diagnostic tools and of possible changes in admission policy remain uncertain. PMID:8944582

Clinical features of pathologic childhood aerophagia: early recognition and essential diagnostic criteria.

PubMed

Hwang, Jin-Bok; Choi, Won Joung; Kim, Jun Sik; Lee, Sang Yun; Jung, Chul-Ho; Lee, Young Hwan; Kam, Sin

2005-11-01

This study investigated the early recognition and diagnosis of pathologic childhood aerophagia to avoid unnecessary diagnostic approaches and serious complications. Between 1995 and 2003, data from 42 consecutive patients with pathologic childhood aerophagia, aged 2 to 16 years, were reviewed. An esophageal air sign was defined as an abnormal air shadow on the proximal esophagus adjacent to the trachea on a full-inflated chest radiograph. Of the 42 patients, the chief complaints were abdominal distention (52.4%), recurrent abdominal pain syndrome (21.4%), chronic diarrhea (11.9%), acute abdominal pain (7.1%) and others (7.2%). Mean symptom duration before diagnosis was 10.6 months (range, 1 to 60 months), and it exceeded 12 months for 16 (38.1%) patients. The clinical features common to all patients were abdominal distention that increased progressively during the day, increased flatus on sleep, increased bowel sound on auscultation and an air-distended stomach with increased gas in the small and large bowel by radiography. Visible or audible air swallowing (26.2%) and repetitive belching (9.5%) were also noted. Esophageal air sign was observed in 76.2% of the patients and in 9.7% of the controls (P=0.0001). The subgroups of pathologic childhood aerophagia divided by underlying associations were pathologic childhood aerophagia without severe mental retardation (76.2%), which consisted of psychological stresses and uncertain condition, and pathologic childhood aerophagia with severe mental retardation (23.8%). The common manifestations of pathologic childhood aerophagia may be its essential diagnostic criteria, and esophageal air sign may be useful for the early recognition of pathologic childhood aerophagia. Our observations show that the diagnostic clinical profiles suggested by Rome II criteria should be detailed and made clearer if they are to serve as diagnostic criteria for pathologic childhood aerophagia.

Comparisons of methamphetamine psychotic and schizophrenic symptoms: a differential item functioning analysis.

PubMed

Srisurapanont, Manit; Arunpongpaisal, Suwanna; Wada, Kiyoshi; Marsden, John; Ali, Robert; Kongsakon, Ronnachai

2011-06-01

The concept of negative symptoms in methamphetamine (MA) psychosis (e.g., poverty of speech, flatten affect, and loss of drive) is still uncertain. This study aimed to use differential item functioning (DIF) statistical techniques to differentiate the severity of psychotic symptoms between MA psychotic and schizophrenic patients. Data of MA psychotic and schizophrenic patients were those of the participants in the WHO Multi-Site Project on Methamphetamine-Induced Psychosis (or WHO-MAIP study) and the Risperidone Long-Acting Injection in Thai Schizophrenic Patients (or RLAI-Thai study), respectively. To confirm the unidimensionality of psychotic syndromes, we applied the exploratory and confirmatory factor analyses (EFA and CFA) on the eight items of Manchester scale. We conducted the DIF analysis of psychotic symptoms observed in both groups by using nonparametric kernel-smoothing techniques of item response theory. A DIF composite index of 0.30 or greater indicated the difference of symptom severity. The analyses included the data of 168 MA psychotic participants and the baseline data of 169 schizophrenic patients. For both data sets, the EFA and CFA suggested a three-factor model of the psychotic symptoms, including negative syndrome (poverty of speech, psychomotor retardation and flatten/incongruous affect), positive syndrome (delusions, hallucinations and incoherent speech) and anxiety/depression syndrome (anxiety and depression). The DIF composite indexes comparing the severity differences of all eight psychotic symptoms were lower than 0.3. The results suggest that, at the same level of syndrome severity (i.e., negative, positive, and anxiety/depression syndromes), the severity of psychotic symptoms, including the negative ones, observed in MA psychotic and schizophrenic patients are almost the same. Copyright © 2011 Elsevier Inc. All rights reserved.

Does intolerance of uncertainty predict anticipatory startle responses to uncertain threat?

PubMed

Nelson, Brady D; Shankman, Stewart A

2011-08-01

Intolerance of uncertainty (IU) has been proposed to be an important maintaining factor in several anxiety disorders, including generalized anxiety disorder, obsessive-compulsive disorder, and social phobia. While IU has been shown to predict subjective ratings and decision-making during uncertain/ambiguous situations, few studies have examined whether IU also predicts emotional responding to uncertain threat. The present study examined whether IU predicted aversive responding (startle and subjective ratings) during the anticipation of temporally uncertain shocks. Sixty-nine participants completed three experimental conditions during which they received: no shocks, temporally certain/predictable shocks, and temporally uncertain shocks. Results indicated that IU was negatively associated with startle during the uncertain threat condition in that those with higher IU had a smaller startle response. IU was also only related to startle during the uncertain (and not the certain/predictable) threat condition, suggesting that it was not predictive of general aversive responding, but specific to responses to uncertain aversiveness. Perceived control over anxiety-related events mediated the relation between IU and startle to uncertain threat, such that high IU led to lowered perceived control, which in turn led to a smaller startle response. We discuss several potential explanations for these findings, including the inhibitory qualities of IU. Overall, our results suggest that IU is associated with attenuated aversive responding to uncertain threat. Copyright © 2011 Elsevier B.V. All rights reserved.

Evidence of improved fluid management in patients receiving haemodialysis following a self-affirmation theory-based intervention: A randomised controlled trial.

PubMed

Wileman, Vari; Chilcot, Joseph; Armitage, Christopher J; Farrington, Ken; Wellsted, David M; Norton, Sam; Davenport, Andrew; Franklin, Gail; Da Silva Gane, Maria; Horne, Robert; Almond, Mike

2016-01-01

Haemodialysis patients are at risk of serious health complications; yet, treatment non-adherence remains high. Warnings about health risks associated with non-adherence may trigger defensive reactions. We studied whether an intervention based on self-affirmation theory reduced resistance to health-risk information and improved fluid treatment adherence. In a cluster randomised controlled trial, 91 patients either self-affirmed or completed a matched control task before reading about the health-risks associated with inadequate fluid control. Patients' perceptions of the health-risk information, intention and self-efficacy to control fluid were assessed immediately after presentation of health-risk information. Interdialytic weight gain (IDWG), excess fluid removed during haemodialysis, is a clinical measure of fluid treatment adherence. IDWG data were collected up to 12 months post-intervention. Self-affirmed patients had significantly reduced IDWG levels over 12 months. However, contrary to predictions derived from self-affirmation theory, self-affirmed participants and controls did not differ in their evaluation of the health-risk information, intention to control fluid or self-efficacy. A low-cost, high-reach health intervention based on self-affirmation theory was shown to reduce IDWG over a 12-month period, but the mechanism by which this apparent behaviour change occurred is uncertain. Further work is still required to identify mediators of the observed effects.

Waon Therapy for Managing Chronic Heart Failure　- Results From a Multicenter Prospective Randomized WAON-CHF Study.

PubMed

Tei, Chuwa; Imamura, Teruhiko; Kinugawa, Koichiro; Inoue, Teruo; Masuyama, Tohru; Inoue, Hiroshi; Noike, Hirofumi; Muramatsu, Toshihiro; Takeishi, Yasuchika; Saku, Keijiro; Harada, Kazumasa; Daida, Hiroyuki; Kobayashi, Youichi; Hagiwara, Nobuhisa; Nagayama, Masatoshi; Momomura, Shinichi; Yonezawa, Kazuya; Ito, Hiroshi; Gojo, Satoshi; Akaishi, Makoto; Miyata, Masaaki; Ohishi, Mitsuru

2016-01-01

Waon therapy improves heart failure (HF) symptoms, but further evidence in patients with advanced HF remains uncertain. In 19 institutes, we prospectively enrolled hospitalized patients with advanced HF, who had plasma levels of B-type natriuretic peptide (BNP) >500 pg/ml on admission and BNP >300 pg/ml regardless of more than 1 week of medical therapy. Enrolled patients were randomized into Waon therapy or control groups. Waon therapy was performed once daily for 10 days with a far infrared-ray dry sauna maintained at 60℃ for 15 min, followed by bed rest for 30 min covered with a blanket. The primary endpoint was the ratio of BNP before and after treatment. In total, 76 Waon therapy and 73 control patients (mean age 66 years, men 61%, mean plasma BNP 777 pg/ml) were studied. The groups differed only in body mass index and the frequency of diabetes. The plasma BNP, NYHA classification, 6-min walk distance (6MWD), and cardiothoracic ratio significantly improved only in the Waon therapy group. Improvements in NYHA classification, 6MWD, and cardiothoracic ratio were significant in the Waon therapy group, although the change in plasma BNP did not reach statistical significance. No serious adverse events were observed in either group. Waon therapy, a holistic soothing warmth therapy, showed clinical advantages in safety and efficacy among patients with advanced HF.

Ambiguity aversion in schizophrenia: An fMRI study of decision-making under risk and ambiguity.

PubMed

Fujino, Junya; Hirose, Kimito; Tei, Shisei; Kawada, Ryosaku; Tsurumi, Kosuke; Matsukawa, Noriko; Miyata, Jun; Sugihara, Genichi; Yoshihara, Yujiro; Ideno, Takashi; Aso, Toshihiko; Takemura, Kazuhisa; Fukuyama, Hidenao; Murai, Toshiya; Takahashi, Hidehiko

2016-12-01

When making decisions in everyday life, we often have to choose between uncertain outcomes. Economic studies have demonstrated that healthy people tend to prefer options with known probabilities (risk) than those with unknown probabilities (ambiguity), which is referred to as "ambiguity aversion." However, it remains unclear how patients with schizophrenia behave under ambiguity, despite growing evidence of their altered decision-making under uncertainty. In this study, combining economic tools and functional magnetic resonance imaging (fMRI), we assessed the attitudes toward risk/ambiguity and investigated the neural correlates during decision-making under risk/ambiguity in schizophrenia. Although no significant difference in attitudes under risk was observed, patients with schizophrenia chose ambiguity significantly more often than the healthy controls. Attitudes under risk and ambiguity did not correlate across patients with schizophrenia. Furthermore, unlike in the healthy controls, activation of the left lateral orbitofrontal cortex was not increased during decision-making under ambiguity compared to under risk in schizophrenia. These results suggest that ambiguity aversion, a well-established subjective bias, is attenuated in patients with schizophrenia, highlighting the need to distinguish between risk and ambiguity when assessing decision-making under these situations. Our findings, comprising important clinical implications, contribute to improved understanding of the mechanisms underlying altered decision-making in patients with schizophrenia. Copyright © 2016 Elsevier B.V. All rights reserved.

Iranian family caregivers' challenges and issues in caring of multiple sclerosis patients: A descriptive explorative qualitative study.

PubMed

Masoudi, Reza; Abedi, Heidar Ali; Abedi, Parvin; Mohammadianinejad, Seyed Ehsan

2014-07-01

The broad spectrum of problems caused by multiple sclerosis (MS) imposes heavy responsibility to caregivers in caring of their patients. Therefore, they encounter many issues and challenges in this situation. The purpose of this study was to explore the experiences and challenges of MS family caregivers. A qualitative design, based on a thematic analysis approach, was used to reach the study aim. Data were collected and analyzed concurrently through in-depth unstructured interviews, field notes, and observations that were held with 23 participants (14 family caregivers and 9 MS patients) at two referral centers in Ahvaz, Iran. THREE MAJOR THEMES WERE EXTRACTED FROM THE ANALYSIS OF THE TRANSCRIPTS: "emotional exhaustion of caregivers," "uncertain atmosphere of caring," and "insularity care." The first theme consisted of three subthemes: "stressful atmosphere of caring," "conflict and animism," and "continuing distress affecting the caregiver." The second theme consisted of three subthemes: "unstable and complicacy of disease," "caring with trial and error," and "frequent hospitalization of patients," and the third theme consisted of two subthemes: "caring gap and disintegration" and "lack of sufficient support." This study will be useful to healthcare system for managing the challenges of MS patients' family caregivers. Improving the conditions and performance of family caregivers is crucial in order to provide high-quality care to people with MS.

Cerulean Warbler Occurrence Atlas for Military Installations

DTIC Science & Technology

2010-04-01

Army Ammuniton Plant (Closed) IN NO 2009 Army IOWA ARMY AMMUNITION PLANT IA UNCERTAIN 2009 USACE J. Percy Priest Lake TN UNCERTAIN 2009 USACE J...Stonewall Jackson Lake WV UNCERTAIN 2009 USACE Summersville Lake WV no POC Army Sunflower Army Ammunition Plant KS no POC USACE Sutton Lake WV UNCERTAIN

Prognostic Effect of Carcinoma In Situ in Muscle-invasive Urothelial Carcinoma Patients Receiving Neoadjuvant Chemotherapy

PubMed Central

Thomas, Derek E.; Kaimakliotis, Hristos Z.; Rice, Kevin R.; Pereira, Jose A.; Johnston, Paul; Moore, Marietta L.; Reed, Angela; Cregar, Dylan M.; Franklin, Cindy; Loman, Rhoda L.; Koch, Michael O.; Bihrle, Richard; Foster, Richard S.; Masterson, Timothy A.; Gardner, Thomas A.; Sundaram, Chandru P.; Powell, Charles R.; Beck, Stephen D.W.; Grignon, David J.; Cheng, Liang; Albany, Costantine; Hahn, Noah M.

2017-01-01

We performed a single-institution retrospective analysis of 137 patients with muscle-invasive urothelial carcinoma who underwent neoadjuvant chemotherapy and radical cystectomy to assess the prognostic significance of carcinoma in situ (CIS). The pathologic complete response rates were significantly decreased for patients with CIS identified on transurethral resection of the bladder tumor before treatment. The long-term follow-up data from patients with isolated CIS at cystectomy revealed prolonged progression-free and overall survival. Background Carcinoma in situ (CIS) is a poor prognostic finding in urothelial carcinoma. However, its significance in muscle-invasive urothelial carcinoma (MIUC) treated with neoadjuvant chemotherapy (NAC) is uncertain. We assessed the effect of CIS found in pretreatment transurethral resection of bladder tumor (TURBT) biopsies on the pathologic and clinical outcomes. Materials and Methods Subjects with MIUC treated with NAC before cystectomy were identified. The pathologic complete response (pCR) rates stratified by TURBT CIS status were compared. The secondary analyses included tumor response, progression-free survival (PFS), overall survival (OS), and an exploratory post hoc analysis of patients with pathologic CIS only (pTisN0) at cystectomy. Results A total of 137 patients with MIUC were identified. TURBT CIS was noted in 30.7% of the patients. The absence of TURBT CIS was associated with a significantly increased pCR rate (23.2% vs. 9.5%; odds ratio, 4.08; 95% confidence interval, 1.19–13.98; P = .025). Stage pTisN0 disease was observed in 19.0% of the TURBT CIS patients. TURBT CIS status did not significantly affect the PFS or OS outcomes. Post hoc analysis of the pTisN0 patients revealed prolonged median PFS (104.5 vs. 139.9 months; P = .055) and OS (104.5 vs. 152.3 months; P = .091) outcomes similar to those for the pCR patients. Conclusion The absence of CIS on pretreatment TURBT in patients with MIUC undergoing NAC was associated with increased pCR rates, with no observed differences in PFS or OS. Isolated CIS at cystectomy was frequently observed, with lengthy PFS and OS durations similar to those for pCR patients. Further studies aimed at understanding the biology and clinical effect of CIS in MIUC are warranted. PMID:28040424

DISCOVERY AND FOLLOW-UP OF A NEARBY GALAXY FROM THE ARECIBO ZONE OF AVOIDANCE SURVEY

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

McIntyre, T. P.; Henning, P. A.; Minchin, R. F.

The Arecibo L-Band Feed Array Zone of Avoidance (ALFA ZOA) Survey has discovered a nearby galaxy, ALFA ZOA J1952+1428, at a heliocentric velocity of +279 km s{sup -1}. The galaxy was discovered at low Galactic latitude by 21 cm emission from neutral hydrogen (H I). We have obtained follow-up observations with the Expanded Very Large Array and the 0.9 m Southeastern Association for Research in Astronomy optical telescope. The H I distribution overlaps an uncataloged, potential optical counterpart. The H I linear size is 1.4 kpc at our adopted distance of D = 7 Mpc, but the distance estimate ismore » uncertain as Hubble's law is unreliable at low recessional velocities. The optical counterpart has m{sub B} = 16.9 mag and B - R = 0.1 mag. These characteristics, including M{sub H} {sub i} = 10{sup 7.0} M{sub sun} and L{sub B} = 10{sup 7.5} L{sub sun}, if at 7 Mpc, indicate that this galaxy is a blue compact dwarf, but this remains uncertain until further follow-up observations are complete. Optical follow-up observations are ongoing and near-infrared follow-up observations have been scheduled.« less

Antimicrobial agents for preventing peritonitis in peritoneal dialysis patients.

PubMed

Campbell, Denise; Mudge, David W; Craig, Jonathan C; Johnson, David W; Tong, Allison; Strippoli, Giovanni Fm

2017-04-08

Peritoneal dialysis (PD) is an important therapy for patients with end-stage kidney disease and is used in more than 200,000 such patients globally. However, its value is often limited by the development of infections such as peritonitis and exit-site and tunnel infections. Multiple strategies have been developed to reduce the risk of peritonitis including antibiotics, topical disinfectants to the exit site and antifungal agents. However, the effectiveness of these strategies has been variable and are based on a small number of randomised controlled trials (RCTs). The optimal preventive strategies to reduce the occurrence of peritonitis remain unclear.This is an update of a Cochrane review first published in 2004. To evaluate the benefits and harms of antimicrobial strategies used to prevent peritonitis in PD patients. We searched the Cochrane Kidney and Transplant's Specialised Register to 4 October 2016 through contact with the Information Specialist using search terms relevant to this review. Studies contained in the Specialised Register are identified through search strategies specifically designed for CENTRAL, MEDLINE, and EMBASE; handsearching conference proceedings; and searching the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. RCTs or quasi-RCTs in patients receiving chronic PD, which evaluated any antimicrobial agents used systemically or locally to prevent peritonitis or exit-site/tunnel infection were included. Two authors independently assessed risk of bias and extracted data. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratio (RR) with 95% confidence intervals (CI). Thirty-nine studies, randomising 4435 patients, were included. Twenty additional studies have been included in this update. The risk of bias domains were often unclear or high; risk of bias was judged to be low in 19 (49%) studies for random sequence generation, 12 (31%) studies for allocation concealment, 22 (56%) studies for incomplete outcome reporting, and in 12 (31%) studies for selective outcome reporting. Blinding of participants and personnel was considered to be at low risk of bias in 8 (21%) and 10 studies (26%) for blinding of outcome assessors. It should be noted that blinding of participants and personnel was not possible in many of the studies because of the nature of the intervention or control treatment.The use of oral or topical antibiotic compared with placebo/no treatment, had uncertain effects on the risk of exit-site/tunnel infection (3 studies, 191 patients, low quality evidence: RR 0.45, 95% CI 0.19 to 1.04) and the risk of peritonitis (5 studies, 395 patients, low quality evidence: RR 0.82, 95% CI 0.57 to 1.19).The use of nasal antibiotic compared with placebo/no treatment had uncertain effects on the risk of exit-site/tunnel infection (3 studies, 338 patients, low quality evidence: RR 1.34, 95% CI 0.62 to 2.87) and the risk of peritonitis (3 studies, 338 patients, low quality evidence: RR 0.94, 95% CI 0.67 to 1.31).Pre/perioperative intravenous vancomycin compared with no treatment may reduce the risk of early peritonitis (1 study, 177 patients, low quality evidence: RR 0.08, 95% CI 0.01 to 0.61) but has an uncertain effect on the risk of exit-site/tunnel infection (1 study, 177 patients, low quality evidence: RR 0.36, 95% CI 0.10 to 1.32).The use of topical disinfectant compared with standard care or other active treatment (antibiotic or other disinfectant) had uncertain effects on the risk of exit-site/tunnel infection (8 studies, 973 patients, low quality evidence, RR 1.00, 95% CI 0.75 to 1.33) and the risk of peritonitis (6 studies, 853 patients, low quality evidence: RR 0.83, 95% CI 0.65 to 1.06).Antifungal prophylaxis with oral nystatin/fluconazole compared with placebo/no treatment may reduce the risk of fungal peritonitis occurring after a patient has had an antibiotic course (2 studies, 817 patients, low quality evidence: RR 0.28, 95% CI 0.12 to 0.63).No intervention reduced the risk of catheter removal or replacement. Most of the available studies were small and of suboptimal quality. Only six studies enrolled 200 or more patients. In this update, we identified limited data from RCTs and quasi-RCTs which evaluated strategies to prevent peritonitis and exit-site/tunnel infections. This review demonstrates that pre/peri-operative intravenous vancomycin may reduce the risk of early peritonitis and that antifungal prophylaxis with oral nystatin or fluconazole reduces the risk of fungal peritonitis following an antibiotic course. However, no other antimicrobial interventions have proven efficacy. In particular, the use of nasal antibiotic to eradicate Staphylococcus aureus, had an uncertain effect on the risk of peritonitis and raises questions about the usefulness of this approach. Given the large number of patients on PD and the importance of peritonitis, the lack of adequately powered and high quality RCTs to inform decision making about strategies to prevent peritonitis is striking.

Correlation between model observer and human observer performance in CT imaging when lesion location is uncertain

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

Leng, Shuai; Yu, Lifeng; Zhang, Yi

2013-08-15

Purpose: The purpose of this study was to investigate the correlation between model observer and human observer performance in CT imaging for the task of lesion detection and localization when the lesion location is uncertain.Methods: Two cylindrical rods (3-mm and 5-mm diameters) were placed in a 35 × 26 cm torso-shaped water phantom to simulate lesions with −15 HU contrast at 120 kV. The phantom was scanned 100 times on a 128-slice CT scanner at each of four dose levels (CTDIvol = 5.7, 11.4, 17.1, and 22.8 mGy). Regions of interest (ROIs) around each lesion were extracted to generate imagesmore » with signal-present, with each ROI containing 128 × 128 pixels. Corresponding ROIs of signal-absent images were generated from images without lesion mimicking rods. The location of the lesion (rod) in each ROI was randomly distributed by moving the ROIs around each lesion. Human observer studies were performed by having three trained observers identify the presence or absence of lesions, indicating the lesion location in each image and scoring confidence for the detection task on a 6-point scale. The same image data were analyzed using a channelized Hotelling model observer (CHO) with Gabor channels. Internal noise was added to the decision variables for the model observer study. Area under the curve (AUC) of ROC and localization ROC (LROC) curves were calculated using a nonparametric approach. The Spearman's rank order correlation between the average performance of the human observers and the model observer performance was calculated for the AUC of both ROC and LROC curves for both the 3- and 5-mm diameter lesions.Results: In both ROC and LROC analyses, AUC values for the model observer agreed well with the average values across the three human observers. The Spearman's rank order correlation values for both ROC and LROC analyses for both the 3- and 5-mm diameter lesions were all 1.0, indicating perfect rank ordering agreement of the figures of merit (AUC) between the average performance of the human observers and the model observer performance.Conclusions: In CT imaging of different sizes of low-contrast lesions (−15 HU), the performance of CHO with Gabor channels was highly correlated with human observer performance for the detection and localization tasks with uncertain lesion location in CT imaging at four clinically relevant dose levels. This suggests the ability of Gabor CHO model observers to meaningfully assess CT image quality for the purpose of optimizing scan protocols and radiation dose levels in detection and localization tasks for low-contrast lesions.« less

Haemoglobin Levels in Acute Coronary Syndrome Patients Admitted in Cardiology Intensive Care Units in a Tertiary Care Hospital.

PubMed

Naqvil, Syed Mujtaba Hussain; Rao, T Ramesh Kumar; Chandra, Shobha Jagdish

2015-06-01

Epidemiology of abnormal haemoglobin levels and its association with severity of coronary artery disease in Indian patients is uncertain. This prospective observational study was conducted to determine the haemoglobin levels in acute coronary syndrome (ACS) patients and the association of anaemia with the severity of coronary artery disease (CAD) on coronary angiography (CAG). The patients diagnosed with ACS (ST-elevated and non-elevated MI, unstable angina) based on ECG and cardiac enzymes and admitted in cardiology ICU were enrolled in the study after fulfilling study criteria and the baseline haemoglobin level was recorded. The severity of coronary disease of patients who underwent coronary angiography was recorded. A total of 162 patients were enrolled for the study. The overall haemoglobin of patients was 11.99 ± 2.24 g/dl with 12.46 ± 2.33 g/dl in males and 11.17 ± 1.82 g/dl in females (p < 0.05). Anaemia was found in 62.96% patients with no significant gender difference (p > 0.05), however abnormal haemoglobin level (Hb > 16g/dl) was found exclusively in 7.7% males. One hundred one patients underwent coronary angiography and anaemia was present in 60 patients (58.82%) and absent in 41 (40.59%). The difference in mean haemoglobin levels in anaemic patients with single, double, and triple vessel disease was significant (p < 0.05) and corresponding levels in non-anaemic patients were insignificant (p > 0.05). A weak correlation was observed between the haemoglobin level of patients and the percentage of obstruction in CAG (r = 0.26). The odds of having triple vessel disease in anaemic patient are 1.77 (95% CI 0.71 to 4.43). However, the association between anaemia and the severity of coronary artery disease was statistically found to be non-significant. The mean haemoglobin levels decreased as the severity of CAD increased in CAG, however the association was not established between anaemia and the severity of coronary artery disease statistically.

[Current understanding of iron overload hazard in patients with myelodysplastic syndrome].

PubMed

Song, Lu-Xi; Su, Ji-Ying; Zhang, Zhen; Chang, Chun-Kang

2013-04-01

Patients with myelodysplastic syndromes (MDS) become dependent on blood transfusions and develop into transfusional iron overload, which is exacerbated by increased absorption of dietary iron in response to ineffective erythropoiesis. However, it is uncertain whether there is an association among iron accumulation, clinical complications, and decreased likelihood of survival in MDS patients. Thereby our current understanding of the effects of transfusion dependency and iron overload in MDS are discussed. Particular emphasis should be placed on further characterizing the role of redox-active forms of labile iron and oxidative stress in iron overload, decreased life expectancy and increased risk of leukemic transformation in MDS patients with iron overload.

[Strategy of liver resection during chemotherapy for otherwise unresectable colorectal metastases].

PubMed

Tanaka, Kuniya; Kumamoto, Takafumi; Takeda, Kazuhisa; Nojiri, Kazunori; Endo, Itaru

2013-07-01

With multidisciplinary management of patients with effective chemotherapy that can downstage metastases, more patients with previously inoperable disease can benefit from surgery. Surgery in isolation may be approaching technical limits, but now is likely to help more patients because of success of complementary strategies, particularly newer chemotherapy and targeted therapy. Leaving behind disappearing metastases after chemotherapy, margin-positive resection, staged liver resection, and liver-first reversed management permit potentially curative surgery for patients previously unable to survive resection. Further, survival benefit from maximum debulking surgery, like ovarian cancer, for colorectal liver metastases is uncertain at present, but likely. Individualized multidisciplinary treatment planning using such strategies is essential.

Infertility among kidney transplant recipients.

PubMed

Ghazizadeh, Shirin; Lessan-Pezeshki, Mahboob; Khatami, Mohammd R; Mahdavi-Mazdeh, Mitra; Abbasi, Mohammad R; Azmandian, Jalal; Razeghi, Effat; Seifi, Sepideh; Ahmadi, Farrokh; Maziar, Sima

2007-03-01

We studied 122 women with a transplanted kidney to evaluate their reproductive performance. 15 of the patients were either post-menopausal or underwent hysterectomy and 33 were unmarried. Of the 76 married reproductive age women, 10 (13.1%) were infertile. Three had male factor infertility, three had ovulatory problems and in four cases, the cause was uncertain. Six of these patients were actively treated by ovulation induction with or without IUI and two of these patients became pregnant. The remaining four patients refused treatment for infertility. We conclude that the incidence of infertility among kidney transplant recipients is similar to the general population, but they are less motivated to be treated for infertility.

Eddington's demon: inferring galaxy mass functions and other distributions from uncertain data

NASA Astrophysics Data System (ADS)

Obreschkow, D.; Murray, S. G.; Robotham, A. S. G.; Westmeier, T.

2018-03-01

We present a general modified maximum likelihood (MML) method for inferring generative distribution functions from uncertain and biased data. The MML estimator is identical to, but easier and many orders of magnitude faster to compute than the solution of the exact Bayesian hierarchical modelling of all measurement errors. As a key application, this method can accurately recover the mass function (MF) of galaxies, while simultaneously dealing with observational uncertainties (Eddington bias), complex selection functions and unknown cosmic large-scale structure. The MML method is free of binning and natively accounts for small number statistics and non-detections. Its fast implementation in the R-package dftools is equally applicable to other objects, such as haloes, groups, and clusters, as well as observables other than mass. The formalism readily extends to multidimensional distribution functions, e.g. a Choloniewski function for the galaxy mass-angular momentum distribution, also handled by dftools. The code provides uncertainties and covariances for the fitted model parameters and approximate Bayesian evidences. We use numerous mock surveys to illustrate and test the MML method, as well as to emphasize the necessity of accounting for observational uncertainties in MFs of modern galaxy surveys.

Treatment of ballism and pseudobulbar affect with sertraline.

PubMed

Okun, M S; Riestra, A R; Nadeau, S E

2001-10-01

The pathogenesis of ballism is uncertain and may involve more than one mechanism; treatment is not always efficacious. To provide evidence of a nondopaminergic mechanism and the potential for a prompt and nearly complete response to a serotonergic agent. Report of 2 separate trials of sertraline hydrochloride in a single patient. Complete remission of symptoms within 48 hours of each drug trial. Sertraline may offer an alternative with a better adverse effect profile than dopamine receptor blockers in the treatment of patients with ballism.

Influence of control group therapy on the benefit from dose-dense chemotherapy in early breast cancer: a systemic review and meta-analysis.

PubMed

Goldvaser, Hadar; Majeed, Habeeb; Ribnikar, Domen; Šeruga, Boštjan; Ocaña, Alberto; Cescon, David W; Amir, Eitan

2018-06-01

Results from clinical trials of adjuvant dose-dense chemotherapy in patients with breast cancer are inconsistent. A systematic search of MEDLINE identified studies comparing the efficacy of dose-dense adjuvant chemotherapy to a standard treatment. The primary analysis included studies that used identical regimens in the experimental and control groups, but varied only dose density. A secondary analysis included studies that used either different drugs or doses in the experimental and the control groups. Hazard ratios (HRs) and 95% confidence intervals were computed for disease-free survival (DFS) and overall survival (OS) and pooled in a meta-analysis. Subgroup analyses and meta-regression explored drug schedules utilized in control groups and the influence of clinicopathologic variables on benefit from dose-dense therapy. The primary analysis included 5 studies comprising 9819 patients while the secondary analysis included 6 studies comprising 9679 patients. Dose-dense treatment significantly improved DFS (HR 0.85, p < 0.001) and OS (HR 0.86, p = 0.008) in the primary analysis. Similar results were observed in the secondary analysis. Dose-dense schedule was important primarily in studies utilizing paclitaxel every 3 weeks as the control group (interaction p = 0.04 for DFS interaction p = 0.001 for OS). A significantly greater relative magnitude of benefit was observed in pre-menopausal women and those with nodal involvement, but there was no influence of hormone receptor status on results. Adjuvant dose-dense regimens improve breast cancer outcomes. It remains uncertain whether the observed benefit reflects the impact of dose density or the inferiority of paclitaxel every 3 weeks as a control group.

Physician decision-making in the management of work related upper extremity injuries.

PubMed

Szekeres, Mike; Macdermid, Joy C; Katchky, Adam; Grewal, Ruby

2018-05-22

Physicians working in a tertiary care injured worker clinic are faced with clinical decision-making that must balance the needs of patients and society in managing complex clinical problems that are complicated by the work-workplace context. The purpose of this study is to describe and characterize the decision-making process of upper extremity specialized surgeons when managing injured workers within a specialized worker's compensation clinic. Surgeons were interviewed in a semi-structured manner. Following each interview, the surgeon was also observed in a clinic visit during a new patient assessment, allowing observation of the interactional patterns between surgeon and patient, and comparison of the process described in the interview to what actually occurred during clinic visits. The primary central theme emerging from the surgeon interviews and the clinical observation was the focus on the importance of comprehensive assessment to make the first critical decision: an accurate diagnosis. Two subthemes were also found. The first of these involved the decision whether to proceed to management strategies or to continue with further investigation if the correct diagnosis is uncertain. Once the central theme of diagnosis was achieved, a second subtheme was highlighted; selecting appropriate management options, given the complexities of managing the injured worker, the workplace, and the compensation board. This study illustrates that upper extremity surgeons rely on their training and experience with upper extremity conditions to follow a sequential but iterative decision-making process to provide a more definitive diagnosis and treatment plan for workers with injuries that are often complex. The surgeons are challenged by the context which takes them out of their familiar zone of typical clinical practice to deal with the interactions between the injury, worker, work, workplace and insurer.

Electronic Monitoring Systems to Assess Urinary Incontinence: A Health Technology Assessment

PubMed Central

Nevis, Immaculate; Kabali, Conrad; Anh Tu, Hong; Ekanayake, Samanthika; Mistry, Jigna; Wells, David; Ali, Arshia; Walter, Melissa; Higgins, Caroline

2018-01-01

Background Urinary incontinence is involuntary leakage of urine and can affect people of all ages. Incidence rises as people age, often because of reduced mobility or conditions affecting the nervous system, such as dementia and stroke. Urinary incontinence can be a distressing condition and can harm a person's physical, financial, social, and emotional well-being. People with urinary incontinence are susceptible to skin irritation, pressure sores, and urinary tract infections. Urinary incontinence is also associated with an increased risk of falls in older adults. This health technology assessment examined the effectiveness of, budget impact of, and patient values and preferences about electronic monitoring systems to assess urinary incontinence for residents of long-term care homes or geriatric hospital inpatients with complex conditions. Methods A clinical evidence review of the published clinical literature was conducted to June 9, 2017. Critical appraisal of the clinical evidence included assessment of risk of bias and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria to reflect the certainty of the evidence. We calculated the funding required for an electronic urinary incontinence monitoring system in the first year of implementation (when facilities would buy the systems) and in subsequent years. We interviewed six people with urinary incontinence and two caregivers, who described ways urinary incontinence affected daily life. Results We included one observational study in the clinical review. Most of the 31 participants in the observational study were female (78%) and required high levels of care, primarily because of cognitive impairment. The quality of evidence for all outcomes was very low owing to potential risk of bias and indirectness. We are consequently uncertain about how electronic monitoring systems affect management of urinary incontinence. For patients living in long-term care homes who are eligible for the technology, we estimated that an electronic monitoring system to assess urinary incontinence would cost $6.4 million in the first year of implementation and $1.6 million in subsequent years. Patients said urinary incontinence reduced their independence and social life and adversely affected their quality of life. Incontinence made them embarrassed and reduced their self-esteem. Several respondents mentioned how expensive supplies to manage incontinence were. Conclusions The effectiveness of using the electronic monitoring system to assess urinary incontinence is uncertain because of the very low quality of the evidence. Introducing electronic monitoring systems would result in incremental costs, and there would be savings only if the systems substantially reduced incontinence. PMID:29844845

Electronic Monitoring Systems to Assess Urinary Incontinence: A Health Technology Assessment.

PubMed

2018-01-01

Urinary incontinence is involuntary leakage of urine and can affect people of all ages. Incidence rises as people age, often because of reduced mobility or conditions affecting the nervous system, such as dementia and stroke. Urinary incontinence can be a distressing condition and can harm a person's physical, financial, social, and emotional well-being. People with urinary incontinence are susceptible to skin irritation, pressure sores, and urinary tract infections. Urinary incontinence is also associated with an increased risk of falls in older adults.This health technology assessment examined the effectiveness of, budget impact of, and patient values and preferences about electronic monitoring systems to assess urinary incontinence for residents of long-term care homes or geriatric hospital inpatients with complex conditions. A clinical evidence review of the published clinical literature was conducted to June 9, 2017. Critical appraisal of the clinical evidence included assessment of risk of bias and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria to reflect the certainty of the evidence.We calculated the funding required for an electronic urinary incontinence monitoring system in the first year of implementation (when facilities would buy the systems) and in subsequent years.We interviewed six people with urinary incontinence and two caregivers, who described ways urinary incontinence affected daily life. We included one observational study in the clinical review. Most of the 31 participants in the observational study were female (78%) and required high levels of care, primarily because of cognitive impairment. The quality of evidence for all outcomes was very low owing to potential risk of bias and indirectness. We are consequently uncertain about how electronic monitoring systems affect management of urinary incontinence.For patients living in long-term care homes who are eligible for the technology, we estimated that an electronic monitoring system to assess urinary incontinence would cost $6.4 million in the first year of implementation and $1.6 million in subsequent years.Patients said urinary incontinence reduced their independence and social life and adversely affected their quality of life. Incontinence made them embarrassed and reduced their self-esteem. Several respondents mentioned how expensive supplies to manage incontinence were. The effectiveness of using the electronic monitoring system to assess urinary incontinence is uncertain because of the very low quality of the evidence. Introducing electronic monitoring systems would result in incremental costs, and there would be savings only if the systems substantially reduced incontinence.

Allocating conservation resources between areas where persistence of a species is uncertain.

PubMed

McDonald-Madden, Eve; Chadès, Iadine; McCarthy, Michael A; Linkie, Matthew; Possingham, Hugh P

2011-04-01

Research on the allocation of resources to manage threatened species typically assumes that the state of the system is completely observable; for example whether a species is present or not. The majority of this research has converged on modeling problems as Markov decision processes (MDP), which give an optimal strategy driven by the current state of the system being managed. However, the presence of threatened species in an area can be uncertain. Typically, resource allocation among multiple conservation areas has been based on the biggest expected benefit (return on investment) but fails to incorporate the risk of imperfect detection. We provide the first decision-making framework for confronting the trade-off between information and return on investment, and we illustrate the approach for populations of the Sumatran tiger (Panthera tigris sumatrae) in Kerinci Seblat National Park. The problem is posed as a partially observable Markov decision process (POMDP), which extends MDP to incorporate incomplete detection and allows decisions based on our confidence in particular states. POMDP has previously been used for making optimal management decisions for a single population of a threatened species. We extend this work by investigating two populations, enabling us to explore the importance of variation in expected return on investment between populations on how we should act. We compare the performance of optimal strategies derived assuming complete (MDP) and incomplete (POMDP) observability. We find that uncertainty about the presence of a species affects how we should act. Further, we show that assuming full knowledge of a species presence will deliver poorer strategic outcomes than if uncertainty about a species status is explicitly considered. MDP solutions perform up to 90% worse than the POMDP for highly cryptic species, and they only converge in performance when we are certain of observing the species during management: an unlikely scenario for many threatened species. This study illustrates an approach to allocating limited resources to threatened species where the conservation status of the species in different areas is uncertain. The results highlight the importance of including partial observability in future models of optimal species management when the species of concern is cryptic in nature.

Treatment outcome of intravenous artesunate in patients with severe malaria in the Netherlands and Belgium

PubMed Central

2012-01-01

Background Intravenous (IV) artesunate is the treatment of choice for severe malaria. In Europe, however, no GMP-manufactured product is available and treatment data in European travellers are scarce. Fortunately, artesunate became available in the Netherlands and Belgium through a named patient programme. This is the largest case series of artesunate treated patients with severe malaria in Europe. Methods Hospitalized patients treated with IV artesunate between November 2007 and December 2010 in the Netherlands and Belgium were retrospectively evaluated. Patient characteristics, treatment and clinical outcome were recorded on a standardized form and mortality, parasite clearance times and the occurrence of adverse events were evaluated. Results Of the 68 treated patients, including 55 with severe malaria, two patients died (2/55 = 3.6%). The mean time to 50% parasite clearance (PCT50), 90% and 99% were 4.4 hours (3.9 - 5.2), 14.8 hours (13.0 - 17.2), and 29.5 hours (25.9 - 34.4) respectively. Artesunate was well tolerated. However, an unusual form of haemolytic anaemia was observed in seven patients. The relationship with artesunate remains uncertain. Conclusions Data from the named patient programme demonstrate that IV artesunate is effective and well-tolerated in European travellers lacking immunity. However, increased attention needs to be paid to the possible development of haemolytic anaemia 2-3 weeks after start of treatment. Treatment of IV artesunate should be limited to the period that IV treatment is required and should be followed by a full oral course of an appropriate anti-malarial drug. PMID:22462806

Depression in dialysis patients.

PubMed

King-Wing Ma, Terry; Kam-Tao Li, Philip

2016-08-01

Depression is the most common psychiatric illness in patients with end-stage renal disease (ESRD). The reported prevalence of depression in dialysis population varied from 22.8% (interview-based diagnosis) to 39.3% (self- or clinician-administered rating scales). Such differences were attributed to the overlapping symptoms of uraemia and depression. Systemic review and meta-analysis of observational studies showed that depression was a significant predictor of mortality in dialysis population. The optimal screening tool for depression in dialysis patients remains uncertain. The Beck Depression Inventory (BDI), Patient Health Questionnaire (PHQ) and Center for Epidemiologic Studies Depression Scale (CESD) have been validated for screening purposes. Patients who scored ≥14 using BDI should be referred to a psychiatrist for early evaluation. Structured Clinical Interview for DSM disorders (SCID) remains the gold standard for diagnosis. Non-pharmacological treatment options include cognitive behavioural therapy and exercise training programs. Although frequent haemodialysis may have beneficial effects on patients' physical and mental well-being, it cannot and should not be viewed as a treatment of depression. Selective serotonin reuptake inhibitors (SSRIs) are generally effective and safe in ESRD patients, but most studies were small, non-randomized and uncontrolled. The European Renal Best Practice (ERBP) guideline suggests a trial of SSRI for 8 to 12 weeks in dialysis patients who have moderate-major depression. The treatment effect should be re-evaluated after 12 weeks to avoid prolonging ineffective medication. This review will discuss the current understanding in the diagnosis and management of depression in dialysis patients. © 2016 Asian Pacific Society of Nephrology.

Giant hidradenocarcinoma: a report of malignant transformation from nodular hidradenoma.

PubMed

Lim, S C; Lee, M J; Lee, M S; Kee, K H; Suh, C H

1998-10-01

A giant hidradenocarcinoma presented by a 75-year-old female is reported. The patient had a malignant transformation within a nodular hidradenoma involving the right postauricular area, which was treated by mass removal and a right radical neck dissection with a free-flap covering. Malignant hidradenocarcinoma is the least common adnexal tumor of uncertain origin. They are usually malignant from their inception, but some develop from a benign counterpart. To the authors' knowledge, only three cases have been reported previously. Two histologically distinct components were seen in this tumor: (i) typical nodular hidradenoma, which constituted a small part of the tumor; and (ii) carcinoma with areas of transition. The secretory cells of hidradenocarcinoma showed decapitation secretion on light and electron microscopic observations, which is evidence of apocrine differentiation. Histologically, this case was concluded as a hidradenocarcinoma arising from a long-standing nodular hidradenoma. A literature review is presented and the histological, immunohistochemical and ultrastructural features are described.

Observations on Leadership, Problem Solving, and Preferred Futures of Universities

ERIC Educational Resources Information Center

Puncochar, Judith

2013-01-01

A focus on enrollments, rankings, uncertain budgets, and branding efforts to operate universities could have serious implications for discussions of sustainable solutions to complex problems and the decision-making processes of leaders. The Authentic Leadership Model for framing ill-defined problems in higher education is posited to improve the…

Application of the Auto-Tuned Land Assimilation System (ATLAS) to ASCAT and SMOS soil moisture retrieval products

USDA-ARS?s Scientific Manuscript database

Land data assimilations are typically based on highly uncertain assumptions regarding the statistical structure of observation and modeling errors. Left uncorrected, poor assumptions can degrade the quality of analysis products generated by land data assimilation systems. Recently, Crow and van de...

Modeled Watershed Runoff Associated with Variations in Precipitation Data, with Implications for Contaminant Fluxes: Initial Results

EPA Science Inventory

Precipitation is one of the primary forcing functions of hydrologic and watershed fate and transport models; however, in light of advances in precipitation estimates across watersheds, data remain highly uncertain. A wide variety of simulated and observed precipitation data are a...

Idiopathic anaphylaxis.

PubMed

Fenny, Nana; Grammer, Leslie C

2015-05-01

Idiopathic anaphylaxis is a diagnosis of exclusion after other causes have been thoroughly evaluated and excluded. The pathogenesis of idiopathic anaphylaxis remains uncertain, although increased numbers of activated lymphocytes and circulating histamine-releasing factors have been implicated. Signs and symptoms of patients diagnosed with idiopathic anaphylaxis are indistinguishable from the manifestations of other forms of anaphylaxis. Treatment regimens are implemented based on the frequency and severity of patient symptoms and generally include the use of epinephrine autoinjectors, antihistamines, and steroids. The prognosis of idiopathic anaphylaxis is generally favorable with well-established treatment regimens and effective patient education. Copyright © 2015 Elsevier Inc. All rights reserved.

The role of ultrasonography in examination of the stability of Tile-B2 pelvic fractures: 7 case reports and a literature review.

PubMed

Zhang, Bin-Fei; Zhang, Hong; Wang, Peng-Fei; Wang, Hu; Lei, Jin-Lai; Fu, Ya-Hui; Cong, Yu-Xuan; Huang, Hai; Huo, Xiao-Ming; Zhuang, Yan; Zhang, Kun

2017-09-01

Determining whether a Tile-B2 pelvic fracture is stable is very challenging. We sought to identify the role of ultrasonography in determining the stability of Tile-B2 pelvic fractures. We collected the clinical data of patients with Tile-B2 pelvic fractures who presented at Xi'an Hong-Hui Hospital between June 1, 2016, and August 5, 2016. The treatment strategy of each patient was determined by a team of senior surgeons in the department. A single sinologist observed the movement of the fracture sites in patients during rest, under compression, and during separation to determine fracture stability. According to the pelvic fracture stability assessment, an appropriate treatment strategy was redetermined. Overall, 7 patients, including 5 women and 2 men, with Tile-B2 pelvic fractures were included in this case series. During the initial examination, senior surgeons recommended that 2 patients should undergo internal fixation and 4 patients, conservative treatment; treatment was undecided for 1 patient. After ultrasonography examination, 4 patients underwent surgery via the Stoppa (n = 2) or ilioinguinal approach (n = 1) or cannulated screw fixation (n = 1). The rest of the patients (n = 3) received conventional treatment. Follow-up ranged from 6 to 10 months. Most of the patients showed excellent functions based on their last Majeed grading scores. There were no complications during the follow-up. Using ultrasonography examination, the preoperative treatment plan in 1 patient was changed, and the uncertain preoperative plan in 1 patient was identified. Preoperative assessment of stability using ultrasonography may assist surgeons in making appropriate treatment choices for patients with Tile-B2 pelvic fractures.

Weight reduction in schizophrenics by molindone.

PubMed

Gardos, G; Cole, J O

1977-03-01

The weight-reducing property of molindone, a recently introduced antipsychotic drug, was tested in 9 hospitalized chronic schizophrenic patients. There was an average weight loss of 7.6 kg after 3 months on molindone; most of the loss occurred during the first month. The mechanism producing this weight loss is uncertain, but a central anorexigenic effect may be an important factor.

Use of point-of-care ultrasound to evaluate for penile fracture in a child.

PubMed

Lam, Samuel H F

2015-02-01

Penile fracture is a urologic emergency requiring prompt surgical intervention. Ultrasound may help clarify the diagnosis in cases of uncertain history and physical examination. The author presents a case of suspected pediatric penile fracture, in which point-of-care ultrasound helped to rule out the condition and facilitated disposition of the patient.

Brain Regions Involved in the Learning and Application of Reward Rules in a Two-Deck Gambling Task

ERIC Educational Resources Information Center

Hartstra, E.; Oldenburg, J. F. E.; Van Leijenhorst, L.; Rombouts, S. A. R. B.; Crone, E. A.

2010-01-01

Decision-making involves the ability to choose between competing actions that are associated with uncertain benefits and penalties. The Iowa Gambling Task (IGT), which mimics real-life decision-making, involves learning a reward-punishment rule over multiple trials. Patients with damage to ventromedial prefrontal cortex (VMPFC) show deficits…

Blazar flaring patterns (B-FlaP) classifying blazar candidate of uncertain type in the third Fermi-LAT catalogue by artificial neural networks

NASA Astrophysics Data System (ADS)

Chiaro, G.; Salvetti, D.; La Mura, G.; Giroletti, M.; Thompson, D. J.; Bastieri, D.

2016-11-01

The Fermi-Large Area Telescope (LAT) is currently the most important facility for investigating the GeV γ-ray sky. With Fermi-LAT, more than three thousand γ-ray sources have been discovered so far. 1144 (˜40 per cent) of the sources are active galaxies of the blazar class, and 573 (˜20 per cent) are listed as blazar candidate of uncertain type (BCU), or sources without a conclusive classification. We use the empirical cumulative distribution functions and the artificial neural networks for a fast method of screening and classification for BCUs based on data collected at γ-ray energies only, when rigorous multiwavelength analysis is not available. Based on our method, we classify 342 BCUs as BL Lacs and 154 as flat-spectrum radio quasars, while 77 objects remain uncertain. Moreover, radio analysis and direct observations in ground-based optical observatories are used as counterparts to the statistical classifications to validate the method. This approach is of interest because of the increasing number of unclassified sources in Fermi catalogues and because blazars and in particular their subclass high synchrotron peak objects are the main targets of atmospheric Cherenkov telescopes.

Uptake, Results, and Outcomes of Germline Multiple-Gene Sequencing After Diagnosis of Breast Cancer.

PubMed

Kurian, Allison W; Ward, Kevin C; Hamilton, Ann S; Deapen, Dennis M; Abrahamse, Paul; Bondarenko, Irina; Li, Yun; Hawley, Sarah T; Morrow, Monica; Jagsi, Reshma; Katz, Steven J

2018-05-10

Low-cost sequencing of multiple genes is increasingly available for cancer risk assessment. Little is known about uptake or outcomes of multiple-gene sequencing after breast cancer diagnosis in community practice. To examine the effect of multiple-gene sequencing on the experience and treatment outcomes for patients with breast cancer. For this population-based retrospective cohort study, patients with breast cancer diagnosed from January 2013 to December 2015 and accrued from SEER registries across Georgia and in Los Angeles, California, were surveyed (n = 5080, response rate = 70%). Responses were merged with SEER data and results of clinical genetic tests, either BRCA1 and BRCA2 (BRCA1/2) sequencing only or including additional other genes (multiple-gene sequencing), provided by 4 laboratories. Type of testing (multiple-gene sequencing vs BRCA1/2-only sequencing), test results (negative, variant of unknown significance, or pathogenic variant), patient experiences with testing (timing of testing, who discussed results), and treatment (strength of patient consideration of, and surgeon recommendation for, prophylactic mastectomy), and prophylactic mastectomy receipt. We defined a patient subgroup with higher pretest risk of carrying a pathogenic variant according to practice guidelines. Among 5026 patients (mean [SD] age, 59.9 [10.7]), 1316 (26.2%) were linked to genetic results from any laboratory. Multiple-gene sequencing increasingly replaced BRCA1/2-only testing over time: in 2013, the rate of multiple-gene sequencing was 25.6% and BRCA1/2-only testing, 74.4%;in 2015 the rate of multiple-gene sequencing was 66.5% and BRCA1/2-only testing, 33.5%. Multiple-gene sequencing was more often ordered by genetic counselors (multiple-gene sequencing, 25.5% and BRCA1/2-only testing, 15.3%) and delayed until after surgery (multiple-gene sequencing, 32.5% and BRCA1/2-only testing, 19.9%). Multiple-gene sequencing substantially increased rate of detection of any pathogenic variant (multiple-gene sequencing: higher-risk patients, 12%; average-risk patients, 4.2% and BRCA1/2-only testing: higher-risk patients, 7.8%; average-risk patients, 2.2%) and variants of uncertain significance, especially in minorities (multiple-gene sequencing: white patients, 23.7%; black patients, 44.5%; and Asian patients, 50.9% and BRCA1/2-only testing: white patients, 2.2%; black patients, 5.6%; and Asian patients, 0%). Multiple-gene sequencing was not associated with an increase in the rate of prophylactic mastectomy use, which was highest with pathogenic variants in BRCA1/2 (BRCA1/2, 79.0%; other pathogenic variant, 37.6%; variant of uncertain significance, 30.2%; negative, 35.3%). Multiple-gene sequencing rapidly replaced BRCA1/2-only testing for patients with breast cancer in the community and enabled 2-fold higher detection of clinically relevant pathogenic variants without an associated increase in prophylactic mastectomy. However, important targets for improvement in the clinical utility of multiple-gene sequencing include postsurgical delay and racial/ethnic disparity in variants of uncertain significance.

Moderate to high use of opioid analgesics are associated with an increased risk of Clostridium difficile infection.

PubMed

Mora, Andrea L; Salazar, Miguel; Pablo-Caeiro, Juan; Frost, Craig P; Yadav, Yashoo; DuPont, Herbert L; Garey, Kevin W

2012-04-01

Risk factors for Clostridium difficile infection (CDI) include use of broad-spectrum antibiotics, advanced age and lack of an appropriate immune response. Whether antiperistaltics such as opioid analgesics also increase the risk of CDI is uncertain. The purpose of this preliminary study was to determine whether opioid analgesics increase the risk of developing CDI in hospitalized patients receiving broad-spectrum antibiotics. Hospitalized patients were assessed for incidence of CDI in relation to usage of opioid analgesics controlling for other known risk factors for CDI. During the study period, a total of 32,775 patients were identified of whom 192 had CDI. In univariate analysis, incidence of CDI increased significantly with moderate or high usage of opioids (P < 0.0001). One hundred of 21,396 (0.47%) patients who did not receive opioids developed CDI. Twenty-two of 6955 patients (0.32%) with mild usage of opioids developed CDI [odds ratio (OR): 0.68; 95% confidence interval (CI): 0.43-1.1; P = 0.10]. Thirty of 33,203 (0.93%) with moderate usage developed CDI (OR: 2.0; 95% CI: 1.3-3.0; P = 0.0009). Forty of 1029 (3.7%) patients with high usage of opioids developed CDI (OR: 8.3; 95% CI: 5.7-12.1; P < 0.0001). Similar results were observed using a multivariate Cox proportional hazard model. Moderate to high use of opioid analgesics were associated with an increased risk of CDI.

Low-dose oral microemulsion ciclosporin for severe, refractory ulcerative colitis.

PubMed

de Saussure, P; Soravia, C; Morel, P; Hadengue, A

2005-08-01

The optimal modalities of treatment with oral microemulsion ciclosporin in patients with severe, steroid-refractory ulcerative colitis are uncertain. To assess the applicability, in terms of efficacy and tolerability, of a standard oral microemulsion ciclosporin treatment protocol targeting relatively low blood ciclosporin concentrations, in patients with severe, steroid-resistant ulcerative colitis. Patients with a severe attack of ulcerative colitis and no satisfactory response to intravenous corticosteroids were started on oral microemulsion ciclosporin. Dosages were adapted according to a standard protocol, targeting a blood predose ciclosporin concentration (C0) of 100-200 ng/mL. Patients without a clinical response on day 8 were scheduled for colectomy. Sixteen patients were enrolled. A clinical response was observed in 14/16 (88%). The mean clinical activity index scores and concentrations of C-reactive protein on days 0, 4 and 8 were 11.8, 6.7 and 4.1, and 50.3, 19.3 and 9.7 mg/L respectively. The mean C0 (days 0-8) was 149 pg/mL. The mean creatinine clearance rates on days 0 and 8 were 88 and 96 mL/min. One patient had an acute elevation of transaminases that resulted in discontinuing ciclosporin. Even when dosed for a target C0 of 100-200 ng/mL, oral microemulsion ciclosporin for severe, steroid-refractory ulcerative colitis achieves an efficacy similar to that attained with higher, potentially more toxic levels. The oral route should replace intravenous treatment in this clinical setting.

The role of nailfold capillary dropout on mortality in systemic sclerosis.

PubMed

Tieu, Joanna; Hakendorf, Paul; Woodman, Richard J; Patterson, Karen; Walker, Jenny; Roberts-Thomson, Peter

2018-05-01

Semi-quantitative wide-field nailfold capillaroscopy (NFC) is a simple technique with proven utility in the early diagnosis of systemic sclerosis (SSc). Its role in prognosis, however, remains uncertain. To investigate the possible utility of NFC in predicting survival. Patients with SSc listed on the South Australian Scleroderma Register (SASR) with prior NFC performed at Flinders Medical Centre from 1991 to 2015 were included in this study. Baseline demographic data, diagnosis, scleroderma antibody status and mortality status were also collected for each patient. The cohort consisted of 99 patients with limited cutaneous SSc, 30 patients with diffuse cutaneous SSc and 23 with an overlap scleroderma syndrome. Fifty-six patients died during the period of study (censured end June 2015). Patients with diffuse scleroderma had significantly greater capillary dropout compared with limited and overlap scleroderma (P < 0.001). In univariate analysis, both capillary dropout scores (log-rank χ 2 = 8.75, P = 0.003) and antibody status (log-rank χ 2 = 13.94, P = 0.003) were associated with mortality. ANOVA showed a significant association between antibody status and capillary dropout (P < 0.001). In Cox regression, adjustment for capillary dropout attenuated the impact of autoantibody group on survival. Nailfold capillary dropout was significantly associated with mortality and the severity of dropout attenuates survival dictated by antibody status. Together these observations support the hypothesis that capillary dropout is on the causal pathway between induction of scleroderma associated autoantibodies and mortality. © 2018 Royal Australasian College of Physicians.

Genetic Programming and Frequent Itemset Mining to Identify Feature Selection Patterns of iEEG and fMRI Epilepsy Data

PubMed Central

Smart, Otis; Burrell, Lauren

2014-01-01

Pattern classification for intracranial electroencephalogram (iEEG) and functional magnetic resonance imaging (fMRI) signals has furthered epilepsy research toward understanding the origin of epileptic seizures and localizing dysfunctional brain tissue for treatment. Prior research has demonstrated that implicitly selecting features with a genetic programming (GP) algorithm more effectively determined the proper features to discern biomarker and non-biomarker interictal iEEG and fMRI activity than conventional feature selection approaches. However for each the iEEG and fMRI modalities, it is still uncertain whether the stochastic properties of indirect feature selection with a GP yield (a) consistent results within a patient data set and (b) features that are specific or universal across multiple patient data sets. We examined the reproducibility of implicitly selecting features to classify interictal activity using a GP algorithm by performing several selection trials and subsequent frequent itemset mining (FIM) for separate iEEG and fMRI epilepsy patient data. We observed within-subject consistency and across-subject variability with some small similarity for selected features, indicating a clear need for patient-specific features and possible need for patient-specific feature selection or/and classification. For the fMRI, using nearest-neighbor classification and 30 GP generations, we obtained over 60% median sensitivity and over 60% median selectivity. For the iEEG, using nearest-neighbor classification and 30 GP generations, we obtained over 65% median sensitivity and over 65% median selectivity except one patient. PMID:25580059

Impact of previous vascular burden on in-hospital and long-term mortality in patients with ST-segment elevation myocardial infarction.

PubMed

Consuegra-Sánchez, Luciano; Melgarejo-Moreno, Antonio; Galcerá-Tomás, José; Alonso-Fernández, Nuria; Díaz-Pastor, Angela; Escudero-García, Germán; Jaulent-Huertas, Leticia; Vicente-Gilabert, Marta

2014-06-01

Patients with a current acute coronary syndrome and previous ischemic heart disease, peripheral arterial disease, and/or cerebrovascular disease are reported to have a poorer outcome than those without these previous conditions. It is uncertain whether this association with outcome is observed at long-term follow-up. Prospective observational study, including 4247 patients with ST-segment elevation myocardial infarction. Detailed clinical data and information on previous ischemic heart disease, peripheral arterial disease, and cerebrovascular disease ("vascular burden") were recorded. Multivariate models were performed for in-hospital and long-term (median, 7.2 years) all-cause mortality. One vascular territory was affected in 1131 (26.6%) patients and ≥ 2 territories in 221 (5.2%). The total in-hospital mortality rate was 12.3% and the long-term incidence density was 3.5 deaths per 100 patient-years. A background of previous ischemic heart disease (odds ratio = 0.83; P = .35), peripheral arterial disease (odds ratio = 1.30; P = .34), or cerebrovascular disease (stroke) (odds ratio = 1.15; P = .59) was not independently predictive of in-hospital death. In an adjusted model, previous cerebrovascular disease and previous peripheral arterial disease were both predictors of mortality at long-term follow-up (hazard ratio = 1.57; P < .001; and hazard ratio = 1.34; P = .001; respectively). Patients with ≥ 2 diseased vascular territories showed higher long-term mortality (hazard ratio = 2.35; P < .001), but not higher in-hospital mortality (odds ratio = 1.07; P = .844). In patients with a diagnosis of ST-segment elevation acute myocardial infarction, the previous vascular burden determines greater long-term mortality. Considered individually, previous cerebrovascular disease and peripheral arterial disease were predictors of mortality at long-term after hospital discharge. Copyright © 2013 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

Erlotinib versus Radiation Therapy for Brain Metastases in Patients with EGFR-Mutant Lung Adenocarcinoma

PubMed Central

Gerber, Naamit K.; Yamada, Yoshiya; Rimner, Andreas; Shi, Weiji; Riely, Gregory J.; Beal, Kathryn; Yu, Helena A.; Chan, Timothy A.; Zhang, Zhigang; Wu, Abraham J.

2017-01-01

Purpose/Objectives Radiation therapy (RT) is the principal modality in the treatment of patients with brain metastases (BM). However, given the activity of EGFR tyrosine kinase inhibitors in the central nervous system (CNS), it is uncertain whether upfront brain RT is necessary for patients with EGFR-mutant lung adenocarcinoma with BM. Methods and Materials Patients with EGFR-mutant lung adenocarcinoma and newly diagnosed BM were identified. Results 222 patients were identified. Exclusion criteria included prior erlotinib use, presence of a de novo erlotinib resistance mutation, or incomplete data. Of the remaining 110 patients, 63 were treated with erlotinib, 32 with whole-brain RT (WBRT), and 15 with stereotactic radiosurgery (SRS). Median OS for the whole cohort was 33 months. There was no significant difference in OS between the WBRT and erlotinib groups (median 35 vs. 26 months, p = .62), while patients treated with SRS had a longer OS compared with the erlotinib group (median, 64 months, p = .004). Median time to ICP was 17 months. There was a longer time to ICP in patients who received WBRT vs. erlotinib upfront (median 24 vs. 16 months, p = .04). Patients in the erlotinib or SRS group were more likely to fail intracranially as a component of first failure, while WBRT patients were more likely to fail outside the brain (p = .004). Conclusions The survival of patients with EGFR-mutant adenocarcinoma with BM is notably long, whether they receive upfront erlotinib or brain RT. We observed longer intracranial control with WBRT, even though the WBRT patients had a higher burden of intracranial disease. Despite the equivalent survival between the WBRT and erlotinib group, this study underscores the role of WBRT in producing durable intracranial control in comparison to a targeted biologic agent with known CNS activity. PMID:24679729

Cooperative learning neural network output feedback control of uncertain nonlinear multi-agent systems under directed topologies

NASA Astrophysics Data System (ADS)

Wang, W.; Wang, D.; Peng, Z. H.

2017-09-01

Without assuming that the communication topologies among the neural network (NN) weights are to be undirected and the states of each agent are measurable, the cooperative learning NN output feedback control is addressed for uncertain nonlinear multi-agent systems with identical structures in strict-feedback form. By establishing directed communication topologies among NN weights to share their learned knowledge, NNs with cooperative learning laws are employed to identify the uncertainties. By designing NN-based κ-filter observers to estimate the unmeasurable states, a new cooperative learning output feedback control scheme is proposed to guarantee that the system outputs can track nonidentical reference signals with bounded tracking errors. A simulation example is given to demonstrate the effectiveness of the theoretical results.

Learning accurate very fast decision trees from uncertain data streams

NASA Astrophysics Data System (ADS)

Liang, Chunquan; Zhang, Yang; Shi, Peng; Hu, Zhengguo

2015-12-01

Most existing works on data stream classification assume the streaming data is precise and definite. Such assumption, however, does not always hold in practice, since data uncertainty is ubiquitous in data stream applications due to imprecise measurement, missing values, privacy protection, etc. The goal of this paper is to learn accurate decision tree models from uncertain data streams for classification analysis. On the basis of very fast decision tree (VFDT) algorithms, we proposed an algorithm for constructing an uncertain VFDT tree with classifiers at tree leaves (uVFDTc). The uVFDTc algorithm can exploit uncertain information effectively and efficiently in both the learning and the classification phases. In the learning phase, it uses Hoeffding bound theory to learn from uncertain data streams and yield fast and reasonable decision trees. In the classification phase, at tree leaves it uses uncertain naive Bayes (UNB) classifiers to improve the classification performance. Experimental results on both synthetic and real-life datasets demonstrate the strong ability of uVFDTc to classify uncertain data streams. The use of UNB at tree leaves has improved the performance of uVFDTc, especially the any-time property, the benefit of exploiting uncertain information, and the robustness against uncertainty.

Outcome of endovascular treatment for acute basilar artery occlusion in the modern era: a single institution experience.

PubMed

Li, Chuanhui; Zhao, Wenbo; Wu, Chuanjie; Shang, Shuyi; Chen, Jian; Ren, Ming; Duan, Jiangang; Ma, Qingfeng; Li, Guilin; Zhang, Yunzhou; Zhang, Hongqi; Jiao, Liqun; Ji, Xunming

2018-06-01

The beneficial effect of endovascular treatment (EVT) for patients with acute basilar artery occlusion (ABAO) remains uncertain. The purpose of the present study was to evaluate clinical outcome of EVT for patients with ABAO and analyze prognostic factors of good outcome. From our prospectively established database, we reviewed all patients with ABAO receiving EVT during January 2014 to December 2016. Baseline characteristics and outcomes were evaluated. Favorable functional outcome was defined as modified Rankin Scale score of 0 to 3 assessed at 3-month follow-up. The association between clinical and procedural characteristics and functional outcome was assessed. Of the 68 patients included, 50 patients (73.5%) received mechanical thrombectomy with stent retriever device. Successful reperfusion (thrombolysis in cerebral infarction grades 2b-3) was achieved in 61 patients (89.7%). Overall favorable functional outcome was reached by 31 patients (45.6%). In univariate analysis, Glasgow Coma Scale sum score, baseline National Institutes of Health stroke scale score (NIHSS), and baseline glycemia level were identified predicting good clinical outcome. Multivariate analysis showed that lower NIHSS was the only independent risk factor of favorable functional outcome (OR 0.832; 95% CI, 0.715-0.968; p = 0.018). No difference of favorable outcomes was observed between the subgroups of time to EVT < 6 h and ≽ 6 h. Data in the present study suggests that EVT for ABAO patients should be reasonable within 24 h of symptom onset. The most important factor determining clinical outcome is initial stroke severity.

Four Japanese male patients with juvenile retinoschisis: only three have mutations in the RS1 gene.

PubMed

Hayashi, Takaaki; Omoto, Satoshi; Takeuchi, Tomokazu; Kozaki, Kenichi; Ueoka, Yasuo; Kitahara, Kenji

2004-11-01

To describe the clinical phenotypes of four unrelated Japanese male patients with juvenile retinoschisis and to investigate occurrences of mutations in the RS1 gene. Observational case series and experimental study. Fundus examinations, fluorescein angiography, and single-flash electroretinography (ERG) were carried out. In one patient, optical coherence tomography (OCT) was performed. The coding regions of the RS1 gene that encodes retinoschisin were amplified by polymerase chain reaction (PCR). The PCR products were purified and directly sequenced. The four affected patients showed cystoid- or wheel-like foveal changes with a little or no fluorescein leakage and negative b-wave patterns in both eyes. The OCT images of foveal retinoschisis disclosed that splitting occurs in the putative fibers of Henle. In three patients, we identified three different missense mutations (p.S73P, p.Y89C, p.R209C) in the functionally important discoidin domain of the RS1 gene. The p.S73P mutation has not been previously reported. In contrast, no nucleotide substitutions were detected in the fourth patient whose parents were unrelated and asymptomatic. No other member of this family for three generations has had juvenile retinoschisis. Because serine 73 is conserved in the mouse ortholog and other discoidin proteins, the proline 73 allele is therefore very likely to encode a defective retinoschisin. Although the inheritance pattern is uncertain in the patient without the RS1 mutation, the clinical and ERG findings were indistinguishable from those of patients with RS1 mutations. This finding points to the genetic heterogeneity of juvenile retinoschisis.

The Cramér-Rao Bounds and Sensor Selection for Nonlinear Systems with Uncertain Observations.

PubMed

Wang, Zhiguo; Shen, Xiaojing; Wang, Ping; Zhu, Yunmin

2018-04-05

This paper considers the problems of the posterior Cramér-Rao bound and sensor selection for multi-sensor nonlinear systems with uncertain observations. In order to effectively overcome the difficulties caused by uncertainty, we investigate two methods to derive the posterior Cramér-Rao bound. The first method is based on the recursive formula of the Cramér-Rao bound and the Gaussian mixture model. Nevertheless, it needs to compute a complex integral based on the joint probability density function of the sensor measurements and the target state. The computation burden of this method is relatively high, especially in large sensor networks. Inspired by the idea of the expectation maximization algorithm, the second method is to introduce some 0-1 latent variables to deal with the Gaussian mixture model. Since the regular condition of the posterior Cramér-Rao bound is unsatisfied for the discrete uncertain system, we use some continuous variables to approximate the discrete latent variables. Then, a new Cramér-Rao bound can be achieved by a limiting process of the Cramér-Rao bound of the continuous system. It avoids the complex integral, which can reduce the computation burden. Based on the new posterior Cramér-Rao bound, the optimal solution of the sensor selection problem can be derived analytically. Thus, it can be used to deal with the sensor selection of a large-scale sensor networks. Two typical numerical examples verify the effectiveness of the proposed methods.

Determinants of parental decision to abort or continue after non-aneuploid ultrasound-detected fetal abnormalities.

PubMed

Pryde, P G; Isada, N B; Hallak, M; Johnson, M P; Odgers, A E; Evans, M I

1992-07-01

This study evaluated factors influencing the decision to abort after abnormalities in the karyotypically normal fetus were found through ultrasonography. We reviewed all pregnancies complicated by ultrasound-detected abnormalities managed on our service from April 1990 through August 1991 (N = 262). Cases with associated karyotypic abnormalities were excluded (N = 35), as were cases diagnosed after the legal gestational age limit for abortion (N = 68). The remaining 159 cases were stratified into prognosis groups of "severe," "uncertain," and "mild." The prognostic severity of the ultrasound abnormality strongly correlated with the decision to abort (P less than .0001). Rates of termination were 0, 12, and 66% in the "mild," "uncertain," and "severe" groups, respectively. The patients' age, gravidity, and parity, and the fetal gestational age at diagnosis did not differ significantly between the groups. 1) In non-aneuploid pregnancies with an ultrasound diagnosis of fetal abnormality, the major predictor of the decision to abort was the severity of fetal prognosis. 2) The gestational age at diagnosis was not an important variable in the decision to abort for fetal structural abnormalities. 3) Parents who had fetuses with abnormalities associated with uncertain prognoses usually opted to continue the pregnancy. This appeared to be particularly true for defects that were potentially correctable in utero or by neonatal intervention (even if investigational).

Smoothing-based compressed state Kalman filter for joint state-parameter estimation: Applications in reservoir characterization and CO2 storage monitoring

NASA Astrophysics Data System (ADS)

Li, Y. J.; Kokkinaki, Amalia; Darve, Eric F.; Kitanidis, Peter K.

2017-08-01

The operation of most engineered hydrogeological systems relies on simulating physical processes using numerical models with uncertain parameters and initial conditions. Predictions by such uncertain models can be greatly improved by Kalman-filter techniques that sequentially assimilate monitoring data. Each assimilation constitutes a nonlinear optimization, which is solved by linearizing an objective function about the model prediction and applying a linear correction to this prediction. However, if model parameters and initial conditions are uncertain, the optimization problem becomes strongly nonlinear and a linear correction may yield unphysical results. In this paper, we investigate the utility of one-step ahead smoothing, a variant of the traditional filtering process, to eliminate nonphysical results and reduce estimation artifacts caused by nonlinearities. We present the smoothing-based compressed state Kalman filter (sCSKF), an algorithm that combines one step ahead smoothing, in which current observations are used to correct the state and parameters one step back in time, with a nonensemble covariance compression scheme, that reduces the computational cost by efficiently exploring the high-dimensional state and parameter space. Numerical experiments show that when model parameters are uncertain and the states exhibit hyperbolic behavior with sharp fronts, as in CO2 storage applications, one-step ahead smoothing reduces overshooting errors and, by design, gives physically consistent state and parameter estimates. We compared sCSKF with commonly used data assimilation methods and showed that for the same computational cost, combining one step ahead smoothing and nonensemble compression is advantageous for real-time characterization and monitoring of large-scale hydrogeological systems with sharp moving fronts.

Deleterious effects of interruption followed by reintroduction of enzyme replacement therapy on a lysosomal storage disorder.

PubMed

Schneider, Ana Paula; Matte, Ursula; Pasqualim, Gabriela; Tavares, Angela Maria Vicente; Mayer, Fabiana Quoos; Martinelli, Barbara; Ribas, Graziela; Vargas, Carmen Regla; Giugliani, Roberto; Baldo, Guilherme

2016-10-01

Temporary interruption of enzyme replacement therapy (ERT) in patients with different lysosomal storage disorders may happen for different reasons (adverse reactions, issues with reimbursement, logistic difficulties, and so forth), and the impact of the interruption is still uncertain. In the present work, we studied the effects of the interruption of intravenous ERT (Laronidase, Genzyme) followed by its reintroduction in mice with the prototypical lysosomal storage disorder mucopolysaccharidosis type I, comparing to mice receiving continuous treatment, untreated mucopolysaccharidosis type I mice, and normal mice. In the animals which treatment was temporarily interrupted, we observed clear benefits of treatment in several organs (liver, lung, heart, kidney, and testis) after reintroduction, but a worsening in the thickness of the aortic wall was detected. Furthermore, these mice had just partial improvements in behavioral tests, suggesting some deterioration in the brain function. Despite worsening is some disease aspects, urinary glycosaminoglycans levels did not increase during interruption, which indicates that this biomarker commonly used to monitor treatment in patients should not be used alone to assess treatment efficacy. The deterioration observed was not caused by the development of serum antienzyme antibodies. All together our results suggest that temporary ERT interruption leads to deterioration of function in some organs and should be avoided whenever possible. Copyright © 2016 Elsevier Inc. All rights reserved.

Can hemozoin alone cause host anaemia?

PubMed

Sun, Jun; Wang, Su-Wen; Jin, Chang-Long; Zeng, Xiao-Li; Piao, Xing-Yu; Bai, Ling; Tang, Dan-Li; Ji, Chang-Le

2016-12-01

Both schistosomes and malaria parasites produce hemozoin and cause host anaemia. However, the relationship between anaemia and hemozoin is unclear. Although some studies have proposed that hemozoin is related to anaemia in malaria patients, whether hemozoin alone can cause anaemia in patients infected by malaria parasites or schistosomes is uncertain. To investigate the effect of hemozoin on hosts, β-haematin was injected intravenously to normal mice. Then, liver and spleen tissues were observed. Mouse blood was examined. Red blood cells (RBCs), white blood cells (WBCs) and haemoglobin were analysed. Macrophage changes in the spleens and marrow cells were compared using immunofluorescence and H&E or Giemsa stain, respectively. We found that after 15 injections of β-haematin, a large amount of β-haematin was observed to deposit in the livers and spleens. Splenomegaly and bone marrow mild hyperplasia were detected. The average number of RBCs, average number of WBCs and average concentration of haemoglobin decreased significantly from 9.36 × 10 12 cells/L to 8.7 × 10 12 cells/L, 3.8 × 10 9 cells/L to 1.7 × 10 9 cells/L and 142.8 g/L to 131.8 g/L, respectively. In specific, the number of macrophages in the spleens greatly increased after β-haematin infection. The results showed that injections of β-haematin alone can cause anaemia possibly through hypersplenism.

Cluster synchronization transmission of different external signals in discrete uncertain network

NASA Astrophysics Data System (ADS)

Li, Chengren; Lü, Ling; Chen, Liansong; Hong, Yixuan; Zhou, Shuang; Yang, Yiming

2018-07-01

We research cluster synchronization transmissions of different external signals in discrete uncertain network. Based on the Lyapunov theorem, the network controller and the identification law of uncertain adjustment parameter are designed, and they are efficiently used to achieve the cluster synchronization and the identification of uncertain adjustment parameter. In our technical scheme, the network nodes in each cluster and the transmitted external signal can be different, and they allow the presence of uncertain parameters in the network. Especially, we are free to choose the clustering topologies, the cluster number and the node number in each cluster.

Impact of insurance carrier, prior authorization, and socioeconomic status on appropriate use of SPECT myocardial perfusion imaging in private community-based office practice.

PubMed

Doukky, Rami; Hayes, Kathleen; Frogge, Nathan; Nazir, Noreen T; Collado, Fareed M; Williams, Kim A

2015-05-01

The impact of health insurance carrier and socioeconomic status (SES) on the adherence to appropriate use criteria (AUC) for radionuclide myocardial perfusion imaging (MPI) is unknown. Health insurance carrier's prior authorization and patient's SES impact adherence to AUC for MPI in a fee-for-service setting. We conducted a prospective cohort study of 1511 consecutive patients who underwent outpatient MPI in a multi-site, office-based, fee-for-service setting. The patients were stratified according to the 2009 AUC into appropriate/uncertain appropriateness and inappropriate use groups. Insurance status was categorized as Medicare (does not require prior authorization) vs commercial (requires prior authorization). Socioeconomic status was determined by the median household income in the ZIP code of residence. The proportion of patients with Medicare was 33% vs 67% with commercial insurance. The rate of inappropriate use was higher among patients with commercial insurance vs Medicare (55% vs 24%; P < 0.001); this difference was not significant after adjusting for confounders known to impact AUC determination (odds ratio: 1.06, 95% confidence interval: 0.62-1.82, P = 0.82). The mean annual household income in the residential areas of patients with inappropriate use as compared to those with appropriate/uncertain use was $72 000 ± 21 000 vs $68 000 ± 20 000, respectively (P < 0.001). After adjusting for covariates known to impact AUC determination, SES (top vs bottom quartile income area) was not independently predictive of inappropriate MPI use (odds ratio: 0.9, 95% confidence interval: 0.53-1.52, P = 0.69). Insurance carriers prior authorization and SES do not seem to play a significant role in determining physicians adherence to AUC for MPI. © 2015 Wiley Periodicals, Inc.

Green, Yellow, and Red risk perception in everyday life - a communication tool.

PubMed

Stensgaard, A; DunnGalvin, A; Nielsen, D; Munch, M; Bindslev-Jensen, C

2017-07-01

Adolescents have the highest risk for food allergy-related fatalities. Our main aim was to investigate the level of risk in everyday social situations as perceived by adolescents/young adults with peanut allergy, their families, and their friends. The web-based 'Colours Of Risks' (COR) questionnaire was completed by 70 patients (aged 12-23 years), 103 mothers and fathers, 31 siblings (aged 12-26 years), and 42 friends (aged 12-24 years). COR deals with six main contexts (home, school/university, work, visiting/social activities, special occasions/parties, and vacations), each with 1-12 items. Response categories are green (I feel safe), yellow (I feel uncertain), or red (I feel everything is risky). There was a high level of agreement between participants in defining situations as safe, uncertain, or risky, but female patients and mothers rated fewer situations as safe compared to male patients and fathers. Being with close friends and family, and attending planned parties without alcohol were perceived as situations of low risk. While 94% of patients took an epinephrine auto-injector (EAI) into risky situations, only 65% took it into safe situations. In contrast to the close family, 31% of the friends did not know the patient had an EAI, and fewer knew how to administer the EAI. Young adults with peanut allergy face challenges when moving from the safe home with ready assistance if needed, to independence with unpredictable surroundings and less certain help. Perceived 'safe' situations may in fact be the riskiest, as patients often do not take the EAI with them. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Breast lesions of uncertain malignant nature and limited metastatic potential: Proposals to improve their recognition and clinical management

PubMed Central

Rakha, Emad A.; Badve, Sunil; Eusebi, Vincenzo; Reis-Filho, Jorge S.; Fox, Stephen B.; Dabbs, David J.; Decker, Thomas; Hodi, Zsolt; Ichihara, Shu; Lee, Andrew HS.; Palacios, José; Richardson, Andrea L.; Vincent-Salomon, Anne; Schmitt, Fernando C.; Tan, Puay-Hoon; Tse, Gary M.; Ellis, Ian O.

2016-01-01

Breast lesions comprise a family of heterogeneous entities with variable patterns of presentation, morphology and clinical behaviour. The majority of breast lesions are traditionally classified into benign and malignant conditions and their behaviour can, in the vast majority of cases, be predicted with a reasonable degree of accuracy. However, there remain lesions which show borderline features and lie in a grey-zone between benign and malignant as their behaviour cannot be predicted reliably. Defined pathological categorisation of such lesions is challenging and for some entities is recognised to be subjective and include a range of diagnoses, and forms of terminology, which may trigger over-treatment or under-treatment. The rarity of these lesions makes acquisition of clinical evidence problematic and limits the development of a sufficient evidence base to support informed decision making by clinicians and patients. Emerging molecular evidence is providing a greater understanding of the biology of these lesions, but this may or may not be reflected in their clinical behaviour. Herein we discuss some breast lesions that are associated with uncertainty regarding classification, behaviour and hence management. These include biologically invasive malignant lesions associated with uncertain metastatic potential such as low-grade adenosquamous carcinoma, low-grade fibromatosis-like spindle cell carcinoma and encapsulated papillary carcinoma. Other lesions remain of uncertain malignant nature such as mammary cylindroma, atypical microglandular adenosis, mammary pleomorphic adenoma and infiltrating epitheliosis. The concept of categories of 1) breast lesions of uncertain malignant nature and 2) breast lesions of limited metastatic potential, are proposed with details of which histological entities could be included in each category, and their management implications are discussed. PMID:26348644

"It wasn't a disaster or anything": Parents' experiences of their child's uncertain chromosomal microarray result.

PubMed

Wilkins, Ella J; Archibald, Alison D; Sahhar, Margaret A; White, Susan M

2016-11-01

Chromosomal microarray is an increasingly utilized diagnostic test, particularly in the pediatric setting. However, the clinical significance of copy number variants detected by this technology is not always understood, creating uncertainties in interpreting and communicating results. The aim of this study was to explore parents' experiences of an uncertain microarray result for their child. This research utilized a qualitative approach with a phenomenological methodology. Semi-structured interviews were conducted with nine parents of eight children who received an uncertain microarray result for their child, either a 16p11.2 microdeletion or 15q13.3 microdeletion. Interviews were transcribed verbatim and thematic analysis was used to identify themes within the data. Participants were unprepared for the abnormal test result. They had a complex perception of the extent of their child's condition and a mixed understanding of the clinical relevance of the result, but were accepting of the limitations of medical knowledge, and appeared to have adapted to the result. The test result was empowering for parents in terms of access to medical and educational services; however, they articulated significant unmet support needs. Participants expressed hope for the future, in particular that more information would become available over time. This research has demonstrated that parents of children who have an uncertain microarray result appeared to adapt to uncertainty and limited availability of information and valued honesty and empathic ongoing support from health professionals. Genetic health professionals are well positioned to provide such support and aid patients' and families' adaptation to their situation as well as promote empowerment. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Percutaneous Intraductal Radiofrequency Ablation for Extrahepatic Distal Cholangiocarcinoma: A Method for Prolonging Stent Patency and Achieving Better Functional Status and Quality of Life

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

Wu, Tian-tian, E-mail: matthewwu1979@hotmail.com; Li, Wei-min, E-mail: weimin-li-surgery@126.com; Li, Hu-cheng, E-mail: hucheng-li-surgery@126.com

PurposeThe clinical efficacy of intraductal radiofrequency ablation (RFA) with Habib™ EndoHPB catheter, a newly developed intervention for malignant extrahepatic biliary obstruction, remains uncertain. The aim of this study was to investigate the clinical efficacy of intraductal RFA.MethodsData from 71 patients with extrahepatic distal cholangiocarcinoma were retrospectively analyzed. The study patients were divided into RFA and control groups. The RFA group had undergone percutaneous transhepatic intraductal RFA with a Habib™ EndoHPB catheter, followed by placement of covered or uncovered biliary self-expandable metallic stents (SEMs) whereas the control group had undergone percutaneous transhepatic covered or uncovered SEMs placement. Procedure-related complications, stent patency,more » patient survival, and postoperative serum bilirubin concentrations were compared between the two groups. The Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) questionnaire was administered to evaluate functional status, improvement in clinical manifestations, and quality of life.ResultsThe RFA group had a longer median stent patency than the control group (p = 0.001 for uncovered SEMs placement). Higher functional well-being, hepatobiliary-specific cancer subscale, Trial Outcome Index, and total FACT-Hep scores were observed during post-procedure follow-up in the RFA group. However, median survival did not differ significantly between the two groups (p > 0.05).ConclusionsProlongation of stent patency and better functional status and quality of life, which are all important clinical endpoints, were observed in patients treated with intraductal RFA. Prospective randomized controlled clinical trials are necessary to further investigate the clinical efficacy and long-term benefits of intraductal RFA.« less

Psychophsyiological reactivity during uncertainty and ambiguity processing in high and low worriers.

PubMed

Kirschner, Hans; Hilbert, Kevin; Hoyer, Jana; Lueken, Ulrike; Beesdo-Baum, Katja

2016-03-01

Intolerance of uncertainty (IU) has been linked to Generalized Anxiety Disorder (GAD), but studies experimentally manipulating uncertainty have mostly failed to find differences between GAD patients and controls, possible due to a lack of distinction between uncertainty and ambiguity. This study therefore investigated reactivity to ambiguity in addition to uncertainty in high worriers (HW) and low worriers (LW). We hypothesized an interpretation bias between the groups during ambiguity tasks, while uncertainty would facilitate threat processing of subsequent aversive stimuli. HW (N = 23) and LW (N = 23) completed a paradigm comprising the anticipation and perception of pictures with dangerous, safe, or ambiguous content. Anticipatory cues were certain (always correct information about the following picture) or uncertain (no information). Subjective ratings, reaction times and skin conductance responses (SCRs) were recorded. HW rated particularly ambiguous pictures as more aversive and showed longer reaction times to all picture conditions compared to LW. SCRs were also larger in HW compared to LW, particularly during uncertain but also safe anticipation. No group differences were observed during perception of stimuli. All participants were female. HW was used as subclinical phenotype of GAD. Intolerance of ambiguity seems to be related to individual differences in worry and possibly to the development of GAD. Threat-related interpretations differentiating HW and LW occurred particularly for ambiguous pictures but were not accompanied by increased autonomic arousal during the picture viewing. This disparity between subjective rating and arousal may be the result of worrying in response to intolerance of uncertainty, restraining physiological responses. Copyright © 2015 Elsevier Ltd. All rights reserved.

Absence of histopathological changes of ileum and colon in functional chronic diarrhea associated with bile acid malabsorption, assessed by SeHCAT test: a prospective study.

PubMed

Sciarretta, G; Furno, A; Morrone, B; Malaguti, P

1994-07-01

Chronic diarrhea of unknown origin is often associated with bile acid malabsorption, the pathogenetic role of which is uncertain. The aim of this study was to identify morphological abnormalities in the ileal and colonic mucosa in patients with this disorder. We performed a prospective and blinded histopathological study (between June 1991 and November 1992) of endoscopic biopsies of the distal ileum and colon of 23 patients suffering from chronic diarrhea of unknown origin. In 14, the SeHCAT (75-selena-homo-cholic acid taurine) test was abnormal owing to bile acid malabsorption; in the other nine, the diarrhea control group, the test results were normal. A detailed evaluation of surface epithelium, immune response and inflammatory changes was made. in two patients and two controls, mild villous atrophy was observed; there was also slight inflammation of the ileal and colonic mucosa occurring with the same frequency in both groups. A slight replacement of goblet cells was more evident in the diarrhea control group. Chronic diarrhea of unknown origin associated with bile acid malabsorption does not involve specific morphological changes of ileal or colonic mucosa, and its pathogenesis must be looked for in dysfunction of the ileum and/or colon.

Pleomorphic dermal sarcoma: a more aggressive neoplasm than previously estimated.

PubMed

Tardío, Juan C; Pinedo, Fernando; Aramburu, José A; Suárez-Massa, Dolores; Pampín, Ana; Requena, Luis; Santonja, Carlos

2016-02-01

Pleomorphic dermal sarcoma (PDS) is a rare neoplasm sharing pathological features with atypical fibroxanthoma, but adding tumor necrosis, invasion beyond superficial subcutis or vascular or perineural infiltration. Although its metastatic risk has been estimated to be less than 5%, its real outcome is presently uncertain because of its rarity and to the lack of homogeneous criteria used in reported cases. Retrospective clinicopathological study of 18 cases of PDS. The lesions presented as tumors or plaques (size: 7-70 mm) on the head of elderly patients (median: 81 years), without a gender predominance. Histopathologically, they consisted of spindle cells arranged in a fascicular pattern, containing pleomorphic epithelioid and giant multinucleated cells in varying proportions, and usually exhibiting numerous mitotic figures and infiltrative tumor margins. No immunoexpression for cytokeratins, S100 protein, desmin or CD34 was observed. Necrosis and venous invasion were found in three tumors each (17%). Follow-up was available in 15 cases (median: 33 months). Three patients (20%) had local recurrences, all with incomplete primary surgical resections. Three patients (20%) developed distant metastases in the skin, regional lymph nodes and/or lungs and died from the disease. Our data suggest that PDS may be a more aggressive neoplasm than previously estimated. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Computer tomographic assessment of postoperative peripancreatic collections after distal pancreatectomy.

PubMed

Uchida, Yuichiro; Masui, Toshihiko; Sato, Asahi; Nagai, Kazuyuki; Anazawa, Takayuki; Takaori, Kyoichi; Uemoto, Shinji

2018-03-27

Peripancreatic collections occur frequently after distal pancreatectomy. However, the sequelae of peripancreatic collections vary from case to case, and their clinical impact is uncertain. In this study, the correlations between CT findings of peripancreatic collections and complications after distal pancreatectomy were investigated. Ninety-six consecutive patients who had undergone distal pancreatectomy between 2010 and 2015 were retrospectively investigated. The extent and heterogeneity of peripancreatic collections and background clinicopathological characteristics were analyzed. The extent of peripancreatic collections was calculated based on three-dimensional computed tomography images, and the degree of heterogeneity of peripancreatic collections was assessed based on the standard deviation of their density on computed tomography. Of 85 patients who underwent postoperative computed tomography imaging, a peripancreatic collection was detected in 77 (91%). Patients with either a large extent or a high degree of heterogeneity of peripancreatic collection had a significantly higher rate of clinically relevant pancreatic fistula than those without (odds ratio 5.95, 95% confidence interval 2.12-19.72, p = 0.001; odds ratio 8.0, 95% confidence interval 2.87-24.19, p = 0.0001, respectively). A large and heterogeneous peripancreatic collection was significantly associated with postoperative complications, especially clinically relevant postoperative pancreatic fistula. A small and homogenous peripancreatic collection could be safely observed.

Bacteremia in blood or marrow transplantation patients: clinical risk factors for infection and emerging antibiotic resistance.

PubMed

Bock, Allison M; Cao, Qing; Ferrieri, Patricia; Young, Jo-Anne H; Weisdorf, Daniel J

2013-01-01

Bacterial infections continue to be a leading cause of mortality and morbidity in patients who undergo blood and marrow transplantations (BMTs). The relative importance of different clinical features (donor type, graft cell source, and conditioning regimen) on the incidence and timing of posttransplantation bacterial infections is uncertain, but a detailed analysis could better guide prevention and therapy. We retrospectively analyzed the incidence and risk factors for early bacterial infections, as well as patterns of antibiotic resistance. We observed 613 bacteremic events among 349 of 834 patients who underwent BMT treated at the University of Minnesota from 2005 to 2010 (cumulative incidence 42%; 95% confidence interval [CI], 38-45). Donor type (allogeneic vs autologous) had the greatest impact on the incidence of bacteremia within 100 days posttransplantation. Among allogeneic transplantations, myeloablative (MA), compared to reduced-intensity conditioning (RIC) was associated with a significantly greater risk of bacteremia, as was the development of acute graft-versus-host disease (aGVHD). Additionally, patients who underwent BMT, compared to the contemporaneous hospital population, developed infections with more frequent resistance to antibiotics used in the treatment against commonly isolated bacterial organisms. These findings have important clinical implications regarding the use and selection of both prophylactic and empiric antibiotic regimens. Copyright © 2013 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Electroconvulsive therapy in treatment-resistant schizophrenia: prediction of response and the nature of symptomatic improvement.

PubMed

Chanpattana, Worrawat; Sackeim, Harold A

2010-12-01

The clinical features of patients with schizophrenia who respond to electroconvulsive therapy (ECT) are uncertain. There is a longstanding belief that the duration of illness and/or the presence of affective symptoms associate with good prognosis. There is also little information on the nature of symptomatic improvement with this treatment. We examined the demographic and clinical history features associated with response, the symptom profile predictive of response, and the profile of symptomatic improvement. Using a standardized protocol, 253 patients with treatment-resistant schizophrenia were prospectively treated with a combination of ECT and flupenthixol. Of this group, 138 patients (54.5%) met the response criteria. Independence of sex, longer duration of current episode, and greater severity of baseline negative symptoms were predictive of poorer outcome. Duration of illness had weak relations with outcome only among females. There were marked sex differences in other clinical features and symptoms associated with response. In contrast, no sex differences were observed in the nature of symptomatic improvement. Treatment resulted in marked improvement in specific positive symptoms, with an intermediate effect on affective symptoms and no effect or worsening of specific negative symptoms. The findings challenge recommendations that long duration of illness or absence of affective symptoms portends poor response to ECT in patients with treatment-resistant schizophrenia. Sex may play a critical role in determining the features of the illness that predict outcome.

Calibration of hydrological models using flow-duration curves

NASA Astrophysics Data System (ADS)

Westerberg, I. K.; Guerrero, J.-L.; Younger, P. M.; Beven, K. J.; Seibert, J.; Halldin, S.; Freer, J. E.; Xu, C.-Y.

2011-07-01

The degree of belief we have in predictions from hydrologic models will normally depend on how well they can reproduce observations. Calibrations with traditional performance measures, such as the Nash-Sutcliffe model efficiency, are challenged by problems including: (1) uncertain discharge data, (2) variable sensitivity of different performance measures to different flow magnitudes, (3) influence of unknown input/output errors and (4) inability to evaluate model performance when observation time periods for discharge and model input data do not overlap. This paper explores a calibration method using flow-duration curves (FDCs) to address these problems. The method focuses on reproducing the observed discharge frequency distribution rather than the exact hydrograph. It consists of applying limits of acceptability for selected evaluation points (EPs) on the observed uncertain FDC in the extended GLUE approach. Two ways of selecting the EPs were tested - based on equal intervals of discharge and of volume of water. The method was tested and compared to a calibration using the traditional model efficiency for the daily four-parameter WASMOD model in the Paso La Ceiba catchment in Honduras and for Dynamic TOPMODEL evaluated at an hourly time scale for the Brue catchment in Great Britain. The volume method of selecting EPs gave the best results in both catchments with better calibrated slow flow, recession and evaporation than the other criteria. Observed and simulated time series of uncertain discharges agreed better for this method both in calibration and prediction in both catchments. An advantage with the method is that the rejection criterion is based on an estimation of the uncertainty in discharge data and that the EPs of the FDC can be chosen to reflect the aims of the modelling application, e.g. using more/less EPs at high/low flows. While the method appears less sensitive to epistemic input/output errors than previous use of limits of acceptability applied directly to the time series of discharge, it still requires a reasonable representation of the distribution of inputs. Additional constraints might therefore be required in catchments subject to snow and where peak-flow timing at sub-daily time scales is of high importance. The results suggest that the calibration method can be useful when observation time periods for discharge and model input data do not overlap. The method could also be suitable for calibration to regional FDCs while taking uncertainties in the hydrological model and data into account.

Calibration of hydrological models using flow-duration curves

NASA Astrophysics Data System (ADS)

Westerberg, I. K.; Guerrero, J.-L.; Younger, P. M.; Beven, K. J.; Seibert, J.; Halldin, S.; Freer, J. E.; Xu, C.-Y.

2010-12-01

The degree of belief we have in predictions from hydrologic models depends on how well they can reproduce observations. Calibrations with traditional performance measures such as the Nash-Sutcliffe model efficiency are challenged by problems including: (1) uncertain discharge data, (2) variable importance of the performance with flow magnitudes, (3) influence of unknown input/output errors and (4) inability to evaluate model performance when observation time periods for discharge and model input data do not overlap. A new calibration method using flow-duration curves (FDCs) was developed which addresses these problems. The method focuses on reproducing the observed discharge frequency distribution rather than the exact hydrograph. It consists of applying limits of acceptability for selected evaluation points (EPs) of the observed uncertain FDC in the extended GLUE approach. Two ways of selecting the EPs were tested - based on equal intervals of discharge and of volume of water. The method was tested and compared to a calibration using the traditional model efficiency for the daily four-parameter WASMOD model in the Paso La Ceiba catchment in Honduras and for Dynamic TOPMODEL evaluated at an hourly time scale for the Brue catchment in Great Britain. The volume method of selecting EPs gave the best results in both catchments with better calibrated slow flow, recession and evaporation than the other criteria. Observed and simulated time series of uncertain discharges agreed better for this method both in calibration and prediction in both catchments without resulting in overpredicted simulated uncertainty. An advantage with the method is that the rejection criterion is based on an estimation of the uncertainty in discharge data and that the EPs of the FDC can be chosen to reflect the aims of the modelling application e.g. using more/less EPs at high/low flows. While the new method is less sensitive to epistemic input/output errors than the normal use of limits of acceptability applied directly to the time series of discharge, it still requires a reasonable representation of the distribution of inputs. Additional constraints might therefore be required in catchments subject to snow. The results suggest that the new calibration method can be useful when observation time periods for discharge and model input data do not overlap. The new method could also be suitable for calibration to regional FDCs while taking uncertainties in the hydrological model and data into account.

Soil respiration is not limited by reductions in microbial biomass during long-term soil incubations

USDA-ARS?s Scientific Manuscript database

Declining rates of soil respiration are reliably observed during long-term laboratory incubations, but the cause is uncertain. We explored different controls on soil respiration during long-term soil incubations. Following a 707 day incubation (30 C) of soils from cultivated and forested plots at Ke...

Caught in Uncertain Futures, Now: A Reflexive Moment

ERIC Educational Resources Information Center

Reyes, Reynaldo, III

2016-01-01

This reflexive vignette reveals the emotional risks of ethnographic work by a Chicano researcher, educator, and advocate doing work in the Texas-Mexico Borderlands, caught at the intersection of vulnerable Latina/o youth and their possible futures. Data in this creative piece are derived from field notes of one classroom observation from an…

Is There a History of Educational Philosophy? John White vs the Historical Evidence

ERIC Educational Resources Information Center

Muir, James R.

2004-01-01

In his recent review of Amelie Rorty's collection, "Philosophers on Education: New Historical Perspectives," John White makes the uncontroversial observation that the future of philosophy of education within Educational Studies is uncertain. He chooses to be optimistic, hoping that "the climate in which philosophising about education, whether by…

Post-Observation Conferences with Bilingual Pre-Service Teachers: Revoicing and Rehearsing

ERIC Educational Resources Information Center

Wall, Dorothy J.; Hurie, Andrew H.

2017-01-01

Pre-service teachers need support in developing their teacher identities as they navigate the uncertain and complex terrain of student teaching and face the pressures of high-stakes accountability. This support is particularly important for bilingual pre-service teachers as they negotiate the many complexities of the bilingual classroom, and as…

Incentive Control Strategies for Decision Problems with Parametric Uncertainties

NASA Astrophysics Data System (ADS)

Cansever, Derya H.

The central theme of this thesis is the design of incentive control policies in large scale systems with hierarchical decision structures, under the stipulation that the objective functionals of the agents at the lower level of the hierarchy are uncertain to the top-level controller (the leader). These uncertainties are modeled as a finite -dimensional parameter vector whose exact value constitutes private information to the relevant agent at the lower level. The approach we have adopted is to design incentive policies for the leader such that the dependence of the decision of the agents on the uncertain parameter is minimized. We have identified several classes of problems for which this approach is feasible. In particular, we have constructed policies whose performance is arbitrarily close to the solution of a version of the same problem that does not involve uncertainties. We have also shown that for a certain class of problem wherein the leader observes a linear combination of the agents' decisions, the leader can achieve the performance he would obtain if he had observed each decision separately.

Interplanetary particles and fields, November 22 - December 6, 1977: Helios, Voyager, and IMP observations between 0.6 AU and 1.6 AU

NASA Technical Reports Server (NTRS)

Burlaga, L. F.; Lepping, R. P.; Weber, R.; Armstrong, T.; Goodrich, C.; Sullivan, J.; Gurnett, D.; Kellogg, P.; Keppler, E.; Mariani, F.

1979-01-01

The principal interplanetary events observed are described and analyzed. Three flow systems were observed: (1) a corotating stream and a stream interface associated with a coronal hole; (2) a shock wave and an energetic particle event associated with a 2-B flare; and (3) an isolated shock wave of uncertain origin. Data from 28 experiments and 6 spacecraft provide measurements of solar wind plasma, magnetic fields, plasma waves, radio waves, energetic electrons, and low energy protons.

Physicians’ Religious Topic Avoidance during Clinical Interactions

PubMed Central

Villagran, Melinda M.; MacArthur, Brenda L.; Lee, Lauren E.; Ledford, Christy J. W.; Canzona, Mollie R.

2017-01-01

Religious and spiritual (R/S) conversations at the end-of-life function to help patients and their families find comfort in difficult circumstances. Physicians who feel uncertain about how to discuss topics related to religious beliefs may seek to avoid R/S conversations with their patients. This study utilized a two-group objective structured clinical examination with a standardized patient to explore differences in physicians’ use of R/S topic avoidance tactics during a clinical interaction. Results indicated that physicians used more topic avoidance tactics in response to patients’ R/S inquiries than patients’ R/S disclosures; however, the use of topic avoidance tactics did not eliminate the need to engage in patient-initiated R/S interactions. PMID:28481290

Determinants of the relationship between cost and survival time after elective adult cardiac surgery.

PubMed

Ho, K M

2014-05-01

Cardiac surgery is increasingly performed on elderly patients with multiple comorbid conditions, but the determinants of the relationship between cost and survival time after cardiac surgery for patients with a serious cardiac condition remain uncertain. Using the long-term outcome data of a cohort study on adult cardiac surgical patients, the relationship between cost and survival time after cardiac surgery from a hospital service perspective was determined. The total cost for each patient was estimated by the costs of the surgical procedures, intra-aortic balloon pump utilisation, operating theatre utilisation, blood products, intensive care unit stay and cumulative hospital stay up to a median follow-up time of 30 months. Of the 2131 patients considered in this study, a total cost >A$100,000 per life-year after cardiac surgery was observed only in 171 patients (8.0%, 95% confidence interval 6.9 to 9.3%). Age, Charlson Comorbidity Index and EuroSCORE were all related to the cost per life-year after cardiac surgery, but EuroSCORE (odds ratio 1.26 per score increment, 95% confidence interval 1.18 to 1.35, P=0.001) was, by far, the most important determinant and explained 32% of the variability in cost per life-year after cardiac surgery. Patients with a high EuroSCORE were associated with a substantially longer length of intensive care unit stay and cumulative hospital stay, as well as a shorter survival time after cardiac surgery compared to patients with a lower EuroSCORE. Of all the subgroups of patients examined, only patients with a EuroSCORE >5 were consistently associated with a cost >A$100,000 per life-year (cost per life-year $183,148, 95% confidence interval 125, 394 to 240, 902).

Multilineage dysplasia is associated with a poorer prognosis in patients with de novo acute myeloid leukemia with intermediate-risk cytogenetics and wild-type NPM1.

PubMed

Rozman, María; Navarro, José-Tomás; Arenillas, Leonor; Aventín, Anna; Giménez, Teresa; Alonso, Esther; Perea, Granada; Camós, Mireia; Navarrete, Mayda; Tuset, Esperanza; Florensa, Lourdes; Millá, Fuensanta; Nomdedéu, Josep; de la Banda, Esmeralda; Díaz-Beyá, Marina; Pratcorona, Marta; Garrido, Ana; Navarro, Blanca; Brunet, Salut; Sierra, Jorge; Esteve, Jordi

2014-10-01

Acute myeloid leukemia (AML) with myelodysplasia-related changes is characterized by the presence of multilineage dysplasia (MLD), frequently related to high-risk cytogenetics and poor outcome. However, the presence of MLD does not modify the favorable prognostic impact of NPM1 mutation. The prognosis of patients with AML presenting marked dysplasia lacking high-risk cytogenetics and NPM1 mutation is uncertain. We evaluated the prognostic impact of MLD in 177 patients with intermediate-risk cytogenetics AML (IR-AML) and wild-type NPM1. Patients were categorized as MLD-WHO (WHO myelodysplasia criteria; n = 43, 24 %), MLD-NRW (significant MLD non-reaching WHO criteria; n = 16, 9 %), absent MLD (n = 80, 45 %), or non-evaluable MLD (n = 38, 22 %). No differences concerning the main characteristics were observed between patients with or without MLD. Outcome of patients with MLD-WHO and MLD-NRW was similar, and significantly worse than patients lacking MLD. The presence of MLD (66 vs. 80 %, p = 0.03; HR, 95 % CI = 2.3, 1.08-4.08) and higher leukocyte count at diagnosis was the only variable associated with lower probability of complete remission after frontline therapy. Concerning survival, age and leukocytes showed an independent prognostic value, whereas MLD showed a trend to a negative impact (p = 0.087, HR, 95 % CI = 1.426, 0.95-2.142). Moreover, after excluding patients receiving an allogeneic stem cell transplantation in first CR, MLD was associated with a shorter survival (HR, 95 % CI = 1.599, 1.026-2.492; p = 0.038). In conclusion, MLD identifies a subgroup of patients with poorer outcome among patients with IR-AML and wild-type NPM1.

Analysis of chromosomal abnormalities by CGH-array in patients with dysmorphic and intellectual disability with normal karyotype

PubMed Central

Pratte-Santos, Rodrigo; Ribeiro, Katyanne Heringer; Santos, Thainá Altoe; Cintra, Terezinha Sarquis

2016-01-01

ABSTRACT Objective To investigate chromosomal abnormalities by CGH-array in patients with dysmorphic features and intellectual disability with normal conventional karyotype. Methods Retrospective study, carried out from January 2012 to February 2014, analyzing the CGH-array results of 39 patients. Results Twenty-six (66.7%) patients had normal results and 13 (33.3%) showed abnormal results - in that, 6 (15.4%) had pathogenic variants, 6 (15.4%) variants designated as uncertain and 1 (2.5%) non-pathogenic variants. Conclusion The characterization of the genetic profile by CGH-array in patients with intellectual disability and dysmorphic features enabled making etiologic diagnosis, followed by genetic counseling for families and specific treatment. PMID:27074231

A survey of doctors at a UK teaching hospital to assess understanding of recent changes to consent law.

PubMed

O'Brien, J W; Natarajan, M; Shaikh, I

2017-06-01

The UK Supreme Court recently ruled that when consenting patients for treatments or procedures, clinicians must also discuss any associated material risks. We surveyed medical staff at a large UK teaching hospital in order to ascertain knowledge of consent law and current understanding of this change. Email survey sent to medical staff in all specialities at Norfolk and Norwich University Hospital in February 2016. 245 responses (141 Consultants and 104 junior doctors, response rate 32%). 82% consent patients for procedures at least monthly and 23% daily. 31% were not familiar with the concept of material risk. 35% were familiar with the recent change in consent law, 41% were not. 18% were "very uncertain" and 64% "a little uncertain" that their consenting process meets current legal requirements. >92% think that landmark cases and changes in law should be discussed through professional bodies and circulated better locally. The majority were not familiar with the concept of material risk and recent legal changes. A majority were not confident that their practice meets current requirements, suggesting that recent changes in consent law may not be widely understood at this hospital. We suggest more guidance and education may be necessary than is currently available. Increased understanding of recent changes to consent law will reduce the risk taken by NHS trusts and offer patients a service compliant with Supreme Court guidance.

Safety and efficacy of empirical interleukin-1 inhibition using anakinra in AA amyloidosis of uncertain aetiology.

PubMed

Lane, Thirusha; Wechalekar, Ashutosh D; Gillmore, Julian D; Hawkins, Philip N; Lachmann, Helen J

2017-09-01

AA amyloidosis is a serious complication of persistent inflammation, which, untreated will progress to renal failure and death. Effective suppression of the underlying inflammatory disease is the focus of treatment. However, in approximately 20% of cases the underlying condition remains uncertain, presenting a dilemma as to choice of treatment. We conducted a retrospective study of a cohort of 11 patients diagnosed with AA amyloidosis of unknown aetiology, who had been empirically treated with anakinra. In anakinra-responders, median pre-treatment SAA was 74 (IQR 34-190) mg/L, and median on-treatment SAA was 6 (4-16) mg/L (p = .0047), with the response having been maintained for a median on-treatment follow-up of 1.8 (1-7.6) years. Six dialysis patients were treated effectively and safely with 100 mg anakinra three times weekly post-dialysis. Four patients remained well on daily anakinra post-renal transplant. Five anakinra-responders showed regression and three showed stabilization of amyloid load on serial SAP scintigraphy. This small cohort shows that even in potentially high risk cases with organ damage secondary to AA amyloidosis or in the presence of a renal graft, anakinra, when used appropriately and carefully monitored, has proved remarkably effective and well tolerated. Longer follow-up of this off-label use is required.

Medical students’ attitude toward suicide attempters

PubMed Central

Nebhinani, Naresh; Chahal, Savita; Jagtiani, Amit; Nebhinani, Mamta; Gupta, Rajiv

2016-01-01

Background: Majority of health professionals have unfavorable attitudes toward the patients presenting with self-harm, which further compromises their therapeutic endeavors and outcomes. Objectives: This study was aimed to assess the medical students' attitudes toward suicide attempters. Materials and Methods: A cross-sectional study was conducted in a tertiary care medical institute of Haryana, a Northern state of India. Two hundred and five final year medical students were recruited through total enumeration method. “Suicide Opinion Questionnaire” was administered to assess their attitudes toward suicide attempters. Results: Only minority had previous exposure of managing any suicidal patient and attended suicide prevention programs. Majority agreed for suicide attempters being lonely and depressed. Nearly half of the students reported small family, disturbed interpersonal relationship, weak personality, self-punishment approach, cultural inhibitions in emotional expression, national instability, and disbelief in afterlife, as a major push to attempt suicide. Compared to boys, girls reported the greater contribution of weak personality and self-destructive behaviors and lesser contribution of family disturbances and religious convictions as suicide triggers. They held favorable attitude for only one-third of the attitudinal statement, and they were uncertain for two-third of the attitudinal statements. Conclusions: Such a high proportion of uncertain responses imply toward lack of awareness and clinical expertise for managing suicide attempters. It also signifies the urgent need for enhancing their educational and clinical exposure, to improve their attitudes toward patients presenting with self-harm. PMID:28163403

Study of telomere length and different markers of oxidative stress in patients with Parkinson's disease.

PubMed

Watfa, G; Dragonas, C; Brosche, T; Dittrich, R; Sieber, C C; Alecu, C; Benetos, A; Nzietchueng, R

2011-04-01

Many studies have shown that short telomere length (TL) is associated with high oxidative stress and various age-related diseases. Parkinson's disease (PD) is an age-related disease, and although its pathogenic mechanism is uncertain, oxidative stress is believed to be implicated in this pathology. The aim of this case-control study was to assess both TL and the different markers of oxidative stress in elderly patients with PD compared to age control subjects. 20 PD patients and 15 age-matched controls, >65 years were studied. TL was measured by Southern blotting from DNA samples extracted from white blood cells. Superoxide dismutase (SOD) activity and plasma levels of total glutathione and protein carbonyls were determined. There was a trend for lower TL in PD patients: 6.06 ± 0.81 kb in PD versus 6.45 ± 0.73 kb in controls (p = 0.08). No significant difference was found between the two groups in terms of oxidative stress markers. In controls, age was the main determinant of telomere shortening (r = -0.547; p = 0.03) whereas, in PD patients, telomere shortening was mainly dependent on plasmatic concentrations of carbonyl proteins (r= -0.544; p=0.044). In PD patients, a negative association was observed between plasma carbonyl protein levels and SOD activity (r= -0.622, p=0.004). In PD, TL is shorter in presence of high oxidative stress as measured by carbonyl protein levels. The absence of telomere attrition with age among patients with PD could reflect a telomere regulation by mechanisms other than age.

Medical students' experiences of professional lapses and patient rights abuses in a South African health sciences faculty.

PubMed

Vivian, Lauraine M H; Naidu, Claudia S; Keikelame, Mpoe J; Irlam, James

2011-10-01

To elicit South African medical students' experiences of witnessing patient rights abuses and professional lapses during their clinical training in order to inform an appropriate and effective response. During June and July 2009 at the University of Cape Town Faculty of Health Sciences, the authors surveyed 223 fourth-, fifth-, and sixth-year medical students in selected clinical rotations concerning abuses they had observed. Volunteers were later interviewed individually. The authors coded interview transcripts for key themes using a constant-comparative grounded theory approach. Of 223 students surveyed, 183 (82%) responded, 130 (71%) of whom reported witnessing patient rights abuses and professional lapses, including physical abuse (38%), verbal abuse (37%), disrespect for patients' dignity (25%), and inadequately informing patients about their treatment (25%). Students attributed abuse to stressed health workers, overburdened facilities, and disempowered patients. Most students who witnessed abuse (59%) did not actively respond, and 64% of survey respondents felt unprepared or uncertain about challenging abuses in the future. Interviews with 28 students yielded detailed accounts of the abuses witnessed and of students' emotional reactions, coping strategies, and responses. Most students did not report abuses; they feared reprisal or doubted it would make a difference. This study demonstrates the disjunction between what these students were taught about human rights and ethics and what they witnessed in clinical settings. The high prevalence of patient rights abuses experienced by these students highlights the need to align medical ethics and human rights with medico-legal protocols in theory and clinical practice.

IBS-like symptoms in patients with ulcerative colitis

PubMed Central

Gracie, David J; Ford, Alexander C

2015-01-01

Ulcerative colitis (UC) and irritable bowel syndrome (IBS) are chronic gastrointestinal disorders that, until recently, have been considered dichotomous conditions falling on either side of a functional-organic divide. However, persistent gastrointestinal symptoms, akin to those of IBS, are observed in up to one in three patients with quiescent UC. Whether these lower gastrointestinal symptoms are secondary to coexistent IBS or occult UC disease activity is uncertain, but when objective evidence of disease activity is lacking, escalation of conventional pharmacotherapy in such patients is often ineffective. The etiologies of both UC and IBS remain unclear, but dysregulation of the enteric nervous system, an altered microbiome, low-grade mucosal inflammation, and activation of the brain–gut axis is common to both; this suggests that some overlap between the two conditions is plausible. How best to investigate and manage IBS-type symptoms in UC patients remains unclear. Studies that have assessed patients with UC who meet criteria for IBS for subclinical inflammation have been conflicting in their results. Although evidence-based treatments for IBS exist, their efficacy in UC patients reporting these types of symptoms remains unclear. Given the disturbances in gut microbiota in UC, and the possible role of the brain–gut axis in the generation of such symptoms, treatments such as probiotics, fecal transfer, antidepressants, or psychological therapies would seem logical approaches to use in this group of patients. However, there are only limited data for all of these therapies; this suggests that randomized controlled trials to investigate their efficacy in this setting may be warranted. PMID:25733921

IBS-like symptoms in patients with ulcerative colitis.

PubMed

Gracie, David J; Ford, Alexander C

2015-01-01

Ulcerative colitis (UC) and irritable bowel syndrome (IBS) are chronic gastrointestinal disorders that, until recently, have been considered dichotomous conditions falling on either side of a functional-organic divide. However, persistent gastrointestinal symptoms, akin to those of IBS, are observed in up to one in three patients with quiescent UC. Whether these lower gastrointestinal symptoms are secondary to coexistent IBS or occult UC disease activity is uncertain, but when objective evidence of disease activity is lacking, escalation of conventional pharmacotherapy in such patients is often ineffective. The etiologies of both UC and IBS remain unclear, but dysregulation of the enteric nervous system, an altered microbiome, low-grade mucosal inflammation, and activation of the brain-gut axis is common to both; this suggests that some overlap between the two conditions is plausible. How best to investigate and manage IBS-type symptoms in UC patients remains unclear. Studies that have assessed patients with UC who meet criteria for IBS for subclinical inflammation have been conflicting in their results. Although evidence-based treatments for IBS exist, their efficacy in UC patients reporting these types of symptoms remains unclear. Given the disturbances in gut microbiota in UC, and the possible role of the brain-gut axis in the generation of such symptoms, treatments such as probiotics, fecal transfer, antidepressants, or psychological therapies would seem logical approaches to use in this group of patients. However, there are only limited data for all of these therapies; this suggests that randomized controlled trials to investigate their efficacy in this setting may be warranted.

Prospective Monitoring of Donor-specific Anti-HLA Antibodies After Intestine/Multivisceral Transplantation: Significance of De Novo Antibodies.

PubMed

Kubal, Chandrashekhar; Mangus, Richard; Saxena, Romil; Lobashevsky, Andrew; Higgins, Nancy; Fridell, Jonathan; Tector, A Joseph

2015-08-01

Presence of circulating donor-specific antibodies (DSA) may be associated with worse clinical outcomes after intestine/multivisceral transplantation. In 79 intestine/multivisceral recipients, sera were prospectively screened for DSA by Luminex Single antigen test at 1, 3, 6, 9, 12, 18, 24, and 36 months after transplantation. Standard immunosuppression included thymoglobulin-rituximab induction and tacrolimus-prednisone maintenance. C4d staining was performed retrospectively on biopsies in patients that developed acute rejection (AR). Twenty-two (28%) patients developed de novo DSA at a median posttransplant period of 3 (1-36) months. De novo DSA were observed in 10 of 40 liver-including and 12 of 39 liver-excluding transplants (P = 0.57). Occurrence of AR was slightly higher in patients with de novo DSA (45% vs 33%, respectively; P = 0.41). Similarly, chronic rejection (14% vs 5%; P = 0.21) and graft loss due to AR (18% vs 7%; P = 0.14) were numerically higher in patients with de novo DSA. Only 35% patients experiencing AR had circulating de novo DSA at the time of AR. Antibody-mediated rejection was diagnosed in 6 patients based on C4d staining, of these 2 patients had circulating de novo DSA at the time of biopsy. De novo DSA formation, particularly early in the posttransplant course may be associated with trends toward worse outcomes. However, its significance in the pathophysiology of AR remains uncertain. Studies focusing mechanisms of DSA-related graft injury and intragraft DSA detection might provide further insight into this issue.

Accelerated ischemic vascular retinopathy after intravitreally injected bevacizumab for central retinal vein occlusion in elderly patients

PubMed Central

Isola, Vincenzo; Pece, Alfredo; Massironi, Claudio; Reposi, Simone; Dimastrogiovanni, Fabio

2013-01-01

Background: Ischemic changes in the retinal circulation are an uncommon but severe adverse vascular reaction to intravitreal bevacizumab (Avastin®, Genentech, San Francisco, CA, USA/Roche, Basel, Switzerland) for central retinal vein occlusion (CRVO). In the two cases reported here, ischemic changes in the retina vasculature following intravitreal bevacizumab for CRVO were observed with the aim of describing the clinical and angiographic features of these changes. Methods: Two elderly patients with recent-onset CRVO received one off-label intravitreal injection of bevacizumab 0.05 mL/1.25 mg. Results: In Case 1, the patient’s pre-treatment visual acuity was 20/400. At 3 weeks post injection, the patient could count fingers at a distance of 1 ft (30 cm) and fluorescein angiography showed reduction in intraretinal hemorrhages and areas of retinal non-perfusion. However, at 6 weeks these were markedly increased compared with those seen in the photograph taken 3 weeks after treatment. In Case 2, the patient’s pre-treatment visual acuity was 20/200. At 1 month post injection, vision had decreased to 20/400 and fluorescein angiography showed severe macular ischemia with a remarkable capillary dropout throughout the macula. Conclusion: Ischemic retinal injury may be an uncommon but severe adverse vascular reaction to intravitreal bevacizumab for CRVO. Although progression of retinal ischemia in CRVO could be observed shortly after intravitreal bevacizumab, whether this is a drug- or procedure-related effect or part of the natural history of the condition remains uncertain. PMID:23467497

Characterizing traffic under uncertain disruptions : an experimental approach.

DOT National Transportation Integrated Search

2013-03-01

The objective of the research is to study long-term traffic patterns under uncertain disruptions using : data collected from human subjects who simultaneously make route choices in controlled PC-based : laboratory experiments. Uncertain disruptions t...

Relationship between red meat allergy and sensitization to gelatin and galactose-α-1,3-galactose.

PubMed

Mullins, Raymond James; James, Hayley; Platts-Mills, Thomas A E; Commins, Scott

2012-05-01

We have observed patients clinically allergic to red meat and meat-derived gelatin. We describe a prospective evaluation of the clinical significance of gelatin sensitization, the predictive value of a positive test result, and an examination of the relationship between allergic reactions to red meat and sensitization to gelatin and galactose-α-1,3-galactose (α-Gal). Adult patients evaluated in the 1997-2011 period for suspected allergy/anaphylaxis to medication, insect venom, or food were skin tested with gelatin colloid. In vitro (ImmunoCAP) testing was undertaken where possible. Positive gelatin test results were observed in 40 of 1335 subjects: 30 of 40 patients with red meat allergy (12 also clinically allergic to gelatin), 2 of 2 patients with gelatin colloid-induced anaphylaxis, 4 of 172 patients with idiopathic anaphylaxis (all responded to intravenous gelatin challenge of 0.02-0.4 g), and 4 of 368 patients with drug allergy. Test results were negative in all patients with venom allergy (n = 241), nonmeat food allergy (n = 222), and miscellaneous disorders (n = 290). ImmunoCAP results were positive to α-Gal in 20 of 24 patients with meat allergy and in 20 of 22 patients with positive gelatin skin test results. The results of gelatin skin testing and anti-α-Gal IgE measurements were strongly correlated (r = 0.46, P < .01). α-Gal was detected in bovine gelatin colloids at concentrations of approximately 0.44 to 0.52 μg/g gelatin by means of inhibition RIA. Most patients allergic to red meat were sensitized to gelatin, and a subset was clinically allergic to both. The detection of α-Gal in gelatin and correlation between the results of α-Gal and gelatin testing raise the possibility that α-Gal IgE might be the target of reactivity to gelatin. The pathogenic relationship between tick bites and sensitization to red meat, α-Gal, and gelatin (with or without clinical reactivity) remains uncertain. Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Familial intra-areolar polythelia with mammary hypoplasia.

PubMed

Rintala, A; Norio, R

1982-01-01

Dysplastic divided nipples (intra-areolar polythelia) have been found bilaterally in a mother, her two daughters and one son. Two of the patients had mammary hypoplasia, one had unilateral hypoplasia of the pectoral muscle and duplication of the renal pelvis and ureter. The mammary findings are consistent with autosomal dominant inheritance. Whether they represent a new mammo-renal syndrome is uncertain. Reconstructive surgery was performed on two patients. Due to the deformity the mother was unable to nurse her children; following reconstructive surgery the daughter was able to feed her baby normally.

Practical approach to hip pain.

PubMed

Karrasch, Christopher; Lynch, Scott

2014-07-01

Hip pain is a common complaint among patients presenting to outpatient clinics. Stratifying patients based on age, acuity, and location of pain (extra-articular vs intra-articular) can help to aid in appropriate imaging and timely referral to an orthopedic surgeon. A thorough history and an organized physical examination combined with radiographs are usually sufficient to diagnose most hip complaints. If the diagnosis remains uncertain, magnetic resonance imaging, usually with intra-articular gadolinium, is the imaging modality of choice in diagnosing both intra-articular and extra-articular pathologies. Copyright © 2014 Elsevier Inc. All rights reserved.

Intervening to reduce the risk of future disability from multiple sclerosis: are we there yet?

PubMed

Dahdaleh, Maurice; Alroughani, Raed; Aljumah, Mohammed; AlTahan, Abdulrahman; Alsharoqi, Issa; Bohlega, Saeed A; Daif, Abdulkader; Deleu, Dirk; Inshasi, Jihad; Karabudak, Rana; Sahraian, Mohammed A; Taha, Karim; Yammout, Bassem I; Zakaria, Magd

2017-10-01

Disease-modifying therapies (DMTs) delay or may prevent the progression of patients with high-risk clinically isolated syndrome (CIS) to clinically definite multiple sclerosis (MS), and from relapsing-remitting MS to secondary progressive MS. Current evidence on the effects of DMT on disability in MS is supported by the use of the Expanded Disability Status Scale (EDSS), which is dominated by ambulation, and usually used as a secondary outcome measure. Less is known about the long-term effects of DMTs on other aspects of functional status, particularly cognition, which is a key determinant of ability to work. The time scale for measurements of disability is at most a few years, with scant data from more than 10 years of observation. Longer prospective follow-up of large numbers of patients with CIS is needed to determine whether early intervention with a DMT influences long-term disease progression. Finally, the emergence of the radiologically isolated syndrome (RIS) as a clinical entity has shifted the debate about when to intervene to an even earlier time frame. Balancing the significant side-effects associated with DMT in general and the expected outcome of pharmacologic intervention is increasingly problematic for managing patients with uncertain prognosis, as many patients may have low-risk CIS, benign MS or patients with RIS only. Preventing long-term disability in MS should be recognised more clearly as an important outcome in its own right, with disability measured more consistently with more sensitive instruments beyond the use of the EDSS.

Hyper-responsivity to losses in the anterior insula during economic choice scales with depression severity.

PubMed

Engelmann, J B; Berns, G S; Dunlop, B W

2017-12-01

Commonly observed distortions in decision-making among patients with major depressive disorder (MDD) may emerge from impaired reward processing and cognitive biases toward negative events. There is substantial theoretical support for the hypothesis that MDD patients overweight potential losses compared with gains, though the neurobiological underpinnings of this bias are uncertain. Twenty-one unmedicated patients with MDD were compared with 25 healthy controls (HC) using functional magnetic resonance imaging (fMRI) together with an economic decision-making task over mixed lotteries involving probabilistic gains and losses. Region-of-interest analyses evaluated neural signatures of gain and loss coding within a core network of brain areas known to be involved in valuation (anterior insula, caudate nucleus, ventromedial prefrontal cortex). Usable fMRI data were available for 19 MDD and 23 HC subjects. Anterior insula signal showed negative coding of losses (gain > loss) in HC subjects consistent with previous findings, whereas MDD subjects demonstrated significant reversals in these associations (loss > gain). Moreover, depression severity further enhanced the positive coding of losses in anterior insula, ventromedial prefrontal cortex, and caudate nucleus. The hyper-responsivity to losses displayed by the anterior insula of MDD patients was paralleled by a reduced influence of gain, but not loss, stake size on choice latencies. Patients with MDD demonstrate a significant shift from negative to positive coding of losses in the anterior insula, revealing the importance of this structure in value-based decision-making in the context of emotional disturbances.

Interactive videoconsultation is a feasible method for neurological in-patient assessment.

PubMed

Craig, J; Patterson, V; Russell, C; Wootton, R

2000-11-01

To evaluate the feasibility of interactive videoconsultation (IATV) as a means by which neurologists might assess patients admitted with neurological symptoms to hospitals distant from a neurological centre, we studied 25 unselected patients using interactive videoconsultation (IATV) and then validated the IATV diagnoses and management plans at a later face-to-face consultation. IATV consultation led to an eventual diagnosis in 23 out of 25 patients, with one diagnosis being changed and one remaining uncertain. The IATV management plans were felt to be appropriate for all patients in study. Twelve patients were able to be discharged from hospital on the same day as IATV on the advice of the neurologist. It is therefore practical to assess patients admitted with neurological symptoms to distant hospitals using IATV and this may result in more efficient use of in-patient resources.

Anti-TNF therapy induced immune neutropenia in Crohns disease- report of 2 cases and review of literature.

PubMed

Sebastian, Shaji; Ashton, Katherine; Houston, Yasmine; Diggory, Tina Mary; Dore, Philip

2012-07-01

Transient neutropenia is reported in some patients on biologic therapy. We report two cases of severe neutropenia in patients with Crohn`s disease following treatment with anti-TNF therapy. In both cases neutrophil specific granulocyte autoantibodies were detected during period of neutropenia and disappeared on cessation of anti-TNF therapy. These may indicate that anti-TNF agents may produce autoimmune agranulocytosis by triggering production granulocyte autoantibodies. The long term management strategy for patients with anti-TNF therapy induced autoimmune neutropenia is uncertain. Copyright © 2012 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Neovascular glaucoma in a patient with X-linked juvenile retinoschisis.

PubMed

Zuo, Chengguo; Chen, Changzheng; Xing, Yiqiao; Du, Lei

2005-09-01

To report the rubeosis iridis and neovascular glaucoma findings in one patient of X-linked juvenile retinoschisis(XLRS). Color fundus photography, fluorescein angiography (FFA), OCT and B-scan were performed in a patient with X-linked juvenile retinoschisis complicated with neovascular glaucoma. Color fundus photography, fluorescein angiography (FFA), OCT and B-scan unveiled a rare condition of XLRS complicated with neovascular glaucoma. XLRS may complicate with neovascular glaucoma. It is necessary to test OCT, FFA, ERG and carefully examine the fundus of the follow eye when it comes to uncertain neovascular glaucoma of youth and child. And only in this way, can we exclude XLRS.

Use of the SeHCAT test in the investigation of diarrhoea.

PubMed

Ford, G A; Preece, J D; Davies, I H; Wilkinson, S P

1992-04-01

The SeHCAT test was used to investigate possible bile acid malabsorption in 166 patients presenting to a district general hospital with chronic diarrhoea of uncertain cause. Eighty-four (51%) patients had impaired SeHCAT retention. These included 23 of 28 patients with a possible type I abnormality (terminal ileal resection or disease, previous pelvic radiotherapy), 20 of 74 with a possible type II abnormality (idiopathic diarrhoea), 32 of 45 with a possible type III abnormality (post-cholecystectomy, post-vagotomy), and 9 of 19 with diarrhoea associated with diabetes. Patients with severe bile acid malabsorption demonstrated a good response to cholestyramine whereas the response in patients with a mildly abnormal SeHCAT retention was variable. Bile acid malabsorption is an important cause of diarrhoea in patients presenting with unexplained chronic diarrhoea.

Comparison of SPET brain perfusion and 18F-FDG brain metabolism in patients with chronic fatigue syndrome.

PubMed

Abu-Judeh, H H; Levine, S; Kumar, M; el-Zeftawy, H; Naddaf, S; Lou, J Q; Abdel-Dayem, H M

1998-11-01

Chronic fatigue syndrome is a clinically defined condition of uncertain aetiology. We compared 99Tcm-HMPAO single photon emission tomography (SPET) brain perfusion with dual-head 18F-FDG brain metabolism in patients with chronic fatigue syndrome. Eighteen patients (14 females, 4 males), who fulfilled the diagnostic criteria of the Centers for Disease Control for chronic fatigue syndrome, were investigated. Thirteen patients had abnormal SPET brain perfusion scans and five had normal scans. Fifteen patients had normal glucose brain metabolism scans and three had abnormal scans. We conclude that, in chronic fatigue syndrome patients, there is discordance between SPET brain perfusion and 18F-FDG brain uptake. It is possible to have brain perfusion abnormalities without corresponding changes in glucose uptake.

A novel medical information management and decision model for uncertain demand optimization.

PubMed

Bi, Ya

2015-01-01

Accurately planning the procurement volume is an effective measure for controlling the medicine inventory cost. Due to uncertain demand it is difficult to make accurate decision on procurement volume. As to the biomedicine sensitive to time and season demand, the uncertain demand fitted by the fuzzy mathematics method is obviously better than general random distribution functions. To establish a novel medical information management and decision model for uncertain demand optimization. A novel optimal management and decision model under uncertain demand has been presented based on fuzzy mathematics and a new comprehensive improved particle swarm algorithm. The optimal management and decision model can effectively reduce the medicine inventory cost. The proposed improved particle swarm optimization is a simple and effective algorithm to improve the Fuzzy interference and hence effectively reduce the calculation complexity of the optimal management and decision model. Therefore the new model can be used for accurate decision on procurement volume under uncertain demand.

Global tracking for a class of uncertain nonlinear systems with unknown sign-switching control direction by output feedback

NASA Astrophysics Data System (ADS)

Roux Oliveira, Tiago; Jacoud Peixoto, Alessandro; Hsu, Liu

2015-09-01

This paper addresses the design of a sliding mode controller for a class of high-order uncertain nonlinear plants with unmatched state-dependent nonlinearities and unknown sign of the high frequency gain, i.e., the control direction is assumed unknown. Differently from most previous studies, the control direction is allowed to switch its sign. We show that it is possible to obtain global exact tracking using only output-feedback by coupling a relay periodic switching function with a norm state observer. One significant advantage of the new scheme is its robustness and improved transient response under arbitrary changes of the control direction which have been theoretically demonstrated for jump variations and successfully tested by simulations. The proposed controller is also evaluated with a DC motor control experiment.

Finite-time output feedback control of uncertain switched systems via sliding mode design

NASA Astrophysics Data System (ADS)

Zhao, Haijuan; Niu, Yugang; Song, Jun

2018-04-01

The problem of sliding mode control (SMC) is investigated for a class of uncertain switched systems subject to unmeasurable state and assigned finite (possible short) time constraint. A key issue is how to ensure the finite-time boundedness (FTB) of system state during reaching phase and sliding motion phase. To this end, a state observer is constructed to estimate the unmeasured states. And then, a state estimate-based SMC law is designed such that the state trajectories can be driven onto the specified integral sliding surface during the assigned finite time interval. By means of partitioning strategy, the corresponding FTB over reaching phase and sliding motion phase are guaranteed and the sufficient conditions are derived via average dwell time technique. Finally, an illustrative example is given to illustrate the proposed method.

State-dependent resource harvesting with lagged information about system states

USGS Publications Warehouse

Johnson, Fred A.; Fackler, Paul L.; Boomer, G Scott; Zimmerman, Guthrie S.; Williams, Byron K.; Nichols, James D.; Dorazio, Robert

2016-01-01

Markov decision processes (MDPs), which involve a temporal sequence of actions conditioned on the state of the managed system, are increasingly being applied in natural resource management. This study focuses on the modification of a traditional MDP to account for those cases in which an action must be chosen after a significant time lag in observing system state, but just prior to a new observation. In order to calculate an optimal decision policy under these conditions, possible actions must be conditioned on the previous observed system state and action taken. We show how to solve these problems when the state transition structure is known and when it is uncertain. Our focus is on the latter case, and we show how actions must be conditioned not only on the previous system state and action, but on the probabilities associated with alternative models of system dynamics. To demonstrate this framework, we calculated and simulated optimal, adaptive policies for MDPs with lagged states for the problem of deciding annual harvest regulations for mallards (Anas platyrhynchos) in the United States. In this particular example, changes in harvest policy induced by the use of lagged information about system state were sufficient to maintain expected management performance (e.g. population size, harvest) even in the face of an uncertain system state at the time of a decision.

Management of Neuropathic Chronic Pain with Methadone Combined with Ketamine: A Randomized, Double Blind, Active-Controlled Clinical Trial.

PubMed

Rigo, Flavia Karine; Trevisan, Gabriela; Godoy, Maria C; Rossato, Mateus Fortes; Dalmolin, Gerusa D; Silva, Mariane A; Menezes, Mirian S; Caumo, Wolnei; Ferreira, Juliano

2017-03-01

Methadone and ketamine are used in neuropathic pain management. However, the benefits of both drugs association are uncertain in the treatment of neuropathic pain. Our primary objective was test the hypothesis that oral methadone combined with oral ketamine is more effective than oral methadone or ketamine alone in reducing neuropathic pain. We conducted a randomized, double blind, active-controlled parallel-group clinical trial. Forty-two patients with neuropathic pain refractory to conventional therapy were randomly assigned to receive oral methadone (n = 14), ketamine (n = 14), or methadone plus ketamine (n = 14) over a 3-month period. During these 90 days, we observed pain scores using a visual analogical scale (VAS), allodynia, burning/shooting pain, and some side effects. All treatments were effective in reducing pain scores by at least 40%. However, a significant improvement in pain was observed only in the ketamine alone group compared with both the methadone or methadone/ketamine groups. No significant differences were observed among the treatment groups for the reduction of burning or shooting pain, while ketamine alone was more effective than methadone or methadone/ketamine for the reduction of allodynia. Formal assessment for awareness of the allocation was not performed, some co-intervention bias may have occurred, our results could be only relevant to the patient population investigated and the use of VAS as the primary outcome detect changes in pain intensity but not to assess neuropathic pain symptoms. This study indicates that ketamine was better than methadone or methadone/ketamine for treating neuropathic pain.Key words: Multimodal analgesia, refractory pain, NMDA receptor, opioid.

Nitrous Oxide 70% for Procedural Analgosedation in a Pediatric Emergency Department With or Without Intranasal Fentanyl?: Analgesic Efficacy and Adverse Events if Combined With Intranasal Fentanyl.

PubMed

Seiler, Michelle; Landolt, Markus A; Staubli, Georg

2017-07-03

Nitrous oxide 70% (N20 70%) is an excellent medication for procedural analgosedation in a pediatric emergency department. However, its analgesic efficacy remains uncertain for painful procedures; therefore, a combination with intranasal fentanyl (INF), an opioid, was suggested. This study aimed at observing and assessing the analgesic efficacy and rate of adverse events using N20 70% with and without INF. Children who received N20 70% in a tertiary children's hospital emergency department from January 1, 2014 to June 30, 2015 were included in this observational study with prospective data collection. Physicians decided individually whether INF was administered. Medical staff documented the child's behavior during the procedure, adverse events, and satisfaction rate. A total of 442 children were included; 206 (46.6%) received INF. Group differences regarding patient behavior were not statistically significant; however, N20 70% application time was longer in the INF group (P = .02). Nausea was the most frequent adverse event with 13.1% in the INF group versus 8.1% without INF. Inadequate procedural analgosedation was documented only in the INF group, affecting 1.8% of all patients (P = .002). In contrast, anxiety was exclusively observed in the group without INF, which was presumably misjudged pain (P = .03); the satisfaction rate in the INF group was 95.6% compared with 98.7% without INF. Because of the study design and limitations, no conclusions about adding INF to N20 70% can be made. Additional research is needed to investigate the effect of combining N20 70% with INF.

Benefits and Harms of Plant-Based Cannabis for Posttraumatic Stress Disorder: A Systematic Review.

PubMed

O'Neil, Maya E; Nugent, Shannon M; Morasco, Benjamin J; Freeman, Michele; Low, Allison; Kondo, Karli; Zakher, Bernadette; Elven, Camille; Motu'apuaka, Makalapua; Paynter, Robin; Kansagara, Devan

2017-09-05

Cannabis is available from medical dispensaries for treating posttraumatic stress disorder (PTSD) in many states of the union, yet its efficacy in treating PTSD symptoms remains uncertain. To identify ongoing studies and review existing evidence regarding the benefits and harms of plant-based cannabis preparations in treating PTSD in adults. MEDLINE, the Cochrane Library, and other sources from database inception to March 2017. English-language systematic reviews, trials, and observational studies with a control group that reported PTSD symptoms and adverse effects of plant-based cannabis use in adults with PTSD. Study data extracted by 1 investigator was checked by a second reviewer; 2 reviewers independently assessed study quality, and the investigator group graded the overall strength of evidence by using standard criteria. Two systematic reviews, 3 observational studies, and no randomized trials were found. The systematic reviews reported insufficient evidence to draw conclusions about benefits and harms. The observational studies found that compared with nonuse, cannabis did not reduce PTSD symptoms. Studies had medium and high risk of bias, and overall evidence was judged insufficient. Two randomized trials and 6 other studies examining outcomes of cannabis use in patients with PTSD are ongoing and are expected to be completed within 3 years. Very scant evidence with medium to high risk of bias. Evidence is insufficient to draw conclusions about the benefits and harms of plant-based cannabis preparations in patients with PTSD, but several ongoing studies may soon provide important results. U.S. Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Quality Enhancement Research Initiative. (PROSPERO: CRD42016033623).

Clinical variability of neuroacanthocytosis syndromes-a series of six patients with long follow-up.

PubMed

Dulski, J; Sołtan, W; Schinwelski, M; Rudzińska, M; Wójcik-Pędziwiatr, M; Wictor, L; Schön, F; Puschmann, A; Klempíř, J; Tilley, L; Roth, J; Tacik, P; Fujioka, S; Drozdowski, W; Sitek, E J; Wszolek, Z; Sławek, J

2016-08-01

To provide clinical clues to differential diagnosis in patients with chorea and other movement disorders with blood acanthocytes. We present a long-term video accompanied follow-up of six Caucasian patients with neuroacanthocytosis from several centers, three diagnosed with chorea-acanthocytosis (ChAc): 34-y.o.(no.1), 36-y.o.(no.2), 43-y.o.(no.3), two diagnosed with McLeod Syndrome (MLS): 52-y.o.(no.4), 61-y.o.(no.5) and one 63-y.o.(no.6), a brother of no.5, with clinical suspicion of MLS. Additionally we report pathological findings of the mother of two brothers with MLS reported in our series with acanthocytes on peripheral blood smear The patients had an unremarkable family history and were asymptomatic until adulthood. Patients no. 1,2,4,5,6 developed generalized chorea and patient no. 3 had predominant bradykinesia. Patients no. 1,2,3 had phonic and motor tics, additionally patients no. 1 and 2 exhibited peculiar oromandibular dystonia with tongue thrusting. In patients no. 2 and 3 dystonic supination of feet was observed, patient no. 3 subsequently developed bilateral foot drop. Patients no. 2 and 4 had signs of muscle atrophy. Tendon reflexes were decreased or absent and electroneurography demonstrated sensorimotor neuropathy in patients no. 1,2,3,4,5, except no. 6. Generalized seizures were seen in patients no. 2,3,5,6 and myoclonic jerks in patient no. 1. Cognitive deterioration was reported in patients no. 1,2,3,5,6. Serum creatine kinase levels were elevated in all six patients. We highlight the variability of clinical presentation of neuroacanthocytosis syndromes and the long time from the onset to diagnosis with the need to screen the blood smears in uncertain cases, however, as in one of our cases acanthocytes may even be not found. Based on our observations and data from the literature we propose several red flags that should raise the suspicion of an NA syndrome in a patient with a movement disorder: severe orofacial dyskinesia with tongue and lip-biting (typical of ChAc), feeding dystonia, psychiatric and cognitive disturbances, seizures, peripheral neuropathy, elevation of creatine kinase, elevation of transaminases, hepatosplenomegaly, cardiomyopathy and arrhythmias, and an X-linked pattern of inheritance (McLeod Syndrome, MLS). Copyright © 2016 Elsevier B.V. All rights reserved.

High-sensitivity cardiac troponin I and risk of heart failure in patients with suspected acute coronary syndrome: a cohort study.

PubMed

Stelzle, Dominik; Shah, Anoop S V; Anand, Atul; Strachan, Fiona E; Chapman, Andrew R; Denvir, Martin A; Mills, Nicholas L; McAllister, David A

2018-01-01

Heart failure may occur following acute myocardial infarction, but with the use of high-sensitivity cardiac troponin assays we increasingly diagnose patients with minor myocardial injury. Whether troponin concentrations remain a useful predictor of heart failure in patients with acute coronary syndrome is uncertain. We identified all consecutive patients (n = 4748) with suspected acute coronary syndrome (61 ± 16 years, 57% male) presenting to three secondary and tertiary care hospitals. Cox-regression models were used to evaluate the association between high-sensitivity cardiac troponin I concentration and subsequent heart failure hospitalization. C-statistics were estimated to evaluate the predictive value of troponin for heart failure hospitalization. Over 2071 years of follow-up there were 83 heart failure hospitalizations. Patients with troponin concentrations above the upper reference limit (URL) were more likely to be hospitalized with heart failure than patients below the URL (118/1000 vs. 17/1000 person years, adjusted hazard ratio: 7.0). Among patients with troponin concentrations

Altered subjective reward valuation among female heavy marijuana users.

PubMed

Hefner, Kathryn R; Starr, Mark J

2017-02-01

Maladaptive decision-making is a cardinal feature of drug use, contributing to ongoing use, and reflecting alterations in how drug users assess uncertain reward value. Accumulating evidence indicates the consequences of heavy marijuana use are worse for female versus male animals and humans, but research assessing sex differences in reward-related decision-making among marijuana users remains scarce. We examined sex differences in the subjective valuation of certain and uncertain rewards among heavy marijuana users (52; 26 male and 26 female) and controls (52; 26 male and 26 female). We offered male and female heavy marijuana users and controls monetary rewards of certain and uncertain (probabilistic) values. We measured how preferences for uncertain rewards varied by the objective value of those rewards, moderators of reward uncertainty, Marijuana Group and Sex. Men were more sensitive to changes in the objective value of uncertain rewards than women. However, this effect of Sex differed by Marijuana Group. Female heavy marijuana users were more sensitive to changes in uncertain reward value, particularly when the "stakes" were high (i.e., greater difference between potential uncertain rewards), than female controls. Female heavy marijuana users' sensitivity to changes in the value of high stakes uncertain rewards was comparable to male marijuana users and controls. In contrast, male marijuana users' sensitivity to changes in the value of high stakes uncertain rewards did not differ from male controls. These results suggest sex differences in sensitivity to high risk rewards may be one pathway contributing to severer consequences of heavy marijuana use among women. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Altered subjective reward valuation among female heavy marijuana users

PubMed Central

Hefner, Kathryn R.; Starr, Mark. J.

2016-01-01

Maladaptive decision-making is a cardinal feature of drug use, contributing to ongoing use, and reflecting alterations in how drug users assess uncertain reward value. Accumulating evidence indicates the consequences of heavy marijuana use are worse for female versus male animals and humans, but research assessing sex differences in reward-related decision-making among marijuana users remains scarce. We examined sex differences in the subjective valuation of certain and uncertain rewards among heavy marijuana users (52; 26 male and 26 female) and controls (52; 26 male and 26 female). We offered male and female heavy marijuana users and controls monetary rewards of certain and uncertain (probabilistic) values. We measured how preferences for uncertain rewards varied by the objective value of those rewards, moderators of reward uncertainty, marijuana use, and sex. Men were more sensitive to changes in the objective value of uncertain rewards than women. However, this effect of sex differed by marijuana group. Female heavy marijuana users were more sensitive to changes in uncertain reward value, particularly when the ‘stakes’ were high (i.e., greater difference between potential uncertain rewards), than female controls. Female heavy marijuana users’ sensitivity to changes in the value of high stakes uncertain rewards was comparable to male marijuana users and controls. In contrast, male marijuana users’ sensitivity to changes in the value of high stakes uncertain rewards did not differ from male controls. These results suggest sex differences in sensitivity to high risk rewards may be one pathway contributing to severer consequences of heavy marijuana use among women. PMID:27936816

"Appropriateness of colonoscopy according to EPAGE II in a low resource setting: a cross sectional study from Sri Lanka".

PubMed

Samarakoon, Yasara; Gunawardena, Nalika; Pathirana, Aloka; Hewage, Sumudu

2018-05-29

Due to finite resources, the clinical decision to subject a patient to colonoscopy needs to be based on the evidence, regardless of its availability, affordability and safety. This study assessed the appropriateness of colonoscopies conducted in selected study settings in Sri Lanka. In the absence of local guidelines, audit was based on European Panel on Appropriateness of Gastrointestinal Endoscopy II (EPAGE II) criteria. This cross-sectional study assessed consecutive patients who underwent colonoscopy between June to August 2015 at four main hospitals in Sri Lanka. Interviewer administered questionnaire and secondary data were collected by trained health staff. Indications were assessed according to EPAGE II criteria. Out of 325 patients, male female proportions were 57.2 and 42.8%. Mean (SD) age was 54.9 (12.1) years. Colonoscopies were appropriate in 61.2% (95% CI 55.8-66.3), uncertain in 28.6% (95% CI 23.9-33.7) and inappropriate in 10.2% (95% CI 7.3-13.9). Colonoscopy to evaluate abdominal pain has highest percentage of inappropriateness of 10.0%. However, 9.5% of these colonoscopies revealed Colo-Rectal Cancer (CRC), reflecting differences in the profile of local CRC patients. Colonoscopies with appropriate or uncertain indications are three times more likely to have a relevant finding than inappropriate indications (42.5% vs. 18.2%; OR 3.32, 95% CI 1.33-8.3; P = 0.008). Majority of colonoscopies are appropriate. However, it cannot be neglected that every one in ten patients undergo inappropriate colonoscopy. Proportion of inappropriateness was highest for the indication of chronic abdominal pain, of which, 9.5% of patients were diagnosed with CRC. This may reflect the different profile of local CRC patients in terms of symptom manifestation and other characteristics. In conclusion, the authors recommend formulation of national guidelines for colonoscopy indications based on current best evidence and local patient profile. Use of such prepared local guidelines will improve the efficient use of finite resources.

Randomized, Controlled Trial of an Advance Care Planning Video Decision Support Tool for Patients With Advanced Heart Failure.

PubMed

El-Jawahri, Areej; Paasche-Orlow, Michael K; Matlock, Dan; Stevenson, Lynne Warner; Lewis, Eldrin F; Stewart, Garrick; Semigran, Marc; Chang, Yuchiao; Parks, Kimberly; Walker-Corkery, Elizabeth S; Temel, Jennifer S; Bohossian, Hacho; Ooi, Henry; Mann, Eileen; Volandes, Angelo E

2016-07-05

Conversations about goals of care and cardiopulmonary resuscitation (CPR)/intubation for patients with advanced heart failure can be difficult. This study examined the impact of a video decision support tool and patient checklist on advance care planning for patients with heart failure. This was a multisite, randomized, controlled trial of a video-assisted intervention and advance care planning checklist versus a verbal description in 246 patients ≥64 years of age with heart failure and an estimated likelihood of death of >50% within 2 years. Intervention participants received a verbal description for goals of care (life-prolonging care, limited care, and comfort care) and CPR/intubation plus a 6-minute video depicting the 3 levels of care, CPR/intubation, and an advance care planning checklist. Control subjects received only the verbal description. The primary analysis compared the proportion of patients preferring comfort care between study arms immediately after the intervention. Secondary outcomes were CPR/intubation preferences and knowledge (6-item test; range, 0-6) after intervention. In the intervention group, 27 (22%) chose life-prolonging care, 31 (25%) chose limited care, 63 (51%) selected comfort care, and 2 (2%) were uncertain. In the control group, 50 (41%) chose life-prolonging care, 27 (22%) selected limited care, 37 (30%) chose comfort care, and 8 (7%) were uncertain (P<0.001). Intervention participants (compared with control subjects) were more likely to forgo CPR (68% versus 35%; P<0.001) and intubation (77% versus 48%; P<0.001) and had higher mean knowledge scores (4.1 versus 3.0; P<0.001). Patients with heart failure who viewed a video were more informed, more likely to select a focus on comfort, and less likely to desire CPR/intubation compared with patients receiving verbal information only. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01589120. © 2016 American Heart Association, Inc.

Early effects of resident work-hour restrictions on patient safety: a systematic review and plea for improved studies.

PubMed

Baldwin, Keith; Namdari, Surena; Donegan, Derek; Kamath, Atul F; Mehta, Samir

2011-01-19

since the inception of the eighty-hour work week, work hour restrictions have incited considerable debate. Work hour policies were designed to prevent medical errors and to reduce patient morbidity and mortality. It is unclear whether work hour restrictions have been helpful in medicine in general and in orthopaedic surgery specifically. This systematic review of the literature was designed to determine the success of these restrictions in terms of patient mortality, medical errors, and complications. a systematic review of the literature was performed to determine if work hour rules have improved patient and systems-based outcomes and reduced physician errors as measured by mortality, medical errors, and complications. A random effects model was utilized to determine whether patient mortality rates were improved under the new rules. the odds of patient death before implementation of the work hour rules were 1.12 (95% confidence interval, 1.07 to 1.17) times those after implementation. These differences were consistent across disciplines. The data concerning medical or surgical complications before and after the institution of the work hour rules were mixed. There was little information in these studies concerning direct medical errors. The odds of death in nonteaching cohorts were not significantly different from that in teaching cohorts. there appears to be a decrease in mortality following the institution of work hour rules. The difference seen in teaching cohorts is not significantly different from that in nonteaching cohorts. It is unclear whether this difference would have been observed even without work hour restrictions. No study has shown a reduction in mortality for orthopaedic patients in teaching cohorts that was greater than that observed in nonteaching cohorts. Because of methodological concerns and the lack of current literature linking physician fatigue and physician underperformance with patient mortality, it is unclear whether the goals of the work hour reductions have been achieved. Furthermore, because of a lack of a so-called dose-response relationship between work hour reduction and patient mortality, it is uncertain whether further reductions would be beneficial. therapeutic Level III. See Instructions to Authors for a complete description of levels of evidence.

Cross-border reprogenetic services.

PubMed

Couture, V; Drouin, R; Tan, S-L; Moutquin, J-M; Bouffard, C

2015-01-01

The purpose of this review is to synthesize the current knowledge on the international movement of patients and biopsied embryo cells for pre-implantation genetic diagnosis and its different applications. Thus far, few attempts have been made to identify the specific nature of this phenomenon called 'cross-border reprogenetic services'. There is scattered evidence, both empirical and speculative, suggesting that these services raise major issues in terms of service provision, risks for patients and the children-to-come, the legal liabilities of physicians, as well as social justice. To compile this evidence, this review uses the narrative overview protocol combined with thematic analysis. Five major themes have emerged from the literature at the conjunction of cross-border treatments and reprogenetics: 'scope', 'scale', 'motivations', 'concerns', and 'governance'. Similar themes have already been observed in the case of other medical tourism activities, but this review highlights their singularity with reprogenetic services. It emphasizes the diagnostic and autologous feature of reprogenetics, the constant risk of misdiagnosis, the restriction on certain tests for medically controversial conditions, and the uncertain accessibility of genetic counseling in cross-border settings. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Short-term stream water temperature observations permit rapid assessment of potential climate change impacts

Treesearch

Peter Caldwell; Catalina Segura; Shelby Gull Laird; Ge Sun; Steven G. McNulty; Maria Sandercock; Johnny Boggs; James M. Vose

2015-01-01

Assessment of potential climate change impacts on stream water temperature (Ts) across large scales remains challenging for resource managers because energy exchange processes between the atmosphere and the stream environment are complex and uncertain, and few long-term datasets are available to evaluate changes over time. In this study, we...

The role of place-based social learning [Chapter 7

Treesearch

Daniel R. Williams

2017-01-01

Hummel's observations on the limits of science to inform practice provides a useful starting point for a book chapter devoted to examining post-normal environmental policy where the "facts are uncertain, values in dispute, stakes high, and decisions urgent" (Funtowicz and Ravetz 1993, 739, 744). Central to the argument here is that the integration of...

Observed and projected C change in the Southeastern US

Treesearch

John Coulston; David Wear; Jim Vose

2015-01-01

Over the past century forest regrowth in Europe and North America expanded forest carbon (C) sinks and offset C emissions but future C accumulation is uncertain due to the effects of land use changes, management, disturbance, and climate change. Policy makers need insights into forest C dynamics as they anticipate emissions futures and goals. Using a completely...

An uncertainty analysis of the hydrogen source term for a station blackout accident in Sequoyah using MELCOR 1.8.5

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

Gauntt, Randall O.; Bixler, Nathan E.; Wagner, Kenneth Charles

2014-03-01

A methodology for using the MELCOR code with the Latin Hypercube Sampling method was developed to estimate uncertainty in various predicted quantities such as hydrogen generation or release of fission products under severe accident conditions. In this case, the emphasis was on estimating the range of hydrogen sources in station blackout conditions in the Sequoyah Ice Condenser plant, taking into account uncertainties in the modeled physics known to affect hydrogen generation. The method uses user-specified likelihood distributions for uncertain model parameters, which may include uncertainties of a stochastic nature, to produce a collection of code calculations, or realizations, characterizing themore » range of possible outcomes. Forty MELCOR code realizations of Sequoyah were conducted that included 10 uncertain parameters, producing a range of in-vessel hydrogen quantities. The range of total hydrogen produced was approximately 583kg 131kg. Sensitivity analyses revealed expected trends with respected to the parameters of greatest importance, however, considerable scatter in results when plotted against any of the uncertain parameters was observed, with no parameter manifesting dominant effects on hydrogen generation. It is concluded that, with respect to the physics parameters investigated, in order to further reduce predicted hydrogen uncertainty, it would be necessary to reduce all physics parameter uncertainties similarly, bearing in mind that some parameters are inherently uncertain within a range. It is suspected that some residual uncertainty associated with modeling complex, coupled and synergistic phenomena, is an inherent aspect of complex systems and cannot be reduced to point value estimates. The probabilistic analyses such as the one demonstrated in this work are important to properly characterize response of complex systems such as severe accident progression in nuclear power plants.« less

Immune thrombocytopenia: No longer ‘idiopathic’

PubMed Central

McCRAE, KEITH

2012-01-01

Immune thrombocytopenia (ITP) is a common hematologic disorder. Its pathogenesis involves both accelerated platelet destruction and impaired platelet production. First-line agents are usually effective initially but do not provide long-term responses. Splenectomy remains an effective long-term therapy, as does rituximab (Rituxan) in a subset of patients. Thrombopoietic agents offer a new alternative, although their place in the overall management of ITP remains uncertain. PMID:21632906

Different Treatment Stages in Medical Diagnosis using Fuzzy Membership Matrix

NASA Astrophysics Data System (ADS)

Sundaresan, T.; Sheeja, G.; Govindarajan, A.

2018-04-01

The field of medicine is the most important and developing area of applications of fuzzy set theory. The nature of medical documentation and uncertain information gathered in the use of fuzzy triangular matrix. In this paper, procedures are presented for medical diagnosis and treatment-stages, patient and drug is constructed in fuzzy membership matrix. Examples are given to verify the proposed approach.

Adaptive neural output-feedback control for nonstrict-feedback time-delay fractional-order systems with output constraints and actuator nonlinearities.

PubMed

Zouari, Farouk; Ibeas, Asier; Boulkroune, Abdesselem; Cao, Jinde; Mehdi Arefi, Mohammad

2018-06-01

This study addresses the issue of the adaptive output tracking control for a category of uncertain nonstrict-feedback delayed incommensurate fractional-order systems in the presence of nonaffine structures, unmeasured pseudo-states, unknown control directions, unknown actuator nonlinearities and output constraints. Firstly, the mean value theorem and the Gaussian error function are introduced to eliminate the difficulties that arise from the nonaffine structures and the unknown actuator nonlinearities, respectively. Secondly, the immeasurable tracking error variables are suitably estimated by constructing a fractional-order linear observer. Thirdly, the neural network, the Razumikhin Lemma, the variable separation approach, and the smooth Nussbaum-type function are used to deal with the uncertain nonlinear dynamics, the unknown time-varying delays, the nonstrict feedback and the unknown control directions, respectively. Fourthly, asymmetric barrier Lyapunov functions are employed to overcome the violation of the output constraints and to tune online the parameters of the adaptive neural controller. Through rigorous analysis, it is proved that the boundedness of all variables in the closed-loop system and the semi global asymptotic tracking are ensured without transgression of the constraints. The principal contributions of this study can be summarized as follows: (1) based on Caputo's definitions and new lemmas, methods concerning the controllability, observability and stability analysis of integer-order systems are extended to fractional-order ones, (2) the output tracking objective for a relatively large class of uncertain systems is achieved with a simple controller and less tuning parameters. Finally, computer-simulation studies from the robotic field are given to demonstrate the effectiveness of the proposed controller. Copyright © 2018 Elsevier Ltd. All rights reserved.

Using an ensemble smoother to evaluate parameter uncertainty of an integrated hydrological model of Yanqi basin

NASA Astrophysics Data System (ADS)

Li, Ning; McLaughlin, Dennis; Kinzelbach, Wolfgang; Li, WenPeng; Dong, XinGuang

2015-10-01

Model uncertainty needs to be quantified to provide objective assessments of the reliability of model predictions and of the risk associated with management decisions that rely on these predictions. This is particularly true in water resource studies that depend on model-based assessments of alternative management strategies. In recent decades, Bayesian data assimilation methods have been widely used in hydrology to assess uncertain model parameters and predictions. In this case study, a particular data assimilation algorithm, the Ensemble Smoother with Multiple Data Assimilation (ESMDA) (Emerick and Reynolds, 2012), is used to derive posterior samples of uncertain model parameters and forecasts for a distributed hydrological model of Yanqi basin, China. This model is constructed using MIKESHE/MIKE11software, which provides for coupling between surface and subsurface processes (DHI, 2011a-d). The random samples in the posterior parameter ensemble are obtained by using measurements to update 50 prior parameter samples generated with a Latin Hypercube Sampling (LHS) procedure. The posterior forecast samples are obtained from model runs that use the corresponding posterior parameter samples. Two iterative sample update methods are considered: one based on an a perturbed observation Kalman filter update and one based on a square root Kalman filter update. These alternatives give nearly the same results and converge in only two iterations. The uncertain parameters considered include hydraulic conductivities, drainage and river leakage factors, van Genuchten soil property parameters, and dispersion coefficients. The results show that the uncertainty in many of the parameters is reduced during the smoother updating process, reflecting information obtained from the observations. Some of the parameters are insensitive and do not benefit from measurement information. The correlation coefficients among certain parameters increase in each iteration, although they generally stay below 0.50.

Morphological response contributes to patient selection for rescue liver resection in chemotherapy patients with initially un-resectable colorectal liver metastasis.

PubMed

Suzuki, Koichi; Muto, Yuta; Ichida, Kosuke; Fukui, Taro; Takayama, Yuji; Kakizawa, Nao; Kato, Takaharu; Hasegawa, Fumi; Watanabe, Fumiaki; Kaneda, Yuji; Kikukawa, Rina; Saito, Masaaki; Tsujinaka, Shingo; Futsuhara, Kazushige; Takata, Osamu; Noda, Hiroshi; Miyakura, Yasuyuki; Kiyozaki, Hirokazu; Konishi, Fumio; Rikiyama, Toshiki

2017-08-01

Morphological response is considered an improved surrogate to the Response Evaluation Criteria in Solid Tumors (RECIST) model with regard to predicting the prognosis for patients with colorectal liver metastases. However, its use as a decision-making tool for surgical intervention has not been examined. The present study assessed the morphological response in 50 patients who underwent chemotherapy with or without bevacizumab for initially un-resectable colorectal liver metastases. Changes in tumor morphology between heterogeneous with uncertain borders and homogeneous with clear borders were defined as an optimal response (OR). Patients were also assessed as having an incomplete response (IR), and an absence of marked changes was assessed as no response (NR). No significant difference was observed in progression-free survival (PFS) between complete response/partial response (CR/PR) and stable disease/progressive disease (SD/PD), according to RECIST. By contrast, PFS for OR/IR patients was significantly improved compared with that for NR patients (13.2 vs. 8.7 months; P=0.0426). Exclusion of PD enhanced the difference in PFS between OR/IR and NR patients (15.1 vs. 9.3 months; P<0.0001), whereas no difference was observed between CR/PR and SD. The rate of OR and IR in patients treated with bevacizumab was 47.4% (9/19), but only 19.4% (6/31) for patients that were not administered bevacizumab. Comparison of the survival curves between OR/IR and NR patients revealed similar survival rates at 6 months after chemotherapy, but the groups exhibited different survival rates subsequent to this period of time. Patients showing OR/IR within 6 months appeared to be oncologically stable and could be considered as candidates for surgical intervention, including rescue liver resection. Comparing the pathological and morphological features of the tumor with representative optimal response, living tumor cells were revealed to be distributed within the area of vascular reconstruction induced by bevacizumab, resulting in a predictive value for prognosis in the patients treated with bevacizumab. The present findings provided the evidence for physicians to consider patients with previously un-resectable metastatic colorectal cancer as candidates for surgical treatment. Morphological response is a useful decision-making tool for evaluating these patients for rescue liver resection following chemotherapy.

Neural basis of uncertain cue processing in trait anxiety.

PubMed

Zhang, Meng; Ma, Chao; Luo, Yanyan; Li, Ji; Li, Qingwei; Liu, Yijun; Ding, Cody; Qiu, Jiang

2016-02-19

Individuals with high trait anxiety form a non-clinical group with a predisposition for an anxiety-related bias in emotional and cognitive processing that is considered by some to be a prerequisite for psychiatric disorders. Anxious individuals tend to experience more worry under uncertainty, and processing uncertain information is an important, but often overlooked factor in anxiety. So, we decided to explore the brain correlates of processing uncertain information in individuals with high trait anxiety using the learn-test paradigm. Behaviorally, the percentages on memory test and the likelihood ratios of identifying novel stimuli under uncertainty were similar to the certain fear condition, but different from the certain neutral condition. The brain results showed that the visual cortex, bilateral fusiform gyrus, and right parahippocampal gyrus were active during the processing of uncertain cues. Moreover, we found that trait anxiety was positively correlated with the BOLD signal of the right parahippocampal gyrus during the processing of uncertain cues. No significant results were found in the amygdala during uncertain cue processing. These results suggest that memory retrieval is associated with uncertain cue processing, which is underpinned by over-activation of the right parahippocampal gyrus, in individuals with high trait anxiety.

Education of healthcare professionals for preventing pressure ulcers.

PubMed

Porter-Armstrong, Alison P; Moore, Zena Eh; Bradbury, Ian; McDonough, Suzanne

2018-05-25

Pressure ulcers, also known as bed sores or pressure sores, are localised areas of tissue damage arising due to excess pressure and shearing forces. Education of healthcare staff has been recognised as an integral component of pressure ulcer prevention. These educational programmes are directed towards influencing behaviour change on the part of the healthcare professional, to encourage preventative practices with the aim of reducing the incidence of pressure ulcer development. To assess the effects of educational interventions for healthcare professionals on pressure ulcer prevention. In June 2017 we searched the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE (including In-Process & Other Non-Indexed Citations); Ovid Embase and EBSCO CINAHL Plus. We also searched clinical trials registries for ongoing and unpublished studies, and scanned reference lists of relevant included studies as well as reviews, meta-analyses and health technology reports to identify additional studies. There were no restrictions with respect to language, date of publication or study setting. We included randomised controlled trials (RCTs) and cluster-RCTs, that evaluated the effect of any educational intervention delivered to healthcare staff in any setting to prevent pressure ulceration. Two review authors independently assessed titles and abstracts of the studies identified by the search strategy for eligibility. We obtained full versions of potentially relevant studies and two authors independently screened these against the inclusion criteria. We identified five studies that met the inclusion criteria for this review: four RCTs and one cluster-RCT. The study characteristics differed in terms of healthcare settings, the nature of the interventions studied and outcome measures reported. The cluster-RCT, and two of the RCTs, explored the effectiveness of education delivered to healthcare staff within residential or nursing home settings, or nursing home and hospital wards, compared to no intervention, or usual practices. Educational intervention in one of these studies was embedded within a broader, quality improvement bundle. The other two individually randomised controlled trials explored the effectiveness of educational intervention, delivered in two formats, to nursing staff cohorts.Due to the heterogeneity of the studies identified, pooling was not appropriate and we have presented a narrative overview. We explored a number of comparisons (1) education versus no education (2) components of educational intervention in a number of combinations and (3) education delivered in different formats. There were three primary outcomes: change in healthcare professionals' knowledge, change in healthcare professionals' clinical behaviour and incidence of new pressure ulcers.We are uncertain whether there is a difference in health professionals' knowledge depending on whether they receive education or no education on pressure ulcer prevention (hospital group: mean difference (MD) 0.30, 95% confidence interval (CI) -1.00 to 1.60; 10 participants; nursing home group: MD 0.30, 95% CI -0.77 to 1.37; 10 participants). This was based on very low-certainty evidence from one study, which we downgraded for serious study limitations, indirectness and imprecision.We are uncertain whether there is a difference in pressure ulcer incidence with the following comparisons: training, monitoring and observation, versus monitoring and observation (risk ratio (RR) 0.63, 95% CI 0.37 to 1.05; 345 participants); training, monitoring and observation, versus observation alone (RR 1.21, 95% CI 0.60 to 2.43; 325 participants) or, monitoring and observation versus observation alone (RR 1.93, 95% CI 0.96 to 3.88; 232 participants). This was based on very low-certainty evidence from one study, which we downgraded for very serious study limitations and imprecision. We are uncertain whether multilevel intervention versus attention control makes any difference to pressure ulcer incidence. The report presented insufficient data to enable further interrogation of this outcome.We are uncertain whether education delivered in different formats such as didactic education versus video-based education (MD 4.60, 95% CI 3.08 to 6.12; 102 participants) or e-learning versus classroom education (RR 0.92, 95% CI 0.80 to 1.07; 18 participants), makes any difference to health professionals' knowledge of pressure ulcer prevention. This was based on very low-certainty evidence from two studies, which we downgraded for serious study limitations and study imprecision.None of the included studies explored our other primary outcome: change in health professionals' clinical behaviour. Only one study explored the secondary outcomes of interest, namely, pressure ulcer severity and patient and carer reported outcomes (self-assessed quality of life and functional dependency level respectively). However, this study provided insufficient information to enable our independent assessment of these outcomes within the review. We are uncertain whether educating healthcare professionals about pressure ulcer prevention makes any difference to pressure ulcer incidence, or to nurses' knowledge of pressure ulcer prevention. This is because the included studies provided very low-certainty evidence. Therefore, further information is required to clarify the impact of education of healthcare professionals on the prevention of pressure ulcers.

Interobserver agreement for post mortem renal histopathology and diagnosis of acute tubular necrosis in critically ill patients.

PubMed

Glassford, Neil J; Skene, Alison; Guardiola, Maria B; Chan, Matthew J; Bagshaw, Sean M; Bellomo, Rinaldo; Solez, Kim

2017-12-01

The renal histopathology of critically ill patients dying with acute kidney injury (AKI) in intensive care units of high income countries remains uncertain. Retrospective observational assessment of interobserver agreement in the reporting of renal post mortem histopathology, and the ability of pathologists blinded to the clinical context to independently identify the presence of pre-mortem AKI from digital images of histological sections from 34 critically ill patients dying in teaching hospitals in Australia and Canada. We identified a heterogeneous cohort with a median age of 65 years (interquartile range [IQR], 56.5-77), APACHE II score of 27 (IQR, 19-33), and sepsis as the most common admission diagnosis (12/34; 35%). The most common proximate causes of death were cardiovascular (19/34; 56%) and respiratory (7/34; 21%) failure. AKI was common, with 23 patients (68%) developing RIFLE-F AKI, and 21 patients (62%) receiving renal replacement therapy. Structured reporting for tubular inflammation showed excellent agreement (kappa = 1), but no other subdomain demonstrated better than moderate agreement (kappa < 0.6). Only fair agreement (55.9% of cases; kappa = 0.23) was demonstrated on the diagnosis of moderate to severe acute tubular necrosis (ATN). Pathologist A predicted RIFLE-I or worse AKI with the diagnosis of ATN, with an overall accuracy of 61.8%; pathologist B predicted AKI with an accuracy of 35.3%. Post mortem assessment of the renal histopathology in critically ill patients is neither robust nor reproducible; independent pathologists agree poorly on the diagnosis of ATN, and their structural assessment appears dissociated from ante-mortem renal function.

The decision-making capacity of elderly hospitalized patients: validation of a test on their choice of return home.

PubMed

Romdhani, Mouna; Abbas, Rachid; Peyneau, Cécile; Koskas, Pierre; Houenou Quenum, Nadège; Galleron, Sandrine; Drunat, Olivier

2018-03-01

Elderly hospitalized patients have uncertain or questionable capacity to make decisions about their care. Determining whether an elderly patient possesses decision-making capacity to return at home is a major concern for geriatricians in everyday practice. To construct and internally validate a new tool, the dream of home test (DROM-test), as support for decision making hospitalization discharge destination for the elderly in the acute or sub-acute care setting. The DROM-test consists of 10 questions and 4 vignettes based upon the 4 relevant criteria for decision-making: capacity to understand information, to appreciate and reason about medical risks and to communicate a choice. A prospective observational study was conducted during 6 months in 2 geriatric care units in Bretonneau Hospital (Assistance publique, Hôpitaux de Paris). We compared the patient decision of DROM-test regarding discharge recommendations with those of an Expert committee and of the team in charge of the patient. 102 were included: mean age 83.1 + 6.7 [70; 97], 66.67% females. Principal components analysis revealed four dimensions: choice, understanding, reasoning and understanding. The area under the ROC curve was 0.64 for the choice dimension, 0.59 for the understanding, 0.53 for the reasoning and 0.52 for the apprehension. Only the choice dimension was statistically associated with the decision of the committee of experts (p=0.017). Even though Drom-test has limitations, it provides an objective way to ascertain decision-making capacity for hospitalised elderly patients.

Early autologous stem cell transplantation for chronic lymphocytic leukemia: long-term follow-up of the German CLL Study Group CLL3 trial.

PubMed

Dreger, Peter; Döhner, Hartmut; McClanahan, Fabienne; Busch, Raymonde; Ritgen, Matthias; Greinix, Hildegard; Fink, Anna-Maria; Knauf, Wolfgang; Stadler, Michael; Pfreundschuh, Michael; Dührsen, Ulrich; Brittinger, Günter; Hensel, Manfred; Schetelig, Johannes; Winkler, Dirk; Bühler, Andreas; Kneba, Michael; Schmitz, Norbert; Hallek, Michael; Stilgenbauer, Stephan

2012-05-24

The CLL3 trial was designed to study intensive treatment including autologous stem cell transplantation (autoSCT) as part of first-line therapy in patients with chronic lymphocytic leukemia (CLL). Here, we present the long-term outcome of the trial with particular focus on the impact of genomic risk factors, and we provide a retrospective comparison with patients from the fludarabine-cyclophosphamide-rituximab (FCR) arm of the German CLL Study Group (GCLLSG) CLL8 trial. After a median observation time of 8.7 years (0.3-12.3 years), median progression-free survival (PFS), time to retreatment, and overall survival (OS) of 169 evaluable patients, including 38 patients who did not proceed to autoSCT, was 5.7, 7.3, and 11.3 years, respectively. PFS and OS were significantly reduced in the presence of 17p- and of an unfavorable immunoglobulin heavy variable chain mutational status, but not of 11q-. Five-year nonrelapse mortality was 6.5%. When 110 CLL3 patients were compared with 126 matched patients from the FCR arm of the CLL8 trial, 4-year time to retreatment (75% vs 77%) and OS (86% vs 90%) was similar despite a significant benefit for autoSCT in terms of PFS. In summary, early treatment intensification including autoSCT can provide very effective disease control in poor-risk CLL, although its clinical benefit in the FCR era remains uncertain. The trial has been registered with www.clinicaltrials.gov as NCT00275015.

Mass-forming cholangiocarcinoma and adenocarcinoma of unknown primary: can they be distinguished on liver MRI?

PubMed

Al Ansari, Najwa; Kim, Bong Soo; Srirattanapong, Saowanee; Semelka, Charles T A; Ramalho, Miguel; Altun, Ersan; Woosley, John T; Calvo, Benjamin; Semelka, Richard C

2014-12-01

To determine MR features suggestive of mass-forming cholangiocarcinoma (CCA) or liver metastases of adenocarcinoma of unknown primary (AUP), and to compare the ability of two experienced radiologists to establish the correct diagnosis. 61 patients with CCA or AUP, with MRIs were placed into two groups: population 1, 28 patients with certain diagnosis of either CCA or AUP; and population 2, 33 patients with uncertain diagnosis. Using population 1 with known diagnosis, two investigators formulated imaging criteria for CCA or AUP, which represented phase 1 of the study. In phase 2, two independent radiologists categorized the patients in populations 1 and 2 as CCA or AUP using the formulated criteria. This categorization was compared with the patient medical records and pathologist review. Findings were tested for statistical significance. In phase 1, solitary lesion, multifocal lesions with dominant lesion, capsule retraction, and porta hepatis lymphadenopathy were features of CCA; multifocal lesions with similar size, and ring enhancement were features of AUP. The number of lesions, capsule retraction, and early tumor enhancement pattern were observed to be significant features (P < 0.05). In phase 2, agreement between the two radiologists was good (k = 0.663). For population 1, the agreement was good (k = 0.659), and was fair for population 2 (k = 0.293). Concordance between the two radiologists, medical record, and the pathologist was found in 41/61 (67%) patients. Distinctive features of CCA and AUP are identifiable on MRI images, which may aid the radiologist to establish the correct diagnosis.

Treatment strategy for metastatic prostate cancer with extremely high PSA level: reconsidering the value of vintage therapy.

PubMed

Yamada, Yasutaka; Sakamoto, Shinichi; Amiya, Yoshiyasu; Sasaki, Makoto; Shima, Takayuki; Komiya, Akira; Suzuki, Noriyuki; Akakura, Koichiro; Ichikawa, Tomohiko; Nakatsu, Hiroomi

2018-05-04

The prognostic significance of initial prostate-specific antigen (PSA) level for metastatic prostate cancer remains uncertain. We investigated the differences in prognosis and response to hormonal therapies of metastatic prostate cancer patients according to initial PSA levels. We analyzed 184 patients diagnosed with metastatic prostate cancer and divided them into three PSA level groups as follows: low (<100 ng ml -1 ), intermediate (100-999 ng ml -1 ), and high (≥1000 ng ml -1 ). All patients received androgen deprivation therapy (ADT) immediately. We investigated PSA progression-free survival (PFS) for first-line ADT and overall survival (OS) within each of the three groups. Furthermore, we analyzed response to antiandrogen withdrawal (AW) and alternative antiandrogen (AA) therapies after development of castration-resistant prostate cancer (CRPC). No significant differences in OS were observed among the three groups (P = 0.654). Patients with high PSA levels had significantly short PFS for first-line ADT (P = 0.037). Conversely, patients in the high PSA level group had significantly longer PFS when treated with AW than those in the low PSA level group (P = 0.047). Furthermore, patients with high PSA levels had significantly longer PFS when provided with AA therapy (P = 0.049). PSA responders to AW and AA therapies had significantly longer survival after CRPC development than nonresponders (P = 0.011 and P < 0.001, respectively). Thus, extremely high PSA level predicted favorable response to vintage sequential ADT and AW. The current data suggest a novel aspect of extremely high PSA value as a favorable prognostic marker after development of CRPC.

Is tenofovir involved in hypophosphatemia and decrease of tubular phosphate reabsorption in HIV-positive adults?

PubMed

Badiou, Stéphanie; De Boever, Corinne Merle; Terrier, Nathalie; Baillat, Vincent; Cristol, Jean-Paul; Reynes, Jacques

2006-05-01

Tubulopathy with hypophosphatemia have been observed in HIV-positive patients receiving a tenofovir-containing regimen. However, the real incidence and prevalence of hypophosphatemia and their relation to tubular reabsorption disorders in tenofovir-treated patients remain uncertain. The aim of our study was to explore the effect of tenofovir on phosphatemia and on tubular phosphate reabsorption. In a first transversal study, 145 HIV-positive adults (44+/-9 years) receiving tenofovir 300 mg daily with a mean exposure of 11+/-9 months were included. In a second prospective study, 29 HIV-positive antiretroviral experienced adults (44+/-10 years) were evaluated before introduction of tenofovir 300 mg daily (M0) and at 3 months (M3) and 6 months (M6), thereafter. Phosphate, creatinine, glucose and protein levels were determined in plasma and urine. The ratio of maximal reabsorption capacity (TmPO4)/glomerular filtration rate (GFR) was determined by using the normogramm of Walton and Bijvoet. In the transversal study, 26% of patients had hypophosphatemia (<0.84 mmol/l) while 47% of patients had a decreased TmPO4/GFR (<0.8 mmol/l). In the prospective study, baseline prevalence of hypophosphatemia (<0.84 mmol/l) and decreased TmPO4/GFR (<0.8mmol/l) was 31 and 41%, respectively. Three and 6 months after starting tenofovir, there is no significant change in mean phosphate levels (M0:0.91 mmol/l, M3:0.97 mmol/l, M6:0.98 mmol/l) and mean TmPO4/GFR (M0:0.80 mmol/l, M3:0.88 mmol/l, M6:0.84 mmol/l). Moreover, prevalence of hypophosphatemia (M3:28%, M6:28%) and decreased TmPO4/GFR (M3:41%, M6:45%) remained stable. Hypophosphatemia linked to a decreased proximal tubular reabsorption was frequently observed in HIV-positive adults independently of the use of tenofovir. In this preliminary study, no worsening effect on phosphatemia and tubular phosphate reabsorption was observed 6 months after introduction of tenofovir in treatment experienced patients.

Meaningful use in the safety net: a rapid ethnography of patient portal implementation at five community health centers in California.

PubMed

Ackerman, Sara L; Sarkar, Urmimala; Tieu, Lina; Handley, Margaret A; Schillinger, Dean; Hahn, Kenneth; Hoskote, Mekhala; Gourley, Gato; Lyles, Courtney

2017-09-01

US health care institutions are implementing secure websites (patient portals) to achieve federal Meaningful Use (MU) certification. We sought to understand efforts to implement portals in "safety net" health care systems that provide services for low-income populations. Our rapid ethnography involved visits at 4 California safety net health systems and in-depth interviews at a fifth. Visits included interviews with clinicians and executives ( n  = 12), informal focus groups with front-line staff ( n  = 35), observations of patient portal sign-up procedures and clinic work, review of marketing materials and portal use data, and a brief survey ( n  = 45). Our findings demonstrate that the health systems devoted considerable effort to enlisting staff support for portal adoption and integrating portal-related work into clinic routines. Although all health systems had achieved, or were close to achieving, MU benchmarks, patients faced numerous barriers to portal use and our participants were uncertain how to achieve and sustain "meaningful use" as defined by and for their patients. Health systems' efforts to achieve MU certification united clinic staff under a shared ethos of improved quality of care. However, MU's assumptions about patients' demand for electronic access to health information and ability to make use of it directed clinics' attention to enrollment and message routing rather than to the relevance and usability of a tool that is minimally adaptable to the safety net context. We found a mismatch between MU-based metrics of patient engagement and the priorities and needs of safety net patient populations. © The Author 2017. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Telescopic observations - Visual, photographic, polarimetric. [of planet Mars

NASA Technical Reports Server (NTRS)

Martin, Leonard J.; James, Philip B.; Dollfus, Audouin; Iwasaki, Kyosuke; Beish, Jeffrey D.

1992-01-01

The paper divides the high points of telescopic observations of Mars into three time periods: historical, missions support (recent), and present. Particular attention is given to visual and photographic observations, with brief discussions of spectroscopic and polarization studies. Major topics of Martian phenomena included are albedo features, polar caps, dust storms, and white clouds. The interannual variability of the recessions of seasonal polar caps has been compared to dust storm activity, but this relationship remains uncertain. Only a very limited number of canals can be related to markings on the Viking images. The remainder are argued to be optical illusions created by observers pushing their perceived resolution beyond practical limits.

Medical malpractice liability crisis meets markets: stress in unexpected places.

PubMed

Berenson, Robert A; Kuo, Sylvia; May, Jessica H

2003-09-01

While the causes of rapidly rising medical malpractice insurance premiums remain contentious and unsettled, the consequences are rippling through communities, threatening to diminish patients' access to care and increase health care costs, with an uncertain impact on quality, according to findings from the Center for Studying Health System Change's (HSC) 2002-03 site visits to 12 nationally representative communities. The severity of malpractice insurance problems varied across communities, with some physicians changing how and where they care for patients. For example, rather than treat patients in their offices, more physicians are referring patients to emergency departments. And many physicians, especially those practicing in high-risk specialties, are unwilling to provide emergency department on-call coverage because of malpractice liability concerns.

Life is uncertain. death is certain. Buddhism and palliative care.

PubMed

Masel, Eva K; Schur, Sophie; Watzke, Herbert H

2012-08-01

It is part of a palliative care assessment to identify patients' spiritual needs. According to Buddhism, suffering is inherent to all human beings. Advice on how suffering can be reduced in the course of serious illness might be helpful to patients with incurable and progressive diseases. Palliative care could benefit from Buddhist insights in the form of compassionate care and relating death to life. Buddhist teachings may lead to a more profound understanding of incurable diseases and offer patients the means by which to focus their minds while dealing with physical symptoms and ailments. This might not only be beneficial to followers of Buddhism but to all patients. Copyright © 2012 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

Improving Hospital-wide Patient Scheduling Decisions by Clinical Pathway Mining.

PubMed

Gartner, Daniel; Arnolds, Ines V; Nickel, Stefan

2015-01-01

Recent research has highlighted the need for solving hospital-wide patient scheduling problems. Inpatient scheduling, patient activities have to be scheduled on scarce hospital resources such that temporal relations between activities (e.g. for recovery times) are ensured. Common objectives are, among others, the minimization of the length of stay (LOS). In this paper, we consider a hospital-wide patient scheduling problem with LOS minimization based on uncertain clinical pathways. We approach the problem in three stages: First, we learn most likely clinical pathways using a sequential pattern mining approach. Second, we provide a mathematical model for patient scheduling and finally, we combine the two approaches. In an experimental study carried out using real-world data, we show that our approach outperforms baseline approaches on two metrics.

Diversified models for portfolio selection based on uncertain semivariance

NASA Astrophysics Data System (ADS)

Chen, Lin; Peng, Jin; Zhang, Bo; Rosyida, Isnaini

2017-02-01

Since the financial markets are complex, sometimes the future security returns are represented mainly based on experts' estimations due to lack of historical data. This paper proposes a semivariance method for diversified portfolio selection, in which the security returns are given subjective to experts' estimations and depicted as uncertain variables. In the paper, three properties of the semivariance of uncertain variables are verified. Based on the concept of semivariance of uncertain variables, two types of mean-semivariance diversified models for uncertain portfolio selection are proposed. Since the models are complex, a hybrid intelligent algorithm which is based on 99-method and genetic algorithm is designed to solve the models. In this hybrid intelligent algorithm, 99-method is applied to compute the expected value and semivariance of uncertain variables, and genetic algorithm is employed to seek the best allocation plan for portfolio selection. At last, several numerical examples are presented to illustrate the modelling idea and the effectiveness of the algorithm.

Psychological Counseling of Female Fertility Preservation Patients

PubMed Central

Lawson, Angela K.; Klock, Susan C.; Pavone, Mary Ellen; Hirshfeld-Cytron, Jennifer; Smith, Kristin N.; Kazer, Ralph R.

2015-01-01

Young cancer patients are increasingly interested in preserving their fertility prior to undergoing gonadotoxic therapies. Although the medical safety and treatment protocols for fertility preservation have been well documented, limited research has addressed the emotional issues which arise in fertility preservation patients. We briefly review the literature on the psychosocial issues in adult female fertility preservation treatment and describe our experiences within this patient population patient. Our findings suggest that several important issues to be addressed during the psychological counseling of adult female fertility preservation patients include: 1) pre-existing psychological distress in patients undergoing treatment, 2) choice of fertility preservation strategy in the face of an uncertain relationship future, 3) decision making regarding use of third party reproduction (e.g., sperm/egg donation, gestational surrogacy), 4) treatment expectations regarding pregnancy and miscarriage, 5) ethical issues related to treatment including the creation, cryopreservation, and disposition of embryos/oocytes, and 6) decision regret from patients who declined fertility preservation. PMID:25996581

Rocker-soled shoes and walking distance in patients with calf claudication.

PubMed

Richardson, J K

1991-07-01

Calf claudication is the major clinical manifestation of peripheral vascular occlusive disease in a significant number of patients. Although claudication causes substantial patient disability, most patients are treated conservatively because of the risks of surgical therapy and the uncertain efficacy of drug therapy. It was hypothesized that rocker-soled shoes would decrease the work of the plantar flexors and therefore increase walking distance in patients with calf claudication. To test this hypothesis, walking distances in patients with calf claudication using rocker-soled shoes and a placebo shoe insert were compared. Rocker-soled shoes significantly increased both the total distance walked and the distance at which patients were initially bothered by symptoms by 77m (37%, p less than .0005) and 89m (91%, p = .003), respectively. It was concluded that rocker-soled shoes may reduce disability in patients with calf claudication by increasing walking distance.

Education Creates Welcoming Environment for Transgender Patients.

PubMed

Ehrenfeld, Jesse; Gridley, Samantha

2016-08-01

The ED often is the access point of choice for transgender patients who may be reluctant to interact with providers. Experts say there is a need for training and education of how to present a gender-affirming healthcare environment. Recommended steps include a review of policies, along with corresponding changes to electronic and paper intake forms to ensure that the language used is inclusive of all genders. While blanket discrimination may be declining, experts note that some providers are uncertain about how to interact with a transgender patient. It's always best to ask patients for their preferred name and pronoun and to repeat this exercise every three to six months for return patients, as gender identify can be fluid. To ease anxiety for transgender patients, consider developing a navigator program that will pair any transgender patient who requests the service with a trained advocate who can support and guide the patient through the system.

The relationship between red meat allergy and sensitization to gelatin and galactose-alpha-1,3-galactose

PubMed Central

Mullins, Raymond James; James, Hayley; Platts-Mills, Thomas A.E.; Commins, Scott

2012-01-01

Background We have observed patients clinically allergic to red meat and meat-derived gelatin. Objective We describe a prospective evaluation of the clinical significance of gelatin sensitization, the predictive value of a positive test and an examination of the relationship between allergic reactions to red meat and sensitization to gelatin and alpha-Gal. Methods Adult patients evaluated 1997-2011 for suspected allergy/anaphylaxis to medication, insect venom or food were skin tested with gelatin colloid. In vitro (ImmunoCap) testing was undertaken where possible. Results Positive gelatin tests were observed in 40/1335 individuals; 30/40 patients with red meat allergy (12 also clinically allergic to gelatin); 2/2 with gelatin colloid anaphylaxis; 4/172 with idiopathic anaphylaxis (all responded to intravenous gelatin challenge of 0.02 to 0.4g); 4/368 with drug allergy. Testing was negative in all patients with venom allergy (n=241), non-meat food allergy (n=222), and miscellaneous disorders (n=290). ImmunoCap was positive to alpha-Gal in 20/24 meat allergics and in 20/22 with positive gelatin skin tests. The results of gelatin skin testing and anti-alpha-Gal IgE were strongly correlated (r=0.46; P<0.01). Alpha-Gal was detected in bovine gelatin colloids at concentrations of ~ 0.44 to 0.52ug/gm gelatin by inhibition radioimmunoassay. Conclusion Most patients allergic to red meat were sensitized to gelatin and a subset was clinically allergic to both. The detection of alpha-Gal in gelatin and correlation between the results of alpha-Gal and gelatin testing raises the possibility that alpha-Gal IgE may be the target of reactivity to gelatin. The pathogenic relationship between tick bites and sensitization to red meat, alpha-Gal and gelatin (with or without clinical reactivity) remains uncertain. PMID:22480538

Adjuvant Lapatinib and Trastuzumab for Early Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer: Results From the Randomized Phase III Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization Trial

PubMed Central

Holmes, Eileen; Baselga, José; de Azambuja, Evandro; Dueck, Amylou C.; Viale, Giuseppe; Zujewski, Jo Anne; Goldhirsch, Aron; Armour, Alison; Pritchard, Kathleen I.; McCullough, Ann E.; Dolci, Stella; McFadden, Eleanor; Holmes, Andrew P.; Tonghua, Liu; Eidtmann, Holger; Dinh, Phuong; Di Cosimo, Serena; Harbeck, Nadia; Tjulandin, Sergei; Im, Young-Hyuck; Huang, Chiun-Sheng; Diéras, Véronique; Hillman, David W.; Wolff, Antonio C.; Jackisch, Christian; Lang, Istvan; Untch, Michael; Smith, Ian; Boyle, Frances; Xu, Binghe; Gomez, Henry; Suter, Thomas; Gelber, Richard D.; Perez, Edith A.

2016-01-01

Background Lapatinib (L) plus trastuzumab (T) improves outcomes for metastatic human epidermal growth factor 2–positive breast cancer and increases the pathologic complete response in the neoadjuvant setting, but their role as adjuvant therapy remains uncertain. Methods In the Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization trial, patients with centrally confirmed human epidermal growth factor 2–positive early breast cancer were randomly assigned to 1 year of adjuvant therapy with T, L, their sequence (T→L), or their combination (L+T). The primary end point was disease-free survival (DFS), with 850 events required for 80% power to detect a hazard ratio (HR) of 0.8 for L+T versus T. Results Between June 2007 and July 2011, 8,381 patients were enrolled. In 2011, due to futility to demonstrate noninferiority of L versus T, the L arm was closed, and patients free of disease were offered adjuvant T. A protocol modification required P ≤ .025 for the two remaining pairwise comparisons. At a protocol-specified analysis with a median follow-up of 4.5 years, a 16% reduction in the DFS hazard rate was observed with L+T compared with T (555 DFS events; HR, 0.84; 97.5% CI, 0.70 to 1.02; P = .048), and a 4% reduction was observed with T→L compared with T (HR, 0.96; 97.5% CI, 0.80 to 1.15; P = .61). L-treated patients experienced more diarrhea, cutaneous rash, and hepatic toxicity compared with T-treated patients. The incidence of cardiac toxicity was low in all treatment arms. Conclusion Adjuvant treatment that includes L did not significantly improve DFS compared with T alone and added toxicity. One year of adjuvant T remains standard of care. PMID:26598744

Use of the SeHCAT test in the investigation of diarrhoea.

PubMed Central

Ford, G. A.; Preece, J. D.; Davies, I. H.; Wilkinson, S. P.

1992-01-01

The SeHCAT test was used to investigate possible bile acid malabsorption in 166 patients presenting to a district general hospital with chronic diarrhoea of uncertain cause. Eighty-four (51%) patients had impaired SeHCAT retention. These included 23 of 28 patients with a possible type I abnormality (terminal ileal resection or disease, previous pelvic radiotherapy), 20 of 74 with a possible type II abnormality (idiopathic diarrhoea), 32 of 45 with a possible type III abnormality (post-cholecystectomy, post-vagotomy), and 9 of 19 with diarrhoea associated with diabetes. Patients with severe bile acid malabsorption demonstrated a good response to cholestyramine whereas the response in patients with a mildly abnormal SeHCAT retention was variable. Bile acid malabsorption is an important cause of diarrhoea in patients presenting with unexplained chronic diarrhoea. PMID:1409191

Tectal gliomas: assessment of malignant progression, clinical management, and quality of life in a supposedly benign neoplasm.

PubMed

Mohme, Malte; Fritzsche, Friederike S; Mende, Klaus C; Matschke, Jakob; Löbel, Ulrike; Kammler, Gertrud; Westphal, Manfred; Emami, Pedram; Martens, Tobias

2018-06-01

OBJECTIVE Tectal gliomas constitute a rare and inhomogeneous group of lesions with an uncertain clinical course. Because these supposedly benign tumors are frequently followed up by observation over many years, the authors undertook this analysis of their own case series in an effort to demonstrate that the clinical course is highly variable and that there is a potential for a progressive biology. METHODS Clinical data analysis of 23 cases of tectal glioma (involving 9 children and 14 adults) was performed retrospectively. Radiographic data were analyzed longitudinally and MR images were evaluated for tumor volume, contrast enhancement, and growth progression. Quality of life was assessed using the EORTC BN20 and C30 questionnaires during follow-up in a subgroup of patients. RESULTS The patients' mean age at diagnosis was 29.2 years. The main presenting symptom at diagnosis was hydrocephalus (80%). Six patients were treated by primary tumor resection (26.1%), 3 patients underwent biopsy followed by resection (13.1%), and 3 patients underwent biopsy only (13.1%). For additional treatment of hydrocephalus, 14 patients (60.9%) received shunts and/or endoscopic third ventriculostomy. Radiographic tumor progression was observed in 47.9% of the 23 cases. The mean time between diagnosis and growth progression was 51.5 months, and the mean time to contrast enhancement was 69.7 months. Histopathological analysis was obtained in 12 cases (52.2%), resulting in 5 cases of high-grade glioma (3 cases of glioblastoma multiforme [GBM], grade IV, and 2 of anaplastic astrocytoma, grade III), 5 cases of pilocytic astrocytoma, 1 diffuse astrocytoma, and 1 ganglioglioma. Malignant progression was observed in 2 cases, with 1 case progressing from a diffuse astrocytoma (grade II) to a GBM (grade IV) within a period of 13 years. Quality-of-life measurements demonstrated distinct functional deficits compared to a healthy sample as well as glioma control cohorts. CONCLUSIONS Analysis of this case series shows that a major subpopulation of tectal gliomas show progression and malignant transformation in children as well as in adolescents. These tumors therefore cannot be considered inert lesions and require histological confirmation and close follow-up. Quality-of-life questionnaires show that tectal glioma patients might benefit from special psychological support in emotional, social, and cognitive functionality.

A Computational Framework to Control Verification and Robustness Analysis

NASA Technical Reports Server (NTRS)

Crespo, Luis G.; Kenny, Sean P.; Giesy, Daniel P.

2010-01-01

This paper presents a methodology for evaluating the robustness of a controller based on its ability to satisfy the design requirements. The framework proposed is generic since it allows for high-fidelity models, arbitrary control structures and arbitrary functional dependencies between the requirements and the uncertain parameters. The cornerstone of this contribution is the ability to bound the region of the uncertain parameter space where the degradation in closed-loop performance remains acceptable. The size of this bounding set, whose geometry can be prescribed according to deterministic or probabilistic uncertainty models, is a measure of robustness. The robustness metrics proposed herein are the parametric safety margin, the reliability index, the failure probability and upper bounds to this probability. The performance observed at the control verification setting, where the assumptions and approximations used for control design may no longer hold, will fully determine the proposed control assessment.

H∞ control for uncertain linear system over networks with Bernoulli data dropout and actuator saturation.

PubMed

Yu, Jimin; Yang, Chenchen; Tang, Xiaoming; Wang, Ping

2018-03-01

This paper investigates the H ∞ control problems for uncertain linear system over networks with random communication data dropout and actuator saturation. The random data dropout process is modeled by a Bernoulli distributed white sequence with a known conditional probability distribution and the actuator saturation is confined in a convex hull by introducing a group of auxiliary matrices. By constructing a quadratic Lyapunov function, effective conditions for the state feedback-based H ∞ controller and the observer-based H ∞ controller are proposed in the form of non-convex matrix inequalities to take the random data dropout and actuator saturation into consideration simultaneously, and the problem of non-convex feasibility is solved by applying cone complementarity linearization (CCL) procedure. Finally, two simulation examples are given to demonstrate the effectiveness of the proposed new design techniques. Copyright © 2018 ISA. Published by Elsevier Ltd. All rights reserved.

Adaptive Output-Feedback Neural Control of Switched Uncertain Nonlinear Systems With Average Dwell Time.

PubMed

Long, Lijun; Zhao, Jun

2015-07-01

This paper investigates the problem of adaptive neural tracking control via output-feedback for a class of switched uncertain nonlinear systems without the measurements of the system states. The unknown control signals are approximated directly by neural networks. A novel adaptive neural control technique for the problem studied is set up by exploiting the average dwell time method and backstepping. A switched filter and different update laws are designed to reduce the conservativeness caused by adoption of a common observer and a common update law for all subsystems. The proposed controllers of subsystems guarantee that all closed-loop signals remain bounded under a class of switching signals with average dwell time, while the output tracking error converges to a small neighborhood of the origin. As an application of the proposed design method, adaptive output feedback neural tracking controllers for a mass-spring-damper system are constructed.

Artificial bias typically neglected in comparisons of uncertain atmospheric data

NASA Astrophysics Data System (ADS)

Pitkänen, Mikko R. A.; Mikkonen, Santtu; Lehtinen, Kari E. J.; Lipponen, Antti; Arola, Antti

2016-09-01

Publications in atmospheric sciences typically neglect biases caused by regression dilution (bias of the ordinary least squares line fitting) and regression to the mean (RTM) in comparisons of uncertain data. We use synthetic observations mimicking real atmospheric data to demonstrate how the biases arise from random data uncertainties of measurements, model output, or satellite retrieval products. Further, we provide examples of typical methods of data comparisons that have a tendency to pronounce the biases. The results show, that data uncertainties can significantly bias data comparisons due to regression dilution and RTM, a fact that is known in statistics but disregarded in atmospheric sciences. Thus, we argue that often these biases are widely regarded as measurement or modeling errors, for instance, while they in fact are artificial. It is essential that atmospheric and geoscience communities become aware of and consider these features in research.

Observer-based state tracking control of uncertain stochastic systems via repetitive controller

NASA Astrophysics Data System (ADS)

Sakthivel, R.; Susana Ramya, L.; Selvaraj, P.

2017-08-01

This paper develops the repetitive control scheme for state tracking control of uncertain stochastic time-varying delay systems via equivalent-input-disturbance approach. The main purpose of this work is to design a repetitive controller to guarantee the tracking performance under the effects of unknown disturbances with bounded frequency and parameter variations. Specifically, a new set of linear matrix inequality (LMI)-based conditions is derived based on the suitable Lyapunov-Krasovskii functional theory for designing a repetitive controller which guarantees stability and desired tracking performance. More precisely, an equivalent-input-disturbance estimator is incorporated into the control design to reduce the effect of the external disturbances. Simulation results are provided to demonstrate the desired control system stability and their tracking performance. A practical stream water quality preserving system is also provided to show the effectiveness and advantage of the proposed approach.

75 FR 60371 - Requirements of a Statement Disclosing Uncertain Tax Positions; Correction

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-30

... Requirements of a Statement Disclosing Uncertain Tax Positions; Correction AGENCY: Internal Revenue Service... the IRS to require corporations to file a schedule disclosing uncertain tax positions related to the tax return as required by the IRS. FOR FURTHER INFORMATION CONTACT: Kathryn Zuba, (202) 622-3400 (not...

Uncertain Times 2012: Afterschool Programs Still Struggling in Today's Economy

ERIC Educational Resources Information Center

Afterschool Alliance, 2012

2012-01-01

"Uncertain Times 2012," conducted by the Afterschool Alliance between April 25 and June 8, 2012, assesses the impact of economic conditions on afterschool programs. While many studies have evaluated the impact of programs, "Uncertain Times" is the only research to examine the fiscal health of afterschool programs and their…

Alcohol's effects on emotionally motivated attention, defensive reactivity and subjective anxiety during uncertain threats.

PubMed

Bradford, Daniel E; Motschman, Courtney A; Starr, Mark J; Curtin, John J

2017-11-01

Developing a better understanding of how and under what circumstances alcohol affects the emotions, cognitions and neural functions that precede and contribute to dangerous behaviors during intoxication may help to reduce their occurrence. Alcohol intoxication has recently been shown to reduce defensive reactivity and anxiety more during uncertain vs certain threat. However, alcohol's effects on emotionally motivated attention to these threats are unknown. Alcohol may disrupt both affective response to and attentional processing of uncertain threats making intoxicated individuals less able to avoid dangerous and costly behaviors. To test this possibility, we examined the effects of a broad range of blood alcohol concentrations on 96 participants' sub-cortically mediated defensive reactivity (startle potentiation), retrospective subjective anxiety (self-report) and cortically assessed emotionally motivated attention (probe P3 event related potential) while they experienced visually cued uncertain and certain location electric shock threat. As predicted, alcohol decreased defensive reactivity and subjective anxiety more during uncertain vs certain threat. In a novel finding, alcohol dampened emotionally motivated attention during uncertain but not certain threat. This effect appeared independent of alcohol's effects on defensive reactivity and subjective anxiety. These results suggest that alcohol intoxication dampens processing of uncertain threats while leaving processing of certain threats intact. © The Author (2017). Published by Oxford University Press.

[Therapy of multiple myeloma: indications and options].

PubMed

Peest, D; Ganser, A

2007-12-01

The multiple myeloma (MM) has an incidence of 3-4/100,000 in the Caucasian population. MM has to be distinguished from smouldering MM and monoclonal gammopathy of uncertain significance (MGUS). In younger patients (<65 years) a good long-term remission is the aim of therapy, while in the elderly patients with comorbidities the aim is a good partial remission with good quality of life. In the elderly this can be achieved with a combination of melphalan and prednisone. High-dose chemotherapy, often as a tandem transplantation, is part of standard therapy of MM patients <65 years. However, allogeneic stem cell transplantation is the only curative approach. New substances approved for treatment of relapsed MM include bortezomib, thalidomide, and lenalidomide.

Herpes simplex virus type 2 recurrent meningitis (Mollaret's meningitis): a consideration for the recurrent pathogenesis.

PubMed

Sato, Rumi; Ayabe, Mitsuyoshi; Shoji, Hiroshi; Ichiyama, Takashi; Saito, Yumiko; Hondo, Ryo; Eizuru, Yoshito

2005-11-01

We report a 44-year-old Japanese woman with herpes simplex virus (HSV) type 2 recurrent meningitis (Mollaret's meningitis). The diagnosis was confirmed by nested polymerase chain reaction in her cerebrospinal fluid, but the patient's conventional HSV antibodies by complement fixation, neutralizing test or enzyme immunoassay showed low titres with low lymphoproliferative response. Several similar cases are discussed. Although the reason for the recurrent pathogenesis is uncertain, our report suggests that the low immune response including immune evasion may be involved in the pathogenesis of HSV type 2 recurrent meningitis. For this patient, long-term suppressive and patient-initiated therapies were conducted to prevent the recurrence of meningitis.

An update on the diagnosis and treatment of chronic idiopathic neutropenia.

PubMed

Dale, David C; Bolyard, Audrey A

2017-01-01

Neutropenia lasting for at least for 3 months and not attributable to drugs or a specific genetic, infectious, inflammatory, autoimmune or malignant cause is called chronic idiopathic neutropenia (CIN). CIN and autoimmune neutropenia (AIN) are very similar and overlapping conditions. The clinical consequences depend upon the severity of neutropenia, but it is not considered a premalignant condition. Long-term observational studies in children indicate that the disease often lasts for 3-5 years in children, then spontaneously remits, but it rarely remits in adult cases. The value of antineutrophil antibody testing in both children and adults is uncertain. Most recent data suggest that CIN and AIN are immune-mediated diseases, but there are no new clinical or genetic tests to aid in diagnosis. Treatment with granulocyte colony stimulating factor (G-CSF) is effective to increase blood neutrophils in almost all cases; this treatment is reserved, however, for patients with both neutropenia and evidence of recurrent fevers, inflammatory symptoms and infections. There is little or no evidence to indicate that G-CSF treatment predisposes to myeloid malignancies in this population. It is important to recognize CIN and AIN, the most common causes of chronic neutropenia in both children and adults. If the neutropenia is not severe, that is more than 0.5 × 10/l, most patients can be observed and not treated prophylactically with antibiotics or a growth factor. When neutropenia is severe, treatment with G-CSF is often beneficial.

An update on the diagnosis and treatment of chronic idiopathic neutropenia

PubMed Central

Dale, David C.; Bolyard, Audrey Anna

2017-01-01

Purpose of Review Neutropenia lasting for at least for 3 months and not attributable to drugs or a specific genetic, infectious, inflammatory, autoimmune or malignant cause is called chronic idiopathic neutropenia. (CIN) CIN and autoimmune neutropenia (AIN) are very similar and overlapping conditions. The clinical consequences depend upon the severity of neutropenia, but it is not considered a premalignant condition. Recent findings Long-term observational studies in children indicate that the disease often lasts for 3 to 5 years in children, then spontaneously remits, but it rarely remits in adult cases. The value of anti-neutrophil antibody testing in both children and adults is uncertain. Most recent data suggest that CIN and AIN are immune mediated diseases, but there are no new clinical or genetic tests to aid in diagnosis. Treatment with granulocyte colony stimulating factor (G-CSF) is effective to increase blood neutrophils in almost all cases; this treatment is reserved, however for patients with both neutropenia and evidence of recurrent fevers, inflammatory symptoms and infections. There is little or no evidence to indicate that G-CSF treatment predisposes to myeloid malignancies in this population. Summary It is important to recognize CIN and AIN, the most common causes of chronic neutropenia in both children and adults. If the neutropenia is not severe, i.e. > 0.5 × 109/L, most patients can be observed and not treated prophylactically with antibiotics or a growth factor. When neutropenia is severe treatment with G-CSF is often beneficial. PMID:27841775

Cancer-associated thrombosis: prevention and treatment

PubMed Central

Brose, K.M.J.; Lee, A.Y.Y.

2008-01-01

Patients with cancer are at high risk to develop venous thromboembolism, and they are also more likely to develop complications from anticoagulant treatment. Because little research has focused on the oncology population to date, the optimal methods of prophylaxis and treatment remain uncertain in some clinical situations. Currently, low molecular weight heparin and warfarin are the most frequently used pharmacologic agents; however, they have their limitations. Other therapeutic options, such as inferior caval filters, are poorly studied and remain controversial. A summary of the most recent evidence on the prevention and treatment of venous thromboembolism in cancer patients is presented here. PMID:18231650

OBSERVABLE INDICATORS OF THE SENSITIVITY OF PM2.5 NITRATE TO EMISSION REDUCTIONS PART I: DERIVATION OF THE ADJUSTED GAS RATIO AND APPLICABILITY AT REGULATORY-RELEVANT TIME SCALES

EPA Science Inventory

Chemical transport models have frequently been used to evaluate the impacts of emission reductions on inorganic PM2.5. However, such models are limited in their accuracy by uncertain estimates of the spatial and temporal characterization of emissions and meteorology. Site-speci...

Assessing net ecosystem carbon exchange of U.S. terrestrial ecosystems by integrating eddy covariance flux measurements and satellite observations

Treesearch

Jingfeng Xiaoa; Qianlai Zhuang; Beverly E. Law; Dennis D. Baldocchi; Jiquan Chen; al. et.

2011-01-01

More accurate projections of future carbon dioxide concentrations in the atmosphere and associated climate change depend on improved scientific understanding of the terrestrial carbon cycle. Despite the consensus that U.S. terrestrial ecosystems provide a carbon sink, the size, distribution, and interannual variability of this sink remain uncertain. Here we report a...

d Subunit-Containing GABA[subscript A] Receptor Prevents Overgeneralization of Fear in Adult Mice

ERIC Educational Resources Information Center

Zhang, Wen-Hua; Zhou, Jin; Pan, Han-Qing; Wang, Xiao-Yang; Liu, Wei-Zhu; Zhang, Jun-Yu; Yin, Xiao-Ping; Pan, Bing-Xing

2017-01-01

The role of d subunit-containing GABA[subscript A] receptor (GABA[subscript A](d)R) in fear generalization is uncertain. Here, by using mice with or without genetic deletion of GABA[subscript A](d)R and using protocols in which the conditioned tone stimuli were cross presented with different nonconditioned stimuli, we observed that when the two…

Interactions in Massive Colliding Wind Binaries

NASA Technical Reports Server (NTRS)

Corcoran, M.

2012-01-01

The most massive stars (M> 60 Solar Mass) play crucial roles in altering the chemical and thermodynamic properties of their host galaxies. Stellar mass is the fundamental stellar parameter that determines their ancillary properties and which ultimately determines the fate of these stars and their influence on their galactic environs. Unfortunately, stellar mass becomes observationally and theoretically less well constrained as it increases. Theory becomes uncertain mostly because very massive stars are prone to strong, variable mass loss which is difficult to model. Observational constraints are uncertain too. Massive stars are rare, and massive binary stars (needed for dynamical determination of mass) are rarer still: and of these systems only a fraction have suitably high orbital inclinations for direct photometric and spectroscopic radial-velocity analysis. Even in the small number of cases in which a high-inclination binary near the upper mass limit can be identified, rotational broadening and contamination of spectral line features from thick circumstellar material (either natal clouds or produced by strong stellar wind driven mass loss from one or both of he stellar components) biases the analysis. In the wilds of the upper HR diagram, we're often left with indirect and circumstantial means of determining mass, a rather unsatisfactory state of affairs.

Trained Eyes: Experience Promotes Adaptive Gaze Control in Dynamic and Uncertain Visual Environments

PubMed Central

Taya, Shuichiro; Windridge, David; Osman, Magda

2013-01-01

Current eye-tracking research suggests that our eyes make anticipatory movements to a location that is relevant for a forthcoming task. Moreover, there is evidence to suggest that with more practice anticipatory gaze control can improve. However, these findings are largely limited to situations where participants are actively engaged in a task. We ask: does experience modulate anticipative gaze control while passively observing a visual scene? To tackle this we tested people with varying degrees of experience of tennis, in order to uncover potential associations between experience and eye movement behaviour while they watched tennis videos. The number, size, and accuracy of saccades (rapid eye-movements) made around ‘events,’ which is critical for the scene context (i.e. hit and bounce) were analysed. Overall, we found that experience improved anticipatory eye-movements while watching tennis clips. In general, those with extensive experience showed greater accuracy of saccades to upcoming event locations; this was particularly prevalent for events in the scene that carried high uncertainty (i.e. ball bounces). The results indicate that, even when passively observing, our gaze control system utilizes prior relevant knowledge in order to anticipate upcoming uncertain event locations. PMID:23951147

Successful Surgical Stabilization of Rib Fractures Despite Candida Colonization of the Mediastinum.

PubMed

Ju, Tammy; Rivas, Lisbi; Sarani, Babak

2018-04-06

Pleural space or chest wall infection is a contraindication for surgical stabilization of rib fractures (SSRF) due to the risk of hardware infection. However, the exact degree of risk is uncertain. SSRF is associated with decreased need for mechanical ventilation and pneumonia. Here, we describe a poly-trauma patient with candida colonization of the mediastinum who successfully underwent SSRF. Copyright © 2018. Published by Elsevier Inc.

Collecting and Storing Malignant, Borderline Malignant Neoplasms, and Related Samples From Young Patients With Cancer

ClinicalTrials.gov

2017-12-11

Acute Undifferentiated Leukemia; Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Childhood Acute Lymphoblastic Leukemia; Childhood Acute Myeloid Leukemia/Other Myeloid Malignancies; Childhood Chronic Myelogenous Leukemia; Chronic Lymphocytic Leukemia; Hairy Cell Leukemia; Juvenile Myelomonocytic Leukemia; Mast Cell Leukemia; Neoplasm of Uncertain Malignant Potential; Prolymphocytic Leukemia; Secondary Acute Myeloid Leukemia; T-cell Large Granular Lymphocyte Leukemia; Unspecified Childhood Solid Tumor, Protocol Specific

Nursing students’ attitude towards suicide attempters: A study from rural part of Northern India

PubMed Central

Nebhinani, Mamta; Nebhinani, Naresh; Tamphasana, L.; Gaikwad, Achla D.

2013-01-01

Context: Majority of health professionals have unfavorable attitudes towards patients presenting with self-harm, which further compromises their willingness and outcome of care. Aims: To assess the nursing students’ attitudes toward suicide attempters. Settings and Design: Cross-sectional study was conducted in two nursing colleges of north India. Material and Methods: Three hundred and eight nursing students were recruited through total enumeration method from May to June 2012. ‘Suicide opinion questionnaire’ was administered to assess their attitudes towards suicide attempters. Statistical Analysis Used: Descriptive statistics was employed with Statistical Package for Social Sciences version 14.0 for Windows. Results: Majority were single females, from urban locality, with the mean age of 20 years. Only minority had previous exposure to suicide prevention programs and management of such cases. Majority of students agreed for mental illness, disturbed family life, and depression as major push to attempt suicide. They held favorable attitude for half of the attitudinal statement, but they were uncertain for rest half of the statements. Conclusions: They generally had favorable attitude towards suicide attempters. Their uncertain response highlights the need for enhancing educational exposure of nursing students and new staff at the earliest opportunity, to carve their favorable attitude towards patients presenting with self-harm. PMID:24347946

The SIESTA Trial: A Randomized Study Investigating the Efficacy, Safety, and Tolerability of Acupressure versus Sham Therapy for Improving Sleep Quality in Patients with End-Stage Kidney Disease on Hemodialysis

PubMed Central

Cho, Yeoungjee; Pascoe, Elaine M.; Hawley, Carmel M.; Oliver, Veronica; Frazier, Jeremy; Jarvis, Elizabeth; Tan, Ken-Soon; Liu, Xusheng; Gobe, Glenda

2017-01-01

Objectives. To compare the effectiveness of real acupressure versus sham acupressure therapy in improving sleep quality in patients receiving hemodialysis (HD) or hemodiafiltration (HDF). Methods. A multicenter, single-blind, randomized controlled trial was conducted in two Australian dialysis units located in Princess Alexandra Hospital and Logan Hospital, respectively. Forty-two subjects with self-reported poor sleep quality were randomly assigned to real (n = 21) or sham (n = 21) acupressure therapy delivered thrice weekly for four consecutive weeks during routine dialysis sessions. The primary outcome was the Pittsburgh Sleep Quality Index (PSQI) score measured at week four adjusted for baseline PSQI measurements. Secondary outcomes were quality of life (QOL) (SF-8), adverse events, and patient acceptability (treatment acceptability questionnaire, TAQ). Results. The two groups were comparable on global PSQI scores (difference 0.19, 95% confidence interval [CI] −1.32 to 1.70) and on the subscale scores. Similar results were observed for QOL both in the mental (difference −3.88, 95% CI −8.63 to 0.87) and the physical scores (difference 2.45, 95% CI −1.69 to 6.58). There were no treatment-related adverse events and acupressure was perceived favorably by participants. Conclusion. Acupressure is a safe, well-tolerated, and highly acceptable therapy in adult hemodialysis patients in a Western healthcare setting with uncertain implications for therapeutic efficacy. PMID:28316636

Iranian family caregivers’ challenges and issues in caring of multiple sclerosis patients: A descriptive explorative qualitative study

PubMed Central

Masoudi, Reza; Abedi, Heidar Ali; Abedi, Parvin; Mohammadianinejad, Seyed Ehsan

2014-01-01

Background: The broad spectrum of problems caused by multiple sclerosis (MS) imposes heavy responsibility to caregivers in caring of their patients. Therefore, they encounter many issues and challenges in this situation. The purpose of this study was to explore the experiences and challenges of MS family caregivers. Materials and Methods: A qualitative design, based on a thematic analysis approach, was used to reach the study aim. Data were collected and analyzed concurrently through in-depth unstructured interviews, field notes, and observations that were held with 23 participants (14 family caregivers and 9 MS patients) at two referral centers in Ahvaz, Iran. Findings: Three major themes were extracted from the analysis of the transcripts: “emotional exhaustion of caregivers,” “uncertain atmosphere of caring,” and “insularity care.” The first theme consisted of three subthemes: “stressful atmosphere of caring,” “conflict and animism,” and “continuing distress affecting the caregiver.” The second theme consisted of three subthemes: “unstable and complicacy of disease,” “caring with trial and error,” and “frequent hospitalization of patients,” and the third theme consisted of two subthemes: “caring gap and disintegration” and “lack of sufficient support.” Conclusions: This study will be useful to healthcare system for managing the challenges of MS patients’ family caregivers. Improving the conditions and performance of family caregivers is crucial in order to provide high-quality care to people with MS. PMID:25183985

Intensive Hemodialysis Associates with Improved Survival Compared with Conventional Hemodialysis

PubMed Central

Lindsay, Robert M.; Cuerden, Meaghan S.; Garg, Amit X.; Port, Friedrich; Austin, Peter C.; Moist, Louise M.; Pierratos, Andreas; Chan, Christopher T.; Zimmerman, Deborah; Lockridge, Robert S.; Couchoud, Cécile; Chazot, Charles; Ofsthun, Norma; Levin, Adeera; Copland, Michael; Courtney, Mark; Steele, Andrew; McFarlane, Philip A.; Geary, Denis F.; Pauly, Robert P.; Komenda, Paul; Suri, Rita S.

2012-01-01

Patients undergoing conventional maintenance hemodialysis typically receive three sessions per week, each lasting 2.5–5.5 hours. Recently, the use of more intensive hemodialysis (>5.5 hours, three to seven times per week) has increased, but the effects of these regimens on survival are uncertain. We conducted a retrospective cohort study to examine whether intensive hemodialysis associates with better survival than conventional hemodialysis. We identified 420 patients in the International Quotidian Dialysis Registry who received intensive home hemodialysis in France, the United States, and Canada between January 2000 and August 2010. We matched 338 of these patients to 1388 patients in the Dialysis Outcomes and Practice Patterns Study who received in-center conventional hemodialysis during the same time period by country, ESRD duration, and propensity score. The intensive hemodialysis group received a mean (SD) 4.8 (1.1) sessions per week with a mean treatment time of 7.4 (0.87) hours per session; the conventional group received three sessions per week with a mean treatment time of 3.9 (0.32) hours per session. During 3008 patient-years of follow-up, 45 (13%) of 338 patients receiving intensive hemodialysis died compared with 293 (21%) of 1388 patients receiving conventional hemodialysis (6.1 versus 10.5 deaths per 100 person-years; hazard ratio, 0.55 [95% confidence interval, 0.34–0.87]). The strength and direction of the observed association between intensive hemodialysis and improved survival were consistent across all prespecified subgroups and sensitivity analyses. In conclusion, there is a strong association between intensive home hemodialysis and improved survival, but whether this relationship is causal remains unknown. PMID:22362910

Effect of tranexamic acid on intraoperative blood loss and transfusion requirements in patients undergoing excision of intracranial meningioma.

PubMed

Hooda, Bhavna; Chouhan, Rajendra Singh; Rath, Girija Prasad; Bithal, Parmod Kumar; Suri, Ashish; Lamsal, Ritesh

2017-07-01

Surgical excision of meningioma is often complicated by significant blood loss requiring blood transfusion with its attendant risks. Although tranexamic acid is used to reduce perioperative blood loss, its blood conservation effect is uncertain in neurosurgery. Sixty adults undergoing elective craniotomy for meningioma excision were randomized to receive either tranexamic acid or placebo, initiated prior to skin incision. Patients in the tranexamic acid group received intravenous bolus of 20mg/kg over 20min followed by an infusion of 1mg/kg/h till the conclusion of surgery. Intraoperative blood loss, transfusion requirements and estimation of surgical hemostasis using a 5-grade scale were noted. Postoperatively, the extent of tumor excision on CT scan and complications were observed. Demographics, tumor characteristics, amount of fluid infusion, and duration of surgery and anesthesia were comparable between the two groups. The amount of blood loss was significantly less in tranexamic acid group compared to placebo (830mlvs 1124ml; p=0.03). The transfusion requirement was less in tranexamic acid group (p>0.05). The patients in tranexamic acid group fared better on a 5-grade surgical hemostasis scale with more patients showing good hemostasis (p=0.007). There were no significant differences between the groups with regards to extent of tumor removal, perioperative complications, hospital stay or neurologic outcome. To conclude, administration of tranexamic acid significantly reduced blood loss in patients undergoing excision of meningioma. Fewer patients in the tranexamic acid group received blood transfusions. Surgical field hemostasis was better achieved in patients who received tranexamic acid. Copyright © 2017 Elsevier Ltd. All rights reserved.

Improving outcomes of hospitalized patients: the Physician Relationships, Improvising, and Sensemaking intervention protocol.

PubMed

Leykum, Luci K; Lanham, Holly J; Provost, Shannon M; McDaniel, Reuben R; Pugh, Jacqueline

2014-11-26

Our goal is to improve the safety and effectiveness of inpatient care. Rather than focus on improving process of care, we focus on the social structure within physician teams. We have developed the Physician Relationships, Improvising, and Sensemaking (PRISm) intervention to improve the way physician teams round, enabling them to better relate, make sense of their patients' conditions, and improvise in uncertain clinical situations. We are currently studying the impact of PRISm on adverse events and complications in hospitalized patients. This manuscript describes the PRISm intervention. PRISm is a structured communication tool consisting of three components: daily briefings before rounds; use of the Situation, Task, Intent, Concern, and Calibrate (STICC) framework during rounds as part of the discussion of individual patients; and debriefings after rounds. We are implementing the PRISm intervention on eight inpatient medical and surgical physician teams in the South Texas Veterans Health Care System. We are assessing PRISm impact on the way team members relate to each other, round, and discuss patients through pre- and post-implementation observations and surveys. We are also assessing PRISm impact on complications and adverse events. Finally, we are interviewing physicians regarding their experience using the intervention. Our results will allow us to begin to understand the potential impact of interventions designed to improve how providers relate to each other, improvise, and make sense of what is happening as a strategy for improving inpatient care. Our in-depth data collection will enable us to assess how relationships, improvising, and sensemaking influence patient outcomes, potentially through creating shared mental models or enhancing distributed cognition during clinical reasoning. Finally, our results will lay the groundwork for larger implementation studies to improve clinical outcomes through improving how providers, and providers, patients, and caregivers, relate.

Workarounds to Barcode Medication Administration Systems: Their Occurrences, Causes, and Threats to Patient Safety

PubMed Central

Koppel, Ross; Wetterneck, Tosha; Telles, Joel Leon; Karsh, Ben-Tzion

2008-01-01

The authors develop a typology of clinicians' workarounds when using barcoded medication administration (BCMA) systems. Authors then identify the causes and possible consequences of each workaround. The BCMAs usually consist of handheld devices for scanning machine-readable barcodes on patients and medications. They also interface with electronic medication administration records. Ideally, BCMAs help confirm the five “rights” of medication administration: right patient, drug, dose, route, and time. While BCMAs are reported to reduce medication administration errors—the least likely medication error to be intercepted— these claims have not been clearly demonstrated. The authors studied BCMA use at five hospitals by: (1) observing and shadowing nurses using BCMAs at two hospitals, (2) interviewing staff and hospital leaders at five hospitals, (3) participating in BCMA staff meetings, (4) participating in one hospital's failure-mode-and-effects analyses, (5) analyzing BCMA override log data. The authors identified 15 types of workarounds, including, for example, affixing patient identification barcodes to computer carts, scanners, doorjambs, or nurses' belt rings; carrying several patients' prescanned medications on carts. The authors identified 31 types of causes of workarounds, such as unreadable medication barcodes (crinkled, smudged, torn, missing, covered by another label); malfunctioning scanners; unreadable or missing patient identification wristbands (chewed, soaked, missing); nonbarcoded medications; failing batteries; uncertain wireless connectivity; emergencies. The authors found nurses overrode BCMA alerts for 4.2% of patients charted and for 10.3% of medications charted. Possible consequences of the workarounds include wrong administration of medications, wrong doses, wrong times, and wrong formulations. Shortcomings in BCMAs' design, implementation, and workflow integration encourage workarounds. Integrating BCMAs within real-world clinical workflows requires attention to in situ use to ensure safety features' correct use. PMID:18436903

[Benign multicystic peritoneal mesothelioma (BMPM) - a surprising differential diagnosis in case of an expected intraabdominal abscess formation].

PubMed

Lipp, Michael Josef; Jusufi, Maximilian Stanley; Backer, Christoph; Feyerabend, Bernd; Weilert, Hauke; Oldhafer, Karl Jürgen

2017-03-01

The benign multicystic peritoneal mesothelioma is a rare disease. Most frequently, young women in reproductive age are affected by this disease. Nevertheless, there are known cases of multicystic peritoneal mesothelioma in male patients. The pathogenesis remains uncertain. Whereas asbestos fibers can cause the development of malignant mesothelioma, the exposure to asbestos particles cannot induce this type of mesothelioma. An inflammatory genesis is discussed as well as the idea of a neoplastic development. Since a high rate of recurrence after surgery is observed, an aggressive surgical treatment is recommended. The complete resection of affected tissue is recently considered to be the therapy of choice. The combination of complete surgical tumor reduction with an intraperitoneal hyperthermic chemotherapy (HIPEC) seems to be promising. Although malignant transformation is detected very rarely a close follow up in centers with high surgical and oncological expertise is recommended. © Georg Thieme Verlag KG Stuttgart · New York.

Mefloquine adverse effects with atypical facial lesions in an overweight patient.

PubMed

Descloux, Elodie; De Monbrison, Frédérique; Basselin, Cécile; Vial, Thierry; Peyron, François

2010-09-01

The recommended dosage of mefloquine to treat Plasmodium falciparum infection is 25 mg/kg, with no recommendation for dosage exceeding 1500 mg. We describe an original case of adverse reaction to mefloquine in an overweight patient. Case report. A 32-year-old woman weighing 139 kg presented with uncomplicated P. falciparum infection after returning from Cameroon. She received 3250 mg of mefloquine (i.e. 23 mg/kg) administered in four doses. On day 2, she developed neuropsychiatric disorders and facial lesions. Nasal mucocutaneous vesicles and bullae, depressive mood, mild thrombocytopenia and hepatic cytolysis were evidenced. Parasitemia was negative. Recovery was complete on day 17. High mefloquine serum levels were measured (8.030 mg/L on day 3, 6.880 mg/L on day 8, and 3.370 mg/L on day 17). The causal relationship between mefloquine and the occurrence of these adverse effects is probable. However, as no viral or bacteriological investigations were performed, the drug responsibility remains uncertain. Mefloquine-induced bullous and facial lesions reversible upon drug withdrawal have already been described. The associated neuropsychiatric symptoms were strongly suggestive of mefloquine adverse effects, as such events are more frequently observed in cases of overdosage. Our case emphasizes the difficulties of dosage adaptation in overweight patients. Copyright © 2010 Elsevier Ltd. All rights reserved.

SIMPLE MEASURES ARE AS EFFECTIVE AS INVASIVE TECHNIQUES IN THE DIAGNOSIS OF PULMONARY TUBERCULOSIS IN MALAWI

PubMed Central

Bell, David J; Dacombe, Russell; Graham, Stephen M; Hicks, Alexander; Cohen, Danielle; Chikaonda, Tarsizio; French, Neil; Molyneux, Malcolm E; Zijlstra, Ed E; Squire, S Bertel; Gordon, Stephen B

2010-01-01

Setting Detection of smear-positive pulmonary tuberculosis (PTB) cases is vital for tuberculosis control. Methods to augment sputum collection are available but their additional benefit is uncertain in resource-limited settings. Objective To compare the diagnostic yields using five methods to obtain sputum from adults diagnosed with smear-negative PTB in Malawi. Design Self-expectorated sputum was collected under supervision for microscopy and mycobacterial culture in the study laboratory. Confirmed smear-negative patients, provided physiotherapy-assisted sputum and induced sputum followed, the next morning, by gastric washing and bronchoalveolar-lavage samples. Results 150 patients, diagnosed with smear-negative PTB by the hospital service, were screened. 39 (26%) were smear-positive from supervised self-expectorated sputum examined in the study laboratory. The remaining 111 confirmed smear-negative patients were enrolled; 89% were HIV positive. Seven additional smear-positive cases were diagnosed using the augmented sputum collection techniques. No differences were observed in the numbers of cases detected using the different methods. 44 (95.6%) of the 46 smear-positive cases could be detected from self-expectorated and physiotherapy-assisted samples Conclusions For countries like Malawi, the best use of limited resources to detect smear-positive PTB cases would be to improve the quality of self-expectorated sputum collection and microscopy. The additional diagnostic yield using bronchoalveolar-lavage after induced sputum is limited. PMID:19105886

Nonmelanoma skin cancer and risk of all-cause and cancer-related mortality: a systematic review.

PubMed

Barton, Virginia; Armeson, Kent; Hampras, Shalaka; Ferris, Laura K; Visvanathan, Kala; Rollison, Dana; Alberg, Anthony J

2017-05-01

Some reports suggest that a history of nonmelanoma skin cancer (NMSC) may be associated with increased mortality. NMSCs have very low fatality rates, but the high prevalence of NMSC elevates the importance of the possibility of associated subsequent mortality from other causes. The variable methods and findings of existing studies leave the significance of these results uncertain. To provide clarity, we conducted a systematic review to characterize the evidence on the associations of NMSC with: (1) all-cause mortality, (2) cancer-specific mortality, and (3) cancer survival. Bibliographic databases were searched through February 2016. Cohort studies published in English were included if adequate data were provided to estimate mortality ratios in patients with-versus-without NMSC. Data were abstracted from the total of eight studies from independent data sources that met inclusion criteria (n = 3 for all-cause mortality, n = 2 for cancer-specific mortality, and n = 5 for cancer survival). For all-cause mortality, a significant increased risk was observed for patients with a history of squamous cell carcinoma (SCC) (mortality ratio estimates (MR) 1.25 and 1.30), whereas no increased risk was observed for patients with a history of basal cell carcinoma (BCC) (MRs 0.96 and 0.97). Based on one study, the association with cancer-specific mortality was stronger for SCC (MR 2.17) than BCC (MR 1.15). Across multiple types of cancer both SCC and BCC tended to be associated with poorer survival from second primary malignancies. Multiple studies support an association between NMSC and fatal outcomes; the associations tend to be more potent for SCC than BCC. Additional investigation is needed to more precisely characterize these associations and elucidate potential underlying mechanisms.

Accuracy of ultrasound for the prediction of placenta accreta.

PubMed

Bowman, Zachary S; Eller, Alexandra G; Kennedy, Anne M; Richards, Douglas S; Winter, Thomas C; Woodward, Paula J; Silver, Robert M

2014-08-01

Ultrasound has been reported to be greater than 90% sensitive for the diagnosis of accreta. Prior studies may be subject to bias because of single expert observers, suspicion for accreta, and knowledge of risk factors. We aimed to assess the accuracy of ultrasound for the prediction of accreta. Patients with accreta at a single academic center were matched to patients with placenta previa, but no accreta, by year of delivery. Ultrasound studies with views of the placenta were collected, deidentified, blinded to clinical history, and placed in random sequence. Six investigators prospectively interpreted each study for the presence of accreta and findings reported to be associated with its diagnosis. Sensitivity, specificity, positive predictive, negative predictive value, and accuracy were calculated. Characteristics of accurate findings were compared using univariate and multivariate analyses. Six investigators examined 229 ultrasound studies from 55 patients with accreta and 56 controls for 1374 independent observations. 1205/1374 (87.7% overall, 90% controls, 84.9% cases) studies were given a diagnosis. There were 371 (27.0%) true positives; 81 (5.9%) false positives; 533 (38.8%) true negatives, 220 (16.0%) false negatives, and 169 (12.3%) with uncertain diagnosis. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 53.5%, 88.0%, 82.1%, 64.8%, and 64.8%, respectively. In multivariate analysis, true positives were more likely to have placental lacunae (odds ratio [OR], 1.5; 95% confidence interval [CI], 1.4-1.6), loss of retroplacental clear space (OR, 2.4; 95% CI, 1.1-4.9), or abnormalities on color Doppler (OR, 2.1; 95% CI, 1.8-2.4). Ultrasound for the prediction of placenta accreta may not be as sensitive as previously described. Copyright © 2014 Mosby, Inc. All rights reserved.

Impaired Left Ventricular Filling in COPD and Emphysema: Is It the Heart or the Lungs?

PubMed Central

Smith, Benjamin M.; Prince, Martin R.; Hoffman, Eric A.; Bluemke, David A.; Liu, Chia-Ying; Rabinowitz, Dan; Hueper, Katja; Parikh, Megha A.; Gomes, Antoinette S.; Michos, Erin D.; Lima, João A. C.; Barr, R. Graham

2013-01-01

Background: COPD and heart failure with preserved ejection fraction overlap clinically, and impaired left ventricular (LV) filling is commonly reported in COPD. The mechanism underlying these observations is uncertain, but may include upstream pulmonary dysfunction causing low LV preload or intrinsic LV dysfunction causing high LV preload. The objective of this study is to determine if COPD and emphysema are associated with reduced pulmonary vein dimensions suggestive of low LV preload. Methods: The population-based Multi-Ethnic Study of Atherosclerosis (MESA) COPD Study recruited smokers aged 50 to 79 years who were free of clinical cardiovascular disease. COPD was defined by spirometry. Percent emphysema was defined as regions < −910 Hounsfield units on full-lung CT scan. Ostial pulmonary vein cross-sectional area was measured by contrast-enhanced cardiac magnetic resonance and expressed as the sum of all pulmonary vein areas. Linear regression was used to adjust for age, sex, race/ethnicity, body size, and smoking. Results: Among 165 participants, the mean (± SD) total pulmonary vein area was 558 ± 159 mm2 in patients with COPD and 623 ± 145 mm2 in control subjects. Total pulmonary vein area was smaller in patients with COPD (−57 mm2; 95% CI, −106 to −7 mm2; P = .03) and inversely associated with percent emphysema (P < .001) in fully adjusted models. Significant decrements in total pulmonary vein area were observed among participants with COPD alone, COPD with emphysema on CT scan, and emphysema without spirometrically defined COPD. Conclusions: Pulmonary vein dimensions were reduced in COPD and emphysema. These findings support a mechanism of upstream pulmonary causes of underfilling of the LV in COPD and in patients with emphysema on CT scan. PMID:23764937

Congenital lobar emphysema: 30-year case series in two university hospitals*

PubMed Central

Cataneo, Daniele Cristina; Rodrigues, Olavo Ribeiro; Hasimoto, Erica Nishida; Schmidt, Aurelino Fernandes; Cataneo, Antonio José Maria

2013-01-01

OBJECTIVE: To review the cases of patients with congenital lobar emphysema (CLE) submitted to surgical treatment at two university hospitals over a 30-year period. METHODS: We reviewed the medical records of children with CLE undergoing surgical treatment between 1979 and 2009 at the Botucatu School of Medicine Hospital das Clínicas or the Mogi das Cruzes University Hospital. We analyzed data regarding symptoms, physical examination, radiographic findings, diagnosis, surgical treatment, and postoperative follow-up. RESULTS: During the period studied, 20 children with CLE underwent surgery. The mean age at the time of surgery was 6.9 months (range, 9 days to 4 years). All of the cases presented with symptoms at birth or during the first months of life. In all cases, chest X-rays were useful in defining the diagnosis. In cases of moderate respiratory distress, chest CT facilitated the diagnosis. One patient with severe respiratory distress was misdiagnosed with hypertensive pneumothorax and underwent chest tube drainage. Only patients with moderate respiratory distress were submitted to bronchoscopy, which revealed no tracheobronchial abnormalities. The surgical approach was lateral muscle-sparing thoracotomy. The left upper and middle lobes were the most often affected, followed by the right upper lobe. Lobectomy was performed in 18 cases, whereas bilobectomy was performed in 2 (together with bronchogenic cyst resection in 1 of those). No postoperative complications were observed. Postoperative follow-up time was at least 24 months (mean, 60 months), and no late complications were observed. CONCLUSIONS: Although CLE is an uncommon, still neglected disease of uncertain etiology, the radiological diagnosis is easily made and surgical treatment is effective. PMID:24068262

21 CFR 20.47 - Situations in which confidentiality is uncertain.

Code of Federal Regulations, 2011 CFR

2011-04-01

... submitted or divulged the data or information or who would be affected by disclosure before determining whether or not such data or information is available for public disclosure. [42 FR 15616, Mar. 22, 1977... uncertain. In situations where the confidentiality of data or information is uncertain and there is a...

21 CFR 20.47 - Situations in which confidentiality is uncertain.

Code of Federal Regulations, 2014 CFR

2014-04-01

... submitted or divulged the data or information or who would be affected by disclosure before determining whether or not such data or information is available for public disclosure. [42 FR 15616, Mar. 22, 1977... uncertain. In situations where the confidentiality of data or information is uncertain and there is a...

21 CFR 20.47 - Situations in which confidentiality is uncertain.

Code of Federal Regulations, 2012 CFR

2012-04-01

... submitted or divulged the data or information or who would be affected by disclosure before determining whether or not such data or information is available for public disclosure. [42 FR 15616, Mar. 22, 1977... uncertain. In situations where the confidentiality of data or information is uncertain and there is a...

21 CFR 20.47 - Situations in which confidentiality is uncertain.

Code of Federal Regulations, 2013 CFR

2013-04-01

... submitted or divulged the data or information or who would be affected by disclosure before determining whether or not such data or information is available for public disclosure. [42 FR 15616, Mar. 22, 1977... uncertain. In situations where the confidentiality of data or information is uncertain and there is a...

21 CFR 20.47 - Situations in which confidentiality is uncertain.

Code of Federal Regulations, 2010 CFR

2010-04-01

... submitted or divulged the data or information or who would be affected by disclosure before determining whether or not such data or information is available for public disclosure. [42 FR 15616, Mar. 22, 1977... uncertain. In situations where the confidentiality of data or information is uncertain and there is a...

Millennial Teachers and Multiculturalism: Considerations for Teaching in Uncertain Times

ERIC Educational Resources Information Center

Hallman, Heidi L.

2017-01-01

Purpose: This paper aims to explore the intersection of generational traits of millennial teachers, multiculturalism and teaching in an era of Uncertain Times. Uncertain Times, as a framework for the paper, characterizes changing aspects of the current era in which we live, such as the rise of the internet and interconnectivity, globalization and…

Evaluation and uncertainty analysis of regional-scale CLM4.5 net carbon flux estimates

NASA Astrophysics Data System (ADS)

Post, Hanna; Hendricks Franssen, Harrie-Jan; Han, Xujun; Baatz, Roland; Montzka, Carsten; Schmidt, Marius; Vereecken, Harry

2018-01-01

Modeling net ecosystem exchange (NEE) at the regional scale with land surface models (LSMs) is relevant for the estimation of regional carbon balances, but studies on it are very limited. Furthermore, it is essential to better understand and quantify the uncertainty of LSMs in order to improve them. An important key variable in this respect is the prognostic leaf area index (LAI), which is very sensitive to forcing data and strongly affects the modeled NEE. We applied the Community Land Model (CLM4.5-BGC) to the Rur catchment in western Germany and compared estimated and default ecological key parameters for modeling carbon fluxes and LAI. The parameter estimates were previously estimated with the Markov chain Monte Carlo (MCMC) approach DREAM(zs) for four of the most widespread plant functional types in the catchment. It was found that the catchment-scale annual NEE was strongly positive with default parameter values but negative (and closer to observations) with the estimated values. Thus, the estimation of CLM parameters with local NEE observations can be highly relevant when determining regional carbon balances. To obtain a more comprehensive picture of model uncertainty, CLM ensembles were set up with perturbed meteorological input and uncertain initial states in addition to uncertain parameters. C3 grass and C3 crops were particularly sensitive to the perturbed meteorological input, which resulted in a strong increase in the standard deviation of the annual NEE sum (σ ∑ NEE) for the different ensemble members from ˜ 2 to 3 g C m-2 yr-1 (with uncertain parameters) to ˜ 45 g C m-2 yr-1 (C3 grass) and ˜ 75 g C m-2 yr-1 (C3 crops) with perturbed forcings. This increase in uncertainty is related to the impact of the meteorological forcings on leaf onset and senescence, and enhanced/reduced drought stress related to perturbation of precipitation. The NEE uncertainty for the forest plant functional type (PFT) was considerably lower (σ ∑ NEE ˜ 4.0-13.5 g C m-2 yr-1 with perturbed parameters, meteorological forcings and initial states). We conclude that LAI and NEE uncertainty with CLM is clearly underestimated if uncertain meteorological forcings and initial states are not taken into account.

Artificial intelligence framework for simulating clinical decision-making: a Markov decision process approach.

PubMed

Bennett, Casey C; Hauser, Kris

2013-01-01

In the modern healthcare system, rapidly expanding costs/complexity, the growing myriad of treatment options, and exploding information streams that often do not effectively reach the front lines hinder the ability to choose optimal treatment decisions over time. The goal in this paper is to develop a general purpose (non-disease-specific) computational/artificial intelligence (AI) framework to address these challenges. This framework serves two potential functions: (1) a simulation environment for exploring various healthcare policies, payment methodologies, etc., and (2) the basis for clinical artificial intelligence - an AI that can "think like a doctor". This approach combines Markov decision processes and dynamic decision networks to learn from clinical data and develop complex plans via simulation of alternative sequential decision paths while capturing the sometimes conflicting, sometimes synergistic interactions of various components in the healthcare system. It can operate in partially observable environments (in the case of missing observations or data) by maintaining belief states about patient health status and functions as an online agent that plans and re-plans as actions are performed and new observations are obtained. This framework was evaluated using real patient data from an electronic health record. The results demonstrate the feasibility of this approach; such an AI framework easily outperforms the current treatment-as-usual (TAU) case-rate/fee-for-service models of healthcare. The cost per unit of outcome change (CPUC) was $189 vs. $497 for AI vs. TAU (where lower is considered optimal) - while at the same time the AI approach could obtain a 30-35% increase in patient outcomes. Tweaking certain AI model parameters could further enhance this advantage, obtaining approximately 50% more improvement (outcome change) for roughly half the costs. Given careful design and problem formulation, an AI simulation framework can approximate optimal decisions even in complex and uncertain environments. Future work is described that outlines potential lines of research and integration of machine learning algorithms for personalized medicine. Copyright © 2012 Elsevier B.V. All rights reserved.

Differential cellular localization of Epstein-Barr virus and human cytomegalovirus in the colonic mucosa of patients with active or quiescent inflammatory bowel disease.

PubMed

Ciccocioppo, Rachele; Racca, Francesca; Scudeller, Luigia; Piralla, Antonio; Formagnana, Pietro; Pozzi, Lodovica; Betti, Elena; Vanoli, Alessandro; Riboni, Roberta; Kruzliak, Peter; Baldanti, Fausto; Corazza, Gino Roberto

2016-02-01

The role of human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) in the exacerbation of inflammatory bowel disease (IBD) is still uncertain. We prospectively investigated the presence of EBV and HCMV infection in both epithelial and immune cells of colonic mucosa of IBD patients, both refractory and responders to standard therapies, in comparison with patients suffering from irritable bowel syndrome who were considered as controls, by using quantitative real-time polymerase chain reaction, immunohistochemistry and in situ hybridization, in an attempt to assess viral localization, DNA load, life cycle phase and possible correlation with disease activity indexes. We obtained clear evidence of the presence of high DNA loads of both viruses in either enterocytes or immune cells of refractory IBD patients, whereas we observed low levels in the responder group and an absence of detectable copies in all cell populations of controls. Remarkably, the values of EBV and HCMV DNA in inflamed mucosa were invariably higher than in non-inflamed areas in both IBD groups, and the EBV DNA loads in the cell populations of diseased mucosa of refractory IBD patients positively correlated with the severity of mucosal damage and clinical indexes of activity. Moreover, EBV infection resulted the most prevalent either alone or in combination with HCMV, while immunohistochemistry and in situ hybridization did not allow us to distinguish between the different phases of viral life cycle. Finally, as regards treatment, these novel findings could pave the way for the use of new antiviral molecules in the treatment of this condition.

Hashimoto thyroiditis is more frequent than expected when diagnosed by cytology which uncovers a pre-clinical state

PubMed Central

2010-01-01

Background Our Thyroid-Multidisciplinary Clinic is a large referral site for thyroid diseases. Thyroid biopsies are mainly performed for thyroid cancer screening. Yet, Hashimoto thyroiditis (HT) is being too frequently diagnosed. The prevalence of HT is reported as 0.3-1.2% or twice the prevalence of type 1 diabetes. However, the prevalence of HT confirmed by cytology is still uncertain. To evaluate different aspects of thyroid physiopathology including prevalence of Hashimoto's, a database of clinical features, ultrasound images and cytology results of patients referred for FNA of thyroid nodules was prospectively developed. Methods We retrospectively studied 811 consecutive patients for whom ultrasound guided thyroid FNA biopsies were performed at our clinic over 2.5 year period (Mar/2006-Sep/2008). Results The analysis of our database revealed that from 761 patients, 102 (13.4%) had HT, from whom 56 (7.4%) were euthyroid or had sub-clinical (non-hypothyroid) disease, and 46 (6%) were clinically hypothyroid. Conclusions This is the first study to show such a high prevalence of HT diagnosed by ultrasound-guided FNA. More strikingly, the prevalence of euthyroid HT, appears to be >5% similar to that of type 2 diabetes. Based on our results, there might be a need to follow up on cytological Hashimoto's to monitor for thyroid failure, especially in high risk states, like pregnancy. The potential risk for thyroid cancer in patients with biopsy-proven inflammation of thyroid epithelium remains to be established prospectively. However, it may explain the increased risk for thyroid cancer observed in patients with elevated but within normal TSH. PMID:21172028

Evaluation Intravenous Drip Cephazolin Prophylaxis of Breast Cancer Surgery Site Infection.

PubMed

Yang, Sufang; Liu, Guohua; Tang, Danling; Cai, De

2017-09-01

The efficacy of antibiotic prophylaxis for the prevention of surgical site infection (SSI) after breast cancer surgery remains uncertain. The authors of a recent Cochrane meta-analysis based on 15 randomized trials were unable to draw a definitive conclusion. The purpose of this study was to determine the effectiveness of prophylactic antibiotics for the prevention of SSI after breast cancer surgery and the risk factors for SSI. Breast cancer patients who underwent mastectomy at the authors' institution were enrolled in this study. All the patients give cephazolin by intravenous drip within 1 hour before surgery. Surgical site infection was defined using Centers for Disease Control criteria. Risk factors were abstracted from the electronic medical record. Pearson χ test, Student t test, and multivariable logistic regression were used for the analysis. Four hundred fifty-eight patients undergoing mastectomy were enrolled in this study, including 293 with intravenous drip cephazolin and 165 without. Among them, an overall SSI rate of 6.1% was observed; 4.2% of patients without prophylactic antibiotics developed SSI compared with 7.2% with antibiotics (P = 0.210). Factors associated with SSI were hypertension, diabetes, length of stay (d), age, and length of stay. Weight, duration of surgery, No. of drains, surgical procedure, and type of breast disease were not associated with increased SSI rates. Surgical site infection rates among patients who did and did not receive cephazolin after mastectomy had no significantly different. What is more, the authors should focus on advanced age, hypertension, diabetes, length of stay, and length of stay to decrease development of postoperative SSI rates.

Use of prophylactic postoperative antibiotics during surgical drain presence following mastectomy.

PubMed

Edwards, Brandy L; Stukenborg, George J; Brenin, David R; Schroen, Anneke T

2014-10-01

National guidelines recommend one dose of perioperative antibiotics for breast surgery and discourage postoperative continuation. However, reported skin and soft tissue infection (SSI) rates after mastectomy range from 1-26 %, higher than expected for clean cases. Utility of routine or selective postoperative antibiotic use for duration of drain presence following mastectomy remains uncertain. This study included all female patients who underwent mastectomy without reconstruction at our institution between 2005 and 2012. SSI was defined using CDC criteria or clinical diagnosis of cellulitis. Information on risk factors for infection (age, body mass index [BMI], smoking status, diabetes, steroid use), prior breast cancer treatment, drain duration, and antibiotic use was abstracted from medical records. Multivariable logistic regression was used to assess the association between postoperative antibiotic use and the occurrence of SSI, adjusting for concurrent risk factors. Among 480 patients undergoing mastectomy without reconstruction, 425 had sufficient documentation for analysis. Of these, 268 were prescribed antibiotics (63 %) at hospital discharge. An overall SSI rate of 7.3 % was observed, with 14 % of patients without postoperative antibiotics developing SSI compared with 3.4 % with antibiotics (p < 0.0001). Factors independently associated with SSI were smoking and advancing age. Diabetes, steroid use, BMI, prior breast surgery, neoadjuvant chemotherapy, prior radiation, concomitant axillary surgery, and drain duration were not associated with increased SSI rates. SSI rates among patients who did and did not receive postoperative antibiotics after mastectomy were significantly different, particularly among smokers and women of advanced age. These patient subgroups may warrant special consideration for postoperative antibiotics.

Use of Prophylactic Postoperative Antibiotics During Surgical Drain Presence Following Mastectomy

PubMed Central

Edwards, Brandy L.; Stukenborg, George J.; Brenin, David R.; Schroen, Anneke T.

2015-01-01

Background National guidelines recommend one dose of perioperative antibiotics for breast surgery and discourage postoperative continuation. However, reported skin and soft tissue infection (SSI) rates after mastectomy range from 1–26 %, higher than expected for clean cases. Utility of routine or selective postoperative antibiotic use for duration of drain presence following mastectomy remains uncertain. Methods This study included all female patients who underwent mastectomy without reconstruction at our institution between 2005 and 2012. SSI was defined using CDC criteria or clinical diagnosis of cellulitis. Information on risk factors for infection (age, body mass index [BMI], smoking status, diabetes, steroid use), prior breast cancer treatment, drain duration, and antibiotic use was abstracted from medical records. Multivariable logistic regression was used to assess the association between postoperative antibiotic use and the occurrence of SSI, adjusting for concurrent risk factors. Results Among 480 patients undergoing mastectomy without reconstruction, 425 had sufficient documentation for analysis. Of these, 268 were prescribed antibiotics (63 %) at hospital discharge. An overall SSI rate of 7.3 % was observed, with 14 % of patients without postoperative antibiotics developing SSI compared with 3.4 % with antibiotics (p < 0.0001). Factors independently associated with SSI were smoking and advancing age. Diabetes, steroid use, BMI, prior breast surgery, neoadjuvant chemotherapy, prior radiation, concomitant axillary surgery, and drain duration were not associated with increased SSI rates. Conclusions SSI rates among patients who did and did not receive postoperative antibiotics after mastectomy were significantly different, particularly among smokers and women of advanced age. These patient subgroups may warrant special consideration for postoperative antibiotics. PMID:25138078

Clinical characteristics of hospital-onset Pneumocystis pneumonia and genotypes of Pneumocystis jirovecii in a single tertiary centre in Korea.

PubMed

Kim, Tark; Lee, Sang-Oh; Hong, Hyo-Lim; Lee, Ju Young; Kim, Sung-Han; Choi, Sang-Ho; Kim, Mi-Na; Kim, Yang Soo; Woo, Jun Hee; Sung, Heungsup

2015-02-26

Pneumocystis pneumonia (PCP) may develop as a clinical manifestation of nosocomial pneumonia by means of either reactivation of resident P. jirovecii or de novo infection. However, there have been no studies describing the clinical characteristics of hospital-onset PCP. A retrospective review of medical records was performed to identify episodes of hospital-onset PCP in a tertiary care centre in Korea between May 2007 and January 2013. We investigated whether human-to-human contact during hospitalisation contributed to PCP development by molecular analysis of the genes encoding mitochondrial large ribosomal subunit (mtLSU) rRNA and dihydropteroate synthase (DHPS) and a review of hospitalisation history. During the study period, 129 patients (130 episodes) were diagnosed with PCP. Of these, respiratory specimens from 94 patients during 95 PCP episodes were available for analysis. Sixteen episodes (16.8%) were categorised as hospital-onset PCP. There was a trend toward a higher proportion of haematological malignancy (43.8% [7/16] vs. 20.3% [16/79]; P = 0.058) in patients with hospital-onset PCP compared to patients with community-onset PCP. mtLSU genotype 1 was the most common, occurring in 41 (43.2%) patients. There were four possible cases of nosocomial transmission. Mutation in DHPS was not observed in any PCP episode. PCP can be one of the causes of nosocomial pneumonia, although the mode of acquisition and transmission of P. jirovecii remains uncertain. mtLSU genotype 1 is the predominant P. jirovecii strain in Korea.

Probable Diagnosis of a Patient with Niemann-Pick Disease Type C: Managing Pitfalls of Exome Sequencing.

PubMed

Zeiger, William A; Jamal, Nasheed I; Scheuner, Maren T; Pittman, Patricia; Raymond, Kimiyo M; Morra, Massimo; Mishra, Shri K

2018-02-17

Here, we present a case of a 31-year-old man with progressive cognitive decline, ataxia, and dystonia. Extensive laboratory, radiographic, and targeted genetic studies over the course of several years failed to yield a diagnosis. Initial whole exome sequencing through a commercial laboratory identified several variants of uncertain significance; however, follow-up clinical examination and testing ruled each of these out. Eventually, repeat whole exome sequencing identified a known pathogenic intronic variant in the NPC1 gene (NM_000271.4, c.1554-1009G>A) and an additional heterozygous exonic variant of uncertain significance in the NPC1 gene (NM_000271.4, c.2524T>C). Follow-up biochemical testing was consistent with a diagnosis of probable Niemann-Pick disease Type C (NP-C). This case illustrates the potential of whole exome sequencing for diagnosing rare complex neurologic diseases. It also identifies several potential common pitfalls that must be navigated by clinicians when interpreting commercial whole exome sequencing results.

Morcellator's Port-site Metastasis of a Uterine Smooth Muscle Tumor of Uncertain Malignant Potential After Minimally Invasive Myomectomy.

PubMed

Bogani, Giorgio; Ditto, Antonino; Martinelli, Fabio; Signorelli, Mauro; Chiappa, Valentina; Lorusso, Domenica; Sabatucci, Ilaria; Carcangiu, Maria L; Fiore, Marco; Gronchi, Alessandro; Raspagliesi, Francesco

2016-01-01

Since the safety warning from the US Food and Drug Administration on the use of power morcellators, minimally invasive procedures involving the removal of uterine myomas and large uteri are under scrutiny. Growing evidence suggests that morcellation of undiagnosed uterine malignancies is associated with worse survival outcomes of patients affected by uterine sarcoma. However, to date, only limited data regarding morcellation of low-grade uterine neoplasms are available. In the present article, we reported a case of a (morcellator) port-site implantation of a smooth muscle tumor that occurred 6 years after laparoscopic morcellation of a uterine smooth muscle tumor of uncertain potential. This case highlights the effects of intra-abdominal morcellation, even in low-grade uterine neoplasms. Caution should be used when determining techniques for tissue extraction; the potential adverse consequences of morcellation should be more fully explored. Copyright © 2016 AAGL. Published by Elsevier Inc. All rights reserved.

Occupational Asthma in Antibiotic Manufacturing Workers: Case Reports and Systematic Review

PubMed Central

Díaz Angulo, Sara; Szram, Joanna; Welch, Jenny; Cannon, Julie; Cullinan, Paul

2011-01-01

Background. The risks of occupational asthma (OA) from antibiotics are uncertain. We report 4 new cases and a systematic review of the literature. Methods. Cases were identified through a specialist clinic, each underwent specific provocation testing (SPT). We subsequently reviewed the published literature. Results. The patients were employed in the manufacture of antibiotics; penicillins were implicated in three cases, in the fourth erythromycin, not previously reported to cause OA. In two, there was evidence of specific IgE sensitisation. At SPT each developed a late asthmatic reaction and increased bronchial hyperresponsiveness. 36 case reports have been previously published, 26 (citing penicillins or cephalosporins). Seven cross-sectional workplace-based surveys found prevalences of 5–8%. Conclusions. OA in antibiotic manufacturers may be more common than is generally recognised. Its pathogenesis remains unclear; immunological tests are of uncertain value and potential cases require confirmation with SPT. Further study of its frequency, mechanisms, and diagnosis is required. PMID:21603168

Erlotinib Versus Radiation Therapy for Brain Metastases in Patients With EGFR-Mutant Lung Adenocarcinoma

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

Gerber, Naamit K.; Yamada, Yoshiya; Rimner, Andreas

2014-06-01

Purpose/Objectives: Radiation therapy (RT) is the principal modality in the treatment of patients with brain metastases (BM). However, given the activity of EGFR tyrosine kinase inhibitors in the central nervous system, it is uncertain whether upfront brain RT is necessary for patients with EGFR-mutant lung adenocarcinoma with BM. Methods and Materials: Patients with EGFR-mutant lung adenocarcinoma and newly diagnosed BM were identified. Results: 222 patients were identified. Exclusion criteria included prior erlotinib use, presence of a de novo erlotinib resistance mutation, or incomplete data. Of the remaining 110 patients, 63 were treated with erlotinib, 32 with whole brain RT (WBRT), andmore » 15 with stereotactic radiosurgery (SRS). The median overall survival (OS) for the whole cohort was 33 months. There was no significant difference in OS between the WBRT and erlotinib groups (median, 35 vs 26 months; P=.62), whereas patients treated with SRS had a longer OS than did those in the erlotinib group (median, 64 months; P=.004). The median time to intracranial progression was 17 months. There was a longer time to intracranial progression in patients who received WBRT than in those who received erlotinib upfront (median, 24 vs 16 months, P=.04). Patients in the erlotinib or SRS group were more likely to experience intracranial failure as a component of first failure, whereas WBRT patients were more likely to experience failure outside the brain (P=.004). Conclusions: The survival of patients with EGFR-mutant adenocarcinoma with BM is notably long, whether they receive upfront erlotinib or brain RT. We observed longer intracranial control with WBRT, even though the WBRT patients had a higher burden of intracranial disease. Despite the equivalent survival between the WBRT and erlotinib group, this study underscores the role of WBRT in producing durable intracranial control in comparison with a targeted biologic agent with known central nervous system activity.« less

Effect of music therapy on oncologic staff bystanders: a substantive grounded theory.

PubMed

O'Callaghan, Clare; Magill, Lucanne

2009-06-01

Oncologic work can be satisfying but also stressful, as staff support patients and families through harsh treatment effects, uncertain illness trajectories, and occasional death. Although formal support programs are available, no research on the effects of staff witnessing patients' supportive therapies exists. This research examines staff responses to witnessing patient-focused music therapy (MT) programs in two comprehensive cancer centers. In Study 1, staff were invited to anonymously complete an open-ended questionnaire asking about the relevance of a music therapy program for patients and visitors (what it does; whether it helps). In Study 2, staff were theoretically sampled and interviewed regarding the personal effects of witnessing patient-centered music therapy. Data from each study were comparatively analyzed according to grounded theory procedures. Positive and negative cases were evident and data saturation arguably achieved. In Study 1, 38 staff unexpectedly described personally helpful emotional, cognitive, and team effects and consequent improved patient care. In Study 2, 62 staff described 197 multiple personal benefits and elicited patient care improvements. Respondents were mostly nursing (57) and medical (13) staff. Only three intrusive effects were reported: audibility, initial suspicion, and relaxation causing slowing of work pace. A substantive grounded theory emerged applicable to the two cancer centers: Staff witnessing MT can experience personally helpful emotions, moods, self-awarenesses, and teamwork and thus perceive improved patient care. Intrusive effects are uncommon. Music therapy's benefits for staff are attributed to the presence of live music, the human presence of the music therapist, and the observed positive effects in patients and families. Patient-centered oncologic music therapy in two cancer centers is an incidental supportive care modality for staff, which can reduce their stress and improve work environments and perceived patient care. Further investigation of the incidental benefits for oncologic staff witnessing patient-centered MT, through interpretive and positivist measures, is warranted.

Association of the hOGG1 Ser326Cys polymorphism with sporadic amyotrophic lateral sclerosis.

PubMed

Coppedè, Fabio; Mancuso, Michelangelo; Lo Gerfo, Annalisa; Carlesi, Cecilia; Piazza, Selina; Rocchi, Anna; Petrozzi, Lucia; Nesti, Claudia; Micheli, Dario; Bacci, Andrea; Migliore, Lucia; Murri, Luigi; Siciliano, Gabriele

2007-06-13

Amyotropic lateral sclerosis (ALS) is a fatal and progressive neurodegenerative disease causing the loss of motoneurons of the brain and the spinal cord. The etiology of ALS is still uncertain, but males are at increased risk for the disease than females. Several studies have suggested that motoneurons in ALS might be subjected to the double insult of increased DNA oxidative damage and deficiencies in DNA repair systems. Particularly, increased levels of 8-oxoguanine and impairments of the DNA base excision repair system have been observed in neurons of ALS patients. There is evidence that the Ser326Cys polymorphism of the human 8-oxoguanine DNA glycosylase 1 (hOGG1) gene is associated with a reduced DNA repair activity. To evaluate the role of the hOGG1 Ser326Cys polymorphism in sporadic ALS (sALS), we screened 136 patients and 129 matched controls. In the total population, we observed association between both the Cys326 allele (p=0.02) and the combined Ser326Cys+Cys326Cys genotype (OR=1.65, 95% CI=1.06-2.88) and increased risk of disease. After stratification by gender, the Cys326 allele (p=0.01), both the Ser326Cys genotype (OR=2.14, 95% CI=1.09-4.19) and the combined Ser326Cys+Cys326Cys genotype (OR=2.15, 95% CI=1.16-4.01) were associated with sALS risk only in males. No significant association between the Ser326Cys polymorphism and disease phenotype, including age and site of onset and disease progression, was observed. Present results suggest a possible involvement of the hOGG1 Ser326Cys polymorphism in sALS pathogenesis.

Increased brain serotonin turnover in panic disorder patients in the absence of a panic attack: reduction by a selective serotonin reuptake inhibitor.

PubMed

Esler, Murray; Lambert, Elisabeth; Alvarenga, Marlies; Socratous, Florentia; Richards, Jeff; Barton, David; Pier, Ciaran; Brenchley, Celia; Dawood, Tye; Hastings, Jacqueline; Guo, Ling; Haikerwal, Deepak; Kaye, David; Jennings, Garry; Kalff, Victor; Kelly, Michael; Wiesner, Glen; Lambert, Gavin

2007-08-01

Since the brain neurotransmitter changes characterising panic disorder remain uncertain, we quantified brain noradrenaline and serotonin turnover in patients with panic disorder, in the absence of a panic attack. Thirty-four untreated patients with panic disorder and 24 matched healthy volunteers were studied. A novel method utilising internal jugular venous sampling, with thermodilution measurement of jugular blood flow, was used to directly quantify brain monoamine turnover, by measuring the overflow of noradrenaline and serotonin metabolites from the brain. Radiographic depiction of brain venous sinuses allowed differential venous sampling from cortical and subcortical regions. The relation of brain serotonin turnover to serotonin transporter genotype and panic disorder severity were evaluated, and the influence of an SSRI drug, citalopram, on serotonin turnover investigated. Brain noradrenaline turnover in panic disorder patients was similar to that in healthy subjects. In contrast, brain serotonin turnover, estimated from jugular venous overflow of the metabolite, 5-hydroxyindole acetic acid, was increased approximately 4-fold in subcortical brain regions and in the cerebral cortex (P < 0.01). Serotonin turnover was highest in patients with the most severe disease, was unrelated to serotonin transporter genotype, and was reduced by citalopram (P < 0.01). Normal brain noradrenaline turnover in panic disorder patients argues against primary importance of the locus coeruleus in this condition. The marked increase in serotonin turnover, in the absence of a panic attack, possibly represents an important underlying neurotransmitter substrate for the disorder, although this point remains uncertain. Support for this interpretation comes from the direct relationship which existed between serotonin turnover and illness severity, and the finding that SSRI administration reduced serotonin turnover. Serotonin transporter genotyping suggested that increased whole brain serotonin turnover most likely derived not from impaired serotonin reuptake, but from increased firing in serotonergic midbrain raphe neurons projecting to both subcortical brain regions and the cerebral cortex.

REDOSER project: optimising biological therapy dose for rheumatoid arthritis and spondyloarthritis patients.

PubMed

González-Álvaro, Isidoro; Blasco, Antonio J; Lázaro, Pablo; Sánchez-Piedra, Carlos; Almodovar, Raquel; Bachiller-Corral, Javier; Balsa, Alejandro; Caliz, Rafael; Candelas, Gloria; Fernández-Carballido, Cristina; García-Aparicio, Angel; García-Magallón, Blanca; García-Vicuña, Rosario; Gómez-Centeno, Antonio; Ortiz, Ana M; Sanmartí, Raimon; Sanz, Jesús; Tejera, Beatriz

2017-11-01

Reducing the dose of biological therapy (BT) when patients with immune-mediated arthritis achieve a sustained therapeutic goal may help to decrease costs for national health services and reduce the risk of serious infection. However, there is little information about whether such a decision can be applied universally. Therefore, the objective of this study was to develop appropriateness criteria for reducing the dose of BT in patients with rheumatoid arthritis (RA), axial spondyloarthritis (axSpA), and peripheral spondyloarthritis (pSpA). The RAND/UCLA appropriateness method was coordinated by experts in the methodology. Five rheumatologists with clinical research experience in RA and/or SpA selected and precisely defined the variables considered relevant when deciding to reduce the dose of BT in the 3 diseases, in order to define patient profiles. Ten rheumatologists with experience in prescribing BT anonymously rated each profile on a scale of 1 (completely inappropriate) to 9 (completely appropriate) after revising a summary of the evidence obtained from 4 systematic literature reviews carried out specifically for this project. A total of 2,304 different profiles were obtained for RA, 768 for axSpA, and 3,072 for pSpA. Only 327 (14.2%) patient profiles in RA, 80 (10.4%) in axSpA, and 154 (5%) in pSpA were considered appropriate for reducing the dose of BT. By contrast, 749 (32.5%) patient profiles in RA, 270 (35.3%) in axSpA, and 1,243 (40.5%) in pSpA were considered inappropriate. The remaining profiles were considered uncertain. Appropriateness criteria for reducing the dose of BT were developed in 3 inflammatory conditions. These criteria can help clinicians treating these disorders to optimize the BT dose. However, further research is needed, since more than 50% of the profiles were considered uncertain and the real prevalence of each profile in daily clinical practice remains unknown.

Dread of uncertain pain: An event-related potential study

PubMed Central

Huang, Yujing; Shang, Qian; Dai, Shenyi; Ma, Qingguo

2017-01-01

Humans experience more stress about uncertain situations than certain situations. However, the neural mechanism underlying the uncertainty of a negative stimulus has not been determined. In the present study, event-related potential was recorded to examine neural responses during the dread of unpredictable pain. We used a cueing paradigm in which predictable cues were always followed by electric shocks, unpredictable cues by electric shocks at a 50/50 ratio and safe cues by no electric shock. Visual analogue scales following electric shocks were presented to quantify subjective anxiety levels. The behavioral results showed that unpredictable cues evoked high-level anxiety compared with predictable cues in both painful and unpainful stimulation conditions. More importantly, the ERPs results revealed that unpredictable cues elicited a larger P200 at parietal sites than predictable cues. In addition, unpredictable cues evoked larger P200 compared with safe cues at frontal electrodes and compared with predictable cues at parietal electrodes. In addition, larger P3b and LPP were observed during perception of safe cues compared with predictable cues at frontal and central electrodes. The similar P3b effect was also revealed in the left sites. The present study underlined that the uncertain dread of pain was associated with threat appraisal process in pain system. These findings on early event-related potentials were significant for a neural marker and development of therapeutic interventions. PMID:28832607

Control of linear uncertain systems utilizing mismatched state observers

NASA Technical Reports Server (NTRS)

Goldstein, B.

1972-01-01

The control of linear continuous dynamical systems is investigated as a problem of limited state feedback control. The equations which describe the structure of an observer are developed constrained to time-invarient systems. The optimal control problem is formulated, accounting for the uncertainty in the design parameters. Expressions for bounds on closed loop stability are also developed. The results indicate that very little uncertainty may be tolerated before divergence occurs in the recursive computation algorithms, and the derived stability bound yields extremely conservative estimates of regions of allowable parameter variations.

The importance of proper bioinformatics analysis and clinical interpretation of tumor genomic profiling: a case study of undifferentiated sarcoma and a constitutional pathogenic BRCA2 mutation and an MLH1 variant of uncertain significance.

PubMed

Varga, Elizabeth; Chao, Elizabeth C; Yeager, Nicholas D

2015-09-01

Next-generation sequencing (NGS) technology is increasingly utilized to identify therapeutic targets for patients with malignancy. This technology also has the capability to reveal the presence of constitutional genetic alterations, which may have significant implications for patients and their family members. Here we present the case of a 23 year old Caucasian patient with recurrent undifferentiated sarcoma who had NGS-based tumor analysis using an assay which simultaneously analyzed the entire coding sequence of 236 cancer-related genes (3769 exons) plus 47 introns from 19 genes often rearranged or altered in cancer. Pathogenic alterations were reported in tumor as the predicted protein alterations, BRCA2 "R645fs*15″ and MLH1 "E694*". Because constitutional BRCA2 and MLH1 gene mutations are associated with Hereditary Breast Ovarian Cancer Syndrome (HBOCS) and Lynch syndrome respectively, sequence analysis of DNA isolated from peripheral blood was performed. The presence of the alterations, BRCA2 c.1929delG and MLH1 c.2080G>T, corresponding to the previously reported predicted protein alterations, were confirmed by Sanger sequencing in the constitutional DNA. An additional DNA finding was reported in this analysis, MLH1 c.2081A>C at the neighboring nucleotide. Further evaluation of the family revealed that all alterations were paternally inherited and the two MLH1 substitutions were in cis, more appropriately referred to as MLH1 c.2080_2081delGAinsTC, which is classified as a variant of uncertain significance. This case illustrates important considerations related to appropriate interpretation of NGS tumor results and follow-up of patients with potentially deleterious constitutional alterations.

Improving care for patients whose recovery is uncertain. The AMBER care bundle: design and implementation.

PubMed

Carey, Irene; Shouls, Susanna; Bristowe, Katherine; Morris, Michelle; Briant, Linda; Robinson, Carole; Caulkin, Ruth; Griffiths, Mathew; Clark, Kieron; Koffman, Jonathan; Hopper, Adrian

2015-03-01

Despite preferences to the contrary, 53% of deaths in England occur in hospital. Difficulties in managing clinical uncertainty can result in delayed recognition that a person may be approaching the end of life, and a failure to address his/her preferences. Planning and shared decision-making for hospital patients need to improve where an underlying condition responds poorly to acute medical treatment and there is a risk of dying in the next 1-2 months. This paper suggests an approach to improve this care. A care bundle (the AMBER care bundle) was designed by a multiprofessional development team, which included service users, utilising the model for improvement following an initial scoping exercise. The care bundle includes two identification questions, four subsequent time restricted actions and systematic daily follow-up. This paper describes the development and implementation of a care bundle. From August 2011 to July 2012, 638 patients received care supported by the AMBER care bundle. In total 42.8% died in hospital and a further 14.5% were readmitted as emergencies within 30 days of discharge. Clinical outcome measures are in development. It has been possible to develop a care bundle addressing a complex area of care which can be a lever for cultural change. The implementation of the AMBER care bundle has the potential to improve care of clinically uncertain hospital patients who may be approaching the end of life by supporting their recognition and prompting discussion of their preferences. Outcomes associated with its use are currently being formally evaluated. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Improving care for patients whose recovery is uncertain. The AMBER care bundle: design and implementation.

PubMed

Carey, Irene; Shouls, Susanna; Bristowe, Katherine; Morris, Michelle; Briant, Linda; Robinson, Carole; Caulkin, Ruth; Griffiths, Mathew; Clark, Kieron; Koffman, Jonathan; Hopper, Adrian

2015-12-01

Despite preferences to the contrary, 53% of deaths in England occur in hospital. Difficulties in managing clinical uncertainty can result in delayed recognition that a person may be approaching the end of life, and a failure to address his/her preferences. Planning and shared decision-making for hospital patients need to improve where an underlying condition responds poorly to acute medical treatment and there is a risk of dying in the next 1-2 months. This paper suggests an approach to improve this care. A care bundle (the AMBER care bundle) was designed by a multiprofessional development team, which included service users, utilising the model for improvement following an initial scoping exercise. The care bundle includes two identification questions, four subsequent time restricted actions and systematic daily follow-up. This paper describes the development and implementation of a care bundle. From August 2011 to July 2012, 638 patients received care supported by the AMBER care bundle. In total 42.8% died in hospital and a further 14.5% were readmitted as emergencies within 30 days of discharge. Clinical outcome measures are in development. It has been possible to develop a care bundle addressing a complex area of care which can be a lever for cultural change. The implementation of the AMBER care bundle has the potential to improve care of clinically uncertain hospital patients who may be approaching the end of life by supporting their recognition and prompting discussion of their preferences. Outcomes associated with its use are currently being formally evaluated. 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/

Randomized controlled trial of a video decision support tool for cardiopulmonary resuscitation decision making in advanced cancer.

PubMed

Volandes, Angelo E; Paasche-Orlow, Michael K; Mitchell, Susan L; El-Jawahri, Areej; Davis, Aretha Delight; Barry, Michael J; Hartshorn, Kevan L; Jackson, Vicki Ann; Gillick, Muriel R; Walker-Corkery, Elizabeth S; Chang, Yuchiao; López, Lenny; Kemeny, Margaret; Bulone, Linda; Mann, Eileen; Misra, Sumi; Peachey, Matt; Abbo, Elmer D; Eichler, April F; Epstein, Andrew S; Noy, Ariela; Levin, Tomer T; Temel, Jennifer S

2013-01-20

Decision making regarding cardiopulmonary resuscitation (CPR) is challenging. This study examined the effect of a video decision support tool on CPR preferences among patients with advanced cancer. We performed a randomized controlled trial of 150 patients with advanced cancer from four oncology centers. Participants in the control arm (n = 80) listened to a verbal narrative describing CPR and the likelihood of successful resuscitation. Participants in the intervention arm (n = 70) listened to the identical narrative and viewed a 3-minute video depicting a patient on a ventilator and CPR being performed on a simulated patient. The primary outcome was participants' preference for or against CPR measured immediately after exposure to either modality. Secondary outcomes were participants' knowledge of CPR (score range of 0 to 4, with higher score indicating more knowledge) and comfort with video. The mean age of participants was 62 years (standard deviation, 11 years); 49% were women, 44% were African American or Latino, and 47% had lung or colon cancer. After the verbal narrative, in the control arm, 38 participants (48%) wanted CPR, 41 (51%) wanted no CPR, and one (1%) was uncertain. In contrast, in the intervention arm, 14 participants (20%) wanted CPR, 55 (79%) wanted no CPR, and 1 (1%) was uncertain (unadjusted odds ratio, 3.5; 95% CI, 1.7 to 7.2; P < .001). Mean knowledge scores were higher in the intervention arm than in the control arm (3.3 ± 1.0 v 2.6 ± 1.3, respectively; P < .001), and 65 participants (93%) in the intervention arm were comfortable watching the video. Participants with advanced cancer who viewed a video of CPR were less likely to opt for CPR than those who listened to a verbal narrative.

Study of the Therapeutic Effects of Intercessory Prayer (STEP) in cardiac bypass patients: a multicenter randomized trial of uncertainty and certainty of receiving intercessory prayer.

PubMed

Benson, Herbert; Dusek, Jeffery A; Sherwood, Jane B; Lam, Peter; Bethea, Charles F; Carpenter, William; Levitsky, Sidney; Hill, Peter C; Clem, Donald W; Jain, Manoj K; Drumel, David; Kopecky, Stephen L; Mueller, Paul S; Marek, Dean; Rollins, Sue; Hibberd, Patricia L

2006-04-01

Intercessory prayer is widely believed to influence recovery from illness, but claims of benefits are not supported by well-controlled clinical trials. Prior studies have not addressed whether prayer itself or knowledge/certainty that prayer is being provided may influence outcome. We evaluated whether (1) receiving intercessory prayer or (2) being certain of receiving intercessory prayer was associated with uncomplicated recovery after coronary artery bypass graft (CABG) surgery. Patients at 6 US hospitals were randomly assigned to 1 of 3 groups: 604 received intercessory prayer after being informed that they may or may not receive prayer; 597 did not receive intercessory prayer also after being informed that they may or may not receive prayer; and 601 received intercessory prayer after being informed they would receive prayer. Intercessory prayer was provided for 14 days, starting the night before CABG. The primary outcome was presence of any complication within 30 days of CABG. Secondary outcomes were any major event and mortality. In the 2 groups uncertain about receiving intercessory prayer, complications occurred in 52% (315/604) of patients who received intercessory prayer versus 51% (304/597) of those who did not (relative risk 1.02, 95% CI 0.92-1.15). Complications occurred in 59% (352/601) of patients certain of receiving intercessory prayer compared with the 52% (315/604) of those uncertain of receiving intercessory prayer (relative risk 1.14, 95% CI 1.02-1.28). Major events and 30-day mortality were similar across the 3 groups. Intercessory prayer itself had no effect on complication-free recovery from CABG, but certainty of receiving intercessory prayer was associated with a higher incidence of complications.

Physicians' Attitudes About Multiplex Tumor Genomic Testing

PubMed Central

Gray, Stacy W.; Hicks-Courant, Katherine; Cronin, Angel; Rollins, Barrett J.; Weeks, Jane C.

2014-01-01

Purpose Although predictive multiplex somatic genomic tests hold the potential to transform care by identifying targetable alterations in multiple cancer genes, little is known about how physicians will use such tests in practice. Participants and Methods Before the initiation of enterprise-wide multiplex testing at a major cancer center, we surveyed all clinically active adult cancer physicians to assess their current use of somatic testing, their attitudes about multiplex testing, and their genomic confidence. Results A total of 160 physicians participated (response rate, 61%): 57% were medical oncologists; 29%, surgeons; 14% radiation oncologists; 37%, women; and 83%, research principal investigators. Twenty-two percent of physicians reported low confidence in their genomic knowledge. Eighteen percent of physicians anticipated testing patients infrequently (≤ 10%), whereas 25% anticipate testing most patients (≥ 90%). Higher genomic confidence was associated with wanting to test a majority of patients (adjusted odds ratio [OR], 6.09; 95% CI, 2.1 to 17.5) and anticipating using actionable (adjusted OR, 2.46; 95% CI, 1.2 to 5.2) or potentially actionable (adjusted OR, 2.89; 95% CI, 1.1 to 7.9) test results to inform treatment recommendations. Forty-two percent of physicians endorsed disclosure of uncertain genomic findings to patients. Conclusion Physicians at a tertiary-care National Cancer Institute–designated comprehensive cancer center varied considerably in how they planned to incorporate predictive multiplex somatic genomic tests into practice and in their attitudes about the disclosure of genomic information of uncertain significance. Given that many physicians reported low genomic confidence, evidence-based guidelines and enhanced physician genomic education efforts may be needed to ensure that genomically guided cancer care is adequately delivered. PMID:24663044

40 CFR 725.15 - Determining applicability when microorganism identity or use is confidential or uncertain.

Code of Federal Regulations, 2010 CFR

2010-07-01

... microorganism identity or use is confidential or uncertain. 725.15 Section 725.15 Protection of Environment... microorganism identity or use is confidential or uncertain. (a) Consulting EPA. Persons intending to conduct... on the Inventory, in § 725.239 or in subpart M of this part. (1) Confidential identity or use. In...

40 CFR 725.15 - Determining applicability when microorganism identity or use is confidential or uncertain.

Code of Federal Regulations, 2012 CFR

2012-07-01

... microorganism identity or use is confidential or uncertain. 725.15 Section 725.15 Protection of Environment... microorganism identity or use is confidential or uncertain. (a) Consulting EPA. Persons intending to conduct... on the Inventory, in § 725.239 or in subpart M of this part. (1) Confidential identity or use. In...

40 CFR 725.15 - Determining applicability when microorganism identity or use is confidential or uncertain.

Code of Federal Regulations, 2014 CFR

2014-07-01

... microorganism identity or use is confidential or uncertain. 725.15 Section 725.15 Protection of Environment... microorganism identity or use is confidential or uncertain. (a) Consulting EPA. Persons intending to conduct... on the Inventory, in § 725.239 or in subpart M of this part. (1) Confidential identity or use. In...

40 CFR 725.15 - Determining applicability when microorganism identity or use is confidential or uncertain.

Code of Federal Regulations, 2013 CFR

2013-07-01

... microorganism identity or use is confidential or uncertain. 725.15 Section 725.15 Protection of Environment... microorganism identity or use is confidential or uncertain. (a) Consulting EPA. Persons intending to conduct... on the Inventory, in § 725.239 or in subpart M of this part. (1) Confidential identity or use. In...

40 CFR 725.15 - Determining applicability when microorganism identity or use is confidential or uncertain.

Code of Federal Regulations, 2011 CFR

2011-07-01

... microorganism identity or use is confidential or uncertain. 725.15 Section 725.15 Protection of Environment... microorganism identity or use is confidential or uncertain. (a) Consulting EPA. Persons intending to conduct... on the Inventory, in § 725.239 or in subpart M of this part. (1) Confidential identity or use. In...

Sex chromosome aneuploidies and copy-number variants: a further explanation for neurodevelopmental prognosis variability?

PubMed

Le Gall, Jessica; Nizon, Mathilde; Pichon, Olivier; Andrieux, Joris; Audebert-Bellanger, Séverine; Baron, Sabine; Beneteau, Claire; Bilan, Frédéric; Boute, Odile; Busa, Tiffany; Cormier-Daire, Valérie; Ferec, Claude; Fradin, Mélanie; Gilbert-Dussardier, Brigitte; Jaillard, Sylvie; Jønch, Aia; Martin-Coignard, Dominique; Mercier, Sandra; Moutton, Sébastien; Rooryck, Caroline; Schaefer, Elise; Vincent, Marie; Sanlaville, Damien; Le Caignec, Cédric; Jacquemont, Sébastien; David, Albert; Isidor, Bertrand

2017-08-01

Sex chromosome aneuploidies (SCA) is a group of conditions in which individuals have an abnormal number of sex chromosomes. SCA, such as Klinefelter's syndrome, XYY syndrome, and Triple X syndrome are associated with a large range of neurological outcome. Another genetic event such as another cytogenetic abnormality may explain a part of this variable expressivity. In this study, we have recruited fourteen patients with intellectual disability or developmental delay carrying SCA associated with a copy-number variant (CNV). In our cohort (four patients 47,XXY, four patients 47,XXX, and six patients 47,XYY), seven patients were carrying a pathogenic CNV, two a likely pathogenic CNV and five a variant of uncertain significance. Our analysis suggests that CNV might be considered as an additional independent genetic factor for intellectual disability and developmental delay for patients with SCA and neurodevelopmental disorder.

A retrospective cohort study of patients treated with anti-tuberculous therapy for presumed ocular tuberculosis.

PubMed

Damato, Erika Marie; Dawson, Sarah; Liu, Xiaoxuan; Mukherjee, Chandoshi; Horsburgh, John; Denniston, Alastair K; Moran, Edward; Dedicoat, Martin; Murray, Philip Ian

2017-12-04

Uveitis involving the posterior segment is a significant and potentially blinding condition. The diagnosis and treatment of patients with uveitis associated with tuberculosis remains controversial, and commonly, patients are systemically well. Use of the interferon-gamma release assays has added to the controversy, as the significance of a positive test may be uncertain. We aim to report the outcomes of anti-tuberculous treatment in a cohort of patients treated in Birmingham, for presumed "ocular tuberculosis", based on clinical findings, systemic assessment and specific testing for tuberculosis. We found that in our cohort of 41 patients treated between 2010 and 2014, the majority achieved disease-free remission, even in cases where anti-tuberculous treatment was delayed. Despite controversy, this study strongly supports the use of anti-tuberculous therapy in such patients and highlights the need for formal prospective trials and treatment protocols.

Possible world based consistency learning model for clustering and classifying uncertain data.

PubMed

Liu, Han; Zhang, Xianchao; Zhang, Xiaotong

2018-06-01

Possible world has shown to be effective for handling various types of data uncertainty in uncertain data management. However, few uncertain data clustering and classification algorithms are proposed based on possible world. Moreover, existing possible world based algorithms suffer from the following issues: (1) they deal with each possible world independently and ignore the consistency principle across different possible worlds; (2) they require the extra post-processing procedure to obtain the final result, which causes that the effectiveness highly relies on the post-processing method and the efficiency is also not very good. In this paper, we propose a novel possible world based consistency learning model for uncertain data, which can be extended both for clustering and classifying uncertain data. This model utilizes the consistency principle to learn a consensus affinity matrix for uncertain data, which can make full use of the information across different possible worlds and then improve the clustering and classification performance. Meanwhile, this model imposes a new rank constraint on the Laplacian matrix of the consensus affinity matrix, thereby ensuring that the number of connected components in the consensus affinity matrix is exactly equal to the number of classes. This also means that the clustering and classification results can be directly obtained without any post-processing procedure. Furthermore, for the clustering and classification tasks, we respectively derive the efficient optimization methods to solve the proposed model. Experimental results on real benchmark datasets and real world uncertain datasets show that the proposed model outperforms the state-of-the-art uncertain data clustering and classification algorithms in effectiveness and performs competitively in efficiency. Copyright © 2018 Elsevier Ltd. All rights reserved.

Uncertain programming models for portfolio selection with uncertain returns

NASA Astrophysics Data System (ADS)

Zhang, Bo; Peng, Jin; Li, Shengguo

2015-10-01

In an indeterminacy economic environment, experts' knowledge about the returns of securities consists of much uncertainty instead of randomness. This paper discusses portfolio selection problem in uncertain environment in which security returns cannot be well reflected by historical data, but can be evaluated by the experts. In the paper, returns of securities are assumed to be given by uncertain variables. According to various decision criteria, the portfolio selection problem in uncertain environment is formulated as expected-variance-chance model and chance-expected-variance model by using the uncertainty programming. Within the framework of uncertainty theory, for the convenience of solving the models, some crisp equivalents are discussed under different conditions. In addition, a hybrid intelligent algorithm is designed in the paper to provide a general method for solving the new models in general cases. At last, two numerical examples are provided to show the performance and applications of the models and algorithm.

[On the recurrence risk with partial larynx resections (author's transl)].

PubMed

Flach, M

1978-06-01

28 cases of recurrences after 127 vertical and horizontal partial larynx resections (22 per cent) were analysed. Unfavourable preconditions for partial resections are the affliction of the ary cartilage and arrest of vocal chord movility. The hemiresections according to Hautant have the heighest recidivation percentage (40 per cent) judging from the observations available. Radical operations after failured partial resections are uncertain as to their prognoses.

Hypoglycaemia, chronic kidney disease and death in type 2 diabetes: the Hong Kong diabetes registry

PubMed Central

2014-01-01

Background In patients with type 2 diabetes, chronic kidney disease (CKD) is associated with increased risk of hypoglycaemia and death. Yet, it remains uncertain whether hypoglycaemia-associated mortality is modified by CKD. Methods Type 2 diabetic patients, with or without CKD at enrolment were observed between 1995 and 2007, and followed up till 2009 at hospital medical clinics. We used additive interaction, estimated by relative excess risk due to interaction (RERI) and attributable proportion due to interaction (AP) to examine possible synergistic effects between CKD and severe hypoglycaemia (defined as hospitalisations due to hypoglycaemia in the 12 months prior to enrolment) on the risk of death. Results In this cohort of 8,767 type 2 diabetic patients [median age: 58 (interquartile range: 48 to 68) years; disease duration: 5 (1 to 11) years, men: 47.0%], 1,070 (12.2%) had died during a median follow-up period of 6.66 years (3.42-10.36) with 60,379 person-years.Upon enrolment, 209 patients had severe hypoglycaemia and 194 developed severe hypoglycaemia during follow-up (15 patients had both). In multivariable analysis and using patients without severe hypoglycaemia nor CKD as the referent group (683 deaths in 7,598 patients), severe hypoglycaemia alone (61 deaths in 272 patients) or CKD alone (267 death in 781 patients) were associated with increased risk of death [Hazard ratio, HR: 1.81(95%CI: 1.38 to 2.37) and 1.63 (1.38 to 1.93) respectively]. Having both risk factors (59 deaths in 116 patients) greatly enhanced the HR of death to 3.91 (2.93 to 5.21) with significant interaction (RERI: 1.46 and AP: 0.37, both p-values < 0.05). Conclusions Severe hypoglycaemia and CKD interact to increase risk of death in type 2 diabetes patients. PMID:24927961

The use of proton pump inhibitors in an Italian hospital: focus on oncologic and critical non-ICU patients.

PubMed

Meli, Maria; Raffa, Maria Pia; Malta, Renato; Morreale, Ilaria; Aprea, Luigi; D'Alessandro, Natale

2015-12-01

Proton pump inhibitors (PPIs) are among the most misused drugs both at the community and hospital level. Recently, possible risks have been underscored, suggesting the importance of limiting PPI use to proven indications. To survey the appropriateness of PPI use in a University hospital in Italy. Setting Azienda Ospedaliera Universitaria Policlinico 'P. Giaccone', in Palermo, Italy. A one day-observational study, reviewing patients' medical records to identify treatments with PPIs and the indications for their use. After discharge, a subgroup of the cohort was followed up to assess the continuation of therapy at home. Appropriateness was evaluated according to the indications stated in the official product information sheet and supported by the AIFA notes. Prevalence and appropriateness of PPI use in the hospital and after discharge. In the index day 62.9 % of 343 evaluable patients received a PPI. In only 29.1 % of these, the treatment could be considered appropriate. The most frequent reasons for inappropriate treatment were stress ulcer prophylaxis in low risk patients and unwarranted gastro-protection in drug treated patients. 30.9 % of patients received PPIs for uncertain indications: of these, 25.7 % were "critical" patients admitted in non-ICU wards. Furthermore, as much as 88.2 % of anticancer drug treated patients received PPIs as gastroprotective agents. At discharge 48.6 % of patients received a prescription to continue PPI therapy at home and 75.9 % of the 83 followed up patients were found to be still taking these drugs after on average 3 months from discharge. This study confirms a high proportion of inappropriate PPI therapy into the hospital that translates in a prolonged unnecessary administration in the community setting. Further studies are needed to assess the cost-effectiveness of PPI therapy in subgroups of patients at moderate risk for gastric complications to optimize current guidelines.

Streamflow forecasting and data assimilation: bias in precipitation, soil moisture states, and groundwater fluxes.

NASA Astrophysics Data System (ADS)

McCreight, J. L.; Gochis, D. J.; Hoar, T.; Dugger, A. L.; Yu, W.

2014-12-01

Uncertainty in precipitation forcing, soil moisture states, and model groundwater fluxes are first-order sources of error in streamflow forecasting. While near-surface estimates of soil moisture are now available from satellite, very few soil moisture observations below 5 cm depth or groundwater discharge estimates are available for operational forecasting. Radar precipitation estimates are subject to large biases, particularly during extreme events (e.g. Steiner et al., 2010) and their correction is not typically available in real-time. Streamflow data, however, are readily available in near-real-time and can be assimilated operationally to help constrain uncertainty in these uncertain states and improve streamflow forecasts. We examine the ability of streamflow observations to diagnose bias in the three most uncertain variables: precipitation forcing, soil moisture states, and groundwater fluxes. We investigate strategies for their subsequent bias correction. These include spinup and calibration strategies with and without the use of data assimilation and the determination of the proper spinup timescales. Global and spatially distributed multipliers on the uncertain states included in the assimilation state vector (e.g. Seo et al., 2003) will also be evaluated. We examine real cases and observing system simulation experiments for both normal and extreme rainfall events. One of our test cases considers the Colorado Front Range flood of September 2013 where the range of disagreement amongst five precipitation estimates spanned a factor of five with only one exhibiting appreciable positive bias (Gochis et al, submitted). Our experiments are conducted using the WRF-Hydro model with the NoahMP land surface component and the data assimilation research testbed (DART). A variety of ensemble data assimilation approaches (filters) are considered. ReferencesGochis, DJ, et al. "The Great Colorado Flood of September 2013" BAMS (Submitted 4-7-14). Seo, DJ, V Koren, and N Cajina. "Real-time variational assimilation of hydrologic and hydrometeorological data into operational hydrologic forecasting." J Hydromet (2003). Steiner, Matthias, JA Smith, SJ Burges, CV Alonso, and RW Darden. "Effect of bias adjustment and rain gauge data quality control on radar rainfall estimation." WRR (1999).

Bi-directional interaction between hypoglycaemia and cognitive impairment in elderly patients treated with glucose-lowering agents: a systematic review and meta-analysis.

PubMed

Mattishent, K; Loke, Y K

2016-02-01

To examine the bi-directional relationship, whereby hypoglycaemia is a risk factor for dementia, and where dementia increases risk of hypoglycaemia in older patients with diabetes mellitus treated with glucose-lowering agents. We searched MEDLINE and EMBASE over a 10-year span from 2005 to 2015 (with automated PubMed updates to August 2015) for observational studies of the association between hypoglycaemia and cognitive impairment or dementia in participants aged >55 years. Assessment of study validity was based on ascertainment of hypoglycaemia, dementia and risk of confounding. We conducted random effects inverse variance meta-analyses, and assessed heterogeneity using the I(2) statistic. We screened 1177 citations, and selected 12 studies, of which nine were suitable for meta-analysis. There were a total of 1,439,818 participants, with a mean age of 75 years. Meta-analysis of five studies showed a significantly increased risk of dementia in patients who had hypoglycaemic episodes: pooled odds ratio 1.68 [95% confidence interval (CI) 1.45, 1.95]. We also found a significantly increased risk of hypoglycaemia in patients with dementia: pooled odds ratio from five studies 1.61 (95% CI 1.25, 2.06). Limitations of the study were heterogeneity in the meta-analysis, and uncertain ascertainment of dementia and hypoglycaemic outcomes and temporal relationships. Publication bias may have favoured the reporting of more significant findings. Our meta-analysis shows a bi-directional relationship between cognitive impairment and hypoglycaemia in older patients. Glucose-lowering therapy should be carefully tailored and monitored in older patients who are susceptible to cognitive decline. © 2015 John Wiley & Sons Ltd.

Juvenile Moyamoya and Craniosynostosis in a Child with Deletion 1p32p31: Expanding the Clinical Spectrum of 1p32p31 Deletion Syndrome and a Review of the Literature

PubMed Central

Prontera, Paolo; Rogaia, Daniela; Mencarelli, Amedea; Ottaviani, Valentina; Guercini, Giorgio; Bersano, Anna; Stangoni, Gabriela

2017-01-01

Moyamoya angiopathy (MA) is a rare cerebrovascular disorder characterised by the progressive occlusion of the internal carotid artery. Its aetiology is uncertain, but a genetic background seems likely, given the high MA familial rate. To investigate the aetiology of craniosynostosis and juvenile moyamoya in a 14-year-old male patient, we performed an array-comparative genomic hybridisation revealing a de novo interstitial deletion of 8.5 Mb in chromosome region 1p32p31. The deletion involved 34 protein coding genes, including NF1A, whose haploinsufficiency is indicated as being mainly responsible for the 1p32-p31 chromosome deletion syndrome phenotype (OMIM 613735). Our patient also has a deleted FOXD3 of the FOX gene family of transcription factors, which plays an important role in neural crest cell growth and differentiation. As the murine FOXD3−/− model shows craniofacial anomalies and abnormal common carotid artery morphology, it can be hypothesised that FOXD3 is involved in the pathogenesis of the craniofacial and vascular defects observed in our patient. In support of our assumption, we found in the literature another patient with a syndromic form of MA who had a deletion involving another FOX gene (FOXC1). In addition to describing the clinical history of our patient, we have reviewed all of the available literature concerning other patients with a 1p32p31 deletion, including cases from the Decipher database, and we have also reviewed the genetic disorders associated with MA, which is a useful guide for the diagnosis of syndromic form of MA. PMID:28926972

The impact of serial radon and hyperthermia exposure in a therapeutic adit on pivotal cytokines of bone metabolism in rheumatoid arthritis and osteoarthritis.

PubMed

Lange, Uwe; Dischereit, Gabriel; Tarner, Ingo; Frommer, Klaus; Neumann, Elena; Müller-Ladner, Ulf; Kürten, Bernhard

2016-11-01

Secondary osteoporosis is a frequent complication of rheumatoid arthritis (RA) and the result of an imbalance of catabolic and anabolic mechanisms of bone metabolism. The effects of serial low-dose radon and hyperthermia (LDRnHT) exposure in a therapeutic adit (12 applications in 3 weeks) on the serum levels of the cytokines osteoprotegerin (OPG), receptor activator of NF kappa-B ligand (RANKL), tumor necrosis factor-α (TNF-α), and also on the RANKL/OPG ratio were investigated in 25 RA patients and an age-matched control of 24 patients with osteoarthritis (OA). Cytokine measurements were performed at baseline and after completion of LDRnHT. Anti-CCP antibodies (ACPA) were measured in RA patients in parallel. Medication in both groups was limited to non-steroidal anti-inflammatory drugs, and low-dose prednisolone (16 of 24 RA patients) as needed. RA and OA patients showed a significant decrease of TNF-α levels (p < 0.001). Both groups showed significantly decreased levels of RANKL (RA: p < 0.001, OA: p < 0.01). Only the RA patients presented a significant increase of OPG (p < 0.01) and decrease of the RANKL/OPG ratio (p < 0.01), and the ACPA levels (p < 0.001). LDRnHT results in a reduction of osteocatabolic and an increase of osteoanabolic cytokines, which represents the molecular basis for inhibiting osteoclastic activity in secondary osteoporosis and explains in part the effect of LDRnHT this physical therapy modality in a key inflammatory disease. Although reduced ACPA levels were observed under the therapy and although this could potentially contribute to an osteoprotective effect, in this case, it is rather uncertain as the reduction was only minor in magnitude.

Reversible brain atrophy and cognitive impairment in an adolescent Japanese patient with primary adrenal Cushing's syndrome.

PubMed

Ohara, Nobumasa; Suzuki, Hiroshi; Suzuki, Akiko; Kaneko, Masanori; Ishizawa, Masahiro; Furukawa, Kazuo; Abe, Takahiro; Matsubayashi, Yasuhiro; Yamada, Takaho; Hanyu, Osamu; Shimohata, Takayoshi; Sone, Hirohito

2014-01-01

Endogenous Cushing's syndrome is an endocrine disease resulting from chronic exposure to excessive glucocorticoids produced in the adrenal cortex. Although the ultimate outcome remains uncertain, functional and morphological brain changes are not uncommon in patients with this syndrome, and generally persist even after resolution of hypercortisolemia. We present an adolescent patient with Cushing's syndrome who exhibited cognitive impairment with brain atrophy. A 19-year-old Japanese male visited a local hospital following 5 days of behavioral abnormalities, such as money wasting or nighttime wandering. He had hypertension and a 1-year history of a rounded face. Magnetic resonance imaging (MRI) revealed apparently diffuse brain atrophy. Because of high random plasma cortisol levels (28.7 μg/dL) at 10 AM, he was referred to our hospital in August 2011. Endocrinological testing showed adrenocorticotropic hormone-independent hypercortisolemia, and abdominal computed tomography demonstrated a 2.7 cm tumor in the left adrenal gland. The patient underwent left adrenalectomy in September 2011, and the diagnosis of cortisol-secreting adenoma was confirmed histologically. His hypertension and Cushingoid features regressed. Behavioral abnormalities were no longer observed, and he was classified as cured of his cognitive disturbance caused by Cushing's syndrome in February 2012. MRI performed 8 months after surgery revealed reversal of brain atrophy, and his subsequent course has been uneventful. In summary, the young age at onset and the short duration of Cushing's syndrome probably contributed to the rapid recovery of both cognitive dysfunction and brain atrophy in our patient. Cushing's syndrome should be considered as a possible etiological factor in patients with cognitive impairment and brain atrophy that is atypical for their age.

Systematic review with meta-analysis: the effect of tobacco smoking on the natural history of ulcerative colitis.

PubMed

To, N; Ford, A C; Gracie, D J

2016-07-01

Tobacco smoking is associated with a reduced risk of developing ulcerative colitis (UC). A high proportion of UC patients perceive a benefit in disease outcomes secondary to smoking. However, the effects of smoking on the natural history of UC are uncertain. To conduct a systematic review and meta-analysis of the effects of tobacco smoking on the natural history of UC. A search of MEDLINE, EMBASE and EMBASE classic was carried out (up to December 2015) to identify observational studies reporting data on smoking and rates of colectomy, flare of disease activity, proximal disease extension, and development of pouchitis following panproctocolectomy and ileal pouch-anal anastomosis in patients with UC. Dichotomous data were pooled to obtain odds ratios (ORs), with 95% confidence intervals (CIs). The search identified 16 eligible studies: five (2615 patients) studying colectomy; four (620 patients) reporting on flare of disease activity; four (687 patients) examining proximal disease extension and three (355 patients) assessing development of pouchitis. Compared with nonsmokers, the odds of colectomy (OR = 0.89; 95% CI 0.62-1.26), flare of disease activity (OR = 1.26; 95% CI 0.65-2.44), proximal extension of disease (OR = 0.57; 95% CI 0.20-1.66) or the development of pouchitis (OR = 0.57; 95% CI 0.21-1.53) were not significantly lower in smokers. Smoking may not improve the natural history of ulcerative colitis. Given the health benefits of smoking cessation and the lack of clear benefit in ulcerative colitis, smoking cessation advice should be incorporated into guidance on the management of ulcerative colitis. © 2016 John Wiley & Sons Ltd.

Increase in overall mortality risk in patients with type 2 diabetes receiving glipizide, glyburide or glimepiride monotherapy versus metformin: a retrospective analysis.

PubMed

Pantalone, K M; Kattan, M W; Yu, C; Wells, B J; Arrigain, S; Jain, A; Atreja, A; Zimmerman, R S

2012-09-01

It remains uncertain if differences in mortality risk exist among the sulfonylureas, especially in patients with documented coronary artery disease (CAD). The purpose of this study was to assess the overall mortality risk of the individual sulfonylureas versus metformin in a large cohort of patients with type 2 diabetes. A retrospective cohort study was conducted using an academic health centre enterprise-wide electronic health record (EHR) system to identify 23 915 patients with type 2 diabetes who initiated monotherapy with metformin (N = 12774), glipizide (N = 4325), glyburide (N = 4279) or glimepiride (N = 2537), ≥ 18 years of age, with and without a history of CAD, and not on insulin or a non-insulin injectable at baseline. The patients were followed for mortality by documentation in the EHR and Social Security Death Index. Multivariable Cox models with propensity analysis were used to compare cohorts. An increase in overall mortality risk was observed in the entire cohort with glipizide (HR 1.64; 95% CI 1.39-1.94), glyburide (HR 1.59; 95% CI 1.35-1.88), and glimepiride (HR 1.68; 95% CI 1.37-2.06) versus metformin; however, in those patients with documented CAD, a statistically significant increase in overall mortality risk was only found with glipizide (HR 1.41; 95% CI 1.07-1.87) and glyburide (HR 1.38; 95% CI 1.04-1.83) versus metformin. Glipizide, glyburide and glimepiride are associated with an increased risk of overall mortality versus metformin. Our results suggest that if a sulfonylurea is required to obtain glycaemic control, glimepiride may be the preferred sulfonylurea in those with underlying CAD. © 2012 Blackwell Publishing Ltd.

Changing epidemiology of AA amyloidosis: clinical observations over 25 years at a single national referral centre.

PubMed

Lane, Thirusha; Pinney, Jennifer H; Gilbertson, Janet A; Hutt, David F; Rowczenio, Dorota M; Mahmood, Shameem; Sachchithanantham, Sajitha; Fontana, Marianna; Youngstein, Taryn; Quarta, Candida C; Wechalekar, Ashutosh D; Gillmore, Julian D; Hawkins, Philip N; Lachmann, Helen J

2017-09-01

Systemic AA amyloidosis is a serious complication of chronic inflammation; however, there are relatively few published data on its incidence. We investigated the changing epidemiology of AA amyloidosis over a 25-year period at a single national referral centre. We conducted a retrospective study of all patients diagnosed with AA amyloidosis who had attended the centre between 1990 and 2014 inclusive. Six hundred and twenty-five patients were studied in three cohorts: C1: 1990-1997; C2: 1998-2006; C3: 2007-2014. Mean age at presentation increased from 46 in C1 to 56 in C3 (p < .0001). The proportion of South Asian patients increased from 4% in C1 to 17% in C3 (p = .0006). Comparison of underlying diseases between C1 and C3 revealed a reduction in patients with juvenile idiopathic arthritis from 25% to 2% (p < .0001), but an increase in patients with chronic infection due to intravenous recreational drug use from 1% to 13% (p < .0001), and uncharacterized inflammatory disorders from 10% to 27% (p <.0001). More patients were in end-stage renal failure at presentation in C3 (29%) than C1 (15%) (p = .0028). Median age at death was later in C3 (62 years) than C1 (54 years) (p = .0012). These data suggest both falling incidence and better outcome in AA amyloidosis over a quarter of a century, reflecting advances in therapeutics and overall management of complex chronic disease in an ageing population. AA amyloidosis of uncertain aetiology presents an emerging major problem. Newer techniques such as next-generation sequencing may aid diagnosis and effective treatment, thereby improving overall survival.

Our Sun IV: The Standard Model and Helioseismology: Consequences of Uncertainties in Input Physics and in Observed Solar Parameters

NASA Technical Reports Server (NTRS)

Boothroyd, Arnold I.; Sackmann, I.-Juliana

2001-01-01

Helioseismic frequency observations provide an extremely accurate window into the solar interior; frequencies from the Michaelson Doppler Imager (MDI) on the Solar and Heliospheric Observatory (SOHO) spacecraft, enable the adiabatic sound speed and adiabatic index to be inferred with an accuracy of a few parts in 10(exp 4) and the density with an accuracy of a few parts in 10(exp 3). This has become a Serious challenge to theoretical models of the Sun. Therefore, we have undertaken a self-consistent, systematic study of the sources of uncertainties in the standard solar models. We found that the largest effect on the interior structure arises from the observational uncertainties in the photospheric abundances of the elements, which affect the sound speed profile at the level of 3 parts in 10(exp 3). The estimated 4% uncertainty in the OPAL opacities could lead to effects of 1 part in 10(exp 3); the approximately 5%, uncertainty in the basic pp nuclear reaction rate would have a similar effect, as would uncertainties of approximately 15% in the diffusion constants for the gravitational settling of helium. The approximately 50% uncertainties in diffusion constants for the heavier elements would have nearly as large an effect. Different observational methods for determining the solar radius yield results differing by as much as 7 parts in 10(exp 4); we found that this leads to uncertainties of a few parts in 10(exp 3) in the sound speed int the solar convective envelope, but has negligible effect on the interior. Our reference standard solar model yielded a convective envelope position of 0.7135 solar radius, in excellent agreement with the observed value of 0.713 +/- 0.001 solar radius and was significantly affected only by Z/X, the pp rate, and the uncertainties in helium diffusion constants. Our reference model also yielded envelope helium abundance of 0.2424, in good agreement with the approximate range of 0.24 to 0.25 inferred from helioseismic observations; only extreme Z/X values yielded envelope helium abundance outside this range. We found that other current uncertainties, namely, in the solar age and luminosity, in nuclear rates other than the pp reaction, in the low-temperature molecular opacities, and in the low-density equation of state, have no significant effect on the quantities that can be inferred from helioseismic observations. The predicted pre-main-sequence lithium depletion is uncertain by a factor of 2. The predicted neutrino capture rate is uncertain by approximately 30% for the Cl-27 experiment and by approximately 3% for Ga-71 experiments, while the B-8 neutrino flux is uncertain by approximately 30%.

Optimal Decision Making in a Class of Uncertain Systems Based on Uncertain Variables

NASA Astrophysics Data System (ADS)

Bubnicki, Z.

2006-06-01

The paper is concerned with a class of uncertain systems described by relational knowledge representations with unknown parameters which are assumed to be values of uncertain variables characterized by a user in the form of certainty distributions. The first part presents the basic optimization problem consisting in finding the decision maximizing the certainty index that the requirement given by a user is satisfied. The main part is devoted to the description of the optimization problem with the given certainty threshold. It is shown how the approach presented in the paper may be applied to some problems for anticipatory systems.

Uncertain sightings and the extinction of the Ivory-billed Woodpecker.

PubMed

Solow, Andrew; Smith, Woollcott; Burgman, Mark; Rout, Tracy; Wintle, Brendan; Roberts, David

2012-02-01

The extinction of a species can be inferred from a record of its sightings. Existing methods for doing so assume that all sightings in the record are valid. Often, however, there are sightings of uncertain validity. To date, uncertain sightings have been treated in an ad hoc way, either excluding them from the record or including them as if they were certain. We developed a Bayesian method that formally accounts for such uncertain sightings. The method assumes that valid and invalid sightings follow independent Poisson processes and use noninformative prior distributions for the rate of valid sightings and for a measure of the quality of uncertain sightings. We applied the method to a recently published record of sightings of the Ivory-billed Woodpecker (Campephilus principalis). This record covers the period 1897-2010 and contains 39 sightings classified as certain and 29 classified as uncertain. The Bayes factor in favor of extinction was 4.03, which constitutes substantial support for extinction. The posterior distribution of the time of extinction has 3 main modes in 1944, 1952, and 1988. The method can be applied to sighting records of other purportedly extinct species. ©2011 Society for Conservation Biology.

Lower Risk of Death With SGLT2 Inhibitors in Observational Studies: Real or Bias?

PubMed

Suissa, Samy

2018-01-01

Two recent observational studies reported a remarkably lower rate of all-cause death associated with sodium-glucose cotransporter 2 inhibitor (-SGLT2i) use in all patients with type 2 diabetes and not only those at increased cardiovascular risk. The >50% lower mortality rates reported in these studies are much greater than those found in the BI 10773 (Empagliflozin) Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME) and CANagliflozin cardioVascular Assessment Study (CANVAS) randomized trials. We show that these observational studies are affected by time-related biases, including immortal time bias and time-lag bias, which tend to exaggerate the benefits observed with a drug. The Comparative Effectiveness of Cardiovascular Outcomes in New Users of SGLT-2 Inhibitors (CVD-REAL) study, based on 166,033 users of SGLT2i and 1,226,221 users of other glucose-lowering drugs (oGLD) identified from health care databases of six countries, was affected by immortal time bias. Indeed, the immortal time between the first oGLD prescription and the first SGLT2i prescription was omitted from the analysis, which resulted in increasing the rate of death in the oGLD group and thus producing the appearance of a lower risk of death with SGLT2i use. The Swedish study compared 10,879 SGLT2i/dipeptidyl peptidase 4 inhibitor (DPP-4i) users with 10,879 matched insulin users. Such comparisons involving second-line therapies with a third-line therapy can introduce time-lag bias, as the patients may not be at the same stage of diabetes. This bias is compounded by the fact that the users of insulin had already started their insulin before cohort entry, unlike the new users of SGLT2i. Finally, the study also introduces immortal time bias with respect to the effects of SGLT2i relative to DPP-4i. In conclusion, the >50% lower rate of death with SGLT2i in type 2 diabetes reported by two recent observational studies is likely exaggerated by immortal time and time-lag biases. It thus remains uncertain whether the benefit seen with empagliflozin in the EMPA-REG OUTCOME trial applies to all SGLT2i and to all patients with type 2 diabetes, not only those at increased cardiovascular risk. While observational studies can provide crucial real-world evidence for the effects of medications, they need to be carefully conducted to avoid such major time-related biases. © 2017 by the American Diabetes Association.

Dipeptidyl peptidase-4 inhibitors and risk of heart failure in type 2 diabetes: systematic review and meta-analysis of randomised and observational studies.

PubMed

Li, Ling; Li, Sheyu; Deng, Ke; Liu, Jiali; Vandvik, Per Olav; Zhao, Pujing; Zhang, Longhao; Shen, Jiantong; Bala, Malgorzata M; Sohani, Zahra N; Wong, Evelyn; Busse, Jason W; Ebrahim, Shanil; Malaga, German; Rios, Lorena P; Wang, Yingqiang; Chen, Qunfei; Guyatt, Gordon H; Sun, Xin

2016-02-17

To examine the association between dipeptidyl peptidase-4 (DPP-4) inhibitors and the risk of heart failure or hospital admission for heart failure in patients with type 2 diabetes. Systematic review and meta-analysis of randomised and observational studies. Medline, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov searched up to 25 June 2015, and communication with experts. Randomised controlled trials, non-randomised controlled trials, cohort studies, and case-control studies that compared DPP-4 inhibitors against placebo, lifestyle modification, or active antidiabetic drugs in adults with type 2 diabetes, and explicitly reported the outcome of heart failure or hospital admission for heart failure. Teams of paired reviewers independently screened for eligible studies, assessed risk of bias, and extracted data using standardised, pilot tested forms. Data from trials and observational studies were pooled separately; quality of evidence was assessed by the GRADE approach. Eligible studies included 43 trials (n=68,775) and 12 observational studies (nine cohort studies, three nested case-control studies; n=1,777,358). Pooling of 38 trials reporting heart failure provided low quality evidence for a possible similar risk of heart failure between DPP-4 inhibitor use versus control (42/15,701 v 33/12,591; odds ratio 0.97 (95% confidence interval 0.61 to 1.56); risk difference 2 fewer (19 fewer to 28 more) events per 1000 patients with type 2 diabetes over five years). The observational studies provided effect estimates generally consistent with trial findings, but with very low quality evidence. Pooling of the five trials reporting admission for heart failure provided moderate quality evidence for an increased risk in patients treated with DPP-4 inhibitors versus control (622/18,554 v 552/18,474; 1.13 (1.00 to 1.26); 8 more (0 more to 16 more)). The pooling of adjusted estimates from observational studies similarly suggested (with very low quality evidence) a possible increased risk of admission for heart failure (adjusted odds ratio 1.41, 95% confidence interval 0.95 to 2.09) in patients treated with DPP-4 inhibitors (exclusively sitagliptin) versus no use. The relative effect of DPP-4 inhibitors on the risk of heart failure in patients with type 2 diabetes is uncertain, given the relatively short follow-up and low quality of evidence. Both randomised controlled trials and observational studies, however, suggest that these drugs may increase the risk of hospital admission for heart failure in those patients with existing cardiovascular diseases or multiple risk factors for vascular diseases, compared with no use. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Comparisons of Prognosis between Surgically and Clinically Diagnosed Idiopathic Pulmonary Fibrosis Using Gap Model

PubMed Central

Lee, Sang Hoon; Kim, Song Yee; Kim, Dong Soon; Kim, Young Whan; Chung, Man Pyo; Uh, Soo Taek; Park, Choon Sik; Jeong, Sung Hwan; Park, Yong Bum; Lee, Hong Lyeol; Shin, Jong Wook; Lee, Eun Joo; Lee, Jin Hwa; Jegal, Yangin; Lee, Hyun Kyung; Kim, Yong Hyun; Song, Jin Woo; Park, Moo Suk

2016-01-01

Abstract Although a multidisciplinary approach has become an important criterion for an idiopathic pulmonary fibrosis (IPF) diagnosis, lung biopsies remain crucial. However, the prognosis of patients with surgically diagnosed IPF (sIPF) is uncertain. We aimed to investigate the prognosis of patients with clinically diagnosed IPF (cIPF) and sIPF. In this retrospective observational study, the Korean Interstitial Lung Disease Study Group conducted a national survey to evaluate the clinical, physiological, radiological, and survival characteristics of patients with IPF from January 1, 2003 to December 31, 2007. Patients were recruited from 54 universities and teaching hospitals across the Republic of Korea. IPF diagnoses were established according to the 2002 American Thoracic Society (ATS)/European Respiratory Society criteria (ERS) guideline. A total of 1685 patients with IPF (1027 cIPF and 658 sIPF) were enrolled. Patients with sIPF were significantly younger, predominantly female, and nonsmokers (all P < 0.001). sIPF group had significantly better initial pulmonary function. The proportion of computed tomography-based honeycomb findings of patients with cIPF was higher than in those with sIPF (P < 0.001). A Kaplan-Meier analysis showed that the sIPF group had a better prognosis (P = 0.001). A survival analysis showed that age, pulmonary function parameters, pulmonary oxygen tension, honeycombing change, and combined lung cancer had a significant influence on patient prognosis. However, there was no significant difference in prognosis between the cIPF and sIPF groups after adjusting for GAP (gender, age, physiology) stage. The patients with sIPF had better clinical features than those with cIPF. However, after adjusting for GAP stage, the sIPF group showed similar prognoses as the cIPF group. This study showed that after adjusting for GAP stage, the prognosis of patients with IPF is the same regardless of the diagnostic method used. PMID:26986154

Increased odds and predictive rates of MMPI-2-RF scale elevations in patients with psychogenic non-epileptic seizures and observed sex differences.

PubMed

Del Bene, Victor A; Arce Rentería, Miguel; Maiman, Moshe; Slugh, Mitch; Gazzola, Deana M; Nadkarni, Siddhartha S; Barr, William B

2017-07-01

The Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF) is a self-report instrument, previously shown to differentiate patients with epileptic seizures (ES) and psychogenic non-epileptic seizures (PNES). At present, the odds of MMPI-2-RF scale elevations in PNES patients, as well as the diagnostic predictive value of such scale elevations, remain largely unexplored. This can be of clinical utility, particularly when a diagnosis is uncertain. After looking at mean group differences, we applied contingency table derived odds ratios to a sample of ES (n=92) and PNES (n=77) patients from a video EEG (vEEG) monitoring unit. We also looked at the positive and negative predictive values (PPV, NPV), as well as the false discovery rate (FDR) and false omission rate (FOR) for scales found to have increased odds of elevation in PNES patients. This was completed for the overall sample, as well as the sample stratified by sex. The odds of elevations related to somatic concerns, negative mood, and suicidal ideation in the PNES sample ranged from 2 to 5 times more likely. Female PNES patients had 3-6 times greater odds of such scale elevations, while male PNES patients had odds of 5-15 times more likely. PPV rates ranged from 53.66% to 84.62%, while NPV rates ranged from 47.52% to 90.91%. FDR across scales ranged from 15.38% to 50%, while the FOR ranged from 9.09% to 52.47%. Consistent with prior research, PNES patients have greater odds of MMPI-2-RF scale elevations, particularly related to somatic concerns and mood disturbance. Female PNES patients endorsed greater emotional distress, including endorsement of suicide related items. Elevations of these scales could aid in differentiating PNES from ES patients, although caution is warranted due to the possibility of both false positives and the incorrect omissions of PNES cases. Copyright © 2017 Elsevier Inc. All rights reserved.

Different clinical presentation and management of temporal bone fibrous dysplasia in children.

PubMed

Mierzwiński, Józef; Kosowska, Justyna; Tyra, Justyna; Haber, Karolina; Drela, Maria; Paczkowski, Dariusz; Burduk, Paweł

2018-01-15

Fibrous dysplasia is a slowly progressive benign fibro-osseous disorder that involves one or multiple bones with a unilateral distribution in most cases. It is a lesion of unknown etiology, uncertain pathogenesis, and diverse histopathology. Temporal bone involvement is the least frequently reported type, especially in children. We reviewed available articles regarding fibrous dysplasia with temporal bone involvement in children and added four patients aged 7 to 17 years who were diagnosed and treated in our institution from 2006 to 2017. The patients' clinical picture comprised head deformity, external canal stenosis, headache, progressive conductive and/or sensorineural hearing loss, tinnitus, and sudden deafness. Two patients had experienced severe episodic vertigo with nausea and vomiting. Two were referred to us with external canal obstruction and secondary cholesteatoma formation with broad middle ear destruction. One was diagnosed with acute mastoiditis and intracranial complications. Optimal management of fibrous dysplasia is unclear and can be challenging, especially in children. In our two patients with disease expansion and involvement of important structures, surgical treatment was abandoned and a "wait-and-scan" policy was applied. The other two were qualified for surgical treatment. One patient underwent two surgeries: modified lateral petrosectomy (canal left open) with pathological tissue removal, cavity obliteration, and subsequent tympanoplasty. Another patient with extensive destruction of the left temporal bone underwent canal wall down mastoidectomy with perisinus abscess drainage and revision 12 months later. Tympanoplasty was unsatisfactory in both patients because of slow progression of the middle ear pathology. None of our patients underwent pharmacological treatment. In younger patients, observation and a "wait-and-scan" protocol is relevant until significant function, or cosmetic deficits are obvious. Surgery is not preferred and should be delayed until puberty because fibrous dysplasia has a tendency to stabilize after adolescence. In patients with severe symptoms medical treatment can be implemented, but safety of this treatment in children remain controversial.

Comparisons of Prognosis between Surgically and Clinically Diagnosed Idiopathic Pulmonary Fibrosis Using Gap Model: A Korean National Cohort Study.

PubMed

Lee, Sang Hoon; Kim, Song Yee; Kim, Dong Soon; Kim, Young Whan; Chung, Man Pyo; Uh, Soo Taek; Park, Choon Sik; Jeong, Sung Hwan; Park, Yong Bum; Lee, Hong Lyeol; Shin, Jong Wook; Lee, Eun Joo; Lee, Jin Hwa; Jegal, Yangin; Lee, Hyun Kyung; Kim, Yong Hyun; Song, Jin Woo; Park, Moo Suk

2016-03-01

Although a multidisciplinary approach has become an important criterion for an idiopathic pulmonary fibrosis (IPF) diagnosis, lung biopsies remain crucial. However, the prognosis of patients with surgically diagnosed IPF (sIPF) is uncertain. We aimed to investigate the prognosis of patients with clinically diagnosed IPF (cIPF) and sIPF. In this retrospective observational study, the Korean Interstitial Lung Disease Study Group conducted a national survey to evaluate the clinical, physiological, radiological, and survival characteristics of patients with IPF from January 1, 2003 to December 31, 2007. Patients were recruited from 54 universities and teaching hospitals across the Republic of Korea. IPF diagnoses were established according to the 2002 American Thoracic Society (ATS)/European Respiratory Society criteria (ERS) guideline. A total of 1685 patients with IPF (1027 cIPF and 658 sIPF) were enrolled. Patients with sIPF were significantly younger, predominantly female, and nonsmokers (all P < 0.001). sIPF group had significantly better initial pulmonary function. The proportion of computed tomography-based honeycomb findings of patients with cIPF was higher than in those with sIPF (P < 0.001). A Kaplan-Meier analysis showed that the sIPF group had a better prognosis (P = 0.001). A survival analysis showed that age, pulmonary function parameters, pulmonary oxygen tension, honeycombing change, and combined lung cancer had a significant influence on patient prognosis. However, there was no significant difference in prognosis between the cIPF and sIPF groups after adjusting for GAP (gender, age, physiology) stage. The patients with sIPF had better clinical features than those with cIPF. However, after adjusting for GAP stage, the sIPF group showed similar prognoses as the cIPF group. This study showed that after adjusting for GAP stage, the prognosis of patients with IPF is the same regardless of the diagnostic method used.

An adherence based cost-consequence model comparing bimatoprost 0.01% to bimatoprost 0.03%.

PubMed

Wong, William B; Patel, Vaishali D; Kowalski, Jonathan W; Schwartz, Gail

2013-09-01

Estimate the long-term direct medical costs and clinical consequences of improved adherence with bimatoprost 0.01% compared to bimatoprost 0.03% in the treatment of glaucoma. A cost-consequence model was constructed from the perspective of a US healthcare payer. The model structure included three adherence levels (high, moderate, low) and four mean deviation (MD) defined health states (mild, moderate, severe glaucoma, blindness) for each adherence level. Clinical efficacy in terms of IOP reduction was obtained from the randomized controlled trial comparing bimatoprost 0.01% with bimatoprost 0.03%. Medication adherence was based on observed 12 month rates from an analysis of a nationally representative pharmacy claims database. Patients with high, moderate and low adherence were assumed to receive 100%, 50% and 0% of the IOP reduction observed in the clinical trial, respectively. Each 1 mmHg reduction in IOP was assumed to result in a 10% reduction in the risk of glaucoma progression. Worse glaucoma severity health states were associated with higher medical resource costs. Outcome measures were total costs, proportion of patients who progress and who become blind, and years of blindness. Deterministic sensitivity analyses were performed on uncertain model parameters. The percentage of patients progressing, becoming blind, and the time spent blind slightly favored bimatoprost 0.01%. Improved adherence with bimatoprost 0.01% led to higher costs in the first 2 years; however, starting in year 3 bimatoprost 0.01% became less costly compared to bimatoprost 0.03% with a total reduction in costs reaching US$3433 over a lifetime time horizon. Deterministic sensitivity analyses demonstrated that results were robust, with the majority of analyses favoring bimatoprost 0.01%. Application of 1 year adherence and efficacy over the long term are limitations. Modeling the effect of greater medication adherence with bimatoprost 0.01% compared with bimatoprost 0.03% suggests that differences may result in improved economic and patient outcomes.

Cost-effectiveness of supervised exercise, stenting, and optimal medical care for claudication: results from the Claudication: Exercise Versus Endoluminal Revascularization (CLEVER) trial.

PubMed

Reynolds, Matthew R; Apruzzese, Patricia; Galper, Benjamin Z; Murphy, Timothy P; Hirsch, Alan T; Cutlip, Donald E; Mohler, Emile R; Regensteiner, Judith G; Cohen, David J

2014-11-11

Both supervised exercise (SE) and stenting (ST) improve functional status, symptoms, and quality of life compared with optimal medical care (OMC) in patients with claudication. The relative cost-effectiveness of these strategies is not well defined. The Claudication: Exercise Versus Endoluminal Revascularization (CLEVER) study randomized patients with claudication due to aortoiliac stenosis to a 6-month SE program, to ST, or to OMC. Participants who completed 6-month follow-up (n=98) were included in a health economic analysis through 18 months. Costs were assessed using resource-based methods and hospital billing data. Quality-adjusted life-years were estimated using the EQ-5D. Markov modeling based on the in-trial results was used to explore the impact of assumptions about the longer term durability of observed differences in quality of life. Through 18 months, mean healthcare costs were $5178, $9804, and $14 590 per patient for OMC, SE, and ST, respectively. Measured quality-adjusted life-years through 18 months were 1.04, 1.16, and 1.20. In our base case analysis, which assumed that observed differences in quality of life would dissipate after 5 years, the incremental cost-effectiveness ratios were $24 070 per quality-adjusted life-year gained for SE versus OMC, $41 376 for ST versus OMC, and $122 600 for ST versus SE. If the treatment effect of ST was assumed to be more durable than that of SE, the incremental cost-effectiveness ratio for ST versus SE became more favorable. Both SE and ST are economically attractive by US standards relative to OMC for the treatment of claudication in patients with aortoiliac disease. ST is more expensive than SE, with uncertain incremental benefit. www.clinicaltrials.gov, Unique identifier: NCT00132743. © 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Trends in CD4 counts in HIV-infected patients with HIV viral load monitoring while on combination antiretroviral treatment: results from The TREAT Asia HIV Observational Database

PubMed Central

2010-01-01

Background The aim of this study was to examine the relationship between trends in CD4 counts (slope) and HIV viral load (VL) after initiation of combination antiretroviral treatment (cART) in Asian patients in The TREAT Asia HIV Observational Database (TAHOD). Methods Treatment-naive HIV-infected patients who started cART with three or more and had three or more CD4 count and HIV VL tests were included. CD4 count slopes were expressed as changes of cells per microliter per year. Predictors of CD4 count slopes from 6 months after initiation were assessed by random-effects linear regression models. Results A total of 1676 patients (74% male) were included. The median time on cART was 4.2 years (IQR 2.5-5.8 years). In the final model, CD4 count slope was associated with age, concurrent HIV VL and CD4 count, disease stage, hepatitis B or C co-infection, and time since cART initiation. CD4 count continues to increase with HIV VL up to 20 000 copies/mL during 6-12 months after cART initiation. However, the HIV VL has to be controlled below 5 000, 4 000 and 500 copies/mL for the CD4 count slope to remain above 20 cells/microliter per year during 12-18, 18-24, and beyond 24 months after cART initiation. Conclusions After cART initiation, CD4 counts continued to increase even when the concurrent HIV VL was detectable. However, HIV VL needed to be controlled at a lower level to maintain a positive CD4 count slope when cART continues. The effect on long-term outcomes through the possible development of HIV drug resistance remains uncertain. PMID:21182796

Super-Eight: The brightest z~8 Galaxies

NASA Astrophysics Data System (ADS)

Holwerda, Benne; Bouwens, R.; Bradley, L.; Calvi, V.; Illingworth, G.; Labbe, I.; Magee, D.; Oesch, P.; Roberts-Borsani, G.; Smit, R.

2016-08-01

What are the properties of the most massive z~8 galaxies ('Super-Eights') and how luminous can these galaxies become at that epoch? Answering these questions is challenging due to the rarity of luminous z~8 galaxies and the large field-to-field variations in their volume densities. Indeed, the full wide-area CANDELS program only shows 3 z~8 galaxy candidates brighter than 25.5 mag and all of these candidates conspicuously lie in the same CANDELS field (EGS). One of our strongest new probes for particularly luminous z~8 galaxies are the WFC3 Pure-Parallel (PP) programs. Particularly intriguing are 8 bright z~8 candidates in these observations. These candidates have similar luminosities as the 3 brightest z~8 candidates from CANDELS (all spectroscopically confirmed). However, the uncertain contamination levels at extreme bright end of z~8 selection mean that follow-up observations are critical. We propose highly-efficient pointed HST and Spitzer/IRAC observations to determine if these candidates are indeed at z~8. We estimate that anywhere from 50 to 100% of the targeted sources will be confirmed to be at z~8 based on our results from CANDELS. The estimate is very uncertain due to very large cosmic variance in the CANDELS result and contamination from rare low-redshift sources. When combined with CANDELS, our observations would provide us the strongest current constraints on the volume density of bright, massive galaxies in the early Universe (serving as a guide to models of their build-up) and also provide valuable targets for future spectroscopy (e.g. with JWST), useful for probing the ionization state of the IGM.

Super-Eight: The brightest z 8 Galaxies

NASA Astrophysics Data System (ADS)

Holwerda, Benne

2016-10-01

What are the properties of the most massive z 8 galaxies (Super-Eights) and how luminous can these galaxies become at that epoch? Answering these questions is challenging due to the rarity of luminous z 8 galaxies and the large field-to-field variations in their volume densities. Indeed, the full wide-area CANDELS program only shows 3 z 8 galaxy candidates brighter than 25.5 mag and all of these candidates conspicuously lie in the same CANDELS field (EGS). One of our strongest new probes for particularly luminous z 8 galaxies are the WFC3 Pure-Parallel (PP) programs. Particularly intriguing are 8 bright z 8 candidates in these observations. These candidates have similar luminosities as the 3 brightest z 8 candidates from CANDELS (all spectroscopically confirmed). However, the uncertain contamination levels at extreme bright end of z 8 selection mean that follow-up observations are critical. We propose highly-efficient pointed HST and Spitzer/IRAC observations to determine if these candidates are indeed at z 8. We estimate that anywhere from 50 to 100% of the targeted sources will be confirmed to be at z 8 based on our results from CANDELS. The estimate is very uncertain due to very large cosmic variance in the CANDELS result and contamination from rare low-redshift sources.When combined with CANDELS, our observations would provide us the strongest current constraints on the volume density of bright, massive galaxies in the early Universe (serving as a guide to models of their build-up) and also provide valuable targets for future spectroscopy (e.g. with JWST), useful for probing the ionization state of the IGM.

Anorexia nervosa and gender identity disorder in biologic males: a report of two cases.

PubMed

Winston, Anthony P; Acharya, Sudha; Chaudhuri, Shreemantee; Fellowes, Lynette

2004-07-01

Gender identity disorder is a rare disorder of uncertain etiology. The emphasis on body shape in this disorder suggests that there may be an association with anorexia nervosa. We report two cases of anorexia nervosa and gender identity disorder in biologic males who presented to an eating disorders service. One was treated successfully as an outpatient and subsequently underwent gender reassignment surgery. The other patient required admission and prolonged psychotherapy. Differences between the two cases are discussed. Issues of gender identity should be considered in the assessment of male patients presenting with anorexia nervosa. Copyright 2004 by Wiley Periodicals, Inc.

Symptomatic Overlap and Therapeutic Opportunities in Primary Headache.

PubMed

Cady, Roger; Garas, Sandy Yacoub; Patel, Ketu; Peterson, Andrew; Wenzel, Richard

2015-08-01

Headache, a nearly universal experience, remains costly, disabling, and often suboptimally managed. The most common presentations in the United States are migraine, tension-type headache (TTH) and "sinus" headache, but their extensive symptomatic overlap suggests that these conditions can be approached as variations in the same underlying pathology and managed accordingly. We use case studies of patients with varying prior diagnoses (none, migraine, TTH, and sinus headache), as well as a 4-question diagnostic screening tool, to illustrate how pharmacists can use this conceptual framework to simplify identification, management, and referral of patients with primary headache conditions of uncertain etiology. © The Author(s) 2014.

Pacing as a Treatment for Reflex-Mediated (Vasovagal, Situational, or Carotid Sinus Hypersensitivity) Syncope: A Systematic Review for the 2017 ACC/AHA/HRS Guideline for the Evaluation and Management of Patients With Syncope: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society.

PubMed

Varosy, Paul D; Chen, Lin Y; Miller, Amy L; Noseworthy, Peter A; Slotwiner, David J; Thiruganasambandamoorthy, Venkatesh

2017-08-01

To determine, using systematic review of the biomedical literature, whether pacing reduces risk of recurrent syncope and relevant clinical outcomes among adult patients with reflex-mediated syncope. MEDLINE (through PubMed), EMBASE, and the Cochrane Central Register of Controlled Trials (through October 7, 2015) were searched for randomized trials and observational studies examining pacing and syncope, and the bibliographies of known systematic reviews were also examined. Studies were rejected for poor-quality study methods and for the lack of the population, intervention, comparator, or outcome(s) of interest. Of 3,188 citations reviewed, 10 studies met the inclusion criteria for systematic review, including a total of 676 patients. These included 9 randomized trials and 1 observational study. Of the 10 studies, 4 addressed patients with carotid sinus hypersensitivity, and the remaining 6 addressed vasovagal syncope. Among the 6 open-label (unblinded) studies, we found that pacing was associated with a 70% reduction in recurrent syncope (relative risk [RR]: 0.30; 95% confidence interval [CI]: 0.15-0.60). When the 2 analyzable studies with double-blinded methodology were considered separately, there was no clear benefit (RR: 0.73; 95% CI: 0.25-2.1), but confidence intervals were wide. The strongest evidence was from the randomized, double-blinded ISSUE-3 (Third International Study on Syncope of Uncertain Etiology) trial, which demonstrated a benefit of pacing among patients with recurrent syncope and asystole documented by implantable loop recorder. There are limited data with substantive evidence of outcome ascertainment bias, and only 2 studies with a double-blinded study design have been conducted. The evidence does not support the use of pacing for reflex-mediated syncope beyond patients with recurrent vasovagal syncope and asystole documented by implantable loop recorder. Copyright © 2017 American College of Cardiology Foundation, American Heart Association, Inc., and Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Pacing as a treatment for reflex-mediated (vasovagal, situational, or carotid sinus hypersensitivity) syncope: A systematic review for the 2017 ACC/AHA/HRS guideline for the evaluation and management of patients with syncope: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society.

PubMed

Varosy, Paul D; Chen, Lin Y; Miller, Amy L; Noseworthy, Peter A; Slotwiner, David J; Thiruganasambandamoorthy, Venkatesh

2017-08-01

To determine, using systematic review of the biomedical literature, whether pacing reduces risk of recurrent syncope and relevant clinical outcomes among adult patients with reflex-mediated syncope. MEDLINE (through PubMed), EMBASE, and the Cochrane Central Register of Controlled Trials (through October 7, 2015) were searched for randomized trials and observational studies examining pacing and syncope, and the bibliographies of known systematic reviews were also examined. Studies were rejected for poor-quality study methods and for the lack of the population, intervention, comparator, or outcome(s) of interest. Of 3,188 citations reviewed, 10 studies met the inclusion criteria for systematic review, including a total of 676 patients. These included 9 randomized trials and 1 observational study. Of the 10 studies, 4 addressed patients with carotid sinus hypersensitivity, and the remaining 6 addressed vasovagal syncope. Among the 6 open-label (unblinded) studies, we found that pacing was associated with a 70% reduction in recurrent syncope (relative risk [RR]: 0.30; 95% confidence interval [CI]: 0.15-0.60). When the 2 analyzable studies with double-blinded methodology were considered separately, there was no clear benefit (RR: 0.73; 95% CI: 0.25-2.1), but confidence intervals were wide. The strongest evidence was from the randomized, double-blinded ISSUE-3 (Third International Study on Syncope of Uncertain Etiology) trial, which demonstrated a benefit of pacing among patients with recurrent syncope and asystole documented by implantable loop recorder. There are limited data with substantive evidence of outcome ascertainment bias, and only 2 studies with a double-blinded study design have been conducted. The evidence does not support the use of pacing for reflex-mediated syncope beyond patients with recurrent vasovagal syncope and asystole documented by implantable loop recorder. Copyright © 2017 American College of Cardiology Foundation, American Heart Association, Inc., and Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Pacing as a Treatment for Reflex-Mediated (Vasovagal, Situational, or Carotid Sinus Hypersensitivity) Syncope: A Systematic Review for the 2017 ACC/AHA/HRS Guideline for the Evaluation and Management of Patients With Syncope: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society.

PubMed

Varosy, Paul D; Chen, Lin Y; Miller, Amy L; Noseworthy, Peter A; Slotwiner, David J; Thiruganasambandamoorthy, Venkatesh

2017-08-01

To determine, using systematic review of the biomedical literature, whether pacing reduces risk of recurrent syncope and relevant clinical outcomes among adult patients with reflex-mediated syncope. MEDLINE (through PubMed), EMBASE, and the Cochrane Central Register of Controlled Trials (through October 7, 2015) were searched for randomized trials and observational studies examining pacing and syncope, and the bibliographies of known systematic reviews were also examined. Studies were rejected for poor-quality study methods and for the lack of the population, intervention, comparator, or outcome(s) of interest. Of 3188 citations reviewed, 10 studies met the inclusion criteria for systematic review, including a total of 676 patients. These included 9 randomized trials and 1 observational study. Of the 10 studies, 4 addressed patients with carotid sinus hypersensitivity, and the remaining 6 addressed vasovagal syncope. Among the 6 open-label (unblinded) studies, we found that pacing was associated with a 70% reduction in recurrent syncope (relative risk [RR]: 0.30; 95% confidence interval [CI]: 0.15-0.60). When the 2 analyzable studies with double-blinded methodology were considered separately, there was no clear benefit (RR: 0.73; 95% CI: 0.25-2.1), but confidence intervals were wide. The strongest evidence was from the randomized, double-blinded ISSUE-3 (Third International Study on Syncope of Uncertain Etiology) trial, which demonstrated a benefit of pacing among patients with recurrent syncope and asystole documented by implantable loop recorder. There are limited data with substantive evidence of outcome ascertainment bias, and only 2 studies with a double-blinded study design have been conducted. The evidence does not support the use of pacing for reflex-mediated syncope beyond patients with recurrent vasovagal syncope and asystole documented by implantable loop recorder. © 2017 by the American College of Cardiology Foundation, the American Heart Association, Inc., and the Heart Rhythm Society.

Treatment decisions on antidepressants in nursing homes: a qualitative study.

PubMed

Iden, Kristina Riis; Hjørleifsson, Stefan; Ruths, Sabine

2011-12-01

To explore decision-making on treatment with antidepressants among doctors and nurses in nursing homes. A qualitative study based on interviews with three focus groups comprising eight physicians engaged full time, eight physicians engaged part time, and eight registered nurses, respectively. The interview guide comprised questions on initiating, evaluating, and withdrawing treatment with antidepressants. The interviews were audio-recorded, transcribed, and analysed by systematic text condensation. The first theme was the diagnostic process. The informants expressed difficulty in differentiating between depression and sorrow resulting from loss in old age. Further, the doctors reported that they relied on nurses' observations and rarely carried out systematic diagnostic work and follow-up of patients with depression. The second theme was treatment. Antidepressants were usually the only type of treatment provided, and patients were kept on medication even though staff felt uncertain whether this was effective. The third theme was who really determines the treatment. Registered nurses reported that unskilled and auxiliary nursing staff requested drug treatment, and doctors felt some pressure from the nurses to prescribe antidepressants. This study suggests that the quality of diagnosis and treatment for depression in nursing homes needs to be improved in Norway. Doctors should be more available and take responsibility and leadership in medical decisions.

Cost effectiveness of a general practice chronic disease management plan for coronary heart disease in Australia.

PubMed

Chew, Derek P; Carter, Robert; Rankin, Bree; Boyden, Andrew; Egan, Helen

2010-05-01

The cost effectiveness of a general practice-based program for managing coronary heart disease (CHD) patients in Australia remains uncertain. We have explored this through an economic model. A secondary prevention program based on initial clinical assessment and 3 monthly review, optimising of pharmacotherapies and lifestyle modification, supported by a disease registry and financial incentives for quality of care and outcomes achieved was assessed in terms of incremental cost effectiveness ratio (ICER), in Australian dollars per disability adjusted life year (DALY) prevented. Based on 2006 estimates, 263 487 DALYs were attributable to CHD in Australia. The proposed program would add $115 650 000 to the annual national heath expenditure. Using an estimated 15% reduction in death and disability and a 40% estimated program uptake, the program's ICER is $8081 per DALY prevented. With more conservative estimates of effectiveness and uptake, estimates of up to $38 316 per DALY are observed in sensitivity analysis. Although innovation in CHD management promises improved future patient outcomes, many therapies and strategies proven to reduce morbidity and mortality are available today. A general practice-based program for the optimal application of current therapies is likely to be cost-effective and provide substantial and sustainable benefits to the Australian community.

Ginkgo biloba Extract for Patients with Early Diabetic Nephropathy: A Systematic Review

PubMed Central

Zhang, Lei; Mao, Wei; Guo, Xinfeng; Wu, Yifan; Li, Chuang; Lu, Zhaoyu; Su, Guobin; Li, Xiaoyan; Liu, Zhuangzhu; Guo, Rong; Jie, Xina; Wen, Zehuai; Liu, Xusheng

2013-01-01

Objectives. To evaluate the effectiveness and safety of a Ginkgo biloba extract for patients with early diabetic nephropathy. Methods. Randomised controlled trials (RCTs) conducted on adults with early diabetic nephropathy which used Gingko biloba extract were included. The major databases were searched, and manufacturers of Gingko biloba products were contacted for information on any published or unpublished studies. Two authors independently extracted the data from the included studies. Data analysis was conducted using Review Manager 5.0 software. Results. Sixteen RCTs were included. Ginkgo biloba extract decreased the urinary albumin excretion rate (UAER), fasting blood glucose (FBG), serum creatinine (SCR), and blood urea nitrogen (BUN). The extract also improved hemorheology. The methodological quality in the included studies was low. The explicit generation of the allocation sequence was described in only 6 trials. None of the included trials were confirmed to use blinding. Three studies had observed adverse events. One study using angiotensin-converting enzyme inhibitor (ACEi) reported mild cough in both groups. No serious adverse effects were reported. Conclusions. Gingko biloba extract is a valuable drug which has prospect in treating early diabetic nephropathy, especially with high UAER baseline level. The safety for early diabetic nephropathy is uncertain. Long-term, double-blinded RCTs with large sample sizes are still needed to provide stronger evidence. PMID:23533513

Consideration Sets and Their Role in Modelling Doctor Recommendations About Contraceptives.

PubMed

Fiebig, Denzil G; Viney, Rosalie; Knox, Stephanie; Haas, Marion; Street, Deborah J; Hole, Arne R; Weisberg, Edith; Bateson, Deborah

2017-01-01

Decisions about prescribed contraception are typically the result of a consultation between a woman and her doctor. In order to better understand contraceptive choice within this environment, stated preference methods are utilized to ask doctors about what contraceptive options they would discuss with different types of women. The role of doctors is to confine their discussion to a subset of products that best match their patient. This subset of options forms the consideration set from which the ultimate recommendation is made. Given the existence of consideration sets we address the issue of how to model appropriately the ultimate recommendations. The estimated models enable us to characterize doctor recommendations and how they vary with patient attributes and to highlight where recommendations are clear and when they are uncertain. The results also indicate systematic variation in recommendations across different types of doctors, and in particular we observe that some doctors are reluctant to embrace new products and instead recommend those that are more familiar. Such effects are one possible explanation for the relatively low uptake of more cost effective longer acting reversible contraceptives and indicate that further education and training of doctors may be warranted. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

New horizons: the management of hypertension in people with dementia

PubMed Central

Harrison, Jennifer Kirsty; Van Der Wardt, Veronika; Conroy, Simon Paul; Stott, David J.; Dening, Tom; Gordon, Adam Lee; Logan, Pip; Welsh, Tomas James; Taggar, Jaspal; Harwood, Rowan; Gladman, John R. F.

2016-01-01

Abstract The optimal management of hypertension in people with dementia is uncertain. This review explores if people with dementia experience greater adverse effects from antihypertensive medications, if cognitive function is protected or worsened by controlling blood pressure (BP) and if there are subgroups of people with dementia for whom antihypertensive therapy is more likely to be harmful. Robust evidence is scant, trials of antihypertensive medications have generally excluded those with dementia. Observational data show changes in risk association over the life course, with high BP being a risk factor for cognitive decline in mid-life, while low BP is predictive in later life. It is therefore possible that excessive BP lowering in older people with dementia might harm cognition. From the existing literature, there is no direct evidence of benefit or harm from treating hypertension in people with dementia. So what practical steps can the clinician take? Assess capacity, establish patient preferences when making treatment decisions, use ambulatory monitoring to thoroughly assess BP, individualise and consider deprescribing where side effects (e.g. hypotension) outweigh the benefits. Future research might include pragmatic randomised trials of targeted deprescribing, which include patient-centred outcome measures to help support decision-making and studies to address mechanistic uncertainties. PMID:27836926

Gastroesophageal reflux disease in children.

PubMed

Barnhart, Douglas C

2016-08-01

Despite the frequency with which antireflux procedures are performed, decisions about gastroesophageal reflux disease treatment remain challenging. Several factors contribute to the difficulties in managing gastroesophageal reflux. First, the distinction between physiologic and pathologic gastroesophageal reflux (gastroesophageal reflux disease-GERD) is not always clear. Second, measures of the extent of gastroesophageal reflux often poorly correlate to symptoms or other complications attributed to reflux in infants and children. A third challenge is that the outcome of antireflux procedures, predominately fundoplications, are relatively poorly characterized. All of these factors contribute to difficulty in knowing when to recommend antireflux surgery. One of the manifestations of the uncertainties surrounding GERD is the high degree of variability in the utilization of pediatric antireflux procedures throughout the United States. Pediatric surgeons are frequently consulted for GERD and fundoplication, uncertainties notwithstanding. Although retrospective series and anecdotal observations support fundoplication in some patients, there are many important questions for which sufficient high-quality data to provide a clear answer is lacking. In spite of this, surgeons need to provide guidance to patients and families while awaiting the development of improved evidence to aid in these recommendations. The purpose of this article is to define what is known and what is uncertain, with an emphasis on the most recent evidence. Copyright © 2016 Elsevier Inc. All rights reserved.

Access to investigational medicinal products for minors in Europe: ethical and regulatory issues in negotiating children's access to investigational medicines.

PubMed

Pinxten, Wim; Nys, Herman; Dierickx, Kris

2010-12-01

Patients who search for a better treatment, an increased quality of life, or even a chance to preserve life itself may claim to have an interest in accessing investigational medicinal products (IMP), particularly when no validated treatment for their disease or condition exists. For many, awaiting the uncertain and time-consuming process of converting an IMP into an approved drug may not appear a realistic option, as prognoses may be grim and a dramatic outcome may seem hard to avert. Gaining access to an IMP, however, often proves to be a difficult enterprise with a highly uncertain outcome. In addition, the process of seeking access to IMP is surrounded by various ethical issues that will be explored in this article. This paper explores the ethical concerns in two potential tracks of seeking access to IMP for minors: on an individual basis, or collectively, as a patient organisation. In this discourse, several unique ethical and regulatory concerns related to the direct negotiation of access to IMP for minor patients are identified, with a focus on product safety, the recruitment of research subjects, the unnoticed entry of market mechanisms in the recruitment of research subjects, and the sidelining of third parties in the recruitment process. The paper concludes with a concise reflection on the way forward. The quest for access to investigational drugs is particularly relevant to paediatric practice, in which a significant share of the drugs prescribed has never been tested in children or labelled for use in the paediatric population.

Inter-arm blood pressure difference in hospitalized elderly patients--is it consistent?

PubMed

Grossman, Alon; Weiss, Avraham; Beloosesky, Yichayaou; Morag-Koren, Nira; Green, Hefziba; Grossman, Ehud

2014-07-01

Inter-arm blood pressure difference (IAD) is recognized as a risk factor for cardiovascular mortality. Its reproducibility in the elderly is unknown. The authors determined the prevalence and reproducibility of IAD in hospitalized elderly patients. Blood pressure was measured simultaneously in both arms on two different days in elderly individuals hospitalized in a geriatric ward. The study included 364 elderly patients (mean age, 85±5 years). Eighty-four patients (23%) had systolic IAD >10 and 62 patients (17%) had diastolic IAD >10 mm Hg. A total of 319 patients had two blood pressure measurements. Systolic and diastolic IAD remained in the same category in 203 (64%) and 231 (72%) patients, respectively. Correlations of systolic and diastolic IAD between the two measurements were poor. Consistency was not affected by age, body mass index, comorbidities, or treatment. IAD is extremely common in hospitalized elderly patients, but, because of poor consistency, its clinical significance in this population is uncertain. ©2014 Wiley Periodicals, Inc.

Pregnancy in patients with chronic renal disease.

PubMed Central

Bear, R. A.

1978-01-01

Pregnancy is not invariably contra-indicated in patients with pre-existing renal disease. Clinical data now exist that permit the clinician to distinguish such patients who are likely to experience difficulty during pregnancy from those in whom pregnancy can be undertaken with high expectation of success. Patients suffering from systemic lupus erythematosus, active or inactive, with or without lupus nephritis, should avoid pregnancy. Patients with other forms of chronic renal disease in whom the serum creatinine concentration prior to pregnancy is less than 1.5 mg/dL are not exposed to increased maternal or fetal risk. On the other hand, patients with serum creatinine values exceeding 1.6 mg/dL experience a high incidence of maternal and fetal complications and should avoid pregnancy. The life expectancy of recipients of a renal transplant is uncertain, and these patients should receive counselling as to the advisability of undertaking pregnancy. The maternal risk in such patients is not inordinately high, but the fetal risk is considerable. PMID:350371

Diagnoses behind patients with hard-to-classify tremor and normal DaT-SPECT: a clinical follow up study.

PubMed

Menéndez-González, Manuel; Tavares, Francisco; Zeidan, Nahla; Salas-Pacheco, José M; Arias-Carrión, Oscar

2014-01-01

The [(123)I]ioflupane-a dopamine transporter radioligand-SPECT (DaT-SPECT) has proven to be useful in the differential diagnosis of tremor. Here, we investigate the diagnoses behind patients with hard-to-classify tremor and normal DaT-SPECT. Therefore, 30 patients with tremor and normal DaT-SPECT were followed up for 2 years. In 18 cases we were able to make a diagnosis. The residual 12 patients underwent a second DaT-SPECT, were then followed for additional 12 months and thereafter the diagnosis was reconsidered again. The final diagnoses included cases of essential tremor, dystonic tremor, multisystem atrophy, vascular parkinsonism, progressive supranuclear palsy, corticobasal degeneration, fragile X-associated tremor ataxia syndrome, psychogenic parkinsonism, iatrogenic parkinsonism and Parkinson's disease. However, for 6 patients the diagnosis remained uncertain. Larger series are needed to better establish the relative frequency of the different conditions behind these cases.

Sickle Cell Crisis and the Acute Abdomen

PubMed Central

Nazem, Ahmad; Walker, Mark

1986-01-01

Abdominal pain is one of the most common symptoms in sickle cell crisis, and its cause remains controversial. Simple vaso-occlusive crisis may be an explanation. The abdominal pain may also reflect an acute surgical abdomen. A patient presented with sickle cell crisis and abdominal pain; he had a periappendiceal abscess at the site of an appendiceal stump five months after appendectomy. The role of sickle cell anemia in the pathogenesis of this abscess is uncertain. PMID:3531534

Neuroblastoma in a patient with Sotos' syndrome.

PubMed Central

Nance, M A; Neglia, J P; Talwar, D; Berry, S A

1990-01-01

Sotos' syndrome, or cerebral gigantism, is a disorder of growth regulation. Tumours have occasionally been reported in children with Sotos' syndrome, but it is uncertain whether this is a coincidence, or whether it is aetiologically related to the underlying disorder of growth. We report a 15 month old child with a paraspinal neuroblastoma and Sotos' syndrome and suggest that children with this condition may be at higher risk for developing tumours than the general population. Images PMID:2319581

Duration of oral antibiotic therapy for the treatment of adult acne: a retrospective analysis investigating adherence to guideline recommendations and opportunities for cost-savings.

PubMed

Straight, Chelsey E; Lee, Young H; Liu, Guodong; Kirby, Joslyn S

2015-05-01

The duration of oral antibiotic acne therapy for adolescents compared with guidelines was recently investigated; however it was uncertain if duration of antibiotics for adult acne therapy differed. This study aimed to evaluate duration of oral antibiotics for adult acne compared with guidelines and determine possible cost-savings. This was a retrospective cohort study of MarketScan Commercial Claims and Encounters database that incorporated claims data to determine duration and costs of antibiotic treatment among adults ages 21 years and older. Of 17,448 courses, 84.5% (14,737) aligned with duration guidelines, although 12,040 (69.0%) courses did not include concomitant topical retinoid therapy. Mean savings of $592.26 per person could result if prolonged courses met guidelines. Mean (median) costs of generic and branded formulations for the most frequent course duration (90-179 days) were $103.77 ($54.27) and $1421.61 ($1462.25), respectively. Actual patient prescription adherence is uncertain and database lacks information regarding acne severity, patient physical characteristics, and clinical outcomes. The majority of oral antibiotic course durations follow guidelines, although topical retinoids are underused. Costs of antibiotic therapy were lower for shorter courses and those using generic medications; the cost-effectiveness of these modifications has not been investigated. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Reflexology has no immediate haemodynamic effect in patients with chronic heart failure: a double blind randomised controlled trial.

PubMed

Jones, Jenny; Thomson, Patricia; Lauder, William; Howie, Kate; Leslie, Stephen J

2013-08-01

This study measured the effects of reflexology in 12 reflexology-naive patients with chronic heart failure in a placebo-controlled, double blind randomised controlled study design. Outcomes included 'beat-to-beat' non-invasive continuous measurement of cardiovascular parameters and measurement of state of anxiety and pain/discomfort. There were no changes in any of the haemodynamic parameters measured (all p > 0.05). Perceived state of anxiety was significantly reduced post treatment in the control group only (p = 0.03). Reflexology applied to the feet of patients with chronic heart failure appears to have no immediate haemodynamic effects. While any long term treatment effect is uncertain, it would appear that reflexology is safe for use in this patient group. Copyright © 2013 Elsevier Ltd. All rights reserved.

Thrombophilia screening--at the right time, for the right patient, with a good reason.

PubMed

Stegnar, Mojca

2010-12-01

Thrombophilia can be identified in about half of all patients presenting with venous thromboembolism (VTE). Thrombophilia screening for various indications has increased tremendously, but whether the results of such tests help in the clinical management of patients is uncertain. Here, current recommendations for thrombophilia screening in selected groups of patients, and considerations whether other high-risk subjects should be tested are reviewed. The methods for determination of the most common thrombophilic defects (antithrombin, protein C, protein S deficiencies, Factor V Leiden and prothrombin G20210A) associated with strong to moderate risk of VTE are described, indicating the timing and location of thrombophilia screening. Circumstances when a positive result of thrombophilia screening helps clinicians decide if adjustments of the anticoagulant regime are needed are discussed. Finally, psychological, social and ethical dilemmas associated with thrombophilia screening are indicated.

Generalized Distributed Consensus-based Algorithms for Uncertain Systems and Networks

DTIC Science & Technology

2010-01-01

time linear systems with markovian jumping parameters and additive disturbances. SIAM Journal on Control and Optimization, 44(4):1165– 1191, 2005... time marko- vian jump linear systems , in the presence of delayed mode observations. Proceed- ings of the 2008 IEEE American Control Conference, pages...Markovian Jump Linear System state estimation . . . . 147 6 Conclusions 152 A Discrete- Time Coupled Matrix Equations 156 A.1 Properties of a special

Minimum time search in uncertain dynamic domains with complex sensorial platforms.

PubMed

Lanillos, Pablo; Besada-Portas, Eva; Lopez-Orozco, Jose Antonio; de la Cruz, Jesus Manuel

2014-08-04

The minimum time search in uncertain domains is a searching task, which appears in real world problems such as natural disasters and sea rescue operations, where a target has to be found, as soon as possible, by a set of sensor-equipped searchers. The automation of this task, where the time to detect the target is critical, can be achieved by new probabilistic techniques that directly minimize the Expected Time (ET) to detect a dynamic target using the observation probability models and actual observations collected by the sensors on board the searchers. The selected technique, described in algorithmic form in this paper for completeness, has only been previously partially tested with an ideal binary detection model, in spite of being designed to deal with complex non-linear/non-differential sensorial models. This paper covers the gap, testing its performance and applicability over different searching tasks with searchers equipped with different complex sensors. The sensorial models under test vary from stepped detection probabilities to continuous/discontinuous differentiable/non-differentiable detection probabilities dependent on distance, orientation, and structured maps. The analysis of the simulated results of several static and dynamic scenarios performed in this paper validates the applicability of the technique with different types of sensor models.

Minimum Time Search in Uncertain Dynamic Domains with Complex Sensorial Platforms

PubMed Central

Lanillos, Pablo; Besada-Portas, Eva; Lopez-Orozco, Jose Antonio; de la Cruz, Jesus Manuel

2014-01-01

The minimum time search in uncertain domains is a searching task, which appears in real world problems such as natural disasters and sea rescue operations, where a target has to be found, as soon as possible, by a set of sensor-equipped searchers. The automation of this task, where the time to detect the target is critical, can be achieved by new probabilistic techniques that directly minimize the Expected Time (ET) to detect a dynamic target using the observation probability models and actual observations collected by the sensors on board the searchers. The selected technique, described in algorithmic form in this paper for completeness, has only been previously partially tested with an ideal binary detection model, in spite of being designed to deal with complex non-linear/non-differential sensorial models. This paper covers the gap, testing its performance and applicability over different searching tasks with searchers equipped with different complex sensors. The sensorial models under test vary from stepped detection probabilities to continuous/discontinuous differentiable/non-differentiable detection probabilities dependent on distance, orientation, and structured maps. The analysis of the simulated results of several static and dynamic scenarios performed in this paper validates the applicability of the technique with different types of sensor models. PMID:25093345

N-terminal pro-brain natriuretic peptide and high-sensitivity troponin in the evaluation of acute chest pain of uncertain etiology. A PITAGORAS substudy.

PubMed

Sanchis, Juan; Bardají, Alfredo; Bosch, Xavier; Loma-Osorio, Pablo; Marín, Francisco; Sánchez, Pedro L; Calvo, Francisco; Avanzas, Pablo; Hernández, Carolina; Serrano, Silvia; Carratalá, Arturo; Barrabés, José A

2013-07-01

High-sensitivity troponin assays have improved the diagnosis of acute coronary syndrome in patients presenting with chest pain and normal troponin levels as measured by conventional assays. Our aim was to investigate whether N-terminal pro-brain natriuretic peptide provides additional information to troponin determination in these patients. A total of 398 patients, included in the PITAGORAS study, presenting to the emergency department with chest pain and normal troponin levels as measured by conventional assay in 2 serial samples (on arrival and 6 h to 8h later) were studied. The samples were also analyzed in a central laboratory for high-sensitivity troponin T (both samples) and for N-terminal pro-brain natriuretic peptide (second sample). The endpoints were diagnosis of acute coronary syndrome and the composite endpoint of in-hospital revascularization or a 30-day cardiac event. Acute coronary syndrome was adjudicated to 79 patients (20%) and the composite endpoint to 59 (15%). When the N-terminal pro-brain natriuretic peptide quartile increased, the diagnosis of acute coronary syndrome also increased (12%, 16%, 23% and 29%; P=.01), as did the risk of the composite endpoint (6%, 13%, 16% and 24%; P=.004). N-terminal pro-brain natriuretic peptide elevation (>125ng/L) was associated with both endpoints (relative risk= 2.0; 95% confidence interval, 1.2-3.3; P=.02; relative risk=2.4; 95% confidence interval, 1.4-4.2; P=.004). However, in the multivariable models adjusted by clinical and electrocardiographic data, a predictive value was found for high-sensitivity T troponin but not for N-terminal pro-brain natriuretic peptide. In low-risk patients with chest pain of uncertain etiology evaluated using high-sensitivity T troponin, N-terminal pro-brain natriuretic peptide does not contribute additional predictive value to diagnosis or the prediction of short-term outcomes. Copyright © 2012 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

The use of contrasted transvaginal sonography in the diagnosis of gynecologic diseases: a preliminary study.

PubMed

Testa, Antonia Carla; Ferrandina, Gabriella; Fruscella, Erika; Van Holsbeke, Caroline; Ferrazzi, Enrico; Leone, Francesco P G; Arduini, Domenico; Exacoustos, Caterina; Bokor, Daniela; Scambia, Giovanni; Timmerman, Dirk

2005-09-01

The purpose of this study was to evaluate the efficacy of a new contrast-dedicated ultrasound technology, contrast-tuned imaging (CnTI), implemented on an endovaginal probe and using the second-generation contrast agent SonoVue (Bracco International BV, Amsterdam, the Netherlands), compared with the standard ultrasound examination in different gynecologic diseases. Eighty-nine patients were enrolled in the study in 4 different clinical centers. The study included 40 patients with uncertain pelvic adnexal masses, 10 patients with pelvic masses indicative of recurrences of gynecologic tumors, 26 patients with uterine pathologic features, and 13 patients with cervical lesions. Application of CnTI technology after the SonoVue injection gave a picture of the intralesional microvascularization dramatically different from that obtained during color Doppler examination. Of the 40 pelvic masses, 15 (37.5%) were considered benign and 25 (62.5%) were considered malignant at B-mode and color Doppler examinations. Contrast-enhanced sonography showed no intralesional contrast perfusion in 11 (73%) of 15 cases, and all these were benign at final diagnosis. Of the 4 (27%) cases that had perfusion, 2 were malignant. Conversely, of the 25 cases with positive findings at color Doppler examination and therefore expected to show the appearance of contrast tissue-filling morphologic characteristics, 13 (52%) were malignant at final diagnosis. For evaluation of uterine pathologic features, the CnTI-SonoVue technology did not appear to be superior to the B-mode and color Doppler examinations; however, for the evaluation of cervical cancer, CnTI-SonoVue technology revealed a better definition of the margins of the neoplastic lesions in 4 (40%) of 10 cases. In the evaluation of uncertain pelvic masses, the CnTI technology led to an improvement in the ability of the practitioner to differentiate benign from malignant adnexal lesions.

Randomized Controlled Trial of a Video Decision Support Tool for Cardiopulmonary Resuscitation Decision Making in Advanced Cancer

PubMed Central

Volandes, Angelo E.; Paasche-Orlow, Michael K.; Mitchell, Susan L.; El-Jawahri, Areej; Davis, Aretha Delight; Barry, Michael J.; Hartshorn, Kevan L.; Jackson, Vicki Ann; Gillick, Muriel R.; Walker-Corkery, Elizabeth S.; Chang, Yuchiao; López, Lenny; Kemeny, Margaret; Bulone, Linda; Mann, Eileen; Misra, Sumi; Peachey, Matt; Abbo, Elmer D.; Eichler, April F.; Epstein, Andrew S.; Noy, Ariela; Levin, Tomer T.; Temel, Jennifer S.

2013-01-01

Purpose Decision making regarding cardiopulmonary resuscitation (CPR) is challenging. This study examined the effect of a video decision support tool on CPR preferences among patients with advanced cancer. Patients and Methods We performed a randomized controlled trial of 150 patients with advanced cancer from four oncology centers. Participants in the control arm (n = 80) listened to a verbal narrative describing CPR and the likelihood of successful resuscitation. Participants in the intervention arm (n = 70) listened to the identical narrative and viewed a 3-minute video depicting a patient on a ventilator and CPR being performed on a simulated patient. The primary outcome was participants' preference for or against CPR measured immediately after exposure to either modality. Secondary outcomes were participants' knowledge of CPR (score range of 0 to 4, with higher score indicating more knowledge) and comfort with video. Results The mean age of participants was 62 years (standard deviation, 11 years); 49% were women, 44% were African American or Latino, and 47% had lung or colon cancer. After the verbal narrative, in the control arm, 38 participants (48%) wanted CPR, 41 (51%) wanted no CPR, and one (1%) was uncertain. In contrast, in the intervention arm, 14 participants (20%) wanted CPR, 55 (79%) wanted no CPR, and 1 (1%) was uncertain (unadjusted odds ratio, 3.5; 95% CI, 1.7 to 7.2; P < .001). Mean knowledge scores were higher in the intervention arm than in the control arm (3.3 ± 1.0 v 2.6 ± 1.3, respectively; P < .001), and 65 participants (93%) in the intervention arm were comfortable watching the video. Conclusion Participants with advanced cancer who viewed a video of CPR were less likely to opt for CPR than those who listened to a verbal narrative. PMID:23233708

Distributed micro-releases of bioterror pathogens : threat characterizations and epidemiology from uncertain patient observables.

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

Wolf, Michael M.; Marzouk, Youssef M.; Adams, Brian M.

2008-10-01

Terrorist attacks using an aerosolized pathogen preparation have gained credibility as a national security concern since the anthrax attacks of 2001. The ability to characterize the parameters of such attacks, i.e., to estimate the number of people infected, the time of infection, the average dose received, and the rate of disease spread in contemporary American society (for contagious diseases), is important when planning a medical response. For non-contagious diseases, we address the characterization problem by formulating a Bayesian inverse problem predicated on a short time-series of diagnosed patients exhibiting symptoms. To keep the approach relevant for response planning, we limitmore » ourselves to 3.5 days of data. In computational tests performed for anthrax, we usually find these observation windows sufficient, especially if the outbreak model employed in the inverse problem is accurate. For contagious diseases, we formulated a Bayesian inversion technique to infer both pathogenic transmissibility and the social network from outbreak observations, ensuring that the two determinants of spreading are identified separately. We tested this technique on data collected from a 1967 smallpox epidemic in Abakaliki, Nigeria. We inferred, probabilistically, different transmissibilities in the structured Abakaliki population, the social network, and the chain of transmission. Finally, we developed an individual-based epidemic model to realistically simulate the spread of a rare (or eradicated) disease in a modern society. This model incorporates the mixing patterns observed in an (American) urban setting and accepts, as model input, pathogenic transmissibilities estimated from historical outbreaks that may have occurred in socio-economic environments with little resemblance to contemporary society. Techniques were also developed to simulate disease spread on static and sampled network reductions of the dynamic social networks originally in the individual-based model, yielding faster, though approximate, network-based epidemic models. These reduced-order models are useful in scenario analysis for medical response planning, as well as in computationally intensive inverse problems.« less

Synchronization transmission of laser pattern signal within uncertain switched network

NASA Astrophysics Data System (ADS)

Lü, Ling; Li, Chengren; Li, Gang; Sun, Ao; Yan, Zhe; Rong, Tingting; Gao, Yan

2017-06-01

We propose a new technology for synchronization transmission of laser pattern signal within uncertain network with controllable topology. In synchronization process, the connection of dynamic network can vary at all time according to different demands. Especially, we construct the Lyapunov function of network through designing a special semi-positive definite function, and the synchronization transmission of laser pattern signal within uncertain network with controllable topology can be realized perfectly, which effectively avoids the complicated calculation for solving the second largest eignvalue of the coupling matrix of the dynamic network in order to obtain the network synchronization condition. At the same time, the uncertain parameters in dynamic equations belonging to network nodes can also be identified accurately via designing the identification laws of uncertain parameters. In addition, there are not any limitations for the synchronization target of network in the new technology, in other words, the target can either be a state variable signal of an arbitrary node within the network or an exterior signal.

Combined Limb-Sparing Surgery and Radiation Therapy to Treat Sarcomas of the Hands and Feet: Long-Term Cancer Outcomes and Morbidity

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

Bishop, Andrew J.; Zagars, Gunar K.; Moon, Bryan S.

Purpose: The purpose of this study was to investigate local control, survival outcomes, and complication rates of patients treated with limb-sparing surgery and radiation therapy (RT) for soft tissue sarcomas (STS) of the hands and feet. Methods and Materials: We reviewed the medical records of 85 consecutive patients treated for STS of the hands (n=38, 45%) and feet (n=47, 55%) between 1966 and 2012. The median age was 41 years (range, 10-82 years of age). Sixty-seven patients (79%) received postoperative RT after resection of their tumor (median dose, 60 Gy; range, 45-70 Gy). The remaining 18 patients (21%) were treated with preoperative RT followed by tumormore » resection (median dose, 50 Gy; range, 50-64 Gy). Results: Median follow-up was 140 months (range, 24-442 months). Five-year local control, overall survival, and disease-specific survival rates were 86%, 89%, and 89%, respectively. Positive or uncertain surgical margin status was the only factor adversely associated with local recurrence (19% vs 6% for negative margins, P=.046) but this lost significance on multivariate analysis when adjusting for RT dose ≥64 Gy. Of the 12 patients who had local relapses, 6 (50%) were salvaged, and only 2 of those required salvage amputation. Five patients had grade ≥3 late RT sequelae, with 2 patients (2%) having moderate limitations of limb function and 3 patients (4%) having severe limitations requiring procedures for skin ulceration. Conclusions: Limb-sparing surgery combined with RT provides excellent local control outcomes for sarcomas arising in the hands or feet. In patients who have local recurrence, salvage without amputation is possible. The excellent cancer control outcomes observed, considering the minimal impact on limb function, support use of combined modality, limb-sparing local therapy for STS arising in the hands or feet.« less

Combined Limb-Sparing Surgery and Radiation Therapy to Treat Sarcomas of the Hands and Feet: Long-Term Cancer Outcomes and Morbidity.

PubMed

Bishop, Andrew J; Zagars, Gunar K; Moon, Bryan S; Lin, Patrick P; Lewis, Valerae O; Guadagnolo, B Ashleigh

2015-08-01

The purpose of this study was to investigate local control, survival outcomes, and complication rates of patients treated with limb-sparing surgery and radiation therapy (RT) for soft tissue sarcomas (STS) of the hands and feet. We reviewed the medical records of 85 consecutive patients treated for STS of the hands (n=38, 45%) and feet (n=47, 55%) between 1966 and 2012. The median age was 41 years (range, 10-82 years of age). Sixty-seven patients (79%) received postoperative RT after resection of their tumor (median dose, 60 Gy; range, 45-70 Gy). The remaining 18 patients (21%) were treated with preoperative RT followed by tumor resection (median dose, 50 Gy; range, 50-64 Gy). Median follow-up was 140 months (range, 24-442 months). Five-year local control, overall survival, and disease-specific survival rates were 86%, 89%, and 89%, respectively. Positive or uncertain surgical margin status was the only factor adversely associated with local recurrence (19% vs 6% for negative margins, P=.046) but this lost significance on multivariate analysis when adjusting for RT dose ≥64 Gy. Of the 12 patients who had local relapses, 6 (50%) were salvaged, and only 2 of those required salvage amputation. Five patients had grade ≥3 late RT sequelae, with 2 patients (2%) having moderate limitations of limb function and 3 patients (4%) having severe limitations requiring procedures for skin ulceration. Limb-sparing surgery combined with RT provides excellent local control outcomes for sarcomas arising in the hands or feet. In patients who have local recurrence, salvage without amputation is possible. The excellent cancer control outcomes observed, considering the minimal impact on limb function, support use of combined modality, limb-sparing local therapy for STS arising in the hands or feet. Copyright © 2015 Elsevier Inc. All rights reserved.

An Application of Semi-parametric Estimator with Weighted Matrix of Data Depth in Variance Component Estimation

NASA Astrophysics Data System (ADS)

Pan, X. G.; Wang, J. Q.; Zhou, H. Y.

2013-05-01

The variance component estimation (VCE) based on semi-parametric estimator with weighted matrix of data depth has been proposed, because the coupling system model error and gross error exist in the multi-source heterogeneous measurement data of space and ground combined TT&C (Telemetry, Tracking and Command) technology. The uncertain model error has been estimated with the semi-parametric estimator model, and the outlier has been restrained with the weighted matrix of data depth. On the basis of the restriction of the model error and outlier, the VCE can be improved and used to estimate weighted matrix for the observation data with uncertain model error or outlier. Simulation experiment has been carried out under the circumstance of space and ground combined TT&C. The results show that the new VCE based on the model error compensation can determine the rational weight of the multi-source heterogeneous data, and restrain the outlier data.

Performance recovery of a class of uncertain non-affine systems with unmodelled dynamics: an indirect dynamic inversion method

NASA Astrophysics Data System (ADS)

Yi, Bowen; Lin, Shuyi; Yang, Bo; Zhang, Weidong

2018-02-01

This paper presents an output feedback indirect dynamic inversion (IDI) approach for a class of uncertain nonaffine systems with input unmodelled dynamics. Compared with previous approaches to achieve performance recovery, the proposed method aims at dealing with a broader class of nonaffine-in-control systems with triangular structure. An IDI state feedback law is designed first, in which less knowledge of the model plant is needed compared to earlier approximate dynamic inversion methods, thus yielding more robust performance. After that, an extended high-gain observer is designed to accomplish the task with output feedback. Finally, we prove that the designed IDI controller is equivalent to an adaptive proportional-integral (PI) controller, with respect to both time response equivalence and robustness equivalence. The conclusion implies that for the studied strict-feedback non-affine systems with unmodelled dynamics, there always exits a PI controller to stabilise the systems. The effectiveness and benefits of the designed approach are verified by three examples.

Search asymmetries: parallel processing of uncertain sensory information.

PubMed

Vincent, Benjamin T

2011-08-01

What is the mechanism underlying search phenomena such as search asymmetry? Two-stage models such as Feature Integration Theory and Guided Search propose parallel pre-attentive processing followed by serial post-attentive processing. They claim search asymmetry effects are indicative of finding pairs of features, one processed in parallel, the other in serial. An alternative proposal is that a 1-stage parallel process is responsible, and search asymmetries occur when one stimulus has greater internal uncertainty associated with it than another. While the latter account is simpler, only a few studies have set out to empirically test its quantitative predictions, and many researchers still subscribe to the 2-stage account. This paper examines three separate parallel models (Bayesian optimal observer, max rule, and a heuristic decision rule). All three parallel models can account for search asymmetry effects and I conclude that either people can optimally utilise the uncertain sensory data available to them, or are able to select heuristic decision rules which approximate optimal performance. Copyright © 2011 Elsevier Ltd. All rights reserved.

Synthetic Spectral Ananlysis of the Nova-Like Variable KQ Mon

NASA Astrophysics Data System (ADS)

Wolfe, Aaron; Sion, E.

2011-01-01

KQ Mon is classified as a nova-like variable with an uncertain orbital period of 0.128 d. Optical spectra (Zwitter, T. & Munari, U.1994, A&AS, 107, 503) reveal no emission lines but strong Balmer absorption features. High speed flickering has been observed indicative of accretion. IUE spectra reveal deep absorption lines due to C III, C II, Si III, Si IV, C IV, He II but no P Cygni profiles indicative of outflow. Its classification in Ritter and Kolb (2006) as a UX UMa type nova-like is uncertain. We have carried out the first synthetic spectral analysis of the IUE archival spectra of KQ Mon with realistic accretion disk models with vertical structure and high gravity photosphere models. The results of our model atmosphere and model accretion disk analyses are presented. We discuss the properties that we have derived for KQ Mon and compare KQ Mon with other nova-like variables viewed at low inclination. This work was supported in part by NSF grant AST0807892 to Villanova University.

Spatial planning using probabilistic flood maps

NASA Astrophysics Data System (ADS)

Alfonso, Leonardo; Mukolwe, Micah; Di Baldassarre, Giuliano

2015-04-01

Probabilistic flood maps account for uncertainty in flood inundation modelling and convey a degree of certainty in the outputs. Major sources of uncertainty include input data, topographic data, model structure, observation data and parametric uncertainty. Decision makers prefer less ambiguous information from modellers; this implies that uncertainty is suppressed to yield binary flood maps. Though, suppressing information may potentially lead to either surprise or misleading decisions. Inclusion of uncertain information in the decision making process is therefore desirable and transparent. To this end, we utilise the Prospect theory and information from a probabilistic flood map to evaluate potential decisions. Consequences related to the decisions were evaluated using flood risk analysis. Prospect theory explains how choices are made given options for which probabilities of occurrence are known and accounts for decision makers' characteristics such as loss aversion and risk seeking. Our results show that decision making is pronounced when there are high gains and loss, implying higher payoffs and penalties, therefore a higher gamble. Thus the methodology may be appropriately considered when making decisions based on uncertain information.

The observed properties of Fast Radio Bursts

NASA Astrophysics Data System (ADS)

Ravi, Vikram

2018-06-01

I present an empirical study of the properties of fast radio bursts (FRBs): Gigahertz-frequency, dispersed pulses of extragalactic origin. I focus my investigation on a sample of seventeen FRBs detected at the Parkes radio telescope with largely self-consistent instrumentation. Of this sample, six are temporally unresolved, eight exhibit evidence for scattering in inhomogeneous plasma, and five display potentially intrinsic temporal structure. The characteristic scattering timescales at a frequency of 1 GHz range between 0.005 ms and 32 ms; moderate evidence exists for a relation between FRB scattering timescales and dispersion measures. Additionally, I present constraints on the fluences of Parkes FRBs, accounting for their uncertain sky-positions, and use the multiple-beam detection of FRB 010724 (the Lorimer burst) to measure its fluence to be 800 ± 400 Jy ms. FRBs, including the repeating FRB 121102, appear to manifest with a plethora of characteristics, and it is uncertain at present whether they share a common class of progenitor object, or arise from a selection of independent progenitors.

The Indecision Model of Psychophysical Performance in Dual-Presentation Tasks: Parameter Estimation and Comparative Analysis of Response Formats

PubMed Central

García-Pérez, Miguel A.; Alcalá-Quintana, Rocío

2017-01-01

Psychophysical data from dual-presentation tasks are often collected with the two-alternative forced-choice (2AFC) response format, asking observers to guess when uncertain. For an analytical description of performance, psychometric functions are then fitted to data aggregated across the two orders/positions in which stimuli were presented. Yet, order effects make aggregated data uninterpretable, and the bias with which observers guess when uncertain precludes separating sensory from decisional components of performance. A ternary response format in which observers are also allowed to report indecision should fix these problems, but a comparative analysis with the 2AFC format has never been conducted. In addition, fitting ternary data separated by presentation order poses serious challenges. To address these issues, we extended the indecision model of psychophysical performance to accommodate the ternary, 2AFC, and same–different response formats in detection and discrimination tasks. Relevant issues for parameter estimation are also discussed along with simulation results that document the superiority of the ternary format. These advantages are demonstrated by fitting the indecision model to published detection and discrimination data collected with the ternary, 2AFC, or same–different formats, which had been analyzed differently in the sources. These examples also show that 2AFC data are unsuitable for testing certain types of hypotheses. matlab and R routines written for our purposes are available as Supplementary Material, which should help spread the use of the ternary format for dependable collection and interpretation of psychophysical data. PMID:28747893

Learning and inference using complex generative models in a spatial localization task.

PubMed

Bejjanki, Vikranth R; Knill, David C; Aslin, Richard N

2016-01-01

A large body of research has established that, under relatively simple task conditions, human observers integrate uncertain sensory information with learned prior knowledge in an approximately Bayes-optimal manner. However, in many natural tasks, observers must perform this sensory-plus-prior integration when the underlying generative model of the environment consists of multiple causes. Here we ask if the Bayes-optimal integration seen with simple tasks also applies to such natural tasks when the generative model is more complex, or whether observers rely instead on a less efficient set of heuristics that approximate ideal performance. Participants localized a "hidden" target whose position on a touch screen was sampled from a location-contingent bimodal generative model with different variances around each mode. Over repeated exposure to this task, participants learned the a priori locations of the target (i.e., the bimodal generative model), and integrated this learned knowledge with uncertain sensory information on a trial-by-trial basis in a manner consistent with the predictions of Bayes-optimal behavior. In particular, participants rapidly learned the locations of the two modes of the generative model, but the relative variances of the modes were learned much more slowly. Taken together, our results suggest that human performance in a more complex localization task, which requires the integration of sensory information with learned knowledge of a bimodal generative model, is consistent with the predictions of Bayes-optimal behavior, but involves a much longer time-course than in simpler tasks.

Robust adaptive controller design for a class of uncertain nonlinear systems using online T-S fuzzy-neural modeling approach.

PubMed

Chien, Yi-Hsing; Wang, Wei-Yen; Leu, Yih-Guang; Lee, Tsu-Tian

2011-04-01

This paper proposes a novel method of online modeling and control via the Takagi-Sugeno (T-S) fuzzy-neural model for a class of uncertain nonlinear systems with some kinds of outputs. Although studies about adaptive T-S fuzzy-neural controllers have been made on some nonaffine nonlinear systems, little is known about the more complicated uncertain nonlinear systems. Because the nonlinear functions of the systems are uncertain, traditional T-S fuzzy control methods can model and control them only with great difficulty, if at all. Instead of modeling these uncertain functions directly, we propose that a T-S fuzzy-neural model approximates a so-called virtual linearized system (VLS) of the system, which includes modeling errors and external disturbances. We also propose an online identification algorithm for the VLS and put significant emphasis on robust tracking controller design using an adaptive scheme for the uncertain systems. Moreover, the stability of the closed-loop systems is proven by using strictly positive real Lyapunov theory. The proposed overall scheme guarantees that the outputs of the closed-loop systems asymptotically track the desired output trajectories. To illustrate the effectiveness and applicability of the proposed method, simulation results are given in this paper.

Functional expansion of sensorimotor representation and structural reorganization of callosal connections in lower limb amputees.

PubMed

Simões, Elington L; Bramati, Ivanei; Rodrigues, Erika; Franzoi, Ana; Moll, Jorge; Lent, Roberto; Tovar-Moll, Fernanda

2012-02-29

Previous studies have indicated that amputation or deafferentation of a limb induces functional changes in sensory (S1) and motor (M1) cortices, related to phantom limb pain. However, the extent of cortical reorganization after lower limb amputation in patients with nonpainful phantom phenomena remains uncertain. In this study, we combined functional magnetic resonance (fMRI) and diffusion tensor imaging (DTI) to investigate the existence and extent of cortical and callosal plasticity in these subjects. Nine "painless" patients with lower limb amputation and nine control subjects (sex- and age-matched) underwent a 3-T MRI protocol, including fMRI with somatosensory stimulation. In amputees, we observed an expansion of activation maps of the stump in S1 and M1 of the deafferented hemisphere, spreading to neighboring regions that represent the trunk and upper limbs. We also observed that tactile stimulation of the intact foot in amputees induced a greater activation of ipsilateral S1, when compared with controls. These results demonstrate a functional remapping of S1 in lower limb amputees. However, in contrast to previous studies, these neuroplastic changes do not appear to be dependent on phantom pain but do also occur in those who reported only the presence of phantom sensation without pain. In addition, our findings indicate that amputation of a limb also induces changes in the cortical representation of the intact limb. Finally, DTI analysis showed structural changes in the corpus callosum of amputees, compatible with the hypothesis that phantom sensations may depend on inhibitory release in the sensorimotor cortex.

Neurodevelopmental outcome in prenatally diagnosed isolated agenesis of the corpus callosum.

PubMed

Folliot-Le Doussal, Lise; Chadie, Alexandra; Brasseur-Daudruy, Marie; Verspyck, Eric; Saugier-Veber, Pascale; Marret, Stéphane

2018-01-01

Neurodevelopmental outcome in children with agenesis of the corpus callosum (ACC) is correlated with the presence or absence of associated brain abnormalities. Indeed, neurodevelopmental outcome shows severe disabilities when the ACC is not isolated whereas in isolated forms, the neurologic development is mainly normal. Contrary to data in several published studies, the prognosis remains uncertain even in isolated forms, which may lead in France to medical termination of pregnancy. To evaluate long-term neurodevelopmental outcome in children with prenatally diagnosed isolated ACC. This is a follow-up study conducted in Normandy (France). It included a cohort of 25 children born between January 1991 and June 2016, with a prenatal diagnosis of isolated ACC and who were followed for at least two years. The average follow-up was 8±5years. ACC was complete in 17 patients (68%), partial in 5 (20%) and hypoplastic in 3 (12%). Whereas global motor development was normal in each case, normal neurodevelopmental outcome or mild disabilities occurred in 88% children and moderate/severe neuro-disabilities were present in 12% of children. Wechsler Intelligence Scale for Children-IV evaluations and Intellectual Total Quotients were within normal range, but we observed lower scores in verbal comprehension, social judgment, executive functions. A lower score in morphosyntax was observed among 52% of children with oral language disorders. Neurodevelopmental outcome was favorable in most of our patients with isolated ACC, but mild learning disabilities emerged in older children. Long-term follow-up until school age is essential to provide early diagnosis and appropriate care support. Copyright © 2017 Elsevier B.V. All rights reserved.

[The Clinical Significance of Serum Alpha-fetoprotein in Diagnosing Hepatocellular Carcinoma in a Health Screening Population].

PubMed

Ko, Young Sun; Bae, Joo Hwan; Sinn, Dong Hyun; Gwak, Geum Youn; Kang, Wonseok; Paik, Yong Han; Choi, Moon Seok; Lee, Joon Hyeok; Koh, Kwang Cheol; Paik, Seung Woon

2017-04-25

Serum alpha-fetoprotein (AFP) measurement is commonly included in a health check-up program in Korea. However, its benefits remain uncertain. We analyzed whether AFP measurement should be included in a general health check-up program to screen for hepatocellular carcinoma (HCC). A total of 36,552 adults aged 18 years or older-who participated in a routine health examination including AFP determination between January 2009 and December 2009 at the Health Promotion Center, Samsung Medical Center, South Korea-were analyzed. High risk of HCC was defined as positivity for hepatitis B surface antigen, anti-hepatitis C virus antibody or having liver cirrhosis. AFP level >10 ng/mL was observed in 27 participants (0.1%) and primary liver cancer was diagnosed in 9 patients (6 HCC and 3 cholangiocarcinoma). Among 1,619 participants with high risk factors of HCC, AFP level >10 ng/mL was observed in 16 participants, of which, 4 diagnoses were made. Sensitivity, specificity, positive predictive value, and negative predictive value of AFP for HCC was 0.66, 0.99, 0.25 and 0.99, respectively, for high risk participants. Among 34,933 participants without risk factors for HCC, 11 patients (<0.1%) showed elevated AFP levels above 10 ng/mL, and no case was diagnosed with primary liver cancer during a median follow-up period of 36 months (range: 0-48 months). AFP elevation was rare in participants without risk factors for HCC, and was unable to screen for HCC in this population. We discourage routine AFP measurements for asymptomatic adults without risk factors of HCC.

Specific mutations in the beta-catenin gene (CTNNB1) correlate with local recurrence in sporadic desmoid tumors.

PubMed

Lazar, Alexander J F; Tuvin, Daniel; Hajibashi, Shohrae; Habeeb, Sultan; Bolshakov, Svetlana; Mayordomo-Aranda, Empar; Warneke, Carla L; Lopez-Terrada, Dolores; Pollock, Raphael E; Lev, Dina

2008-11-01

Desmoid fibromatosis is a rare, nonmetastatic neoplasm marked by local invasiveness and relentless recurrence. Molecular determinants of desmoid recurrence remain obscure. beta-Catenin deregulation has been commonly identified in sporadic desmoids although the incidence of CTNNB1 (the gene encoding beta-catenin) mutations is uncertain. Consequently, we evaluated the prevalence of CTNNB1 mutations in a large cohort of sporadic desmoids and examined whether mutation type was relevant to desmoid outcome. Desmoid specimens (195 tumors from 160 patients, 1985 to 2005) and control dermal scars were assembled into a clinical data-linked tissue microarray. CTNNB1 genotyping was performed on a 138-sporadic desmoid subset. Immunohistochemical scoring was performed per standard criteria and data were analyzed using Kaplan-Meier and other indicated methods. CTNNB1 mutations were observed in 117 of 138 (85%) of desmoids. Three discrete mutations in two codons of CTNNB1 exon 3 were identified: 41A (59%), 45F (33%), and 45P (8%, excluded from further analysis because of rarity). Five-year recurrence-free survival was significantly poorer in 45F-mutated desmoids (23%, P < 0.0001) versus either 41A (57%) or nonmutated tumors (65%). Nuclear beta-catenin expression was observed in 98% of specimens and intensity was inversely correlated with incidence of desmoid recurrence (P < 0.01). In conclusion, CTNNB1 mutations are highly common in desmoid tumors. Furthermore, patients harboring CTNNB1 (45F) mutations are at particular risk for recurrence and therefore may especially benefit from adjuvant therapeutic approaches.

Economic Evaluation of Community-Based Case Management of Patients Suffering From Chronic Obstructive Pulmonary Disease.

PubMed

Sørensen, Sabrina Storgaard; Pedersen, Kjeld Møller; Weinreich, Ulla Møller; Ehlers, Lars

2017-06-01

To analyse the cost effectiveness of community-based case management for patients suffering from chronic obstructive pulmonary disease (COPD). The study took place in the third largest municipality in Denmark and was conducted as a randomised controlled trial with 12 months of follow-up. A total of 150 patients with COPD were randomised into two groups receiving usual care and case management in addition to usual care. Case management included among other things self care proficiency, medicine compliance, and care coordination. Outcome measure for the analysis was the incremental cost-effectiveness ratio (ICER) as cost per quality-adjusted life year (QALY) from the perspective of the healthcare sector. Costs were valued in British Pounds (£) at price level 2016. Scenario analyses and probabilistic sensitivity analyses were conducted in order to assess uncertainty of the ICER estimate. The intervention resulted in a QALY improvement of 0.0146 (95% CI -0.0216; 0.0585), and a cost increase of £494 (95% CI -1778; 2766) per patient. No statistically significant difference was observed either in costs or effects. The ICER was £33,865 per QALY gained. Scenario analyses confirmed the robustness of the result and revealed slightly lower ICERs of £28,100-£31,340 per QALY. Analysis revealed that case management led to a positive incremental QALY, but were more costly than usual care. The highly uncertain ICER somewhat exceeds for instance the threshold value used by the National Institute of Health and Care Excellence (NICE). No formally established Danish threshold value exists. ClinicalTrials.gov Identifier: NCT01512836.

Empirical Support for DSM-IV Schizoaffective Disorder: Clinical and Cognitive Validators from a Large Patient Sample

PubMed Central

DeRosse, Pamela; Burdick, Katherine E.; Lencz, Todd; Siris, Samuel G.; Malhotra, Anil K.

2013-01-01

Objective The diagnosis of schizoaffective disorder has long maintained an uncertain status in psychiatric nosology. Studies comparing clinical and biological features of patients with schizoaffective disorder to patients with related disorders [e.g., schizophrenia and bipolar disorder] can provide an evidence base for judging the validity of the diagnostic category. However, because most prior studies of schizoaffective disorder have only evaluated differences between groups at a static timepoint, it is unclear how these disorders may be related when the entire illness course is taken into consideration. Methods We ascertained a large cohort [N = 993] of psychiatric patients with a range of psychotic diagnoses including schizophrenia with no history of major affective episodes [SZ−; N = 371], schizophrenia with a superimposed mood syndrome [SZ+; N = 224], schizoaffective disorder [SAD; N = 129] and bipolar I disorder with psychotic features [BPD+; N = 269]. Using cross-sectional data we designed key clinical and neurocognitive dependent measures that allowed us to test longitudinal hypotheses about the differences between these diagnostic entities. Results Large differences between diagnostic groups on several demographic and clinical variables were observed. Most notably, groups differed on a putative measure of cognitive decline. Specifically, the SAD group demonstrated significantly greater post-onset cognitive decline compared to the BP+ group, with the SZ− and SZ+ group both exhibiting levels of decline intermediate to BPD+ and SAD. Conclusions These results suggest that schizoaffective disorder may possess distinct features. Contrary to earlier formulations, schizoaffective disorder may be a more severe form of illness. PMID:23737946

Empirical support for DSM-IV schizoaffective disorder: clinical and cognitive validators from a large patient sample.

PubMed

DeRosse, Pamela; Burdick, Katherine E; Lencz, Todd; Siris, Samuel G; Malhotra, Anil K

2013-01-01

The diagnosis of schizoaffective disorder has long maintained an uncertain status in psychiatric nosology. Studies comparing clinical and biological features of patients with schizoaffective disorder to patients with related disorders [e.g., schizophrenia and bipolar disorder] can provide an evidence base for judging the validity of the diagnostic category. However, because most prior studies of schizoaffective disorder have only evaluated differences between groups at a static timepoint, it is unclear how these disorders may be related when the entire illness course is taken into consideration. We ascertained a large cohort [N = 993] of psychiatric patients with a range of psychotic diagnoses including schizophrenia with no history of major affective episodes [SZ-; N = 371], schizophrenia with a superimposed mood syndrome [SZ+; N = 224], schizoaffective disorder [SAD; N = 129] and bipolar I disorder with psychotic features [BPD+; N = 269]. Using cross-sectional data we designed key clinical and neurocognitive dependent measures that allowed us to test longitudinal hypotheses about the differences between these diagnostic entities. Large differences between diagnostic groups on several demographic and clinical variables were observed. Most notably, groups differed on a putative measure of cognitive decline. Specifically, the SAD group demonstrated significantly greater post-onset cognitive decline compared to the BP+ group, with the SZ- and SZ+ group both exhibiting levels of decline intermediate to BPD+ and SAD. These results suggest that schizoaffective disorder may possess distinct features. Contrary to earlier formulations, schizoaffective disorder may be a more severe form of illness.

Evaluation of Vitamin C for Adjuvant Sepsis Therapy

PubMed Central

2013-01-01

Abstract Significance: Evidence is emerging that parenteral administration of high-dose vitamin C may warrant development as an adjuvant therapy for patients with sepsis. Recent Advances: Sepsis increases risk of death and disability, but its treatment consists only of supportive therapies because no specific therapy is available. The characteristics of severe sepsis include ascorbate (reduced vitamin C) depletion, excessive protein nitration in microvascular endothelial cells, and microvascular dysfunction composed of refractive vasodilation, endothelial barrier dysfunction, and disseminated intravascular coagulation. Parenteral administration of ascorbate prevents or even reverses these pathological changes and thereby decreases hypotension, edema, multiorgan failure, and death in animal models of sepsis. Critical Issues: Dehydroascorbic acid appears to be as effective as ascorbate for protection against microvascular dysfunction, organ failure, and death when injected in sepsis models, but information about pharmacodynamics and safety in human subjects is only available for ascorbate. Although the plasma ascorbate concentration in critically ill and septic patients is normalized by repletion protocols that use high doses of parenteral ascorbate, and such doses are tolerated well by most healthy subjects, whether such large amounts of the vitamin trigger adverse effects in patients is uncertain. Future Directions: Further study of sepsis models may determine if high concentrations of ascorbate in interstitial fluid have pro-oxidant and bacteriostatic actions that also modify disease progression. However, the ascorbate depletion observed in septic patients receiving standard care and the therapeutic mechanisms established in models are sufficient evidence to support clinical trials of parenteral ascorbate as an adjuvant therapy for sepsis. Antioxid. Redox Signal. 19, 2129–2140. PMID:23682970

Acute and mid-term outcomes after treatment of multiple, recurrent restenoses of the lower limb arteries.

PubMed

Meyborg, M; Engelbertz, C; Lüders, F; Gebauer, K; Malyar, N M; Reinecke, H

2015-06-01

Recanalization of long segmental occlusions of femoropopliteal arteries can be achieved by angioplasty and implantation of nitinol stents with high procedural success rates. However, due to recurrent in-stent restenoses (ISR) some patients need repeated interventions and their intermediate success rates are uncertain. Patients who were treated in our center from March 2008 through February 2011 due to symptomatic ISR (as determined by Duplex sonography) were retrospectively included in the study. After endovascular treatment of their ISR, they were prospectively evaluated with regard to recurrent ISR of the target lesions. A total of 36 limbs (=lesions) in 32 patients (69% male, mean age 69±9 years) were successfully treated by balloon-angioplasty. Adjunctive cutting balloons and drug eluting balloons were used in 78% and 8%, respectively. Mean follow-up was 326 days. Recurrent ISR occurred in 10 (28%) lesions, while 26 (78%) lesions showed no recurrence of ISR. In a multivariate logistic regression analysis, age, gender, cardiovascular risk factors, renal failure and medication with cilostazol were not significantly associated with recurrent ISR. Moreover, the number of previous interventions of the target lesions was not an independent predictor of recurrent ISR. Patients with multiple recurrences of ISR seem to have the same prospects of acute and mid-term success for endovascular treatment as those with first presentation of ISR. However, this observation has to be confirmed by prospective, large scale studies with a longer follow-up period to determine the significance of endovascular intervention within the scope of different revascularization approaches for treatment of recurrent ISR.

Relationships between iron dose, hospitalizations and mortality in incident haemodialysis patients: a propensity-score matched approach.

PubMed

Varas, Javier; Ramos, Rosa; Aljama, Pedro; Pérez-García, Rafael; Moreso, Francesc; Pinedo, Miguel; Ignacio Merello, José; Stuard, Stefano; Canaud, Bernard; Martín-Malo, Alejandro

2018-01-01

Intravenous iron management is common in the haemodialysis population. However, the safest dosing strategy remains uncertain, in terms of the risk of hospitalization and mortality. We aimed to determine the effects of cumulative monthly iron doses on mortality and hospitalization. This multicentre observational retrospective propensity-matched score study included 1679 incident haemodialysis patients. We measured baseline demographic variables, haemodialysis clinical parameters and laboratory analytical values. We compared outcomes among quartiles of cumulative iron dose (mg/kg/month). We implemented propensity-score matching (PSM) to reduce confounding due to indication. In the PSM cohort (330 patients), we compared outcomes between groups that received cumulative iron doses above and below 5.66 mg/kg/month. Kaplan-Meier analyses showed that the high iron dose group had significantly worse survival than the low iron dose group. A univariate analysis indicated that the monthly iron dose could significantly predict mortality. However, a multivariate regression did not confirm that finding. The multivariate regression analysis revealed that iron doses  >5.58 mg/kg/month were not associated with elevated mortality risk, but they were associated with elevated risks of all-cause and cardiovascular-related hospitalizations. These results were ratified in the PSM population. Intravenous iron administration is advisable for maintaining haemoglobin levels in patients that receive haemodialysis. Our data suggested that large monthly iron doses, adjusted for body weight, were associated with more hospitalizations, but not with mortality or infection-related hospitalizations. © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Importance of spontaneous nystagmus detection in the differential diagnosis of acute vertigo.

PubMed

Pavlin-Premrl, Davor; Waterston, John; McGuigan, Sean; Infeld, Bernard; Sultana, Ron; O'Sullivan, Richard; Gerraty, Richard P

2015-03-01

Vertigo is a common cause of emergency department attendance. Detection of spontaneous nystagmus may be a useful sign in distinguishing vestibular neuritis from other vestibular diagnoses. We aimed to assess the contribution of spontaneous nystagmus in the diagnosis of acute vertigo. We enrolled consecutive consenting patients arriving at a single emergency department with acute vertigo. There was no declared protocol for the emergency department staff. A standardized history and examination was conducted by the investigators. Observation for spontaneous nystagmus, its response to visual fixation, and testing the vestibulo-ocular reflex with the horizontal head impulse test were the chief examination components. MRI was obtained within 24 hours. Clinical criteria and MRI were used to reach the final diagnosis. The investigators' physical findings and final neurological diagnosis were compared with the initial emergency department examination findings and the referral diagnosis. There were 28 patients, 15 with vestibular neuritis, six with benign paroxysmal positional vertigo, one with stroke, suspected clinically, and three with migraine. In three the diagnosis remained uncertain. Spontaneous nystagmus was seen in all 15 patients with vestibular neuritis, fixation-suppressed in eight of 11 tested for this. The head impulse test was positive in 12 of 15 with vestibular neuritis. The emergency department referral diagnosis was correct in six of 23 patients. The ability to detect spontaneous nystagmus is useful in vestibular diagnosis, both in support of a diagnosis of vestibular neuritis and in avoiding false positive diagnoses of benign paroxysmal positional vertigo. Copyright © 2014 Elsevier Ltd. All rights reserved.

Altered brain activation and connectivity during anticipation of uncertain threat in trait anxiety.

PubMed

Geng, Haiyang; Wang, Yi; Gu, Ruolei; Luo, Yue-Jia; Xu, Pengfei; Huang, Yuxia; Li, Xuebing

2018-06-08

In the research field of anxiety, previous studies generally focus on emotional responses following threat. A recent model of anxiety proposes that altered anticipation prior to uncertain threat is related with the development of anxiety. Behavioral findings have built the relationship between anxiety and distinct anticipatory processes including attention, estimation of threat, and emotional responses. However, few studies have characterized the brain organization underlying anticipation of uncertain threat and its role in anxiety. In the present study, we used an emotional anticipation paradigm with functional magnetic resonance imaging (fMRI) to examine the aforementioned topics by employing brain activation and general psychophysiological interactions (gPPI) analysis. In the activation analysis, we found that high trait anxious individuals showed significantly increased activation in the thalamus, middle temporal gyrus (MTG), and dorsomedial prefrontal cortex (dmPFC), as well as decreased activation in the precuneus, during anticipation of uncertain threat compared to the certain condition. In the gPPI analysis, the key regions including the amygdala, dmPFC, and precuneus showed altered connections with distributed brain areas including the ventromedial prefrontal cortex (vmPFC), dorsolateral prefrontal cortex (dlPFC), inferior parietal sulcus (IPS), insula, para-hippocampus gyrus (PHA), thalamus, and MTG involved in anticipation of uncertain threat in anxious individuals. Taken together, our findings indicate that during the anticipation of uncertain threat, anxious individuals showed altered activations and functional connectivity in widely distributed brain areas, which may be critical for abnormal perception, estimation, and emotion reactions during the anticipation of uncertain threat. © 2018 Wiley Periodicals, Inc.

[Perivascular epithelioid cell tumor, not otherwise specified: a clinicopathologic and immunohistochemical analysis of 31 cases].

PubMed

Cai, Jun-Na; Shi, Min; Wang, Jian

2011-04-01

To study the clinicopathologic characteristics of perivascular epithelioid cell tumor (PEComa), not otherwise specified (NOS) and to evaluate the diagnostic criteria for malignancy. The clinical and pathologic features of 31 cases of PEComa-NOS were reviewed. The follow-up data available were analyzed. There were a total of 24 females and 7 males. The age of the patients ranged from 13 to 66 years (mean = 40 years). The site of tumor occurrence included gynecologic organs (n = 12), intraabdominal/peritoneal soft tissue (n = 10), gastrointestinal tract (n = 4), thigh (n = 2), mediastinum (n = 1), left groin (n = 1) and urinary bladder (n = 1). None of the cases was associated with tuberous sclerosis complex. Histologic examination showed that 23 cases (74%) were clear cell sugar tumor-like, 4 cases (13%) were clear cell myomelanocytic tumor-like and 4 cases (13%) were of mixed epithelioid-spindled morphology. According to the classification system proposed by Folpe et al, 19 cases (61%) were classified as malignant, 7 cases (23%) as PEComa of uncertain malignant potential and 5 cases (16%) as benign. The expression rates of HMB45, smooth muscle actin and desmin in tested cases were 100% (31/31), 67% (14/21) and 6/18, respectively. Follow-up data (1 to 56 months) were available in 23 cases (74%). Amongst the 16 cases of malignant PEComa, 7 patients were still alive with no evidence of disease, 6 patients were alive with unresectable or recurrent/metastatic disease and 3 patients died of the disease. The local recurrence and metastasis in those 16 cases were 6 cases and 5 cases, respectively. One of the 4 patients with PEComa of uncertain malignant potential died, while the remaining 3 patients and all of the patients with benign PEComa had an uneventful clinical course. The classification system of PEComas proposed by Folpe et al. is reliable in routine practice. Correlation with the clinical and radiologic findings however is prudent when dealing with core biopsy specimens or sampling from exploration laparotomy. Owing to the histologic heterogeneity of this entity, thorough understanding of the morphologic spectrum is essential in arriving at a correct diagnosis.

Particle filter based hybrid prognostics for health monitoring of uncertain systems in bond graph framework

NASA Astrophysics Data System (ADS)

Jha, Mayank Shekhar; Dauphin-Tanguy, G.; Ould-Bouamama, B.

2016-06-01

The paper's main objective is to address the problem of health monitoring of system parameters in Bond Graph (BG) modeling framework, by exploiting its structural and causal properties. The system in feedback control loop is considered uncertain globally. Parametric uncertainty is modeled in interval form. The system parameter is undergoing degradation (prognostic candidate) and its degradation model is assumed to be known a priori. The detection of degradation commencement is done in a passive manner which involves interval valued robust adaptive thresholds over the nominal part of the uncertain BG-derived interval valued analytical redundancy relations (I-ARRs). The latter forms an efficient diagnostic module. The prognostics problem is cast as joint state-parameter estimation problem, a hybrid prognostic approach, wherein the fault model is constructed by considering the statistical degradation model of the system parameter (prognostic candidate). The observation equation is constructed from nominal part of the I-ARR. Using particle filter (PF) algorithms; the estimation of state of health (state of prognostic candidate) and associated hidden time-varying degradation progression parameters is achieved in probabilistic terms. A simplified variance adaptation scheme is proposed. Associated uncertainties which arise out of noisy measurements, parametric degradation process, environmental conditions etc. are effectively managed by PF. This allows the production of effective predictions of the remaining useful life of the prognostic candidate with suitable confidence bounds. The effectiveness of the novel methodology is demonstrated through simulations and experiments on a mechatronic system.

Suppression and enhancement of transcriptional noise by DNA looping

NASA Astrophysics Data System (ADS)

Vilar, Jose M. G.; Saiz, Leonor

2014-06-01

DNA looping has been observed to enhance and suppress transcriptional noise but it is uncertain which of these two opposite effects is to be expected for given conditions. Here, we derive analytical expressions for the main quantifiers of transcriptional noise in terms of the molecular parameters and elucidate the role of DNA looping. Our results rationalize paradoxical experimental observations and provide the first quantitative explanation of landmark individual-cell measurements at the single molecule level on the classical lac operon genetic system [Choi, L. Cai, K. Frieda, and X. S. Xie, Science 322, 442 (2008), 10.1126/science.1161427].

[Clinical characteristics, complications and mortality in 506 patients with infective endocarditis and determinants of survival rate at 10 years].

PubMed

Oyonarte, Miguel; Montagna, Rodrigo; Braun, Sandra; Rojo, Pamela; Jara, José L; Cereceda, Mauricio; Morales, Marcelo; Nazzal, Carolina; Nazal, Carolina; Alonso, Faustino

2012-12-01

Rates of morbidity and mortality in Infective Endocarditis (IE) remain high and prognosis in this disease is still difficult and uncertain. To study IE in Chile in its active phase during inpatient hospital stay and long term survival rates. Observational prospective national cohort study of 506 consecutive patients included between June 1,1998 and July 31, 2008, from 37 Chilean hospitals (secondary and tertiary centers) nationwide. The main findings were the presence of Rheumatic valve disease in 22.1 % of patients, a history of intravenous drug abuse (IVDA) only in 0.7%, the presence of Staphylococcus aureus in 29.2% of blood cultures, negative blood cultures in 33.2%, heart failure in 51.7% and native valve involvement in 86% of patients. Echocardiographic diagnosis was achieved in 94% of patients. Hospital mortality was 26.1% and its prognostics factors were persisting infection (Odds ratio (OR) 6.43, Confidence Interval (CI) 1.45-28.33%), failure of medical treatment and no surgical intervention (OR 48.8; CI 6.67-349.9). Five and 10 years survival rates were 75.6 and 48.6%, respectively. The significant prognostic factors for long term mortality, determined by multivariate analysis were the presence of diabetes, Staphylococcus aureus infection, sepsis, heart failure, renal failure and lack of surgical treatment during the IE episode. The microbiologic diagnosis of IE must be urgently improved in Chile. Mortality rates are still high (26.1%) partly because of a high incidence of negative blood cultures and the need for more surgical valve interventions during in-hospital period. Long term prognostic factors for mortality should be identified early to improve outcome.

Do clinicians prescribe exercise similarly in patients with different cardiovascular diseases? Findings from the EAPC EXPERT working group survey.

PubMed

Hansen, Dominique; Rovelo Ruiz, Gustavo; Doherty, Patrick; Iliou, Marie-Christine; Vromen, Tom; Hinton, Sally; Frederix, Ines; Wilhelm, Matthias; Schmid, Jean-Paul; Abreu, Ana; Ambrosetti, Marco; Garcia-Porrero, Esteban; Coninx, Karin; Dendale, Paul

2018-05-01

Background Although disease-specific exercise guidelines for cardiovascular disease (CVD) are widely available, it remains uncertain whether these different exercise guidelines are integrated properly for patients with different CVDs. The aim of this study was to assess the inter-clinician variance in exercise prescription for patients with various CVDs and to compare these prescriptions with recommendations from the EXercise Prescription in Everyday practice and Rehabilitative Training (EXPERT) tool, a digital decision support system for integrated state-of-the-art exercise prescription in CVD. Design The study was a prospective observational survey. Methods Fifty-three CV rehabilitation clinicians from nine European countries were asked to prescribe exercise intensity (based on percentage of peak heart rate (HR peak )), frequency, session duration, programme duration and exercise type (endurance or strength training) for the same five patients. Exercise prescriptions were compared between clinicians, and relationships with clinician characteristics were studied. In addition, these exercise prescriptions were compared with recommendations from the EXPERT tool. Results A large inter-clinician variance was found for prescribed exercise intensity (median (interquartile range (IQR)): 83 (13) % of HR peak ), frequency (median (IQR): 4 (2) days/week), session duration (median (IQR): 45 (18) min/session), programme duration (median (IQR): 12 (18) weeks), total exercise volume (median (IQR): 1215 (1961) peak-effort training hours) and prescription of strength training exercises (prescribed in 78% of all cases). Moreover, clinicians' exercise prescriptions were significantly different from those of the EXPERT tool ( p < 0.001). Conclusions This study reveals significant inter-clinician variance in exercise prescription for patients with different CVDs and disagreement with an integrated state-of-the-art system for exercise prescription, justifying the need for standardization efforts regarding integrated exercise prescription in CV rehabilitation.