bluuebunny/crossref_metadata_2025 huggingface dataset:
APACHE IV Versus PPI for Predicting Community Hospital ICU Mortality
Authors: Shrope-Mok Shaffer R. , Propst Katie A. , Iyengar Rajesh
Published: December 2009

Background: Both the Acute Physiology and Chronic Health Evaluation (APACHE) IV and Palliative Performance Index (PPI) are scales used to estimate intensive care unit (ICU) prognosis and mortality. Objective: To Compare the diagnostic utility of the PPI and APACHE IV and their subsequent implications in predicting ICU mortality at a community hospital. Design: This was a Prospective Cohort Study. Setting: The study was conducted at the Community hospital ICU. Patients: Participants were 211 patients admitted from December 24, 2008 to June 11, 2009. Measurements: An observer gathered appropriate data and performed the APACHE IV and PPI scales within 24 hours of admission. Results were then analyzed using standard formulae. Results: The study included 211 participants in total with 211 participants in the PPI group (n = 211) and 162 in the APACHE IV group (n = 162). The APACHE score and PPI were found to be significant for predicting ICU mortality (P value of P < .002 and 99% CI of 13.74 to 20.32, P value of P < .001and 99% CI of 3.70 to 4.61, respectively). APACHE IV demonstrated a sensitivity of 84.6%, specificity of 96.0%, PPV of 64.7%, and NPV of 98.6%. In contrast, the PPI possessed a sensitivity of 69.2%, specificity of 96.0%, PPV of 64.7%, and NPV of 97.8%. Limitations: Limitations may have occurred with the subjective nature of the PPI and Glasgow Coma Scale (GCS), along with meeting criterion for the APACHE IV. Conclusion: This prospective cohort study in the ICU of a community hospital demonstrated that both the APACHE IV and PPI were significant tools for predicting ICU mortality. When contrasting the 2 scales, the APACHE IV could more accurately rule in mortality when mortality occurred and rule out mortality when survival occurred.
Perceived Value and Cost of Providing Emergency Medication Kits to Home Hospice Patients in Maryland
Authors: Walker Kathryn A. , McPherson Mary Lynn
Published: December 2009

Many hospices have adopted the use of ‘‘emergency medication kits’’ (EMK) to allow for management of emergent symptoms and to prevent unscheduled patient interventions. The purpose of this study was to compare perceptions of hospice managers and clinicians regarding the value of EMK and to assess outcomes. Clinical managers and clinicians reported that EMK were valuable in preventing emergency department visits, unscheduled nursing visits, pharmacy deliveries, and increased satisfaction. A hospice using EMK reported fewer calls requiring unscheduled interventions (18% vs 33%) and resulted in cost savings (US$23.04 per call vs US$31.62 per call). Hospice managers and clinicians perceived EMK to be valuable in areas of quality, cost, and satisfaction. There appears to be an advantage to routinely providing EMK for home hospice patients.
Antimicrobial Use Among Patients Receiving Palliative Care Consultation
Authors: Chun Erin Diviney , Rodgers Phillip E. , Vitale Caroline A. , Collins Curtis D. , Malani Preeti N.
Published: December 2009

Background: We sought to characterize antimicrobial use among patients receiving palliative care consultation. Methods: Retrospective review of patients seen by the Palliative Care Service at the University of Michigan Health System from January 2008 to May 2008. Results: Of 131 patients seen in consultation, 70 received antimicrobials. We identified 92 infections among these 70 patients; therapy for 54 (58.7%) was empiric. Empiric therapy was most commonly prescribed for respiratory infection and urinary tract infection. Piperacillin/tazobactam (P/T) was the most frequently used agent, with 26 patients receiving P/T (37.1%); 22 of 26 received this agent empirically (84.6%, P = .005). Vancomycin was prescribed to 23 patients (32.9%). Sixteen patients (22.9%) died in hospital; another 31 were enrolled in hospice care. Conclusions: Our results suggest significant use of empiric, broad-spectrum antimicrobial therapy among hospitalized patients near the end of life. We advocate for careful assessment of potential benefits and treatment burdens of antimicrobial therapy, especially when palliation is the goal.
Treatment of Lower Extremity Edema by Subcutaneous Drainage in Palliative Care of Advanced Cancer Patients
Authors: Bar-Sela Gil , Omer Anat , Flechter Ezequiel , Zalman Daniela
Published: December 2009

Background: Lower extremity edema is a problem in patients with advanced cancer, causing decreased physical function and reduced movement. Methods: Eight patients with advanced cancer were treated by subcutaneous needles inserted in the inner and outer sides of the ankles and attached to an enclosed drainage bag, or by creating subcutaneous tracts in both ankles. Results: All patients lost weight after 24 hours. A total of 4 patients reported enhanced mobilization and 5 patients had significant improvement of mobilization that improved their quality of life. Conclusions: Subcutaneous drainage can improve edema in the lower limbs or the lower body segment, contributing to patient comfort at his end-of-life period. A prospective study with better evaluation of patient quality of life is ongoing in our center.
Objective and Subjective Nutritional Assessment of Patients with Cancer in Palliative Care
Authors: Ang Yee Kwang  , Kandiah Mirnalini
Published: December 2009

This study aimed to evaluate the nutritional status of patients with cancer in palliative care and to examine the interrelationship between objective and subjective nutritional assessment measures. Patients’ nutritional status in a palliative care unit of a Malaysian government hospital and a hospice facility were assessed using anthropometric measurements, weight loss at 1/6 months, and the scored patient-generated subjective global assessment (PG-SGA). Moderate-to-severe malnutrition was observed in a range from 31% to 69% using both measurements. Common nutritional impact symptoms were pain, xerostomia, and anorexia. Patient-generated subjective global assessment scores were significantly correlated with anthropometric measurements (P < .050). The PG-SGA is equally informative as objective indicators and is recommended as a quickly applied tool for nutritional status assessment of patients with cancer in palliative care.
The Needs, Current Knowledge, and Attitudes of Care Staff Toward the Implementation of Palliative Care in Old Age Homes
Authors: Lo Raymond S. K. , Kwan Bonnie H. F. , Lau Kay P. K. , Kwan Cecilia W. M. , Lam L.M. , Woo Jean
Published: December 2009

This study aims to explore in depth the needs, current knowledge, and attitudes of all ranks of old age home staff. A large-scale qualitative study with 13 semistructured focus groups was conducted in Hong Kong. Key themes were extracted by framework analysis. Three major themes were extracted, including role as a service provider, current knowledge, and attitude toward palliative care. There was a marked difference in familiarity with the concept of ‘‘palliative care’’ between different groups of staff, yet both shared the motivation for enhancement. The biggest concerns for the staff were elderly residents’ readiness to accept palliative care, manpower, and resources. Care staff, regardless of rank, seemed to welcome and be ready to adopt a palliative care approach in caring for old age home residents, though not without worries and concerns.
Experimental Failure Analysis of Glass-Epoxy Laminated Composite Bolted-Joints with Clearance Under Preload
Authors: Sen Faruk , Pakdil Murat , Sayman Onur , Benli Semih
Published: December 2009

In this study, a failure analysis of glass-epoxy laminated composite bolted-joints with bolt/hole clearance under various torques was carried out. To estimate the effects of joint geometry and fiber orientation on the failure strength and failure mode, parametric studies were conducted experimentally. The two different geometrical parameters were the edge distance-to-hole diameter ratio (E/D) and plate width-to-hole diameter ratio (W/D), E/D ratio was selected from 1 to 5, and W/D ratio was chosen from 2 to 5. The bolt preload torque was also carried out as 0, 3, and 6 Nm. To investigate the material parameters effect, laminated plates were oriented as three different stacking sequences [90o]8, [45o]8, and [0o] 8. The experiments were carried out with a clearance between the diameters of the bolt and the circular hole of 5 and 6 mm, respectively. According to experimental results, failure mode and bearing strength are strongly influenced by both material parameters and geometrical parameters. Additionally, when a torque is applied to the bolted-joints, the failure mechanism is affected by its increasing values.
Incidence of Appropriate Cardioverter-Defibrillator Shocks and Mortality in Patients With Heart Failure Treated With Combined Cardiac Resynchronization Plus Implantable Cardioverter-Defibrillator Therapy Versus Implantable Cardioverter-Defibrillator Therapy
Authors: Desai Harit , Aronow Wilbert S. , Ahn Chul , Tsai Fausan S. , Lai Hoang M. , Gandhi Kaushang , Amin Harshad , Frishman William H. , Kalapatapu Kumar , Cohen Martin , Sorbera Carmine
Published: December 2009

Of 529 patients with heart failure and a mean left ventricular ejection fraction of 29%, 209 (40%) were treated with cardiac resynchronization therapy (CRT) plus an implantable cardioverter-defibrillator (ICD) and 320 (60%) with an ICD. Mean follow-up was 34 months for both groups. Stepwise logistic regression analysis showed that significant independent variables for appropriate ICD shocks were statins (risk ratio = 0.35, P < .0001), smoking (risk ratio = 2.52, P < .0001), and digoxin (risk ratio = 1.92, P = .0001). Significant independent variables for time to deaths were use of CRT (risk ratio = 0.32, P = .0006), statins (risk ratio = 0.18, P < .0001), angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (risk ratio = 0.10, P < .0001), hypertension (risk ratio = 24.15, P < .0001), diabetes (risk ratio = 2.54, P = .0005), and age (risk ratio = 1.06, P < .0001). In conclusion, statins reduced and smoking and digoxin increased appropriate ICD shocks. Use of CRT, statins, and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers reduced mortality and hypertension, diabetes, and older age increased mortality.
Trimetazidine Shortens QTc Interval in Patients With Ischemic Heart Failure
Authors: Zemljic Gregor , Bunc Matjaz , Vrtovec Bojan
Published: December 2009

Background: Trimetazidine improves functional class and left ventricular function in patients with heart failure; however, its potential impact on QTc interval remains undefined. We analyzed the effects of trimetazidine on QTc interval in patients with ischemic heart failure. Methods: A prospective trial included 42 patients with ischemic heart failure (New York Heart Association [NYHA] 2 or 3) and reduced left ventricular ejection fraction (<55%), who were randomly allocated to conventional therapy plus trimetazidine in a modulated release formulation (35 mg twice daily; 22 patients) or conventional therapy alone (20 patients; controls). We measured QTc interval at baseline and after 1 month. Results: At baseline, QTc interval duration was similar in both groups (443 ± 41 milliseconds in trimetazidine group vs 446 ± 27 milliseconds in controls, P = .62). After 1 month, QTc interval decreased in the trimetazidine group (404 ± 36 milliseconds, P = .0002) but not in controls (452 ± 25 milliseconds, P = .74). QTc interval shortening with trimetazidine was more pronounced in patients with prolonged (>440 milliseconds) baseline QTc interval (—45 ± 38 milliseconds) than in patients with normal QTc interval (—19 ± 19 milliseconds P = .04). Significant QTc interval shortening (>20 milliseconds) was present in 14 of 22 patients (64%) in trimetazidine group compared to 3 of 20 (15%) patients in control group (P = .002). Conclusions: Trimetazidine therapy is associated with QTc interval shortening in patients with ischemic heart failure.
Prophylactic antivirals may be helpful in prevention of varicella-zoster virus reactivation in myeloma, but are they safe?
Authors: Dasanu Constantin A , Alexandrescu Doru T
Published: December 2009

Purpose. Retrospective analysis of two recent multiple myeloma (MM) clinical trials suggested that the use of bortezomib may be associated with an increased incidence of herpes zoster infections. Therefore, prophylactic use of antivirals has been advocated by some authors. This article explores the potential risks and pitfalls linked to routine acyclovir prophylaxis in bortezomib-treated MM.

Summary. Use of antivirals can be associated with important nephro- and neurotoxicity. The nephrotoxicity induced by MM itself and its supportive therapies, superimposed to aging and inherent immunosuppression in myeloma, makes the development of renal impairment even more likely. On the other hand, sensory neuropathy is known to occur both during myeloma progression and in the setting of bortezomib therapy. Furthermore, preexisting nephropathy in MM patients can contribute to the occurrence of serious neurologic toxicity with acyclovir.

Conclusions. Long-term acyclovir prophylaxis in MM patients treated with bortezomib may cause severe renal and neurological toxicity. Prevention of these complications can be achieved through either withholding of the antivirals or a very close monitoring of both neurologic status and renal function in this patient population. This highlights the importance of both clinician’s and pharmacist’s involvement in optimization of myeloma patient care.
Dose-rounding of adjuvant chemotherapy for breast cancer: an audit of toxicity
Authors: Jenkins Peter , Wallis Richard
Published: December 2009

Purpose. Dose-rounding of chemotherapy is increasingly being used in oncology departments to improve the efficiency of outpatient clinics. There is, however, no published data on the effect of this strategy on drug toxicity.

Methods. We have analysed acute chemotherapy side effects in a cohort of 662 consecutive patients receiving adjuvant FEC (5-fluorouracil, epirubicin, cyclophosphamide) for breast cancer. A dose-rounding algorithm was used to deliver drug doses that were within 5% of the standard dose based on body surface area.

Results. Patients receiving a rounded dose of chemotherapy that was higher than that calculated from their body surface area were not at increased risk of acute haematological or non-haematological toxicity.

Conclusions. Dose-rounding of adjuvant FEC within the range ±5% is not associated with any difference in acute chemotherapy side effects. Longer term follow-up is required to determine whether patients receiving rounded doses below that calculated from their body surface area are at increased risk of relapse.
Reducing workplace cytotoxic surface contamination using a closed-system drug transfer device
Authors: Siderov Jim , Kirsa Sue , McLauchlan Robert
Published: December 2009

Background. The potential for staff exposure to antineoplastic agents exists in the workplace despite current recommended safe handling procedures. Reliance on cytotoxic drug safety cabinets (CDSC) to provide total protection from exposure to hazardous drugs is insufficient. Preventing workplace contamination is the best strategy to minimise exposure. PhaSeal® is a commercially available system for ensuring the leak-free transfer of hazardous drugs, fitting both the NIOSH and ISOPP definitions of a closed system. To date, there have been no published studies examining the use of a closed system drug transfer device (PhaSeal®) under Australian conditions.

The purpose of this study is to determine the impact of a closed system drug transfer device on cytotoxic surface contamination in the cytotoxic preparation areas of two Australian metropolitan public hospitals.

Method. This was a pre- and post-intervention study in which chemical contamination was tested at baseline then at five and 12 months after the introduction of the a closed system drug transfer device. Cyclophosphamide was used as a surrogate marker for all cytotoxic drugs. Surface wipe sampling was performed at specified sites within the cytotoxic suite using a standardized technique. Commercial products of cyclophosphamide were also sampled.

Results. After five months, contamination was reduced in 13 of the 22 sites sampled (59%), with four of these samples showing undetectable levels of contamination. Two other site samples (9%) remained unchanged. The total contamination of surfaces tested was reduced by 24%. After five months hospital 1 withdrew from the study. After 12 months, surface contamination was reduced in 75% of sample sites. The total contamination of surfaces tested was reduced by 68%. The wipes of the external surface of commercial products detected cyclophosphamide contamination.

Conclusion. When used inside a CDSC, the closed system drug transfer device PhaSeal® further reduces surface contamination, in some instances to undetectable levels.
Grids and Clouds: Making Workflow Applications Work in Heterogeneous Distributed Environments
Authors: Deelman Ewa
Published: December 2009

Scientific workflows are frequently being used to model complex phenomena, to analyze instrumental data, to tie together information from distributed sources, and to pursue other scientific endeavors. Out of necessity, these complex applications need to execute in distributed environments and make use of a number of heterogeneous resources. In this paper we describe some of these applications and illustrate techniques that improve their performance and reliably in distributed environments, such as grids and clouds. Although clouds were first introduced in the business arena, they have a potential to be provide on-demand resources for scientific computations.
Burned! the Impact of Work Aspects, Injury, and Job Satisfaction On Unionized Cooks’ Intentions To Leave the Cooking Occupation
Authors: Young Cheri A. , Corsun David L.
Published: December 2009

The hospitality industry is marked by chronic labor shortages and high turnover in the cooking occupation, yet research on occupational (as opposed to job or organizational) turnover antecedents in this context is scarce. This study explores the variables that drive cooks’ intent to leave their chosen occupation, focusing on administratively controllable elements of the work environment. A survey of 213 unionized cooks employed in 13 hotels, ranging from three to five stars, in a major U.S. city illuminated path relationships between the antecedents of (a) work demands, (b) kitchen conditions, (c) management’s concern for food quality, and (d) work engagement, and the outcomes of (a) injuries, (b) job satisfaction, and (c) occupational turnover intent. Results show that the population of cooks may warrant contextually-specific models of occupational turnover intent.
Contemporary Thinking About Causation in Evaluation: A Dialogue With Tom Cook and Michael Scriven
Authors: Cook Thomas D. , Scriven Michael , Coryn Chris L. S. , Evergreen Stephanie D. H.
Published: December 2009

Legitimate knowledge claims about causation have been a central concern among evaluators and applied researchers for several decades and often have been the subject of heated debates. In recent years these debates have resurfaced with a renewed intensity, due in part to the priority currently being given to randomized experiments by many funders of evaluation studies, such as the Institute for Educational Sciences. In this dialogue, which took place at Western Michigan University in October 2008, two of the field’s leading theorists and methodologists, Thomas D. Cook and Michael Scriven, described their current thinking and views about causation and causal inference in evaluation. They also discussed recent methodological developments for cause-probing investigations that sometimes produce results comparable to those produced by randomized experiments. Both Cook and Scriven prepared clarifying postscripts after reading the edited transcript.
Time-Frequency Analysis of Small Frequency Variations in Civil Engineering Structures Under Weak and Strong Motions Using a Reassignment Method
Authors: Michel Clotaire , Gueguen Philippe
Published: December 2009

The analysis of strong and weak motion recordings in existing structures is critical for understanding both the damaging process during earthquakes and their structural behavior. The time—frequency representation is one of the existing methods to get information on the frequency variations in buildings, which may indicate either damage or degradation. In this article, we use standard time—frequency methods with amplitude normalization and reassignment method in order to observe smaller variations in earthquake recordings in buildings. The method used in this article is first validated on strong recordings from the R. Millikan Library (Pasadena, California) and later applied to weak earthquakes recorded in the Grenoble City Hall (France). This method detects torsion activation and very small frequency variations under weak motion. We show that these variations are probably due to variations of the input motion and cannot be attributed to variations in the parameters of the structural system.
A Classification and Regression Trees (CART) Model of Parallel Structure and Long-term Prediction Prognosis of Machine Condition
Authors: Van Tung Tran  , Yang Bo-Suk , Chit Chiow Tan Andy
Published: December 2009

This article presents a combined prediction model involving the parallel of classification and regression trees (CART) model, namely p-CART, and a long-term direct prediction methodology of time series techniques to predict the future stages of the machine’s operating conditions. p-CART model consists of multiple CART models which are connected in parallel. Each sub-model in the p-CART is trained independently. Based on the observations, these sub-models are subsequently used to predict the future values of the machine’s operating conditions separately with the same embedding dimension but different observations’ indices. Finally, the predicted results of sub-models are combined to produce the final results of the predicting process. Real trending data acquired from condition monitoring routine of compressor are employed to evaluate the proposed method. A comparative study of the predicted results obtained from traditional CART and p-CART models is also carried out to appraise the prediction capability of the proposed model.
Time Domain Characteristics of Electrical Measures for a Piezoelectric Thin Film to Identify Defects in the Substrate
Authors: Ali Rizwaan , Mahapatra D.R. , Gopalakrishnan S.
Published: December 2009

A reduced 3D continuum model of dynamic piezoelectricity in a thin-film surface-bonded to the substrate/host is presented in this article. While employing large area flexible thin piezoelectric films for novel applications in device/diagnostics, the feasibility of the proposed model in sensing the surface and/or sub-surface defects is demonstrated through simulations — which involve metallic beams with cracks and composite beam with delaminations of various sizes. We have introduced a set of electrical measures to capture the severity of the damage in the existing structures. Characteristics of these electrical measures in terms of the potential difference and its spatial gradients are illustrated in the time domain. Sensitivity studies of the proposed measures in terms of the defected areas and their region of occurence relative to the sensing film are reported. The simulations’ results for electrical measures for damaged hosts/substrates are compared with those due to undamaged hosts/ substrates, which show monotonicity with high degree of sensitivity to variations in the damage parameters.
Global and Local Fiber Optic Sensors for Health Monitoring of Civil Engineering Infrastructure Retrofit with FRP Materials
Authors: Guoliang Jiang  , Dawood Mina , Peters Kara , Rizkalla Sami
Published: December 2009

Fiber-reinforced polymer (FRP) materials are currently used for strengthening civil engineering structures and bridges. The effectiveness of the strengthening system is highly dependent on the bond characteristics of the FRP material to the external surface of the structure. This article presents the application of two types of fiber optic sensors, which can be embedded in FRP materials to monitor the global and local behavior of the strengthened structure, respectively. The global sensor is designed to evaluate the overall condition of a structure based on the measured elongation of the FRP layer along the entire span of the structure. The success of this low-cost global sensor has been demonstrated using a full-scale prestressed concrete bridge girder that was loaded up to failure. The test results indicate that this type of sensor can be used to identify major changes in the overall behavior of the structure such as cracking of prestressed members or yielding of the internal reinforcement. The second sensor component consists of fiber Bragg grating sensors. The sensors were used to monitor the behavior of steel double-lap shear specimens tested under tensile loading up to failure. The measurements were used to identify abnormal structural behaviors such as epoxy cracking and/or FRP debonding. The test results compared well to the numerical values obtained from a three dimensional shear-lag model that was previously developed to predict the sensor response.
The effect of intensive glucose control on all-cause and cardiovascular mortality, myocardial infarction and stroke in persons with type 2 diabetes mellitus: a systematic review and meta-analysis
Authors: Marso Steven P. , Kennedy Kevin F. , House John A. , McGuire Darren K.
Published: December 2009

We performed a meta-analysis of studies evaluating the effect of intensive glucose control on major adverse cardiovascular events in patients with type 2 diabetes from 1990 to 2009. A search of the published literature and the Cochran Central Register for Controlled Trials was performed using pre-specified inclusion criteria consisting of randomised controlled trials evaluating intensive glycaemic control and reporting the individual endpoints of all-cause mortality, non-fatal myocardial infarction, and non-fatal stroke. Incident rate ratios for these endpoints were calculated using standard meta-analytic techniques of pooled data from eligible trials. Six reports from four randomised trials including 27,544 patients met the pre-specified inclusion criteria. Mean follow-up was 5.4 years; haemoglobin A1C at study end was 6.6% vs. 7.4% in patients randomised to intensive compared with conventional glucose control. Intensive glucose control did not affect the incident rate ratio for all-cause mortality (1.01, 95% confidence interval 0.86—1.18, p=0.54) or stroke (1.02, 95% confidence interval 0.88—1.20, p=0.62). However, there was a statistically significant 14% reduction in non-fatal myocardial infarction in patients randomised to intensive glucose control (0.86, 95% confidence interval 0.77—0.97, p=0.015). Although intensification of glucose control did not affect mortality or non-fatal stroke, the risk for non-fatal myocardial infarction was significantly reduced in patients with type 2 diabetes.
A Robust, Multi-criteria Modeling Approach for Optimizing Aeromedical Evacuation Asset Emplacement
Authors: Bastian Nathaniel D.
Published: December 2009

According to current force health protection policy, the U.S. Army’s Health Service Support system is designed to maintain a healthy force and to conserve the combat strength of deployed soldiers. Specifically, this system remains particularly effective by employing standardized aeromedical evacuation assets and providing a responsive field-sited medical treatment facility for the wounded soldiers evacuated from the battlefield. Since the beginning of Operation Enduring Freedom, military commanders have faced a significant combinatorial challenge integrating these life-saving yet limited air evacuation assets into a fully-functional, comprehensive system for the entire theatre, which deserves thorough analysis for decision-making. This work describes a robust, multi-criteria decision analysis methodology using a scenario-based, stochastic optimization goal-programming model that U.S. Army medical planners can use as a strategic and tactical aeromedical evacuation asset-planning tool to help bolster and improve the current air evacuation system in Afghanistan. Specifically, this model optimizes over a set of expected scenarios with stochastically-determined casualty locations to emplace the minimum number of helicopters at each medical treatment facility necessary to maximize the coverage of the theatre-wide casualty demand and the probability of meeting that demand, while minimizing the maximal medical treatment facility evacuation site total vulnerability to enemy attack.
Engineering the New Combat Support Hospital
Authors: Fulton Lawrence V. , Perry Mark J. , Wood Suzanne J. , Bewley Lee
Published: December 2009

In the following study we evaluate the optimal arrangement of deployable medical capability components (intensive care units (ICUs), intermediate care wards (ICWs), and operating room (OR) suites) given scenarios designed to represent stability operations through major combat operations. These capabilities are then compared to achievable medical capability based on certain engineering design characteristics (e.g., bed capacity) of the proposed modular combat support hospital (CSH). If all scenarios are equally weighted, then the optimal ratio of capability per 1000 admissions is about 15 OR suites to 42 ICUs to 165 ICWs or about 1:3:11. Applying service engineering assembly limitations, the optimal selection of capability assemblies over all 27 scenarios is estimated.
Endothelial progenitor cell senescence is there a role for estrogen?
Authors: Imanishi Toshio , Tsujioka Hiroto , Akasaka Takashi
Published: December 2009

Recent studies have demonstrated that aging or senescence constitutes a potential limitation to the ability of endothelial progenitor cells (EPCs) to sustain ischemic tissue repair. Excess amount of reactive oxygen species (ROS) is involved in senescence, causing defective neovascularization. Conversely, estrogens have been shown to accelerate recovery of the endothelium after vascular injury. Estrogen reduces EPC senescence through augmentation of telomerase activity. In addition, the inhibition of EPC senescence by estrogen in vitro may improve the functional activity of EPCs in a way that is important for potential cell therapy. This review describes current understanding of EPC senescence and the role of estrogen in preventing EPC senescence.
Current pharmacotherapeutic concepts for the treatment of cardiovascular disease in diabetics
Authors: Highlander Peter , Shaw Graham P.
Published: December 2009

With the growing worldwide obesity epidemic, obesity, type 2 diabetes mellitus and hypertension leading to premature cardiovascular events, are increasingly prevalent. Diabetes mellitus is a significant public health concern and more aggressive management of the condition and its complications, particularly cardiovascular disease, is warranted. Endothelial cell dysfunction is now known to be present at the earliest stages of metabolic syndrome, and insulin resistance and may precede the clinical diagnosis of type 2 diabetes mellitus by several years. The current focus on endothelial cell function as a potential target of pharmacotherapy in the management of cardiovascular disease in diabetics seems warranted, though not all drugs currently prescribed target endothelial cell function equally. In this review, we consider the six classes of drugs currently prescribed for the treatment of hypertension as they impact endothelial cell function and advocate for the development of novel drugs that can repair the endothelium and enhance nitric oxide availability thus preventing future cardiovascular events.
Review: Discordant findings in color-coded duplex-sonography and magnetic resonance angiography in symptomatic internal carotid artery stenosis: implications for diagnostic work-up and early intervention
Authors: Eyding Jens , Krogias Christos , Seemann Marcus , Gold Ralf , Mumme Achim
Published: December 2009

Background: Magnetic resonance angiography (MRA) is supposed to be the new ’gold standard’ in the diagnosis of atherosclerotic disease of the extracranial arteries.

Methods: A case report is presented on a patient in whom discordant findings of the status of the left internal carotid artery (ICA) were identified in color-coded duplex-sonography and MRA.

Results: Left ICA stenosis was suspected in duplex-sonography, yet not confirmed in contrast-enhanced (CE) MRA reconstruction. Diagnosis was confirmed after surgery and in subsequent analysis of the original CE-MRI data.

Conclusions: The analysis of source images must not be missed in MRA examinations. Conventional duplex-sonography may be superior in the estimation of the embolic potential of vascular lesions. Advanced CE techniques may therefore be adequate tools in differentiating patients eligible for carotid endarterectomy (CEA) or carotid stenting, avoiding the risk of peri-interventional iatrogenic complications. It should urgently be further improved and validated.
Review: Chemotherapy-induced diarrhea: pathophysiology, frequency and guideline-based management
Authors: Stein Alexander , Voigt Wieland , Jordan Karin
Published: December 2009

Diarrhea is one of the main drawbacks for cancer patients. Possible etiologies could be radiotherapy, chemotherapeutic agents, decreased physical performance, graft versus host disease and infections. Chemotherapy-induced diarrhea (CID) is a common problem, especially in patients with advanced cancer. The incidence of CID has been reported to be as high as 50-80% of treated patients (≥30% CTC grade 3-5), especially with 5-fluorouracil bolus or some combination therapies of irinotecan and fluoropyrimidines (IFL, XELIRI). Regardless of the molecular targeted approach of tyrosine kinase inhibitors and antibodies, diarrhea is a common side effect in up to 60% of patients with up to 10% having severe diarrhea. Furthermore, the underlying pathophysiology is still under investigation. Despite the number of clinical trials evaluating therapeutic or prophylactic measures in CID, there are just three drugs recommended in current guidelines: loperamide, deodorized tincture of opium and octreotide. Newer strategies and more effective agents are being developed to reduce the morbidity and mortality associated with CID. Recent research focusing on the prophylactic use of antibiotics, budesonide, probiotics or activated charcoal still have to define the role of these drugs in the routine clinical setting. Whereas therapeutic management and clinical work-up of patients presenting with diarrhea after chemotherapy are rather well defined, prediction and prevention of CID is an evolving field. Current research focuses on establishing predictive factors for CID like uridine diphosphate glucuronosyltransferase-1A1 polymorphisms for irinotecan or dihydropyrimidine-dehydrogenase insufficiency for fluoropyrimidines.
Review: Targeted therapies in small cell lung cancer: a review
Authors: Abidin Aidalena Z. , Garassino Marina C. , Califano Raffaele , Harle Amelie , Blackhall Fiona
Published: December 2009

Small cell lung cancer (SCLC) is an aggressive form of lung cancer that is characterized by a rapid doubling time, early onset of dissemination and high sensitivity to chemotherapy. Despite the potential for cure in patients with limited disease with concurrent chemoradiation and an initial good response to chemotherapy in extensive disease, there is a high chance of disease relapse with an overall poor median survival for both stages. With increasing translational research and a better understanding of the molecular basis of cancer, a number of molecular targets have been identified in various preclinical studies. This review summarizes potentially viable targets and new agents that have been developed and employed in recent, ongoing and future clinical trials to attempt to improve clinical outcomes in this disease.
Characteristics of Drug and Dietary Supplement Inquiries by College Athletes
Authors: Ambrose Peter J. , Tsourounis Candy , Olander Rachel , Uryasz Frank
Published: December 2009

Background:

In the United States, the National Center for Drug Free Sport manages the drug-testing programs for athletes of the National Collegiate Athletic Association (NCAA). Through its Resource Exchange Center (REC), Drug Free Sport supports athletic staff and athletes with information regarding drugs and dietary supplements.

Purpose:

To characterize the types of drug-related and dietary supplement–related inquiries submitted to Drug Free Sport through the REC.

Study Design:

Cross-sectional study.

Methods:

All inquiries submitted to the REC for the period of September 1, 2005, through June 30, 2006, were reviewed. The data were categorized by the method of inquiry submission; the name of the substance in question; the sex, sport, and NCAA division of the athlete involved; the nature of the inquiry; and the response provided by the REC regarding the NCAA’s status of the substance in question.

Results:

Pseudoephedrine, acetaminophen/hydrocodone, and albuterol were the most commonly self-searched medications; stimulants accounted for the majority of banned medications. Dietary supplements accounted for 80% of all inquiries submitted to the REC via the Banned Drug Inquiry Form. Among all dietary supplements, creatine was the most commonly inquired. Banned substances accounted for 29% of all inquiries.

Conclusions:

There were more than 10 000 inquiries regarding the status of medications, dietary supplements, and other substances for NCAA athletes during the 2005–2006 academic year. It is helpful for athletes to have resources that help them navigate banned-substance lists and so avoid the inadvertent use of banned substances.

Clinical Relevance:

Educating athletes regarding the stimulant content of various dietary supplements and addressing the lack of clinical trials to support stated claims and safety appear critical.
Association of high-level MCL-1 expression with in vitro and in vivo prednisone resistance in MLL-rearranged infant acute lymphoblastic leukemia
Authors: Stam Ronald W. , Den Boer Monique L. , Schneider Pauline , de Boer Jasper , Hagelstein Jill , Valsecchi Maria G. , de Lorenzo Paola , Sallan Stephen E. , Brady Hugh J. M. , Armstrong Scott A. , Pieters Rob
Published: December 2009

MLL-rearranged acute lymphoblastic leukemia (ALL) represents an unfavorable type of leukemia that often is highly resistant to glucocorticoids such as prednisone and dexamethasone. Because response to prednisone largely determines clinical outcome of pediatric patients with ALL, overcoming resistance to this drug may be an important step toward improving prognosis. Here, we show how gene expression profiling identifies high-level MCL-1 expression to be associated with prednisolone resistance in MLL-rearranged infant ALL, as well as in more favorable types of childhood ALL. To validate this observation, we determined MCL-1 expression with quantitative reverse transcription–polymerase chain reaction in a cohort of MLL-rearranged infant ALL and pediatric noninfant ALL samples and confirmed that high-level MCL-1 expression is associated with prednisolone resistance in vitro. In addition, MCL-1 expression appeared to be significantly higher in MLL-rearranged infant patients who showed a poor response to prednisone in vivo compared with prednisone good responders. Finally, down-regulation of MCL-1 in prednisolone-resistant MLL-rearranged leukemia cells by RNA interference, to some extent, led to prednisolone sensitization. Collectively, our findings suggest a potential role for MCL-1 in glucocorticoid resistance in MLL-rearranged infant ALL, but at the same time strongly imply that high-level MCL-1 expression is not the sole mechanism providing resistance to these drugs.
Short-term inhibition of p53 combined with keratinocyte growth factor improves thymic epithelial cell recovery and enhances T-cell reconstitution after murine bone marrow transplantation
Authors: Kelly Ryan M. , Goren Emily M. , Taylor Patricia A. , Mueller Scott N. , Stefanski Heather E. , Osborn Mark J. , Scott Hamish S. , Komarova Elena A. , Gudkov Andrei V. , Holländer Georg A. , Blazar Bruce R.
Published: December 2009

Myeloablative conditioning before bone marrow transplantation (BMT) results in thymic epithelial cell (TEC) injury, T-cell immune deficiency, and susceptibility to opportunistic infections. Conditioning regimen–induced TEC damage directly contributes to slow thymopoietic recovery after BMT. Keratinocyte growth factor (KGF) is a TEC mitogen that stimulates proliferation and, when given before conditioning, reduces TEC injury. Some TEC subsets are refractory to KGF and functional T-cell responses are not fully restored in KGF-treated BM transplant recipients. Therefore, we investigated whether the addition of a pharmacologic inhibitor, PFT-β, to transiently inhibit p53 during radiotherapy could spare TECs from radiation-induced damage in congenic and allogeneic BMTs. Combined before BMT KGF + PFT-β administration additively restored numbers of cortical and medullary TECs and improved thymic function after BMT, resulting in higher numbers of donor-derived, naive peripheral CD4+ and CD8+ T cells. Radiation conditioning caused a loss of T-cell zone fibroblastic reticular cells (FRCs) and CCL21 expression in lymphoid stroma. KGF + PFT-β treatment restored both FRC and CCL21 expression, findings that correlated with improved T-cell reconstitution and an enhanced immune response against Listeria monocytogenes infection. Thus, transient p53 inhibition combined with KGF represents a novel and potentially translatable approach to promote rapid and durable thymic and peripheral T-cell recovery after BMT.
Donor statin treatment protects against severe acute graft-versus-host disease after related allogeneic hematopoietic cell transplantation
Authors: Rotta Marcello , Storer Barry E. , Storb Rainer F. , Martin Paul J. , Heimfeld Shelly , Peffer Amanda , Maloney David G. , Deeg H. Joachim , Sandmaier Brenda M. , Appelbaum Frederick R. , Mielcarek Marco
Published: December 2009

We retrospectively analyzed outcomes among 567 patients with hematologic malignancies who had hematopoietic cell transplantation from human leukocyte antigen-identical sibling donors between 2001 and 2007 for a correlation between statin use and risk of graft-versus-host disease (GVHD). Compared with allografts where neither the donor nor recipient was treated with a statin at the time of transplantation (n = 464), statin use by the donor and not the recipient (n = 75) was associated with a decreased risk of grade 3-4 acute GVHD (multivariate hazard ratio, 0.28; 95% confidence interval, 0.1-0.9). Statin use by both donor and recipient (n = 12) was suggestively associated with a decreased risk of grade 3 or 4 acute GVHD (multivariate hazard ratio, 0.00; 95% confidence interval, undefined), whereas statin use by the recipient and not the donor (n = 16) did not confer GVHD protection. Risks of chronic GVHD, recurrent malignancy, nonrelapse mortality, and overall mortality were not significantly affected by donor or recipient statin exposure. Statin-associated GVHD protection was restricted to recipients with cyclosporine-based postgrafting immunosuppression and was not observed among those given tacrolimus (P = .009). These results suggest that donor statin treatment may be a promising strategy to prevent severe acute GVHD without compromising immunologic control of the underlying malignancy.
Two-transcript gene expression classifiers in the diagnosis and prognosis of human diseases
Authors: Edelman Lucas B , Toia Giuseppe , Geman Donald , Zhang Wei , Price Nathan D
Published: December 2009

Background

Identification of molecular classifiers from genome-wide gene expression analysis is an important practice for the investigation of biological systems in the post-genomic era - and one with great potential for near-term clinical impact. The 'Top-Scoring Pair' (TSP) classification method identifies pairs of genes whose relative expression correlates strongly with phenotype. In this study, we sought to assess the effectiveness of the TSP approach in the identification of diagnostic classifiers for a number of human diseases including bacterial and viral infection, cardiomyopathy, diabetes, Crohn's disease, and transformed ulcerative colitis. We examined transcriptional profiles from both solid tissues and blood-borne leukocytes.

Results

The algorithm identified multiple predictive gene pairs for each phenotype, with cross-validation accuracy ranging from 70 to nearly 100 percent, and high sensitivity and specificity observed in most classification tasks. Performance compared favourably with that of pre-existing transcription-based classifiers, and in some cases was comparable to the accuracy of current clinical diagnostic procedures. Several diseases of solid tissues could be reliably diagnosed through classifiers based on the blood-borne leukocyte transcriptome. The TSP classifier thus represents a simple yet robust method to differentiate between diverse phenotypic states based on gene expression profiles.

Conclusion

Two-transcript classifiers have the potential to reliably classify diverse human diseases, through analysis of both local diseased tissue and the immunological response assayed through blood-borne leukocytes. The experimental simplicity of this method results in measurements that can be easily translated to clinical practice.
Inhibition of HIV-1 integrase nuclear import and replication by a peptide bearing integrase putative nuclear localization signal
Authors: Levin Aviad , Armon-Omer Ayelet , Rosenbluh Joseph , Melamed-Book Naomi , Graessmann Adolf , Waigmann Elisabeth , Loyter Abraham
Published: December 2009

Background

The integrase (IN) of human immunodeficiency virus type 1 (HIV-1) has been implicated in different steps during viral replication, including nuclear import of the viral pre-integration complex. The exact mechanisms underlying the nuclear import of IN and especially the question of whether it bears a functional nuclear localization signal (NLS) remain controversial.

Results

Here, we studied the nuclear import pathway of IN by using multiple in vivo and in vitro systems. Nuclear import was not observed in an importin α temperature-sensitive yeast mutant, indicating an importin α-mediated process. Direct interaction between the full-length IN and importin α was demonstrated in vivo using bimolecular fluorescence complementation assay (BiFC). Nuclear import studies in yeast cells, with permeabilized mammalian cells, or microinjected cultured mammalian cells strongly suggest that the IN bears a NLS domain located between residues 161 and 173. A peptide bearing this sequence -NLS-IN peptide- inhibited nuclear accumulation of IN in transfected cell-cycle arrested cells. Integration of viral cDNA as well as HIV-1 replication in viral cell-cycle arrested infected cells were blocked by the NLS-IN peptide.

Conclusion

Our present findings support the view that nuclear import of IN occurs via the importin α pathway and is promoted by a specific NLS domain. This import could be blocked by NLS-IN peptide, resulting in inhibition of viral infection, confirming the view that nuclear import of the viral pre-integration complex is mediated by viral IN.