Risk stratification for the development of venous thromboembolism in hospitalized patients with cancer.

Essentials The Khorana score is validated for risk of venous thromboembolism (VTE) in cancer outpatients. We conducted a multicenter analysis of medically hospitalized cancer patients. Patients with a higher Khorana score on admission were more likely to develop VTE. The Khorana score is predictive of in-hospital, symptomatic VTE development. SUMMARY: Introduction The Khorana score is a validated risk assessment score for estimating the risk of symptomatic venous thromboembolism (VTE) in outpatients with cancer. The objective of this study was to assess the Khorana score for predicting the development of VTE in cancer patients during hospital admission. Methods We conducted an analysis of consecutive, adult cancer patients hospitalized for medical reasons between January and June 2010 in three academic medical centers. Information on objectively diagnosed, symptomatic VTE during hospitalization, use of anticoagulant thromboprophylaxis (TP) and Khorana score variables at the time of admission was collected. Results A total of 1398 patients were included. Mean age was 62 years, 51.2% were male, and mean BMI was 25.9 kg m-2 . The most frequent reasons for hospitalization were chemotherapy administration (22.3%), followed by pain control and palliation (21.4%). The overall incidence of VTE was 2.9% (95% CI, 2.0-3.8%), occurring in 5.4% (95% CI, 1.9-8.9%) of the high-, 3.2% (95% CI, 2.0-4.4%) of the intermediate- and 1.4% (95% CI, 0.3-2.6%), of the low-risk groups. High-risk patients were more likely than low-risk patients to have VTE (OR, 3.9; 95% CI, 1.4-11.2). Conclusion The Khorana score is predictive of in-hospital, symptomatic VTE development in cancer patients who are hospitalized for medical reasons and may be a useful tool for tailoring inpatient anticoagulant thromboprophylaxis.

Influenza vaccination status and outcomes among influenza-associated hospitalizations in Columbus, Ohio (2012-2015).

Prior studies suggest that the influenza vaccine is protective against some outcomes in hospitalized patients infected with influenza despite vaccination. We utilized surveillance data from Columbus, Ohio to investigate this association over multiple influenza seasons and age groups. Data on laboratory-confirmed influenza-associated hospitalizations were collected as a part of the Influenza Hospitalization Surveillance Project for the 2012-2013, 2013-2014, and 2014-2015 influenza seasons. The association between influenza vaccination status was examined in relation to the outcomes of severe influenza and diagnosis of pneumonia among patients receiving antiviral treatment. Data were analyzed using multivariable logistic regression. We observed no overall association between influenza vaccination status and severe influenza among hospitalized patients. During the 2013-2014 season, those who were vaccinated were 41% less likely to be diagnosed with pneumonia compared with those who were unvaccinated (OR = 0·59 95% CI 0·41-0·86). The influenza vaccine may provide a secondary preventive function against pneumonia among influenza cases requiring hospitalization. However, a protective effect was only observed in 2013-2014, an influenza H1N1 dominant year. Differences in circulating influenza virus strains and vaccine matching to the circulating strains during influenza seasons may impact this association.

Nine-year audit of post-dural puncture headache in a tertiary obstetric hospital in Singapore.

BACKGROUND: The KK Women's and Children's Hospital is a tertiary obstetric unit with approximately 11000 deliveries per year. Epidural analgesia is used in about 40% of laboring women. We reviewed the incidence and management of post-dural puncture headache over a nine-year period. METHODS: A retrospective audit of labor epidural analgesia database records from 1 June 2005 to 31 May 2014 was conducted, identifying an "event" as an accidental dural puncture, an inadvertent intrathecal catheter insertion and/or development of a post-dural puncture headache. RESULTS: A total of 43434 epidural records were reviewed. Sixty-three events were identified (an incidence of 0.15%). Women had median age of 30years and median body mass index of 27.6kg/m2; 69.8% (44/63) delivered vaginally. Procedures performed by less experienced anesthesiologists and those performed outside office hours were associated with a higher incidence of accidental dural puncture. An intrathecal catheter was inserted in 52 of 58 women (89.7%). Headache developed in 24 of 38 (63.1%) women in whom there was a witnessed accidental dural puncture. Most women who developed post-dural puncture headache presented during the primary admission (36/39; 92.3%). Paracetamol and non-steroidal anti-inflammatory drugs were the most commonly prescribed medications. Six women (9.5%) received an epidural blood patch which led to resolution of headache. CONCLUSION: A retrospective audit over a nine-year period at a tertiary teaching hospital found the overall incidence of post-dural puncture headache and associated events to be 0.15%, with a decreasing trend coinciding with improvement in the teaching and supervision of trainees in labor epidural procedures.

Fitness activity classification by using multiclass support vector machines on head-worn sensors.

Fitness activity classification on wearable devices can provide activity-specific information and generate more accurate performance metrics. Recently, optical head-mounted displays (OHMD) like Google Glass, Sony SmartEyeglass and Recon Jet have emerged. This paper presents a novel method to classify fitness activities using head-worn accelerometer, barometric pressure sensor and GPS, with comparisons to other common mounting locations on the body. Using multiclass SVM on head-worn sensors, we obtained an average F-score of 96.66% for classifying standing, walking, running, ascending/descending stairs and cycling. The best sensor location combinations were found to be on the ankle plus another upper body location. Using three or more sensors did not show a notable improvement over the best two-sensor combinations.

Efficient use of longitudinal CD4 counts and viral load measures in survival analysis.

CD4 counts and viral loads are dynamic quantities that change with time in HIV-infected persons. Commonly used single summary measures, such as viral load set point or early CD4 count, do not explicitly account for changes in viral load or CD4 counts or other features of the overall time course of these measures. However, the efficient use of all repeated measurements within each subject is often a challenge made more difficult by sparse and irregular sampling over time. Here, we illustrate how functional principal component (FPC) analysis provides an effective statistical approach for exploiting the patterns in CD4 count and viral load data over time. We demonstrate the method by using data from Kenyan women who acquired HIV-1 during follow-up in a cohort that practices high-risk activities and were subsequently followed up prospectively from early infection. The FPC scores for each woman obtained using this method served as informative summary statistics for the CD4 count and viral load trajectories. Similar to baseline CD4 count or viral set point, the first FPC score can be interpreted as a single-value summary measure of an individual's overall CD4 count or viral load. However, unlike most single-value summaries of CD4 count or viral load trajectories, the first FPC score summarizes the dynamics of these quantities and is seen to reveal specific features of the trajectories associated with mortality in this cohort. Moreover, the FPC scores are shown to be a more powerful prognostic factor than other common summaries when used in survival analysis.

Pituitary network connectivity as a mechanism for the luteinising hormone surge.

Ovulation in vertebrates is caused by a surge of luteinising hormone (LH) from the pituitary. The LH surge is initiated by rising oestradiol concentration, although the precise mechanism of oestradiol action in humans and primates is not yet understood. Recent advances in labelling and three-dimensional imaging have revealed a rich pituitary structure of interwoven networks of different cell types. In the present study, we develop a mathematical model to test the hypothesis that oestradiol modulation of connectivity between pituitary cells can underlie the LH surge. In the model, gonadotrophin-releasing hormone (GnRH) pulses stimulate LH secretion by two independent mechanisms. The first mechanism corresponds to the well known direct action of GnRH on gonadotrophs, which is inhibited by the rising oestradiol concentration. The second mechanism of GnRH action is to stimulate a recurrent network of pituitary cells; in this case, the folliculostellate cells, which in turn stimulate LH secretion from the gonadotrophs. The network activity is modelled by a one-dimensional ordinary differential equation. The key to the LH surge in the model lies in the assumption that oestradiol modulates network connectivity. When the circulating oestradiol concentration is low, the network is barely connected, and cannot maintain a recurrent signal. When the oestradiol concentration is high, the network is highly connected, and maintains a high level of activity even after GnRH stimulation, thereby leading to a surge of LH secretion.

Comparisons of intraocular pressure measurements: Goldmann applanation tonometry, noncontact tonometry, Tono-Pen tonometry, and dynamic contour tonometry.

AIMS: To compare intraocular pressure (IOP) readings between Tono-Pen tonometry and GAT, between noncontact tonometry (NCT) and GAT, and between dynamic contour tonometry (DCT) and Goldmann applanation tonometry (GAT). The correlation between IOP reading and possible confounder was identified. METHODS: This observational cross-sectional study enrolled sixty-two healthy subjects. All IOP and ocular pulse amplitude (OPA) measurements were taken by a single ophthalmologist; mean keratometric power (MK), central corneal thickness (CCT), and lens thickness (LT) were measured by a single experienced technician. RESULTS: Stepwise multiple regression analysis indicated that GAT (P=0.017) and DCT (P=0.002) readings correlated positively with MK; GAT, NCT, and Tono-Pen readings correlated positively with CCT (P<0.05); NCT (P=0.035), and DCT (P=0.016) readings correlated negatively with LT; GAT (P=0.006) and Tono-Pen (P=0.009) readings correlated positively with OPA. CONCLUSIONS: The K, CCT, LT, and OPA are confounders in tonometry readings.

Non-surgical interventions for threatened and recurrent miscarriages.

Many surgical and non-surgical interventions are used in the management of threatened and recurrent miscarriages. Evidence-based management of recurrent miscarriages requires investigations into the underlying aetiology. When a specific cause is identified, directed treatment may reduce miscarriage rates. Combined aspirin and heparin for antiphospholipid syndrome, and screening and treatment of bacterial vaginosis between ten and 22 weeks of pregnancy with clindamycin, are the only interventions proven to be useful in randomised controlled trials (RCTs). The use of periconceptional metformin for polycystic ovarian (PCO) syndrome is promising, though data from RCTs are still required. The use of heparin in inherited thrombophilias, bromocriptine in hyperprolactinaemia and luteinising hormone suppression in fertile patients with PCO syndrome are more controversial. In threatened miscarriages, or when no cause is found, treatment becomes empirical. Supportive care may reduce miscarriage rates. Dydrogesterone, a progesterone derivative, may further reduce miscarriage rates. Bed rest and avoidance of sexual intercourse, though commonly advised, are of no proven benefit. Use of uterine relaxing agents, human chorionic gonadotrophin, immunotherapy and vitamins remain controversial in idiopathic recurrent miscarriages.

Development of a quantitative Light Cycler real-time RT-PCR for detection of avian reovirus.

A robust, ultrasensitive, and accurate quantitative assay was developed for avian reovirus (ARV) with the Light Cycler SYBR Green-based real-time reverse transcription-PCR (real-time LC RT-PCR). The assay exhibited high specificity as all negative controls and other avian pathogens, such as Newcastle disease virus (NDV), infectious bronchitis virus (IBV), infectious bursal disease virus (IBDV), avian influenza virus (AIV), and mycoplasma synovia (MS), failed to show any positive detection. A minimum of 39 copies/microl of ARV genomic RNA could be detected by the assay. By dilution analysis, the real-time LC RT-PCR developed in this study was 3-log more sensitive than the conventional RT-PCR for the detection of ARV. The vaccine and field isolates of ARV were detected by the real-time LC RT-PCR. As a result of the high sensitivity and specificity of the assay with a relatively rapid and simple procedure, the real-time LC RT-PCR will be useful as a routine assay for the clinical diagnosis of ARV infection.

Drug utilization pattern of Chinese herbal medicines in a general hospital in Taiwan.

PURPOSE: Drug utilization studies are important for the optimization of drug therapy and have received a great attention in recent years. Most of the information on drug use patterns has been derived from studies in modern Western medicines; however, studies regarding the drug utilization of traditional Chinese medicine (CM) are few. The present study was the first clinical research to evaluate the drug utilization patterns of Chinese herbal medicines in a general hospital in Taiwan. METHODS: Data were collected prospectively from the patients attending the Traditional Medicine Center of Taipei Veteran General Hospital under CM drug treatments. The study was carried out over a period of 1 year, from January 2002 to December 2002. Core drug use indicators, such as the average number of drugs per prescriptions, the dosing frequency of prescriptions, and the most common prescribed CM herbs and formulae were evaluated. The primary diagnosis and the CM drugs prescribed for were also revealed. All data were analyzed by descriptive statistics. RESULTS: A total of 10 737 patients, representing 52 255 CM drugs, were screened during the study period. Regarding the prescriptions, the average number of drugs per prescription was 4.87 and 37.21% of prescriptions were composed by five drugs. Most of prescriptions (91.38%) were prescribed for three times a day. The most often prescribed Chinese herb was Hong-Hwa (5.76%) and the most common Chinese herbal formula was Jia-Wey-Shiau-Yau-San (3.80%). The most frequent main diagnosis was insomnia (15.58%), followed by menopause (5.22%) and constipation (5.09%). CONCLUSION: The survey revealed the drug use pattern of CMs in a general hospital. The majority of CM prescriptions were composed by 3-6 drugs and often prescribed for three times a day. Generally, the rational drug uses of CM drugs were provided with respect to the various diagnoses.

Rational pharmacotherapy in the diabetic hypertension: analysis-prescribing patterns in a general hospital in Taiwan.

OBJECTIVES: To examine prescribing at a 2800-bed hospital, also providing ambulatory services for 9000 visits per day, with a view to assessing the extent to which it followed international guidelines for treating diabetic hypertension. METHOD: Patients receiving antidiabetic and antihypertensive drugs concomitantly during the 4-week study period were included. RESULT: Of the 5015 eligible patients, most received combination antidiabetic therapy. Oral antidiabetic agents used alone or in combination included (in descending order) metformin, glibenclamide, gliclazide, glipizide, glimepiride and alpha-glucosidase inhibitors. Gliclazide accounted for most of the oral antidiabetic drug expenditure. Sulfonylurea plus metformin was the most popular regimen. Prescriptions for long-acting sulfonylureas did not differ between elderly and younger patients. For blood pressure control, calcium-channel blockers were most commonly used alone and overall, although current guidelines suggest that they should be second-line treatments. Inappropriate use of immediate-release nifedipine was noted. The combination, atenolol >100 mg/day and hydrochlorothiazide 50 mg/day (or an equivalent) were extensively used. Among 54.7% patients treated with combination antihypertensives, calcium-channel blockers and an angiotensin-converting enzyme inhibitor were most commonly used. CONCLUSION: Most diabetic hypertensive patients were treated with combination therapy for glucose and blood pressure control. Prescriptions for antihypertensive drugs often differed from current guidelines, especially in the choice of agents and their combinations.

Self-assembly of 10-microm-sized objects into ordered three-dimensional arrays.

This paper describes the self-assembly of small objects--polyhedral metal plates with largest dimensions of 10 to 30 microm--into highly ordered, three-dimensional arrays. The plates were fabricated using photolithography and electrodeposition techniques, and the faces of the plates were functionalized to be hydrophobic or hydrophilic using self-assembled monolayers (SAMs). Self-assembly occurs in water through capillary interactions between thin films of a hydrophobic liquid (a liquid prepolymer adhesive) coated onto the hydrophobic faces of the plates; coalescence of the adhesive films reduces the interfacial free energy of the system and drives self-assembly. By altering the size and surface-patterning of the plates, the external morphologies of the aggregates were varied. Curing the adhesive furnished mechanically stable aggregates that were characterized by scanning electron microscopy (SEM). For assemblies formed by plates partially composed of a sacrificial material, a subsequent etching step furnished fully open, three-dimensional microstructures. This work validates the use of capillary interactions for three-dimensional mesoscale self-assembly in the 10-microm-size regime and opens new avenues for the fabrication of complex, three-dimensional microscructures.

Strategic parameter-driven routing models for multidestination traffic in telecommunication networks.

We present mathematical models that determine the optimal parameters for strategically routing multidestination traffic in an end-to-end network setting. Multidestination traffic refers to a traffic type that can be routed to any one of a multiple number of destinations. A growing number of communication services is based on multidestination routing. In this parameter-driven approach, a multidestination call is routed to one of the candidate destination nodes in accordance with predetermined decision parameters associated with each candidate node. We present three different approaches: (1) a link utilization (LU) approach, (2) a network cost (NC) approach, and (3) a combined parametric (CP) approach. The LU approach provides the solution that would result in an optimally balanced link utilization, whereas the NC approach provides the least expensive way to route traffic to destinations. The CP approach, on the other hand, provides multiple solutions that help leverage link utilization and cost. The LU approach has in fact been implemented by a long distance carrier resulting in a considerable efficiency improvement in its international direct services, as summarized.

Forming electrical networks in three dimensions by self-assembly

Self-assembly of millimeter-scale polyhedra, with surfaces patterned with solder dots, wires, and light-emitting diodes, generated electrically functional, three-dimensional networks. The patterns of dots and wires controlled the structure of the networks formed; both parallel and serial connections were generated.

Geometric control of switching between growth, apoptosis, and differentiation during angiogenesis using micropatterned substrates.

Past studies using micropatterned substrates coated with adhesive islands of extracellular matrix revealed that capillary endothelial cells can be geometrically switched between growth and apoptosis. Endothelial cells cultured on single islands larger than 1500 microm2 spread and progressed through the cell cycle, whereas cells restricted to areas less than 500 microm2 failed to extend and underwent apoptosis. The present study addressed whether island geometries that constrained cell spreading to intermediate degrees, neither supporting cell growth nor inducing apoptosis, cause cells to differentiate. Endothelial cells cultured on substrates micropatterned with 10-microm-wide lines of fibronectin formed extensive cell-cell contacts and spread to approximately 1000 microm2. Within 72 h, cells shut off both growth and apoptosis programs and underwent differentiation, resulting in the formation of capillary tube-like structures containing a central lumen. Accumulation of extracellular matrix tendrils containing fibronectin and laminin beneath cells and reorganization of platelet endothelial cell adhesion molecule-positive cell-cell junctions along the lengths of the tubes preceded the formation of these structures. Cells cultured on wider (30-microm) lines also formed cell-cell contacts and aligned their actin cytoskeleton, but these cells spread to larger areas (2200 microm2), proliferated, and did not form tubes. Use of micropatterned substrates revealed that altering the geometry of cell spreading can switch endothelial cells among the three major genetic programs that govern angiogenesis-growth, apoptosis and differentiation. The system presented here provides a well-defined adhesive environment in which to further investigate the steps involved in angiogenesis.

Design and self-assembly of open, regular, 3D mesostructures

Self-assembly provides the basis for a procedure used to organize millimeter-scale objects into regular, three-dimensional arrays ("crystals") with open structures. The individual components are designed and fabricated of polyurethane by molding; selected faces are coated with a thin film of liquid, metallic alloy. Under mild agitation in warm, aqueous potassium bromide solution, capillary forces between the films of alloy cause self-assembly. The structures of the resulting, self-assembled arrays are determined by structural features of the component parts: the three-dimensional shape of the components, the pattern of alloy on their surfaces, and the shape of the alloy-coated surfaces. Self-assembly of appropriately designed chiral pieces generates helices.

A strategy for the generation of surfaces presenting ligands for studies of binding based on an active ester as a common reactive intermediate: a surface plasmon resonance study.

This paper describes the immobilization of ten proteins and two low-molecular-weight ligands on mixed self-assembled monolayers (SAMs) of alkanethiolates on gold generated from the tri(ethylene glycol)-terminated thiol 1 (HS(CH2)11(OCH2CH2)3OH) (chi(1) = 1.0-0.0) and the longer, carboxylic acid-terminated thiol2(HS(CH2)11(OCH2-CH2)6OCH2CO2H) (chi(2) = 0.0-1.0). The immobilization was achieved by a two-step procedure: generation of reactive N-hydroxysuccinimidyl esters from the carboxylic acid groups of 2 in the SAM and coupling of these groups with amines on the protein or ligand. Because this method involves a common reactive intermediate that is easily prepared, it provides a convenient method for attaching ligands to SAMs for studies using surface plasmon resonance spectroscopy (and, in principle, other bioanalytical methods that use derivatized SAMs on gold, silver, and other surfaces). These SAMs were resistant to nonspecific adsorption of proteins having a wide range of molecular weights and isoelectric points. The pH of the coupling buffer, the concentration of protein, the ionic strength of the solution of protein, and the molecular weight of the protein all influenced the amount of the protein that was immobilized. For the proteins investigated in detail--carbonic anhydrase and lysozyme--the highest quantities of immobilized proteins were obtained when using a low ionic strength solution at a value of pH approximately one unit below the isoelectric point (pI) of the protein, at a concentration of approximately 0.5 mg mL-1. Comparisons of the kinetic and thermodynamic constants describing binding of carbonic anhydrase and vancomycin to immobilized benzenesulfonamide and N-alpha-Ac-Lys-D-Ala-D-Ala groups, respectively, on mixed SAMs (by methods described in this paper) and in the carboxymethyl dextran matrix of commercially available substrates yielded (for these systems) essentially indistinguishable values of Kd, koff, and kon.

Using microcontact printing to pattern the attachment of mammalian cells to self-assembled monolayers of alkanethiolates on transparent films of gold and silver.

This paper describes a convenient methodology for patterning substrates for cell culture that allows the positions and dimensions of attached cells to be controlled. The method uses self-assembled monolayers (SAMs) of terminally substituted alkanethiolates (R(CH2)11-15S-) adsorbed on optically transparent films of gold or silver to control the properties of the substrates. SAMs terminated in methyl groups adsorb protein and SAMs terminated in oligo(ethylene glycol) groups resist entirely the adsorption of protein. This methodology uses microcontact printing (microCP)-an experimentally simple, nonphotolithographic process-to pattern the formation of SAMs at the micrometer scale; microCP uses an elastomeric stamp having at its surface a pattern in relief to transfer an alkanethiol to a surface of gold or silver in the same pattern. Patterned SAMs having hydrophobic, methyl-terminated lines 10, 30, 60, and 90 microm in width and separated by protein-resistant regions 120 microm in width were prepared and coated with fibronectin; the protein adsorbed only to the methyl-terminated regions. Bovine capillary endothelial cells attached only to the fibronectin-coated, methyl-terminated regions of the patterned SAMs. The cells remained attached to the SAMs and confined to the pattern of underlying SAMs for at least 5-7 days. Because the substrates are optically transparent, cells could be visualized by inverted microscopy and by fluorescence microscopy after fixing and staining with fluorescein-labeled phalloidin.

A knowledge-base generating hierarchical fuzzy-neural controller.

We present an innovative fuzzy-neural architecture that is able to automatically generate a knowledge base, in an extractable form, for use in hierarchical knowledge-based controllers. The knowledge base is in the form of a linguistic rule base appropriate for a fuzzy inference system. First, we modify Berenji and Khedkar's (1992) GARIC architecture to enable it to automatically generate a knowledge base; a pseudosupervised learning scheme using reinforcement learning and error backpropagation is employed. Next, we further extend this architecture to a hierarchical controller that is able to generate its own knowledge base. Example applications are provided to underscore its viability.