Diagnostic accuracy of history taking, physical examination and imaging for phalangeal, metacarpal and carpal fractures: a systematic review update.

BACKGROUND: The standard diagnostic work-up for hand and wrist fractures consists of history taking, physical examination and imaging if needed, but the supporting evidence for this work-up is limited. The purpose of this study was to systematically examine the diagnostic accuracy of tests for hand and wrist fractures. METHODS: A systematic search for relevant studies was performed. Methodological quality was assessed and sensitivity (Se), specificity (Sp), accuracy, positive predictive value (PPV) and negative predictive value (NPV) were extracted from the eligible studies. RESULTS: Of the 35 eligible studies, two described the diagnostic accuracy of history taking for hand and wrist fractures. Physical examination with or without radiological examination for diagnosing scaphoid fractures (five studies) showed Se, Sp, accuracy, PPV and NPV ranging from 15 to 100%, 13-98%, 55-73%, 14-73% and 75-100%, respectively. Physical examination with radiological examination for diagnosing other carpal bone fractures (one study) showed a Se of 100%, with the exception of the triquetrum (75%). Physical examination for diagnosing phalangeal and metacarpal fractures (one study) showed Se, Sp, accuracy, PPV and NPV ranging from 26 to 55%, 13-89%, 45-76%, 41-77% and 63-75%, respectively. Imaging modalities of scaphoid fractures showed predominantly low values for PPV and the highest values for Sp and NPV (24 studies). Magnetic Resonance Imaging (MRI), Computed Tomography (CT), Ultrasonography (US) and Bone Scintigraphy (BS) were comparable in diagnostic accuracy for diagnosing a scaphoid fracture, with an accuracy ranging from 85 to 100%, 79-100%, 49-100% and 86-97%, respectively. Imaging for metacarpal and finger fractures showed Se, Sp, accuracy, PPV and NPV ranging from 73 to 100%, 78-100%, 70-100%, 79-100% and 70-100%, respectively. CONCLUSIONS: Only two studies were found on the diagnostic accuracy of history taking for hand and wrist fractures in the current review. Physical examination was of moderate use for diagnosing a scaphoid fracture and of limited use for diagnosing phalangeal, metacarpal and remaining carpal fractures. MRI, CT and BS were found to be moderately accurate for the definitive diagnosis of clinically suspected carpal fractures

Oscillatory surface rheotaxis of swimming E. coli bacteria

Bacterial contamination of biological conducts, catheters or water resources is a major threat to public health and can be amplified by the ability of bacteria to swim upstream. The mechanisms of this rheotaxis, the reorientation with respect to flow gradients, often in complex and confined environments, are still poorly understood. Here, we follow individual E. coli bacteria swimming at surfaces under shear flow with two complementary experimental assays, based on 3D Lagrangian tracking and fluorescent flagellar labelling and we develop a theoretical model for their rheotactic motion. Three transitions are identified with increasing shear rate: Above a first critical shear rate, bacteria shift to swimming upstream. After a second threshold, we report the discovery of an oscillatory rheotaxis. Beyond a third transition, we further observe coexistence of rheotaxis along the positive and negative vorticity directions. A full theoretical analysis explains these regimes and predicts the corresponding critical shear rates. The predicted transitions as well as the oscillation dynamics are in good agreement with experimental observations. Our results shed new light on bacterial transport and reveal new strategies for contamination prevention.Comment: 12 pages, 5 figure

Drug-drug interactions with tyrosine-kinase inhibitors:A clinical perspective

In the past decade, many tyrosine-kinase inhibitors have been introduced in oncology and haemato-oncology. Because this new class of drugs is extensively used, serious drug-drug interactions are an increasing risk. In this Review, we give a comprehensive overview of known or suspected drug-drug interactions between tyrosine-kinase inhibitors and other drugs. We discuss all haemato-oncological and oncological tyrosine-kinase inhibitors that had been approved by Aug 1, 2013, by the US Food and Drug Administration or the European Medicines Agency. Various clinically relevant drug interactions with tyrosine-kinase inhibitors have been identified. Most interactions concern altered bioavailability due to altered stomach pH, metabolism by cytochrome P450 isoenzymes, and prolongation of the QTc interval. To guarantee the safe use of tyrosine-kinase inhibitors, a drugs review for each patient is needed. This Review provides specific recommendations to guide haemato-oncologists, oncologists, and clinical pharmacists, through the process of managing drug-drug interactions during treatment with tyrosine-kinase inhibitors in daily clinical practice

Potential merits for space robotics from novel concepts of actuation for soft robotics

Autonomous robots in dynamic and unstructured environments require high performance, energy efficient and reliable actuators. In this paper we give an overview of the first results of two lines of research regarding the novel actuation principle we introduced: Series-Parallel Elastic Actuation (SPEA). Firstly, we introduce the SPEA concept and present first prototypes and results. Secondly, we discuss the potential of self-healing materials in robotics, and discuss the results on the first self-healing pneumatic cell and selfhealing mechanical fuse. Both concepts have the potential to improve performance, energy efficiency and reliability

Clinical implications of food-drug interactions with small-molecule kinase inhibitors

During the past two decades, small-molecule kinase inhibitors have proven to be valuable in the treatment of solid and haematological tumours. However, because of their oral administration, the intrapatient and interpatient exposure to small-molecule kinase inhibitors (SMKIs) is highly variable and is affected by many factors, such as concomitant use of food and herbs. Food-drug interactions are capable of altering the systemic bioavailability and pharmacokinetics of these drugs. The most important mechanisms underlying food-drug interactions are gastrointestinal drug absorption and hepatic metabolism through cytochrome P450 isoenzymes. As food-drug interactions can lead to therapy failure or severe toxicity, knowledge of these interactions is essential. This Review provides a comprehensive overview of published studies involving food-drug interactions and herb-drug interactions for all registered SMKIs up to Oct 1, 2019. We critically discuss US Food and Drug Administration (FDA) and European Medicines Agency (EMA) guidelines concerning food-drug interactions and offer clear recommendations for their management in clinical practice

Monolayer dual gate transistors with a single charge transport layer

A dual gate transistor was fabricated using a self-assembled monolayer as the semiconductor. We show the possibility of processing a dielectric on top of the self-assembled monolayer without deteriorating the device performance. The two gates of the transistor accumulate charges in the monomolecular transport layer and artifacts caused by the semiconductor thickness are negated. We investigate the electrical transport in a dual gate self-assembled monolayer field-effect transistor and present a detailed analysis of the importance of the contact geometry in monolayer field-effect transistors.

Applying a cost-based pricing model for innovative cancer treatments subject to indication expansion:A case study for pembrolizumab and daratumumab

BACKGROUND: Expanding the indication of already approved immuno-oncology drugs presents treatment opportunities for patients but also strains healthcare systems. Cost-based pricing models are discussed as a possibility for cost containment. This study focuses on two drugs, pembrolizumab (Keytruda) and daratumumab (Darzalex), to explore the potential effect of indication broadening on the estimated price when using the cost-based pricing (CBP) model proposed by Uyl-de Groot and Löwenberg (2018). METHODS: The model was used to calculate cumulative yearly prices, cumulative prices per indication, and non-cumulative indication-based prices using inputs such as research and development (R&amp;D) costs, manufacturing costs, eligible patient population, and a profit margin. A deterministic stepwise analysis and scenario analysis were conducted to examine how sensitive the estimated price is to the different input assumptions. RESULTS: The yearly cumulative cost-based prices (CBPs) ranged from €52 to €885 for pembrolizumab per vial and €823 to €31,941 for daratumumab per vial. Prices were higher in initial years or indications due to smaller patient populations, decreased over time or after additional indications. Sensitivity analysis showed that the number of eligible patients had the most significant impact on the estimated price. In the scenario analysis the profit margin contributed most to a higher CBPs for both drugs. Lower estimates resulted from assumed lower R&amp;D costs. DISCUSSION: The estimated CBPs are consistently lower than Dutch list prices for pembrolizumab (€2,861), mainly resulting from larger patient populations in registered indications. However, daratumumab's list prices fall within the range of modeled CBPs depending on the year or indication (€4,766). Both CBPs decrease over time or with additional indications. The number of eligible patients and initial R&amp;D costs have the most significant influence on the CBPs. These findings contribute to the ongoing discussions on pharmaceutical pricing, especially concerning cancer drugs with expanding indications.</p

Clinical pharmacokinetics and metabolism of irinotecan (CPT-11)

CPT-11 belongs to the class of topoisomerase I inhibitors, and it acts as a prodrug of SN-38, which is approximately 100-1000-fold more cytotoxic than the parent drug. CPT-11 has shown a broad spectrum of antitumor activity in preclinical models as well as clinically, with responses observed in various disease types including colorectal, lung, cervical, and ovarian cancer. The pharmacokinetics and metabolism of CPT-11 are extremely complex and have been the subject of intensive investigation in recent years. Both CPT-11 and SN-38 are known in an active lactone form and an inactive carboxylate form, between which an equilibrium exists that depends on the pH and the presence of binding proteins. CPT-11 is subject to extensive metabolic conversion by various enzyme systems, including esterases to form SN-38, UGT1A1 mediating glucuronidation of SN-38, as well as CYP3A4, which forms several pharmacologically inactive oxidation products. Elimination routes of CPT-11 also depend on the presence of drug-transporting proteins, notably P-glycoprotein and canalicular multispecific organic anion transporter, present on the bile canalicular membrane. The various processes mediating drug elimination, either through metabolic breakdown or excretion, likely impact substantially on interindividual variability in drug handling. Strategies to individualize CPT-11 administration schedules based on patient differences in enzyme or protein expression or by coadministration of specific agents modulating side effects are under way and may ultimately lead to more selective chemotherapeutic use of this agent