Population pharmacokinetics and model-based dosing optimization of teicoplanin in elderly critically ill patients with pneumonia.

PURPOSE: To evaluate the population pharmacokinetics and pharmacodynamics of teicoplanin in elderly critically ill patients with pneumonia for optimal dosages. METHODS: Fifteen critically ill patients (9 men) ≥ 60 years received teicoplanin 6 mg/kg for three doses followed by standard maintenance doses (6 mg/kg q24h) with renal dosing adjustment. Serial plasma samples from all patients were analyzed simultaneously by population pharmacokinetic modeling using NONMEM. Probability of target attainment (PTA) was calculated through Monte Carlo simulations for various dosing regimens to achieve adequate systemic exposures. RESULTS: The median (interquartile range, IQR) age, body mass index, and creatinine clearance (CrCl) was 75 (64-78) years, 22.5 (20.8-25.4) kg/m2, and 64 (47-106) mL/min, respectively. The median (IQR) peak and trough concentration was 46.5 (42.7-51.0) and 8.7 (7.2-9.5) mg/L. The population pharmacokinetic model showed slower clearance (CL) and larger peripheral volume of distribution (V2) in patients with reduced CrCl: CL (L/h) = 0.629 × (CrCl/64)0.656, V2 (L) = 55.7 × (CrCl/64)-0.665. Model-based simulations showed PTAs ≥85% only for higher-dose regimens (12 mg/kg) up to an MIC of 0.5 mg/L. CONCLUSIONS: Standard teicoplanin dosages for pneumonia may provide inadequate systemic exposures in elderly critically ill patients. High-dose regimens should be considered as empiric therapy or for less susceptible pathogens.

Particle Manipulation in 2D Space Using a Capacitive Micromachined Ultrasonic Transducer.

Ultrasonic particle manipulation is a noncontact method for controlling microscale objects, such as cells or microparticles, using an acoustic field. In this study, a 2D array of capacitive micromachined ultrasonic transducers (CMUTs), placed horizontally in immersion, generated ultrasonic waves in the vertical direction, and the oil's surface increased due to the radiation force of the ultrasonic waves. In addition, the radiation force directly exerted a force on a floating particle. By measuring the movement of the reflected laser light by the moving oil surface, the height of the oil's surface deformed by the acoustic radiation force (ARF) was measured. The ARF made a floating particle, as well as the oil's surface, move. The particle moved radially away from the surface position above the transducer, and its velocity was determined by its position on the fluid's surface. When a single channel was operated, it moved 0.4 mm at an average speed of 90 µm/s, and when two adjacent channels were operated, it moved 1.2 mm at a speed of 272 µm/s. The particles moved in any direction on the surface of the oil by controlling the actuation channel using an electrical switch.

Forward-Looking Ultrasound Wearable Scanner System for Estimation of Urinary Bladder Volume.

Accurate measurement of bladder volume is an important tool for evaluating bladder function. In this study, we propose a wearable bladder scanner system that can continuously measure bladder volume in daily life for urinary patients who need urodynamic studies. The system consisted of a 2-D array, which included integrated forward-looking piezoelectric transducers with thin substrates. This study aims to estimate the volume of the bladder using a small number of piezoelectric transducers. A least-squares method was implemented to optimize an ellipsoid in a quadratic surface equation for bladder volume estimation. Ex-vivo experiments of a pig bladder were conducted to validate the proposed system. This work presents the potential of the approach for wearable bladder monitoring, which has similar measurement accuracy compared to the commercial bladder imaging system. The wearable bladder scanner can be improved further as electronic voiding diaries by adding a few more features to the current function.

Fatal Events Associated with Adverse Drug Reactions in the Korean National Pharmacovigilance Database.

Adverse drug reactions (ADRs) pose a global public health threat, substantially contributing to death. Due to the relative paucity of clinical evidence regarding fatal ADRs, this study was performed to characterize the epidemiology of fatal ADRs in Korea. This was a retrospective, cross-sectional analysis of ADR cases reported to the Korea Adverse Event Reporting System from 2010 to 2019. All ADRs were coded using the World Health Organization-Adverse Reaction Terminology system and classified as either fatal or non-fatal events. Logistic regression was performed to identify factors associated with fatal events. Among 289,756 ADR records, 629 fatal events (0.2%) occurred. The most common causative agent of fatal ADRs was antibacterials (20.3%), followed by antimycobacterials (5.4%), analgesics (4.0%), and contrast media (1.9%). Among antimicrobials, vancomycin was most frequently implicated without significantly increasing the risk of fatal events. The risk for fatal ADRs was significantly increased with male sex; advanced age; polypharmacy; piperacillin/ß-lactamase inhibitor; cefotetan; ceftriaxone; combination antimycobacterial therapy consisting of rifampicin, isoniazid, pyrazinamide, and ethambutol; morphine; and iopromide (reporting odds ratio > 1, p < 0.05 for all). Although fatal ADRs are uncommon (<1%) in Korea, they are primarily caused by commonly used medications including antibiotics, analgesics, and contrast media.

Efficacy and safety of thread embedding acupuncture combined with acupuncture for chronic low back pain: A randomized, controlled, assessor-blinded, multicenter clinical trial.

BACKGROUND: Low back pain is a very common disease. Many patients with chronic low back pain (CLBP) have been treated by complementary and alternative medicine such as acupuncture (AT) treatment. A type of AT, thread embedding acupuncture (TEA), consists of a thread that can continually stimulate at the AT points and has mechanical and chemical effects. Although TEA was widely used in clinical practice, there was little evidence of its efficacy and safety for CLBP. METHODS: This clinical trial was randomized, controlled, assessor-blinded, two-armed, parallel, and conducted in multiple centers. Four Korean medical institutions recruited 38 outpatients with CLBP. The participants were randomly allocated to a treatment group (TEA combined with AT) or a control group (only AT) in a 1:1 ratio. All participants received conventional AT twice a week for 8 weeks (16 sessions) at 15 AT points (GV3 and bilateral BL23, BL24, BL25, BL26, BL40, BL60, and EX-B5) and the treatment group participants additionally received TEA once a week for 8 weeks (8 sessions) on 10 AT points in the multifidus, spinal erector, and lumbar quadrate muscles. The primary outcome measure of this study was the change of visual analog scale (VAS) from baseline (0 week) to the end of intervention (8 weeks). Secondary outcome measures included clinically relevant improvement (minimal clinically important difference) and 3% to 50% decrease on VAS, disability level (Korean version of Roland and Morris disability questionnaire), quality of life (Korean version of European quality of life 5dimension), global assessment (patient global impression of change), economic analysis, credibility test, and safety assessment. RESULTS: The treatment group showed a significant reduction in VAS scores when compared with the control group (-33.7 ±â€Š25.1 vs -15.6 ±â€Š17.0, P = .013). As for the secondary outcome measures, the treatment group showed significant difference in 50% decrease on VAS and patient global impression of change. There was no serious adverse event associated with TEA and AT. CONCLUSION: This clinical trial documents the efficacy and safety of TEA combined with AT for the management of CLBP.

Frequency modulation of laser ultrasound transducer using carbon nanotube-coated polyethylene microsphere.

An ultrasound transducer was fabricated by dropping a multi-walled carbon nanotube solution containing a mixture of carbon nanotubes and ethoxyethanol directly on the surface of polyethylene microspheres. The frequency modulation depended on the diameter of the polyethylene microspheres. To investigate this relationship, three types of polyethylene microspheres with different diameters were used in simulations and experiments. These specimens were attached to polydimethylsiloxane and glass plates. A comparison revealed that the 50 µm diameter polyethylene spheres coated with carbon nanotubes had the highest ultrasound frequency. This work showed that smaller polyethylene microspheres generate higher ultrasound frequencies.

Multipoint-Detection Strain Sensor with a Single Electrode Using Optical Ultrasound Generated by Carbon Nanotubes.

With the development of wearable devices, strain sensors have attracted large interest for the detection of human motion, movement, and breathing. Various strain sensors consisting of stretchable conductive materials have been investigated based on resistance and capacitance differences according to the strain. However, this method requires multiple electrodes for multipoint detection. We propose a strain sensor capable of multipoint detection with a single electrode, based on the ultrasound pulse-echo method. It consists of several transmitters of carbon nanotubes (CNTs) and a single polyvinylidene fluoride receiver. The strain sensor was fabricated using CNTs embedded in stretchable polydimethylsiloxane. The received data are characterized by the different times of transmission from the CNTs of each point depending on the strain, i.e., the sensor can detect the positions of the CNTs. This study demonstrates the application of the multipoint strain sensor with a single electrode for measurements up to a strain of 30% (interval of 1%). We considered the optical and acoustic energy losses in the sensor design. In addition, to evaluate the utility of the sensor, finger bending with three-point CNTs and flexible phantom bending with six-point CNTs for the identification of an S-curve having mixed expansion and compression components were carried out.

Single-Shot Waterless Low-Profile Photoacoustic System: Near-Field Volumetric Imaging In Vivo for Blood Vessels Based on Capacitive Micromachined Ultrasonic Transducer (CMUT).

Intensive research on photoacoustics (PA) for imaging of the living human body, including the skin, vessels, and tumors, has recently been conducted. We propose a PA measurement system based on a capacitive micromachined ultrasonic transducer (CMUT) with waterless coupling, short measurement time (<1 s), backward light irradiation, and a low-profile ultrasonic receiver unit (<1 cm). We fabricate a 64-element CMUT ring array with 6.2 mm diameter and 10.4 MHz center frequency in air, and 100% yield and uniform element response. To validate the PA tissue characterization, we employ pencil lead and red ink as solid and liquid models, respectively, and a living body to target moles and vessels. The system implements a near-field imaging system consisting of a 6 mm polydimethylsiloxane (PDMS) matching layer between the object and CMUT, which has a 3.7 MHz center frequency in PDMS. Experiments were performed in a waterless contact on the PDMS and the laser was irradiated with a 1 cm diameter. The experimental results show the feasibility of this near-field PA imaging system for position and depth detection of skin, mole, vessel cells, etc. Therefore, a system applicable to a low-profile compact biomedical device is presented.