Novel innovative computer-based test (Inno-CBT) item types for national licensing examinations for health care professionals.

BACKGROUND: An effective test mechanism to evaluate clinical knowledge and skills of the entry-level healthcare professionals is important for providing clinical competency and improving patient care. This study aimed to develop novel, innovative computer-based test (Inno-CBT) item types for application in the national examination of Korean healthcare professionals. METHODS: This exploratory study was conducted from May 2021 to March 2022 by a team of faculty members from pharmacy schools in South Korea. A literature search using PubMed, Google Scholar, RISS, Web of Science, and KoreaMed was performed. Forum presentations, media articles, and previous reports by the Korea Health Personnel Licensing Examination Institute (KHPLEI) were included. Workshops were held, information and ideas were collected and conceptualized, and item types were designed, drafted, and refined. By repeating this process, the Inno-CBT item types were finalized. RESULTS: Forty-one Inno-CBT item types with 28 subtypes were developed. New digital technologies, such as a reactive responsive media interface, an animation insertion, multimedia embedding, and network surfing, were utilized in these novel types. It was anticipated that these Inno-CBT item types would effectively measure abilities in healthcare knowledge, problem-solving skills, and professional behaviors. Some potential barriers to implementing the Inno-CBT item types include item difficulty, operational unfamiliarity, complexity in scoring protocols, and network security. CONCLUSIONS: A variety of styles of novel Inno-CBT item types were developed to evaluate the multifaceted and in-depth professional abilities required for healthcare professionals. Prior to implementing these item types in the national examination, item validation and technical support should be conducted.

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.

Objective structured clinical examination as a competency assessment tool of students' readiness for advanced pharmacy practice experiences in South Korea: a pilot study.

BACKGROUND: The assessment of pharmacy students' readiness to begin the education of an advanced pharmacy practice experience (APPE) in clinical pharmacy settings continues to gain increasing attention. This study aimed to develop an objective structured clinical examination (OSCE) in the core domains acquired through an introductory pharmacy practice experience (IPPE), for evaluating its appropriateness as a tool of assessing clinical pharmacist competency for APPEs in Korean pharmacy students throughout a pilot study. METHODS: OSCE's core competency domains and case scenarios were developed through a literature review, ideation by researchers, and external experts' consensus by a Delphi method. A prospective single-arm pilot test was conducted to implement the OSCE for Korean pharmacy students who completed a 60-h course of in-class simulation IPPE. Their competencies were assessed by four assessors in each OSCE station with a pass-fail grading system accompanied by a scoring rubric. RESULTS: OSCE competency areas including patient counseling, provision of drug information, over-the-counter (OTC) counseling, and pharmaceutical care services were developed with four interactive and one non-interactive cases. Twenty pharmacy students participated in the OSCE pilot test, and their competencies were evaluated by 20 assessors. The performance rate was the lowest in the area of patient counseling for a respiratory inhaler (32.1%) and the highest (79.7%) in OTC counseling for constipation. The students had an average performance rate of 60.4% in their communication skills. Most participants agreed on the appropriateness, necessity, and effectiveness of the OSCE in evaluating pharmacy students' clinical performance and communication skills. CONCLUSIONS: The OSCE model can be used to assess pharmacy students' readiness for off-campus clinical pharmacy practice experience. Our pilot study suggests the necessity of conducting an OSCE domain-based adjustment of difficulty levels, and strengthening simulation-based IPPE education.

Development of simultaneous quantitative analytical method for metabolites of hexosamine biosynthesis pathway in lung cancer cells using ultra-high-performance liquid chromatography-tandem mass spectrometry.

The hexosamine biosynthesis pathway (HBP) is a glucose metabolism pathway that produces uridine diphosphate N-acetyl glucosamine (UDP-GlcNAc). Substantial changes in HBP, including elevated HBP flux and UDP-GlcNAc levels, are associated with cancer pathogenesis. Particularly, cancer cells expressing oncogenic Kirsten rat sarcoma virus (KRAS) are highly dependent on HBP for growth and survival. To differentiate between HBP metabolites in KRAS wild-type (WT) and mutant (MT) lung cancer cells, a simultaneous quantitative method for analyzing seven HPB metabolites was developed using ultra-high-performance liquid chromatography-tandem mass spectrometry. A simple method without complicated preparation steps, such as derivatization or isotope labeling, was optimized for the simultaneous analysis of highly hydrophilic HBP metabolites, and the developed method was successfully verified. The intra- and inter-day coefficients of variation were less than 15% for all HBP metabolites, and the recovery was 89.67-114.5%. All results of the validation list were in accordance with ICM M10 guidelines. Through this method, HBP metabolites in lung cancer cells were accurately quantified, and it was confirmed that all HBP metabolites were upregulated in KRAS MT cells compared with KRAS WT lung cancer cells. We expect that this will be a useful tool for metabolic research on cancer and for the development of new drugs for cancer treatment.

A Validated Chiral LC-MS/MS Method for the Enantioselective Determination of (S)-(+)- and (R)-(-)-Ibuprofen in Dog Plasma: Its Application to a Pharmacokinetic Study.

The purpose of this study was to develop a method for simultaneously separating ibuprofen enantiomers using electrospray ionization (ESI) liquid chromatography with tandem mass spectrometry (LC-MS/MS). LC-MS/MS was operated with negative ionization and multiple reaction monitoring modes; transitions were monitored at m/z of 205.1 > 160.9 for ibuprofen enantiomers, 208.1 > 163.9 for (S)-(+)-ibuprofen-d3 [internal standard 1 (IS1)], and 253.1 > 208.9 for (S)-(+)-ketoprofen (IS2), respectively. In a one-step liquid-liquid extraction, 10 µL plasma was extracted with ethyl acetate:methyl tertiary-butyl ether of 7:3. Enantiomer chromatographic separation was carried out with an isocratic mobile phase consisting of 0.008% formic acid in water-methanol (v/v) at a flow rate of 0.4 mL/min on a CHIRALCEL® OJ-3R column (150 × 4.6 mm, 3 µm). This method was fully validated for each enantiomer and results were in compliance with the regulatory guidelines of the U.S. Food and Drug Administration and the Korea Ministry of Food and Drug Safety. The validated assay was executed for nonclinical pharmacokinetic studies after oral and intravenous administration of racemic ibuprofen and dexibuprofen in beagle dogs.

Population pharmacokinetics and pharmacodynamics of cefazolin using total and unbound serum concentrations in patients with high body weight.

The objective of this study was to evaluate the steady state pharmacokinetics and pharmacodynamics of cefazolin in patients with a high body weight. Cefazolin was administered by 0.5-h infusions to 11 patients with total body weight (TBW) ≥120 kg receiving 3 g q8h, and 12 patients with TBW <120 kg receiving 2 g q8h. Total and unbound serum concentration-time data obtained from serial blood samples were analysed simultaneously by population pharmacokinetic modelling using NONMEM. Probability of target attainment (PTA) was calculated for various dosing regimens through Monte Carlo simulations based on the cumulative percentage of the dosing interval that the unbound concentration exceeds the minimum inhibitory concentration (MIC) value for the pathogen at steady state (fTMIC) ≥40%, ≥60% and 100%. A two-compartment model with non-linear protein binding and allometric scaling of the central volume of distribution using TBW best characterized both total and unbound concentration-time data. Unbound clearance was significantly associated with creatinine clearance, and maximum protein binding constant was significantly associated with serum albumin concentration and body mass index (P <0.05). Based on unbound concentration-time profiles, all simulated regimens achieved PTA >90% at MIC values ≤2 mg/L using fTMIC ≥40%, at MIC values ≤1 mg/L using fTMIC ≥60%, and at MIC values ≤0.5 mg/L using fTMIC of 100%. At fTMIC ≥60%, 0.5-h infusion of cefazolin 1 g q8h achieved PTA <90% at MIC values ≥2 mg/L in patients with TBW≥120 kg; however, prolonged-infusion and higher-dose regimens improved PTA to >90%. Overall, cefazolin pharmacokinetics are altered considerably in obese patients. Higher-dose and/or prolonged-infusion cefazolin regimens should be considered in patients with TBW ≥120 kg, particularly those with less-susceptible Gram-negative infections.

Potentially Inappropriate Medication Use in Patients with Dementia.

The objective of this study was to characterize the epidemiology of using potentially inappropriate medications associated with dementia exacerbation (DPIMs) in elderly outpatients with dementia. Electronic medical records were retrospectively reviewed for geriatric patients with dementia who were prescribed at least one medication in 2016 at a tertiary, university-affiliated hospital. The 2015 Beers criteria were used to define DPIMs. Logistic regression was performed to identify factors associated with prescribing DPIMs in patients with dementia. Among 2100 patients included in our study, 987 (47.0%) patients were prescribed at least one DPIM. Benzodiazepines were the most frequently prescribed DPIM followed by anticholinergics, histamine H2-receptor blockers, and zolpidem. The risk of prescribing DPIMs was significantly increased in female patients (odds ratio (OR) 1.355) with polypharmacy (OR 5.146) and multiple comorbidities (OR 1.129) (p < 0.05 for all). Coexistence of Parkinson's disease (OR 1.799), mood disorder (OR 1.373), or schizophrenia (OR 4.116) in patients with dementia further increased the likelihood of receiving DPIMs. In conclusion, DPIMs were commonly used in elderly patients with dementia in Korea with benzodiazepines most frequently prescribed followed by anticholinergics. Female patients using polypharmacy with multiple comorbidities should be closely monitored to minimize unnecessary DPIM use and, ultimately, DPIM-related harms.

Effects of Early Initiation of High-Dose Dexamethasone Therapy on Pro-Inflammatory Cytokines and Mortality in LPS-Challenged Mice.

This study aims to explore the effects of early dexamethasone therapy at low to high doses on the survival and inflammatory responses in lipopolysaccharide (LPS)-challenged mice. We performed two-series experiments to explore the impact of early dexamethasone therapy at different doses (0.5 mg/kg, 1.5 mg/kg, and 5 mg/kg; PO) on pro-inflammatory cytokine levels, including tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), as well as survival in LPS-treated mice (10 mg/kg, IP). Dexamethasone was administered daily from 24 h before and 5 days after LPS challenge. Dose-dependent improved survival was demonstrated with dexamethasone (p < 0.05). Body weight was significantly decreased within 24 h of LPS injection, with significantly greater weight loss in the dexamethasone groups (p < 0.05). Weight changes were significantly associated with the days after LPS administration (p < 0.01), but not with the dexamethasone dose (p > 0.05). Mice treated with high-dose dexamethasone (5 mg/kg) had a significantly lowered serum TNF-α (134.41 ± 15.83 vs. 408.83 ± 18.32) and IL-6 (22.08 ± 4.34 vs. 91.27 ± 8.56) compared with those without dexamethasone. This study provides essential insights that the suppression of early-phase hyperactivation of pro-inflammatory activities through the early initiation of high-dose dexamethasone therapy increases sepsis-related prognosis.

Characterization of Medication Errors in a Medical Intensive Care Unit of a University Teaching Hospital in South Korea.

OBJECTIVES: The objective of this study was to characterize the current status of medication errors (MEs) throughout the medication therapy process from prescribing to use and monitoring in a medical intensive care unit (MICU) in Korea. METHODS: Four trained research pharmacists collected data through retrospectively reviewing electronic medical records for adults hospitalized in the MICU in 2017. The occurrence of MEs was determined through interprofessional team discussion led by an academic faculty pharmacist and a medical intensivist based on the medication administration records (MARs). The type of MEs and the consequent ME-related outcome severity were categorized according to the Pharmaceutical Care Network Europe and the National Coordinating Council for Medication Error Reporting and Prevention, respectively. RESULTS: Overall, electronic medical records for 293 patients with 78,761 MARs were reviewed in this study. At least one type of ME occurred in 271 patients (92.5%) in association with 16,203 MARs (21%), primarily caused by inappropriate dose (35.5%), drug (27.8%), and treatment duration (25.1%). Clinically significant harmful events occurred in 24 patients (8%), including life-threatening (n = 5) and death (n = 2) cases. The 2 patients died of enoxaparin-induced fatal hemorrhage and neutropenia associated with ganciclovir and cefepime. Antibiotics were the most common culprit medications leading to clinically significant harmful events. CONCLUSIONS: In conclusion, MEs are prevalent in the MICU in Korea, most commonly prescribing errors. Although mostly benign, harmful events including deaths may occur due to MEs, mainly associated with antibiotics. Systematic strategies to minimize these potentially fatal MEs are urgently needed.

A Pharmacokinetic Study of Ephedrine and Pseudoephedrine after Oral Administration of Ojeok-San by Validated LC-MS/MS Method in Human Plasma.

A sensitive and reproducible liquid chromatography-tandem mass spectrometry (LC-MS/MS) system was developed and fully validated for the simultaneous determination of ephedrine and pseudoephedrine in human plasma after oral administration of the herbal prescription Ojeok-san (OJS); 2-phenylethylamine was used as the internal standard (IS). Both compounds presented a linear calibration curve (r2 ≥ 0.99) over a concentration range of 0.2-50 ng/mL. The developed method was fully validated in terms of selectivity, lower limit of quantitation, precision, accuracy, recovery, matrix effect, and stability, according to the regulatory guidelines from the U.S. Food and Drug Administration and the Korea Ministry of Food and Drug Safety. This validated method was successfully applied for the pharmacokinetic assessment of ephedrine and pseudoephedrine in 20 healthy Korean volunteers administered OJS.

Comparative Safety Profiles of Sedatives Commonly Used in Clinical Practice: A 10-Year Nationwide Pharmacovigilance Study in Korea.

This study aims to compare the prevalence and seriousness of adverse events (AEs) among sedatives used in critically ill patients or patients undergoing invasive procedures and to identify factors associated with serious AEs. Retrospective cross-sectional analysis of sedative-related AEs voluntarily reported to the Korea Adverse Event Reporting System from 2008 to 2017 was performed. All AEs were grouped using preferred terms and System Organ Classes per the World Health Organization-Adverse Reaction Terminology. Logistic regression was performed to identify factors associated with serious events. Among 95,188 AEs, including 3132 (3.3%) serious events, the most common etiologic sedative was fentanyl (58.8%), followed by pethidine (25.9%). Gastrointestinal disorders (54.2%) were the most frequent AEs. The most common serious AE was heart rate/rhythm disorders (33.1%). Serious AEs were significantly associated with male sex; pediatrics; etiologic sedative with etomidate at the highest risk, followed by dexmedetomidine, ketamine, and propofol; polypharmacy; combined sedative use; and concurrent use of corticosteroids, aspirin, neuromuscular blockers, and antihistamines (reporting odds ratio > 1, p < 0.001 for all). Sedative-induced AEs are most frequently reported with fentanyl, primarily manifesting as gastrointestinal disorders. Etomidate is associated with the highest risk of serious AEs, with the most common serious events being heart rate/rhythm disorders.

Quantification of Teicoplanin Using the HPLC-UV Method for Clinical Applications in Critically Ill Patients in Korea.

A high-performance liquid chromatography-ultraviolet detector (HPLC-UV) method has been used to quantify teicoplanin concentrations in human plasma. However, the limited analytical accuracy of previously bioanalytical methods for teicoplanin has given rise to uncertainty due to the use of an external standard. In this study, an internal standard (IS), polymyxin B, was applied to devise a precise, accurate, and feasible HPLC-UV method. The deproteinized plasma sample containing teicoplanin and an IS of acetonitrile was chromatographed on a C18 column with an acidic mobile phase consisting of NaH2PO4 buffer and acetonitrile (78:22, v/v) by isocratic elution and detection at 220 nm. The linearity was in the range 7.8-500 mg/L calculated by the ratio of the teicoplanin signal to the IS signal. This analytical method, validated by FDA guidelines with ICH Q2 (R1), was successfully applied to analyze the plasma samples of patients in the intensive care unit for treating serious resistant bacterial infectious diseases, such as those by methicillin-resistant Staphylococcus aureus and Enterococcus faecalis. The methods suggested the potential for use in routine clinical practice for therapeutic drug monitoring of teicoplanin, providing both improved accuracy and a wide range of linearity from lower than steady-state trough concentrations (10 mg/L) to much higher concentrations.

Validation of a Questionnaire for Patient Awareness and the Need for a Community-Based Outpatient Antimicrobial Stewardship Program (O-ASP): A Pilot Study.

An outpatient antimicrobial stewardship program (O-ASP) was developed and implemented to promote appropriate antibiotic therapy in outpatient settings. As active patient involvement is a critical component of an effective O-ASP, this study aimed to develop and validate a questionnaire addressing patient awareness for appropriate antibiotic therapy and the need for pharmaceutical care services (PCS) in the O-ASP in Korea. The questionnaire was drafted based on ASPs and PCS guidelines and validated for content and construct validity using the item-content validity index (I-CVI) and Cronbach's alpha, respectively. The estimated I-CVI and Cronbach's alpha were considered excellent or adequate (≥0.8 and 0.70-0.90, respectively) for most of the survey items (17 out of 23 items). The validated questionnaire was utilized in a pilot survey study, including 112 individuals (37% male) with the mean ± SD age of 37 ± 13 years. Among the survey participants, 68% responded that antibiotics had been prescribed appropriately; however, ≥50% showed a lack of knowledge regarding their antibiotic therapy. The participants expressed the need for PCS as part of an O-ASP in the questionnaire (average Likert score ≥3.4/5). In conclusion, our newly validated questionnaire successfully measured patient awareness and knowledge of antimicrobial use and the need for PCS in the O-ASP.

Standardized hot water extract from the leaves of Hydrangea serrata (Thunb.) Ser. alleviates obesity via the AMPK pathway and modulation of the gut microbiota composition in high fat diet-induced obese mice.

Obesity is an increasing health problem worldwide as it is the major risk factor for metabolic diseases. In the present study, we investigated the anti-obesity effects of WHS by examining its effects on high fat diet (HFD)-induced obese mice. Male C57BL/6 mice were fed either a normal diet (ND) or a high fat diet (HFD) with or without WHS. At the end of the experiment, we observed the changes in their body weight and white adipose tissue (WAT) weight and lipid profiles in plasma. We performed western blot and histological analyses of WAT and liver to elucidate the molecular mechanisms of action. We also conducted fecal 16S rRNA analysis for investigating the gut microbiota. Our results indicated that pre- and post-oral administration of WHS significantly prevented body weight gain and reduced body fat weight in HFD-induced obese mice. In addition, WHS was found to improve adipocyte hypertrophy and liver fat accumulation by regulating the AMPK and AKT/mTOR pathways. WHS ameliorated hyperlipidemia by reducing total cholesterol and low-density lipoprotein (LDL) and decreased the energy metabolism-related hormones, leptin and insulin, in mouse plasma. Furthermore, we found that WHS modulated gut dysbiosis by normalizing HFD-induced changes. Taken together, our in vivo data implicate that WHS can be considered as a potential dietary supplement for alleviating obesity.

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.

Clinical impact of early reinsertion of a central venous catheter after catheter removal in patients with catheter-related bloodstream infections.

OBJECTIVE: Early replacement of a new central venous catheter (CVC) may pose a risk of persistent or recurrent infection in patients with a catheter-related bloodstream infection (CRBSI). We evaluated the clinical impact of early CVC reinsertion after catheter removal in patients with CRBSIs. METHODS: We conducted a retrospective chart review of adult patients with confirmed CRBSIs in 2 tertiary-care hospitals over a 7-year period. RESULTS: To treat their infections, 316 patients with CRBSIs underwent CVC removal. Among them, 130 (41.1%) underwent early CVC reinsertion (≤3 days after CVC removal), 39 (12.4%) underwent delayed reinsertion (>3 days), and 147 (46.5%) did not undergo CVC reinsertion. There were no differences in baseline characteristics among the 3 groups, except for nontunneled CVC, presence of septic shock, and reason for CVC reinsertion. The rate of persistent CRBSI in the early CVC reinsertion group (22.3%) was higher than that in the no CVC reinsertion group (7.5%; P = .002) but was similar to that in the delayed CVC reinsertion group (17.9%; P > .99). The other clinical outcomes did not differ among the 3 groups, including rates of 30-day mortality, complicated infection, and recurrence. After controlling for several confounding factors, early CVC reinsertion was not significantly associated with persistent CRBSI (OR, 1.59; P = .35) or 30-day mortality compared with delayed CVC reinsertion (OR, 0.81; P = .68). CONCLUSIONS: Early CVC reinsertion in the setting of CRBSI may be safe. Replacement of a new CVC should not be delayed in patients who still require a CVC for ongoing management.

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.

Renal Dysfunction and Tubulopathy Induced by High-Dose Tenofovir Disoproxil Fumarate in C57BL/6 Mice.

Tenofovir disoproxil fumarate (TDF) is the most preferred antiretroviral medicine in treating human immunodeficiency virus (HIV) and hepatitis B virus (HBV) infections. Recent clinical trials have reported conflicting results on renal toxicity and safety in TDF-treated patients, but reference animal studies, testing high-doses of TDF for renal toxicity, are scarce. In this preclinical study, we investigated whether daily oral TDF administration (200, 500, or 800 mg/kg/d, p.o.) for four weeks induces renal insufficiency in C57BL/6 mice, by evaluating changes in body weight, urine micro-total protein, urinary microalbumin, serum blood urea nitrogen (BUN), and creatinine levels, along with histological examination of kidney samples. In the G3 group (TDF 800 mg/kg/d, p.o.), three mice died on the 17th, 23rd and 26th days, and overall, significant increases in urinary and serum levels were observed after two weeks of TDF treatment. In addition, the proportion of pyknotic epithelial cells and acidophilic cytoplasm in renal tubules was also increased after two weeks, and congestion and hemorrhage were observed in renal tubules after three weeks. Taken together, high-dose TDF treatment of 800 mg/kg/d might lead to renal tubular damage and dysfunction, great enough to cause death in mice, even after a short period of one to two weeks.

Exercise Therapies for Parkinson's Disease: A Systematic Review and Meta-Analysis.

Recently, rehabilitative exercise therapies have been described as an important method of overcoming the limitations of the conventional therapies for Parkinson's disease. The present study aimed to evaluate efficacy and safety of exercise therapies for Parkinson's disease. Randomized controlled trials that evaluated exercise therapies in patients with Parkinson's disease until December 2016 were searched for in five electronic databases: PubMed, CENTRAL, EMBASE, OASIS, and CNKI. Eighteen studies (1,144 patients) were included. The overall methodological quality was not high. Patients who underwent exercise therapies exhibited statistically significant improvements in the total UPDRS, UPDRS II and III, Berg Balance Scale, preferred walking speed, and Timed Up and Go Test compared to patients who underwent nonexercise therapies. In comparison to patients who performed regular activity, patients who underwent exercise therapies exhibited statistically significant improvements in the total UPDRS, UPDRS II, and UPDRS III. Exercise therapies were found to be relatively safe. Exercise therapies might promote improvements in the motor symptoms of Parkinson's disease. However, due to the small number of randomized controlled trials and methodological limitations, we are unable to draw concrete conclusions. Therefore, further studies with better designs will be needed.

Development and Validation of an LC-MS/MS Assay to Quantitate 2',4',6'-Trihydroxyacetophenone in Rat and Dog Plasma and its Application to a Pharmacokinetic Study.

In the present study, a simple, rapid, and reliable bioanalytical method was developed using liquid chromatography with tandem-mass spectrometry (LC-MS/MS) to quantify 2',4',6'-trihydroxyacetophenone (THAP) in rat and dog plasma with 2',4',6'-trihydroxybenzaldehyde as an internal standard (IS). The LC-MS/MS instrument was operated in the multiple reaction monitoring (MRM) mode to detect THAP at m/z transition 166.89 > 82.8 and IS at 152.89 > 82.8, respectively. A simple, one-step protein precipitation (PP) method was employed with acetonitrile for sample preparation. Utilizing a Gemini C18 column, THAP and IS were separated with an isocratic mobile phase consisting of 10 mM ammonium acetate and methanol (10:90, v/v) at a flow rate of 0.2 mL/min. Total chromatographic run time was 2.5 min per sample injection. The standard calibration curve for THAP was linear (r2 ≥ 0.9987) over the concentration range of 0.1 to 100 µg/mL with the lower limit of quantitation (LLOQ) of 0.1 µg/mL (S/N ratio > 10). According to the regulatory guidelines from the U.S. Food and Drug Administration (FDA) and the Korea Ministry of Food and Drug Safety (MFDS), our newly developed biomedical analytical method was fully and adequately validated in terms of selectivity, sensitivity, linearity, intra- and inter-day precision and accuracy, recovery, matrix effect, stability, and dilution integrity. Our validated assay was successfully utilized in a nonclinical pharmacokinetic study of THAP in rats and dogs.