Therapeutic Efficacy of Chinese Patent Medicine Containing Pyrite for Fractures: A Systematic Review and Meta-Analysis.

Background and Objectives: Korean and traditional Chinese medicine state that pyrite is effective for fracture treatment, but supporting clinical data are limited. This systematic review aimed to investigate the therapeutic role of Chinese patent medicine containing pyrite (CPMP) in clinical treatment for fractures. Materials and Methods: Seven electronic databases were searched using the keywords "pyrite", "pyritum", and "zirantong" between inception and December 2022, yielding 29 published clinical studies. Randomized controlled trials that included CPMP were considered eligible regardless of the fracture type. Quality assessment and meta-analysis of the included RCTs were also performed. Results: Most studies showed high heterogeneity (I2 > 50%) and significant results (p < 0.05). Compared to the results of the control group, CPMP was more effective in terms of the primary outcome related to the efficacy rate, including the total effective rate, callus growth rate, bone union, and edema disappearance time (all p < 0.00001) and in terms of secondary outcomes related to pain reduction, namely pain intensity and pain disappearance time, than the control group (both p < 0.01). CPMP was more effective than the control group in terms of erythrocyte sedimentation rate (p < 0.01), hematocrit (p < 0.01), erythrocyte aggregation (p < 0.05), and plasma viscosity (p < 0.05). CPMP did not cause serious side effects, and the incidence of complications was significantly less than that in the control group. Conclusions: CPMP may be a safe and effective alternative treatment for fractures and may be beneficial in preventing postoperative complications, reducing pain, relieving symptoms, and accelerating healing.

Pharmacokinetic Characteristics and Limited Sampling Strategies for Therapeutic Drug Monitoring of Colistin in Patients With Multidrug-Resistant Gram-Negative Bacterial Infections.

BACKGROUND: Colistin is increasingly used as the last therapeutic option for the treatment of multidrug-resistant, Gram-negative bacterial infections. To ensure safe and efficacious use of colistin, therapeutic drug monitoring (TDM) is needed due to its narrow therapeutic window. This study aimed to evaluate the pharmacokinetic (PK) characteristics of colistin and to guide TDM in colistin-treated patients in Korea. METHODS: In a prospective study, we analyzed PK characteristics in 15 patients who intravenously received colistin methanesulfonate twice per day. Colistin methanesulfonate doses were adjusted based on renal function of the subjects. The appropriate blood sampling points for TDM were evaluated by analyzing the correlations between the PK parameters and the plasma concentrations at each time point. RESULTS: The mean values for the minimum, maximum, and average concentrations (Cmin, Cmax, and Caverage) of colistin at steady state were 2.29, 5.5, and 3.38 mg/L, respectively. The dose-normalized Cmin, Cmax, Caverage, and area under the plasma concentration-time curve from 0 to the last measurable concentration (AUClast) showed negative correlations with the creatinine clearance. The combination of the 0- and 2-hour post-dose plasma concentrations was evaluated as the appropriate sampling point for TDM. Two patients reported nephrotoxic adverse events during colistin administration. CONCLUSIONS: Our study clarifies the PK characteristics of successful colistin treatment using TDM. Further evaluations in a larger patient population are needed to confirm the clinical usefulness of colistin TDM.

Comparison of clinical characteristics and outcomes of spontaneous bacterial peritonitis and culture negative neutrocytic ascites.

OBJECTIVE: Ascitic fluid infections (AFI) in cirrhotic patients can be classified into two groups: spontaneous bacterial peritonitis (SBP) and culture-negative neutrocytic ascites (CNNA). The aim of this study was to compare the clinical characteristics and outcomes of the two groups of patients with AFI. METHODS: We retrospectively reviewed the medical records of cirrhotic patients with AFI. We evaluated demographic data, clinical presentations of AFI, laboratory findings, liver function, and mortality rates. RESULTS: Between January 2005 and December 2014, 533 patients with AFI were evaluated; 259 (48.6%) had SBP and 274 (51.4%) CNNA. Ascites neutrophil count (4410/mm3 versus 1046/mm3, p < .001) and the blood culture positive rate (38.1% versus 20.1%, p < .001) were higher in the SBP group, which also had a higher MELD score (24.29 versus 22.05, p = .004). Seven-day mortality was higher in the SBP group (9.4% versus 4.5%, p = .027) but there was no significant difference in 30-day (22.1% versus 17.5%) or 90-day mortality rate (36.1% versus 36.4%). CONCLUSIONS: Patients in the SBP group had a higher MELD score, ascites neutrophil count, and positive blood culture rate. Although seven-day mortality rate was higher in the SBP group, the 30-day and 90-day mortality rates were similar in the two groups.

Clinical Progression and Cytokine Profiles of Middle East Respiratory Syndrome Coronavirus Infection.

Clinical progression over time and cytokine profiles have not been well defined in patients with Middle East respiratory syndrome coronavirus (MERS-CoV) infection. We included 17 patients with laboratory-confirmed MERS-CoV during the 2015 outbreak in Korea. Clinical and laboratory parameters were collected prospectively. Serum cytokine and chemokine levels in serial serum samples were measured using enzyme-linked immunosorbent assay. All patients presented with fever. The median time to defervescence was 18 days. Nine patients required oxygen supplementation and classified into severe group. In the severe group, chest infiltrates suddenly began to worsen around day 7 of illness, and dyspnea developed at the end of the first week and became apparent in the second week. Median time from symptom onset to oxygen supplementation was 8 days. The severe group had higher neutrophil counts during week 1 than the mild group (4,500 vs. 2,200/µL, P = 0.026). In the second week of illness, the severe group had higher serum levels of IL-6 (54 vs. 4 pg/mL, P = 0.006) and CXCL-10 (2,642 vs. 382 pg/mL, P < 0.001). IFN-α response was not observed in mild cases. Our data shows that clinical condition may suddenly deteriorate around 7 days of illness and the serum levels of IL-6 and CXCL-10 was significantly elevated in MERS-CoV patients who developed severe diseases.

Therapeutic efficacy of Chinese patent medicine containing pyrite for fractures: A protocol for systematic review and meta-analysis.

BACKGROUND: Fractures are a condition in which bone continuity is lost or linear deformity occurs. They are a worldwide public health problem and a significant economic burden. The purpose of this study is to analyze the efficacy of Chinese patent medicine containing pyrite (CPMP) through systematic review and meta-analysis of fracture clinical data. METHODS: A literature search will be carried out from the inception of CPMP studies to September 2022 using EMBASE, PubMed, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, Korean Studies Information Service System, National Digital Science Library, and Oriental Medicine Advanced Searching Integrated System. Randomized controlled trials which include CPMP will be considered as eligible regardless of the type of fracture. After screening the literature, extracting the data, and assessing the risk of bias from the included studies, a meta-analysis will be performed using Review Manager version 5.4. RESULTS: This study is expected to provide evidence for the efficacy and safety of CPMP for fractures. CONCLUSION: Our findings will provide evidence to determine whether CPMP can be an effective intervention for patients with fractures, which would expand the possible treatment options.

Electroacupuncture to treat with Overactive Bladder in Postmenopausal Women: study protocol for a multicenter, randomized, controlled, parallel clinical trial.

BACKGROUND: Electroacupuncture has been used for treatment in patients with overactive bladder. This study was conducted to evaluate the efficacy and safety of electroacupuncture for treating overactive bladder of postmenopausal women. METHODS/DESIGN: This is a multicenter, randomized controlled, parallel clinical trial. Two hundred ninety participants with overactive bladder syndrome will be recruited from Dongguk University Bundang Oriental Hospital and Cheonan Korean Medicine Hospital of Daejeon University and randomly allocated into one of two groups in a 1:1 ratio. One group will receive electroacupuncture (EA) and the other acupuncture (AC). The allocation will be concealed from both participants and assessors. The study period will be about 10 weeks, including 6 weeks of electroacupuncture or acupuncture treatment and a four week follow-up period. Both EA group and AT group will undergo acupuncture at 7 fixed points, and the EA group will undergo electronic stimulation at 6 points. The primary outcome will be the average number of micturitions per 24 h based on a 3-day bladder diary. The secondary outcome will comprise the 3-day bladder diary, the overactive bladder symptom score and the results of the King's health questionnaire. DISCUSSION: The results of this trial will provide information regarding the efficacy and safety of electroacupuncture for treating overactive bladder in postmenopausal women. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03260907 . Registered on 24 August 2017.

Emergence of Daptomycin-Nonsusceptible Methicillin-Resistant Staphylococcus aureus Clinical Isolates Among Daptomycin-Naive Patients in Korea.

This study was conducted to assess emergence of daptomycin-nonsusceptible (DAP-NS) phenotype in DAP-naive patients with invasive Staphylococcus aureus (ISA) infections in Korea. A total of 208 S. aureus clinical isolates were selected from a previous prospective study on ISA infections and evaluated for DAP-NS. Although DAP has never been introduced in Korea, five DAP-NS S. aureus strains (2.4%) were identified among 208 S. aureus strains collected from ISA infections. The DAP-NS phenotype was observed only in methicillin-resistant S. aureus (MRSA) strains, but not in methicillin-susceptible S. aureus strains. One DAP-NS MRSA strain belonged to sequence type 72 (ST72) and four were ST5 MRSA strains, three of which were heteroresistant vancomycin (VAN)-intermediate S. aureus. All these five DAP-NS MRSA strains were from healthcare-associated infections without prior exposure to VAN within 30 days. While the ST72 MRSA strain exhibited DAP-NS phenotype via charge repulsion mechanism, four ST5 DAP-NS S. aureus strains had charge-independent DAP-NS mechanism. None of the five DAP-NS strains displayed significant increase in cell wall thickness, indicating that altered cell wall thickness was not associated with the observed DAP-NS phenotype.

Akt activation by Evodiae Fructus extract protects ovary against 4-vinylcyclohexene diepoxide-induced ovotoxicity.

ETHNOPHARMACOLOGICAL RELEVANCE: Evodiae Fructus (EF) is the dried, unripe fruit of Evodia rutaecarpa Benth., and one of the main components of traditional herbal prescriptions issued for the treatment of sterility caused by irregular menstruation in Korea. However, scientific evidence regarding the efficacy and action mechanism of EF is lacking. AIM OF THE STUDY: In this study, the authors established an in vitro screening tool to identify promising new drug candidates in herbal medicines for the prevention and treatment of premature ovarian failure. The protective effects of EF extracts against 4-vinylcyclohexene diepoxide (VCD)-induced ovotoxicity were investigated and the molecular mechanism responsible was sought. MATERIAL AND METHODS: EF extract was prepared by boiling EF in water and its quality was confirmed by high performance liquid chromatography. CHO-K1 (Chinese hamster ovary cells) and COV434 (human ovarian granulosa cells) cells were plated, pretreated with EF extract for 2h and then treated with 1.5mM or 0.5mM VCD for 24h, respectively. Cell viabilities were measured using an MTT assay, and protein levels were determined by western blotting. RESULTS: VCD significantly suppressed the viability of both CHO-K1 and COV434 cells in a dose-dependent manner and induced the apoptosis of CHO-K1 cells at 1.5mM. EF extract dose-dependently blocked the ovotoxicity induced by treatment with VCD. Furthermore, EF extract significantly activated Akt and downstream effectors such as mTOR and GSK-3ß in CHO-K1 cells. The ability of EF extract to prevent cytotoxicity by VCD was antagonized by pretreatment of LY294002, a PI3K/Akt inhibitor. CONCLUSION: EF has the ability to protect ovary cells against VCD-induced ovotoxicity, probably via Akt activation. These results suggest that the beneficial effects of EF might be useful for preventing premature ovarian failure or unexplained infertility caused by environmental factors.

Differences in characteristics between first and breakthrough neutropenic fever after chemotherapy in patients with hematologic disease.

OBJECTIVE: This study was conducted to compare the clinical and microbiological characteristics of first and breakthrough neutropenic fever in hematologic malignancy patients after chemotherapy. METHODS: Breakthrough neutropenic fever was any episode of fever, not present initially, that developed either during antibiotic therapy or within 1 week of discontinuation of therapy. A total of 687 neutropenic fever episodes in 241 patients were observed from April 2003 to March 2014. RESULTS: Blood cultures revealed 210 causative microorganisms: 199 (94.8%) were bacteria and 11 (5.2%) were fungi. Gram-negative bacteria predominated in both types of neutropenic episode (first 75% (120/160) vs. breakthrough 56% (18/32)) and the most common pathogen was Escherichia coli. Antibiotic resistance rates were higher in breakthrough episodes than first episodes (piperacillin/tazobactam 6% vs. 31%, p=0.006; ceftazidime 9% vs. 31%, p=0.025). Inappropriate empirical antibiotic treatment was also more frequent (0% vs. 19%, p=0.001), as was the 30-day mortality rate (4.3% (19/442) vs. 7.9% (19/245), p=0.058), although the latter effect was not statistically significant. CONCLUSION: It is concluded that the epidemiological profile of breakthrough neutropenic fever is different from that of first episode fever. These data reinforce the view that pooled reporting of neutropenic fever may be misleading, and that clinicians should approach breakthrough fever as a distinct entity.

Infected Aortic Aneurysm caused by Mycobacterium bovis after Intravesical Bacillus Calmette-Guérin Treatment for Bladder Cancer.

A 70-year-old man presented with lower back pain and cyanotic changes in his left lower extremity. He was diagnosed with infected aortic aneurysm and infectious spondylitis. He had received intravesical Bacillus Calmette-Guérin (BCG) therapy up to 1 month before the onset of symptoms. The aneurysm was excised and an aorto-biiliac interposition graft was performed. Mycobacterium tuberculosis complex was cultured in the surgical specimens. Real-time polymerase chain reaction (PCR) targeting the senX3-regX3 region, and multiplex PCR using dual-priming oligonucleotide primers targeting the RD1 gene, revealed that the organism isolated was Mycobacterium bovis BCG. The patient took anti-tuberculosis medication for 1 year, and there was no evidence of recurrence at 18 months follow-up.

Discrepancy in perceptions regarding patient participation in hand hygiene between patients and health care workers.

BACKGROUND: Patient participation in hand hygiene programs is regarded as an important component of hand hygiene improvement, but the feasibility of the program is still largely unknown. We examined the perceptions of patients/families and health care workers (HCWs) with regard to patient participation in hand hygiene. METHODS: A cross-sectional survey of patients/families as well as physicians and nurses was performed using an anonymous, self-administered questionnaire in a 1,000-bed teaching hospital in South Korea. RESULTS: A total of 152 physicians, 387 nurses, and 334 patients/families completed the survey. The overall response rate was 84%, 85%, and more than 60% among physicians, nurses, and patients/families, respectively. Whereas 75% of patients/families wished to ask HCWs to clean their hands if they did not do so themselves, only 26% of physicians and 31% of nurses supported the participation of patients (P < .001). The most common reason why HCWs disagreed with patient participation was concern about negative effects on their relationship with patients (54%). Regarding the method of patient involvement, patients preferred to assess hand hygiene performance, whereas physicians preferred patients to ask directly. CONCLUSIONS: There was a significant discrepancy in perceptions regarding patient participation between patients/families and HCWs. Enhanced understanding and acceptance of any new program by both patients and HCWs before its introduction are needed for successful implementation.