OBJECTIVES: To develop a new Chinese medicine (CM)-based drug and to evaluate its safety and effect for suppressing acute respiratory distress syndrome (ARDS) in COVID-19 patients. METHODS: A putative ARDS-suppressing drug Keguan-1 was first developed and then evaluated by a randomized, controlled two-arm trial. The two arms of the trial consist of a control therapy (alpha interferon inhalation, 50 µg twice daily; and lopinavir/ritonavir, 400 and 100 mg twice daily, respectively) and a testing therapy (control therapy plus Keguan-1 19.4 g twice daily) by random number table at 1:1 ratio with 24 cases each group. After 2-week treatment, adverse events, time to fever resolution, ARDS development, and lung injury on newly diagnosed COVID-19 patients were assessed. RESULTS: An analysis of the data from the first 30 participants showed that the control arm and the testing arm did not exhibit any significant differences in terms of adverse events. Based on this result, the study was expanded to include a total of 48 participants (24 cases each arm). The results show that compared with the control arm, the testing arm exhibited a significant improvement in time to fever resolution (P=0.035), and a significant reduction in the development of ARDS (P=0.048). CONCLUSIONS Keguan-1-based integrative therapy was safe and superior to the standard therapy in suppressing the development of ARDS in COVID-19 patients. (Trial registration No. NCT04251871 at www.clinicaltrials.gov ).
Administration, Inhalation ; Adult ; China ; Coronavirus Infections ; diagnosis ; drug therapy ; mortality ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Follow-Up Studies ; Humans ; Integrative Medicine ; Interferon-alpha ; administration & dosage ; Lopinavir ; administration & dosage ; Male ; Middle Aged ; Pandemics ; Pneumonia, Viral ; diagnosis ; drug therapy ; mortality ; Risk Assessment ; Severe Acute Respiratory Syndrome ; diagnosis ; drug therapy ; mortality ; Severity of Illness Index ; Survival Rate

BACKGROUND/AIMS: Hepatic arterial infusion chemotherapy (HAIC) has been reported as an effective treatment for advanced hepatocellular carcinoma. The aim of this study is to compare the effect and safety between a high-dose regimen (750 mg/m2 5-fluorouracil [FU] and 25 mg/m2 cisplatin on day 1–4) and a low-dose regimen (500 mg/m2 5-FU on day 1–3 with 60 mg/m2 cisplatin on day 2). METHODS: A total of 48 patients undergoing HAIC were retrospectively analyzed. Thirty-two patients were treated with the high-dose and 16 patients with the low-dose regimen. RESULTS: Complete response (CR), partial response (PR), stable disease (SD), and progressive disease were noted in one (3.1%), 15 (46.9%), three (9.4%), and 13 patients (40.6%) in the highdose group, and 0 (0%), one (6.3%), eight (50%), and seven patients (43.8%) in the low-dose group (P=0.002). The disease control rate (CR, PR, and SD) did not differ between groups (59.4% vs. 56.3%, P=1.000), but the objective response rate (CR and PR) was significantly higher in the high-dose group (50.0% vs. 6.3%, P=0.003). The median progression free survival did not differ between groups (4.0 vs. 6.0, P=0.734), but overall survival was significantly longer in the high-dose group (not reached vs. 16.0, P=0.028). Fourteen (43.8%) patients in the high-dose group and two patients (12.5%) in the low-dose group experienced grade 3–4 toxicities (P=0.050). CONCLUSIONS: High dose HAIC may achieve better tumor response and may improve overall survival compared to a low-dose regimen. However, the high-dose regimen should be administered cautiously because of the higher incidence of adverse events.
Administration, Metronomic ; Carcinoma, Hepatocellular ; Chemotherapy, Cancer, Regional Perfusion ; Cisplatin ; Disease-Free Survival ; Drug Therapy ; Fluorouracil ; Humans ; Incidence ; Retrospective Studies

OBJECTIVE: To investigate the complications and clinical outcome of children with acute myeloid leukemia (AML) undergoing mitoxantrone-cytarabine-etoposide (MAE) induction therapy. METHODS: A total of 170 children with AML were given MAE induction therapy, and the complications and remission rate were analyzed after treatment. RESULTS: The male/female ratio was 1.33:1 and the mean age was 7.4 years (range 1-15 years). Leukocyte count at diagnosis was 29.52×10/L [range (0.77-351)×10/L]. Of all children, 2 had M0-AML, 24 had M2-AML, 2 had M4-AML, 48 had M5-AML, 3 had M6-AML, 7 had M7-AML, 69 had AML with t(8;21)(q22;q22), and 15 had AML with inv(16)(p13.1q22) or t(16;16)(p13.1;q22). The most common complication was infection (158/170, 92.9%). Among these 158 patients, 22 (13.9%) had agranulocytosis with pyrexia (with no definite focus of infection), and 136 (86.1%) had definite focus of infection (including bloodstream infection). Other complications included non-infectious diarrhea, bleeding, and drug-induced hepatitis. Treatment-related mortality was observed in 10 children, among whom 8 had severe infection, 1 had multiple organ failure, and 1 had respiratory failure. Remission rate was evaluated for 156 children and the results showed a complete remission rate of 85.3%, a partial remission rate of 4.5%, and a non-remission rate of 10.3%. CONCLUSIONS Induction therapy with the MAE regimen helps to achieve a good remission rate in children with AML after one course of treatment. Infection is the main complication and a major cause of treatment-related mortality.
Adolescent ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Child ; Child, Preschool ; Cytarabine ; Drug Administration Schedule ; Etoposide ; Female ; Humans ; Infant ; Leukemia, Myeloid, Acute ; drug therapy ; Male ; Mitoxantrone ; Remission Induction

INTRODUCTION: Timely administration of prophylactic antibiotics within 60 minutes before surgical incision is important for reducing surgical site infections. This quality improvement initiative aimed to work towards achieving 100% compliance with perioperative antibiotic administration. METHODS: We examined the workflow in our Anaesthesia Information Management System (AIMS) and proposed interventions using cause-and-effect analysis of anonymised anaesthetic records from eligible surgical cases extracted from AIMS. This ultimately led to the implementation of an antibiotic pop-up reminder. The overall process was done in a few small plan-do-study-act cycles involving raising awareness, education and reorganisation of AIMS before implementation of the antibiotic pop-up reminder. Data analysis took place from August 2014 to September 2016. Compliance was defined as documented antibiotic administration within 60 minutes before surgical incision, or as documented reason for omission. RESULTS: The median monthly compliance rate, for 33,038 cases before and 28,315 cases after the reminder was implemented, increased from 67.0% at baseline to 94.5%. This increase was consistent and sustained for a year despite frequent personnel turnover. Documentation of antibiotic administration also improved from 81.7% to 99.3%, allowing us to identify and address novel problems that were initially not apparent, and resulting in several department recommendations. These included administering antibiotics later for cases with predicted longer-than-expected preparation times and bringing forward antibiotic administration in lower-segment Caesarean sections. CONCLUSION The use of information technology and implementation of an antibiotic pop-up reminder on AIMS streamlined our work processes and brought us closer to achieving 100% on-time compliance with perioperative antibiotic administration.
Anti-Bacterial Agents ; administration & dosage ; Antibiotic Prophylaxis ; methods ; Documentation ; Drug Administration Schedule ; Electronic Health Records ; Guideline Adherence ; Humans ; Perioperative Period ; Quality Improvement ; Reminder Systems ; Software ; Surgical Procedures, Operative ; standards ; Surgical Wound Infection ; prevention & control

OBJECTIVEThe present study was undertaken to evaluate the subchronic toxicity of lanthanum and to determine the no observed adverse effect level (NOAEL), which is a critical factor in the establishment of an acceptable dietary intake (ADI).

METHODSIn accordance with the Organization for Economic Co-operation and Development (OECD) testing guidelines, lanthanum nitrate was administered once daily by gavage to Sprague-Dawley (SD) rats at dose levels of 0, 1.5, 6.0, 24.0, and 144.0 mg/kg body weight (BW) per day for 90 days, followed by a recovery period of 4 weeks in the 144.0 mg/kg BW per day and normal control groups. Outcome parameters were mortality, clinical symptoms, body and organ weights, serum chemistry, and food consumption, as well as ophthalmic, urinary, hematologic, and histopathologic indicators. The benchmark dose (BMD) approach was applied to estimate a point of departure for the hazard risk assessment of lanthanum.

RESULTSSignificant decreases were found in the 144.0 mg/kg BW group in the growth index, including body weight, organ weights, and food consumption. This study suggests that the NOAEL of lanthanum nitrate is 24.0 mg/kg BW per day. Importantly, the 95% lower confidence value of the benchmark dose (BMDL) was estimated as 9.4 mg/kg BW per day in females and 19.3 mg/kg BW per day in males.

CONCLUSIONThe present subchronic oral exposure toxicity study may provide scientific data for the risk assessment of lanthanum and other rare earth elements (REEs).

Animals ; Blood Chemical Analysis ; Body Weight ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Female ; Lanthanum ; administration & dosage ; toxicity ; Male ; No-Observed-Adverse-Effect Level ; Rats ; Rats, Sprague-Dawley ; Specific Pathogen-Free Organisms ; Toxicity Tests, Subchronic ; Urinalysis

BACKGROUND: The continuous use of biologic agents in the treatment of psoriasis has been reported to result in successful and sustained therapeutic effects and safety. However, some patients choose intermittent and repetitive treatment. OBJECTIVE: To determine the factors for selecting intermittent and repetitive ustekinumab treatment for the management of psoriasis. METHODS: From January 2011 to October 2016, we enrolled 30 psoriasis patients who discontinued ustekinumab treatment and were followed up for psoriasis treatment. We reviewed data regarding patients' clinical characteristics and the treatment they received, and investigated the factors for selecting intermittent treatment. RESULTS: A total of 52 ustekinumab treatment periods were administered to the 30 patients. Of the 52 treatment periods, 34.6% were covered by insurance and 82.4% were discontinued after sufficient improvement had been made or at the patient's request. Further analysis comparing the first and second ustekinumab treatments revealed that the patients who used ustekinumab in second treatment were more likely to be insured. In addition, the rate of patients reaching psoriasis area and severity index (PASI)75 and PASI90 was similar between the first and subsequent ustekinumab treatments. CONCLUSION: We found that the patients who used ustekinumab intermittently were those who were satisfied with the outcome of ustekinumab treatment but could not afford the treatment. These results suggested that economic burden can be a factor for the patients' choice of short-term intermittent treatment. The expansion of insurance coverage can increase the effectiveness of, and patients' satisfaction with, the management of psoriasis.
Biological Factors ; Cost of Illness ; Drug Administration Schedule ; Humans ; Insurance ; Insurance Coverage ; Psoriasis* ; Therapeutic Uses ; Ustekinumab*

Background: Disease-modifying therapy is the standard treatment for patients with multiple sclerosis (MS) in remission. The primary objective of the current analysis was to assess the efficacy and safety of two teriflunomide doses (7 mg and 14 mg) in the subgroup of Chinese patients with relapsing MS included in the TOWER study. Methods: TOWER was a multicenter, multinational, randomized, double-blind, parallel-group (three groups), placebo-controlled study. This subgroup analysis includes 148 Chinese patients randomized to receive either teriflunomide 7 mg (n = 51), teriflunomide 14 mg (n = 43), or placebo (n = 54). Results: Of the 148 patients in the intent-to-treat population, adjusted annualized relapse rates were 0.63 (95% confidence interval [CI]: 0.44, 0.92) in the placebo group, 0.48 (95% CI: 0.33, 0.70) in the teriflunomide 7 mg group, and 0.18 (95% CI: 0.09, 0.36) in the teriflunomide 14 mg group; this corresponded to a significant relative risk reduction in the teriflunomide 14 mg group versus placebo (-71.2%, P = 0.0012). Teriflunomide 14 mg also tended to reduce 12-week confirmed disability worsening by 68.1% compared with placebo (hazard ratio: 0.319, P = 0.1194). There were no differences across all treatment groups in the proportion of patients with treatment-emergent adverse events (TEAEs; 72.2% in the placebo group, 74.5% in the teriflunomide 7 mg group, and 69.8% in the teriflunomide 14 mg group); corresponding proportions for serious adverse events were 11.1%, 3.9%, and 11.6%, respectively. The most frequently reported TEAEs with teriflunomide versus placebo were neutropenia, increased alanine aminotransferase, and hair thinning. Conclusions: Teriflunomide was as effective and safe in the Chinese subpopulation as it was in the overall population of patients in the TOWER trial. Teriflunomide has the potential to meet unmet medical needs for MS patients in China. Trial Registration ClinicalTrials.gov, NCT00751881; https://clinicaltrials.gov/ct2/show/NCT00751881?term=NCT00751881&rank=1.
China ; Crotonates ; administration & dosage ; adverse effects ; therapeutic use ; Double-Blind Method ; Drug Administration Schedule ; Humans ; Immunosuppressive Agents ; administration & dosage ; adverse effects ; therapeutic use ; Multicenter Studies as Topic ; Multiple Sclerosis ; drug therapy ; metabolism ; Proportional Hazards Models ; Toluidines ; administration & dosage ; adverse effects ; therapeutic use

No abstract available.
Administration, Metronomic ; Aged* ; Capecitabine* ; Colorectal Neoplasms* ; Drug Therapy* ; Humans

BACKGROUND/AIMS: Metronomic chemotherapy (MET) is frequently administered in comparatively low doses as a continuous chemotherapeutic agent. The aim of this study was to evaluate the feasibility and overall survival (OS) of MET compared to sorafenib for advanced hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT). METHODS: A total of 54 patients with advanced HCC and PVTT who had undergone MET were analyzed between 2005 and 2013. A total of 53 patients who had undergone sorafenib therapy were analyzed as the control group. The primary endpoint of this study was OS. RESULTS: The median number of MET cycles was two (1-15). The OS values for the MET group and sorafenib group were 158 days (132-184) and 117 days (92-142), respectively (P=0.029). The Cox proportional-hazard model showed that a higher risk of death was correlated with higher serum alpha fetoprotein level (≥400 mg/dL, hazard ratio [HR]=1.680, P=0.014) and Child-Pugh class B (HR=1.856, P=0.008). CONCLUSIONS: MET was associated with more favorable outcomes in terms of overall survival than was sorafenib in patients with advanced HCC with PVTT, especially in patients with poor liver function. Therefore, MET can be considered as a treatment option in patients with advanced HCC with PVTT and poor liver function.
Administration, Metronomic ; alpha-Fetoproteins ; Carcinoma, Hepatocellular* ; Drug Therapy* ; Humans ; Liver* ; Portal Vein ; Thrombosis

OBJECTIVETo investigate acrylamide (ACR)-induced subacute neurotoxic effects on the central nervous system (CNS) at the synapse level in rats.

METHODSThirty-six Sprague Dawley (SD) rats were randomized into three groups, (1) a 30 mg/kg ACR-treated group, (2) a 50 mg/kg ACR-treated group, and (3) a normal saline (NS)-treated control group. Body weight and neurological changes were recorded each day. At the end of the test, cerebral cortex and cerebellum tissues were harvested and viewed using light and electron microscopy. Additionally, the expression of Synapsin I and P-Synapsin I in the cerebral cortex and cerebellum were investigated.

RESULTSThe 50 mg/kg ACR-treated rats showed a significant reduction in body weight compared with untreated individuals (P < 0.05). Rats exposed to ACR showed a significant increase in gait scores compared with the NS control group (P < 0.05). Histological examination indicated neuronal structural damage in the 50 mg/kg ACR treatment group. The active zone distance (AZD) and the nearest neighbor distance (NND) of synaptic vesicles in the cerebral cortex and cerebellum were increased in both the 30 mg/kg and 50 mg/kg ACR treatment groups. The ratio of the distribution of synaptic vesicles in the readily releasable pool (RRP) was decreased. Furthermore, the expression levels of Synapsin I and P-Synapsin I in the cerebral cortex and cerebellum were decreased in both the 30 mg/kg and 50 mg/kg ACR treatment groups.

CONCLUSIONSubacute ACR exposure contributes to neuropathy in the rat CNS. Functional damage of synaptic proteins and vesicles may be a mechanism of ACR neurotoxicity.

Acrylamide ; toxicity ; Animals ; Cerebellum ; cytology ; drug effects ; Cerebral Cortex ; cytology ; drug effects ; Drug Administration Schedule ; Gait ; Gene Expression Regulation ; drug effects ; Male ; Neurons ; drug effects ; Neurotoxicity Syndromes ; pathology ; Rats ; Rats, Sprague-Dawley ; Synapses ; drug effects ; Synapsins ; genetics ; metabolism ; Synaptic Vesicles ; drug effects ; physiology ; Weight Loss ; drug effects