Evaluation of the clinical practice guidelines and consensuses on calcium and vitamin D supplementation in healthy children using the Appraisal of Guidelines for Research and Evaluation II instrument and Reporting Items for Practice Guidelines in Healthcare statement.

Background: This study aimed to assess the methodological and reporting quality of the guidelines and consensus on calcium and vitamin D supplementation in healthy children, and the consistency of these recommendations. Methods: A systematic search of relevant guideline websites and databases, including PubMed, Embase, CNKI, WangFang, and SinoMed, was undertaken from inception to April 7, 2021, by two independent reviewers who assessed the eligible guidelines using the validated Appraisal of Guidelines for Research and Evaluation Instrument II (AGREE II) and the Reporting Items for Practice Guidelines in Healthcare (RIGHT) tools. Overall, the between-reviewer agreement was evaluated using an intra-class correlation coefficient. Results: A total of 24 guidelines and consensuses from 2002 to 2022 were identified from China, the United States, Canada, France, Australia, New Zealand, Europe, and other countries and regions. These were of mixed quality, and scored poorly in the rigor of development, editorial independence, and applicability of the domains of AGREE II. Among the seven domains of the RIGHT checklist, domain one (basic information) had the highest reporting rate (69.3%), whereas domain five (review and quality assurance) had the lowest reporting rate (11.5%). The overall quality of the included guidelines and consensuses was low. Only 12 guidelines were recommended, with modifications. The recommended calcium intake for children of different ages varies greatly (400-1,150 mg/day). Among the included guidelines and consensuses, a vitamin D (VD) prevention dose of 400 IU/day in infants was generally considered safe, and 25-hydroxyvitamin-D [25(OH)D] levels of <20 ng/mL (50 nmol/L) or 20-30 ng/mL (50-75 nmol/L) indicated VD deficiency or insufficiency. However, the recommended amount of VD for children of different age groups and risk strata differed considerably (400-4,000 IU/day or 10-100 µg/day). The choice of VD2 or VD3 supplements and sunlight exposure also differed across the guidelines and consensuses. Conclusion: There is considerable variability in calcium and VD guidelines and consensus development methods in calcium and VD supplementation for healthy children. Therefore, efforts are necessary to strengthen the methodological rigor of guideline development and utilize the best available evidence to underpin recommendations.

The Potential of Glycyrrhizinate in the Management of COVID-19: A Systematic Review of the Efficacy and Safety of Glycyrrhizin Preparations in the Treatment of SARS and MERS.

The SARS-CoV-2 outbreak in 2019 highlighted the fact that no specific medications providing effective treatment have been identified and approved. We explored the possibilities for COVID-19 by systematically reviewing evidence on the efficacy and safety of glycyrrhizin preparations for SARS and MERS. Electronic databases were systematically searched from inception to February 2020 for eligible studies that evaluated the efficacy and safety of glycyrrhizin preparations for SARS and MERS. A quantitative analysis or descriptive analysis was applied. Five retrospective cohort studies were included, and NOS scores ranged from 5-7 points. The clinical symptoms of dry cough, chest distress and dyspnoea improved quickly, and elevated serum levels of aminotransferase decreased after compound glycyrrhizin treatment. The SARS-CoV antibody appeared earlier in the treated group than in the control group ([Formula: see text][Formula: see text]d). Compared to that with conventional medications, the average period from peak to 50% improvement of lesions, in terms of X-ray manifestations, was shorter with compound glycyrrhizin treatment ([Formula: see text]2.1[Formula: see text]d), and treatment reduced the dosage ([Formula: see text][Formula: see text]mg/d) and duration of the corticosteroids used, without other serious adverse reactions. Based on the available evidence regarding glycyrrhizin preparations for treating SARS and MERS, we infer that compound glycyrrhizin could be an optional therapeutic strategy for SARS-CoV-2 infections, especially those complicated with liver damage. Further research using well-designed randomized clinical trials (RCTs) is warranted to determine the dosage and duration of use of compound glycyrrhizin and to monitor its specific adverse effects.

Cost-effectiveness of Dabigatran Compared With Rivaroxaban for Prevention of Stroke and Systemic Embolism in Patients With Atrial Fibrillation in China.

PURPOSE: In China, dabigatran and rivaroxaban are the only approved non-vitamin K antagonist oral anticoagulants for the treatment of atrial fibrillation (AF). The goal of this article was to assess the cost-effectiveness of dabigatran versus rivaroxaban for the prevention of stroke and systemic embolism in Chinese patients with AF from the perspective of the Chinese health care system. METHODS: A Markov model was constructed to estimate the cost-effectiveness of dabigatran versus rivaroxaban. Clinical events were modeled for a lifetime horizon, based on clinical efficacy data from indirect treatment comparisons. The weighted average of the most recent prices of these 2 drugs was used as the drug acquisition cost. Other costs, including follow-up costs and event costs, were collected by using a survey from a panel of local experts. Utility inputs (health state utilities, clinical event disutilities, and event history utility) were obtained from published literature. Sensitivity analyses that included scenario analyses and a probabilistic sensitivity analysis were conducted to examine the robustness of the economic model. FINDINGS: Over a lifetime, patients treated with dabigatran experienced fewer ischemic strokes (2.14 dabigatran vs 2.61 rivaroxaban) and fewer intracranial hemorrhage (0.48 vs 0.94) per 100 patient-years. In the base case analysis, dabigatran had an incremental cost of ¥28,128 but with higher life years (10.38 vs 10.14) and quality-adjusted life years (QALYs) (7.95 vs 7.70). The resulting incremental cost-effectiveness ratio of ¥112,910 per QALY gained and net monetary benefit of ¥12,214 versus rivaroxaban showed that dabigatran was a cost-effective alternative to rivaroxaban. Extensive sensitivity analyses indicated that the results were robust over a wide range of inputs. The probabilistic sensitivity analysis indicated that dabigatran was cost-effective in 84.2% of the 10,000 Monte Carlo simulations compared with rivaroxaban. IMPLICATIONS: Dabigatran reduced the occurrence of clinical events and increased QALYs compared with rivaroxaban. The use of dabigatran for the prevention of stroke and systemic embolism is a cost-effective option compared with rivaroxaban among patients with AF in China.

The Incidence and Risk Factors for Adverse Drug Reactions Related to Tanreqing Injection: A Large Population-Based Study in China.

Background: Tanreqing injection (TRQ) is a traditional Chinese medicine commonly used in China to treat pulmonary diseases presenting as phlegm-heat syndrome. Robust data on the safety of TRQ from real-world observational cohorts are currently lacking. Objective: To evaluate as the incidence, type, and predictors of adverse events (AEs) and adverse drug reactions (ADRs) of TRQ in clinical practice in China. Methods: We conducted a population-based cohort, multicenter study to evaluate the incidence, manifestation, outcomes, and risk factors of AEs and ADRs following TRQ use in China. Between April 2014 and May 2015 a total of 30,322 consecutive inpatients/emergency attendance patients from 90 hospitals across China administrated TRQ were followed-up for 7 days. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using logistic regression to identify predictors of ADRs. Results: The incidence of AEs and ADRs was 1.4 and 0.3%, respectively. Skin and subcutaneous tissue disorders were the most common ADRs. All ADRs were mild or moderate in severity, except for one serious case of anaphylactic reaction. The majority of ADRs (72.8%) occurred in the first 2 h after TRQ administration. Two-thirds of patients (66.1%) in the study were prescribed TRQ off-label, including infants aged ≤24 months. A history of food allergy (OR 4.50, 95% CI: 1.35-15.00), drug allergy (OR 2.77, 95% CI: 1.56-4.94), and fast infusion speed (off-label use) (OR 2.10, 95% CI: 1.27-3.50) were associated with an increased risk of ADRs. Conclusion: TRQ is well tolerated in the general population, yet off-label use is prevalent. Efforts are required to educate prescribers to adhere to the drug label in order to minimize potential patient harm.

Traditional Chinese medicine and drug-induced anaphylaxis: data from the Beijing pharmacovigilance database.

Background Traditional Chinese medicine (TCM) is one of the major triggers for drug-induced anaphylaxis (DIA). Objective We aimed to use the Beijing pharmacovigilance database (BPD) to analyze TCM-induced DIAs in Beijing, China. Setting Drug allergy case reports from the BPD provided by the Beijing Center for Adverse Drug Reaction Monitoring. Method Drug allergy cases from January 2004 to December 2014 were adjudicated. DIA triggered by TCMs were analyzed and compared with those triggered by non-TCM drugs by calculating the reported risk ratio (RRR). We also calculated the RRRs based on severe DIA and death outcomes. Main outcome measure TCMs implicated in DIAs were identified and compared with non-TCM drugs. Results TCMs accounted for 1651 (18.2%) of the total 9074 allergic cases, in which 84.4% (1393/1651) were triggered by injections. Of the TCM allergic cases, 8.5% (141) were DIAs and 7.3% (120) were severe DIAs, and three patients died from injections. The RRR between TCMs and non-TCM-induced DIAs was 0.63. When anaphylactic cases were compared between TCMs to the top four non-TCM drug triggers, RRRs were 0.73 (95% CI 0.61-0.87) for antibiotics, 0.36 (95% CI 0.29-0.44) for radiocontrast agents, 0.55 (95% CI 0.43-0.68) for chemotherapeutics, and 0.29 (95% CI 0.23-0.37) for biologics. Compared to TCM oral or topic formulations, TCM injections had higher RRRs in each of the above comparisons. Conclusion TCM was associated with a decreased risk of DIA compared to non-TCM drugs in drug allergy cases, and the risk was higher for TCM injections.

[Patent Traditional Chinese Medicine for idiopathic male infertility: A bibliometrical study].

OBJECTIVE: To survey the current status of clinical studies on patent Traditional Chinese Medicine (TCM) for idiopathic male infertility in China. METHODS: Using the keywords "oligospermia", "azoospermia", "asthenozoospermia", "infertility" and "sperm", we searched China National Knowledge Internet (CNKI), Wanfang Database and SinoMed for randomized clinical trials (RCT), cohort studies, case-control studies and case series studies focusing on the treatment of male idiopathic infertility using TCM from January 2001 to May 2017. Two individual reviewers screened the literature, extracted the information separately, recorded the titles, authors, related institutions and regions, journals and years of publication, medication studied, and outcomes. The collected data was analyzed using Microsoft Excel and SPSS. RESULTS: Totally, 307 publications were included in this study, including 243 RCTs (79%), 57 case series studies (19%) and 7 retrospective cohort studies (2%). Fifty one patent TCM and in 146 journals were involved. The number of publications gradully increased from 2001 to 2017. The authors were from 243 institutions in 29 provinces, independent municipalities or autonomous regions, mostly in Guangdong, Guangxi, Henan, Beijing and Jiangsu. Majority of the studies focused on the evaluation of the efficacy and safety of the drugs, among which the most studied medication Wuziyanzong Pills (114/307, 37.13%), Fufangxuanju Capsules, Shengjing Capsules, Huangjingzanyu Capsules, and Liuweidihuang Pills. Chinese Journal of Andrology had the highest number of publications. CONCLUSIONS: A rapid progress has been achieved in China in the studies of patent TCM for the treatment of male infertility. However, limitatiors stiu exist, ragarding inbalance among regions, low sample sizes, low quality of studies, poor involvement of phamacisis.

Use of Epinephrine in Patients with Drug-Induced Anaphylaxis: An Analysis of the Beijing Pharmacovigilance Database.

BACKGROUND: Few studies assessing the use of epinephrine in drug-induced anaphylaxis (DIA) in the hospital setting are available. We utilized the Beijing Pharmacovigilance Database (BPD) to evaluate the appropriateness of epinephrine for DIA management. METHODS: DIA cases collected in the BPD from January 2004 to December 2014 were adjudicated and analyzed for demographics, causative drugs, clinical signs, outcomes, initial treatment, route, dosing, and cardiovascular adverse events (CAE) of epinephrine. RESULTS: DIA was primarily caused by antibiotics (38.4%), radiocontrast agents (11.9%), traditional Chinese medicine injections (10.9%), and chemotherapeutic drugs (10.3%). Only 708 (59.5%) patients received epinephrine treatment. Patients who received epinephrine were more likely to experience wheezing (p < 0.001) and respiratory arrest (p < 0.001). Among 518 patients with a complete record of the epinephrine administration route, the percentage of patients receiving it by intramuscular (IM) injection, subcutaneous (SC) injection, intravenous (IV) bolus injection, or IV continuous infusion was 16.9, 31.5, 43.5, and 8.1%, respectively. Among the 427 patients with a record of both the administration route and the dosing, an overdose was more likely with IV bolus (94.1%) in contrast to IM injection (56.6%; p < 0.001) or SC injection (43.7%; p < 0.001). Among the patients analyzed for CAE (n = 349), 17 patients accounted for 19 CAE, and 13 (76.5%) of these patients were overdosed with epinephrine. CONCLUSION: Underuse, inappropriate IV bolus use, and overdosing were the 3 major problems with epinephrine use in DIA in China. Educational training for health care professionals on the appropriate use of epinephrine in managing anaphylactic reactions is suggested.

Post-Marketing Safety Surveillance of the Salvia Miltiorrhiza Depside Salt for Infusion: A Real World Study.

BACKGROUND: Salvia Miltiorrhiza Depside Salt for Infusion (SMDS) is made of a group of highly purified listed drugs. However, its safety data is still reported limitedly. Compared with the clinical trials, its safety in the real world setting is barely assessed. OBJECTIVE: To investigate the safety issues, including adverse events (AEs), adverse events related to SMDS (ADEs), and adverse drug reactions (ADRs) of the SMDS in the real world clinical practice. METHODS: This is a prospective, multicenter, pharmacist-led, cohort study in the real world setting. Consecutive patients prescribed with SMDS were all included in 36 sites. Pharmacists were well trained to standardized collect the patients information, including demographics, medical history, prescribing patterns of SMDS, combined medications, adverse events, laboratory investigations, outcomes of the treatment when discharge, and interventions by pharmacists. Adverse events and adverse drug reactions were collected in details. Multivariate possion regression analysis was applied to identify risk factors associated with ADEs using the significance level (α) 0.05. ClinicalTrials.gov Identifier: NCT01872520. RESULTS: Thirty six hospitals were participated in the study and 30180 consecutive inpatients were included. The median age was 62 (interquartile range [IQR], 50-73) years, and male was 17384 (57.60%) among the 30180 patients. The incidences of the AEs, ADEs and ADRs were 6.40%, 1.57% and 0.79%, respectively. There were 9 kinds of new ADEs which were not on the approved label found in the present study. According to the multivariate analysis, male (RR = 1.381, P = 0.009, 95%CI [1.085~1.759]), more concomitant medications (RR = 1.049, P<0.001, 95%CI [1.041~1.057]), longer duration of SMDS therapy (RR = 1.027, P<0.001, 95%CI [1.013~1.041]), higher drug concentration (RR = 1.003, P = 0.014, 95%CI [1.001~1.006]), and resolvent unapproved (RR = 1.900, P = 0.002, 95%CI [1.260~2.866]) were the independent risk factors of the ADEs. Moreover, following the approved indication (RR = 0.655, P<0.001, 95%CI [0.532~0.807]) was associated with lower incidence of ADEs. CONCLUSIONS: SMDS was well tolerated in the general population. The incidences of the AEs, ADEs and ADRs were 6.40%, 1.57% and 0.79%, respectively. Several risk factors of its ADEs have been identified. It is recommended to follow the instructions when prescribing and administrating SMDS in the real world clinical practice.

Cost-Effectiveness of Dapagliflozin versus Acarbose as a Monotherapy in Type 2 Diabetes in China.

OBJECTIVE: To estimate the long-term cost-effectiveness of dapagliflozin versus acarbose as monotherapy in treatment-naïve patients with type 2 diabetes mellitus (T2DM) in China. METHODS: The Cardiff Diabetes Model, an economic model designed to evaluate the cost-effectiveness of comparator therapies in diabetes was used to simulate disease progression and estimate the long-term effect of treatments on patients. Systematic literature reviews, hospital surveys, meta-analysis and indirect treatment comparison were conducted to obtain model-required patient profiles, clinical data and costs. Health insurance costs (2015¥) were estimated over 40 years from a healthcare payer perspective. Univariate and probabilistic sensitivity analyses were performed. RESULTS: The model predicted that dapagliflozin had lower incidences of cardiovascular events, hypoglycemia and mortality events, was associated with a mean incremental benefit of 0.25 quality-adjusted life-years (QALYs) and with a lower cost of ¥8,439 compared with acarbose. This resulted in a cost saving of ¥33,786 per QALY gained with dapagliflozin. Sensitivity analyses determined that the results are robust. CONCLUSION: Dapagliflozin is dominant compared with acarbose as monotherapy for Chinese T2DM patients, with a little QALY gain and lower costs. Dapagliflozin offers a well-tolerated and cost-effective alternative medication for treatment-naive patients in China, and may have a direct impact in reducing the disease burden of T2DM.

Association between the AUC0-24/MIC Ratio of Vancomycin and Its Clinical Effectiveness: A Systematic Review and Meta-Analysis.

BACKGROUND: A target AUC0-24/MIC ratio of 400 has been associated with its clinical success when treating Staphylococcus aureus infections but is not currently supported by state-of-the-art evidence-based research. OBJECTIVE: This current systematic review aimed to evaluate the available evidence for the association between the AUC0-24/MIC ratio of vancomycin and its clinical effectiveness on hospitalized patients and to confirm the existing target value of 400. METHODS: PubMed, Embase, Web of Sciences, the Cochrane Library and two Chinese literature databases (CNKI, CBM) were systematically searched. Manual searching was also applied. Both RCTs and observational studies comparing the clinical outcomes of high AUC0-24/MIC groups versus low AUC0-24/MIC groups were eligible. Two reviewers independently extracted the data. The primary outcomes were mortality and infection treatment failure. Risk ratios (RRs) with 95% confidence intervals (95%CIs) were calculated. RESULTS: No RCTs were retrieved. Nine cohort studies were included in the meta-analysis. Mortality rates were significantly lower in high AUC0-24/MIC groups (RR = 0.47, 95%CI = 0.31-0.70, p<0.001). The rates of infection treatment failure were also significantly lower in high AUC/MIC groups and were consistent after correcting for heterogeneity (RR = 0.39, 95%CI = 0.28-0.55, p = 0.001). Subgroup analyses showed that results were consistent whether MIC values were determined by broth microdilution (BMD) method or Etest method. In studies using the BMD method, breakpoints of AUC0-24/MIC all fell within 85% to 115% of 400. CONCLUSIONS: This meta-analysis demonstrated that achieving a high AUC0-24/MIC of vancomycin could significantly decrease mortality rates by 53% and rates of infection treatment failure by 61%, with 400 being a reasonable target.

[Erythromycin for improving enteral nutrition tolerance in adult critical patients: a systematic review and meta-analysis].

OBJECTIVE: To systematically review the efficacy and safety of erythromycin on enteral nutrition (EN) tolerance in adult critical care patients. METHODS: Databases including PubMed, EMbase, the Cochrane Library, CNKI and Wangfang data were retrieved up to June, 2013 to collect the randomized controlled trial (RCT) concerning erythromycin in improving EN tolerance or increasing the successful rate of postpyloric EN tube as compared with other treatments. Two reviewers independently screened the literature, extracted the data, and assessed the quality of methodology. Then Meta-analysis was performed using RevMan 5.2 software. RESULTS: A total of 16 RCTs were included. Ten RCTs involving 668 patients were included for evaluating erythromycin in improving EN tolerance. Six RCTs involving 353 patients were included for evaluating erythromycin to increase the successful rate of postpyloric EN tube. The result of Meta-analysis showed that compared with placebo, erythromycin could significantly improve the successful rate of postpyloric EN tube placement [relative risk (RR)=1.82, 95% confidence interval (95%CI) 1.40-2.37, P<0.000 01], while there was no significant difference between erythromycin and metoclopramide (RR=1.04, 95%CI 0.79-1.36, P=0.799). In patients who needed early EN, compared with placebo or blank control, erythromycin had higher successful gastric feeding rate over 5 days (RR=1.89, 95%CI 1.19-3.00, P=0.007). In patients who failed EN, compared with metoclopramide, erythromycin could significantly increase the successful gastric EN rate for 24 hours (RR=1.30, 95%CI 1.02-1.66, P=0.03), 72 hours (RR=1.57, 95%CI 1.15-2.14, P=0.005) and 144 hours (RR=2.04, 95%CI 1.23-3.37, P=0.006). The median time of EN intolerance was postponed in erythromycin group than that in metoclopramide group. Adverse reactions were reported in 5 studies. There was no statistic difference except for the higher diarrhea rate in the combination treatment group compared with erythromycin group. CONCLUSIONS: Postpyloric EN tube placement rate can be improved by erythromycin, which could be a choice of substitute for bedside intubation without fluoroscopy or endoscopic assistance. Based on the evidence, we recommended that intravenous erythromycin in a small dose of approximately 3 mg/kg weight as an option for EN intolerance in critical patients.

Development and validation of a sensitive liquid chromatography-tandem mass spectrometry method for the determination of naringin and its metabolite, naringenin, in human plasma.

A sensitive and specific method was developed for the simultaneous determination of naringin and its metabolite, naringenin, in human plasma by liquid chromatography-tandem mass spectrometry. Hesperidin was used as the internal standard, plasma samples were extracted with ethyl acetate and the analytes were chromatographically separated by using acetonitrile-0.1% formic acid (gradient elution) as the mobile phase. Detection was performed by electrospray ionization mass spectrometry in negative ion mode with multiple reaction monitoring. The lower limit of quantification was 0.5 ng/mL for naringin and naringenin and the linear calibration curves ranged from 0.5 to 200 ng/mL. The intra-run and inter-run precision values were within 8.6 and 7.7% for naringin and between 13.1 and 10.3% for naringenin. The accuracy ranged from 91.3 to 98.2% for naringin and from 90.2 to 97.6 % for naringenin. The validated method was successfully applied to determine concentrations of naringin and naringenin in clinical patients.

Effect of L-carnitine and/or L-acetyl-carnitine in nutrition treatment for male infertility: a systematic review.

The aim of this systematic review was to quantify the efficacy of L-carnitine (LC) and/or L-acetyl-carnitine (LAC) in nutrition treatment for male infertility according to present clinical evidence. Biomedical databases were searched to collect related clinical trials and nine relevant randomized controlled trials (RCTs) were included. The quality of the RCTs was assessed based on their performance in randomization, blinding, and allocation concealment. The meta-analysis compared LC and /or LAC therapy to placebo treatment found significant improvement in pregnancy rate (OR = 4.10, 95% CI (2.08, 8.08), p< 0.0001), total sperm motility (WMD = 7.43, 95% CI (1.72, 13.14), p = 0.04, forward sperm motility (WMD = 11.83, 95% CI (0.49, 23.16), p = 0.04) and atypical sperm cell (WMD = -5.72, 95% CI (-7.89, -3.56), p< 0.00001). However, no significant difference was found in the sperm concentration (WMD = 5.69, 95% CI (-4.47, 15.84), p = 0.27) and semen volume (WMD = 0.28, 95% CI (-0.02, 0.58), p = 0.07). In conclusion, the administration of LC and/or LAC may be effective in improving pregnancy rate and sperm kinetic features in patients affected by male infertility. However, the exact efficacy of carnitines on male infertility needs to be confirmed by further investigations.