The efficacy and safety of prophylactic antibiotics for post-acute stroke infection: A systematic review and meta-analysis.

AIMS: Infections are common complications after stroke and associated with unfavourable outcomes. We aimed to evaluate the efficacy and safety of prophylactic antibiotics for post-acute stroke infection. METHODS: We searched PubMed, Embase, the Cochrane Library, SinoMed, China National Knowledge Infrastructure, WanFang Data, China Science and Technology Journal Database, and clinical trial register platforms from inception to 15 February 2022. We included randomized clinical trials that evaluated the efficacy and safety of prophylactic antibiotics. Primary outcomes were mortality rate and incidence of pneumonia. The pooled risk ratio (RR) and mean differences with 95% confidence interval (CI) were calculated using the random or fixed-effect model depending on heterogeneity. The quality of evidence was evaluated using the Grading of Recommendations, Assessment, Development and Evaluations. RESULTS: Twelve studies (4809 participants) were included. There was no significant difference in the mortality rate (12 trials, n = 4740, RR 1.03 [95% Cl: 0.91-1.16], high-quality evidence), incidence of pneumonia (7 trials, n = 4352, RR 0.94 [95% CI: 0.79-1.11], high-quality evidence) and the incidence of adverse events between the prophylactic antibiotics and control groups. Prophylactic antibiotics significantly reduced the incidence of infections (8 trials, n = 4517, RR 0.72 [95% CI: 0.58-0.89], moderate-quality evidence) and urinary tract infections (7 trials, n = 4352, RR 0.39 [95% CI: 0.3-0.49], moderate-quality evidence). None of the subgroup analyses showed a significant difference in mortality or the incidence of pneumonia. CONCLUSION: For acute stroke patients, prophylactic antibiotics were significantly associated with fewer incidences of any infections and urinary tract infections without significant differences in mortality rate and pneumonia.

Determination of free and total meropenem levels in human plasma and its application for the consistency evaluation of generic drugs.

RATIONALE: The consistency evaluation of generic drugs is important for the overall reformation of drug registration in China. In this study, we used meropenem as a model drug to explore the key techniques for clinical consistency evaluation by studying the plasma protein binding (PPB) ratio of different preparations. Because the free portion of drug is the effective part in vivo, it is essential to measure the free drug concentration in the circulatory system. Therefore, in this study, a fast and accurate high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method was developed to determine the total and free concentrations of meropenem in human plasma. METHODS: Simple protein precipitation procedures were used for the sample processing assay, and ultrafiltration was implemented for the separation of free drugs. Liquid chromatography separation was performed using a hydrophilic interaction liquid chromatography (HILIC) silica column (2.1 × 50 mm, 3 µm). The mobile phase and sample preparation procedures were optimized. Factors affecting the measurement of free drug concentration were also determined. Nonspecific binding of the ultrafiltration membrane was negligible because the recovery rate for post-ultrafiltration was greater than 96%. RESULTS: Under optimal conditions, the drug concentrations were linear from 0.5 to 50 µg/ml for both total and free drug concentrations. The PPB ratio was calculated based on the free and total drug concentrations. The PPB of meropenem varied from 1.4% to 24.2% in different subjects. The validated method was applied to evaluate PPB of four preparations, and the results varied from 6.57 ± 3.19% to 10.40 ± 8.31%. One-way analysis of variance (ANOVA) showed no significant differences between the four preparations. CONCLUSIONS: We established a rapid, robust, and reliable method for the determination of total and free meropenem concentrations using LC-MS/MS with ultrafiltration techniques. The method provided a new perspective for the clinical consistency evaluation of generic drugs.

Medication therapy of high-dose methotrexate: An evidence-based practice guideline of the Division of Therapeutic Drug Monitoring, Chinese Pharmacological Society.

AIMS: A lot of medication risks related to high-dose methotrexate (HDMTX) therapy still remain to be identified and standardized. This study aims to establish an evidence-based practice guideline for individualized medication of HDMTX. METHODS: The practice guideline was launched by the Division of Therapeutic Drug Monitoring, Chinese Pharmacological Society. The guideline was developed following the WHO handbook for guideline development and the methodology of evidence-based medicine (EBM). The guideline was initially registered in the International Practice Guidelines Registry Platform (IPGRP-2017CN021). Systematic reviews were conducted to synthesize available evidence. A multicentre cross-sectional study was conducted using questionnaires to evaluate patients' perception and willingness concerning individualized medication of HDMTX. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to rate the quality of evidence and to grade the strength of recommendations. RESULTS: Multidisciplinary working groups were included in this guideline, including clinicians, pharmacists, methodologists, pharmacologists and pharmacoeconomic specialists. A total of 124 patients were involved to integrate patient values and preferences. Finally, the guideline presents 28 recommendations, regarding evaluation prior to administration (renal function, liver function, pleural effusion, comedications, genetic testing), pre-treatment and routine dosing regimen, therapeutic drug monitoring (necessity, method, timing, target concentration), leucovorin rescue (initial timing, dosage regimen and optimization), and management of toxicities. Of these, 12 are strong recommendations. CONCLUSIONS: We developed an evidence-based practice guideline with respect to HDMTX medication using a rigorous and multidisciplinary approach. This guideline provides comprehensive and practical recommendations involving the whole process of HDMTX administration to health care providers.

Are Proton Pump Inhibitors More Effective Than Histamine-2-Receptor Antagonists for Stress Ulcer Prophylaxis in Critically Ill Patients? A Systematic Review and Meta-Analysis of Cohort Studies.

BACKGROUND: Histamine-2-receptor antagonists (H2RAs) have been largely replaced by proton pump inhibitors (PPIs) for stress ulcer prophylaxis (SUP) despite the inconclusive evidence concerning comparative effectiveness. OBJECTIVE: To compare the effectiveness of PPIs and H2RAs on SUP in real-world setting. METHODS: PubMed, Embase, and the Cochrane Library were searched from inception to September 19, 2021. We included cohort studies comparing PPIs with H2RAs in critically ill adult patients and explicitly reporting the outcome of gastrointestinal (GI) bleeding or mortality. Newcastle-Ottawa Scale was used to assess potential risk of bias. We conducted a random-effects meta-analysis and only the studies with adjusted effect estimates were pooled. The Grading of Recommendations Assessment, Development, and Evaluation system was used to assess the overall quality of the evidence. RESULTS: Thirteen cohort studies (N = 145 149) were eligible and 11 of them available for full texts were of low to moderate risk of bias. Meta-analysis of adjusted effect estimates indicated that PPIs were associated with a significantly higher risk of GI bleeding, compared with H2RAs (8 studies, odds ratio [OR] = 1.98, 95% confidence interval [CI] = 1.30-3.01, low certainty). Post hoc pooling analysis also suggested that PPIs were associated with a slightly higher risk of mortality in comparison with H2RAs (7 studies, OR = 1.27, 95% CI = 1.13-1.42, low certainty). CONCLUSION AND RELEVANCE: The systematic review of cohort studies showed that PPIs were associated with higher risks of GI bleeding and mortality, although the certainty of evidence was low. Overall, we suggest not excluding H2RAs for SUP, while further studies are essential for elucidating the risk stratification, optimal regimen, and specific duration.

Efficacy and Safety Profile of Novel Oral Anticoagulants in the Treatment of Left Atrial Thrombosis: A Systematic Review and Meta-Analysis.

Background: The presence of left atrial/left atrial appendage thrombosis is associated with a higher risk of thromboembolic events in patients with atrial fibrillation. The optimal antithrombotic strategy is not established to date. Objective: Our aim was to compare the efficacy and safety profile of novel oral anticoagulants with warfarin in the treatment of left atrial/left atrial appendage thrombosis. Methods: We conducted a systematic search in PubMed, Embase, Cochrane Library, ClinicalTrials.gov, and 3 Chinese databases for all randomized controlled trials and cohort studies (PROSPERO, CRD42021238952) from inception to 7 May 2021. Two authors independently performed the articles selection, data extraction, and quality assessment. The efficacy outcome was the resolution of left atrial/left atrial appendage thrombosis, and the safety outcomes were bleeding and stroke/transient ischemic attack. Results: One randomized controlled trial and 5 cohort studies were included, with a total of 353 patients. Compared with warfarin, novel oral anticoagulants were associated with increased probability of left atrial/left atrial appendage thrombosis resolution (OR = 2.20; 95% CI, 1.35-3.60; I 2 = 0%). Compared with warfarin, novel oral anticoagulants had a similar risk of bleeding (OR = 0.91; 95% CI, 0.39-2.13; I 2 = 0%). There was no evidence of increased risk of stroke/transient ischemic attack (OR = 0.42; 95% CI, 0.12-1.45; I 2 = 0%). Conclusions: Novel oral anticoagulants were more effective than warfarin in promoting the resolution of left atrial/left atrial appendage thrombosis, without increased risks of bleeding and stroke/transient ischemic attack. Our study provides valuable insight into clinical practice. Further well-designed randomized controlled trials are needed to fully evaluate the benefits and risks in these patients. PROSPERO Registration No.: CRD42021238952.

Direct Oral Anticoagulant for the Treatment of VTE in Cancer Patients: A Systematic Review and Meta-analysis.

BACKGROUND: Recent clinical guidelines suggest direct oral anticoagulants (DOACs) as treatment for cancer-associated thrombosis (CAT), but the strength of such recommendations was not clear. Newly released trials add uncertainties to the benefit and risk assessment between DOACs and conventional therapy (low-molecular-weight heparin [LMWH] or vitamin K antagonists [VKAs]). OBJECTIVE: To evaluate the efficacy and safety of DOACs in patients with CAT, as compared with LMWH and VKAs. METHODS: PubMed, EMBASE, Cochrane Library, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched. Randomized controlled trials (RCTs) that reported outcomes of DOACs for treating CAT were included. Relative risk (RR), risk difference, and 95% CIs were pooled using the Mantel-Haenszel method. RESULTS: A total of 8 RCTs were included. DOACs significantly reduced VTE recurrence (RR = 0.59; 95% CI = 0.48-0.73) compared with conventional therapy. Results were similar in the LMWH and VKA subgroups. DOACs had a higher, though nonsignificant, risk of major bleeding compared with LMWH (RR = 1.33; 95% CI = 0.94-1.89) but lower risk of major bleeding compared with VKAs (RR = 0.60; 95% CI = 0.39-0.93). Findings were consistent across patients with active cancer and history of cancer. CONCLUSION AND RELEVANCE: DOACs have better efficacy to prevent recurrent VTE compared with conventional therapy. Regarding the safety profile, DOACs may carry higher risk of bleeding compared with LMWH but lower risk of bleeding compared with VKAs. Further studies are needed to inform the optimal anticoagulation approach for different types of cancers.

Dopamine agonists for preventing ovarian hyperstimulation syndrome.

BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) is a potentially serious complication of ovarian stimulation in assisted reproduction technology (ART). It is characterised by enlarged ovaries and an acute fluid shift from the intravascular space to the third space, resulting in bloating, increased risk of venous thromboembolism, and decreased organ perfusion. Most cases are mild, but forms of moderate or severe OHSS appear in 3% to 8% of in vitro fertilisation (IVF) cycles. Dopamine agonists were introduced as a secondary prevention intervention for OHSS in women at high risk of OHSS undergoing ART treatment.  OBJECTIVES: To assess the effectiveness and safety of dopamine agonists in preventing OHSS in women at high risk of developing OHSS when undergoing ART treatment. SEARCH METHODS: We searched the following databases from inception to 4 May 2020: Cochrane Gynaecology and Fertility Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL, and PsycINFO for randomised controlled trials (RCTs) assessing the effect of dopamine agonists on OHSS rates. We also handsearched reference lists and grey literature. SELECTION CRITERIA: We considered RCTs for inclusion that compared dopamine agonists with placebo/no intervention or another intervention for preventing OHSS in ART. Primary outcome measures were incidence of moderate or severe OHSS and live birth rate. Secondary outcomes were rates of clinical pregnancy, multiple pregnancy, miscarriage, and adverse events. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles, abstracts, and full texts of publications; selected studies; extracted data; and assessed risk of bias. We resolved disagreements  by consensus. We reported pooled results as odds ratios (OR) and 95% confidence interval (CI) by the Mantel-Haenszel method. We applied GRADE criteria to judge overall quality of the evidence. MAIN RESULTS: The search identified six new RCTs, resulting in 22 included RCTs involving 3171 women at high risk of OHSS for this updated review. The dopamine agonists were cabergoline, quinagolide, and bromocriptine. Dopamine agonists versus placebo or no intervention Dopamine agonists probably lowered the risk of moderate or severe OHSS compared to placebo/no intervention (OR 0.32, 95% CI 0.23 to 0.44; 10 studies, 1202 participants; moderate-quality evidence). This suggests that if the risk of moderate or severe OHSS following placebo/no intervention is assumed to be 27%, the risk following dopamine agonists would be between 8% and 14%. We are uncertain of the effect of dopamine agonists on rates of live birth (OR 0.96, 95% CI 0.60 to 1.55; 3 studies, 362 participants; low-quality evidence). We are also uncertain of the effect of dopamine agonists on clinical pregnancy, multiple pregnancy, miscarriage  or adverse events (very low to low-quality evidence). Dopamine agonists plus co-intervention versus co-intervention Dopamine agonist plus co-intervention (hydroxyethyl starch, human albumin, or withholding ovarian stimulation 'coasting') may decrease the risk of moderate or severe OHSS compared to co-intervention (OR 0.48, 95% CI 0.28 to 0.84; 4 studies, 748 participants; low-quality evidence). Dopamine agonists may improve rates of live birth (OR 1.21, 95% CI 0.81 to 1.80; 2 studies, 400 participants; low-quality evidence). Dopamine agonists may improve rates of clinical pregnancy and miscarriage, but we are uncertain if they improve rates of multiple pregnancy  or adverse events (very low to low-quality evidence). Dopamine agonists versus other active interventions We are uncertain if cabergoline improves the risk of moderate or severe OHSS compared to human albumin (OR 0.21, 95% CI 0.12 to 0.38; 3 studies, 296 participants; very low-quality evidence), prednisolone (OR 0.27, 95% CI 0.05 to 1.33; 1 study; 150 participants; very low-quality evidence), hydroxyethyl starch (OR 2.69, 95% CI 0.48 to 15.10; 1 study, 61 participants; very low-quality evidence), coasting (OR 0.42, 95% CI 0.18 to 0.95; 3 studies, 320 participants; very low-quality evidence), calcium infusion (OR 1.83, 95% CI 0.88 to 3.81; I² = 81%; 2 studies, 400 participants; very low-quality evidence), or diosmin (OR 2.85, 95% CI 1.35 to 6.00; 1 study, 200 participants; very low-quality evidence). We are uncertain of the effect of dopamine agonists on rates of live birth (OR 1.08, 95% CI 0.73 to 1.59; 2 studies, 430 participants; low-quality evidence). We are uncertain of the effect of dopamine agonists on clinical pregnancy, multiple pregnancy or miscarriage (low to moderate-quality evidence). There were no adverse events reported. AUTHORS' CONCLUSIONS: Dopamine agonists probably reduce the incidence of moderate or severe OHSS compared to placebo/no intervention, while we are uncertain of the effect on adverse events and pregnancy outcomes (live birth, clinical pregnancy, miscarriage). Dopamine agonists plus co-intervention may decrease moderate or severe OHSS rates compared to co-intervention only, but we are uncertain whether dopamine agonists affect pregnancy outcomes. When compared to other active interventions, we are uncertain of the effects of dopamine agonists on moderate or severe OHSS and pregnancy outcomes.

Recommendations on off-label use of intravenous azithromycin in children.

OBJECTIVE: Intravenous azithromycin (AZM) has been widely used in children worldwide, but there still remains much concern regarding its off-label use, which urgently needs to be regulated. Therefore, we developed a rapid advice guideline in China to give recommendations of rational use of intravenous AZM in children. METHODS: This guideline focuses on antimicrobial therapy with intravenous AZM in children. The Delphi research method was used to select questions. A systematic literature review was also conducted. Data were pooled and ranked according to the GRADE system. Recommendations were developed based on expert clinical experience, patients' values and preferences, and evidence availability. After an external review, the recommendations were revised and approved. RESULTS: This guideline included eighteen recommendations that covered four domains: (a) Indications: the treatment of pneumonia caused by atypical but common pathogens, such as Mycoplasma pneumoniae, Chlamydia trachomatis or Chlamydophila pneumoniae and Legionella pneumophila, more typical bacteria as well as the treatment of bronchitis of presumed bacterial aetiologies; (b) Usage and dosage: administration route, infusion concentrations, treatment duration, course of sequential treatment, and dosage stratified by age; (c) Adverse reactions and treatment: the management of gastrointestinal reactions, arrhythmias, pain or phlebitis at the infusion site, and anaphylaxis; and (d) Special population: children with renal or liver dysfunction, congenital heart disease, and obesity. This guideline will hopefully help promote a rational use of intravenous AZM in children worldwide. CONCLUSION: This guideline has summarised the evidence and has developed recommendations on the use of intravenous AZM in children worldwide. Further attention and well-designed researches should be conducted on the off-label use of intravenous AZM in children.

Good abdominal drainage fluid penetration and pharmacokinetics analysis of vancomycin for severe acute pancreatitis: A case report.

WHAT IS KNOWN AND OBJECTIVE: The antibiotic concentration in abdominal drainage fluid is very important for the treatment of patients with severe acute pancreatitis (SAP). Previous studies show that quinolones and carbapenems have high abdominal tissue levels, whereas aminoglycosides fail to penetrate into abdominal tissue in sufficient concentrations. However, there are limited data with respect to vancomycin. This case aims to investigate the penetration of vancomycin to abdominal drainage fluid in a 44-year-old SAP patient. CASE SUMMARY: We report a case of a 44-year-old female with SAP, on treatment of vancomycin. The time courses of vancomycin concentration in plasma and abdominal drainage fluid of the patient were described. Simultaneous measurement of abdominal drainage fluid and serum concentrations demonstrated that vancomycin can rapidly penetrate into abdominal tissue in acceptable amounts. WHAT IS NEW AND CONCLUSION: This case demonstrated that it took about 30 minutes for vancomycin to get from plasma to abdominal drainage fluid and about 76% of vancomycin could move into abdominal drainage fluid for SAP patients.

Comparison of lixisenatide in combination with basal insulin vs other insulin regimens for the treatment of patients with type 2 diabetes inadequately controlled by basal insulin: Systematic review, network meta-analysis and cost-effectiveness analysis.

AIMS: To evaluate the comparative efficacy and safety of lixisenatide combined with basal insulin (BI) vs intensive premix insulin (premix), BI plus prandial insulin with the main meal (basal-plus) or progressively covering all meals (basal-bolus) in patients with type 2 diabetes mellitus (T2DM) inadequately controlled by BI, and the long-term cost-effectiveness of lixisenatide from a Chinese healthcare system perspective. MATERIALS AND METHODS: Randomized controlled trials (RCTs) published between 1998 and 2018 were systematically searched. The clinical efficacy and safety of each treatment were compared by network meta-analysis (NMA). The IQVIA CORE Diabetes Model was used to estimate the lifetime quality-adjusted life-years (QALYs) and direct medical costs of patients treated with different strategies. RESULTS: Eight RCTs were finally included. Lixisenatide plus BI showed a similar reduction in HbA1c from baseline compared with premix, basal-plus and basal-bolus. There were significant differences in the change of body weight in favour of lixisenatide plus BI compared with the three insulin regimens. The risk of symptomatic hypoglycaemia of lixisenatide plus BI was significantly lower compared with premix and basal-bolus. Lixisenatide plus BI was cost-effective compared with premix, basal-plus and basal-bolus with incremental cost-effectiveness ratios of Chinese yuan (CNY) 87 219, 48 173 and 48 670 per QALY gained, respectively, under the threshold of three times the gross domestic product (GDP) per capita in China. CONCLUSIONS: Lixisenatide plus BI shows a similar HbA1c reduction compared with insulin regimens, accompanied by lower risk of hypoglycaemia and greater body weight reduction. It is a cost-effective treatment alternative for patients with T2DM inadequately controlled by BI in China.

Efficacy and safety of antiviral treatment for COVID-19 from evidence in studies of SARS-CoV-2 and other acute viral infections: a systematic review and meta-analysis.

BACKGROUND: Antiviral medications are being given empirically to some patients with coronavirus disease 2019 (COVID-19). To support the development of a COVID-19 management guideline, we conducted a systematic review that addressed the benefits and harms of 7 antiviral treatments for COVID-19. METHODS: We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), PubMed and 3 Chinese databases (CNKI, WANFANG and SinoMed) through Apr. 19, medRxiv and Chinaxiv through Apr. 27, and Chongqing VIP through Apr. 30, 2020. We included studies of ribavirin, chloroquine, hydroxychloroquine, umifenovir (arbidol), favipravir, interferon and lopinavir/ritonavir. If direct evidence from COVID-19 studies was not available, we included indirect evidence from studies of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) for efficacy outcomes and other acute respiratory viral infections for safety outcomes. RESULTS: In patients with nonsevere COVID-19 illness, the death rate was extremely low, precluding an important effect on mortality. We found only very low-quality evidence with little or no suggestion of benefit for most treatments and outcomes in both nonsevere and severe COVID-19. An exception was treatment with lopinavir/ritonavir, for which we found low-quality evidence for a decrease in length of stay in the intensive care unit (risk difference 5 d shorter, 95% confidence interval [CI] 0 to 9 d) and hospital stay (risk difference 1 d shorter, 95% CI 0 to 2 d). For safety outcomes, evidence was of low or very low quality, with the exception of treatment with lopinavir/ritonavir for which moderate-quality evidence suggested likely increases in diarrhea, nausea and vomiting. INTERPRETATION: To date, persuasive evidence of important benefit in COVID-19 does not exist for any antiviral treatments, although for each treatment evidence has not excluded important benefit. Additional randomized controlled trials involving patients with COVID-19 will be needed before such treatments can be administered with confidence.

The Benefit of Individualized Vancomycin Dosing Via Pharmacokinetic Tools: A Systematic Review and Meta-analysis.

Background: Various pharmacokinetic (PK) equations and software have been developed to individualize vancomycin dosing. However, the benefit of using any PK information to guide vancomycin dosing has not been fully elucidated. Objective: To appraise available evidence on the effectiveness and safety of individualized vancomycin dosing via PK tools. Methods: PubMed, EMBASE, the Cochrane Library, and 2 Chinese literature databases were searched through August 1, 2019. Randomized controlled trials (RCTs) and cohort studies that reported the PK and clinical outcomes of individualized vancomycin dosing versus empirical dosing were included. Pooled risk ratios (RRs) and mean differences were calculated for dichotomous and continuous outcomes, respectively. Results: A total of 21 studies involving 4346 patients were finally included, of which 3 were RCTs and 18 were cohort studies. Meta-analysis revealed that PK-guided vancomycin dosing significantly increased the attainment of target trough concentration (RR = 1.59; 95% CI = 1.49-1.70) and decreased the incidence of nephrotoxicity (RR = 0.57; 95% CI = 0.46-0.71). Additionally, the available evidence showed that target area under the curve/minimum inhibitory concentration attainment rate and time to target concentration could improve. However, the evidence on clinical outcomes was scarce, and no significant differences were detected in clinical response rate, microbiological eradication rate, mortality, and length of hospital stay between PK-guided vancomycin dosing and empirical dosing strategies. Conclusion and Relevance: Individualized vancomycin dosing via PK tools significantly increases the attainment of target trough concentration and decreases the incidence of nephrotoxicity. Evidence on clinical effectiveness was limited and showed no significant benefit. Further well-designed studies are warranted to assess its clinical effectiveness and inform routine care.

Thalidomide as a treatment for inflammatory bowel disease in children and adolescents: A systematic review.

WHAT IS KNOWN AND OBJECTIVE: Thalidomide is used off-label for the treatment of inflammatory bowel disease (IBD) and not as a first-line treatment option. The instructions clearly state that thalidomide is contraindicated in children because its safety and effectiveness in children are unknown. In this article, we review the efficacy and safety of thalidomide as a treatment for IBD in children and adolescents. METHODS: We searched PubMed, Embase, the Cochrane Library, CNKI, WanFang Data, CBM database [from the date of database establishment to June 2019] and clinical trials [systematic review and meta-analysis, randomized controlled trials (RCTs), cohort studies, case-control studies and case series studies] for studies concerning the use of thalidomide as a treatment for IBD in children and adolescents. RESULTS AND DISCUSSION: Seven studies (two RCTs and five case series), which included 134 children and adolescents (32 with ulcerative colitis, 102 with Crohn's disease), met the inclusion criteria. The included studies showed that the clinical remission rate of thalidomide was 44%-100% and the steroid tapering rate was 50%-100% in children and adolescents with refractory IBD. Peripheral neuropathy was the most common major adverse reaction, and it appeared to be cumulative dose-dependent. WHAT IS NEW AND CONCLUSION: Thalidomide as a treatment for refractory IBD in children and adolescents can improve clinical remission and achieve longer-term maintenance of remission. Peripheral neuropathy is the main adverse drug reaction, and it can be monitored and prevented. It is necessary to fully communicate with parents and obtain informed consent before using this drug.

A Systematic Review and Meta-Analysis of Sputum Purulence to Predict Bacterial Infection in COPD Exacerbations.

The 2020 Global Initiative for Obstructive Lung Disease (GOLD) Report highlights the importance of sputum purulence in the decision to prescribe antibiotics for acute exacerbations. The purpose of this systematic review and meta-analysis was to evaluate the strength of literature supporting inclusion of sputum purulence in criteria utilized to evaluate if antimicrobials are indicated in acute COPD exacerbation. A total of 6 observational studies met inclusion criteria for this meta-analysis. Sputum purulence was defined by visual assessment of color, either subjectively by providers and/or patients or by a colored chart, where green or yellow sputum was considered purulent. Four of the studies were primarily conducted in hospitalized patients, one in the emergency department, and one in the primary care setting. Five studies relied upon expectorated sputum and one used bronchoscopy to obtain sputum samples for bacterial cultures. Compared with mucoid sputum, purulent sputum had a significantly higher probability of positive bacterial culture results (RR = 2.14, 95%CI [1.25, 3.67], p = 0.006, moderate quality). For sensitivity analysis, after removal of studies losing 2 or more points from the New Castle-Ottawa scale, the effect value remained statistically significant. This systematic review and meta-analysis showed a moderate level of evidence that purulent sputum during COPD exacerbation, as defined by yellow or green color, is associated with a significantly higher probability of potentially pathogenic bacteria, supporting GOLD report and NICE recommendations.

Individualized Medication of Voriconazole: A Practice Guideline of the Division of Therapeutic Drug Monitoring, Chinese Pharmacological Society.

BACKGROUND: Voriconazole (VRZ) is a second-generation triazole antifungal agent with broad-spectrum activity. It is available in both intravenous and oral formulations, and is primarily indicated for treating invasive aspergillosis. The most commonly used dose for adults is 4 mg/kg or 200 mg twice daily. VRZ presents nonlinear pharmacokinetics in adults, whereas drug-drug interactions and cytochrome P450 2C19 (CYP2C19) polymorphism are of great concern for VRZ. Because the liquid chromatography method has been widely used for measuring VRZ blood concentration, and target VRZ blood concentration has been recommended in some guidelines regarding efficacy and safety, therapeutic drug monitoring is considered as a useful tool for VRZ-individualized medication. Also, the CYP2C19 genotype test is available for guiding relevant drugs use in some health care facilities. Our objective was to develop an evidence-based practice guideline for VRZ-individualized medication. METHODS: We followed the latest guideline definition from the Institute of Medicine and referred to the World Health Organization handbook for guideline development. The guideline was initially registered in the International Practice Guidelines Registry Platform (IPGRP-2015CN001). The guideline is, in principle, targeted at all Chinese health care providers. The quality of evidence and strength of the recommendations were assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) method. RESULTS: Twenty-six recommendations were formulated regarding therapeutic drug monitoring, special groups of patients, drug safety, off-indication use, and drug-drug interactions. Of them, 12 were strong recommendations. Most quality of evidence was low, very low, or expert opinions. CONCLUSIONS: We developed an evidence-based practice guideline for VRZ-individualized medication, which provided comprehensive and practical recommendations for health care providers. The development of the guideline exposed several research gaps to improve VRZ use.

Pericarditis associated with cytarabine therapy for acute myelocytic leukemia: a case report.

BACKGROUND: The incidence of cytarabine-induced pericarditis is rare. So far, only a few cases have been reported worldwide. DESCRIPTION OF THE CASE: We are reporting a case of a 25-year-old male with acute myeloid leukemia (AML M2a) on chemotherapy who developed acute pericarditis after the administration of a cytarabine-containing regimen. The symptoms gradually improved after symptomatic treatment with steroids and other drugs. CONCLUSIONS: This case demonstrates that, although pericarditis induced by cytarabine is rare, early recognition of this potentially life-threatening complication and appropriate management will usually result in the patient's recovery.

Use of antihypertensive drugs and risk of keratinocyte carcinoma: A meta-analysis of observational studies.

PURPOSE: Current epidemiologic evidence on the association between antihypertensive drugs and keratinocyte carcinoma (KC) risk is inconsistent. We sought to quantify this association by meta-analysis of observational studies. METHODS: We systematically reviewed observational studies published through August 2016 and reported the KC risk (basal cell carcinoma [BCC] and squamous cell carcinoma [SCC]) associated with antihypertensive drugs, including diuretics, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), beta-adrenergic blocking agents (ß-blockers), and calcium channel blockers (CCBs). Random-effects meta-analysis was used to estimate the odds ratio (OR) with 95% confidence interval (CI). RESULTS: Ten eligible studies were included. Compared with nonuse, diuretic use was significantly associated with increased risk of both BCC (OR, 1.10; 95% CI, 1.01-1.20) and SCC (OR, 1.40; 95% CI, 1.19-1.66). Use of ß-blockers or CCBs was associated with increased risk of BCC (but not SCC); the OR with ß-blockers was 1.09 (95% CI, 1.04-1.15) and with CCBs was 1.15 (95% CI, 1.09-1.21). Use of ACE inhibitors or ARBs was associated with decreased risk of both BCC (OR, 0.53; 95% CI, 0.39-0.71) and SCC (OR, 0.58; 95% CI, 0.42-0.80) in high-risk individuals. CONCLUSIONS: Current evidence indicates that use of diuretics might be associated with increased risk of KC, while ACE inhibitors or ARBs might be associated with decreased risk in high-risk individuals. ß-blockers or CCBs might be positively associated with BCC risk. Further postmarketing surveillance studies and investigations to clarify the possible underlying mechanisms are warranted.

Comparative efficacy and safety between amisulpride and olanzapine in schizophrenia treatment and a cost analysis in China: a systematic review, meta-analysis, and cost-minimization analysis.

BACKGROUND: Amisulpride was introduced into China in 2010 as a second-generation atypical antipsychotic, while olanzapine has been on the market since 1999 as one of the leading treatments for schizophrenia in China. Since more Chinese patients are gaining access to amisulpride, the study aims to compare the efficacy, safety, and costs between amisulpride and olanzapine for schizophrenia treatment in China. METHODS: PubMed, Embase, the Cochrane library, China National Knowledge Infrastructure (CNKI) and WanFang database were systematically searched for randomized controlled trials (RCTs) up to July 2018. The Cochrane Risk of Bias tool was utilized to assess the quality of included studies. A meta-analysis was performed to compare the efficacy and safety of amisulpride and olanzapine, followed by a cost-minimization analysis using local drug and medical costs reported in China. RESULTS: Twenty RCTs with 2000 patients were included in the systematic review. There were no significant differences between amisulpride and olanzapine on efficacy measures based on scores from the Positive and Negative Syndrome Scale, the Scale for the Assessment of Negative Symptoms, the Brief Psychiatric Rating Scale and the Clinical Global Impressions-Severity or Improvement. For safety outcomes, amisulpride was associated with lower fasting blood glucose and less abnormal liver functions as well as significantly lower risks of weight gain, constipation, and somnolence; olanzapine was associated with significantly lower risks of insomnia and lactation/amenorrhea/sexual hormone disorder. No significant differences were found in risks of extrapyramidal symptoms (EPS), tremor, akathisia, abnormal corrected QT interval. Cost-minimization analysis showed that amisulpride was likely to be a cost-saving alternative in China, with potential savings of 1358 Chinese Yuan (CNY) per patient for a three-month schizophrenia treatment compared with olanzapine. CONCLUSION: As the first meta-analysis and cost-minimization analysis comparing the efficacy, safety and cost of amisulpride and olanzapine within a Chinese setting, the study suggests that amisulpride may be an effective, well-tolerated, and cost-saving antipsychotic drug alternative in China.

Clinical features and treatment of pediatric patients with drug-induced anaphylaxis: a study based on pharmacovigilance data.

We assessed the clinical features and treatment of pediatric patients with drug-induced anaphylaxis in clinical settings. Pediatric drug-induced anaphylaxis cases collected by the Beijing Pharmacovigilance Database from 2004 to 2014 were analyzed. A total of 91 cases were identified. Drug-induced anaphylaxis was primarily caused by antibiotics (53%). Children of 0-5 years were more likely to develop cyanosis symptoms than children of 13-17 years (OR = 5.14, 95%CI [1.74, 15.20], P = 0.002). Children of 13-17 years were more likely to develop hypotension than children of 6-12 years (OR = 11.79, 95%CI [2.28, 60.87], P = 0.002), and to manifest both neurological symptoms (OR = 3.56, 95%CI [1.26, 10.08], P = 0.015) and severe anaphylaxis than children of 0-5 years (OR = 15.46, 95%CI [1.85, 129.33], P = 0.002). Supratherapeutic doses of epinephrine were more likely with intravenous (IV) bolus (92%) in contrast to either intramuscular (IM) (36%, OR = 19.25, 95%CI [1.77, 209.55], P = 0.009) or subcutaneous (SC) injections (36%, OR = 19.80, 95% CI [1.94, 201.63], P = 0.005). Only 62 (68%) patients received epinephrine treatment as the first-line therapy. CONCLUSION: This study demonstrates that antibiotics were the most common cause of pediatric drug-induced anaphylaxis. Children may present with different anaphylactic signs/symptoms based on age groups. Epinephrine is under-utilized and provider education on the proper management of drug-induced anaphylaxis is warranted. What is Known: • The most common causes of anaphylaxis in children are allergies to foods. Drugs are the second most common cause of pediatric anaphylaxis. • IM epinephrine is the recommended initial treatment of anaphylaxis. What is New: • Drug-induced anaphylaxis in pediatric patients has age-related clinical features. • IV bolus epinephrine was overused and associated with supratherapeutic dosing.