Prospects of marine-derived compounds as potential therapeutic agents for glioma.

CONTEXT: Glioma, the most common primary malignant brain tumour, is a grave health concern associated with high morbidity and mortality. Current treatments, while effective to some extent, are often hindered by factors such as the blood-brain barrier and tumour microenvironment. This underscores the pressing need for exploring new pharmacologically active anti-glioma compounds. METHODS: This review synthesizes information from major databases, including Chemical Abstracts, Medicinal and Aromatic Plants Abstracts, ScienceDirect, SciFinder, Google Scholar, Scopus, PubMed, Springer Link and relevant books. Publications were selected without date restrictions, using terms such as 'Hymenocrater spp.,' 'phytochemical,' 'pharmacological,' 'extract,' 'essential oil' and 'traditional uses.' General web searches using Google and Yahoo were also performed. Articles related to agriculture, ecology, synthetic work or published in languages other than English or Chinese were excluded. RESULTS: The marine environment has been identified as a rich source of diverse natural products with potent antitumour properties. CONCLUSIONS: This paper not only provides a comprehensive review of marine-derived compounds but also unveils their potential in treating glioblastoma multiforme (GBM) based on functional classifications. It encapsulates the latest research progress on the regulatory biological functions and mechanisms of these marine substances in GBM, offering invaluable insights for the development of new glioma treatments.

Seven oral traditional Chinese medicine combined with chemotherapy for the treatment of non-small cell lung cancer: a network meta-analysis.

CONTEXT: Traditional Chinese medicines (TCMs) have emerged as potential adjuvant therapies to treat non-small cell lung cancer. More direct comparative studies must be conducted among various oral TCMs. OBJECTIVE: This network meta-analysis evaluates the efficacy and safety of seven oral TCMs combined with chemotherapy in treating NSCLC. METHODS: The analysis included Zilongjin, Banmao, Hongdoushan, Huachansu, Kanglaite, Xihuang, and Pingxiao TCMs. Randomized-controlled trials (RCTs) were identified from the following databases: China National Infrastructure, Wanfang, PubMed, Embase, and the Cochrane Library up to April 2023. Two researchers independently extracted data. RESULTS: Sixty-eight RCTs (5,099 patients) were included. Compared to chemotherapy, Banmao capsules [odds ratio (OR) = 2.69, 95% confidence interval (CI) 1.96-3.69)] and Huachansu tablets [OR = 2.35, 95%CI (1.81, 3.05)] ranked in the top two in terms of increasing disease control rate. The two main TCMs to improve the objective response rate were Banmao capsules [OR = 3.49, 95%CI (2.17, 5.60)] and Zilongjin tablets [OR = 2.62, 95%CI (1.92, 3.57)]. Zilongjin tablets [OR = 3.47, 95%CI (2.14, 5.63)] and Huachansu tablets [OR = 3.30, 95%CI (1.65, 6.60)] were ranked as the top two in improving Karnofsky performance status. Hongdoushan capsules (SUCRA = 18.8%) and Banmao capsules (SUCRA = 19.8%) were the top two in reducing gastrointestinal toxicity. Zilongjin tablets (SUCRA = 18.9%) and Banmao capsules (SUCRA = 26.6%) were the top two to reduce liver and kidney toxicity. Hongdoushan capsules (SUCRA = 15.7%) and Huachansu tablets (SUCRA = 16.8%) ranked the top two in reducing thrombocytopenia. Banmao capsules (SUCRA = 14.3%) and Zilongjin tablets (SUCRA = 26.3%) were the top two decreasing leukopenia. CONCLUSIONS: Combining oral TCMs with platinum-based chemotherapy has shown superior efficacy compared to platinum-based chemotherapy alone in treating NSCLC.

Pharmacist impact on adherence of valproic acid therapy in pediatric patients with epilepsy using active education techniques.

There is limited information on the impact of active education by a pharmacist in the population of pediatric patients with epilepsy (PWE) in China. The objective of this study was to assess the effect of education by pharmacists on medication adherence and percentage of valproic acid (VPA) samples reaching therapeutic reference range in these patients. This study was conducted at two teaching hospitals in Changsha, China. Patients were retrospectively identified from January 2016 to December 2017. Active education by a pharmacist in both oral and written formats was provided at the intervention hospital whereas standard passive pharmacist service (dispensing and answering questions) was provided at the control hospital. Medication adherence was assessed by the simplified medication adherence questionnaire (SMAQ), and serum concentrations of VPA were collected. The correlation between pharmacist education and medication adherence and percentage of VPA samples reaching therapeutic reference range were analyzed. A total of 2165 patients and 4343 serum VPA concentrations were included in the analysis. For the first therapeutic drug monitoring (TDM) measurement, there was no statistical difference between the two hospitals: 41.3% of VPA samples reached therapeutic range at the intervention hospital compared with 45.4% at the control hospital (χ2 = 3.686, P > 0.05). After pharmacist intervention at the intervention hospital, however, there were significant differences in the percentage of therapeutic VPA samples reaching therapeutic range between the first and the second, third, fourth, and fifth TDM measurements (χ2 = 9.756, P < 0.01; χ2 = 22.840, P < 0.01; χ2 = 15.816, P < 0.01; χ2 = 27.613, P < 0.01). Based on the SMAQ adherence assessment, adherence increased from a minimum of 56.0% to a maximum of 73.9% with stabilization during the last six months of follow-up at the intervention hospital. Both the medication adherence rate and the percentage of VPA samples reaching therapeutic range increased as the result of active education by a pharmacist, suggesting that continuous pharmacist intervention had a positive impact in outpatient pediatric PWE.

Pharmacokinetic interaction between shuanghuanglian and azithromycin injection: a nonlinear mixed-effects model analysis in rats.

1. This study aimed to evaluate the pharmacokinetic interaction of shuanghuanglian (SHL) and azithromycin in rats, and to provide experimental support for rational drug use in clinics. 2. High-performance liquid chromatography with ultraviolet detection (HPLC-UV) and high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) approaches were respectively developed to detect the forsythiaside (active component of SHL) and azithromycin concentrations. Both non-compartmental and compartmental analyzes were employed to calculate pharmacokinetic parameters. A nonlinear mixed-effects modeling method was applied to fit the drug concentration-time data. The influence of drug coadministration on pharmacokinetic parameters was tested using forward inclusion and backward elimination procedures. 3. After drug co-administration, areas under the drug concentration-time curve (AUC) and half-lives (T1/2) of both azithromycin and forsythiaside increased significantly, meanwhile, the drug clearance (CL) decreased compared to single drug administration. Both forsythiaside and azithromycin exposures increased after coadministration. Two-compartment models were suitable to describe the in vivo behavior of both azithromycin and forsythiaside. The coadministration of SHL could significantly decrease the central volume of azithromycin (VCA) and forsythiaside clearance (CLF) decreased after co-intravenous administration of azithromycin. 4. Co-intravenous administration of forsythiaside and azithromycin could significantly increase drug exposures for both drugs. Lower dose can provide sufficient drug exposure to obtain antibacterial activity. The coadministration may be a potential method to increase therapy efficiency while decrease adverse drug reactions.

Assessing fluoroquinolone-associated aortic aneurysm and dissection: Data mining of the public version of the FDA adverse event reporting system.

AIMS: A recent large epidemiological study found fluoroquinolone use is associated with an increased risk of aortic aneurysm or dissection. We aimed to examine fluoroquinolone (ciprofloxacin, levofloxacin and moxifloxacin) associated aortic aneurysm or dissection through data mining of the US Food and Drug Administration Adverse Event Reporting System (FAERS). METHODS: Reports to the FAERS from 1 January 2004 to 31 December 2016 were analysed. Pharmacovigilance tools were used for quantitative detection of signals that is, drug-associated adverse events, including reporting odds ratio, proportional reporting ratio, information component given by a Bayesian confidence propagation neural network and empirical Bayes geometric mean. Sensitivity analyses that limited the data by gender and adverse event date also showed similar trends. RESULTS: Based on 3721 adverse event reports, all three fluoroquinolones are associated with aortic aneurysm, and levofloxacin is associated with aortic dissection. The risk of aortic aneurysm is higher than the aortic dissection. Oral administration of fluoroquinolones is more likely to produce these adverse events. CONCLUSION: The results obtained herein are consistent with clinical observations, suggesting the necessity for further clinical research on aortic aneurysm and dissection associated with fluoroquinolones.

A new derivatization method for the determination of valproic acid in serum using tetramethylammonium hydroxide as a catalyst.

Valproic acid (VPA) pharmacokinetics is highly variable and monitoring of blood levels is necessary to determine its appropriate dosage. This study aimed to establish and validate a novel derivatization method for the determination of VPA. The method was based on the catalytic effect of tetramethylammonium hydroxide using 2,4'-dibromoacetophenone as a derivatization reagent. After derivatization, samples were injected into the HPLC system for analysis. The method showed a good linearity in the range of 1.0-200.7 µg mL-1 , and the limit of quantification was 1 µg mL-1 . All values of the accuracy and relative standard deviations were acceptable for the analyses of biological samples. The recoveries were in the range from 91.6 to 97.4% for VPA with RSD <3.9%. A novel and high conversion-rate derivatization method has been developed and validated for the determination of VPA in human serum. It can be applied to the analysis of VPA in clinic serum samples.

Nutrition support for critically ill patients in China: role of the pharmacist.

BACKGROUND AND OBJECTIVES: The participation of a nutrition support pharmacist (NSP) in a multidisciplinary team (MDT) for patients receiving nutrition support therapy (NST) may lead to more favourable outcomes and fewer complications and adverse events. However, few studies have demonstrated the role of NSPs in MDTs in China. To investigate pharmacy interventions and physician acceptance of these interventions for patients receiving NST in an intensive care unit (ICU). METHODS AND STUDY DESIGN: A prospective study over a 12-month period was conducted in an ICU at an academic hospital in China. Interventions were documented and divided into the following categories: indication of NST, parenteral nutrition (PN) prescription and delivery, enteral nutrition (EN) route and formulation, fluids and electrolytes, laboratory test monitoring, nutritional supplements, and other medication-related problems. Data regarding the intervention categories, timing, acceptance rates, and methods of communication to discuss pharmacy interventions were collected. RESULTS: In total, 247 interventions for 120 patients were identified. The overall acceptance rate of interventions was 85.0% (210/247), and more than half of the interventions (143, 57.9%) were performed during daily follow-up. The most common intervention categories were PN prescription and delivery (81/247, 32.8%), EN route and formula (33/247, 13.4%), indication of NST (33/247, 13.4%), and nutritional supplements (30/247, 12.1%). The most accepted intervention category was PN prescription and delivery (79/81, 97.5%), and the most common method of communication was oral communication during MDT rounds (201/247, 81.4%). CONCLUSIONS: This study demonstrated the unique perspectives offered and importance of having pharmacists as members of MDTs.

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.

The influence of ABCB1 and P2Y12 genetic variants on clinical outcomes in Chinese intracranial artery stenosis patients.

For intracranial artery stenosis patients, high inter-individual variability in response to antiplatelet drug therapy results in recurrent ischemic events. We aimed to evaluate the association of drug-related genetic polymorphisms with adverse clinical outcomes. We consecutively enrolled 157 patients receiving dual-antiplatelet therapy (aspirin plus clopidogrel), and adverse clinical events occurred in 10 patients during the one year follow-up. The P2Y12 polymorphisms (rs9859538 and rs10935842) were associated with increased likelihood of relapse events (OR=2.934, 95%CI=1.022-8.425, P-value=0.045), and the two variants are in complete linkage disequilibrium. The mutation of ABCB1 rs1128503 may decrease the recurrence of clinical events (OR=0.211, 95%CI=0.046-0.957, P-value=0.044). Genetic testing (ABCB1 and P2Y12) may provide useful information to prevent ischemic events prior to the initiation of antiplatelet therapy. This article is protected by copyright. All rights reserved.

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.

Plasma and cerebrospinal fluid population pharmacokinetics of vancomycin in postoperative neurosurgical patients after combined intravenous and intraventricular administration.

PURPOSE: Combined intravenous and intraventricular administration of vancomycin into the cerebrospinal fluid (CSF) has been increasingly utilized for neurosurgical patients, but little is known about the population pharmacokinetics of vancomycin in the plasma and CSF. The aim of our study was to identify significant factors associated with plasma and CSF vancomycin concentrations to guide clinicians with vancomycin dosing. METHODS: Patients with an indwelling ventricular drainage catheter who received intravenous and intraventricular vancomycin were enrolled in this study. Blood and CSF samples were collected at scheduled times and vancomycin concentrations determined. A three-compartmental model (central, peripheral and CSF compartments) was proposed to describe the in vivo behavior of vancomycin. CSF outflow resulted in vancomycin loss, and the clearance of CSF compartment (CLCSF) was used to describe this loss. The nonlinear mixed-effects modeling method was applied to structure the population model, and the stepwise incorporation of seven covariates into the final model was attempted. Simulation was performed with the goal of CSF concentrations reaching or exceeding the minimum inhibitory concentration during therapy. RESULTS: Serum creatinine clearance had a significant influence on clearance of the central compartment. CLCSF had a positive correlation with drainage amount and a negative correlation with elapsed time. Model validation (bootstrap and visual predictive check) demonstrated the stability and performance of the proposed population model. A simple-to-use dosage regimen table was created based on the simulation results. CONCLUSIONS: The proposed final model may be used to guide clinicians with vancomycin dosing in this specific patient population.

Association of ABCB1 promoter methylation with aspirin exposure, platelet function, and clinical outcomes in Chinese intracranial artery stenosis patients.

PURPOSE: DNA methylation typically acts to repress gene transcription. ABCB1 is involved in the intestinal absorption of aspirin. We aimed to investigate the impact of methylation status of ABCB1 promoter on aspirin exposure, platelet function, and clinical outcomes in Chinese intracranial artery stenosis patients receiving antiplatelet treatment. METHODS: Symptomatic intracranial artery stenosis patients (without carrying CYP2C19 loss-of-function alleles) receiving antiplatelet therapy were enrolled in this study. The clinical outcome was the composite events, vascular death, recurrent ischemic stroke, myocardial infarction, or transit ischemic attack. Patients were divided into cases and controls based on the 1-year follow-up. Venous blood samples were collected for methylation level analysis, drug determination, and thromboelastographic assay. The Pearson correlation analysis was used to investigate the association of potential influencing factors and visualize them using three-dimensional plot. Receiver operator curves were applied to compare the diagnostic performance of potential factors and calculate the cut-off values. RESULTS: We assessed 438 patients, 30 (non-carrier of CYP2C19 loss-of-function alleles) experienced adverse clinical events, and 30 patients without clinical events were selected as controls. Total of 34 CpG methylation sites were investigated for ABCB1 methylation. Compared with controls, the cases had significant lower methylation levels (CpG21.22), lower salicylic acid concentration, and lower arachidonic acid inhibition (P value < 0.05). A cut-off point of CpG21.22 0.015 was identified with a specificity of 0.759. CONCLUSION: ABCB1 hypomethylation is associated with lower drug absorption, higher platelet reactivity, and an increased risk of ischemic events in our patients. This may provide important insights into the research of aspirin resistance.

Association of genetic variant and platelet function in patients undergoing neuroendovascular stenting.

INTRODUCTION: The risk of recurrent ischaemic events is related to platelet function, which is often assessed by thromboelastography (TEG). TEG has high interindividual variability. OBJECTIVE: To identify causal variants associated with TEG parameters in patients who receive aspirin and clopidogrel after intra- or extracranial stenting. METHODS: Patients who underwent stenting for extracranial or intracranial stenosis (70-99%) were recruited into the study. Blood samples were obtained for TEG to assess the platelet function before stenting. Aspirin- and clopidogrel-related genetic polymorphisms were determined by the MassARRAY method. Minor allele frequency and Hardy-Weinberg equilibrium (HWE) tests and linkage disequilibrium (LD) analysis were carried out. The influences of genetic polymorphism on TEG parameters were analysed by linear regression. RESULTS: A total of 249 patients were included in this study. Twenty-two selected single nucleotide polymorphisms (SNPs) were genotyped, and no significant deviation from HWE was found for any SNP in the study patients. Four SNPs-rs2104543, rs12772169, rs1998591 and rs1042194-within CYP2C18 were in high LD, and the genetic polymorphisms had a significant impact on the TEG parameters maximal clot strength (MAThrombin) and ADP-induced platelet-fibrin clot strength (MAADP). Patients who carried the loss-of-function CYP2C19*2 (rs4244285) allele were also at risk of increased MAThrombin and MAADP. CONCLUSIONS: Testing for these polymorphisms may be valuable in the identification of patients at high risk of recurrent ischaemic events. Alternative treatments may be considered for these high-risk patients. TRIAL REGISTRATION NUMBER: NCT01925872.

Impact of genetic polymorphisms related to clopidogrel or acetylsalicylic acid pharmacology on clinical outcome in Chinese patients with symptomatic extracranial or intracranial stenosis.

PURPOSE: Recurrent ischemic events in Chinese patients with symptomatic extracranial or intracranial stenosis caused by aspirin or clopidogrel resistance are well known. We aimed to identify the contribution of genetic variants to the events. METHODS: Patients with symptomatic extracranial or intracranial stenosis receiving dual antiplatelet treatment for at least 5 days were enrolled in this study. The primary endpoint was a composite of ischemic events, including recurrent transient ischemic attack, stroke, myocardial infarction, and vascular-related mortality. Twenty-four single nucleotide polymorphisms (SNPs) were assessed and genotyped. The clinical characteristics of enrolled patients were collected from medical records. The influence of genetic polymorphisms on the recurrent ischemic events of the patients was examined. RESULTS: A total of 377 patients were included. During a 12-month follow-up, the composite primary endpoint was observed in 64 patients. The CYP2C19*3 (rs4986893) may increase the occurrence of the primary composite endpoint (OR = 2.56, 95 % CI = 1.29-5.10, P = 0.007), and the mutation of CES1 rs8192950 was associated with the decreased recurrence of ischemic events (OR = 0.53, 95 % CI = 0.30-0.94, P = 0.029). The other SNPs that were tested did not have statistically significant associations with the composite endpoint. CONCLUSIONS: For Chinese patients with symptomatic extracranial or intracranial stenosis treated with clopidogrel, CYP2C19*3 mutation was associated with an increased risk of ischemic events, and the mutation of rs8192950 in CES1 is associated with a decreased risk of recurrent ischemic events. Testing these two SNPs could be of value in the identification of patients at risk for recurrent ischemic events.

Impact of hormone replacement therapy on all-cause and cancer-specific mortality in colorectal cancer: A systematic review and dose‒response meta-analysis of observational studies.

OBJECTIVE: The effect of hormone replacement therapy (HRT) on colorectal cancer (CRC) mortality and all-cause mortality remains unclear. We conducted a systematic review and dose-response meta-analysis to determine the effects of HRT on CRC mortality and all-cause mortality. METHODS: We searched the electronic databases of PubMed, Embase, and The Cochrane Library for all relevant studies published until January 2024 to investigate the effects of HRT exposure on survival rates for patients with CRC. Two reviewers independently extracted individual study data and evaluated the risk of bias between the studies using the Newcastle‒Ottawa Scale. We performed a two-stage random-effects dose-response meta-analysis to examine a possible nonlinear relationship between the year of HRT use and CRC mortality. RESULTS: Ten cohort studies with 480,628 individuals were included. HRT was inversely associated with the risk of CRC mortality (hazard ratios (HR) = 0.77, 95% CI (0.68, 0.87), I2 = 69.5%, p < 0.05). The pooled results of seven cohort studies revealed a significant association between HRT and the risk of all-cause mortality (HR = 0.71, 95% CI (0.54, 0.92), I2 = 89.6%, p < 0.05). A linear dose-response analysis (p for nonlinearity = 0.34) showed a 3% decrease in the risk of CRC for each additional year of HRT use; this decrease was significant (HR = 0.97, 95% CI (0.94, 0.99), p < 0.05). An additional linear (p for nonlinearity = 0.88) dose-response analysis showed a nonsignificant decrease in the risk of all-cause mortality for each additional year of HRT use. CONCLUSIONS: This study suggests that the use of HRT is inversely associated with all-cause and colorectal cancer mortality, thus causing a significant decrease in mortality rates over time. More studies are warranted to confirm this association.

The origin of vitamin B12 levels and risk of all-cause, cardiovascular and cancer specific mortality: A systematic review and dose-response meta-analysis.

BACKGROUND: Vitamin B12 is essential to human but the implications of serum vitamin B12 level for mortality in clinical practice remain unclear. We conducted a systematic review and dose-response meta-analysis to quantify the relationship between vitamin B12 levels and the risk of all-cause, cardiovascular, and cancer mortality. METHODS: Electronic databases of PubMed, Embase, and the Cochrane Library Central Register of Controlled Trials were searched from inception through May 2023. Two reviewers independently extracted individual study data and evaluated the risk of bias among the studies using the Newcastle‒Ottawa Scale. To examine a potential nonlinear relationship between the vitamin B12 levels and all-cause mortality, we performed a two-stage random effects dose‒response meta-analysis. RESULTS: Twenty-two cohort studies (92,346 individuals with 10,704 all-cause deaths) were included. A linear trend dose-response analysis showed that each 100 pmol/L increase in serum vitamin B12 concentration was associated with a 4 % higher risk of all-cause mortality in the general population (adjusted HR 1.04, 95 % confidence interval CI 1.01 to 1.08; n = 8; P non-linearity = 0.11) and a 6 % higher risk for all-cause mortality in older adults (adjusted HR 1.06, 95 % CI 1.01 to 1.13; n = 4; P non-linearity = 0.78). Current evidence was mixed for the association between serum vitamin B12 concentration and cardiovascular mortality and was limited for cancer mortality. The meta-analysis of cohort studies showed a positive association between a high serum vitamin B12 concentration (>600 pmol/L) and all-cause mortality (adjusted HR 1.50, 95 % CI 1.29 to 1.74; n = 10; p < 0.01), CVD mortality (adjusted HR 2.04, 95 % CI 0.99 to 4.19; n = 2; p = 0.02), except cancer mortality (adjusted HR 1.56, 95 % CI 0.82 to 2.95; n = 3). Similarly, serum vitamin B12 concentrations (400-600 pmol/L) were associated with increased all-cause mortality (adjusted HR 1.34, 95 % CI 1.10 to 1.64; n = 9; p < 0.01). CONCLUSIONS: Serum vitamin B12 concentration was positively associated with the risk of all-cause mortality, especially among older adults, with a linear increasing trend. These findings suggested the primary cause of elevated level of serum vitamin B12 concentration should be timely identified and effectively managed in clinical practice.

Cannabinoid hyperemesis syndrome.

BACKGROUND: The purpose of this review is to describe cannabinoid hyperemesis syndrome (CHS), which is thought to be induced by long-term cannabis use, and provide clinical pharmacists with information to manage the hyperemetic phase of CHS. METHOD: Published literature was searched and reviewed using PubMed. RESULTS: CHS is characterized by intractable nausea and vomiting without an obvious organic cause and associated learned compulsive hot water bathing behavior. Patients often seek care in the emergency department (ED) for symptomatic relief. CONCLUSION: CHS is potentially underrecognized and underdiagnosed in the ED, and it should be considered in the differential diagnosis in long-term cannabis use patients with CHS symptoms to avoid unnecessary extensive diagnostic workup including invasive radiologic imaging. Pharmacists have an important role in CHS recognition, education, and symptom management.

Mortality-Related Risk Factors and Novel Antimicrobial Regimens for Carbapenem-Resistant Enterobacteriaceae Infections: A Systematic Review.

Objective: Carbapenem-resistant Enterobacteriaceae (CRE) has become a significant public health problem in the last decade. We aimed to explore the risk factors of mortality in patients with CRE infections and to focus on the current evidence on antimicrobial regimens for CRE infections, particularly from the perspective of mortality. Methods: A systematic literature review was performed by searching the databases of EMBASE, PubMed, and the Cochrane Library to identify studies that evaluated mortality-related risk factors and antimicrobial regimens for CRE infections published from 2012 to 2022. Results: In total, 33 and 28 studies were included to analyze risk factors and antibiotic treatment, respectively. The risk factors most frequently reported as significantly associated with CRE mortality were antibiotic use (92.9%; 26/28 studies), comorbidities (88.7%; 23/26 studies), and hospital-related factors (82.8%; 24/29 studies). In 10 studies that did not contain ceftazidime/avibactam (CAZ-AVI) therapy, seven demonstrated significantly lower mortality in combination therapy than in monotherapy. However, 5 of 6 studies identified no substantial difference between CAZ-AVI monotherapy and CAZ-AVI combination therapy. Six studies reported substantially lower mortality in CAZ-AVI regimens than in other regimens. Conclusion: Several risk factors, particularly antibiotic use and patients' comorbidities, are strong risk factors for CRE mortality. The optimal regimen for CRE infections remains controversial. Combination therapy should be considered when carbapenems, colistin, tigecycline, or aminoglycosides are administered. CAZ-AVI appears to be a promising antibiotic for CRE infections. Most importantly, treatment should be individualized according to the source and severity of the disease or other highly related risk factors.

Successful treatment of Talaromyces marneffei infection in a kidney transplant recipient with voriconazole followed by itraconazole for the first time.

Talaromyces (Penicillium) marneffei (T. marneffei) is an important pathogenic thermally dimorphic fungus in Southeast Asia that leads to a life-threatening systemic mycosis in immunodeficient hosts, especially in AIDS patients. With the increasing AIDS epidemic, the number of patients with T. marneffei infections in mainland China has increased rapidly in recent years. The infection can be life-threatening in people with immunodeficiencies, such as HIV, organ transplantations, autoimmune diseases, and malignant tumors. Here, we present a disseminated T. marneffei infection case in a renal transplant recipient successfully treated with voriconazole followed by itraconazole. We describe the patient's clinical progression from onset symptoms to recovery and review the additional 14 published cases with T. marneffei infections in renal transplant recipients. In addition, we discuss the route of infection and treatment strategies of T. marneffei. Our data suggest that patients with kidney transplantations in T. marneffei infection-endemic areas should presume the possibility of infection and initiate appropriate antifungal treatment.

Hypnotics and infections: disproportionality analysis of the U.S. Food & Drug Administration adverse event reporting system database.

STUDY OBJECTIVES: There is no consensus information on infections associated with nonbenzodiazepines. Knowledge about infections related to newly marketed hypnotics (orexin receptor antagonists and melatonin receptor agonists) is scarce. The study aimed to detect infection signals for nonbenzodiazepines, orexin receptor antagonists, and melatonin receptor agonists by analyzing data from the U.S. Food & Drug Administration adverse event reporting system. METHODS: A disproportionality analysis was performed to quantitatively detect infection signals for hypnotics by calculating the reporting odds ratio and the 95% confidence interval. Data registered in the U.S. Food & Drug Administration adverse event reporting system from 2010-2020 were retrieved. RESULTS: A total of 3,092 patients with infection were extracted for the 3 classes of hypnotic drugs. Nonbenzodiazepines were associated with a higher disproportionality of infections (reporting odds ratio: 1.10; 95% confidence interval, 1.06-1.14). The association of infections was not present for melatonin receptor agonists (reporting odds ratio: 0.86; 95% confidence interval, 0.74-1.00) and orexin receptor antagonists (reporting odds ratio: 0.19; 95% confidence interval, 0.15-0.25). Significant reporting associations were identified for nonbenzodiazepines concerning the categories of bone and joint infections, dental and oral soft tissue infections, upper respiratory tract infections, and urinary tract infections. CONCLUSIONS: Nonbenzodiazepines had a positive signal for infections, while orexin receptor antagonists and melatonin receptor agonists had a negative signal. More research needs to be conducted to confirm this relationship. CITATION: Meng L, Huang J, He Q, et al. Hypnotics and infections: disproportionality analysis of the U.S. Food & Drug Administration adverse event reporting system database. J Clin Sleep Med. 2022;18(9):2229-2235.