Evidence-based Guideline for Therapeutic Drug Monitoring of Vancomycin: 2020 Update by the Division of Therapeutic Drug Monitoring, Chinese Pharmacological Society.

BACKGROUND: Clinical practice guidelines or recommendations often require timely and regular updating as new evidence emerges, because this can alter the risk-benefit trade-off. The scientific process of developing and updating guidelines accompanied by adequate implementation can improve outcomes. To promote better management of patients receiving vancomycin therapy, we updated the guideline for the therapeutic drug monitoring (TDM) of vancomycin published in 2015. METHODS: Our updated recommendations complied with standards for developing trustworthy guidelines, including timeliness and rigor of the updating process, as well as the use of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. We also followed the methodology handbook published by the National Institute for Health and Clinical Excellence and the Spanish National Health System. RESULTS: We partially updated the 2015 guideline. Apart from adults, the updated guideline also focuses on pediatric patients and neonates requiring intravenous vancomycin therapy. The guideline recommendations involve a broadened range of patients requiring TDM, modified index of TDM (both 24-hour area under the curve and trough concentration), addition regarding the necessity and timing of repeated TDM, and initial dose for specific subpopulations. Overall, 1 recommendation was deleted and 3 recommendations were modified. Eleven new recommendations were added, and no recommendation was made for 2 clinical questions. CONCLUSIONS: We updated an evidence-based guideline regarding the TDM of vancomycin using a rigorous and multidisciplinary approach. The updated guideline provides more comprehensive recommendations to inform rational and optimized vancomycin use and is thus of greater applicability.

Efficacy and safety of convalescent plasma for severe COVID-19 based on evidence in other severe respiratory viral infections: a systematic review and meta-analysis.

BACKGROUND: The safety and efficacy of convalescent plasma in severe coronavirus disease 2019 (COVID-19) remain uncertain. To support a guideline on COVID-19 management, we conducted a systematic review and meta-analysis of convalescent plasma in COVID-19 and other severe respiratory viral infections. METHODS: In March 2020, we searched international and Chinese biomedical literature databases, clinical trial registries and prepublication sources for randomized controlled trials (RCTs) and nonrandomized studies comparing patients receiving and not receiving convalescent plasma. We included patients with acute coronavirus, influenza and Ebola virus infections. We conducted a meta-analysis using random-effects models and assessed the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. RESULTS: Of 1099 unique records, 6 studies were eligible, and none of these included patients with COVID-19. One nonrandomized study (n = 40) on convalescent plasma in severe acute respiratory syndrome coronavirus (SARS-CoV) provided uninformative results regarding mortality (relative risk [RR] 0.10, 95% confidence interval [CI] CI 0.01 to 1.70). Pooled estimates from 4 RCTs on influenza (n = 572) showed no convincing effects on deaths (4 RCTs, RR 0.94, 95% CI 0.49 to 1.81), complete recovery (2 RCTs, odds ratio 1.04, 95% CI 0.69 to 1.64) or length of stay (3 RCTs, mean difference -1.62, 95% CI -3.82 to 0.58, d). The quality of evidence was very low for all efficacy outcomes. Convalescent plasma caused few or no serious adverse events in influenza RCTs (RR 0.85, 95% CI 0.56 to 1.29, low-quality evidence). INTERPRETATION: Studies of non-COVID-19 severe respiratory viral infections provide indirect, very low-quality evidence that raises the possibility that convalescent plasma has minimal or no benefit in the treatment of COVID-19 and low-quality evidence that it does not cause serious adverse events.

Efficacy and safety of corticosteroids in COVID-19 based on evidence for COVID-19, other coronavirus infections, influenza, community-acquired pneumonia and acute respiratory distress syndrome: a systematic review and meta-analysis.

BACKGROUND: Very little direct evidence exists on use of corticosteroids in patients with coronavirus disease 2019 (COVID-19). Indirect evidence from related conditions must therefore inform inferences regarding benefits and harms. To support a guideline for managing COVID-19, we conducted systematic reviews examining the impact of corticosteroids in COVID-19 and related severe acute respiratory illnesses. METHODS: We searched standard international and Chinese biomedical literature databases and prepublication sources for randomized controlled trials (RCTs) and observational studies comparing corticosteroids versus no corticosteroids in patients with COVID-19, severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS). For acute respiratory distress syndrome (ARDS), influenza and community-acquired pneumonia (CAP), we updated the most recent rigorous systematic review. We conducted random-effects meta-analyses to pool relative risks and then used baseline risk in patients with COVID-19 to generate absolute effects. RESULTS: In ARDS, according to 1 small cohort study in patients with COVID-19 and 7 RCTs in non-COVID-19 populations (risk ratio [RR] 0.72, 95% confidence interval [CI] 0.55 to 0.93, mean difference 17.3% fewer; low-quality evidence), corticosteroids may reduce mortality. In patients with severe COVID-19 but without ARDS, direct evidence from 2 observational studies provided very low-quality evidence of an increase in mortality with corticosteroids (hazard ratio [HR] 2.30, 95% CI 1.00 to 5.29, mean difference 11.9% more), as did observational data from influenza studies. Observational data from SARS and MERS studies provided very low-quality evidence of a small or no reduction in mortality. Randomized controlled trials in CAP suggest that corticosteroids may reduce mortality (RR 0.70, 95% CI 0.50 to 0.98, 3.1% lower; very low-quality evidence), and may increase hyperglycemia. INTERPRETATION: Corticosteroids may reduce mortality for patients with COVID-19 and ARDS. For patients with severe COVID-19 but without ARDS, evidence regarding benefit from different bodies of evidence is inconsistent and of very low quality.

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.

Antidepressant Use and Risk of Venous Thromboembolism: A Systematic Review and Meta-Analysis.

PURPOSE: Studies provided conflicting results on whether antidepressant use increased the risk of venous thromboembolism (VTE). Our aim was to examine the association between antidepressant use and the risk of VTE. METHODS: Pubmed, Embase, and the Cochrane Library were searched up to March 13, 2018. Case-control studies and cohort studies that examined the association between antidepressant use and the risk of VTE, deep vein thrombosis or pulmonary embolism were included. Several subgroup analyses and sensitivity analyses were conducted. GRADE approach was used to assess the quality of evidence. RESULTS: Nine studies (six case-control studies and three cohort studies) were included. Overall, antidepressant use may be associated with an increased risk of VTE (OR 1.27, 95% CI 1.09 to 1.49); however, no association was observed in studies with low risk of bias (OR 1.27, 95% CI 0.84 to 1.92). No association between selective serotonin reuptake inhibitor use and VTE risk was detected in the overall analysis (OR 1.10, 95% CI 0.90 to 1.34) and in subgroup analysis of studies with low risk of bias. Tricyclic antidepressant may be associated with an increased VTE risk (OR 1.26, 95% CI 1.02 to 1.57), and the quality of evidence was rated as very low by GRADE approach; however, no association was observed when we only included studies with low risk of bias. CONCLUSIONS: There was no association between selective serotonin reuptake inhibitor use and VTE risk. Tricyclic antidepressant may be associated with an increased VTE risk, but the quality of evidence was very low.

Effects of Canagliflozin on Fatty Liver Indexes in Patients with Type 2 Diabetes: A Meta-analysis of Randomized Controlled Trials.

PURPOSE: Non-alcoholic fatty liver disease (NAFLD) affects about 75% of patients with type 2 diabetes mellitus (T2DM). We conducted a meta-analysis to determine the effect of canagliflozin on fatty liver indexes in T2DM patients. METHODS: A literature search of PubMed, Embase and Cochrane was conducted up to March 30, 2017. The liver function test and lipid profile were extracted from randomized controlled trials (RCTs) to evaluate the effect of canagliflozin on fatty liver. Weighted mean differences (WMDs) or relative risks and 95% confidence intervals (CIs) were computed by using either fixed or random-effects models. Sensitivity analysis and publication bias were evaluated. RESULTS: Our results showed that canagliflozin decreased serum concentrations of  alanine amino transferase (WMD: -11.68 [95% CI: -18.95, -10.95]; P<0.001), aspartate amino transferase (WMD: -7.50 [95% CI: -10.61, -4.38]; P<0.001), gamma-glutamyl transferase (WMD: -15.17 [95% CI: -17.73, -12.61]; P<0.001), triglycerides (WMD: -0.10 [95% CI: -0.15, -0.05]; P<0.001) but increased low-density lipoprotein cholesterol (WMD: 0.1 [95% CI: 0.06, 0.13]; P<0.001), high-density lipoprotein cholesterol (WMD: 0.06 [95% CI: 0.05, 0.07]; P<0.001) at week 26 or 52. CONCLUSIONS: Our results indicated that canagliflozin may have a protective effect on fatty liver in T2DM patients. The limitation was that the liver biopsy was hard to obtain in published studies. More RCTs specified on NAFLD are needed to get further information. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

Effectiveness of Pharmacist-led Anticoagulation Management on Clinical Outcomes: A Systematic Review and Meta-Analysis.

OBJECTIVES: We performed this systematic review and meta-analysis to confirm whether patients benefit more from pharmacist-led anticoagulation management than other models. METHODS: We searched PubMed, Embase, Cochrane Library and reference lists of yielded results conducted up to April 25, 2017. RCTs and observational cohort studies and case-control studies which compared the percentage of time within the target therapeutic range (TTR), the percentage of time within the expanded therapeutic range (TER), haemorrhage events, thrombosis events, mortality, patient satisfaction and/or medicine cost saving of pharmacist-led anticoagulation management with other models, and species were limited to humans. Two investigators evaluated methodology and extracted data from included studies independently. Data analysis were performed by STATA 12.0 software and quality of evidence assessment was performed by GRADEprofiler software. RESULTS: 8 RCTs and 9 observational cohort studies with 9919 patients were included eventually with high quality and no publication bias. In RCTs pooled results, TTR (p=0.548 moderate-quality), TER (p=0.285, moderate-quality), total haemorrhage events (p=0.140, low-quality), minor haemorrhage events (p=0.162, low-quality), major haemorrhage events (p=0.237, low-quality), thrombosis events (p=0.615, low-quality) and mortality (p=0.876, low-quality) was not significant between two groups. In observational studies pooled results, TTR (p=0.000, low-quality) was significant higher in pharmacist-led management group and the risk of total haemorrhage events (p=0.000, moderate-quality), minor haemorrhage events (p=0.000, moderate-quality) and thrombosis events (p=0.000, moderate-quality) were significant lower in pharmacist-led management group. Patient satisfaction and medicine cost saving were descriptively reviewed. CONCLUSIONS: According to the grading of evidence, we concluded that the risk of total haemorrhage events, minor haemorrhage events and thrombosis events significantly decreased in pharmacist-led anticoagulation management group compared with other management models and no significant difference in TTR, TER, major haemorrhage events and mortality between two groups. Longer follow-up period RCT studies with large sample size should be done in the future to confirm effectiveness of pharmacist-led anticoagulation management model. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

Therapeutic drug monitoring of vancomycin: a guideline of the Division of Therapeutic Drug Monitoring, Chinese Pharmacological Society.

BACKGROUND: Guideline development should be based on the quality of evidence, balance of benefits and harms, economic evaluation and patients' views and preferences. Therefore, these factors were considered in the development of a new guideline for therapeutic drug monitoring (TDM) of vancomycin. OBJECTIVES: To develop an evidence-based guideline for vancomycin TDM and to promote standardized vancomycin TDM in clinical practice in China. METHODS: We referred to the WHO Handbook for Guideline Development and used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to rate the quality of evidence and grade the strength of recommendations, according to economic evaluation and patients' views and preferences. We used the GRADE Grid method to formulate the recommendations. RESULTS: The guideline presents recommendations about who should receive vancomycin TDM, how to monitor vancomycin efficacy and renal safety, therapeutic trough concentrations, time to start initial vancomycin TDM, loading dose and how to administer and adjust the vancomycin dose. CONCLUSIONS: We developed an evidence-based guideline for vancomycin TDM, which provides recommendations for clinicians and pharmacists to conduct vancomycin TDM in China.

Efficacité et innocuité du plasma de convalescent en cas de forme grave de COVID-19, extrapolée de données relatives à d'autres formes graves d'infections respiratoires virales : revue systématique et méta-analyse.

CONTEXTE: On ne connaît pas encore avec certitude l'innocuité et l'efficacité du plasma de convalescent comme traitement de la forme grave de la maladie à coronavirus 2019 (COVID-2019). Afin d'appuyer la conception de lignes directrices sur la prise en charge de la COVID-19, nous avons effectué une revue systématique et une méta-analyse sur l'utilisation du plasma de convalescent pour le traitement de cette maladie et d'autres formes graves d'infections respiratoires virales. MÉTHODES: En mars 2020, nous avons effectué des recherches dans des bases de données biomédicales internationales et chinoises, des registres d'essais cliniques et des sources prépubliées afin de recenser des essais randomisés et contrôlés (ERC) et des études non randomisées comparant les issues de patients ayant reçu du plasma de convalescent à celles de patients n'en ayant pas reçu. Ont été inclus les patients ayant une infection aiguë attribuable à un coronavirus, au virus de l'influenza ou au virus Ebola. Nous avons également réalisé une méta-analyse à l'aide d'un modèle à effets aléatoires et évalué la qualité des données probantes au moyen de l'approche GRADE (Grading of Recommendations Assessment, Development, and Evaluation). RÉSULTATS: Sur les 1099 études uniques initialement repérées, 6 étaient admissibles, et aucune d'entre elles ne portait sur des patients atteints de la COVID-19. Une étude non randomisée (n = 40) sur l'administration de plasma de convalescent à des patients atteints du coronavirus du syndrome respiratoire aigu sévère (SRAS-CoV) a fourni des données peu concluantes sur le taux de mortalité (risque relatif [RR] 0,10; intervalle de confiance [IC] de 95 % 0,01 à 1,70). Des estimations regroupées provenant de 4 ERC sur l'influenza (n = 572) n'ont pas montré d'effet manifeste sur le taux de mortalité (4 ERC; RR 0,94; IC de 95 % 0,49 à 1,81), le rétablissement complet (2 ERC; rapports de cotes [RC] 1,04; IC de 95 % 0,69 à 1,64) et la durée d'hospitalisation (3 ERC; différence moyenne [DM] −1,62; IC de 95 % −3,82 à 0,58 jours). La qualité des données était très faible pour tous les paramètres relatifs à l'efficacité. Dans les ERC sur l'influenza, aucun ou peu d'événements indésirables graves ont été associés au plasma de convalescent (RR 0,85; IC de 95 % 0,56 à 1,29; données de faible qualité). INTERPRÉTATION: Les études portant sur des formes graves d'infections respiratoires virales autres que la COVID-19 ont fourni des données indirectes de très faible qualité semblant indiquer que le plasma de convalescent n'offre aucun bénéfice ou offre des bénéfices minimes pour le traitement de la COVID-19, de même que des données de faible qualité montrant qu'il n'entraîne pas d'événements indésirables graves.

Efficacité et innocuité des corticostéroïdes dans le traitement de la COVID-19 selon des données pour la COVID-19, d'autres infections aux coronavirus, l'influenza, la pneumonie extrahospitalière et le syndrome de détresse respiratoire aiguë : revue systématique et méta-analyse.

CONTEXTE: Il existe très peu de données directes sur l'administration de corticostéroïdes aux patients atteints de la maladie à coronavirus 2019 (COVID-19). Les données indirectes sur des maladies associées devront donc guider les conclusions quant aux bénéfices et aux préjudices associés à cette pratique. Dans le but d'appuyer la rédaction d'une ligne directrice sur la prise en charge de la COVID-19, nous avons réalisé des revues systématiques sur les effets des corticostéroïdes dans le traitement de la COVID-19 et de maladies respiratoires aiguës sévères associées. MÉTHODES: Dans des bases de données biomédicales chinoises et internationales et des sources de prépublications, nous avons cherché les essais randomisés et contrôlés (ERC) et les études d'observation comparant des patients atteints de la COVID-19, du syndrome respiratoire aigu sévère (SRAS) ou du syndrome respiratoire du Moyen-Orient (SRMO) ayant reçu des corticostéroïdes à des patients semblables n'ayant pas reçu ce type de médicaments. Pour le syndrome de détresse respiratoire aiguë (SDRA), l'influenza et la pneumonie extrahospitalière (PEH), nous avons mis à jour les revues systématiques rigoureuses les plus récentes. Nous avons réalisé des méta-analyses à effets aléatoires pour cerner les risques relatifs, puis nous avons utilisé le risque de référence des patients atteints de la COVID-19 pour calculer les effets absolus. RÉSULTATS: Pour le SDRA, selon 1 petite étude de cohorte sur des patients atteints de la COVID-19 et 7 ERC sur des patients atteints d'une autre maladie (risque relatif : 0,72, intervalle de confiance [IC] de 95 % 0,55­0,93, différence entre les moyennes [DM] 17,3 % plus faible, données de faible qualité), les corticostéroïdes pourraient réduire le risque de mortalité. Chez les patients atteints d'une forme grave de COVID-19 sans SDRA, 2 études d'observation ont généré des données directes de très faible qualité montrant une augmentation du risque de mortalité avec l'administration de corticostéroïdes (rapport de risques 2,30, IC de 95 % 1,00­5,29, DM 11,9 % plus élevé). C'est aussi le cas de données observationnelles sur l'influenza. Des données observationnelles de très faible qualité sur le SRAS et le SRMO montrent peu ou pas de réduction dans le risque de mortalité. Des essais randomisés et contrôlés sur la PEH suggèrent que les corticostéroïdes pourraient réduire le risque de mortalité (risque relatif 0,70, IC de 95 % 0,50­0,98, DM 3,1 % plus faible, données de très faible qualité), et augmenter le risque d'hyperglycémie. INTERPRÉTATION: Les corticostéroïdes pourraient réduire le risque de mortalité pour les patients atteints de la COVID-19 avec SDRA. Pour les patients atteints d'une forme grave de COVID-19 sans SDRA, les données sur les bénéfices provenant de différentes sources sont incohérentes et de très faible qualité.

Efficacité et innocuité des agents antiviraux contre le SRAS-CoV-2, selon des données d'études sur la COVID-19 et d'autres infections virales aiguës : revue systématique et méta-analyse.

CONTEXTE: On donne de façon empirique des agents antiviraux à certains patients atteints de la maladie à coronavirus 2019 (COVID-19). Dans le but d'appuyer la rédaction de lignes directrices sur la prise en charge de la COVID-19, nous avons réalisé une revue systématique des bénéfices et des préjudices associés à 7 traitements antiviraux contre cette infection. MÉTHODES: Nous avons effectué des recherches dans MEDLINE, Embase, le Cochrane Central Register of Controlled Trials (CENTRAL), PubMed et 3 bases de données chinoises (CNKI, Wanfang Data et SinoMed) jusqu'au 19 avril 2020, dans medRxiv et ChinaXiv jusqu'au 27 avril 2020, ainsi que dans Chongqing VIP jusqu'au 30 avril 2020. Nous avons sélectionné des études sur la ribavirine, la chloroquine, l'hydroxychloroquine, l'umifénovir (Arbidol), le favipiravir, l'interféron et le lopinavir/ritonavir. Lorsqu'il n'y avait pas de données directes d'études sur la COVID-19, nous avons retenu des données indirectes d'études sur le syndrome respiratoire aigu sévère (SRAS) et le syndrome respiratoire du Moyen-Orient (SRMO) pour l'analyse de l'efficacité, et d'études sur d'autres infections respiratoires virales aiguës pour l'analyse de l'innocuité. RÉSULTATS: Le taux de décès chez les patients atteints d'une forme sans signe clinique de gravité de COVID-19 était extrêmement bas, ce qui ne permet pas de conclure à un effet important sur la mortalité. Nous n'avons obtenu que des données de très faible qualité indiquant que la plupart des traitements avaient peu ou pas de bénéfices sur les paramètres à l'étude, quelle que soit la gravité de la COVID-19. Seule exception : le traitement au lopinavir/ritonavir, pour lequel nous avons obtenu des données de faible qualité faisant état d'une réduction de la durée du séjour en unité de soins intensifs (différence des risques [DR] 5 jours de moins, intervalle de confiance [IC] de 95 % 0 à 9 jours) et de la durée d'hospitalisation (DR 1 jour de moins, IC de 95 % 0 à 2 jours). En ce qui concerne l'innocuité, les données étaient de faible ou de très faible qualité, sauf pour le traitement au lopinavir/ritonavir, où des données de qualité moyenne laissaient supposer une augmentation probable de la diarrhée, des nausées et des vomissements. INTERPRÉTATION: À l'heure actuelle, rien ne prouve de façon convaincante que les traitements antiviraux apportent des bénéfices importants dans la lutte contre la COVID-19, bien que les données propres à chaque traitement n'excluent pas cette possibilité. D'autres essais randomisés et contrôlés menés auprès de patients atteints de la COVID-19 sont nécessaires avant de pouvoir recourir à ces traitements en toute confiance.

Treatment of critical bleeding events in patients with immune thrombocytopenia: a protocol for a systematic review and meta-analysis.

BACKGROUND: Critical bleeding events in adults and children with ITP are medical emergencies; however, evidence-based treatment protocols are lacking. Due to the severe thrombocytopenia, (typically platelet count less than 20 × 109/L), a critical bleed portends a high risk of death or disability. We plan to perform a systematic review and meta-analysis of treatments for critical bleeding in patients with ITP that will inform evidence-based recommendations. METHODS: Literature searches will be conducted in four electronic databases: Ovid MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and PubMed. Eligible studies will be randomized controlled trials or observational studies that enrolled patients with ITP describing one or more interventions for the management of critical bleeding. Title and abstract screening, full-text screening, data extraction, and risk of bias evaluation will be conducted independently and in duplicate using Covidence and Excel. Outcomes will be pooled for meta-analysis where appropriate or summarized descriptively. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology will be used to evaluate the certainty of the evidence. Primary outcomes of interest will include frequency of critical bleeds, mortality and bleeding-related mortality, bleeding resolution, platelet count, and disability. DISCUSSION: Evidence-based treatments for critical bleeding in patients with ITP are needed to improve patient outcomes and standardize care in the emergency setting. SYSTEMATIC REVIEW REGISTRATION: CRD42020161206.

Proton-Pump Inhibitors to Prevent Gastrointestinal Bleeding - An Updated Meta-Analysis.

BACKGROUND: The goal of this systematic review was to examine the efficacy and safety of proton-pump inhibitors for stress ulcer prophylaxis in critically ill patients. METHODS: We included randomized trials comparing proton-pump inhibitors versus placebo or no prophylaxis in critically ill adults, performed meta-analyses, and assessed certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluations approach. To explore the effect of proton-pump inhibitors on mortality based on disease severity, a subgroup analysis was conducted combining within-trial subgroup data from the two largest trials and assessed credibility using the Instrument for Assessing the Credibility of Effect Modification Analyses. RESULTS: Twelve trials that enrolled 9533 patients were included. Proton-pump inhibitors were associated with a reduced incidence of clinically important upper gastrointestinal bleeding (relative risk [RR], 0.51 [95% confidence interval (CI), 0.34 to 0.76]; high certainty evidence). Proton-pump inhibitors may have little or no effect on mortality (RR, 0.99 [95% CI, 0.93 to 1.05]; low certainty). Within-trial subgroup analysis with intermediate credibility suggested that the effect of proton-pump inhibitors on mortality may differ based on disease severity. Subgroup results raise the possibility that proton-pump inhibitors may decrease 90-day mortality in less severely ill patients (RR, 0.89; 95% CI, 0.80 to 0.98) and may increase mortality in more severely ill patients (RR, 1.08; 95% CI, 0.96 to 1.20]. Proton-pump inhibitors may have no effect on pneumonia and little or no effect on Clostridioides difficile infection (low certainty). CONCLUSIONS: High certainty evidence supports the association of proton-pump inhibitors with decreased upper gastrointestinal bleeding. Proton-pump inhibitors may have little or no effect on mortality, although a decrease in mortality in less severely ill patients and an increase in mortality in more severely ill patients remain possible. (PROSPERO number CRD42023461695.).

Analysis of volatile organic compounds and potential odour compounds in food contact paperboard using headspace two-dimensional GC-QTOF-MS.

The objective was to establish a robust and reliable approach for the characterisation of volatile organic compounds (VOCs) present in food contact paperboard. This was achieved through the utilisation of headspace solid-phase microextraction in tandem with comprehensive two-dimensional (2D) gas chromatography (GC) and quadrupole time-of-flight mass spectrometry (HS-SPME-GC × GC-QTOF-MS). The experimental parameters were optimised, involving the use of a DVB/C-WR/PDMS fibre at a temperature of 80 °C for a duration of 30 min. A total of 344 VOCs comprising aldehydes, ketones, alcohols, ethers, esters, alkanes and aromatic compounds, were tentatively identified in the samples. Twelve compounds believed to be from biogenic sources had a high odour impact making them major contributors to potential taint from the paperboard samples. Significant attention should be devoted to five compounds namely, 2-methylnaphthalene, 2-pentyl-furan, furfural, 1-octen-3-one and 1-octen-3-ol due to their potential adverse impact on the organoleptic qualities of packaged food items and their potential toxicity.Abbreviations: C-WR: carbon wide range; DVB: divinylbenzene; GC-MS: gas chromatography - mass spectrometry; GCxGC-QTOF-MS: comprehensive two-dimensional gas chromatography coupled to quadrupole-time-of-flight - mass spectrometry; HS-SPME: headspace - solid phase microextraction; LOD: limit of detection; LOQ: limit of quantification; OAV: odor activity values; PDMS: polydimethylsiloxane; RI: retention index; TTC: threshold of toxicological concern; VOC: volatile organic compound.

Authentication of recycled and virgin polyethylene terephthalate based on UPLC-Q-TOF-MS using non-volatile organic compounds and chemometrics.

Plastic packaging waste, such as polyethylene terephthalate (PET) has increased significantly in recent decades, arousing a considerable and serious public concern regarding the environment, economy, and policy. Plastic recycling is a useful tool to mitigate this issue. Here, a feasible study was performed to investigate the potential of a novel method for identifying virgin and recycled PET. Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was combined with various chemometrics, as a simple and reliable method that achieved a high discrimination rate for 105 batches of virgin PET (v-PET) and recycled PET (r-PET) based on 202 non-volatile organic compounds (NVOCs). Making use of orthogonal partial least-squares discrimination analysis (OPLS-DA) together with non-parametric tests, 26 marker compounds (i.e. 12 intentionally added substances (IAS) and 14 non-intentionally added substances (NIAS) as well as 31 marker compounds (i.e. 11 IAS and 20 NIAS) obtained from positive and combination of positive and negative ionization modes of UPLC-Q-TOF-MS, respectively, were successfully identified. Moreover, 100% accuracy was obtained using a decision tree (DT). Cross-discrimination based on misclassified samples using various chemometrics allowed the prediction accuracy to be improved and to identify a large sample set, thus greatly enhancing the application scope of this method. The possible origins of these detected compounds can be the plastic itself, as well as contamination from food, medicine, pesticides, industry-related substances, and degradation and polymerization products. As many of these compounds are toxic, especially those pesticide related, this indicates an urgent requirement for closed loop recycling. Overall, this analytical method provides a quick, accurate, and robust way to distinguish virgin from recycled PET and thus addresses the issue of potential virgin PET adulteration thereby detecting fraud in the area of PET recycling.

Cost-effectiveness of endovascular thrombectomy with alteplase versus endovascular thrombectomy alone for acute ischemic stroke secondary to large vessel occlusion.

BACKGROUND: Recent randomized trials have suggested that endovascular thrombectomy (EVT) alone may provide similar functional outcomes as the current standard of care, EVT combined with intravenous alteplase treatment, for acute ischemic stroke secondary to large vessel occlusion. We conducted an economic evaluation of these 2 therapeutic options. METHODS: We constructed a decision analytic model with a hypothetical cohort of 1000 patients to assess the cost-effectiveness of EVT with intravenous alteplase treatment versus EVT alone for acute ischemic stroke secondary to large vessel occlusion from both the societal and public health care payer perspectives. We used studies and data published in 2009-2021 for model inputs, and acquired cost data for Canada and China, representing high- and middle-income countries, respectively. We calculated incremental cost-effectiveness ratios (ICERs) using a lifetime horizon and accounted for uncertainty using 1-way and probabilistic sensitivity analyses. All costs are reported in 2021 Canadian dollars. RESULTS: In Canada, the difference in quality-adjusted life-years (QALYs) gained between EVT with alteplase and EVT alone was 0.10 from both the societal and health care payer perspectives. The difference in cost was $2847 from a societal perspective and $2767 from the payer perspective. In China, the difference in QALYs gained was 0.07 from both perspectives, and the difference in cost was $1550 from the societal perspective and $1607 from the payer perspective. One-way sensitivity analyses showed that the distributions of modified Rankin Scale scores at 90 days after stroke were the most influential factor on ICERs. For Canada, compared to EVT alone, the probability that EVT with alteplase would be cost-effective at a willingness-to-pay threshold of $50 000 per QALY gained was 58.7% from a societal perspective and 58.4% from a payer perspective. The corresponding values for at a willingness-to-pay threshold of $47 185 (3 times the Chinese gross domestic product per capita in 2021) were 65.2% and 67.4%. INTERPRETATION: For patients with acute ischemic stroke due to large vessel occlusion eligible for immediate treatment with both EVT alone and EVT with intravenous alteplase treatment, it is uncertain whether EVT with alteplase is cost-effective compared to EVT alone in Canada and China.

Case report: Olaparib as an experimental therapy in a BRCA2-mutated patient with metastatic ovarian adenocarcinoma that originated from liver cancer.

Secondary ovarian tumor [secondary tumor of the ovary (STO)] is not a frequent disease. To date, there is still a lack of standard treatment for STO due to the relative heterogeneity. Liver cancer metastasis to the ovary is extremely rare, with only 17 living cases having been reported so far, making it impossible to launch large-scale prospective studies and formulate the standard intervention for patients. We herein report a rare case of STO with liver primary cancer metastasis to the ovary and omentum in a 66-year-old woman. The patient underwent debulking surgery with the removal of the uterus, bilateral fallopian tubes, bilateral ovaries, appendix, and a large part of the omentum majus. Next-generation sequencing was conducted after the operation, identifying BRCA2 mutation. Because strongly refusing chemotherapy, she received olaparib as an experimental therapy. After the administration of surgery and olaparib, the serum value of cancer antigen 125 (CA125) and alpha fetoprotein (AFP) decreased dramatically and basically remained within the normal range. So far, she has achieved nearly 2-year survival and lives a relatively normal life with good quality.

Efficacy and Safety of Pharmacoprophylaxis for Venous Thromboembolism in Patients Undergoing Bariatric Surgery: a Systematic Review and Meta-analysis.

This study aims to assess the efficacy and safety of pharmacoprophylaxis regimens for venous thromboembolism (VTE) in patients undergoing bariatric surgery. A total of 15 studies were included. Low molecular-weight heparins (LMWH) and fondaparinux may be equally effective in reducing VTE risk (OR 1.02, 95% confidence interval [CI] 0.14-7.39). Pooled estimate suggested uncertain effects of augmented LMWH dosing on VTE prophylaxis compared with standard dosing (OR 0.57, 95% CI 0.07-4.39), but may increase major bleeding (OR 3.03, 95% CI 0.38-23.96). Very low-quality evidence showed an inconclusive effect of extended prophylaxis on VTE (OR 0.54, 95% CI 0.15-1.90) and major bleeding (OR 1.24, 95% CI 0.92-1.68) compared with restricted prophylaxis. Standard LMWH dosing may be effective and safe. Current evidences are insufficient to support extended prophylaxis.