Systematic Reviews and Meta-analyses of the Procedure-specific Risks of Thrombosis and Bleeding in General Abdominal, Colorectal, Upper Gastrointestinal, and Hepatopancreatobiliary Surgery.

OBJECTIVE: To provide procedure-specific estimates of symptomatic venous thromboembolism (VTE) and major bleeding after abdominal surgery. BACKGROUND: The use of pharmacological thromboprophylaxis represents a trade-off that depends on VTE and bleeding risks that vary between procedures; their magnitude remains uncertain. METHODS: We identified observational studies reporting procedure-specific risks of symptomatic VTE or major bleeding after abdominal surgery, adjusted the reported estimates for thromboprophylaxis and length of follow-up, and estimated cumulative incidence at 4 weeks postsurgery, stratified by VTE risk groups, and rated evidence certainty. RESULTS: After eligibility screening, 285 studies (8,048,635 patients) reporting on 40 general abdominal, 36 colorectal, 15 upper gastrointestinal, and 24 hepatopancreatobiliary surgery procedures proved eligible. Evidence certainty proved generally moderate or low for VTE and low or very low for bleeding requiring reintervention. The risk of VTE varied substantially among procedures: in general abdominal surgery from a median of <0.1% in laparoscopic cholecystectomy to a median of 3.7% in open small bowel resection, in colorectal from 0.3% in minimally invasive sigmoid colectomy to 10.0% in emergency open total proctocolectomy, and in upper gastrointestinal/hepatopancreatobiliary from 0.2% in laparoscopic sleeve gastrectomy to 6.8% in open distal pancreatectomy for cancer. CONCLUSIONS: VTE thromboprophylaxis provides net benefit through VTE reduction with a small increase in bleeding in some procedures (eg, open colectomy and open pancreaticoduodenectomy), whereas the opposite is true in others (eg, laparoscopic cholecystectomy and elective groin hernia repairs). In many procedures, thromboembolism and bleeding risks are similar, and decisions depend on individual risk prediction and values and preferences regarding VTE and bleeding.

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.

Systematic reviews of observational studies of Risk of Thrombosis and Bleeding in General and Gynecologic Surgery (ROTBIGGS): introduction and methodology.

BACKGROUND: Venous thromboembolism (VTE) and bleeding are serious and potentially fatal complications of surgical procedures. Pharmacological thromboprophylaxis decreases the risk of VTE but increases the risk of major post-operative bleeding. The decision to use pharmacologic prophylaxis therefore represents a trade-off that critically depends on the incidence of VTE and bleeding in the absence of prophylaxis. These baseline risks vary widely between procedures, but their magnitude is uncertain. Systematic reviews addressing baseline risks are scarce, needed, and require innovations in methodology. Indeed, systematic summaries of these baseline risk estimates exist neither in general nor gynecologic surgery. We will fill this knowledge gap by performing a series of systematic reviews and meta-analyses of the procedure-specific and patient risk factor stratified risk estimates in general and gynecologic surgeries. METHODS: We will perform comprehensive literature searches for observational studies in general and gynecologic surgery reporting symptomatic VTE or bleeding estimates. Pairs of methodologically trained reviewers will independently assess the studies for eligibility, evaluate the risk of bias by using an instrument developed for this review, and extract data. We will perform meta-analyses and modeling studies to adjust the reported risk estimates for the use of thromboprophylaxis and length of follow up. We will derive the estimates of risk from the median estimates of studies rated at the lowest risk of bias. The primary outcomes are the risk estimates of symptomatic VTE and major bleeding at 4 weeks post-operatively for each procedure stratified by patient risk factors. We will apply the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to rate evidence certainty. DISCUSSION: This series of systematic reviews, modeling studies, and meta-analyses will inform clinicians and patients regarding the trade-off between VTE prevention and bleeding in general and gynecologic surgeries. Our work advances the standards in systematic reviews of surgical complications, including assessment of risk of bias, criteria for arriving at the best estimates of risk (including modeling of the timing of events and dealing with suboptimal data reporting), dealing with subgroups at higher and lower risk of bias, and use of the GRADE approach. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021234119.

Addition of Ezetimibe to statins for patients at high cardiovascular risk: Systematic review of patient-important outcomes.

Ezetimibe is widely used in combination with statins to reduce low-density lipoprotein. We sought to examine the impact of ezetimibe when added to statins on patient-important outcomes. Medline, EMBASE, CINAHL, and CENTRAL were searched through July, 2016. Randomized controlled trials (RCTs) of ezetimibe combined with statins versus statins alone that followed patients for at least 6 months and reported on at least one of all-cause mortality, cardiovascular deaths, non-fatal myocardial infarctions (MI), and non-fatal strokes were included. Pairs of reviewers extracted study data and assessed risk of bias independently and in duplicate. Quality of evidence was assessed using the GRADE approach. We conducted a narrative review with complementary subgroup and sensitivity analyses. IMPROVE-IT study enrolled 93% of all patients enrolled in the 8 included trials. Our analysis of the IMPROVE-IT study results showed that in patients at high risk of cardiovascular events, ezetimibe added to statins was associated with i) a likely reduction in non-fatal MI (17 fewer/1000 treated over 6 years, moderate certainty in evidence); ii) a possible reduction in non-fatal stroke (6 fewer/1000 treated over 6 years, low certainty); iii) no impact on myopathy (moderate certainty); iv) potentially no impact on all-cause mortality and cardiovascular death (both moderate certainty); and v) possibly no impact on cancer (low certainty). Addition of ezetimibe to moderate-dose statins is likely to result in 17 fewer MIs and possibly 6 fewer strokes/1000 treated over 6 years but is unlikely to reduce all-cause mortality or cardiovascular death. Patients who place a high value on a small absolute reduction in MI and are not adverse to use of an additional medication over a long duration may opt for ezetimibe in addition to statin therapy. Our analysis revealed no increased specific harms associated with addition of ezetimibe to statins.