Background Coronavirus disease 2019 (COVID-19) is associated with a high mortality rate, especially in patients with severe illness. We conducted a systematic review and meta-analysis to assess the potential predictors of mortality in patients with COVID-19. Methods PubMed, EMBASE, the Cochrane Library, and three electronic Chinese databases were searched from December 1, 2019 to April 29, 2020. Eligible studies reporting potential predictors of mortality in patients with COVID-19 were identified. Unadjusted prognostic effect estimates were pooled using the random-effects model if data from at least two studies were available. Adjusted prognostic effect estimates were presented by qualitative analysis. Results Thirty-six observational studies were identified, of which 27 were included in the meta-analysis. A total of 106 potential risk factors were tested, and the following important predictors were associated with mortality: advanced age, male sex, current smoking status, preexisting comorbidities (especially chronic kidney, respiratory, and cardio-cerebrovascular diseases), symptoms of dyspnea, complications during hospitalization, corticosteroid therapy and a severe condition. Additionally, a series of abnormal laboratory biomarkers of hematologic parameters, hepatorenal function, inflammation, coagulation, and cardiovascular injury were also associated with fatal outcome. Conclusion We identified predictors of mortality in patients with COVID-19. These findings could help healthcare providers take appropriate measures and improve clinical outcomes in such patients.

Background: Coronavirus disease 2019 (COVID-19) is associated with a high mortality rate, especially in patients with severe illness. We conducted a systematic review and meta-analysis to assess the potential predictors of mortality in patients with COVID-19.Methods: PubMed, EMBASE, the Cochrane Library, and three electronic Chinese databases were searched from December 1, 2019, to April 29, 2020. Eligible studies reporting potential predictors of mortality in patients with COVID-19 were identified. Unadjusted prognostic effect estimates were pooled using the random-effects model if data from at least two studies were available. Adjusted prognostic effect estimates were presented by qualitative analysis.Results: Thirty-six observational studies were identified, of which 27 were included in the meta-analysis. A total of 106 potential risk factors were tested and the following important predictors were associated with mortality: advanced age, male sex, current smoking status, preexisting comorbidities (especially chronic kidney, respiratory, and cardio-cerebrovascular diseases), symptoms of dyspnea, complications during hospitalization, corticosteroid use and a severe condition. Additionally, a series of abnormal laboratory biomarkers of hematologic parameters, hepatorenal function, inflammation, coagulation, and cardiovascular injury were also associated with fatal outcome.Conclusion: We identified predictors of mortality in patients with COVID-19. These findings could help healthcare providers take appropriate measures and improve clinical outcomes in such patients.

Numerous population pharmacokinetic studies on voriconazole have been conducted in recent years. This review aimed to comprehensively summarize the population pharmacokinetic models for voriconazole and to determine which covariates have been identified and which remain to be explored. We searched the PubMed and EMBASE databases from inception to March 2018 for population pharmacokinetic analyses of voriconazole using the nonlinear mixed-effect method. A total of 16 studies were included in this review, of which 11 models were described in adult populations, four were described in pediatric populations, and the remaining study included both adult and pediatric populations. The absorption profiles of voriconazole in both adult and pediatric studies were best described as first-order absorption models. The typical distribution volumes were similar in adult and pediatric patients, but the estimated clearances in pediatric patients were significantly higher than those in adult patients. The most commonly identified covariates were body weight, the cytochrome P450 2C19 genotype, liver function, and concomitant medications. Only one study evaluated the model using an external method. Further population pharmacokinetic studies on pediatric patients aged younger than 2 years are warranted. Furthermore, new or controversial potential covariates, such as inflammation, the cytochrome P450 3A4 genotype, concomitant medications (particularly various types and dosages of proton pump inhibitors and glucocorticoids), and various measures of body weight, should be tested because the unexplained variability remains relatively high. In addition, previously published models should be externally evaluated, and the predictive performance of the various models should be compared.

BackgroundRecently, using the patient’s genotype to guide warfarin dosing has gained interest; however, whether pharmacogenetics-based dosing (PD) improves clinical outcomes compared to conventional dosing (CD) remains unclear. Thus, we performed a meta-analysis to evaluate these two strategies.MethodsThe PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Chinese VIP and Chinese Wan-fang databases were searched. The Cochrane Collaboration’s tool was used to assess the risk of bias in randomized controlled trials (RCTs). The primary outcome was time within the therapeutic range (TTR); the secondary end points were the time to maintenance dose and time to first therapeutic international normalized ratio (INR), an INR greater than 4, adverse events, major bleeding, thromboembolism and death from any cause.ResultsA total of 11 trials involving 2,678 patients were included in our meta-analysis. The results showed that PD did not improve the TTR compared to CD, although PD significantly shortened the time to maintenance dose (MD = -8.80; 95% CI: -11.99 to -5.60; P<0.00001) and the time to first therapeutic INR (MD = -2.80; 95% CI: -3.45 to -2.15; P<0.00001). Additionally, PD significantly reduced the risk of adverse events (RR = 0.86; 95% CI: 0.75 to 0.99; P = 0.03) and major bleeding (RR = 0.36; 95% CI: 0.15 to 0.89, P = 0.03), although it did not reduce the percentage of INR greater than 4, the risk of thromboembolic events and death from any cause. Subgroup analysis showed that PD resulted in a better improvement in the endpoints of TTR and over-anticoagulation at a fixed initial dosage rather than a non-fixed initial dosage.ConclusionsThe use of genotype testing in the management of warfarin anticoagulation was associated with significant improvements in INR-related and clinical outcomes. Thus, genotype-based regimens can be considered a reliable and accurate method to determine warfarin dosing and may be preferred over fixed-dose regimens.Trial Registration PROSPERODatabase registration: CRD42015024127.

BackgroundAntistaphylococcal penicillins (ASPs) and cefazolin have become the most frequent choices for the treatment of methicillin-susceptible Staphylococcus aureus (MSSA) infections. However, the best therapeutic agent to treat MSSA bacteremia remains to be established.MethodsWe conducted a systematic review and meta-analysis to evaluate the efficacy and safety of these two regimens for the treatment of MSSA bacteremia. PubMed, EMBASE and the Cochrane Library from inception to February 2018 were searched. The primary outcome was mortality. The secondary outcomes included treatment failure, recurrence of bacteremia, adverse effects (AEs) and discontinuation due to AEs. Data were extracted and pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated.ResultsA total of ten observational studies met the inclusion criteria. The results indicate that compared to ASPs, cefazolin was associated with significant reduction in mortality (OR, 0.69; 95% CI, 0.58 to 0.82; I2 = 3.4%) and clinical failure (OR, 0.56; 95% CI, 0.37 to 0.85; I2 = 44.9%) without increasing the recurrence of bacteremia (OR, 1.12; 95% CI, 0.94 to 1.34; I2 = 0%). There were no significant differences for the risk of anaphylaxis (OR, 0.91; 95% CI, 0.36 to 2.99; I2 = 0%) or hematotoxicity (OR, 0.56; 95% CI, 0.17 to 1.88; I2 = 0%). However, nephrotoxicity (OR, 0.36; 95% CI, 0.16 to 0.81; I2 = 0%) and hepatotoxicity (OR, 0.12; 95% CI, 0.04 to 0.41; I2 = 0%) were significantly lower in the cefazolin group. Moreover, cefazolin was associated with lower probability of discontinuation due to AEs compared with the ASPs (OR, 0.24; 95% CI, 0.12 to 0.48; I2 = 18%).ConclusionThe results of present study favor the application of cefazolin and should be regarded as important evidence to help make clinical decisions in choosing a treatment option for treating MSSA bacteremia.Electronic supplementary materialThe online version of this article (10.1186/s12879-018-3418-9) contains supplementary material, which is available to authorized users.

Background An increasing number of cases of invasive pulmonary aspergillosis (IPA) complicating influenza have been described. We performed a meta‐analysis to estimate the incidence, risk factors and outcomes of IPA in patients with influenza. Methods A systematic search was conducted in the PubMed, EMBASE and Cochrane Library databases from their inception to 31 August 2021 for eligible studies. Data on the incidence and risk factors of and mortality due to IPA in influenza patients were pooled using a random‐effects model. Sensitivity analyses restricted to severe influenza requiring intensive care unit (ICU) support and multiple subgroup analyses were performed. Results Fourteen studies involving 6024 hospitalised patients with influenza were included. IPA was estimated to occur in 10% of influenza patients, with a mortality rate of 52%. Similar incidence (11%) and mortality (54%) estimates for IPA were observed in the sensitivity analysis including severe cases requiring ICU support. Subgroup analysis by geographical location showed a similar IPA rate between European (10%) and non‐European (11%) studies. The IPA rate in the subset of nine studies using the modified AspICU criteria was 13%. Most subgroup analyses showed ≥50% mortality in IPA patients. Several predictors for IPA susceptibility were identified, including male sex, smoking history, chronic lung disease, influenza A (H1N1), severe conditions requiring supportive therapy, corticosteroid use before admission, solid organ transplant and haematological malignancy. Conclusions The IPA is common in individuals with severe influenza, and the prognosis is particularly poor. Influenza patients, especially those with high‐risk factors, should be thoroughly screened for IPA.

The association of renal function and linezolid-induced thrombocytopenia (LIT) remains controversial. We performed a meta-analysis to determine whether impaired renal function is associated with an increased LIT risk. Methods:We conducted a systematic search of PubMed, EMBASE and the Cochrane Library from inception to February 2021 for eligible studies evaluating the relationship between renal function and LIT. Indictors of renal function included renal impairment (RI), severe RI, hemodialysis status, creatinine clearance rate (Ccr) and estimated glomerular filtration rate (eGFR). Unadjusted and adjusted estimates and 95% confidence intervals (CIs) were calculated separately using a random-effect model.Results: A total of 24 studies with 3580 patients were included in the meta-analysis. RI patients had an increased LIT risk compared to non-RI patients in both the unadjusted (OR 4.15; 95% Cl 2.85 to 6.03; I 2 =0%) and adjusted analyses (OR 4.15; 95% Cl 2.85 to 6.03; I 2 =0%). This association persisted in the subset of studies involving only patients receiving a fixed conventional dose (600 mg every 12 h) and other subgroup analyses by ethnicity, sample size and study quality. Moreover, the LIT risk was significantly higher in patients with severe RI and hemodialysis than in patients without severe RI and hemodialysis. The eGFR and Ccr were significantly lower in LIT patients than in non-LIT patients.Conclusions: Impaired renal function is associated with an increased risk of LIT. A reduced linezolid dose may be considered in RI patients at a low risk of treatment failure, ideally guided by therapeutic drug monitoring.

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