Association Between ACEIs or ARBs Use and Clinical Outcomes in COVID-19 Patients: A Systematic Review and Meta-analysis

Importance: There is a controversy regarding whether or not to continue angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in patients with coronavirus disease 2019 (COVID-19). Objective: To evaluate the association between ACEIs or ARBs use and clinical outcomes in COVID-19 patients. Data Sources: Systematic search of the PubMed, Embase, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials from database inception to May 31, 2020. We also searched the preprint servers medRxiv and SSNR for additional studies. Study Selection: Observational studies and randomized controlled trials reporting the effect of ACEIs or ARBs use on clinical outcomes of adult patients with COVID-19. Data Extraction and Synthesis: Risk of bias of observational studies were evaluated using the Newcastle-Ottawa Scale. Meta-analyses were performed using a random-effects models and effects expressed as Odds ratios (OR) and mean differences with their 95% confidence interval (95%CI). If available, adjusted effects were pooled. Main Outcomes and Measures: The primary outcome was all-cause mortality and secondary outcomes were COVID-19 severity, hospital discharge, hospitalization, intensive care unit admission, mechanical ventilation, length of hospital stay, and troponin, creatinine, procalcitonin, C-reactive protein (CRP), interleukin-6 (IL-6), and D-dimer levels. Results: 40 studies (21 cross-sectional, two case-control, and 17 cohorts) involving 50615 patients were included. ACEIs or ARBs use was not associated with all-cause mortality overall (OR 1.11, 95%CI 0.77-1.60, p=0.56), in subgroups by study design and using adjusted effects. ACEI or ARB use was independently associated with lower COVID-19 severity (aOR 0.56, 95%CI 0.37-0.87, p<0.01). No significant associations were found between ACEIs or ARBs use and hospital discharge, hospitalization, mechanical ventilation, length of hospital stay, and biomarkers. Conclusions and Relevance: ACEIs or ARBs use was not associated with higher all-cause mortality in COVID-19. However, ACEI or ARB use was independently associated with lower COVID-19 severity. Our results support the current international guidelines to continue the use of ACEIs and ARBs in COVID-19 patients with hypertension.

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Cinacalcet Treatment Significantly Improves All-Cause and Cardiovascular Survival in Dialysis Patients: Results from a Meta-Analysis

Kidney & Blood Pressure Research ◽

10.1159/000504139 ◽

2019 ◽

Vol 44 (6) ◽

pp. 1327-1338 ◽

Cited By ~ 1

Author(s):

Yuan Zu ◽

Xiangxue Lu ◽

Jinghong Song ◽

Ling Yu ◽

Han Li ◽

...

Keyword(s):

Cardiovascular Mortality ◽

Observational Studies ◽

Fixed Effects ◽

Meta Analysis ◽

Controlled Trials ◽

Cochrane Central Register ◽

Fixed Effects Model ◽

Long Term Effects ◽

Dialysis Patients ◽

All Cause Mortality

Objective: To assess the long-term effects including all-cause mortality, cardiovascular mortality, and fracture incidence, of cinacalcet on secondary hyperparathyroidism (SHPT) in patients on dialysis. Methods: PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched from their inception to October 2018. Randomized controlled trials (RCTs) and cohort design prospective observational studies assessing cinacalcet for the treatment of SHPT in dialysis patients were included. Data extraction was independently completed by 2 authors who determined the methodological quality of the studies and extracted data in duplicate. Study-specific risk estimates were tested by using a fixed effects model. Results: A total of 14 articles with 38,219 participants were included, of which 10 RCTs with 7,471 participants and 4 prospective observational studies with 30,748 participants fulfilled the eligibility criteria. Compared with no cinacalcet, cinacalcet administration reduced all-cause mortality (relative risk [RR] 0.91, 95% CI 0.89–0.94, p < 0.001) and cardiovascular mortality (RR 0.92, 95% CI 0.89–0.95, p < 0.001), but it did not significantly reduce the incidence of fractures (RR 0.93, 95% CI 0.87–1.00, p = 0.05). Conclusions: The results of this meta-analysis indicated that the treatment of SHPT with cinacalcet may in fact reduce all-cause mortality and cardiovascular mortality among patients receiving maintenance dialysis.

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The effectiveness of pre- and post-operative rehabilitation for lung cancer: A systematic review and meta-analysis on postoperative pulmonary complications and length of hospital stay

Clinical Rehabilitation ◽

10.1177/02692155211043267 ◽

2021 ◽

pp. 026921552110432

Author(s):

Xinyi Xu ◽

Denise Shuk Ting Cheung ◽

Robert Smith ◽

Agnes Yuen Kwan Lai ◽

Chia-Chin Lin

Keyword(s):

Lung Cancer ◽

Hospital Stay ◽

Pulmonary Complication ◽

Length Of Hospital Stay ◽

Pulmonary Complications ◽

Hospital Length Of Stay ◽

Controlled Trials ◽

Cochrane Central Register ◽

Postoperative Pulmonary Complication ◽

Postoperative Pulmonary Complications

Objective: To investigate the effects of rehabilitation either before or after operation for lung cancer on postoperative pulmonary complications and the length of hospital stay. Data sources: MEDLINE, Cochrane Central Register of Controlled Trials, Web of Science, CINAHL Plus, SPORTDiscus, PsycInfo and Embase were searched from inception until June 2021. Review methods: Inclusion criteria were patients scheduled to undergo or had undergone operation for lung cancer, randomised controlled trials comparing rehabilitative interventions initiated before hospital discharge to usual care control. Two reviewers independently assessed eligibility, extracted data and risks of bias. Pooled odds ratios (ORs) or standardised mean differences (SMDs) with 95% Confidence Intervals (CI) were estimated using random-effects meta-analyses. Results: Twenty-three studies were included (12 preoperative, 10 postoperative and 1 perioperative), with 2068 participants. The pooled postoperative pulmonary complication risk and length of hospital stay were reduced after preoperative interventions (OR = 0.32; 95% CI = 0.22, 0.47; I2 = 0.0% and SMD = −1.68 days, 95% CI = −2.23, −1.13; I2 = 77.8%, respectively). Interventions delivered during the immediate postoperative period did not have any significant effects on either postoperative pulmonary complication or length of hospital stay (OR = 0.85; 95% CI = 0.56, 1.29; I2 = 0.0% and SMD = −0.23 days, 95% CI = −1.08, 0.63; I2 = 64.6%, respectively). Meta-regression showed an association between a higher number of supervised sessions and shorter hospital length of stay in preoperative studies (β = −0.17, 95% CI = −0.29, −0.05). Conclusion: Preoperative rehabilitation is effective in reducing postoperative pulmonary complications and length of hospital stay associated with lung cancer surgery. Short-term postoperative rehabilitation in inpatient settings is probably ineffective.

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SO017EFFECT OF HIGH-CUTOFF DIALYSIS FOR ACUTE KIDNEY INJURY SECONDARY TO CAST NEPHROPATHY IN PATIENTS WITH MULTIPLE MYELOMA: A SYSTEMATIC REVIEW AND META-ANALYSIS

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa139.so017 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Blanca Tarragon ◽

Nan Ye ◽

Martin Gallagher ◽

Shaundeep Sen ◽

Jose' M Portoles ◽

...

Keyword(s):

Systematic Review ◽

Multiple Myeloma ◽

Acute Kidney Injury ◽

Clinical Outcomes ◽

Observational Studies ◽

Meta Analysis ◽

Kidney Injury ◽

Controlled Trials ◽

Cast Nephropathy ◽

All Cause Mortality

Abstract Background and Aims The incidence of multiple myeloma (MM) is increasing. Abnormal secretion of serum free light chains (sFLC) can lead to cast nephropathy and severe acute kidney injury (AKI) requiring haemodialysis (HD), which is associated with increased morbidity and mortality. High cut-off (HCO) HD membranes demonstrate better sFLC clearance. However, their role in all-cause mortality and renal recovery remains uncertain. Method A systematic review and meta-analysis was performed examining all randomized controlled trials (RCTs) and observational studies assessing the effect of high cut-off HD compared to conventional HD on clinical outcomes of patients with MM complicated by cast nephropathy induced-severe AKI. Medline, EMBASE, and the Cochrane Central Register of Controlled Trials were searched until September 2019. The primary outcome was all-cause mortality at the end of the study. The secondary outcomes included all-cause mortality at 12 months, haemodialysis independence at 3, 6 and 12 months, biopsy-proven haematologic responses at 90 days and sFLC (kappa and lambda) reduction. Random effect models were used to pool relative risks (RR) with 95% conﬁdence intervals (CIs) for individual studies. Results The search identified 5 studies including 276 patients with a mean follow-up of 18.7 months. There were 2 RCTs and 3 retrospective cohort studies. Compared with patients treated with conventional HD, patients on HCO dialysis did not show survival benefits at 12 months (4 studies, 186 patients, RR 0.79; 95% CI 0.46-1.36), or at the end of the study (5 studies, 276 patients, RR 0.86; 95% CI 0.60-1.25). Although survival benefits at the end of study (3 studies, 88 patients, RR 0.64; 95% CI 0.45-0.90) were seen in observational studies, no differences in all-cause mortality was seen in RCTs (2 studies, 188 patients, RR 1.31; 95% CI 0.50-3.46). Likewise, although the pooled data from the observational studies demonstrated significantly higher rates of HD independence at 90 days (2 trials, 78 patients, RR 2.23; 95% CI 1.09-4.55), this difference disappeared when the data from RCTs were included to the analysis (4 studies, 266 patients, RR 1.28; 95% CI 0.95-1.73). There was no difference in HD Independence at 6 months (2 studies, 188 patients, RR 1.19; 95% CI 0.68-2.06), and 12 months (2 studies, 188 patients, RR 1.14; 95% CI 0.58-2.26) between these two therapies. Patients receiving HCO dialysis, however, had significantly better biopsy-proven haematologic response at 90 days by 40% (3 studies, 176 patients, RR 1,40; 95% CI 1.13-1.74) and a significantly higher kappa light chain reduction (2 studies, 188 patients, standardized mean difference (SMD) 2.37; 95% CI 1.99-2.75; I2 = 0%). Overall, the majority of the studies were of suboptimal quality and underpowered. Conclusion Current evidence from RCTs and observational studies suggest HCO dialysis provides haematological benefits but makes no significant improvement in all-cause mortality and renal outcomes, compared to conventional HD for patients with multiple myeloma associated cast nephropathy. However, there is a trend towards better renal outcomes, therefore further large-scale RCTs are needed to assess the effect of HCO dialysis on clinical outcomes in patients with multiple myeloma complicated by cast-nephropathy.

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Time to reconsider the routine use of tourniquets in total knee arthroplasty surgery

The Bone & Joint Journal ◽

10.1302/0301-620x.103b.bjj-2020-1926.r1 ◽

2021 ◽

pp. 1-10

Author(s):

Imran Ahmed ◽

Amit Chawla ◽

Martin Underwood ◽

Andrew Price ◽

Andrew Metcalfe ◽

...

Keyword(s):

Total Knee Arthroplasty ◽

Blood Loss ◽

Hospital Stay ◽

Knee Arthroplasty ◽

Length Of Hospital Stay ◽

Controlled Trials ◽

Cochrane Central Register ◽

Duration Of Surgery ◽

Total Knee ◽

The Mean

Aims Many surgeons choose to perform total knee arthroplasty (TKA) surgery with the aid of a tourniquet. A tourniquet is a device that fits around the leg and restricts blood flow to the limb. There is a need to understand whether tourniquets are safe, and if they benefit, or harm, patients. The aim of this study was to determine the benefits and harms of tourniquet use in TKA surgery. Methods We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled trials, and trial registries up to 26 March 2020. We included randomized controlled trials (RCTs), comparing TKA with a tourniquet versus without a tourniquet. Outcomes included: pain, function, serious adverse events (SAEs), blood loss, implant stability, duration of surgery, and length of hospital stay. Results We included 41 RCTs with 2,819 participants. SAEs were significantly more common in the tourniquet group (53/901 vs 26/898, tourniquet vs no tourniquet respectively) (risk ratio 1.73 (95% confidence interval (CI) 1.10 to 2.73). The mean pain score on the first postoperative day was 1.25 points higher (95% CI 0.32 to 2.19) in the tourniquet group. Overall blood loss did not differ between groups (mean difference 8.61 ml; 95% CI -83.76 to 100.97). The mean length of hospital stay was 0.34 days longer in the group that had surgery with a tourniquet (95% CI 0.03 to 0.64) and the mean duration of surgery was 3.7 minutes shorter (95% CI -5.53 to -1.87). Conclusion TKA with a tourniquet is associated with an increased risk of SAEs, pain, and a marginally longer hospital stay. The only finding in favour of tourniquet use was a shorter time in theatre. The results make it difficult to justify the routine use of a tourniquet in TKA surgery.

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Dexmedetomidine for Facilitating Mechanical Ventilation Extubation in Difficult-to-Wean ICU Patients: Systematic Review and Meta-Analysis of Clinical Trials

Journal of Intensive Care Medicine ◽

10.1177/0885066620937673 ◽

2020 ◽

pp. 088506662093767

Author(s):

Mitchell S. Buckley ◽

Pamela L. Smithburger ◽

Adrian Wong ◽

Gilles L. Fraser ◽

Michael C. Reade ◽

...

Keyword(s):

Systematic Review ◽

Mechanical Ventilation ◽

Length Of Stay ◽

Clinical Outcomes ◽

Meta Analysis ◽

Controlled Trials ◽

Cochrane Central Register ◽

Icu Patients ◽

Icu Length Of Stay ◽

Increased Risk

Background: Agitation and delirium are common in mechanically ventilated adult intensive care unit (ICU) patients and may contribute to delayed extubation times. Difficult-to-wean ICU patients have been associated with an increased risk of longer ICU length of stays and mortality. The purpose of this systematic review and meta-analysis is to evaluate the evidence of dexmedetomidine facilitating successful mechanical ventilation extubation in difficult-to-wean ICU patients and clinical outcomes. Methods: A literature search was conducted using MEDLINE, EMBASE, PsycINFO, Cumulative Index to Nursing and Allied Health Literature, Global Health, Cochrane Central Register of Controlled Trials, Clinical Trial Registries, and the Health Technology Assessment Database from inception to December 5, 2019. Randomized controlled trials evaluating dexmedetomidine with the intended purpose to facilitate mechanical ventilation liberation in adult ICU patients (≥18 years) experiencing extubation failure were included. The primary outcome of time to extubation was evaluated using the weighted mean difference (WMD), with a random effects model. Secondary analyses included hospital and ICU length of stay, in-hospital mortality, hypotension, and bradycardia. Results: A total of 6 trials (n = 306 patients) were included. Dexmedetomidine significantly reduced the time to extubation (WMD: −11.61 hours, 95% CI: −16.5 to −6.7, P = .005) and ICU length of stay (WMD: −3.04 days; 95% CI: −4.66 to −1.43). Hypotension risk was increased with dexmedetomidine (risk ratio [RR]: 1.62, 95% CI: 1.05-2.51), but there was no difference in bradycardia risk (RR: 3.98, 95% CI: 0.70-22.78). No differences were observed in mortality rates (RR: 1.30, 95% CI: 0.45-3.75) or hospital length of stay (WMD: −2.67 days; 95% CI: −7.73 to 2.39). Conclusions: Dexmedetomidine was associated with a significant reduction in the time to extubation and shorter ICU stay in difficult-to-wean ICU patients. Although hypotension risk was increased with dexmedetomidine, no differences in other clinical outcomes were observed.

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Effect of timing of intubation on clinical outcomes of critically ill patients with COVID-19: a systematic review and meta-analysis of non-randomized cohort studies

Critical Care ◽

10.1186/s13054-021-03540-6 ◽

2021 ◽

Vol 25 (1) ◽

Author(s):

Eleni Papoutsi ◽

Vassilis G. Giannakoulis ◽

Eleni Xourgia ◽

Christina Routsi ◽

Anastasia Kotanidou ◽

...

Keyword(s):

Systematic Review ◽

Mechanical Ventilation ◽

Clinical Outcomes ◽

Critically Ill ◽

Critically Ill Patients ◽

Meta Analysis ◽

Mortality And Morbidity ◽

Icu Admission ◽

All Cause Mortality ◽

Detectable Difference

Abstract Background Although several international guidelines recommend early over late intubation of patients with severe coronavirus disease 2019 (COVID-19), this issue is still controversial. We aimed to investigate the effect (if any) of timing of intubation on clinical outcomes of critically ill patients with COVID-19 by carrying out a systematic review and meta-analysis. Methods PubMed and Scopus were systematically searched, while references and preprint servers were explored, for relevant articles up to December 26, 2020, to identify studies which reported on mortality and/or morbidity of patients with COVID-19 undergoing early versus late intubation. “Early” was defined as intubation within 24 h from intensive care unit (ICU) admission, while “late” as intubation at any time after 24 h of ICU admission. All-cause mortality and duration of mechanical ventilation (MV) were the primary outcomes of the meta-analysis. Pooled risk ratio (RR), pooled mean difference (MD) and 95% confidence intervals (CI) were calculated using a random effects model. The meta-analysis was registered with PROSPERO (CRD42020222147). Results A total of 12 studies, involving 8944 critically ill patients with COVID-19, were included. There was no statistically detectable difference on all-cause mortality between patients undergoing early versus late intubation (3981 deaths; 45.4% versus 39.1%; RR 1.07, 95% CI 0.99–1.15, p = 0.08). This was also the case for duration of MV (1892 patients; MD − 0.58 days, 95% CI − 3.06 to 1.89 days, p = 0.65). In a sensitivity analysis using an alternate definition of early/late intubation, intubation without versus with a prior trial of high-flow nasal cannula or noninvasive mechanical ventilation was still not associated with a statistically detectable difference on all-cause mortality (1128 deaths; 48.9% versus 42.5%; RR 1.11, 95% CI 0.99–1.25, p = 0.08). Conclusions The synthesized evidence suggests that timing of intubation may have no effect on mortality and morbidity of critically ill patients with COVID-19. These results might justify a wait-and-see approach, which may lead to fewer intubations. Relevant guidelines may therefore need to be updated.

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Sulodexide versus Control and the Risk of Thrombotic and Hemorrhagic Events: Meta-Analysis of Randomized Trials

Seminars in Thrombosis and Hemostasis ◽

10.1055/s-0040-1716874 ◽

2020 ◽

Vol 46 (08) ◽

pp. 908-918

Author(s):

Behnood Bikdeli ◽

Saurav Chatterjee ◽

Ajay J. Kirtane ◽

Sahil A. Parikh ◽

Giuseppe M. Andreozzi ◽

...

Keyword(s):

Pulmonary Embolism ◽

Cardiovascular Mortality ◽

Dermatan Sulfate ◽

Meta Analysis ◽

Arterial Disease ◽

Controlled Trials ◽

Cochrane Central Register ◽

Bleeding Events ◽

Random Effects Models ◽

All Cause Mortality

AbstractThrombotic cardiovascular disease (myocardial infarction [MI], stroke, and venous thromboembolism [VTE]) remains a major cause of death and disability. Sulodexide is an oral glycosaminoglycan containing heparan sulfate and dermatan sulfate. We conducted a systematic review and meta-analysis to determine the cardiovascular efficacy, and safety of sulodexide versus control in randomized controlled trials (RCTs). We searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials for RCTs reporting cardiovascular outcomes in patients receiving sulodexide versus control (placebo or no treatment). Outcomes included all-cause mortality, cardiovascular mortality, MI, stroke, deep vein thrombosis (DVT), pulmonary embolism, and bleeding. We used inverse variance random-effects models with odds ratio (OR) as the effect measure. After screening 360 records, 6 RCTs including 7,596 patients (median follow-up duration: 11.6 months) were included. Patients were enrolled for history of MI, VTE, peripheral arterial disease, or cardiovascular risk factors plus nephropathy. Use of sulodexide compared with control was associated with reduced odds of all-cause mortality (OR 0.67, 95% confidence interval [CI] 0.52–0.85, p = 0.001), cardiovascular mortality (OR 0.44, 95% CI 0.22–0.89, p = 0.02), and MI (OR 0.70, 95% CI 0.51–0.96, p = 0.03), and nonsignificantly reduced odds of stroke (OR 0.78, 95% CI 0.45–1.35, p = 0.38). Sulodexide was associated with significantly reduced odds of VTE (OR 0.44, 95% CI 0.24–0.81, p = 0.008), including DVT (OR 0.41, 95% CI 0.26–0.65, p < 0.001), but not pulmonary embolism (OR 0.92, 95% CI 0.40–2.15, p = 0.86). Bleeding events were not significantly different in the two groups (OR 1.14, 95% CI 0.47–2.74, p = 0.48). In six RCTs across a variety of clinical indications, use of sulodexide compared with placebo or no treatment was associated with reduced odds of all-cause mortality, cardiovascular mortality, MI, and DVT, without a significant increase in bleeding. Additional studies with this agent are warranted.

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Therapeutic efficacy, mechanical ventilation, length of hospital stay, and mortality rate in severe COVID‐19 patients treated with tocilizumab

International Journal of Clinical Practice ◽

10.1111/ijcp.14079 ◽

2021 ◽

Cited By ~ 1

Author(s):

Rania M Sarhan ◽

Yasmin M. Madney ◽

Ahmed E. Abou Warda ◽

Marian S. Boshra

Keyword(s):

Mechanical Ventilation ◽

Mortality Rate ◽

Hospital Stay ◽

Therapeutic Efficacy ◽

Length Of Hospital Stay

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Effects of early corticosteroid use in patients with severe coronavirus disease 2019

BMC Infectious Diseases ◽

10.1186/s12879-021-06221-5 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Jong Hoon Hyun ◽

Moo Hyun Kim ◽

Yujin Sohn ◽

Yunsuk Cho ◽

Yae Jee Baek ◽

...

Keyword(s):

Hospital Stay ◽

Clinical Outcomes ◽

Case Fatality ◽

Length Of Hospital Stay ◽

Corticosteroid Treatment ◽

Threshold Value ◽

Steroid Use ◽

Corticosteroid Administration ◽

Significant Difference ◽

Early Use

Abstract Background Coronavirus disease 2019 (COVID-19) is associated with acute respiratory distress syndrome, and corticosteroids have been considered as possible therapeutic agents for this disease. However, there is limited literature on the appropriate timing of corticosteroid administration to obtain the best possible patient outcomes. Methods This was a retrospective cohort study including patients with severe COVID-19 who received corticosteroid treatment from March 2 to June 30, 2020 in seven tertiary hospitals in South Korea. We analyzed the patient demographics, characteristics, and clinical outcomes according to the timing of steroid use. Twenty-two patients with severe COVID-19 were enrolled, and they were all treated with corticosteroids. Results Of the 22 patients who received corticosteroids, 12 patients (55%) were treated within 10 days from diagnosis. There was no significant difference in the baseline characteristics. The initial PaO2/FiO2 ratio was 168.75. The overall case fatality rate was 25%. The mean time from diagnosis to steroid use was 4.08 days and the treatment duration was 14 days in the early use group, while those in the late use group were 12.80 days and 18.50 days, respectively. The PaO2/FiO2 ratio, C-reactive protein level, and cycle threshold value improved over time in both groups. In the early use group, the time from onset of symptoms to discharge (32.4 days vs. 60.0 days, P = 0.030), time from diagnosis to discharge (27.8 days vs. 57.4 days, P = 0.024), and hospital stay (26.0 days vs. 53.9 days, P = 0.033) were shortened. Conclusions Among patients with severe COVID-19, early use of corticosteroids showed favorable clinical outcomes which were related to a reduction in the length of hospital stay.

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