scholarly journals Comparison of COVID-19 outcomes in organ transplant recipients (OTr) and non-transplant patients: a study protocol for rapid review

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Alexis H. Lerner ◽  
Elizabeth J. Klein ◽  
Anna Hardesty ◽  
Orestis A. Panagiotou ◽  
Chelsea Misquith ◽  
...  

Abstract Background The COVID-19 pandemic has devastated the global community with nearly 4.9 million deaths as of October 2021. While organ transplant (OT) recipients (OTr) may be at increased risk for severe COVID-19 due to their chronic immunocompromised state, outcomes for OTr with COVID-19 remain disputed in the literature. This review will examine whether OTr with COVID-19 are at higher risk for severe illness and death than non-immunocompromised individuals. Methods MEDLINE (via Ovid and PubMed) and EMBASE (via Embase.com) will be searched from December 2019 to October 2021 for observational studies (including cohort and case-control) that compare COVID-19 clinical outcomes in OTr to those in individuals without history of OT. The primary outcome of interest will be mortality as defined in each study, with possible further analyses of in-hospital mortality, 28 or 30-day mortality, and all-cause mortality versus mortality attributable to COVID-19. The secondary outcome of interest will be the severity of COVID-19 disease, most frequently defined as requiring intensive care unit admission or mechanical ventilation. Two reviewers will independently screen all abstracts and full-text articles. Potential conflicts will be resolved by a third reviewer and potentially discussion among all investigators. Methodological quality will be appraised using the Newcastle-Ottawa Scale. If data permit, we will perform random-effects meta-analysis with the Sidik-Jonkman estimator and the Hartung-Knapp adjustment for confidence intervals to estimate a summary measure of association between histories of transplant with each outcome. Potential sources of heterogeneity will be explored using meta-regression. Additional analyses will be conducted to explore the potential sources of heterogeneity (e.g., subgroup analysis) considering least minimal adjustment for confounders. Discussion This rapid review will assess the available evidence on whether OTr diagnosed with COVID-19 are at higher risk for severe illness and death compared to non-immunocompromised individuals. Such knowledge is clinically relevant and may impact risk stratification, allocation of organs and healthcare resources, and organ transplantation protocols during this, and future, pandemics. Systematic review registration Open Science Framework (OSF) registration DOI: 10.17605/osf.io/4n9d7.

2021 ◽  
Author(s):  
Kevin C. Maki ◽  
Meredith L. Wilcox ◽  
Mary R. Dicklin ◽  
Rahul Kakkar ◽  
Michael H. Davidson

Abstract Background Cardiovascular disease is an important driver of the increased mortality associated with chronic kidney disease (CKD). Higher left ventricular mass (LVM) predicts increased risk of adverse cardiovascular outcomes and total mortality, but previous reviews have shown no clear association between intervention-induced LVM change and all-cause or cardiovascular mortality in CKD. Methods The primary objective of this meta-analysis was to investigate whether treatment-induced reductions in LVM over periods ≥ 12 months were associated with all-cause mortality in patients with CKD. Cardiovascular mortality was investigated as a secondary outcome. Measures of association in the form of relative risks (RRs) with associated variability and precision (95% confidence intervals [CIs]) were extracted directly from each study, when reported, or were calculated based on the published data, if possible, and pooled RR estimates were determined. Results The meta-analysis included 38 trials with duration ≥ 12 months: 6 of erythropoietin stimulating agents treating to higher vs. lower hemoglobin targets, 10 of renin-angiotensin-aldosterone system inhibitors vs. placebo or another blood pressure lowering agent, 14 of modified hemodialysis regimens, and 8 of other types of interventions. All-cause mortality was reported in 116/2385 (4.86%) subjects in intervention groups and 161/2404 (6.70%) subjects in control groups. The pooled RR estimate of the 24 trials ≥ 12 months with ≥ 1 event in ≥ 1 group was 0.72 (95% CI 0.57 to 0.91, p = 0.005), with little heterogeneity across studies. Directionalities of the associations in intervention subgroups were the same. Sensitivity analyses of ≥ 6 months (31 trials), ≥ 9 months (26 trials), and > 12 months (9 trials), and including studies with no events in either group, demonstrated similar risk reductions to the primary analysis. The point estimate for cardiovascular mortality was similar to all-cause mortality, but not statistically significant: RR 0.66, 95% CI 0.38 to 1.15. Conclusions These results suggest that LVM regression may be a useful surrogate marker for benefits of interventions intended to reduce mortality risk in patients with CKD.


BMC Medicine ◽  
2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Bongani B. Nkambule ◽  
Vuyolwethu Mxinwa ◽  
Zibusiso Mkandla ◽  
Tinashe Mutize ◽  
Kabelo Mokgalaboni ◽  
...  

Abstract Background Antiretroviral therapy (ART) alters platelet reactivity, and as a consequence, patients living with HIV may be at an increased risk of cardiovascular disease (CVD). The current evidence on platelet activation levels in patients with HIV remains inconclusive. We therefore aimed to systematically synthesise evidence on the association of platelet activation in HIV-infected patients on successful treatment. Methods Electronic databases were searched from inception until November 2019. Studies were included if the primary or secondary outcome of the study was to assess platelet activation in HIV-infected patients on ART. The primary outcome of this review included the levels of platelet activation. The pooled effect estimates were calculated using a random-effects meta-analysis model. Results We identified 30 studies comprising of 2325 participants. The pooled estimates showed elevated levels of platelet activation in treatment-naïve HIV-infected patients compared to uninfected controls (Hedges’ g 2.00 [95%CI 1.05, 2.94]; z = 4.12, p < 0.0001). These remained elevated despite successful ART (Hedges’ g 2.05 [95%CI 0.58, 3.52]; z = 2.71, p = 0.0067). Conclusion The levels of platelet activation are elevated in treatment-naïve HIV-infected patients, and these persist during successful ART. Further studies should assess the clinical relevance of monitoring the levels of platelet activation in HIV-infected patients on ART.


BMJ Open ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. e023600 ◽  
Author(s):  
Igho J Onakpoya ◽  
Elizabeth T Thomas ◽  
Joseph J Lee ◽  
Ben Goldacre ◽  
Carl J Heneghan

ObjectiveTo assess the benefits and harms of pregabalin in the management of neuropathic pain.DesignRapid review and meta-analysis of phase III, randomised, placebo-controlled trials.ParticipantsAdults aged 18 years and above with neuropathic pain defined according to the International Association for the Study of Pain criteria.InterventionsPregabalin or placebo.Primary and secondary outcome measuresOur primary outcomes were pain (as measured using validated scales) and adverse events. Our secondary outcomes were sleep disturbance, quality of life, Patient Global Impression of Change, Clinician Global Impression scale, anxiety and depression scores, overall discontinuations and discontinuations because of adverse events.ResultsWe included 28 trials comprising 6087 participants. The neuropathic pain conditions studied were diabetic peripheral neuropathy, postherpetic neuralgia, herpes zoster, sciatica (radicular pain), poststroke pain and spinal cord injury-related pain. Patients who took pregabalin reported significant reductions in pain (numerical rating scale (NRS)) compared with placebo (standardised mean difference (SMD) −0.49 (95% CI −0.66 to −0.32, p<0.00001), very low quality evidence). Pregabalin significantly reduced sleep interference scores (NRS) compared with placebo (SMD −0.38 (95% CI −0.50 to −0.26, p<0.00001), moderate quality evidence. Pregabalin significantly increased the risk of adverse events compared with placebo (RR 1.33 (95% CI 1.23 to 1.44, p<0.00001, low quality evidence)). The risks of experiencing weight gain, somnolence, dizziness, peripheral oedema, fatigue, visual disturbances, ataxia, non-peripheral oedema, vertigo and euphoria were significantly increased with pregabalin. Pregabalin was significantly more likely than placebo to lead to discontinuation of the drug because of adverse events (RR 1.91 (95% CI 1.54 to 2.37, p<0.00001), low quality evidence).ConclusionPregabalin has beneficial effects on some symptoms of neuropathic pain. However, its use significantly increases the risk of a number of adverse events and discontinuation due to adverse events. The quality of the evidence from journal publications is low.


2015 ◽  
Vol 143 (14) ◽  
pp. 2975-2984 ◽  
Author(s):  
Y. XUAN ◽  
L. N. WANG ◽  
W. LI ◽  
H. R. ZI ◽  
Y. GUO ◽  
...  

SUMMARYThe interferon-inducible transmembrane protein 3 (IFITM3), as one of the key genes involved in the interferon pathway, is critical for defending the host against influenza virus, and the rs12252 T>C variant in IFITM3 might be associated with susceptibility to severe influenza. Owing to contradictory and inconclusive results, we performed a meta-analysis to assess the association between rs12252 T>C polymorphism and severe influenza risk. A comprehensive literature search up to 1 August 2014 was conducted in EMBASE, Pubmed, Web of Science, VIP, Wanfang and CNKI databases. Four eligible studies with a total of 445 influenza patients and 3396 controls were included in this meta-analysis. Overall, our results demonstrated a significant association between the IFITM3 rs12252 T>C polymorphism and influenza risk [C vs. T: odds ratio (OR) 1·68, 95% confidence interval (CI) 1·32–2·13; CC vs. CT+TT: OR 2·38, 95% CI 1·52–3·73; CC+CT vs. TT: OR 1·62, 95% CI 1·18–2·22]. Stratification by ethnicity indicated that the variant C allele was associated with an 88% increased risk of influenza in Asians (C vs. T: OR 1·88, 95% CI 1·34–2·62). Moreover, subjects carrying the variant C allele had an increased risk of developing severe illness upon influenza infection (C vs. T: OR 2·70, 95% CI 1·86–3·94). However, no significant association was observed in patients with mild infection (C vs. T: OR 1·26, 95% CI 0·93–1·71). Our meta-analysis suggests that IFITM3 rs12252 T>C polymorphism is significantly associated with increased risk of severe influenza but not with the chance of initial virus infection.


2020 ◽  
Author(s):  
Maya Mellor ◽  
Anne Bast ◽  
Nicholas Jones ◽  
Nia Roberts ◽  
Jose Ordonez-Mena ◽  
...  

Objective: To assess whether people living with HIV (PLWH) are at increased risk of COVID-19 mortality or adverse outcomes, and whether antiretroviral therapy (ART) influences this risk. Design: Rapid review with meta-analysis and narrative synthesis. Methods: We searched databases including Embase, Medline, medRxiv, and Google Scholar up to 26th August 2020 for studies describing COVID-19 outcomes in PLWH and conducted a meta-analysis of higher quality studies. Results: We identified 1,908 studies and included 19 in the review. In a meta-analysis of five studies, PLWH had a higher risk of COVID-19 mortality (hazard ratio (HR) 1.93, 95% Confidence Interval (CI): 1.59-2.34) compared to people without HIV. Risk of death remained elevated for PLWH in a subgroup analysis of hospitalised cohorts (HR 1.54, 95% CI: 1.05-2.24) and studies of PLWH across all settings (HR 2.08, 95%CI: 1.69-2.56). Eight other studies assessed the association between HIV and COVID-19 outcomes, but provided inconclusive, lower-quality evidence due to potential confounding and selection bias. There were insufficient data on the effect of CD4+ T cell count and HIV viral load on COVID-19 outcomes. Eleven studies reported COVID-19 outcomes by ART-regimen. In the two largest studies, tenofovir-disoproxil-fumarate (TDF)-based regimens were associated with a lower risk of adverse COVID-19 outcomes, although these analyses are susceptible to confounding by comorbidities. Conclusion: Evidence is emerging that suggests a moderately increased risk of COVID-19 mortality amongst PLWH. Further investigation into the relationship between COVID-19 outcomes and CD4+ T cell count, HIV viral load, ART and the use of TDF is warranted.


BMJ Open ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. e034135 ◽  
Author(s):  
Jie Li ◽  
Feng Ji ◽  
Junxian Song ◽  
Xiangyang Gao ◽  
Deguo Jiang ◽  
...  

ObjectivesAnxiety has been suggested to be associated with poor outcomes in patients with acute coronary syndrome (ACS). However, results of previous follow-up studies were inconsistent. The aim of this meta-analysis was to evaluate the association between anxiety and clinical outcomes in patients with ACS, and to investigate the potential role of depression underlying the above association.DesignA meta-analysis of prospective follow-up studies.SettingHospitals.ParticipantsPatients with ACS.InterventionsWe included related prospective follow-up studies up through 20 July 2019 that were identified by searching PubMed and Embase databases. A random-effect model was used for the meta-analysis. Anxiety was evaluated by validated instruments at baseline.Primary and secondary outcome measuresWe determined the association between anxiety and risks of mortality and adverse cardiovascular events (MACEs) in patients with ACS.ResultsOur analysis included 17 studies involving 39 038 patients wqith ACS. Anxiety was independently associated with increased mortality risk (adjusted risk ratio (RR) 1.21, 95% CI 1.07 to 1.37, p=0.002) and MACEs (adjusted RR 1.47, 95% CI 1.24 to 1.74, p<0.001) in patients with ACS. Subgroup analyses showed that depression may at least partly confound the association between anxiety and poor outcomes in patients with ACS. Adjustment of depression significantly attenuated the association between anxiety and MACEs (adjusted RR 1.25, 95% CI 1.04 to 1.52, p=0.02). Moreover, anxiety was not significantly associated with mortality risk after adjusting for depression (adjusted RR 0.88, 95% CI 0.66 to 1.17, p=0.37).ConclusionsAnxiety is associated with increased risk of mortality and MACEs in patients with ACS. However, at least part of the association may be confounded by concurrent depressive symptoms in these patients.


2021 ◽  
Vol 2021 ◽  
pp. 1-33
Author(s):  
Leila Karimi ◽  
Somayeh Makvandi ◽  
Amir Vahedian-Azimi ◽  
Thozhukat Sathyapalan ◽  
Amirhossein Sahebkar

Background. Based on what is known at this time, pregnant women are at an increased risk of severe illness from COVID-19 compared to nonpregnant women. Additionally, pregnant women with COVID-19 might have an increased risk of adverse pregnancy outcomes. To investigate the effects of coronavirus disease 2019 (COVID-19) on mortality of pregnant and postpartum women, we performed a systematic review of available published literature on pregnancies affected by COVID-19. Methods. Web of Science, SCOPUS, and MEDLINE- databases were searched for original studies concerning the effect of COVID-19 on mortality of pregnant and postpartum women published by July 10, 2020. Meta-analyses of proportions were used to combine data and report pooled proportions. Results. 117 studies with a total of 11758 pregnant women were included. The age ranged between 15 and 48 years. Most subjects were infected with SARS-CoV-2 in the third trimester. Disease severity was not reported in 1125 subjects. Maternal mortality was 1.3%. In 100% of fatal cases with adequate data, fever alone or with cough was one of the presenting symptoms. Also, dyspnea (58.3%) and myalgia (50%) were the most common symptoms. Sore throat (8.3%) and gastrointestinal symptoms (anorexia, nausea) (8.3%) were rare. The rate of comorbidities was 20% among COVID-19 deaths. The majority of COVID-19-infected women who died had cesarean section (58.3%), 25% had a vaginal delivery, and 16.7% of patients were not full term. Conclusion. COVID-19 infection in pregnant women was associated with higher rates (and pooled proportions) of cesarean section and mortality. Because new data are continuously being generated and published, the findings of this study can be complete and updated with new researches. The results of this study can guide and improve prenatal counseling of COVID-19-infected pregnant women.


2021 ◽  
pp. 2101612
Author(s):  
Fasihul A. Khan ◽  
Iain Stewart ◽  
Gauri Saini ◽  
Karen A. Robinson ◽  
R. Gisli Jenkins

BackgroundBlood derived biomarkers have been extensively described as potential prognostic markers in idiopathic pulmonary fibrosis (IPF), but studies have been limited by analyses using data-dependent thresholds, inconsistent adjustment for confounders and an array of endpoints, thus often yielding ungeneralisable results. Meta-analysis of individual participant data (IPD) is a powerful tool to overcome these limitations. Through systematic review of blood derived biomarkers, sufficient studies with measurements of Matrix Metalloproteinase-7 (MMP-7) were identified to facilitate standardised analyses of the prognostic potential of this biomarker in IPF.MethodsElectronic databases were searched on 12th November 2020 to identify prospective studies reporting outcomes in patients with untreated IPF, stratified according to at least one pre-specified biomarker, measured at either baseline, or change over three months. Individual participant data (IPD) was sought for studies investigating MMP-7 as a prognostic factor. The primary outcome was overall mortality according to standardised MMP-7 z-scores, with a secondary outcome of disease progression in 12 months, all adjusted for age, gender, smoking and baseline FVC.ResultsIPD was available for nine studies out of twelve identified, reporting outcomes from 1664 participants. Baseline MMP-7 levels were associated with increased mortality risk (adjusted HR1.23, 95%CI 1.03;1.48, I2=64.3%) and disease progression (adjusted OR1.27, 95%CI 1.11;1.46, I2=5.9%). In limited studies, three-month change in MMP-7 was not associated with outcomes.ConclusionIPD meta-analysis demonstrated greater baseline MMP-7 levels were independently associated with an increased risk of poor outcomes in patients with untreated IPF, whilst short term changes did not reflect disease progression.


BMJ Open ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. e031291 ◽  
Author(s):  
Rekesh Corepal ◽  
Jessica Faye Hall ◽  
Coralie English ◽  
Amanda Farrin ◽  
Claire F Fitzsimons ◽  
...  

IntroductionSedentary behaviour is defined as any waking behaviour characterised by low energy expenditure ≤1.5 metabolic equivalents while in a sitting, lying or reclining posture. The expanding evidence base suggests that sedentary behaviour may have a detrimental effect on health, well-being and is associated with an increased risk of all-cause mortality. We aim to review process evaluations of randomised controlled trials (RCTs) which included a measure of sedentary behaviour in adults in order to develop an understanding of intervention content, mechanisms of impact, implementation and delivery approaches and contexts, in which interventions were reported to be effective or effective. A secondary aim is to summarise participants, family and staff experiences of such interventions.Methods and analysisTen electronic databases and reference lists from previous similar reviews will be searched. Eligible studies will be process evaluations of RCTs that measure sedentary behaviour as a primary or secondary outcome in adults. As this review will contribute to a programme to develop a community-based intervention to reduce sedentary behaviour in stroke survivors, interventions delivered in schools, colleges, universities or workplaces will be excluded. Two reviewers will perform study selection, data extraction and quality assessment. Disagreements between reviewers will be resolved by a third reviewer. Process evaluation data to be extracted include the aims and methods used in the process evaluation; implementation data; mechanisms of impact; contextual factors; participant, family and staff experiences of the interventions. A narrative approach will be used to synthesise and report qualitative and quantitative data. Reporting of the review will be informed by Preferred Reporting Items for Systematic Review and Meta-Analysis guidance.Ethics and disseminationEthical approval is not required as it is a protocol for a systematic review. Findings will be disseminated through peer-reviewed publications and conference presentations.PROSPERO registration numberCRD42018087403.


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