scholarly journals Platelet activation in adult HIV-infected patients on antiretroviral therapy: a systematic review and meta-analysis

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.

2020 ◽  
Vol 127 (11) ◽  
pp. 1365-1380
Author(s):  
Akif A. Khawaja ◽  
Kirk A. Taylor ◽  
Andrew O. Lovell ◽  
Mark Nelson ◽  
Brian Gazzard ◽  
...  

Rationale: People living with HIV on effective antiretroviral therapy are at increased risk of cardiovascular complications, possibly due to off-target drug effects. Some studies have associated antiretroviral therapy with increased risk of myocardial infarction and endothelial dysfunction, but a link between endothelial function and antiretrovirals has not been established. Objective: To determine the effects of antiretrovirals in common clinical use upon in vitro endothelial function to better understand cardiovascular risk in people living with HIV. Methods and Results: Human umbilical cord vein endothelial cells or human coronary artery endothelial cells were pretreated with the antiretrovirals abacavir sulphate (ABC), tenofovir disoproxil fumarate, or tenofovir alafenamide. Expression of adhesion molecules, ectonucleotidases (CD39 and CD73), tissue factor (TF), endothelial-derived microparticle (EMP) numbers and phenotype, and platelet activation were evaluated by flow cytometry. TF and ectonucleotidase activities were measured using colourimetric plate-based assays. ABC-treated endothelial cells had higher levels of ICAM (intercellular adhesion molecule)-1 and TF expression following TNF (tumor necrosis factor)-α stimulation. In contrast, tenofovir disoproxil fumarate and tenofovir alafenamide treatment gave rise to greater populations of CD39 + CD73 + cells. These cell surface differences were also observed within EMP repertoires. ABC-treated cells and EMP had greater TF activity, while tenofovir disoproxil fumarate- and tenofovir alafenamide-treated cells and EMP displayed higher ectonucleotidase activity. Finally, EMP isolated from ABC-treated cells enhanced collagen-evoked platelet integrin activation and α-granule release. Conclusions: We report differential effects of antiretrovirals used in the treatment of HIV upon endothelial function. ABC treatment led to an inflammatory, prothrombotic endothelial phenotype that promoted platelet activation. In contrast, tenofovir disoproxil fumarate and tenofovir alafenamide conferred potentially cardioprotective properties associated with ectonucleotidase activity. These observations establish a link between antiretrovirals and specific functional effects that provide insight into cardiovascular disease in people living with HIV.


2021 ◽  
Vol 10 (11) ◽  
pp. 2300
Author(s):  
Han-Chang Ku ◽  
Yi-Tseng Tsai ◽  
Sriyani-Padmalatha Konara-Mudiyanselage ◽  
Yi-Lin Wu ◽  
Tsung Yu ◽  
...  

The incidence of herpes zoster (HZ) in patients infected with HIV is higher than that of the general population. However, the incidence of HZ in HIV patients receiving antiretroviral therapy (ART) remains unclear. This meta-analysis aimed to estimate the pooled incidence rate and risk factors for HZ in the post-ART era. We identified studies assessing the incidence of HZ in the post-ART era between 1 January 2000 and 28 February 2021, from four databases. Pooled risk ratios were calculated from 11 articles using a random-effects model. The heterogeneity of the included trials was evaluated by visually inspecting funnel plots, performing random-effects meta-regression and using I2 statistics. Of the 2111 studies screened, we identified 11 studies that were eligible for final inclusion in the systematic review and 8 studies that were eligible for a meta-analysis. The pooled incidence of HZ in the post-ART era (after the introduction of ART in 1997) was 2.30 (95% confidence interval (CI): 1.56–3.05) per 100 person years (PYs). The risks of incidence of HZ among people living with HIV included male sex (AOR: 4.35 (95% CI: 054–2.41)), men who have sex with men (AOR: 1.21 (95% CI: −0.76–1.13)), CD4 count < 200 cells/μL (AOR: 11.59 (95% CI: 0.53–4.38)) and not receiving ART (AOR: 2.89 (95% CI: −0.44–2.56)). The incidence of HZ is substantially lower among HIV infected patients receiving ART than those not receiving ART. Initiating ART immediately after diagnosis to treat all HIV-positive individuals is crucial to minimize the disease burden of HZ.


2020 ◽  
Vol 2020 ◽  
pp. 1-17
Author(s):  
Lu Wang ◽  
Mingmin Xu ◽  
Qianhua Zheng ◽  
Wei Zhang ◽  
Ying Li

Objective. The purpose of this study was to assess the effectiveness and safety of acupuncture for functional constipation (FC). Methods. A rigorous literature search was performed in English (PubMed, Web of Science, the Cochrane Library, and EMBASE) and Chinese (China National Knowledge Infrastructure (CNKI), Chinese Biological Medical (CBM), Wanfang database, and China Science and Technology Journal (VIP)) electronic databases from their inception to October 2019. Included randomized controlled trials (RCTs) compared acupuncture therapy with sham acupuncture or pharmacological therapies. The outcome measures were evaluated, including the primary outcome of complete spontaneous bowel movement (CSBM) and secondary outcomes of Bristol Stool Form Scale (BSFS), constipation symptoms scores (CSS), responder rate, the Patient Assessment of Constipation Quality of Life (PAC-QOL) questionnaire, and safety evaluation. Meta-analysis was performed by using RevMan5.3. Results. The merged data of 28 RCTs with 3525 participants indicated that acupuncture may be efficient for FC by increasing CSBMs (p<0.00001; MD = 0.84 [95% CI, 0.65 to 1.03]; I2 = 0%) and improving constipation symptoms (p=0.03; SMD = −0.4 [95% CI, −0.78 to −0.03]; I2 = 74%), stool formation (p<0.00001; MD = 0.24 [95% CI, 0.15 to 0.34]; I2 = 0%), quality of life (p<0.00001; N = 1, MD = −0.33 [95% CI, −0.45 to −0.21]), and responder rates (p=0.02; RR = 2.16; [95% CI, 1.1 to 4.24]; I2 = 69%) compared with the effects of sham treatment. No increased risk of adverse events was observed (p=0.44; RR = 1.18; [95% CI, 0.77 to 1.81]; I2 = 0%). With regard to medication comparisons, the pooled data indicated that acupuncture was more effective in increasing CSBMs (p=0.004; MD = 0.53 [95% CI, 0.17 to 0.88]; I2 = 88%) and improving patients’ quality of life (p<0.00001; SMD = −0.73 [95% CI, −1.02 to −0.44]; I2 = 64%), with high heterogeneity. However, there were no significant differences in responder rate (p=0.12; RR = 1.31; [95% CI, 0.94 to 1.82]; I2 = 53%), BSFS (p=0.5; MD = 0.17 [95% CI, −0.33 to 0.68]; I2 = 93%), or CSS (p=0.05; SMD = −0.62 [95% CI, −1.23 to −0.01]; I2 = 89%). Regarding safety evaluation, acupuncture was safer than medications (p<0.0001; RR = 0.3; [95% CI, 0.18 to 0.52]; I2 = 30%). Conclusions. Current evidence suggests that acupuncture is an efficient and safe treatment for FC. Acupuncture increased stool frequency, improved stool formation, alleviated constipation symptoms, and improved quality of life. However, the evidence quality was relatively low and the relationship between acupuncture and drugs is not clear. More high-quality trials are recommended in the future. PROSPERO registration number: CRD42019143347.


BMJ Open ◽  
2017 ◽  
Vol 7 (12) ◽  
pp. e019468 ◽  
Author(s):  
Bongani Brian Nkambule ◽  
Zibusiso Mkandla ◽  
Tinashe Mutize ◽  
Phiwayinkosi Vusi Dludla

IntroductionThe incidence of cardiovascular disease (CVD) is now at least threefold higher in HIV-infected patients as compared with the general population. Although platelet activation and reactivity are implicated in the development of CVDs in HIV-infected patients, its precise role remains inconclusive. We aim to assess the association between platelet activation and selected cardiovascular risk factors in HIV-1-infected individuals on highly active antiretroviral treatment (HAART).MethodsThis will be a systematic review and meta-analysis of published studies evaluating the association between platelet activation and CVD risk factors in HAART-treated adults. The search strategy will include medical subject headings words for MEDLINE, and this will be adapted to Embase search headings (Emtree) terms for the EMBASE database. The search will cover literature published between 1 January 1996 to 30 April 2017. Studies will be independently screened by two reviewers using predefined criteria. Relevant eligible full texts will be screened; data will be extracted, and a qualitative synthesis will be conducted. Data extraction will be performed using Review Manager V.5.3. To assess the quality and strengths of evidence across selected studies, the Grading of Recommendations Assessment Development and Evaluation approach will be used. The Cochran’s Q statistic and the I2statistics will be used to analyse statistical heterogeneity between studies. If included studies show high levels of homogeneity, a random effects meta-analysis will be performed using R statistical software.Ethics and disseminationThis will be a review of existing studies and will not require ethical approval. The findings will be disseminated through peer-reviewed publication and presented at local and international conferences. An emerging patient management dilemma is that of the increased incidence of CVD in people living with HIV on HAART. This review may inform treatment and cardiovascular risk stratification of HIV-infected patients at increased risk of developing CVD.PROSPERO registration numberCRD42017062393.


Author(s):  
Davide Bona ◽  
Francesca Lombardo ◽  
Kazuhide Matsushima ◽  
Marta Cavalli ◽  
Valerio Panizzo ◽  
...  

Abstract Introduction The anatomy of the esophageal hiatus is altered during esophagogastric surgery with an increased risk of postoperative hiatus hernia (HH). The purpose of this article was to examine the current evidence on the surgical management and outcomes associated with HH after esophagogastric surgery for cancer. Materials and methods Systematic review and meta-analysis. Web of Science, PubMed, and EMBASE data sets were consulted. Results Twenty-seven studies were included for a total of 404 patients requiring surgical treatment for HH after esophagogastric surgery. The age of the patients ranged from 35 to 85 years, and the majority were males (82.3%). Abdominal pain, nausea/vomiting, and dyspnea were the commonly reported symptoms. An emergency repair was required in 51.5%, while a minimally invasive repair was performed in 48.5%. Simple suture cruroplasty and mesh reinforced repair were performed in 65% and 35% of patients, respectively. The duration between the index procedure and HH repair ranged from 3 to 144 months, with the majority (67%) occurring within 24 months. The estimated pooled prevalence rates of pulmonary complications, anastomotic leak, overall morbidity, and mortality were 14.1% (95% CI = 8.0–22.0%), 1.4% (95% CI = 0.8–2.2%), 35% (95% CI = 20.0–54.0%), and 5.0% (95% CI = 3.0–8.0%), respectively. The postoperative follow-up ranged from 1 to 110 months (mean = 24) and the pooled prevalence of HH recurrence was 16% (95% CI = 13.0–21.6%). Conclusions Current evidence reporting data for HH after esophagogastric surgery is narrow. The overall postoperative pulmonary complications, overall morbidity, and mortality are 14%, 35%, and 5%, respectively. Additional studies are required to define indications and treatment algorithm and evaluate the best technique for crural repair at the index operation in an attempt to minimize the risk of HH.


2021 ◽  
pp. 153575972110531
Author(s):  
Faught Edward

Importance Mostantiseizure medications (ASMs) carry a US Food and Drug Administration–mandated class label warning of increased suicidality risk, based on a meta-analysis comparing suicidality between individuals treated with medications vs placebo in randomized clinical trials done before 2008. ASMs approved since then carry this warning although they were not similarly studied. Objective To review all placebo-controlled phase 2 and 3 studies of 10 ASMs approved since 2008 to evaluate the risk of suicidality of these drugs compared with placebo. Data Sources Primary publications and secondary safety analyses in PubMed of all phase 2 and 3 randomized placebo-controlled epilepsy trials of ASMs approved since 2008, using keywords epilepsy, antiepileptic drugs, seizures, suicidality, suicidal ideation, and the names of individual drugs. Study Selection All phase 2 and 3 randomized clinical trials of adjunctive treatment of drug-resistant epilepsy and their secondary safety analyses. Data Extraction and Synthesis Articles were reviewed for frequency of suicidality (ideation, attempts, and completed suicides). Mode of suicidality ascertainment included treatment-emergent adverse event reports, Standardized Medical Dictionary for Regulatory Activities queries for events in prespecified categories including suicidal ideation and behavior, prospective collection of suicidality data as a prespecified safety outcome using the Columbia-Suicide Severity Rating Scale, and retrospective evaluation by blinded review using the Columbia-Classification Algorithm of Suicide Assessment. A meta-analysis compared risk for drugs vs placebo of each outcome for all drugs overall and by individual drugs and trials. Main Outcomes and Measures Suicidality (total and by ideation), attempts, and completed suicides. Results Excluding studies that did not evaluate suicidality (everolimus and fenfluramine) or did not evaluate it prospectively (lacosamide, ezogabine, and clobazam), 5 drugs were analyzed: eslicarbazepine, perampanel, brivaracetam, cannabidiol, and cenobamate. Suicidality was evaluated in 17 randomized clinical trials of these drugs, involving 5996 patients, of whom 4000 patients were treated with ASMs and 1996 with placebo. There was no evidence of increased risk of suicidal ideation (drugs vs placebo overall risk ratio, .75; 95% CI, .35–1.60) or attempt (risk ratio, .75; 95% CI, .30–1.87) overall or for any individual drug. Suicidal ideation occurred in 12 of 4000 patients treated with ASMs (.30%) vs 7 of 1996 patients treated with placebo (.35%) ( P  =  .74). Three patients treated with ASMs and no patients treated with placebo attempted suicide ( P  =  .22). There were no completed suicides. Conclusions and Relevance There is no current evidence that the 5 ASMs evaluated in this study increase suicidality in epilepsy and merit a suicidality class warning


2020 ◽  
Author(s):  
Abere Woretaw Azagew ◽  
Chilot Kassa Mekonnen ◽  
Abebaw Jember Ferede ◽  
Kassahun Gebeyehu Yazew ◽  
Zewdu Baye Tezera

Abstract Background: Adherence to highly active antiretroviral therapy (HAART) is a public health challenge worldwide. Non-adherence to HAART leads to treatment, immunologic, and virological failure. Despite different interventions made, adherence to HAART among adult people living with HIV (PLWHIV) is still inconsistent across studies, and the effect of serostatus disclosure on adherence to HAART was not studied in Ethiopia. Therefore, the study is aimed to determine the pooled prevalence of adherence to HAART and its relationship with serostatus disclosure among adult PLWHIV in Ethiopia.Methods: We searched 3247 original articles, both published and unpublished on Ethiopia dated from January 2016 to November 2019 by using different search engines. Data were extracted using Microsoft excel. New Castle Ottawa Scale quality assessment tool was used. STATA software version 11 was used for analysis. A random-effects model for meta-analysis was computed. Cochran Q statistics and I2 were used to estimate heterogeneity. Egger’s and Begg’s test was used to assess the publication bias.Results: A total of fifteen articles for systematic review and four articles for meta-analysis were used. The pooled prevalence of adherence to HAART is found to be 81.19% (80.1, 82.3). In the subgroup analysis, the pooled prevalence of adherence to HAART was 79.82% (73.19, 86.45) in the Oromia region, 82.51 %( 73.14, 91.87) in the Amhara region, and 72.7% (63.78, 81.61) in the Southern Nations Nationalities and Peoples’ Region (SNNPR). The serostatus disclosure improves adherence to HAART by nearly three times compared to non-serostatus disclosed PLWHIV (AOR=2.99, 95 %CI: 1.88, 4.77).Conclusions: The pooled prevalence of adherence to HAART among adult PLWHIV in Ethiopia was found to be low compared to WHO antiretroviral treatment recommendations. Having serostatus disclosure improved adherence to HAART.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Soraya Doustmohammadian ◽  
Azam Doustmohammadian ◽  
Marjan Momeni

Abstract Background The novel coronavirus (COVID-19) epidemic initially appeared in Wuhan, Hubei Province, China, on 31 December 2019 and was spread rapidly worldwide. Most underlying diseases reported with COVID-19 patients are diabetes, hypertension, coronary heart diseases, and cerebrovascular disease. We do not know whether individuals with thyroid disease are at increased risk of COVID-19 infection. Methods Two experienced researchers will conduct an electronic search of the databases including PubMed/MEDLINE, the Cochrane Reviews, and the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, Scopus, and ProQuest, for articles published since October 2019. Clinical trials and observational studies will be included. Studies will be screened after de-duplication. A standardized data extraction form will be developed through discussions with the review team and will be revised after piloting. An appropriate risk of bias assessment tool will be used to assess the quality of studies. Two independent reviewers will assess the eligibility, extraction of detailed information, and quality assessment of studies. The results will be pooled for meta-analysis, subgroup analysis and/or descriptive analysis based on the included data conditions. Conclusion Results of this study will provide current evidence on the association of COVID-19 diseases with any thyroid disorders such as hypothyroidism, thyrotoxicosis, and thyroid cancer with or without radioiodine therapy. Findings will be disseminated in peer-reviewed publications and conference presentations. Trial registration PROSPERO registration number: CRD42020184289. https://www.crd.york.ac.uk/PROSPERO/#recordDetails


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.


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