scholarly journals Offline Digital Education for Medical Students: Systematic Review and Meta-Analysis by the Digital Health Education Collaboration (Preprint)

2019 ◽  
Author(s):  
Bhone Myint Kyaw ◽  
Pawel Posadzki ◽  
Gerard Dunleavy ◽  
Monika Semwal ◽  
Ushashree Divakar ◽  
...  

BACKGROUND Medical schools in low- and middle-income countries are facing a shortage of staff, limited infrastructure, and restricted access to fast and reliable internet. Offline digital education may be an alternative solution for these issues, allowing medical students to learn at their own time and pace, without the need for a network connection. OBJECTIVE The primary objective of this systematic review was to assess the effectiveness of offline digital education compared with traditional learning or a different form of offline digital education such as CD-ROM or PowerPoint presentations in improving knowledge, skills, attitudes, and satisfaction of medical students. The secondary objective was to assess the cost-effectiveness of offline digital education, changes in its accessibility or availability, and its unintended/adverse effects on students. METHODS We carried out a systematic review of the literature by following the Cochrane methodology. We searched seven major electronic databases from January 1990 to August 2017 for randomized controlled trials (RCTs) or cluster RCTs. Two authors independently screened studies, extracted data, and assessed the risk of bias. We assessed the quality of evidence using the Grading of Recommendations, Assessment, Development, and Evaluations criteria. RESULTS We included 36 studies with 3325 medical students, of which 33 were RCTs and three were cluster RCTs. The interventions consisted of software programs, CD-ROMs, PowerPoint presentations, computer-based videos, and other computer-based interventions. The pooled estimate of 19 studies (1717 participants) showed no significant difference between offline digital education and traditional learning groups in terms of students’ postintervention knowledge scores (standardized mean difference=0.11, 95% CI –0.11 to 0.32; small effect size; low-quality evidence). Meta-analysis of four studies found that, compared with traditional learning, offline digital education improved medical students’ postintervention skills (standardized mean difference=1.05, 95% CI 0.15-1.95; large effect size; low-quality evidence). We are uncertain about the effects of offline digital education on students’ attitudes and satisfaction due to missing or incomplete outcome data. Only four studies estimated the costs of offline digital education, and none reported changes in accessibility or availability of such education or in the adverse effects. The risk of bias was predominantly high in more than half of the included studies. The overall quality of the evidence was low (for knowledge, skills, attitudes, and satisfaction) due to the study limitations and inconsistency across the studies. CONCLUSIONS Our findings suggest that offline digital education is as effective as traditional learning in terms of medical students’ knowledge and may be more effective than traditional learning in terms of medical students’ skills. However, there is a need to further investigate students’ attitudes and satisfaction with offline digital education as well as its cost-effectiveness, changes in its accessibility or availability, and any resulting unintended/adverse effects.

2018 ◽  
Author(s):  
Bhone Myint Kyaw ◽  
Nakul Saxena ◽  
Pawel Posadzki ◽  
Jitka Vseteckova ◽  
Charoula Konstantia Nikolaou ◽  
...  

BACKGROUND Virtual reality (VR) is a technology that allows the user to explore and manipulate computer-generated real or artificial three-dimensional multimedia sensory environments in real time to gain practical knowledge that can be used in clinical practice. OBJECTIVE The aim of this systematic review was to evaluate the effectiveness of VR for educating health professionals and improving their knowledge, cognitive skills, attitudes, and satisfaction. METHODS We performed a systematic review of the effectiveness of VR in pre- and postregistration health professions education following the gold standard Cochrane methodology. We searched 7 databases from the year 1990 to August 2017. No language restrictions were applied. We included randomized controlled trials and cluster-randomized trials. We independently selected studies, extracted data, and assessed risk of bias, and then, we compared the information in pairs. We contacted authors of the studies for additional information if necessary. All pooled analyses were based on random-effects models. We used the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach to rate the quality of the body of evidence. RESULTS A total of 31 studies (2407 participants) were included. Meta-analysis of 8 studies found that VR slightly improves postintervention knowledge scores when compared with traditional learning (standardized mean difference [SMD]=0.44; 95% CI 0.18-0.69; I2=49%; 603 participants; moderate certainty evidence) or other types of digital education such as online or offline digital education (SMD=0.43; 95% CI 0.07-0.79; I2=78%; 608 participants [8 studies]; low certainty evidence). Another meta-analysis of 4 studies found that VR improves health professionals’ cognitive skills when compared with traditional learning (SMD=1.12; 95% CI 0.81-1.43; I2=0%; 235 participants; large effect size; moderate certainty evidence). Two studies compared the effect of VR with other forms of digital education on skills, favoring the VR group (SMD=0.5; 95% CI 0.32-0.69; I2=0%; 467 participants; moderate effect size; low certainty evidence). The findings for attitudes and satisfaction were mixed and inconclusive. None of the studies reported any patient-related outcomes, behavior change, as well as unintended or adverse effects of VR. Overall, the certainty of evidence according to the GRADE criteria ranged from low to moderate. We downgraded our certainty of evidence primarily because of the risk of bias and/or inconsistency. CONCLUSIONS We found evidence suggesting that VR improves postintervention knowledge and skills outcomes of health professionals when compared with traditional education or other types of digital education such as online or offline digital education. The findings on other outcomes are limited. Future research should evaluate the effectiveness of immersive and interactive forms of VR and evaluate other outcomes such as attitude, satisfaction, cost-effectiveness, and clinical practice or behavior change.


2019 ◽  
Author(s):  
Serena Brusamento ◽  
Bhone Myint Kyaw ◽  
Penny Whiting ◽  
Li Li ◽  
Lorainne Tudor Car

BACKGROUND Reducing childhood morbidity and mortality is challenging, particularly in countries with a shortage of qualified health care workers. Lack of trainers makes it difficult to provide the necessary continuing education in pediatrics for postregistration health professionals. Digital education, teaching and learning by means of digital technologies, has the potential to deliver medical education to a large audience while limiting the number of trainers needed. OBJECTIVE The goal of the research was to evaluate whether digital education can replace traditional learning to improve postregistration health professionals’ knowledge, skills, attitudes, and satisfaction and foster behavior change in the field of pediatrics. METHODS We completed a systematic review of the literature by following the Cochrane methodology. We searched 7 major electronic databases for articles published from January 1990 to August 2017. No language restrictions were applied. We independently selected studies, extracted data, and assessed risk of bias, and pairs of authors compared information. We contacted authors of studies for additional information if necessary. All pooled analyses were based on random effects models. We included individually or cluster randomized controlled trials that compared digital education with traditional learning, no intervention, or other forms of digital education. We assessed the quality of evidence using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) criteria. RESULTS Twenty studies (1382 participants) were included. Participants included pediatricians, physicians, nurses, and midwives. Digital education technologies were assessed including high-fidelity mannequins (6 studies), computer-based education (12 studies), mobile learning (1 study), and virtual reality (1 study). Most studies reported that digital education was either as effective as or more effective than the control intervention for outcomes including skill, knowledge, attitude, and satisfaction. High-fidelity mannequins were associated with higher postintervention skill scores compared with low-fidelity mannequins (standardized mean difference 0.62; 95% CI 0.17-1.06; moderate effect size, low-quality evidence). One study reported physician change in practicing behavior and found similar effects between offline plus online digital education and no intervention. The only study that assessed impact on patient outcome found no difference between intervention and control groups. None of the included studies reported adverse or untoward effects or economic outcomes of the digital education interventions. The risk of bias was mainly unclear or high. The quality of evidence was low due to study inconsistencies, limitations, or imprecision across the studies. CONCLUSIONS Digital education for postregistration health professions education in pediatrics is at least as effective as traditional learning and more effective than no learning. High-fidelity mannequins were found to be more effective at improving skills than traditional learning with low-fidelity mannequins. Computer-based offline/online digital education was better than no intervention for knowledge and skill outcomes and as good as traditional face-to-face learning. This review highlights evidence gaps calling for more methodologically rigorous randomized controlled trials on the topic.


10.2196/12967 ◽  
2019 ◽  
Vol 21 (8) ◽  
pp. e12967 ◽  
Author(s):  
Bhone Myint Kyaw ◽  
Pawel Posadzki ◽  
Sophie Paddock ◽  
Josip Car ◽  
James Campbell ◽  
...  

Background Effective communication skills are essential in diagnosis and treatment processes and in building the doctor-patient relationship. Objective Our aim was to evaluate the effectiveness of digital education in medical students for communication skills development. Broadly, we assessed whether digital education could improve the quality of future doctors’ communication skills. Methods We performed a systematic review and searched seven electronic databases and two trial registries for randomized controlled trials (RCTs) and cluster RCTs (cRCTs) published between January 1990 and September 2018. Two reviewers independently screened the citations, extracted data from the included studies, and assessed the risk of bias. We also assessed the quality of evidence using the Grading of Recommendations, Assessment, Development, and Evaluations assessment (GRADE). Results We included 12 studies with 2101 medical students, of which 10 were RCTs and two were cRCTs. The digital education included online modules, virtual patient simulations, and video-assisted oral feedback. The control groups included didactic lectures, oral feedback, standard curriculum, role play, and no intervention as well as less interactive forms of digital education. The overall risk of bias was high, and the quality of evidence ranged from moderate to very low. For skills outcome, meta-analysis of three studies comparing digital education to traditional learning showed no statistically significant difference in postintervention skills scores between the groups (standardized mean difference [SMD]=–0.19; 95% CI –0.9 to 0.52; I2=86%, N=3 studies [304 students]; small effect size; low-quality evidence). Similarly, a meta-analysis of four studies comparing the effectiveness of blended digital education (ie, online or offline digital education plus traditional learning) and traditional learning showed no statistically significant difference in postintervention skills between the groups (SMD=0.15; 95% CI –0.26 to 0.56; I2=86%; N=4 studies [762 students]; small effect size; low-quality evidence). The additional meta-analysis of four studies comparing more interactive and less interactive forms of digital education also showed little or no difference in postintervention skills scores between the two groups (SMD=0.12; 95% CI: –0.09 to 0.33; I2=40%; N=4 studies [893 students]; small effect size; moderate-quality evidence). For knowledge outcome, two studies comparing the effectiveness of blended online digital education and traditional learning reported no difference in postintervention knowledge scores between the groups (SMD=0.18; 95% CI: –0.2 to 0.55; I2=61%; N=2 studies [292 students]; small effect size; low-quality evidence). The findings on attitudes, satisfaction, and patient-related outcomes were limited or mixed. None of the included studies reported adverse outcomes or economic evaluation of the interventions. Conclusions We found low-quality evidence showing that digital education is as effective as traditional learning in medical students’ communication skills training. Blended digital education seems to be at least as effective as and potentially more effective than traditional learning for communication skills and knowledge. We also found no difference in postintervention skills between more and less interactive forms of digital education. There is a need for further research to evaluate the effectiveness of other forms of digital education such as virtual reality, serious gaming, and mobile learning on medical students’ attitude, satisfaction, and patient-related outcomes as well as the adverse effects and cost-effectiveness of digital education.


2021 ◽  
Vol 10 (3) ◽  
pp. e19410313137
Author(s):  
Luciana Dorochenko Martins ◽  
Márcia Rezende ◽  
Ana Cláudia Chibinski ◽  
Alessandro Dourado Loguercio ◽  
Marcelo Carlos Bortoluzzi ◽  
...  

This systematic review and meta-analysis evaluated if ketorolac reduces the intensity of postoperative pain after impacted third molars surgery in adults compared to the use of tramadol. A comprehensive search was performed in the MEDLINE/PubMed, Scopus, Web of Science, LILACS, BBO, EMBASE, Cochrane Library, SIGLE and grey literature, in accordance with the PRISMA guidelines. The quality of the evidence was evaluated using the GRADE approach. Meta-analysis was performed on studies considered at low risk of bias. After duplicates removal, 4526 articles were identified, but only nine studies were included for qualitative analysis. After updating in 2021, four studies were added, totaling 13 studies included for qualitative analysis. Only two studies, classified at “low” risk of bias, were included in the meta-analysis of the primary outcome. The difference in means for pain intensity (moderate quality of evidence due to imprecision) was – 0.27 (95% CI = – 0.82 to 0.28; p = 0.34). Data from adverse effects (low quality of evidence due to very serious issues in imprecision) was just reported in one study at “low” risk of bias. Data was not heterogeneous (Chi2 test p = 0.14; I2 = 55%). It was not possible to evaluate any secondary outcomes (time to first rescue analgesic drug in h, total amount of analgesics consumed and adverse effects) due to low number of studies included. There is a lack of strong evidence to assure the superiority of ketorolac or tramadol in reducing the postoperative pain after extraction of impacted third molars.


Author(s):  
Bhone Myint Kyaw ◽  
Pawel Posadzki ◽  
Sophie Paddock ◽  
Josip Car ◽  
James Campbell ◽  
...  

BACKGROUND Effective communication skills are essential in diagnosis and treatment processes and in building the doctor-patient relationship. OBJECTIVE Our aim was to evaluate the effectiveness of digital education in medical students for communication skills development. Broadly, we assessed whether digital education could improve the quality of future doctors’ communication skills. METHODS We performed a systematic review and searched seven electronic databases and two trial registries for randomized controlled trials (RCTs) and cluster RCTs (cRCTs) published between January 1990 and September 2018. Two reviewers independently screened the citations, extracted data from the included studies, and assessed the risk of bias. We also assessed the quality of evidence using the Grading of Recommendations, Assessment, Development, and Evaluations assessment (GRADE). RESULTS We included 12 studies with 2101 medical students, of which 10 were RCTs and two were cRCTs. The digital education included online modules, virtual patient simulations, and video-assisted oral feedback. The control groups included didactic lectures, oral feedback, standard curriculum, role play, and no intervention as well as less interactive forms of digital education. The overall risk of bias was high, and the quality of evidence ranged from moderate to very low. For skills outcome, meta-analysis of three studies comparing digital education to traditional learning showed no statistically significant difference in postintervention skills scores between the groups (standardized mean difference [SMD]=–0.19; 95% CI –0.9 to 0.52; I2=86%, N=3 studies [304 students]; small effect size; low-quality evidence). Similarly, a meta-analysis of four studies comparing the effectiveness of blended digital education (ie, online or offline digital education plus traditional learning) and traditional learning showed no statistically significant difference in postintervention skills between the groups (SMD=0.15; 95% CI –0.26 to 0.56; I2=86%; N=4 studies [762 students]; small effect size; low-quality evidence). The additional meta-analysis of four studies comparing more interactive and less interactive forms of digital education also showed little or no difference in postintervention skills scores between the two groups (SMD=0.12; 95% CI: –0.09 to 0.33; I2=40%; N=4 studies [893 students]; small effect size; moderate-quality evidence). For knowledge outcome, two studies comparing the effectiveness of blended online digital education and traditional learning reported no difference in postintervention knowledge scores between the groups (SMD=0.18; 95% CI: –0.2 to 0.55; I2=61%; N=2 studies [292 students]; small effect size; low-quality evidence). The findings on attitudes, satisfaction, and patient-related outcomes were limited or mixed. None of the included studies reported adverse outcomes or economic evaluation of the interventions. CONCLUSIONS We found low-quality evidence showing that digital education is as effective as traditional learning in medical students’ communication skills training. Blended digital education seems to be at least as effective as and potentially more effective than traditional learning for communication skills and knowledge. We also found no difference in postintervention skills between more and less interactive forms of digital education. There is a need for further research to evaluate the effectiveness of other forms of digital education such as virtual reality, serious gaming, and mobile learning on medical students’ attitude, satisfaction, and patient-related outcomes as well as the adverse effects and cost-effectiveness of digital education.


10.2196/14231 ◽  
2019 ◽  
Vol 21 (9) ◽  
pp. e14231 ◽  
Author(s):  
Serena Brusamento ◽  
Bhone Myint Kyaw ◽  
Penny Whiting ◽  
Li Li ◽  
Lorainne Tudor Car

Background Reducing childhood morbidity and mortality is challenging, particularly in countries with a shortage of qualified health care workers. Lack of trainers makes it difficult to provide the necessary continuing education in pediatrics for postregistration health professionals. Digital education, teaching and learning by means of digital technologies, has the potential to deliver medical education to a large audience while limiting the number of trainers needed. Objective The goal of the research was to evaluate whether digital education can replace traditional learning to improve postregistration health professionals’ knowledge, skills, attitudes, and satisfaction and foster behavior change in the field of pediatrics. Methods We completed a systematic review of the literature by following the Cochrane methodology. We searched 7 major electronic databases for articles published from January 1990 to August 2017. No language restrictions were applied. We independently selected studies, extracted data, and assessed risk of bias, and pairs of authors compared information. We contacted authors of studies for additional information if necessary. All pooled analyses were based on random effects models. We included individually or cluster randomized controlled trials that compared digital education with traditional learning, no intervention, or other forms of digital education. We assessed the quality of evidence using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) criteria. Results Twenty studies (1382 participants) were included. Participants included pediatricians, physicians, nurses, and midwives. Digital education technologies were assessed including high-fidelity mannequins (6 studies), computer-based education (12 studies), mobile learning (1 study), and virtual reality (1 study). Most studies reported that digital education was either as effective as or more effective than the control intervention for outcomes including skill, knowledge, attitude, and satisfaction. High-fidelity mannequins were associated with higher postintervention skill scores compared with low-fidelity mannequins (standardized mean difference 0.62; 95% CI 0.17-1.06; moderate effect size, low-quality evidence). One study reported physician change in practicing behavior and found similar effects between offline plus online digital education and no intervention. The only study that assessed impact on patient outcome found no difference between intervention and control groups. None of the included studies reported adverse or untoward effects or economic outcomes of the digital education interventions. The risk of bias was mainly unclear or high. The quality of evidence was low due to study inconsistencies, limitations, or imprecision across the studies. Conclusions Digital education for postregistration health professions education in pediatrics is at least as effective as traditional learning and more effective than no learning. High-fidelity mannequins were found to be more effective at improving skills than traditional learning with low-fidelity mannequins. Computer-based offline/online digital education was better than no intervention for knowledge and skill outcomes and as good as traditional face-to-face learning. This review highlights evidence gaps calling for more methodologically rigorous randomized controlled trials on the topic. Trial Registration PROSPERO CRD42017057793; https://tinyurl.com/y5q9q5o6


BMJ ◽  
2021 ◽  
pp. m4743
Author(s):  
Joshua Z Goldenberg ◽  
Andrew Day ◽  
Grant D Brinkworth ◽  
Junko Sato ◽  
Satoru Yamada ◽  
...  

Abstract Objective To determine the efficacy and safety of low carbohydrate diets (LCDs) and very low carbohydrate diets (VLCDs) for people with type 2 diabetes. Design Systematic review and meta-analysis. Data sources Searches of CENTRAL, Medline, Embase, CINAHL, CAB, and grey literature sources from inception to 25 August 2020. Study selection Randomized clinical trials evaluating LCDs (<130 g/day or <26% of a 2000 kcal/day diet) and VLCDs (<10% calories from carbohydrates) for at least 12 weeks in adults with type 2 diabetes were eligible. Data extraction Primary outcomes were remission of diabetes (HbA 1c <6.5% or fasting glucose <7.0 mmol/L, with or without the use of diabetes medication), weight loss, HbA 1c , fasting glucose, and adverse events. Secondary outcomes included health related quality of life and biochemical laboratory data. All articles and outcomes were independently screened, extracted, and assessed for risk of bias and GRADE certainty of evidence at six and 12 month follow-up. Risk estimates and 95% confidence intervals were calculated using random effects meta-analysis. Outcomes were assessed according to a priori determined minimal important differences to determine clinical importance, and heterogeneity was investigated on the basis of risk of bias and seven a priori subgroups. Any subgroup effects with a statistically significant test of interaction were subjected to a five point credibility checklist. Results Searches identified 14 759 citations yielding 23 trials (1357 participants), and 40.6% of outcomes were judged to be at low risk of bias. At six months, compared with control diets, LCDs achieved higher rates of diabetes remission (defined as HbA 1c <6.5%) (76/133 (57%) v 41/131 (31%); risk difference 0.32, 95% confidence interval 0.17 to 0.47; 8 studies, n=264, I 2 =58%). Conversely, smaller, non-significant effect sizes occurred when a remission definition of HbA 1c <6.5% without medication was used. Subgroup assessments determined as meeting credibility criteria indicated that remission with LCDs markedly decreased in studies that included patients using insulin. At 12 months, data on remission were sparse, ranging from a small effect to a trivial increased risk of diabetes. Large clinically important improvements were seen in weight loss, triglycerides, and insulin sensitivity at six months, which diminished at 12 months. On the basis of subgroup assessments deemed credible, VLCDs were less effective than less restrictive LCDs for weight loss at six months. However, this effect was explained by diet adherence. That is, among highly adherent patients on VLCDs, a clinically important reduction in weight was seen compared with studies with less adherent patients on VLCDs. Participants experienced no significant difference in quality of life at six months but did experience clinically important, but not statistically significant, worsening of quality of life and low density lipoprotein cholesterol at 12 months. Otherwise, no significant or clinically important between group differences were found in terms of adverse events or blood lipids at six and 12 months. Conclusions On the basis of moderate to low certainty evidence, patients adhering to an LCD for six months may experience remission of diabetes without adverse consequences. Limitations include continued debate around what constitutes remission of diabetes, as well as the efficacy, safety, and dietary satisfaction of longer term LCDs. Systematic review registration PROSPERO CRD42020161795.


Author(s):  
Antonio Jose Martin-Perez ◽  
María Fernández-González ◽  
Paula Postigo-Martin ◽  
Marc Sampedro Pilegaard ◽  
Carolina Fernández-Lao ◽  
...  

There is no systematic review that has identified existing studies evaluating the pharmacological and non-pharmacological intervention for pain management in patients with bone metastasis. To fill this gap in the literature, this systematic review with meta-analysis aims to evaluate the effectiveness of different antalgic therapies (pharmacological and non-pharmacological) in the improvement of pain of these patients. To this end, this protocol has been written according to the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P) and registered in PROSPERO (CRD42020135762). A systematic search will be carried out in four international databases: Medline (Via PubMed), Web of Science, Cochrane Library and SCOPUS, to select the randomized controlled clinical trials. The Risk of Bias Tool developed by Cochrane will be used to assess the risk of bias and the quality of the identified studies. A narrative synthesis will be used to describe and compare the studies, and after the data extraction, random effects model and a subgroup analyses will be performed according to the type of intervention, if possible. This protocol aims to generate a systematic review that compiles and synthesizes the best and most recent evidence on the treatment of pain derived from vertebral metastasis.


Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2159
Author(s):  
Charalampos Aktypis ◽  
Maria-Eleni Spei ◽  
Maria Yavropoulou ◽  
Göran Wallin ◽  
Anna Koumarianou ◽  
...  

A broad spectrum of novel targeted therapies with prime antitumor activity and/or ample control of hormonal symptoms together with an overall acceptable safety profile have emerged for patients with metastatic neuroendocrine neoplasms (NENs). In this systematic review and quantitative meta-analysis, the PubMed, EMBASE, Cochrane Central Register of Controlled Trials and clinicaltrials.gov databases were searched to assess and compare the safety profile of NEN treatments with special focus on the cardiovascular adverse effects of biotherapy and molecular targeted therapies (MTTs). Quality/risk of bias were assessed using GRADE criteria. Placebo-controlled randomized clinical trials (RCTs) in patients with metastatic NENs, including medullary thyroid cancer (MTC) were included. A total of 3695 articles and 122 clinical trials registered in clinicaltrials.gov were screened. We included sixteen relevant RCTs comprising 3408 unique patients assigned to different treatments compared with placebo. All the included studies had a low risk of bias. We identified four drug therapies for NENs with eligible placebo-controlled RCTs: somatostatin analogs (SSAs), tryptophan hydroxylase (TPH) inhibitors, mTOR inhibitors and tyrosine kinase inhibitors (TKI). Grade 3 and 4 adverse effects (AE) were more often encountered in patients treated with mTOR inhibitors and TKI (odds ratio [OR]: 2.42, 95% CI: 1.87–3.12 and OR: 3.41, 95% CI: 1.46–7.96, respectively) as compared to SSAs (OR:0.77, 95% CI: 0.47–1.27) and TPH inhibitors (OR:0.77, 95% CI: 0.35–1.69). MTOR inhibitors had the highest risk for serious cardiac AE (OR:3.28, 95% CI: 1.66–6.48) followed by TKIs (OR:1.51, 95% CI: 0.59–3.83). Serious vascular AE were more often encountered in NEN patients treated with mTOR inhibitors (OR: 1.72, 95% CI: 0.64–4.64) and TKIs (OR:1.64, 95% CI: 0.35–7.78). Finally, patients on TKIs were at higher risk for new-onset or exacerbation of pre-existing hypertension (OR:3.31, 95% CI: 1.87–5.86). In conclusion, SSAs and TPH inhibitors appear to be safer as compared to mTOR inhibitors and TKIs with regards to their overall toxicity profile, and cardiovascular toxicities in particular. Special consideration should be given to a patient-tailored approach with anticipated toxicities of targeted NEN treatments together with assessment of cardiovascular comorbidities, assisting clinicians in treatment selection and early recognition/management of cardiovascular toxicities. This approach could improve patient compliance and preserve cardiovascular health and overall quality of life.


Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2459-2459
Author(s):  
Jorn Gerritsma ◽  
Ilja Oomen ◽  
Sanne Meinderts ◽  
C. Ellen van der Schoot ◽  
Bart J. Biemond ◽  
...  

Introduction: Blood transfusions are an important treatment modality for patients with either acute or chronic onset anemia such as trauma, sickle cell disease, and hematological malignancies. Transfusion poses a risk for alloimmunization, which may lead to potentially lethal transfusion reactions. A promising strategy to prevent alloimmunization is extensive matching on blood groups, yet this is a costly procedure and should be reserved for patients at highest risk for alloimmunization. Identification of genetic variants that increase the risk for alloimmunization might help to identify high-risk patients and could be used as a screening tool for patients receiving multiple transfusions. Objectives: To summarize all available evidence on genetic risk factors for alloimmunization after blood transfusion. Design: Systematic review with meta-analysis of observational studies. Studies were only included in the meta-analysis if polymorphisms were tested at least 3 times, and if ethnic background of the population and the control populations were comparable between studies. Data sources: The online databases Embase, MEDLINE and the Cochrane Library were search for relevant articles with search terms: 1) transfusion, 2) alloimmunization 3) genetics. The search was last updated March 2018. Eligibility criteria: 1) Primary study that assessed the association of genetic polymorphisms with transfusion related alloimmunization, 2) a human population, 3) studies with at least 50 patients, 4) full text availability. Data extraction: Two reviewers independently screened articles for eligibility, extracted data using a standardized data extraction form. Extracted data included study setting, study population, participant demographics, baseline characteristics, study methodology, comparisons and outcome, and risk of bias. Primary outcome measure: Alloimmunization after one or more blood transfusions. Risk of bias assessment: The quality of the included studies was assessed by the Q-genie tool for genetic association studies. Results: A total of 2045 cases and 24084 controls were derived from 18 genetic case-control studies that were included in this systematic review. Most commonly studied disease group was sickle cell disease (SCD) (8 studies). Three studies included patients with different diseases and seven studies did not report the underlying disease. Eleven studies identified the association of HLA polymorphisms with alloimmunization and 8 studies focused on non-HLA variants. Overall quality of the included studies was moderate (11 studies), 2 studies were of high quality, and 5 studies were ranked as poor. HLA-DRB1*04 (Odds Ratio 7.16, 95%CI 3.87-13.22, P<0.00001) and HLA-DRB1*15 (OR 3.01, 95%CI 1.84-5.53, P<0.0001) were by meta-analysis significantly associated with anti-Fy(a) formation, although there was considerable heterogeneity (I2=78% and 55% respectively). Moreover, HLA-DRB1*10 (OR 2.64, 95%CI 1.41-4.95, P=0.002), HLA*DRB1*11 (OR 2.11, 95%CI 1.34-3.32, P=0.001), and HLA-DRB1*13 (OR 1.71, 95%CI 1.26-2.33, P=0.0006) were overall associated with anti-Kell formation. Heterogeneity was less prominent with an I2 of 0%, 54% and 19% respectively (Figure 1). No other variants were eligible for meta-analysis. Non-HLA variants were tested less extensively, as most variants were reported by only 1 study. Polymorphisms of genes in the immunomodulatory pathways were assessed most frequently. Of these variants, FC-gamma-receptor 2C.nc-ORF was associated with a decreased risk of alloimmunization in SCD (OR 0.26, 95%CI 0.11-0.64, p=0.003). All other associations that were described as significant by the original articles were summarized in Figure 2. Discussion: There is limited evidence supporting the role of genetic risk factors for alloimmunization. The results of our meta-analysis suggest that several HLA polymorphisms potentially influence antigen presentation of the Duffy(a) and Kell antigen. Once confirmed by experimental studies, these polymorphisms could be used as a screening tool for the prevention of alloimmunization among frequently transfused patients. Overall, the effect of genetic variants on alloimmunization has mostly been assessed by small studies, hampering reliable interpretation of the results. Future studies should include large and well-defined cohorts when performing genetic analysis on this complicated subject. Disclosures No relevant conflicts of interest to declare.


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