Multifactorial interventions for preventing falls in older people living in the community: a systematic review and meta-analysis of 41 trials and almost 20 000 participants

ObjectiveTo assess the longer term effects of multifactorial interventions for preventing falls in older people living in the community, and to explore whether prespecific trial-level characteristics are associated with greater fall prevention effects.DesignSystematic review with meta-analysis and meta-regression.Data sourcesMEDLINE, EMBASE, CINHAL, CENTRAL and trial registries were searched up to 25 July 2018.Study selectionWe included randomised controlled trials (≥12 months’ follow-up) evaluating the effects of multifactorial interventions on falls in older people aged 65 years and over, living in the community, compared with either usual care or usual care plus advice.Review methodsTwo authors independently verified studies for inclusion, assessed risk of bias and extracted data. Rate ratios (RaR) with 95% CIs were calculated for rate of falls, risk ratios (RR) for dichotomous outcomes and standardised mean difference for continuous outcomes. Data were pooled using a random effects model. The Grading of Recommendations, Assessment, Development and Evaluation was used to assess the quality of the evidence.ResultsWe included 41 trials totalling 19 369 participants; mean age 72–85 years. Exercise was the most common prespecified component of the multifactorial interventions (85%; n=35/41). Most trials were judged at unclear or high risk of bias in ≥1 domain. Twenty trials provided data on rate of falls and showed multifactorial interventions may reduce the rate at which people fall compared with the comparator (RaR 0.79, 95% CI 0.70 to 0.88; 20 trials; 10 116 participants; I2=90%; low-quality evidence). Multifactorial interventions may also slightly lower the risk of people sustaining one or more falls (RR 0.95, 95% CI 0.90 to 1.00; 30 trials; 13 817 participants; I2=56%; moderate-quality evidence) and recurrent falls (RR 0.88, 95% CI 0.78 to 1.00; 15 trials; 7277 participants; I2=46%; moderate-quality evidence). However, there may be little or no difference in other fall-related outcomes, such as fall-related fractures, falls requiring hospital admission or medical attention and health-related quality of life. Very few trials (n=3) reported on adverse events related to the intervention. Prespecified subgroup analyses showed that the effect on rate of falls may be smaller when compared with usual care plus advice as opposed to usual care only. Overall, heterogeneity remained high and was not explained by the prespecified characteristics included in the meta-regression.ConclusionMultifactorial interventions (most of which include exercise prescription) may reduce the rate of falls and slightly reduce risk of older people sustaining one or more falls and recurrent falls (defined as two or more falls within a specified time period).Trial registration numberCRD42018102549.

Download Full-text

Prevention of exacerbations in patients with stable non-cystic fibrosis bronchiectasis: a systematic review and meta-analysis of pharmacological and non-pharmacological therapies

BMJ evidence-based medicine ◽

10.1136/bmjebm-2018-110893 ◽

2018 ◽

Vol 23 (3) ◽

pp. 96-103 ◽

Cited By ~ 6

Author(s):

Abd Moain Abu Dabrh ◽

Adam T Hill ◽

Claudia C Dobler ◽

Noor Asi ◽

Wigdan H Farah ◽

...

Keyword(s):

Quality Of Life ◽

Systematic Review ◽

Cystic Fibrosis ◽

Meta Analysis ◽

Moderate Quality ◽

Number Of Patients ◽

Inhaled Antibiotics ◽

Quality Evidence

BackgroundSeveral pharmacological and non-pharmacological therapies are used to treat stable bronchiectasis of non-cystic fibrosis (CF) aetiology.ObjectiveWe conducted a systematic review and meta-analysis to assess the evidence of the effectiveness of pharmacological and non-pharmacological treatment options in patients with stable non-CF bronchiectasis with a focus on reducing exacerbations.Study selectionMultiple databases were searched through September 2017. Outcomes included the number of patients with exacerbation events, mean number of exacerbations, hospitalisations, mortality, quality of life measures, and safety and adverse effects. Meta-analysis was conducted using the random effects model.Findings30 randomised controlled trials enrolled subjects with non-CF bronchiectasis using different interventions. Moderate-quality evidence supported the effect of long-term antibiotics (≥3 months) on lowering the number of patients experiencing exacerbation events (relative risk 0.77 (95% CI 0.68 to 0.89)), reducing number of exacerbations (incidence rate ratio 0.62 (95% CI 0.49 to 0.78)), improving forced expiratory volume (litre) in the first second (FEV1) (weighted mean difference (WMD); 0.02 (95% CI 0.00 to 0.04)), decreasing sputum purulence scores (numerical scale of 1-8) (WMD −0.90 (95% CI −1.58 to −0.22)) and improving quality of life scores assessed by the St George’s Respiratory Questionnaire (WMD −6.07 (95% CI −10.7 to −1.43)). Bronchospasm increased with inhaled antibiotics while diarrhoea increased particularly with oral macrolide therapy.ConclusionsModerate-quality evidence supports long-term antibiotic therapy for preventing exacerbations in stable non-CF bronchiectasis. However, data about the optimum agent, mode of therapy and length of treatment are limited. There is paucity of high-quality evidence to support the management of stable non-CF bronchiectasis including prevention of exacerbations.

Download Full-text

Effects of presurgical interventions on chronic pain after total knee replacement: a systematic review and meta-analysis of randomised controlled trials

BMJ Open ◽

10.1136/bmjopen-2019-033248 ◽

2020 ◽

Vol 10 (1) ◽

pp. e033248 ◽

Cited By ~ 1

Author(s):

Jane Dennis ◽

Vikki Wylde ◽

Rachael Gooberman-Hill ◽

AW Blom ◽

Andrew David Beswick

Keyword(s):

Systematic Review ◽

Chronic Pain ◽

Randomised Controlled Trials ◽

Meta Analysis ◽

Risk Of Bias ◽

Controlled Trials ◽

Moderate Quality ◽

Total Knee ◽

Randomised Controlled ◽

Quality Evidence

ObjectiveNearly 100 000 primary total knee replacements (TKR) are performed in the UK annually. The primary aim of TKR is pain relief, but 10%–34% of patients report chronic pain. The aim of this systematic review was to evaluate the effectiveness of presurgical interventions in preventing chronic pain after TKR.DesignMEDLINE, Embase, CINAHL,The Cochrane Libraryand PsycINFO were searched from inception to December 2018. Screening and data extraction were performed by two authors. Meta-analysis was conducted using a random effects model. Risk of bias was assessed using the Cochrane tool and quality of evidence was assessed by Grading of Recommendations Assessment, Development and Evaluation.Primary and secondary outcomesPain at 6 months or longer; adverse events.InterventionsPresurgical interventions aimed at improving TKR outcomes.ResultsEight randomised controlled trials (RCTs) with data from 960 participants were included. The studies involved nine eligible comparisons. We found moderate-quality evidence of no effect of exercise programmes on chronic pain after TKR, based on a meta-analysis of 6 interventions with 229 participants (standardised mean difference 0.20, 95% CI −0.06 to 0.47, I2=0%). Sensitivity analysis restricted to studies at overall low risk of bias confirmed findings. Another RCT of exercise with no data available for meta-analysis showed no benefit. Studies evaluating combined exercise and education intervention (n=1) and education alone (n=1) suggested similar findings. Adverse event data were reported by most studies, but events were too few to draw conclusions.ConclusionsWe found low to moderate-quality evidence to suggest that neither preoperative exercise, education nor a combination of both is effective in preventing chronic pain after TKR. This review also identified a lack of evaluations of other preoperative interventions, such as multimodal pain management, which may improve long-term pain outcomes after TKR.PROSPERO registration numberCRD42017041382.

Download Full-text

Efficacy and acceptability of psychosocial interventions in asylum seekers and refugees: systematic review and meta-analysis

Epidemiology and Psychiatric Sciences ◽

10.1017/s2045796019000027 ◽

2019 ◽

Vol 28 (04) ◽

pp. 376-388 ◽

Cited By ~ 30

Author(s):

G. Turrini ◽

M. Purgato ◽

C. Acarturk ◽

M. Anttila ◽

T. Au ◽

...

Keyword(s):

Mental Health ◽

Systematic Review ◽

Psychological Distress ◽

Asylum Seekers ◽

Meta Analysis ◽

Psychosocial Interventions ◽

Moderate Quality ◽

Refugees And Asylum Seekers ◽

Quality Evidence

AbstractAimsIn the past few years, there has been an unprecedented increase in the number of forcibly displaced migrants worldwide, of which a substantial proportion is refugees and asylum seekers. Refugees and asylum seekers may experience high levels of psychological distress, and show high rates of mental health conditions. It is therefore timely and particularly relevant to assess whether current evidence supports the provision of psychosocial interventions for this population. We conducted a systematic review and meta-analysis of randomised controlled trials (RCTs) assessing the efficacy and acceptability of psychosocial interventions compared with control conditions (treatment as usual/no treatment, waiting list, psychological placebo) aimed at reducing mental health problems in distressed refugees and asylum seekers.MethodsWe used Cochrane procedures for conducting a systematic review and meta-analysis of RCTs. We searched for published and unpublished RCTs assessing the efficacy and acceptability of psychosocial interventions in adults and children asylum seekers and refugees with psychological distress. Post-traumatic stress disorder (PTSD), depressive and anxiety symptoms at post-intervention were the primary outcomes. Secondary outcomes include: PTSD, depressive and anxiety symptoms at follow-up, functioning, quality of life and dropouts due to any reason.ResultsWe included 26 studies with 1959 participants. Meta-analysis of RCTs revealed that psychosocial interventions have a clinically significant beneficial effect on PTSD (standardised mean difference [SMD] = −0.71; 95% confidence interval [CI] −1.01 to −0.41; I2 = 83%; 95% CI 78–88; 20 studies, 1370 participants; moderate quality evidence), depression (SMD = −1.02; 95% CI −1.52 to −0.51; I2 = 89%; 95% CI 82–93; 12 studies, 844 participants; moderate quality evidence) and anxiety outcomes (SMD = −1.05; 95% CI −1.55 to −0.56; I2 = 87%; 95% CI 79–92; 11 studies, 815 participants; moderate quality evidence). This beneficial effect was maintained at 1 month or longer follow-up, which is extremely important for populations exposed to ongoing post-migration stressors. For the other secondary outcomes, we identified a non-significant trend in favour of psychosocial interventions. Most evidence supported interventions based on cognitive behavioural therapies with a trauma-focused component. Limitations of this review include the limited number of studies collected, with a relatively low total number of participants, and the limited available data for positive outcomes like functioning and quality of life.ConclusionsConsidering the epidemiological relevance of psychological distress and mental health conditions in refugees and asylum seekers, and in view of the existing data on the effectiveness of psychosocial interventions, these interventions should be routinely made available as part of the health care of distressed refugees and asylum seekers. Evidence-based guidelines and implementation packages should be developed accordingly.

Download Full-text

The Prevalence of Opioid Analgesic Use in People with Chronic Noncancer Pain: Systematic Review and Meta-Analysis of Observational Studies

Pain Medicine ◽

10.1093/pm/pnaa322 ◽

2020 ◽

Author(s):

Graeme Wertheimer ◽

Stephanie Mathieson ◽

Christopher G Maher ◽

Chung-Wei Christine Lin ◽

Andrew J McLachlan ◽

...

Keyword(s):

Systematic Review ◽

Observational Studies ◽

Opioid Analgesic ◽

Risk Of Bias ◽

Opioid Use ◽

Chronic Noncancer Pain ◽

Moderate Quality ◽

Meta Regression ◽

Noncancer Pain ◽

Quality Evidence

Abstract Objective To review studies examining the proportion of people with chronic noncancer pain who report consuming opioids and characteristics associated with their use. Design Systematic review. Methods We searched databases from inception to February 8, 2020, and conducted citation tracking. We included observational studies reporting the proportion of adults with chronic noncancer pain who used opioid analgesics. Opioids were categorized as weak (e.g., codeine) or strong (e.g., oxycodone). Study risk of bias was assessed, and Grading of Recommendations Assessment, Development and Evaluations provided a summary of the overall quality. Results were pooled using a random-effects model. Meta-regression determined factors associated with opioid use. Results Sixty studies (N=3,961,739) reported data on opioid use in people with chronic noncancer pain from 1990 to 2017. Of these 46, 77% had moderate risk of bias. Opioid use was reported by 26.8% (95% confidence interval [CI], 23.1–30.8; moderate-quality evidence) of people with chronic noncancer pain. The use of weak opioids (17.3%; 95% CI 11.9–24.4; moderate-quality evidence) was more common than the use of strong opioids (9.8%; 95% CI, 6.8–14.0; low-quality evidence). Meta-regression determined that opioid use was associated with geographic region (P=0.02; lower in Europe than North America), but not sampling year (P=0.77), setting (P=0.06), diagnosis (P=0.34), or disclosure of funding (P=0.77). Conclusions Our review summarized data from over 3.9 million people with chronic noncancer pain reporting their opioid use. Between 1990 and 2017, one-quarter of people with chronic noncancer pain reported taking opioids, and this proportion did not change over time.

Download Full-text

Herbal Medicine for Adult Patients with Cough Variant Asthma: A Systematic Review and Meta-Analysis

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/5853137 ◽

2021 ◽

Vol 2021 ◽

pp. 1-13

Author(s):

Yuan-Bin Chen ◽

Johannah L Shergis ◽

Zhen-Hu Wu ◽

Xin-Feng Guo ◽

Anthony L Zhang ◽

...

Keyword(s):

Systematic Review ◽

Herbal Medicine ◽

Meta Analysis ◽

Current Evidence ◽

Cough Variant Asthma ◽

Assessment Development ◽

Moderate Quality ◽

Severity Scores ◽

Quality Evidence

Introduction. Herbal medicine is commonly used by patients with chronic cough, but the role of herbal medicine for cough variant asthma (CVA) has not yet been clearly defined. For the first time, we performed a meta-analysis to integrate the current evidence of randomized controlled trials (RCTs) on this topic and assess the efficacy of herbal medicine in adults with CVA. Methods. A comprehensive search was conducted in electronic databases to identify RCTs of herbal medicine for adult CVA. Cochrane systematic review methods were followed, and the Grading of Recommendations Assessment, Development, and Evaluation was performed to evaluate the quality of evidence. Results. Twenty-eight RCTs were included. Compared with placebo, moderate-quality evidence from two studies showed that herbal medicine was associated with reduced cough symptom score (CSS) (MD −1.15 points; 95% CI, −1.67 to −0.63) and visual analogue scale (VAS) (MD −1.76 points; 95% CI, −2.66 to −0.86). Compared with montelukast, low- to moderate-quality evidence from 11 studies indicated that herbal medicine was associated with improved Leicester Cough Questionnaire (LCQ) (MD 2.38 points; 95% CI, 1.32 to 3.44), reduced CSS (SMD −0.81 points; 95% CI, −1.09 to −0.53), and VAS (MD −1.34 points; 95% CI, −1.82 to −0.86). There were no significant differences between herbal medicine and ICS plus bronchodilator. Conclusions. In adults with CVA, herbal medicine may result in improved quality of life and reduced cough frequency and severity scores compared with placebo or montelukast. Herbal medicine was not better than ICS plus a bronchodilator but the evidence is very uncertain.

Download Full-text

Efficacy and safety of low and very low carbohydrate diets for type 2 diabetes remission: systematic review and meta-analysis of published and unpublished randomized trial data

BMJ ◽

10.1136/bmj.m4743 ◽

2021 ◽

pp. m4743

Author(s):

Joshua Z Goldenberg ◽

Andrew Day ◽

Grant D Brinkworth ◽

Junko Sato ◽

Satoru Yamada ◽

...

Keyword(s):

Quality Of Life ◽

Systematic Review ◽

Type 2 Diabetes ◽

Weight Loss ◽

Meta Analysis ◽

Risk Of Bias ◽

Low Carbohydrate ◽

Remission Of Diabetes

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.

Download Full-text

Effectiveness of Antalgic Therapies in Patients with Vertebral Bone Metastasis: A Protocol for a Systematic Review and Meta-Analysis

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18083991 ◽

2021 ◽

Vol 18 (8) ◽

pp. 3991

Author(s):

Antonio Jose Martin-Perez ◽

María Fernández-González ◽

Paula Postigo-Martin ◽

Marc Sampedro Pilegaard ◽

Carolina Fernández-Lao ◽

...

Keyword(s):

Systematic Review ◽

Bone Metastasis ◽

Data Extraction ◽

Meta Analysis ◽

Risk Of Bias ◽

Cochrane Library ◽

Pharmacological Intervention ◽

Vertebral Metastasis ◽

Randomized Controlled Clinical Trials

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.

Download Full-text

The prevalence of diabetes in Afghanistan: a systematic review and meta-analysis

BMC Public Health ◽

10.1186/s12889-021-10993-5 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Sohail Akhtar ◽

Jamal Abdul Nasir ◽

Amara Javed ◽

Mariyam Saleem ◽

Sundas Sajjad ◽

...

Keyword(s):

Risk Factors ◽

Systematic Review ◽

Methodological Quality ◽

Meta Analysis ◽

Population Based ◽

Included Study ◽

Cochrane Library ◽

Or Education ◽

Meta Regression

Abstract Background The aim of this paper is to investigate the prevalence of diabetes and its associated risk factors in Afghanistan through a systematic review and meta–analysis. Methods A comprehensive literature search was conducted using EMBASE, PubMed, Web of Sciences, Google Scholar and the Cochrane library, carried out from inception to April 312,020, without language restriction. Meta–analysis was performed using DerSimonian and Laird random-effects models with inverse variance weighting. The existence of publication bias was initially assessed by visual inspection of a funnel plot and then tested by the Egger regression test. Subgroup analyses and meta-regression were used to explore potential sources of heterogeneity. This systematic review was reported by following the PRISMA guidelines and the methodological quality of each included study was evaluated using the STROBE guidelines. Results Out of 64 potentially relevant studies, only 06 studies fulfilled the inclusion criteria and were considered for meta-analysis. The pooled prevalence of diabetes in the general population based on population-based studies were 12.13% (95% CI: 8.86–16.24%), based on a pooled sample of 7071 individuals. Results of univariate meta-regression analysis revealed that the prevalence of diabetes increased with mean age, hypertension and obesity. There was no significant association between sex (male vs female), smoking, the methodological quality of included articles or education (illiterate vs literate) and the prevalence of diabetes. Conclusions This meta-analysis reports the 12.13% prevalence of diabetes in Afghanistan,with the highest prevalence in Kandahar and the lowest in Balkh province. The main risk factors include increasing age, obesity and hypertension. Community-based care and preventive training programmes are recommended. Trial registration This review was registered on PROSPERO (registration number CRD42020172624).

Download Full-text

Clopidogrel plus aspirin versus aspirin alone for acute minor ischaemic stroke or high risk transient ischaemic attack: systematic review and meta-analysis

BMJ ◽

10.1136/bmj.k5108 ◽

2018 ◽

pp. k5108 ◽

Cited By ~ 38

Author(s):

Qiukui Hao ◽

Malavika Tampi ◽

Martin O’Donnell ◽

Farid Foroutan ◽

Reed AC Siemieniuk ◽

...

Keyword(s):

Systematic Review ◽

Ischaemic Stroke ◽

Antiplatelet Therapy ◽

Dual Antiplatelet Therapy ◽

Absolute Risk ◽

Meta Analysis ◽

Risk Of Bias ◽

Controlled Trials ◽

Ischaemic Attack ◽

Quality Evidence

AbstractObjectiveTo assess the effectiveness and safety of dual agent antiplatelet therapy combining clopidogrel and aspirin to prevent recurrent thrombotic and bleeding events compared with aspirin alone in patients with acute minor ischaemic stroke or transient ischaemic attack (TIA).DesignSystematic review and meta-analysis of randomised, placebo controlled trials.Data sourcesMedline, Embase, Cochrane Central Register of Controlled Trials, Cochrane Library, ClinicalTrials.gov, WHO website, PsycINFO, and grey literature up to 4 July 2018.Eligibility criteria for selecting studies and methodsTwo reviewers independently screened potentially eligible studies according to predefined selection criteria and assessed the risk of bias using a modified version of the Cochrane risk of bias tool. A third team member reviewed all final decisions, and the team resolved disagreements through discussion. When reports omitted data that were considered important, clarification and additional information was sought from the authors. The analysis was conducted in RevMan 5.3 and MAGICapp based on GRADE methodology.ResultsThree eligible trials involving 10 447 participants were identified. Compared with aspirin alone, dual antiplatelet therapy with clopidogrel and aspirin that was started within 24 hours of symptom onset reduced the risk of non-fatal recurrent stroke (relative risk 0.70, 95% confidence interval 0.61 to 0.80, I2=0%, absolute risk reduction 1.9%, high quality evidence), without apparent impact on all cause mortality (1.27, 0.73 to 2.23, I2=0%, moderate quality evidence) but with a likely increase in moderate or severe extracranial bleeding (1.71, 0.92 to 3.20, I2=32%, absolute risk increase 0.2%, moderate quality evidence). Most stroke events, and the separation in incidence curves between dual and single therapy arms, occurred within 10 days of randomisation; any benefit after 21 days is extremely unlikely.ConclusionsDual antiplatelet therapy with clopidogrel and aspirin given within 24 hours after high risk TIA or minor ischaemic stroke reduces subsequent stroke by about 20 in 1000 population, with a possible increase in moderate to severe bleeding of 2 per 1000 population. Discontinuation of dual antiplatelet therapy within 21 days, and possibly as early as 10 days, of initiation is likely to maximise benefit and minimise harms.

Download Full-text

Genetic Association Studies of Red Blood Cell Transfusion Related Alloimmunization: A Systematic Review and Meta-Analysis

Blood ◽

10.1182/blood-2019-128199 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 2459-2459

Author(s):

Jorn Gerritsma ◽

Ilja Oomen ◽

Sanne Meinderts ◽

C. Ellen van der Schoot ◽

Bart J. Biemond ◽

...

Keyword(s):

Systematic Review ◽

Genetic Variants ◽

Screening Tool ◽

Association Studies ◽

Data Extraction ◽

Meta Analysis ◽

Genetic Association Studies ◽

Risk Of Bias ◽

Cell Disease

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.

Download Full-text