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American Heart Journal Jun 2017VerifyNow P2Y12 assay is used widely to evaluate residual platelet reactivity in patients taking P2Y12 receptor antagonists. However, a laboratory association between... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
VerifyNow P2Y12 assay is used widely to evaluate residual platelet reactivity in patients taking P2Y12 receptor antagonists. However, a laboratory association between VerifyNow P2Y12 reaction unit (PRU) and hemoglobin, which might lead to wrong interpretation of the data, is reported. We performed these systematic review and meta-analysis to clearly define the relationship between PRU and hemoglobin and to elucidate whether the relationship, if any, is a true biological association or is just a laboratory error.
METHODS
Through a comprehensive electronic and manual search, 10 studies were selected for the cohort level meta-analysis. Among 10 studies, we were able to retrieve the raw data of 5 studies, and a patient-level meta-analysis was performed. Potential publication bias was searched by funnel plot analysis and was actively adjusted, if present, by trim and fill method.
RESULTS
The pooled analysis revealed a significant inverse correlation between PRU and hemoglobin (r=-0.349; P<.001; 10 studies with 4,793 patients). VerifyNow P2Y12 base unit, which reflects off-drug platelet reactivity, was also inversely correlated with hemoglobin (r=-0.526; P<.001; 8 studies with 4,395 patients). % Inhibition (r=0.081; P=.059; 6 studies with 3,832 patients) and ΔPRU (r=-0.037; P=.188; 5 studies with 3,521 patients) were not associated with hemoglobin. A significant inverse association between PRU and hemoglobin was also observed in the patient-level meta-analysis (3,533 patients pooled from 5 studies; r=-0.335; P<.001). Light transmission aggregometry (r=0.160; P=.072; 4 studies with 1,144 patients) and multiple electrode platelet aggregometry (r=-0.029; P=.394; 3 studies with 7,645 patients) showed no significant association with hemoglobin.
CONCLUSIONS
A significant inverse association was observed between PRU and hemoglobin which is likely to be a laboratory error. Clinicians should be aware that this association might lead to wrong interpretation of the data.
Topics: Blood Platelets; Coronary Artery Disease; Hemoglobins; Humans; Platelet Aggregation; Platelet Function Tests; Purinergic P2Y Receptor Antagonists
PubMed: 28577681
DOI: 10.1016/j.ahj.2017.03.006 -
Aesthetic Surgery Journal Mar 2017Platelet rich plasma (PRP) has attracted attention in a number of surgical fields due to a wide variety of potential clinical benefits. Yet PRP has not gained wide... (Review)
Review
BACKGROUND
Platelet rich plasma (PRP) has attracted attention in a number of surgical fields due to a wide variety of potential clinical benefits. Yet PRP has not gained wide popularity in aesthetic surgery as a result of uncertainty surrounding objective clinical evidence.
OBJECTIVES
We aim to describe the current applications, define preparation and activation, explore effectiveness, and propose a classification system to facilitate comparisons across studies.
METHODS
A comprehensive review of the literature regarding the use of platelet rich plasma in aesthetic surgery was performed. Data gathered included: PRP application, study type, subject number, centrifugation, anticoagulation, activation, PRP composition, and outcomes.
RESULTS
Thirty-eight reports were identified. Applications included injection into aging skin (29%), scalp alopecia (26%), lipofilling (21%), fractional laser (13%), and facial surgery (11%). The majority of studies (53%) were case series without controls. Leucocytes were sparsely defined (32%). The concentration of injected and/or baseline platelets was rarely clarified (18%). The mechanism of activation was described in 27 studies (71%), while anticoagulation was uncommonly elucidated (47%). While most studies (95%) claim effectiveness, objective measures were only utilized in 17 studies (47%).
CONCLUSIONS
Current studies produce context-dependent results with a lack of consistent reporting of PRP preparation, composition, and activation in aesthetic applications, making meaningful meta-analysis unrealistic. Thus the method of PRP preparation warrants increased attention. We recommend a set of descriptors, FIT PAAW (described below), to produce scientifically grounded conclusions, facilitating a clearer understanding of the situations in which PRP is effective.
LEVEL OF EVIDENCE
4
Topics: Cosmetic Techniques; Esthetics; Humans; Platelet-Rich Plasma; Plastic Surgery Procedures; Treatment Outcome
PubMed: 28207031
DOI: 10.1093/asj/sjw178 -
Atherosclerosis Jun 2015The efficacy of antiplatelet drugs may differ in specific patient subgroups. We aimed to assess the efficacy and safety of the P2Y12 inhibitors clopidogrel, ticlopidine,... (Meta-Analysis)
Meta-Analysis Review
Efficacy and safety of P2Y12 inhibitors according to diabetes, age, gender, body mass index and body weight: systematic review and meta-analyses of randomized clinical trials.
OBJECTIVE
The efficacy of antiplatelet drugs may differ in specific patient subgroups. We aimed to assess the efficacy and safety of the P2Y12 inhibitors clopidogrel, ticlopidine, prasugrel, ticagrelor, and cangrelor according to diabetes status, age, gender, body mass index, and body weight.
METHODS
Randomized clinical trials (RCTs) of P2Y12 inhibitors reporting information on cardiovascular disease (defined as myocardial infarction, stroke, or cardiovascular death) and bleeding (defined as any bleeding) events among the subgroups diabetes and non-diabetes, age ≥65 and <65 year-old, men and women, body mass index ≥30 and <30 kg/m(2), and body weight ≥60 and <60 kg, were identified in Medline, Embase, Web of Science, and Cochrane Library on August 31st, 2014. For each inhibitor, random-effects meta-analyses were used to estimate the ratio of relative risks (rRR) for cardiovascular and bleeding events among patient subgroups.
RESULTS
Twenty distinct RCTs (233 285 participants, 21 323 cardiovascular and 5183 bleeding events) were identified. Cardiovascular risk reduction with clopidogrel did not significantly differ according to diabetes (rRR: 1.04; 95% CI: 0.95 to 1.13; p = 0.395), age (0.98; 0.88 to 1.09; p = 0.347), gender (0.97; 0.90 to 1.04; p = 0.382), or body mass index (1.11, 0.95 to 1.31; p = 0.191). Results for other inhibitors were comparable, although available data were sparse. Limited data on bleeding events were available.
CONCLUSION
Data from RCTs did not show a different cardiovascular efficacy of clopidogrel in diabetes mellitus and other clinically relevant subgroups. Limited information was available on the efficacy and safety of other P2Y12 inhibitors in specific subgroups.
Topics: Age Factors; Aged; Blood Platelets; Body Mass Index; Body Weight; Cardiovascular Diseases; Comorbidity; Diabetes Mellitus; Drug Resistance; Female; Hemorrhage; Humans; Male; Middle Aged; Obesity; Odds Ratio; Platelet Aggregation; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; Receptors, Purinergic P2Y12; Risk Assessment; Risk Factors; Sex Factors; Treatment Outcome
PubMed: 25897998
DOI: 10.1016/j.atherosclerosis.2015.04.015 -
Seminars in Thrombosis and Hemostasis Jul 2022Increased platelet activity is an important predictor for recurrent cardiovascular events in patients with acute coronary syndromes (ACS). Flow cytometry is an advanced...
Increased platelet activity is an important predictor for recurrent cardiovascular events in patients with acute coronary syndromes (ACS). Flow cytometry is an advanced method for evaluation of platelet activity. We aimed to summarize the current literature on dynamic changes in platelet activity analyzed by flow cytometry in patients with ACS. Employing the guidelines of Preferred Report Items for Systematic Reviews and Meta-Analyses (PRISMA), we searched PubMed and Embase on October 26, 2021, and identified studies measuring platelet activity with flow cytometry in ACS patients in the acute phase (baseline) and at follow-up in a more stable phase. In the 12 included studies, fibrinogen receptor, α-granule secretion, platelet reactivity index, monocyte-platelet aggregates, neutrophil-platelet aggregates, and reticulated platelets were measured. The fibrinogen receptor and α-granule secretion were either unchanged or lower during follow-up measurements than in the acute phase. Platelet reactivity index showed inconsistent results. Values of monocyte-platelet aggregates and neutrophil-platelet aggregates were lower at follow-up than at baseline (-values <0.05). Reticulated platelets were either unchanged (-value >0.64) or lower at 1 to 2 months follow-up (-value 0.04), and also lower at 5 months to 1-year follow-up (-value >0.005) compared with baseline. Overall, flow cytometric analyses of platelet function in ACS patients showed that platelet activity was lower at follow-up than at baseline. However, in some patients, platelet activity remained unchanged from baseline to follow-up, possibly indicating a sustained high platelet activity that may increase the risk of recurrent cardiovascular events.
Topics: Acute Coronary Syndrome; Blood Platelets; Flow Cytometry; Humans; Platelet Activation; Platelet Function Tests
PubMed: 35226948
DOI: 10.1055/s-0042-1742742 -
Journal of Stroke and Cerebrovascular... Jul 2020To assess the prevalence of high on-clopidogrel platelet reactivity (HCPR) in patients with ischaemic stroke or transient ischaemic attack (IS/TIA), their outcome and... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To assess the prevalence of high on-clopidogrel platelet reactivity (HCPR) in patients with ischaemic stroke or transient ischaemic attack (IS/TIA), their outcome and genetic basis of on-treatment response variability in IS/TIA patients.
METHODS
We conducted a comprehensive search of PubMed and EMBASE from their inceptions to March 9, 2019. Studies that reported absolute numbers/percentages of HCRP at any time point after IS/TIA onset evaluated with any type of platelet function tests, clinical outcomes and genotyping data were included.
RESULTS
Among 21 studies of 4312 IS/TIA patients treated with clopidogrel, the pooled prevalence of HCPR was 28% (95%CI: 24-32%; high heterogeneity: I = 88.2%, p < 0.001). Heterogeneity degree diminished across groups defined by the HCPR testing method. Clopidogrel non-responder IS/TIA patients had poorer outcome compared to responders (RR = 2.09, 95%CI: 1.61-2.70; p = 0.036; low heterogeneity across studies: I = 27.4%, p = 0.210). IS/TIA carriers of CYP2C19*2 or CYP2C19*3 loss of function alleles had a higher risk of HCPR compared to wild type (RR = 1.69, 95%CI: 1.47-1.95; p < 0.001; I = 0.01%, p = 0.475).
CONCLUSIONS
This systematic review shows a high prevalence of clopidogrel resistance in IS/TIA and poor outcome in these patients. CYP2C19 polymorphisms may potentially influence clopidogrel resistance.
Topics: Blood Platelets; Clopidogrel; Cytochrome P-450 CYP2C19; Drug Resistance; Humans; Ischemic Attack, Transient; Pharmacogenomic Variants; Platelet Aggregation; Platelet Aggregation Inhibitors; Polymorphism, Genetic; Risk Factors; Stroke; Treatment Outcome
PubMed: 32414579
DOI: 10.1016/j.jstrokecerebrovasdis.2020.104877 -
International Journal of Molecular... Jul 2021In severe COVID-19, which is characterized by blood clots and neutrophil-platelet aggregates in the circulating blood and different tissues, an increased incidence of...
In severe COVID-19, which is characterized by blood clots and neutrophil-platelet aggregates in the circulating blood and different tissues, an increased incidence of cardiovascular complications and venous thrombotic events has been reported. The inflammatory storm that characterizes severe infections may act as a driver capable of profoundly disrupting the complex interplay between platelets, endothelium, and leukocytes, thus contributing to the definition of COVID-19-associated coagulopathy. In this frame, P-selectin represents a key molecule expressed on endothelial cells and on activated platelets, and contributes to endothelial activation, leucocyte recruitment, rolling, and tissue migration. Briefly, we describe the current state of knowledge about P-selectin involvement in COVID-19 pathogenesis, its possible use as a severity marker and as a target for host-directed therapeutic intervention.
Topics: Blood Coagulation Disorders; Blood Platelets; COVID-19; Endothelial Cells; Humans; Leukocytes; P-Selectin
PubMed: 34360707
DOI: 10.3390/ijms22157942 -
COPD Aug 2016Previous studies clearly showed that patients with chronic obstructive pulmonary disease (COPD) are at high risk for cardiovascular events. Platelet activation is... (Meta-Analysis)
Meta-Analysis Review
Previous studies clearly showed that patients with chronic obstructive pulmonary disease (COPD) are at high risk for cardiovascular events. Platelet activation is significantly heightened in these patients, probably because of a chronic inflammatory status. Nevertheless, it is unclear whether antiplatelet treatment may contribute to reduce all-cause mortality in COPD patients. To clarify this issue, we performed a systematic review and meta-analysis including patients with COPD (outpatients or admitted to hospital for acute exacerbation). The primary endpoint was all-cause mortality. We considered studies stratifying the study population according the administration or not of antiplatelet therapy and reporting its relationship with the primary endpoint. Overall, 5 studies including 11117 COPD patients were considered (of those 3069 patients were with acute exacerbation of COPD). IHD was present in 33% of COPD patients [95%CI 31%-35%). Antiplatelet therapy administration was common (47%, 95%CI 46%-48%), ranging from 26% to 61%. Of note, IHD was considered as confounding factor at multivariable analysis in all studies. All-cause mortality was significantly lower in COPD patients receiving antiplatelet treatment (OR 0.81; 95%CI 0.75-0.88). The data was consistent both in outpatients and in those with acute exacerbation of COPD. The pooled studies analysis showed a very low heterogeneity (I(2) : 8%). Additional analyses (meta-regression) showed that antiplatelet therapy administration was effective independently (to potential confounding factors as IHD, cardiovascular drugs and cardiovascular risk factors. In conclusion, our meta-analysis suggested that antiplatelet therapy might significantly contribute to reduce all-cause mortality in COPD patients.
Topics: Cause of Death; Humans; Mortality; Multivariate Analysis; Myocardial Ischemia; Platelet Aggregation Inhibitors; Pulmonary Disease, Chronic Obstructive
PubMed: 26678708
DOI: 10.3109/15412555.2015.1099620 -
Molecular Psychiatry May 2024Previous meta-analyses have documented the association of immune-inflammatory pathways with the pathophysiology of Major Depressive Episode (MDE), as reflected by...
Previous meta-analyses have documented the association of immune-inflammatory pathways with the pathophysiology of Major Depressive Episode (MDE), as reflected by alterations in peripheral blood immune cell counts. However, it remains unclear whether these immunological changes are distinct in individuals experiencing suicidal ideation (SI) or suicidal behavior (SB), beyond the context of an MDE. This systematic review and meta-analysis aimed to examine peripheral immune cell profiles across samples with SI/SB and compare them to healthy controls or patients with MDE. A systematic literature search was conducted in MEDLINE, Embase, and PsycINFO for articles published from inception until June 12, 2023. Two independent reviewers screened the articles for inclusion, extracted data, and assessed the risk of bias using the Newcastle-Ottawa scale. Meta-analyses were performed using a random-effects model to calculate standardized mean differences (SMDs) and 95% confidence intervals (CIs) for immune cell counts or ratios between groups with and without SI/SB. Heterogeneity across studies was assessed using the restricted maximum-likelihood estimator for tau statistic and I-statistic and tested by the Q test. Publication bias was evaluated using the Egger´s test and funnel plots. Meta-regression analyses were conducted to explore the potential moderating effects of age, gender, current or lifetime SI/SB, and the type of self-harming behavior (SI or SB). The study was registered with PROSPERO (CRD42023433089). The systematic review included 30 studies, with data from 19 studies included in the meta-analyses comprising 139 unique comparisons. Eleven different cell populations or ratios were included, comprising 1973 individuals with SI/SB and 5537 comparison subjects. White blood cell (WBC) and neutrophil counts were higher in individuals with SI/SB than in controls (WBC: SMD = 0.458; 95% CI = 0.367-0.548; p value ≤ 0.001; I = 0.002% and; Neutrophils: SMD = 0.581; 95% CI = 0.408-0.753; p < 0.001), indicating an inflammatory process. The neutrophil-to-lymphocyte ratio (NLR) emerged as a potential marker, demonstrating a notable elevation in individuals with SI/SB (SMD = 0.695; 95% CI = 0.054-1.335; p value = 0.033; I = 94.281%; Q test p value ≤ 0.001). The elevated NLR appears to be primarily driven by the increase in neutrophil counts, as no significant differences were found in lymphocyte counts between groups. Comparisons among participants with and without SI/SB and depression revealed similar trends with increased NLR, monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR) observed in depressed individuals with SI/SB compared to those without SI/SB. Broad alteration in the peripheral immune cell populations and their ratios were observed in individuals with SI/SB, indicating an immune activation or dysfunction. Notably, these immunological changes were also evident when comparing MDE individuals with and without SI/SB, suggesting that such immune dysfunction associated with suicidality cannot be solely attributed to or explained by depressive symptoms. The NLR, MLR, and PLR ratios, in combination with novel immune cellular and protein biomarkers, open new avenues in understanding the immunological underpinnings of SI/SB. These findings highlight the potential utility of immune markers as part of a multi-modal approach for risk stratification and therapeutic monitoring in SI/SB.
PubMed: 38802507
DOI: 10.1038/s41380-024-02587-5 -
The Cochrane Database of Systematic... Oct 2014Peripheral arterial disease (PAD) affects between 4% and 12% of people aged 55 to 70 years, and 20% of people over 70 years. A common complaint is intermittent... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Peripheral arterial disease (PAD) affects between 4% and 12% of people aged 55 to 70 years, and 20% of people over 70 years. A common complaint is intermittent claudication, characterised by pain in the legs or buttocks that occurs with exercise and which subsides with rest. Compared with age-matched controls, people with intermittent claudication have a three- to six-fold increase in cardiovascular mortality. Symptoms of intermittent claudication, walking distance, and quality of life can be improved by risk factor modification, smoking cessation, and a structured exercise programme. Antiplatelet treatment is beneficial in patients with intermittent claudication for the reduction of vascular events but has not previously been shown to influence claudication distance. This is an update of a review first published in 2007.
OBJECTIVES
To determine the effect of cilostazol (an antiplatelet treatment) on improving initial and absolute claudication distances, and in reducing mortality and vascular events in patients with stable intermittent claudication.
SEARCH METHODS
For this update, the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched October 2013) and CENTRAL (2013, Issue 9).
SELECTION CRITERIA
Double-blind, randomised controlled trials (RCTs) of cilostazol versus placebo, or versus other antiplatelet agents in patients with stable intermittent claudication.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed trials for selection and independently extracted data. Disagreements were resolved by discussion. We performed the meta-analysis as a fixed-effect model with weighted mean differences (WMDs) and 95% confidence intervals (CIs) for continuous data, and odds ratios (ORs) with 95% CIs for dichotomous data.
MAIN RESULTS
We included fifteen double-blind, RCTs comparing cilostazol with placebo, or medications currently known to increase walking distance e.g. pentoxifylline. There were a total of 3718 randomised participants with treatment durations ranging from six to 26 weeks. All participants had intermittent claudication secondary to PAD. Comparisons included cilostazol twice daily, with dosages of 50 mg, 100 mg and 150 mg compared with placebo, and cilostazol 100 mg, twice daily, compared with pentoxifylline 400 mg, three times daily. The methodological quality of the trials was generally low, with the majority being at an unclear risk for selection bias, performance bias, detection bias and other bias. Attrition bias was generally low, but reporting bias was high or unclear in the majority of the studies. For eight studies data were compatible for comparison by meta-analysis, but data for seven studies were too heterogenous to be pooled. For the studies included in the meta-analysis, for initial claudication distance (ICD - the distance walked on a treadmill before the onset of calf pain) there was an improvement in the cilostazol group for the 100 mg and 50 mg twice daily, compared with placebo (WMD 31.41 metres, 95% CI 22.38 to 40.45 metres; P < 0.00001) and WMD 19.89 metres, 95% CI 9.44 to 30.34 metres; P = 0.0002), respectively. ICD was improved in the cilostazol group for the comparison of cilostazol 150 mg versus placebo and cilostazol 100 mg versus pentoxifylline, but only single studies were used for these analyses. Absolute claudication distance (ACD - the maximum distance walked on a treadmill) was significantly increased in participants taking cilostazol 100 mg and 50 mg twice daily, compared with placebo (WMD 43.12 metres, 95% CI 18.28 to 67.96 metres; P = 0.0007) and WMD 32.00 metres, 95% CI 14.17 to 49.83 metres; P = 0.0004), respectively. As with ICD, ACD was increased in participants taking cilostazol 150 mg versus placebo, but with only one study an association cannot be clearly determined. Two studies comparing cilostazol to pentoxifylline had opposing findings, resulting in an imprecise CI (WMD 13.42 metres (95% CI -43.51 to 70.35 metres; P = 0.64). Ankle brachial index (ABI) was lowered in the cilostazol 100 mg group compared with placebo (WMD 0.06, 95% CI 0.04 to 0.08; P < 0.00001). The single study evaluating ABI for the comparison of cilostazol versus pentoxifylline found no change in ABI.There was no association between treatment type and all-cause mortality for any of the treatment comparisons, but there were very few events, and therefore larger, adequately powered studies will be needed to assess if there is a relationship. Only one study evaluated individual cardiovascular events, and from this study there is no clear evidence of a difference between any of the treatment groups and risk of myocardial infarction or stroke. We evaluated adverse side effects, and in general cilostazol was associated with a higher odds of headache, diarrhoea, abnormal stool, dizziness and palpitations. We only reported quality of life measures descriptively as there was insufficient statistical detail within the studies to combine the results, although there was a possible indication in improvement of quality of life in the cilostazol treatment groups.
AUTHORS' CONCLUSIONS
Cilostazol has been shown to be of benefit in improving walking distance in people with intermittent claudication secondary to PAD. Although there is an increase in adverse side effects, they are generally mild and treatable. There is currently insufficient data on whether taking cilostazol results in a reduction of all-cause mortality and cardiovascular events or an improvement in quality of life. Future research into the effect of cilostazol on intermittent claudication should carefully consider comparability, sample size and homogeneity when designing a study.
Topics: Aged; Cilostazol; Humans; Intermittent Claudication; Middle Aged; Myocardial Infarction; Pentoxifylline; Peripheral Vascular Diseases; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Stroke; Tetrazoles; Walking
PubMed: 25358850
DOI: 10.1002/14651858.CD003748.pub4 -
Tissue Engineering. Part B, Reviews Dec 2017Fetal bovine serum (FBS) is the most commonly used supplement for ex vivo expansion of human mesenchymal stem cells (hMSCs) for bone tissue engineering applications.... (Review)
Review
Fetal bovine serum (FBS) is the most commonly used supplement for ex vivo expansion of human mesenchymal stem cells (hMSCs) for bone tissue engineering applications. However, from a clinical standpoint, it is important to substitute animal-derived products according to current good manufacturing practice (cGMP) guidelines. Humanized alternatives to FBS include three categories of products: human serum (HS), human platelet derivatives (HPDs)-including platelet lysate (PL) or platelet releasate (PR), produced by freeze/thawing or chemical activation of platelet concentrates, respectively, and chemically defined media (serum-free) (CDM). In this systematic literature review, the in vitro and in vivo osteogenic potential of hMSCs expanded in humanized (HS-, HPD-, or CDM-supplemented) media versus hMSCs expanded in FBS-supplemented media, was compared. In addition, PL and PR were compared in terms of their growth factor (GF)/cytokine-content and cell-culture efficacy. When using either 10-20% autologous or pooled HS, 3-10% pooled HPDs or CDM supplemented with GFs, in comparison with 10-20% FBS, a majority of studies reported similar or superior in vitro proliferation and osteogenic differentiation, and in vivo bone formation in ectopic or orthotopic rodent models. Moreover, a trend for higher GF content was observed in PL versus PR, although evidence for cell culture efficacy is limited. In summary, humanized supplements seem at least equally effective as FBS for hMSC expansion and osteogenic differentiation. Although pooled HPDs appear to be the most favorable supplement for large-scale hMSC expansion, further efforts are needed to standardize the preparation and composition of these products in compliance with cGMP standards.
Topics: Animals; Blood Platelets; Bone and Bones; Cell Culture Techniques; Cell Differentiation; Humans; Mesenchymal Stem Cells; Osteogenesis; Regeneration; Tissue Engineering
PubMed: 28610481
DOI: 10.1089/ten.TEB.2017.0093