Vitamin D Binding Protein rs7041 polymorphism and high-residual platelet reactivity in patients receiving dual antiplatelet therapy with clopidogrel or ticagrelor

BackgroundVitamin D deficiency represents a major health problem in general population, especially for its association with cardiovascular disorders and thrombotic risk, even in patients on dual antiplatelet therapy (DAPT). Vitamin D Binding Protein (VDBP) is the main transporter of vitamin D in the bloodstream and genetic polymorphisms of this protein have been shown to account for a significant variability of vitamin D levels and its systemic effects. Contrasting data have linked the rs7041 T → G substitution with cardiovascular disease. However, no study has so far addressed the role of rs7041 polymorphism on platelet reactivity in patients on DAPT, that was the aim of the present study.MethodsPatients treated with DAPT (ASA and clopidogrel or ticagrelor) for an ACS or elective PCI were scheduled for platelet function assessment at 30–90 days post-discharge. Platelet function was assessed by Multiplate® (Roche Diagnostics AG), and VDBP genetic status by polymerase chain reaction and restriction fragment length polymorphism technique. Fasting samples were obtained for main chemistry parameters and vitamin D levels assessment.ResultsWe included 400 patients, 187 (46.8%) receiving clopidogrel and 213 (53.2%) ticagrelor. The genetic polymorphism rs7041 (T → G) was observed in 318 patients, (79.5%), in 38.7% of them in homozygosis. Main clinical and chemistry features did not significantly differ according to genetic status, but for a higher rate of ACE-inhibitors and beta-blockers use among the carriers of the G allele (p = 0.04 and p = 0.01, respectively).VDBP genetic status did not affect the rate of HRPR with ADP-antagonists (25.6% vs 24.6% vs 28.5%, p = 0.59; adjusted OR[95%CI] = 0.94[0.52–1.7], p = 0.83 for T/G patients; adjusted OR[95%CI] = 1.14[0.6–2.2], p = 0.67 for G homozygotes).However, the rate of HRPR with ADP-antagonists was influenced by severe hypovitaminosis D (< 10 ng/ml) only in patients carrying the G allele, especially in homozygosis (T/T: 25.9% vs 26.1%, p = 0.99; G carriers: 22.1% vs 35.3%, p = 0.02, p_interaction = 0.019; adjusted OR[95%CI] = 1.93[1.11–3.34], p = 0.02 for G carriers).ConclusionThe present study shows that rs7041 polymorphism of Vitamin D Binding Protein does not affect platelet reactivity or the rate of HRPR among patients receiving DAPT. However the carriage of the G allele could condition the impact of hypovitaminosis D on the response to antiplatelet agents, increasing the occurrence of HRPR especially in homozygotes, thus suggesting a more significant role of vitamin D deficiency among these patients.     

Prevalence and predictors of high-on treatment platelet reactivity with ticagrelor in ACS patients undergoing stent implantation

BackgroundResidual high-on treatment platelet reactivity (HRPR) predicts outcomes and major cardiovascular events. Ticagrelor has provided pharmacological and clinical evidence of more predictable and more potent antiplatelet effect as compared to clopidogrel. However, so far, few data have investigated the prevalence and predictors of HRPR in unselected patients treated with ticagrelor, that is therefore the aim of the current study.Methods and resultsOur population is represented by 195 patients undergoing coronary stenting for ACS and receiving ASA and ticagrelor. Platelet function was assessed by multiplate impedance aggregometry (MEA) between 1 and 3 months after stenting. Main clinical features and biochemistry parameters were collected. HRPR for ticagrelor was defined for aggregation > 417 AUC after MEA-ADP stimulation. A total of 26 patients, (13.3%), displayed HRPR with ticagrelor. Older age (≥ 70 years, p = 0.002), hypertension (p = 0.02) previous myocardial infarction (p = 0.04), therapy with nitrates and beta-blockers (p = 0.02), diuretics (p = 0.03) and fasting glycaemia (p = 0.05) were associated to HRPR with ticagrelor. By multivariate analysis, age ≥ 70 years (OR [95%CI] = 4.6[1.55–13.8], p = 0.006), concomitant therapy with beta-blockers (OR [95%CI] = 3.2[1.06–9.6], p = 0.04) and platelets count (OR[95%CI] = 1.0007 [1–1.016], p = 0.05) were identified as independent predictors of HRPR with ticagrelor.ConclusionThe present study firstly demonstrates that the occurrence of HRPR in patients treated with ticagrelor is not so futile, as it was observed in 13% of patients treated with ticagrelor. Older age, beta-blockers administration and platelets count are independent predictors of HRPR with ticagrelor.     

Mean platelet volume and high-residual platelet reactivity in patients receiving dual antiplatelet therapy with clopidogrel or ticagrelor

Objective: High on-treatment platelet reactivity (HRPR) is associated with a two- to ninefold increased risk of recurrent ischemic events among patients receiving dual antiplatelet therapy (DAPT) for coronary artery disease. However, its determinants are still poorly understood. The aim of the present study was to assess the impact of mean platelet volume (MPV) on platelet reactivity in patients receiving DAPT after an acute coronary syndrome or PCI.

Methods: Patients treated with DAPT (acetylsalicylic acid [ASA] and clopidogrel or ticagrelor) were scheduled for platelet function assessment at 30 – 90 days post-discharge. By whole blood impedance aggregometry, HRPR was considered for ASPI test > 862 aggregation units (AU)*min (for ASA) and ADP test values ≥ 417 AU*min (for ADP-antagonists).

Results: Our population is represented by a total of 487 patients on DAPT, divided according to MPV tertiles (< 10.4 fl; 10.4 – 11.29 fl; ≥ 11.3 fl). Larger-sized platelets were associated with use of statins (p < 0.001) and beta-blockers (p = 0.03), higher hemoglobin levels (p = 0.002) and lower platelets count (p < 0.001). Higher platelet reactivity was observed at ASPI test in patients with higher MPV (r = 0.12, p = 0.008), but not for ADP-mediated aggregation (r = -0.007, p = 0.88). However, a low prevalence of HRPR was observed with ASA, with no impact of MPV tertiles (1.2 vs 1.1 vs 1.6%, p = 0.70, adjusted OR [95% CI] = 1.05 [0.51 – 1.77], p = 0.87). MPV did not influence the prevalence of HRPR for ADP-antagonists (25.9 vs 1 vs 26.5%, p = 0.89; adjusted OR [95% CI] = 1.1 [0.84 – 1.45], p = 0.50) with similar results among the 259 patients receiving clopidogrel (adjusted OR [95% CI] = 1.15 [0.82 – 1.62], p = 0.43) and the 228 patients on ticagrelor (adjusted OR [95% CI] = 1.46 [0.84 – 2.55], p = 0.18).

Conclusion: In patients receiving DAPT, MPV does not affect the response to major antiplatelet therapies. In fact, MPV elevation does not influence the risk of HRPR with clopidogrel, ticagrelor or ASA.     

Post receptor determinants of acute platelet response to clopidogrel in patients with symptomatic myocardial ischemia

BackgroundClopidogrel resistance is more common in patients with loss-of-function CYP2C19 genotypes. Since adenylate cyclase (AC) and soluble guanylate cyclase (sGC) pathways are variably impaired in patients with ischaemic heart disease, we tested the relevance of these determinants in patients undergoing acute loading with clopidogrel (600 mg) prior to non-emergent coronary stenting.MethodsInhibitory effects of prostaglandin E₁ (PGE₁, an AC activator) and sodium nitroprusside (NP, a sGC activator) on platelet aggregation were determined at baseline and compared with platelet responses to clopidogrel (4 h after administration) assessed as ∆ADP, and Platelet Reactivity Index (∆PRI). Data were analysed according to CYP2C19 genotype.ResultsIn patients without loss of function mutations (n = 18), ∆ADP but not ∆PRI, was directly correlated with baseline PGE₁ responsiveness (r_s = 0.62, p = 0.005)). NP responsiveness did not predict ∆ADP. However there was no relationship between clopidogrel responses and either PGE₁ or NP responsiveness in patients with loss of function mutations. Multivariate correlates of clopidogrel response were both the genotype status (β = −0.609, p < 0.001) and the baseline response to PGE₁ (β = 0.303, p = 0.03).ConclusionsWhile genetically impaired bio-activation markedly limits acute (4 h) clopidogrel response, impaired AC signalling provides an additional cause for clopidogrel resistance.     

Distribution of clinical events across platelet aggregation values in all-comers treated with prasugrel and ticagrelor

The aim of this study was to investigate the distribution of clinical events across the platelet aggregation values in patients treated with prasugrel and ticagrelor. This prospective observational study enrolled 226 patients treated with prasugrel (n = 121) or ticagrelor (n = 105). Adenosine diphosphate (ADP)-induced platelet aggregation was determined by Multiplate Analyzer in the maintenance phase of treatment with prasugrel or ticagrelor. Clinical outcome was evaluated over 12 months. Platelet aggregation values were divided into quartiles. The first quartile comprised values < 8 U, the second quartile values between 8 U and < 15 U, the third one values between 15 U and 23 U, and the forth one values > 23 U. Myocardial infarction events were observed in patients within the third quartile of aggregation values (15–23 U), and were not associated with high on-treatment platelet reactivity (HTPR > 46 U). All bleeding events occurred in patients with aggregation values ≤ 23 U, which corresponded to the 75 percentile (p = 0.031). There was no difference in the distribution of bleeding events between the 1st–3rd quartiles (p = 0.873). In conclusion, patients with ADP-induced aggregation values over 23 U (fourth quartile) were at the lowest risk to develop bleeding during the follow-up.     

Ticagrelor potentiates adenosine-induced stimulation of neutrophil chemotaxis and phagocytosis

In the PLATO study, ticagrelor was associated with fewer pulmonary infections and subsequent deaths than clopidogrel. Neutrophils are a first-line defence against bacterial lung infection; ticagrelor inhibits cellular uptake of adenosine, a known regulator of neutrophil chemotaxis and phagocytosis. We assessed whether the inhibition of adenosine uptake by ticagrelor influences neutrophil chemotaxis and phagocytosis. Neutrophils and erythrocytes were isolated from healthy volunteers. Concentration-dependent effects of adenosine on IL-8-induced neutrophil chemotaxis were investigated and the involved receptors identified using adenosine receptor antagonists. The modulatory effects of ticagrelor on adenosine-mediated changes in neutrophil chemotaxis and phagocytosis of Streptococcus pneumoniae were determined in the presence of erythrocytes to replicate physiological conditions of cellular adenosine uptake. Low-concentration adenosine (10^− 8 M) significantly increased IL-8-induced neutrophil chemotaxis (% neutrophil chemotaxis: adenosine 28.7% ± 4.4 vs. control 22.6% ± 2.4; p < 0.01) by acting on the high-affinity A₁ receptor. Erythrocytes attenuated the effect of adenosine, although this was preserved by ticagrelor and dipyridamole (another inhibitor of adenosine uptake) but not by control or by cangrelor. Similarly, in the presence of erythrocytes, a low concentration of adenosine (10^− 8 M) significantly increased neutrophil phagocytic index compared to control when ticagrelor was present (37.6 ± 6.6 vs. 28.0 ± 6.6; p = 0.028) but had no effect in the absence of ticagrelor. We therefore conclude that the inhibition of cellular adenosine reuptake by ticagrelor potentiates the effects of a nanomolar concentration of adenosine on neutrophil chemotaxis and phagocytosis. This represents a potential mechanism by which ticagrelor could influence host defence against bacterial lung infection.     

Decline in platelet count and long-term post-PCI ischemic events: Implication of the intra-aortic balloon pump

AimsThrombocytopenia (TC) following a percutaneous coronary intervention (PCI) has been associated not only with hemorrhagic, but also with ischemic outcomes. The purpose of this study was to re-examine the relationship of TC with ischemic events at a 1-year follow-up, and investigate the possible associations.Methods and resultsWe studied a real-world, unselected population of ischemic patients undergoing PCI, totaling 861 patients-year, and divided into two groups: with TC (delta platelet count ≥ 25% from baseline to post-PCI during the hospital admission) and without TC. Compared with patients without TC, patients with TC had a higher and earlier incidence of both hemorrhagic and ischemic events. In them, the use of intra-aortic balloon pump (IABP) was ten-fold higher. In Kaplan–Meier curves assessing the contribution of both TC and IABP to outcome, IABP was a univariate detrimental factor additive to the role of TC. In a forced Cox model, the relative decline (delta) in platelet count (p = 0.05) and the use of IABP (p = 0.0001) were both associated with ischemic outcomes. After excluding all patients with IABP, the delta platelet count was no longer significantly associated with ischemic outcomes (p = 0.66). After excluding all patients with shock and all those who undergone thrombolysis, there was still a relationship (p = 0.0042) between the delta platelet count and ischemic events.ConclusionsIn this patient population the use of IABP, but not thrombocytopenia per se, is a possible primary cause of worse ischemic outcomes.     

Shift from darbepoetin-α to continuous erythropoietin receptor activator decreases serum aluminium concentration in patients on hemodialysis

ObjectiveThe response of erythropoietic stimulating agents (ESA) in uremic patients may be associated with the changes of biochemical parameters, metal elements and inflammation status during the shift from one ESA to another.MethodWe compared changes in above mentioned factors after switching from darbepoetin-α (DPO) 20 μg weekly for 10 weeks to continuous erythropoietin receptor activator (CERA) 100 μg monthly for 10 weeks in uremic patients on hemodialysis. The haematocrit (Hct), metal elements and inflammation status are the primary outcome. Subjects included 54 patients without transfusion or bleeding or additional ESAs. Responders (IR, n = 36) were defined as patients with an increase in Hct after the swtich.ResultAlthough there was no significant difference in overall mean Hct after the switch (p = 0.135), there are significantly greater mean number of red blood cells (RBC) (p = 0.006), higher platelet numbers (p = 0.001), larger RBCs (p = 0.017) and higher creatinine (p = 0.04) and total cholesterol (T-CHOL) (p = 0.003) levels. Mean overall aluminium (Al) level decreased significantly (p = 0.001). C-reactive protein (CRP) also decreased (p = 0.016). The overall LDH increased (p = 0.049) and potassium decreased significantly (p = 0.036), which indicating active erythropoiesis. The calcium (Ca) level was significantly higher (p = 0.034) and phosphate was significantly lower (p = 0.028) after the shift. Although there was no significant increase in overall levels of parathyroid hormone (PTH) after the shift (p = 0.061), but the pre-shift and post-shift PTH level was significantly higher in IRs than in non-IRs (p = 0.003 and p = 0.027, respectively). IRs had a significantly lower initial T-CHOL (p = 0.03) and initial CRP (p = 0.012) than non-responders, which may be related to lower inflammation.ConclusionWe found the shift from DPO to CERA results in lower Al levels, a reduced inflammatory response, and an increase in RBC number and PTH level in uremic patients on hemodialysis.     

High HCV cure rates for people who use drugs treated with direct acting antiviral therapy at an urban primary care clinic

BackgroundThough direct acting antivirals (DAAs) promise high cure rates, many providers and payers remain concerned about successful treatment for people who use drugs (PWUD), even among those engaged in opioid agonist treatment (OAT). The efficacy of DAAs among PWUD in real-world settings is unclear.MethodsWe conducted a cohort study of patients initiating HCV treatment between January 2014 and August 2015 (n = 89) at a primary care clinic in the Bronx, NY. Onsite HCV treatment with DAAs was performed by an HCV specialist, with support from a care coordinator funded by the NYC Department of Health. We identified four categories of drug use and drug treatment: (1) no active drug use/not receiving OAT (defined as non-PWUD); (2) no active drug use/receiving OAT; (3) active drug use/not receiving OAT; and (4) active drug use/receiving OAT. The primary outcome was SVR at 12 weeks post-treatment.ResultsOverall SVR rates were 95% (n = 41/43) for non-PWUD and 96% (n = 44/46) for patients actively using drugs and/or receiving OAT [p = 0.95]. There were no differences in SVR rates by drug use or drug treatment category. Compared to non-PWUD, those with no active drug use/receiving OAT had 100% SVR (n = 15/15; p = 1.0), those actively using drugs/not receiving OAT had 90% SVR (n = 9/10; p = 0.47), and those actively using drugs/receiving OAT had 95% SVR (20/21; p = 1.0).ConclusionRegardless of active drug use or OAT, patients who received DAA therapy at an urban primary care clinic achieved high HCV cure rates. We found no clinical evidence to justify restricting access to HCV treatment for patients actively using drugs and/or receiving OAT.     

Effects of n-3 polyunsaturated fatty acids on depressive symptoms,anxiety and emotional state in patients with acute myocardial infarction

BackgroundOur aim was to assess whether an early introduced n-3 polyunsaturated fatty acids (n-3 PUFA) supplementation affects depression symptoms, anxiety and emotional state in patients with acute myocardial infarction (AMI) and no history of mental disorders.MethodsFifty two patients with AMI were enrolled into the study and randomized to the study group (group P; n = 26; standard therapy + n-3 PUFA1 g daily) or the control group (group C; n = 26; standard therapy). The following psychological tests were used at the baseline (3rd day of AMI) and after one month (30 ± 1 days): Beck Depression Inventory (BDI), State-Trait Anxiety Inventory in a specific situation (STAI-S) and as a general trait (STAI-T), Emotional State Questionnaire (ESQ).ResultsThe baseline characteristics, pharmacotherapy and BDI, STAI-S/T and ESQ were similar between both groups. The mean test scores assessed for all patients (group P and C) during the one-month observation were significantly lower for BDI (p = 0.04), STAI-T (p = 0.03), STAI-S (p = 0.01) and harm/loss emotions (p = 0.005). After adjusting for age, sex, body mass index, coronary artery disease severity, ejection fraction, serum troponin level and the baseline tests results, n-3 PUFAintervention revealed additional significant decrease in BDI (p = 0.046), STAI-S (p = 0.03) and harm/loss emotions (p = 0.04).ConclusionsOur study provides novel and preliminary observations – n-3 PUFAsupplementation reveals additional decreasing effects on depressive and anxiety symptoms in early post-MI patients.     

Serum levels of leptin,adiponectin and resistin in patients with ankylosing spondylitis: A systematic review and meta-analysis

ObjectivesVarious studies have researched the serum levels of leptin, adiponectin and resistin in patients with ankylosing spondylitis (AS), but the results were inconclusive. The purpose of this study was to systematically evaluate the correlations between serum levels of these adipokines and AS.MethodsElectronic databases were retrieved to search relevant publications. Pooled standard mean difference (SMD) with 95% confidence interval (CI) was calculated by the random-effect model. Cochrane Q test and I² statistic were used to test heterogeneity. Subgroup analysis and meta-regression were applied to assess possible sources of heterogeneity.ResultsA total of sixteen articles were included. Meta-analysis results indicated no statistical differences between AS patients and normal controls in serum leptin and adiponectin levels (leptin, SMD = 0.829, 95% CI = − 0.116 to 1.774, p = 0.085; adiponectin, SMD = 0.460, 95% CI = − 0.004 to 0.924, p = 0.052). However, AS patients had higher serum resistin levels than controls (SMD = 1.413, 95% CI = 0.294 to 2.531, p = 0.013). Subgroup analyses suggested that Asian and African AS patients as well as patients aged < 40 years had higher serum leptin and resistin levels when compared to controls. Serum adiponectin levels were higher in AS patients compared to controls in subgroup of age ≥ 40, and serum resistin levels in subgroup of BMI ≥ 25. Measurement method was a source of heterogeneity for resistin. Publication bias was not observed and the robustness of study results was confirmed by sensitivity analysis.ConclusionSerum resistin, but not leptin or adiponectin levels may be closely associated with the development of AS.     

Get with the program: Adherence to a smartphone app for smoking cessation

IntroductionAlthough engagement is generally predictive of positive outcomes in technology-based behavioral change interventions, engagement measures remain largely atheoretical and lack treatment-specificity. This study examines the extent to which adherence measures based on the underlying behavioral change theory of an Acceptance and Commitment Therapy (ACT) app for smoking cessation predict smoking outcomes, and user characteristics associated with adherence.MethodsStudy sample was adult daily smokers in a single arm pilot study (n = 84). Using the app's log file data, we examined measures of adherence to four key components of the ACT behavior change model as predictors of smoking cessation and reduction. We also examined baseline user characteristics associated with adherence measures that predict smoking cessation.ResultsFully adherent users (24%) were over four times more likely to quit smoking (OR = 4.45; 95% CI = 1.13, 17.45; p = 0.032). Both an increase in tracking the number of urges passed (OR = 1.02; 95% CI = 1.00, 1.03; p = 0.043) and ACT modules completed (OR = 1.27; 95% CI = 1.01, 1.60; p = 0.042) predicted cessation. Lower baseline acceptance of cravings was associated with over four times higher odds of full adherence (OR = 4.59; 95% CI = 1.35, 15.54; p = 0.014).ConclusionsFull adherence and use of specific ACT theory-based components of the app predicted quitting. Consistent with ACT theory, users with low acceptance were most likely to adhere to the app. Further research is needed on ways to promote app engagement.     

Intracoronary abciximab in diabetic patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention

BackgroundAlthough intracoronary abciximab failed to improve prognosis compared with intravenous route in unselected ST-segment elevation myocardial infarction (STEMI) patients, little is known about the role of intracoronary abciximab in diabetic patients.ObjectivesTo evaluate the efficacy of intracoronary abciximab administration in diabetic patients with STEMI undergoing primary percutaneous coronary intervention (PCI).MethodsReperfusional and clinical outcomes of intracoronary abciximab compared with intravenous bolus abciximab according to diabetic status were evaluated in a pooled analysis of five randomized trials including 3158 STEMI patients. The primary clinical endpoint of the study was the composite of death or reinfarction at 30-day follow-up.ResultsAmong 584 diabetic patients (18.5%), the composite of death or reinfarction was significantly reduced with intracoronary abciximab compared to intravenous abciximab (4.7% vs. 8.8%; rate ratio [RR], 0.50; 95% confidence intervals [CI], 0.26–0.99; p = 0.04), driven by numerically lower deaths (3.7% vs. 6.4%; RR, 0.56; 95% CI, 0.26–1.20; p = 0.13). Moreover, a significant reduction in definite or probable stent thrombosis was observed in patients receiving intracoronary abciximab (1% vs. 3.5%; RR, 0.27; 95% CI, 0.07–0.99; p = 0.04). Although formal tests for interaction were not significant, no clinical benefit was apparent in the cohort of STEMI patients without diabetes (n = 2574).ConclusionsIn diabetic patients with STEMI undergoing primary PCI, intracoronary abciximab may improve clinical outcomes as compared with standard intravenous use. These findings require confirmation in a dedicated randomized trial.     

Escala simplificada para detectar problemas de adherencia (ESPA) al tratamiento antirretroviral

ObjectiveThe purpose is to describe an own-developed scale for medication adherence evaluation of HIV patients under antiretroviral therapy, and to compare it with other previously described methods.MethodsThe six-item scale was compared with a pharmacy record about the delivery of medication. Accordance between scale and a four-item Morisky-type scale (measure 1) and a percentage of doses taken as prescribed during the past two weeks (measure 2) was computed.ResultsThe own-scale showed 93% sensitivity, 70% specificity, a likelyhood ratio of 3.08 and good agreement compared with the pharmacy record (k = 0.62, p < 0.001). Agreement between the scale and measure 1 and measure 2 was very weak (k = 0.12, p = 0.446 and k = 0.10, p = 0.273 respectively). A 39.7% of patients was considered as adherent according with the own-scale and was observed correlation between adherence and clinical outcomes.ConclusionThe scale appears to be a valid instrument to check and detect adherence related problems compared with the pharmacy medication record. Easyness to use make feasible to consider as an adequate tool to detect non-adherent patients or patients with adherence related problems into the daily clinical practice.     

Smartphone-based ecological momentary assessment (EMA) of alcohol and cannabis use in older adults with and without HIV infection

IntroductionEcological momentary assessment (EMA) has been used to characterize substance use among adult populations; however, little is known about the validity of EMA and the patterns and predictors of substance use among older adults with and without HIV infection.MethodsThirty-five (22 HIV-positive, 13 HIV-negative) older adults aged 50–74 were assessed for 14 days and completed up to four smartphone-based surveys per day.ResultsParticipants completed an average of 89.5% of possible EMA surveys. EMA self-reported alcohol and cannabis use were significantly positively correlated with laboratory-assessed, self-reported days of alcohol (r = 0.52, p = 0.002) and cannabis (r = 0.61, p < 0.001) used and quantity of alcohol (r = 0.42, p = 0.013) and cannabis (r = 0.41, p = 0.016) used in the 30 days prior to baseline assessment. In a subset of 15 alcohol or cannabis users, preliminary analyses of the effects of mood and pain on alcohol or cannabis use showed: 1) greater anxious mood predicted substance use at the next EMA survey (OR = 1.737, p = 0.023), 2) greater happiness predicted substance use later in the day (OR = 1.383, p < 0.001), and 3) higher pain level predicted substance use earlier in the day (OR = 0.901, p = 0.005).ConclusionsFindings demonstrate that EMA-measured alcohol and cannabis use has convergent validity among older adults with and without HIV infection. Preliminary results showing predictors of substance use highlight the importance of gathering EMA data to examine daily variability and time-dependent antecedents of substance use among this population.     

[Artículo traducido] Impacto de los corticoides sistémicos en el tiempo de hospitalización en pacientes con COVID-19

ObjectiveThe COVID-19 pandemic has posed a threat to hospital capacity due to the high number of admissions, which has led to the development of various strategies to release and create new hospital beds. Due to the importance of systemic corticosteroids in this disease, we assessed their efficacy in reducing the length of stay (LOS) in hospitals and compared the effect of 3 different corticosteroids on this outcome.MéthodWe conducted a real-world, controlled, retrospective cohort study that analysed data from a hospital database that included 3934 hospitalised patients diagnosed with COVID-19 in a tertiary hospital from April to May 2020. Hospitalised patients who received systemic corticosteroids (CG) were compared with a propensity score control group matched by age, sex and severity of disease who did not receive systemic corticosteroids (NCG). The decision to prescribe CG was at the discretion of the primary medical team.ResultsA total of 199 hospitalized patients in the CG were compared with 199 in the NCG. The LOS was shorter for the CG than for the NCG (median = 3 [interquartile range = 0–10] vs. 5 [2–8.5]; p = 0.005, respectively), showing a 43% greater probability of being hospitalised ≤ 4 days than > 4 days when corticosteroids were used. Moreover, this difference was only noticed in those treated with dexamethasone (76.3% hospitalised ≤ 4 days vs. 23.7% hospitalised > 4 days [p < 0.001]). Serum ferritin levels, white blood cells and platelet counts were higher in the CG. No differences in mortality or intensive care unit admission were observed.ConclusionsTreatment with systemic corticosteroids is associated with reduced LOS in hospitalised patients diagnosed with COVID-19. This association is significant in those treated with dexamethasone, but no for methylprednisolone and prednisone.     

Prognostic importance of markers for inflammation,angiogenesis and apoptosis in high grade glial tumors during temozolomide and radiotherapy

IntroductionAngiogenesis, inflammation and apoptosis have an important place in the carcinogenesis of high-grade gliomas (HGG). We evaluated the postoperative levels and the prognostic importance of tumor necrosis factor-alpha (TNFα), interleukin 6 (IL6), endoglin (CD105), vascular endothelial growth factor (VEGF), M65 and M30 as markers of inflammation, angiogenesis and apoptosis in patients with HGG.Methods and resultsPostoperative pretreatment sera were collected from 44 newly diagnosed patients with HGG. The control group was also consisted of 44 healthy people. The median age of all patients with HGG was 59 (range: 30–80). Temozolomide concurrent with radiotherapy was given to 37 patients. Thereafter 24 patients received consolidation temozolomide monotherapy. Mean chemotherapy cycle was 4.2. Progression free survival and overall survival were 6 (95% CI; 5.16–6.83) and 16 months (95% CI; 13.07–18.93) respectively in patients treated with concurrent chemoradiotherapy and consolidation chemotherapy. Relative to the control cohort endoglin (p = 0.000) and TNFα (p = 0.000) levels were significantly lower; however VEGF (p = 0.030) levels were higher in the patient group. In contrast, there were no significant change in IL-6 levels and the plasma apoptotic markers M65 (p = 0.085) and M30 (p = 0.292). In separate log rank tests, these biological markers did not correlate with survival.Discussion and conclusionIn HGG, a significant decrease in endoglin and TNFα levels was observed, while VEGF levels were significantly increased postoperatively. However, with the power from this patient population, no correlation with survival was observed.     

E-cigarette advertisements,and associations with the use of e-cigarettes and disapproval or quitting of smoking: Findings from the International Tobacco Control (ITC) Netherlands Survey

BackgroundMuch attention has been directed towards the possible effects of e-cigarette advertisements on adolescent never smokers. However, e-cigarette advertising may also influence perceptions and behaviours of adult smokers. The aim of our study was to examine whether noticing e-cigarette advertisements is associated with current use of e-cigarettes, disapproval of smoking, quit smoking attempts, and quit smoking success.MethodsWe used longitudinal data from two survey waves of the ITC Netherlands Survey among smokers aged 16 years and older (n = 1198). Respondents were asked whether they noticed e-cigarettes being advertised on television, on the radio, and in newspapers or magazines in the previous 6 months.ResultsThere was a significant increase in noticing e-cigarette advertisements between 2013 (13.3%) and 2014 (36.0%), across all media. The largest increase was for television advertisements. There was also a substantial increase in current use of e-cigarettes (from 3.1% to 13.3%), but this was not related to noticing advertisements in traditional media (OR = 0.99, p = 0.937). Noticing advertisements was bivariately associated with more disapproval of smoking (Beta = 0.05, p = 0.019) and with a higher likelihood of attempting to quit smoking (OR = 1.37, p = 0.038), but these associations did not reach significance in multivariate analyses. There was no significant association between noticing advertisements and quit smoking success in either the bivariate or multivariate regression analysis (OR = 0.92, p = 0.807).ConclusionNoticing e-cigarette advertisements increased sharply in the Netherlands between 2013 and 2014 along with increased e-cigarette use, but the two appear unrelated. The advertisements did not seem to have adverse effects on disapproval of smoking and smoking cessation.     

Test of association between GABRA2 (SNP rs279871) and adolescent conduct/alcohol use disorders utilizing a sample of clinic referred youth with serious substance and conduct problems,controls and available first degree relatives

Recent findings have linked the GABRA2 gene with antisocial personality disorder and alcohol dependence (AD) in adults and conduct disorder (CD), but not AD symptoms, in children and adolescents. We sought to replicate previous findings and test for an association between a single nucleotide polymorphism (SNP) in the GABRA2 gene (rs279871) and CD among adolescents.MethodsAdolescent patients (n = 371), 13–18 years old, were recruited from a university substance abuse treatment program. Patient siblings (n = 245), parents of patients (n = 355), adolescent controls (n = 185), siblings of controls (n = 163) and parents of controls (n = 263) were included in these analyses (total sample n = 1582). Case-control (using only Caucasian and Hispanic probands) and family-based association tests were completed to test for association between rs279871 and several a priori CD and AD phenotypes.ResultsFor case-control association tests, rs279871 was significantly associated with CD (p = 0.02) but not AD phenotypes; the result did not survive strict correction for multiple testing. All family-based association tests were non-significant (CD p = 0.48; CD symptom count age corrected within sex p = 0.91; AD p = 0.84; alcohol use disorder p = 0.52).ConclusionsConsistent with previous findings, the results do not support the association between GABRA2 SNP rs279871 and AD in adolescents. Our results also do not support an association between rs279871 and CD; the study limitations are reviewed.     

Short term omega-3 polyunsaturated fatty acid supplementation induces favorable changes in right ventricle function and diastolic filling pressure in patients with chronic heart failure; A randomized clinical trial

IntroductionOmega-3 polyunsaturated fatty acids (omega 3-PUFAs) seem to favorably affect cardiac hemodynamics and may benefit the clinical course of heart failure patients. The role of omega 3-PUFAs supplementation on the left and right ventricular function of patients with chronic compensated systolic heart failure, under optimal treatment, was studied.Methods205 consecutive patients with chronic compensated heart failure, due to ischemic (IHF) or dilated cardiomyopathy (DCM)-NYHA classification I–III, under optimal medical treatment, were enrolled. Participants were 1-to-1 randomized on 1000 mg omega 3-PUFA supplementation or no supplementation, in a non-blinded fashion. Echocardiographic assessment was performed at first visit and 6 months after. Plasma BNP and serum creatinine levels were also measured.ResultsAs compared with the control group, BNP levels in omega 3-PUFA intervention group were 34.6% lower (p = 0.001); end-diastolic and end-systolic left ventricle dimensions were decreased by 2.5% (p = 0.047) and 3.7% (p = 0.01), maximum diameter of left atrium was decreased by 8.4% (p = 0.004), left atrium ejection fraction was ameliorated by 6.03% (p = 0.021) and as regards tissue Doppler parameters, TDI_Etv/Atv was decreased in omega 3-PUFA intervention group by 6.3% (p = 0.038). Moreover, improvement in diastolic indices was more prominent in subjects with DCM as compared to IHF patients.ConclusionOmega 3-PUFA supplementation was associated with improved left diastolic function and decreased BNP levels in patients with chronic heart failure. These findings suggest a beneficial role of omega 3-PUFAs on the hemodynamic course of patients with systolic heart failure.