Inclusion Visit Research Articles

Association of the KDIGO Risk Classification with the Prevalence of Heart Failure in Patients with Type 2 Diabetes.

The objectives of this study were to determine the main characteristics associated with the presence of heart failure (HF) in patients with type 2 diabetes (T2DM), and specifically to assess the association of the risk classification proposed by the Kidney Disease Improving Global Outcomes (KDIGO) guidelines with HF. The DIABET-IC study is a multicentre, observational, prospective and analytical study in T2DM patients recruited in Spanish hospitals. This work, which features a cross-sectional design, has been conducted with the data obtained at the inclusion visit. The main dependent variable analysed was the presence of HF. The predictive variables evaluated were the demography, clinic, laboratory testing (including natriuretic peptides) and echocardiography. Patients were classified according to the number of vascular territories with atherosclerotic involvement and the KDIGO risk category. Multivariate logistic regression models were performed to determine the risk posed by the various baseline variables to present HF at the time of study inclusion. The study included 1517 patients from 58 hospitals, with a mean age of 67.3 (standard deviation (SD): 10) years, out of which 33% were women. The mean DM duration was 14 (SD: 11) years. The prevalence of HF was 37%. In a multivariate analysis, the independent predictors of HF were increased age (odds ratio (OR) per 1 year = 1.02; p = 0.006), decreased systolic blood pressure (OR per 1 mmHg = 0.98; p < 0.001), decreased haemoglobin (OR per 1 g/dL = 0.86; p < 0.001), the presence of obstructive sleep apnoea (OR = 1.61; p = 0.006), the absence of hepatic steatosis (OR = 0.59; p = 0.016), the severity of atherosclerotic involvement (OR 1 territory = 1.38 and OR > 1 territory = 2.39; p = 0.02 and p < 0.001 respectively) and the KDIGO risk classification (high-risk OR = 2.46 and very high-risk OR = 3.39; p < 0.001 for both). The KDIGO risk classification is useful to screen for the presence of HF in T2DM patients. Therefore, we believe that it is necessary to carry out a systematic screening for HF in the high- and very high-risk KDIGO categories.

P62.01 PREVALUNG: Evaluation of Lung Cancer Prevalence in Patients With Smocking-associated Atherosclerotic Cardiovascular Diseases

Lung cancer is the leading cause of cancer related death in France and Worldwide. Lung cancer screening based on low dose thoracic computed tomography (low dose CT) in patients selected on age and lifelong tobacco consumption has proven to improve lung cancer related mortality. However, the definition and identification of patients eligible for lung cancer screening is a challenge that may limit lung cancer screening program implementation. Epidemiological data shows that 30 to 40% of patients with lung cancer present a history of cardiovascular disease, mainly atheromatous diseases such as peripheral arterial diseases and coronary artery stenoses. We hypothesized that patients with history of smoking who developed atheromatous disease could represent a population at high risk to develop lung cancer. Our main objective was to evaluate the prevalence of lung cancer among patients with atherosclerotic disease and history of tobacco consumption. Our second objective was to evaluate the lung cancer screening program implemented to measure the prevalence. We implemented a monocentric prospective epidemiological study to evaluate the prevalence of lung cancer among 500 patients with inclusion criteria i.e age 45-75 years old, history of at least 10 years of daily tobacco consumption preceding the onset of an atherosclerotic disease. Principal exclusion criteria were history of active carcinoma < 5 years, symptoms of lung cancer, follow-up for lung nodules and grade IV dyspnea. Patients with inclusion criteria are referred for an inclusion visit (V0) with a thoracic surgeon by adult cardiologists, vascular surgeons and adult cardiac surgeons in charge of the patient. After information and inclusion, a low dose CT scan is scheduled within 7 months and a smoking cessation visit is proposed in case of active smoking. Blood and gut microbiota samples are harvested the day of the low dose CT. Positive low-dose CT are discussed weekly at the multidisciplinary thoracic oncologic staff meeting and managed accordingly to the current European and national recommendations. A clinical follow-up is scheduled by phone at 3, 6 and 12 months after the low-dose CT to evaluate oncologic and cardiovascular events. Between November 2019 and April 2021 we included 487 of the 500 patients scheduled, 330 low dose CT were completed, 7 localized primary lung cancer were resected by minimally invasive lobectomy, 1 patient was treated by radiation alone without pathological proof for a lung nodule, 1 patient was related with systemic therapy for a stage IV primary lung cancer and 2 patients are waiting for surgical resection for clinically localized lung cancers. The implementation of a lung cancer screening program dedicated to patients followed-up for tobacco related atherosclerotic diseases is feasible and will allow to evaluate both lung cancer prevalence and short-term benefits of lung cancer screening in this population.

HCN1 Ion Channel in the Hippocampal CA1 Region Was Involved in Ketamine-Induced Antidepressant Action and Increased BDNF Levels in Mice

Bilateral subthalamic nucleus deep brain stimulation improves motor symptoms and treatment-related complications in patients with Parkinson’s disease. However, some patients have trouble adjusting socially after successful neurosurgery, in part because of “unrealistic” expectations and psychiatric disorders. Preoperative psychological interventions focusing on these aspects could be beneficial for such patients.We compared the outcomes of 2 psychosocial approaches—1 based on cognitive restructuration and 1 consisting of 2 interviews—with those of a control group without preoperative preparation. All patients underwent a psychometric evaluation 2 months before surgery (M−2) and again at 3 (M+3) and 6 months (M+6) after surgery. The psychometric evaluation focused on social adjustment using the social adjustment scale–self-report. The psychiatric profile of the patients was also assessed.Of 73 patients initially enrolled, 62 performed the initial inclusion visit (M−2) and the 2 postoperative visits (M+3, M+6). For these 62 patients (52% male), the overall mean age was 59 ± 6.13 years, and the mean disease duration was 9.44 ± 3.62 years. No specific differences were observed for social adjustment between the groups or visits (M−2, M+3, M+6); however, an interaction was found in the cognitive restructuration group at M+6 for the family dimension of the social adjustment scale–self-report.Our results suggest that even if no overall increase in the social adjustment score was observed, patients with Parkinson’s disease eligible for neurosurgery should undergo preoperative psychosocial therapy to define their expectations and help them in their psychological restructuration. This type of therapy, complementary to psychoeducation, could represent an opportunity to prevent postoperative deception and social maladjustment.

A Virtual Reality Serious Videogame Versus Online Chess Augmentation in Patients with Attention Deficit Hyperactivity Disorder: A Randomized Clinical Trial.

Objective: Serious videogames and virtual reality (VR) have gained increasing interest for treating attention deficit hyperactivity disorder (ADHD). "The Secret Trail of Moon" (TSTM) study is a clinical trial devoted to testing the efficacy of TSTM, a VR serious videogame developed to train in five major cognitive skills usually compromised in patients with ADHD. This study is a three-arm nonequality trial comparing TSTM to online chess training and a control group (CG). This study aims to demonstrate that augmentation with either TSTM or online chess is efficacious in clinically drug-stable patients with ADHD. Materials and Methods: This study is prospective, unicentric, and randomized with a CG. One hundred five patients with ADHD, ages 12-22 years old, and pharmacologically stable were enrolled. Patients were randomized into three groups: TSTM group, online chess group (therapeutic chess [TC]), and CG. Objective and subjective measures of the patient and parents are included. Patient visits differ for each group. TSTM group patients have 15 face-to-face visits: preinclusion visit, inclusion visit, 12 training visits, and final visit. TC and CG patients have 3 face-to-face visits (preinclusion, initial visit, and final visit) and 12 e-mail or phone communications during training (TC) or follow-up (CG group). This study was approved by the local Institutional Review Board (IRB). Results: Not applicable. This is a study protocol. Conclusion: This is the first study testing an augmentation strategy using either a serious videogame or chess in clinically drug-treated patients with ADHD. Using VR serious videogames present with several advantages over traditional videogames. Trial Registration: NCT04355065.

Burden of Disease Among Exacerbating Patients with COPD Treated with Triple Therapy in Spain.

BackgroundThe cost of chronic obstructive pulmonary disease (COPD) in Spain has been studied from different perspectives, but parameters such as the patient’s phenotype have seldom been considered. Our aim was to describe the disease burden of COPD patients with frequent exacerbator phenotype, treated with triple therapy.MethodsAn observational, multicenter study was carried out from December 2017 to November 2018 in pulmonology services among patients ≥40 years with COPD confirmed diagnosis receiving triple therapy (ICS/LAMA/LABA) and history of ≥2 moderate or ≥1 severe exacerbation in the 12 months prior to the inclusion visit. COPD-related healthcare resources were collected over a 12-months period prior to the inclusion visit: pharmacological and non-pharmacological treatments, medical and ER visits, hospitalizations, tests and productivity loss. Costs were updated to €2019. Patients were classified according to blood eosinophil levels: <150 cells/µL and ≥150 cells/µL.ResultsA total of 306 patients were included (77.1% men), with mean age of 69.9 years. Mean COPD exacerbation rate was 2.5/patient/year and 51.3% of patients had ≥150 cells/µL eosinophil level. On average, for the total population, COPD-related visits/patients/year were 6.2. Resource use in moderate exacerbation was higher in patients with eosinophils ≥150 cells/µL, whereas in severe exacerbation was higher in patients with eosinophils <150cells/µL. According to eosinophil levels, total annual mean (SD) costs/patient accounted for €8382 (9863) and €5144 (5444) for patients with eosinophils <150 cells/µL and ≥150 cells/µL, respectively.ConclusionThe impact of exacerbating COPD patients treated with triple therapy in Spain is large, especially among those with eosinophils <150 cells/µL.

Clinical Benefit of Insulin Glargine 300 U/mL Among Patients with Type 2 Diabetes Mellitus Previously Uncontrolled on Basal or Premixed Insulin in Serbia: A Prospective, Observational, Single-Arm, Multicenter, Real-World Study.

IntroductionInsulin glargine 300 U/mL (Gla-300) is a novel glargine formulation which shows slower and more prolonged absorption following subcutaneous administration in comparison to insulin glargine 100 U/mL. In this prospective, observational, single-arm, multicenter, real-world study conducted in Serbia, we evaluated the effectiveness and safety of Gla-300 in patients with type 2 diabetes mellitus (T2DM) previously inadequately controlled with different basal or premix insulin therapy regimes.MethodsA total of 350 patients with T2DM were enrolled by 27 physicians, from date of the first patient in (12 December 2017) to the date of last patient completed/last patient out (30 October 2018), from both medical centers and general hospitals. Patients’ observation and data collection were performed at visit 1 (V1), i.e., the inclusion visit (3–6 months after Gla-300 introduction), including collection of retrospective data from the patients’ medical charts at the time of Gla-300 introduction, and at visit 2 (V2) (3–6 months after V1). The primary objective was to assess the change in glycated hemoglobin (HbA1c) level from day of the Gla-300 initiation to the end of the observational period, while the secondary objectives included other effectiveness, as well as safety and other clinically relevant data.ResultsThe mean age of the 350 patients was 63.4 ± 8.4 years and 56.3% were female. The mean duration of diabetes was 13.4 ± 7.4 years, while the mean duration of insulin therapy prior to Gla-300 initiation was 5.3 ± 3.9 years. There was a significant reduction in HbA1c level at each visit compared to the previous visit (8.63 ± 1.52% at baseline prior to Gla-300 initiation, 7.87 ± 1.13% at V1, 7.45 ± 1.05% at V2; p < 0.01 vs. previous visit) accompanied by significant reduction of all hypoglycemic events (p < 0.01).ConclusionInitiation of Gla-300 therapy significantly improved glycemic control and reduced the risk of hypoglycemia in patients with T2DM inadequately controlled with different basal or premix insulin therapy regimes.FundingSanofi Serbia.

Comparison of Neuropsychological Assessment by Videoconference and Face to Face.

To compare the administration of neuropsychological tests by teleneuropsychology (TeleNP) and face to face (F-F) in order to determine the feasibility and reliability of TeleNP. At the inclusion visit, all participants underwent a traditional F-F neuropsychological assessment as part of their standard care. Four months after inclusion, they were randomized to undergo an additional neuropsychological assessment either by F-F administration or by TeleNP. A total of 150 adults with cognitive complaints, but with no major cognitive or sensorial impairment were included. At 4 months, 69 participants were randomized in the F-F arm and 71 in TeleNP arm (10 lost in the follow-up). The overall satisfaction was high: 87.1% in the TeleNP arm were "very satisfied", and 82.9% indicated no preference between F-F and TeleNP. In agreement with previous data from the literature, neuropsychological assessments gave similar results across both administration conditions for a large majority of tests [Mini-Mental State Examination (MMSE), Free and Cued Selective Reminding Test (FCSRT) French version, Mahieux gestural praxis battery, Frontal Assessment Battery (FAB), time of completion of the Trail making Test (TMT) A and B, number of errors of the TMT B, Rey complex figure test, categorical et phonological verbal fluency tests] and minor differences for others [80-picture naming test (DO-80), FAB, Digit Span forward and backward and number of errors in the TMT A]. TeleNP is a promising method to be able to test patients as an alternative to F-F condition. Before this procedure can be generalized, it is now necessary to standardize the adaptation of certain tests and to test them in populations with more significant cognitive disorders.

Anticoagulant therapy in patients with atrial fibrillation and an implanted cardiac resynchronization therapy device

Aim. To study the efficacy and safety of direct oral anticoagulant (DOAC) therapy after implantation of cardiac resynchronization therapy (CRT) devices in atrial fibrillation (AF) patients with coronary artery disease (CAD) and dilated cardiomyopathy (DCM).Material and methods. The study included 93 patients followed up from 2014 to 2016 (71 men and 22 women) aged 33-85 years (59,7±10,6) with stable CAD (group 1, n=44) and DCM (group 2, n=49). All patients were diagnosed with AF. The left ventricular ejection fraction (LVEF) was 30,6±3,8%; the left ventricular end-diastolic dimension was 230,9±60,8 mm. All patients received anticoagulants for the prevention of thromboembolic events: a vitamin K antagonist (warfarin) or DOAC. The analysis of medical records, as well as ECG records, echocardiographic, 24-hour ECG monitoring data and information from implanted device was carried out. The follow-up period lasted 24 months.Results. After 24-month follow-up, positive dynamics was noted in all patients — LVEF increased from 30,6±3,7% to 39,5±5,8%). In patients with DCM, a more pronounced increase in myocardial contractile function was noted. Stroke within time interval from 12 to 24 months developed in two patients taking warfarin, from different groups. Transient ischemic attacks were observed in 6 patients: in one patient from group 1 during the period from inclusion and 12-month visit, and in 5 patients from 12 to 24 months. Out of 5 patients, two belonged to group 1 and three — to group 2, while one patient took aspirin and the other 4 — warfarin. One patient from group 1 with persistent AF and vitamin K antagonist therapy had left atrial appendage thrombosis. Hemorrhagic strokes and major bleeding have not been reported.Conclusion. Among patients taking DOAC, regardless of the underlying disease (CAD or DCM) and response to CRT, bleeding events were less often recorded, and there were no thromboembolic events.

Impact of an Infant Formula Containing a Novel Fat Blend (Cow’s Milk Fat, Fish and Vegetable Oil) and Prebiotics on Stool Fatty Acid Soaps and Erythrocyte Fatty Acid Profiles in Full-Term Healthy Newborns

Introduction: Recently, new commercial infant formulas have been composed considering novel fat blends and oligosaccharides to better resemble the fatty acid (FA) composition and stereospecific distribution (e.g., increased amount of ß-palmitate) as well as probiotics content of human breast milk. We hypothesized that these newly composed infant formulas may decrease fecal FA soap excretion and may positively affect erythrocyte FA profiles compared with regular formulas. Methods: Healthy infants were randomly assigned to receive a high-sn-2-palmitate formula (>25% of the PA is esterified to the sn-2 position of the glycerol backbone, verum: n = 30) or a “standard” formula containing <10% of PA in sn-2 position and no oligosaccharides (control: n = 27); a non-randomized group of breast-fed infants served as control. Anthropometric data of the infants (body weight, recumbent length, and head circumference) were recorded at inclusion (visit 1) and 6 and 12 weeks after onset of intervention (visits 2 and 3). Blood samples for erythrocyte FA analysis (gas chromatography) were taken at visits 1 and 2; stool samples were collected at visit 2. Results: Quantitative formula intake (mL/kg body weight × day) at visit 2 (verum: 155 ± 30, control: 164 ± 30) and visit 3 (verum: 134 ± 26, control: 134 ± 21) was comparable. Six weeks after onset of intervention, stool total FA soaps, palmitate soaps, and total FAs were similar in both formula-fed groups but significantly higher than in breast-fed infants. During the 6-week intervention, erythrocyte palmitate decreased significantly from baseline in all 3 groups with no group differences (verum: 29.20 ± 1.17 to 27.12 ± 0.66, control: 29.88 ± 2.00 to 27.01 ± 0.94, breast-fed: 30.20 ± 0.86 to 26.84 ± 0.98). For selected FAs, significant changes over time in verum and control group were obvious but without formula effects. Some variations in the FA profile of breast-fed infants compared to both verum and control groups were observed. Conclusions: In contrast to our hypothesis, feeding a newly composed infant formula based on a fat blend with 25% of PA in the sn-2 position of triacylglycerols and supplemented with a prebiotic could not decrease insoluble FA soap excretion compared with a standard product; in this respect, breastfeeding is obviously the best choice. Surprisingly, erythrocyte FA profiles were comparable in formula-fed and breast-fed infants; obvious alterations in FA composition of the respective fat sources and structure did not affect FA incorporation into membranes. Caution should be, however, exercised in drawing robust conclusions in the absence of larger, adequately powered intervention studies.

THE PSYCHOLOGICAL COMPONENT OF THE QUALITY OF LIFE WAS RELATED TO COMPOSITE ENDPOINT IN TREATED PATIENTS WITH ARTERIAL HYPERTENSION

Objective: The aim of our study was to determine association between composite endpoint and quality of life (QL) scale scores in treated patients with arterial hypertension (AH). Design and method: We analyzed database of treated AH patients (n = 125) with concomitant chronic diseases without exacerbation. We assessed relationships between the initial ambulatory blood pressure monitoring (ABPM) data, socio-demographic indicators, QL scale scores, Asthma Control Questionnaire (ACQ) indices and composite endpoint (death for any reason, angina pectoris, transient ischemic attack, development of chronic heart failure, arterial revascularization, frequent ventricular extrasystoles, atrial fibrillation) after 30.1 ± 7.6 months from the inclusion visit. QL questionnaires (J.Siegrist et al.), ACQ (45 patients had asthma) was completed initially, after 6 months and after 12 months, the ABPM session was performed initially and after 12 months, antihypertensive therapy was corrected at all visits. We analyzed the following QL scale scores: 0 scale: mood at the doctor's visit, I scale: physical well-being; II scale: physical performance; III scale: positive psychological well-being; IV scale: negative psychological well-being; V scale: psychological performance; VI scale: social well-being; VII scale: social performance. We used ANOVA for statistical analysis. Results: The baseline mean daytime systolic BP (SBP) was 125.1 ± 10.5; diastolic (DBP) - 76.1 ± 7.3 mm Hg. We found negative correlations between composite endpoint and: III scale scores (positive psychological well-being) (F = -5.3, p &lt; 0.05); 0 scale (mood at the doctor's visit) (F = -5.6, p &lt; 0.05). We identified a positive correlation between endpoint data and V scale scores (psychological performance) (F = 12.2, p &lt; 0.001). The composite endpoint was not correlated with sex, age, BMI, smoking, ambulatory and clinical blood pressure, the number of drugs in concomitant therapy, pulmonary forced vital capacity. At the end of the study, we registered 21 cases included in the composite endpoint: death (2), transient ischemic attack (1), arterial revascularization (4), frequent ventricular extrasystole (3), atrial fibrillation (8), angina pectoris (3). Conclusions: Thus, psychological QL component such as good mood at the doctor's visit (scale 0), positive psychological well-being (scale III) had negative relationship with composite endpoint, at the same time the psychological performance (scale V) had positive correlation with composite endpoint results.

ANTIHYPERTENSIVE EFFECTIVENESS OF SWITCHING TO SINGLE PILL COMBINATION OF PERINDOPRIL/AMLODIPINE IN PATIENTS INEFFECTIVELY TREATED BY ARB-CONTAINING FREE COMBINATIONS (AVANGARD STUDY)

Objective: Objectives. To evaluate the effectiveness of perindopril arginine/ amlodipine single-pill combination (SPC) in patients with grade 1–2 hypertension uncontrolled on previous therapy with ARB-containing free combinations. Design and method: AVANGARD was a multicenter, open-label, 3-month Russian observational study, in 658 patients with suboptimal efficacy (SBP/DBP 140–179/90–109 mm Hg) of previous antihypertensive therapy with two drugs in free combination (one of which was an ARB), who were switched to perindopril arginine/amlodipine SPC. Data were collected at four visits: V1 (inclusion visit and treatment initiation), V2 (2 weeks), V3 (1 month), V4 (3 months). Results: The SBP/DBP values gradually and significantly decreased with Perindopril/amlodipine SPC from 159.9 ± 8.5/ 92.1 ± 7.4 mmHg to 141.3 ± 11.0/83.7 ± 7.5 mmHg after 2 weeks, 131.7 ± 9.2/79.5 ± 6.0 mmHg after 1 month and finally 125.8 ± 7.1 /77.4 ± 5.5 mm Hg; all p &lt; 0.001). The controlled BP was achieved in 36.2%, 73.4 and 93.5% of patients at V2, V3 and V4, respectively. The mean HR followed the same patern (V1: 73.9 ± 7.3 beats per minute (bpm); V4: 68.9 ± 5.0 bpm; p &lt; 0.001). Daytime 24-hour BP variability decreased from V2 to V4, from 4.4 ± 2.9/3.0 ± 2.0 to 3.0 ± 2.2/2.2 ± 1.7 mm Hg (p &lt; 0.001). Treatment acceptability was very high considering couple related adverse events (0,21%) in accordance with the well-known side effects of the drugs (oedema and cough) Conclusions: This study showed the antihypertensive effectiveness of perindopril/amlodipine SPC in hypertensive patients previously uncontrolled on two-drug free combinations containing an ARB.

Longitudinal Changes on Optical Coherence Tomography Angiography in Retinal Vein Occlusion.

Background: To evaluate the longitudinal changes on optical coherence tomography angiography (OCTA) in retinal vein occlusion (RVO). Methods: Retrospective study of patients with RVO treated with intravitreal anti-vascular endothelial growth factors (VEGF) for macular edema. Foveal avascular zone (FAZ) area, vessel density (VD), vessel length density (VLD), and adjusted flow index (AFI) were calculated. The unaffected eye of each participant was used as a control. Results: Twelve RVO eyes were included, receiving 6 ± 3 anti-VEGF injections over a follow-up of 10.4 ± 3.1 months. Compared to fellow eyes, RVO eyes had lower VD and VLD at inclusion (p = 0.07 and p = 0.04) and last visit (p = 0.002 and p < 0.001). VD, AFI, and VLD did not change over time, while FAZ area increased in RVO eyes (+0.016 ± 0.024 mm2, p = 0.04). AFI correlated with duration of disease (r = 0.63, p = 0.02). Visual acuity was inversely related to VD and VLD over the follow-up. Conclusions: OCTA parameters remained stable with sustained anti-VEGF treatment in RVO, while changes in the FAZ area may suggest capillary remodeling after RVO.

Assessment of Wnt pathway selected gene expression levels in peripheral blood mononuclear cells (PBMCs) of postmenopausal patients with low bone mass.

The purpose of the study was to assess the expression of selected genes of the Wnt pathway: APC, AXIN1, CTNNB1, DKK1, GSK3B, KREMEN1, SFRP1, and WNT1 in peripheral blood mononuclear cells (PBMC) of patients, selected in consideration of their bone mineral density (BMD), and the occurrence of low-energy fractures. The study involved 45 postmenopausal women, divided into four groups, according to BMD and fracture history. Measurements of laboratory parameters and RNA expression in PBMC cells were carried out in material, collected once at the inclusion visit. The densitometric examination was performed on all participants. In the analysis of the relative expression levels (RELs) of the studied genes in the entire population, we observed an overexpression for SFRP1 in 100% of samples and WNT1. In addition, the REL of DKK1, APC, and GSK3B genes were slightly elevated versus the calibrator. In contrast, CTNNB1 and AXIN1 presented with a slightly decreased RELs. Analysis did not show any significant differences among the groups in the relative gene expression levels (p < 0.05) of particular genes. However, we have observed quite numerous interesting correlations between the expression of the studied genes and BMD, the presence of fractures, and laboratory parameters, both in the whole studied population as well as in selected groups. In conclusion, the high level of CTNNB1 expression maintains normal BMD and/or protects against fractures. It also appears that the changes in expression levels of the Wnt pathway genes in PBMCs reflect the expected changes in bone tissue.

Exploring the causes of MMSE scoring and administration errors in the clinical trial screening period

AbstractBackgroundAudio recording of eCOA MMSE administration enables identification of both administration and scoring errors. Either can result in incorrect MMSE scores, potentially leading to inclusion of inappropriate subjects and/or biased assessment of change after randomization. Our current analysis explores the effect of protocol design, MMSE scores close to inclusion criteria and visit type on MMSE scoring and/or administration errors.MethodData were pooled from 2 types of early dementia protocols – Type A where MMSE inclusion criteria need only be met at screening, and type B where they needed to be met at both screening and baseline. All assessments were audio recorded and reviewed by independent clinicians for the presence of administration and scoring errors. Operationally, subjects were defined as close to inclusion criteria if their MMSE scores were within 2 points of specified thresholds. Logistic regression with 3‐way interaction was used to explore the hypotheses.Result11,391 MMSE assessments were reviewed, and 2,706 (23.8%) had either an administration and/or scoring error. In both protocol types, administration errors were significantly less likely at baseline than screening, regardless of MMSE score proximity to inclusion threshold. In type A protocols, administration errors were more likely if scores were close to inclusion criteria. For type B protocols this was true only at screening. Scoring errors were significantly less likely at baseline, if MMSE scores were close to inclusion (both protocol types) or not (type A). Scoring errors were significantly more likely at screening but not baseline when scores were close to inclusion (only type A). No direct effect of protocol design was observed on the likelihood of either scoring or administration errors.ConclusionOur data indicate that scoring and administration errors occur more frequently at screening and in subjects with scores close to inclusion criteria. Despite some differences, the effect of protocol design seems less likely to result in errors to the same extent as the other 2 parameters. Given that data coming from subjects close to inclusion criteria at screening are at the highest risk of having a scoring or administration error indicates that data may be manipulated to meet inclusion criteria.

Main factors of adherence to new oral anticoagulants and its dynamics in outpatients with nonvalvular atrial fibrillation: results of the ANTEY study

Aim. To assess adherence to new oral anticoagulants (NOAC) or warfarin therapy and to study the factors influencing adherence in nonvalvular atrial fibrillation (AF) patients on different stages of treatment within the prospective outpatient registry of patients with cardiovascular diseases. Material and methods . The study included 201 patients with nonvalvular AF (males, 118 (58,7%)) from the outpatient registry PROFILE). Mean age was 71,1 ±8,7 years. Study protocol consisted of the inclusion visit (V0), 6-month follow-up visit (V1) and phone contact 1 year after V0 (PC). In V0, all patients were prescribed one of the NOACs. At V1 doctors could recommend warfarin or another NOAC to patients, who have refused taking prescribed NOAC. Medical adherence was determined using the of the National society of evidence-based pharmacotherapy (NSEPh) adherence scale. NSEPh adherence scale allows to grade patients’ adherence to treatment into 4 categories: 1) completely adherent, 2) partially adherent, 3) completely non-adherent, 4) partially non-adherent. Dichotomous grading into adherent (completely adherent) and non-adherent (rest of patients) was also used. Results. Out of 201 included patients, 200 came to V1 (1 patient died). PC was successful in 197 patients (3 patients died). According to NSEPh adherence scale, 155 (77,5%) patients at V1 were completely adherent, 5 (2,5%) — partially adherent, 7 (3,5%) — partially non-adherent, 33 (16,5%) — completely non-adherent. By the PC, 158 (80,2%) patients were completely adherent to the OAC therapy, 6 (3,0%) — partially adherent, 28 (14,2%) — partially non-adherent, 15 (7,6%) — completely non-adherent. At all stages of treatment, the following factors of good adherence remained significant: never-smoking, prior NOAC use, negative history of any treatment-related adverse effects (AEs). Patients with comorbidities and a history of bleeding during OAC therapy were more likely to discontinue initial scheme and violate treatment regimen (p&lt;0,05). Symptomatic course of AF increased adherence by 2,4 times ( р =0,02). According to the questionnaire, the leading reasons for refusing NOAC therapy were the high cost of drugs, the fear of AE and doubts about the need for treatment. The main factors leading to discontinuation of NOAC/OAC treatment were bleeding and the cancellation (often unreasonable) of these medications by other doctors. Conclusion. The results of ANTEY study confirm that factors influencing adherence to NOAC may vary during different phases of treatment. The main reasons that prevent NOAC therapy initiation are the high cost of these drugs, fear of AE and doubts about the need for such treatment. Significant factors of discontinuation were AEs and cancellation of NOAC therapy by doctors from other medical institutions. Factors that positively affect both initiation and long-term use of the drug are never-smoking, prior NOAC use, negative history of any treatment-related AEs.

Epidemiology and Management of Immune Thrombocytopenia in Adult Patients in Algeria: A Non-Interventional, Longitudinal, Nationwide Estimation Study

Background: Immune thrombocytopenia (ITP), is an acquired immune mediated disease characterized by a platelet count of &amp;lt;50×103/mm3, accelerated destruction of platelets from peripheral circulation, and impaired platelet production. Diagnosis is based on exclusion of other causes of thrombocytopenia. Treatment goal is to ensure sufficient platelet count to prevent bleeding. ITP occurs mainly in women, either at the onset of puberty, or in their 3rd/4th decade, with higher mortality in older patients. To date, no accurate epidemiological data on ITP is available for Algeria. This study assessed the incidence (by age, sex, diagnosis stage, and province), prevalence, characteristics, and treatment regimens received by ITP patients (pts) in Algeria. Methods: This non-interventional, longitudinal, nationwide estimation study investigated the epidemiology and care of ITP pts treated in public hospitals in Algeria from September 2017─August 2018. Data were collected at inclusion visit on a case report form. Data on bleeding score and platelet count were also collected after study termination. Pts ≥16 years (y) of age, either previously (before 1st September 2017) or newly (September 2017─August 2018) diagnosed with ITP, having given written consent, were included. The incidence and prevalence of ITP were estimated with Poisson distribution (95% confidence interval [CI]). Results: Overall 1,746 pts were listed, of whom 587 without consent. Of the 1,164 enrolled pts, 1,159 were included (male: 264 [22.8%]); 5 pts (0.4%) were excluded for major protocol deviations. Among eligible pts, 173 (14.9%) were newly and 986 (85.1%) had been previously diagnosed with ITP. No comorbidities conferring bleeding risk were found in 966 pts (83.3%). At diagnosis, median age was 36y (quartiles: 25y, 50y) and platelet count (103/mm3) was 0-30 in 124 (71.7%), 30-50 in 20 (11.6%), and 50-100 in 28 (16.2%) pts. Khellaf score was ≤8 for 45 (26.0%) and &amp;gt;8 for 8 (4.6%) pts; 120 pts (69.4%) had missing Khellaf score. Bleeding risk (as per WHO bleeding score) was low (grade 0) in 50 (28.9%), grade I in 24 (13.9%), grade II in 34 (19.7%), grade III in 52 (30.1%), and grade IV in 13 (7.5%) pts. 55 (31.8%) pts were asymptomatic, 58 (33.5%) were ecchymotic, and 60 (34.7%) were severely hemorrhagic. Steroids comprised the major treatment for both new (n [%]: 136 [78.6]) and previously (795 [80.7]) diagnosed ITP pts. First line ITP treatments included corticosteroids (937 [80.8]), immunoglobulins (39 [3.4]), antineoplastic agents (15 [1.3]), rituximab (14 [1.2]) and antibacterials (2 [0.2]). Last/ongoing treatments at inclusion comprised corticosteroids (712 [72.2]), rituximab (56 [5.7]), immunoglobulins (30 [3.0]), romiplostim (19 [1.9]), and antibacterials (4 [0.4]). Among previously diagnosed ITP pts, 172 (17.4%) had a splenectomy with a median time from ITP diagnosis of 19 months. Incidence of ITP in pts ≥16y was 0.85 cases (95% CI: 0.75, 0.96) per 100,000 inhabitants. Incidence increased with age from 0.5 (95% CI: 0.43, 0.68) in pts aged 15-35y to 2.4 (95% CI: 1.60, 3.51) in pts ≥75y old. Female pts had a higher incidence of ITP (1.2 [95% CI: 1.02, 1.37]) vs male pts (0.5 [95% CI: 0.43, 0.67]; male:female ratio 0.3). Incidence of ITP varied with diagnosis stage (asymptomatic: 0.4 [95% CI: 0.31, 0.45]; ecchymosis: 0.1 [95% CI: 0.10, 0.19]; severe hemorrhage: 0.1 [95% CI: 0.06, 0.13]), and province (lowest: 0.1 [95% CI: 0.02, 0.92] in a public site in Tebessa; highest: 1.6 [95% CI: 0.93, 2.89] in a public site in Sidi Bel Abbès). Prevalence of ITP was 5.7 (95% CI: 5.39, 5.93) per 100,000 inhabitants. Prevalence increased with age from 3.2 (95% CI: 2.78, 3.67) in pts aged 15-25y to 11.9 (95% CI: 9.68, 13.08) in pts aged 65-75y, then decreased in pts ≥85y old (7.6 [95% CI: 4.79, 12.06]). Female pts had a higher prevalence of ITP (8.8 [95% CI: 8.33, 9.29]) vs male pts (2.6 [95% CI: 2.34, 2.85]). Conclusion: The incidence and prevalence of ITP in Algeria were higher in females and increased with age conforming to global trends, but lower than occidental data thus requiring further investigations. Corticosteroids were the most commonly used agents in different lines of treatment; splenectomy was the second option in cases of corticosteroid failure. Rituximab and romiplostim were the last/ongoing treatment before inclusion for a small number of pts. The study highlighted the need for more data on the use of romiplostim prior to splenectomy for adult ITP pts in Algeria. Disclosures Tiaiba: Amgen Middle East:Current Employment.Saad:Amgen Inc:Current Employment.

Comparative Characteristics of Patients with Cerebral Stroke and Myocardial Infarction in Outpatient Practice: Structure of Comorbidity, Risk Factors, Drug Treatment and Outcomes

Aim. To conduct a comparative analysis of clinical and anamnestic characteristics, risk factors, pharmacotherapy and outcomes in patients with previous stroke and myocardial infarction (MI) in outpatient practice based on data from prospective outpatient registries.Material and methods. On the basis of three outpatient clinics in Ryazan, based on the results of treatment in 2012-2013, an outpatient registry of patients who had stroke of any remoteness (REGION-AR) and an outpatient registry of patients who had previous myocardial infarction (REGATA) were created, which included, respectively, 511 patients (212 men, 41.5%) and 481 patients (247 men, 51.4%). Clinical and anamnestic characteristics, risk factors, prescribed pharmacotherapy, and its compliance with clinical guidelines were evaluated.Results. Most of the patients in the REGION-AR and REGATA registries were diagnosed with arterial hypertension (AH; 97.1% and 98.5%), coronary heart disease (СHD; 75.1% and 100%), chronic heart failure (CHF; 74.0% and 94.8%), and the proportion of atrial fibrillation (AF) cases were 20.9% and 23.3%, respectively. The share of smokers was significantly higher (23.4% vs 8.9%; p&lt;0.0001) in the REGATA registry, and the share of people with high blood pressure at the inclusion visit (82.6% vs 67.6 %; p&lt;0.0001) and hypercholesterolemia (63.8% vs 45.8%; p&lt;0.0001) was higher in the REGION-AR registry. In both registries, there was a generally insufficient frequency of proper medication prescriptions, while patients in the REGION registry were statistically significantly less likely to receive mandatory prescriptions in general (44.4% vs 58.2%, p&lt;0.0001), including antihypertensive therapy for hypertension, as well as angiotensin-converting-enzyme (ACE) inhibitors/angiotensin receptor blockers (ARBs) in CHF, beta-blockers in CHF and MI history, statins in CHD, antiplatelet agents in CHD without AF. Over 3 years of follow-up, the degree of compliance of drug prescriptions with clinical recommendations increased both in the REGION-AR registry (from 44.4% to 58.2%) and in the REGATA registry (from 58.2% to 62.9%). For 36 months of prospective observation in the REGION-AR registry, as compared to the REGATA registry, there was a higher mortality rate (22.1% vs 17.0%; p=0.04), moreover the mortality rate among men was higher (22.2% vs 14.2%; p=0.03), and among women it did not differ significantly (22.1% and 20.0%; p=0.56).Conclusion. Outpatient registries of patients who survived after acute cerebrovascular accident and myocardial infarction were comparable in terms of the average age of patients, however, women prevailed in the REGION-AR study, and men - in the REGATA registry. In the registry of patients who had myocardial infarction, СHD, CHF, respiratory and digestive system diseases, chronic kidney disease, obesity were more often diagnosed, less often – heart defects and oncological diseases. This category of patients was more often prescribed ACE inhibitors/ARBs, beta-blockers, statins, antiplatelet agents. The proportion of compliance of prescriptions with clinical guidelines was higher in the registry of patients who underwent MI both at the stage of inclusion and during subsequent prospective observation. In both registries, an improvement in the quality of drug therapy was noted after 3 years of follow-up. Mortality from all causes over 3 years of follow-up was significantly higher in the registry of post-stroke patients compared to the registry of those with MI, and this was due to the higher mortality in men (1.6 times), but among women in the compared studies the death rate did not differ significantly.

Short-term outcomes of patients with neovascular exudative AMD: the effect of COVID-19 pandemic.

PurposeTo estimate the impact of delayed care during the coronavirus disease 2019 (COVID-19) pandemic on the outcomes of patients with neovascular age-related macular degeneration (AMD).MethodsConsecutive patients with diagnosis of neovascular AMD were consecutively enrolled between March 9, 2020, and June 12, 2020, (during and immediately after the Italian COVID-19 quarantine). During the inclusion (or pandemic) visit (V0), patients received a complete ophthalmologic evaluation, including optical coherence tomography (OCT). Best-corrected visual acuity (BCVA) and OCT findings from the two preceding visits (V−1 and V−2) were compared with data at V0.ResultsOne-hundred patients (112 eyes) were enrolled in this study. The time interval between following visits was 110.7 ± 37.5 days within V0 and V−1 and 80.8 ± 39.7 days within V−1 and V−2, respectively (P < 0.0001). BCVA was statistically worse at the V0 visit as compared with the immediately preceding (V−1) visit (0.50 ± 0.43 LogMAR and 0.45 ± 0.38 LogMAR at the V0 and V−1 visits, respectively; P = 0.046). On structural OCT, 91 out of 112 (81.2%) neovascular AMD eyes displayed the evidence of exudative disease activity at the V0 visit, while 77 (68.7%) eyes exhibited signs of exudation at the V−1 visit (P = 0.022). No differences in terms of BCVA and OCT findings were detected between the V−1 and V−2 visits. In multiple regression analysis, the difference in BCVA between V0 and V−1 visits was significantly associated with the interval time within these two visits (P = 0.026).ConclusionThe COVID-19 pandemic-related postponement in patient care proved to be significantly associated with worse short-term outcomes in these patients.

Parkinson’s Disease and Bilateral Subthalamic Nuclei Deep Brain Stimulation: Beneficial Effects of Preoperative Cognitive Restructuration Therapy on Postoperative Social Adjustment

Bilateral subthalamic nucleus deep brain stimulation improves motor symptoms and treatment-related complications in patients with Parkinson's disease. However, some patients have trouble adjusting socially after successful neurosurgery, in part because of "unrealistic" expectations and psychiatric disorders. Preoperative psychological interventions focusing on these aspects could be beneficial for such patients. We compared the outcomes of 2 psychosocial approaches-1 based on cognitive restructuration and 1 consisting of 2 interviews-with those of a control group without preoperative preparation. All patients underwent a psychometric evaluation 2 months before surgery (M-2) and again at 3 (M+3) and 6 months (M+6) after surgery. The psychometric evaluation focused on social adjustment using the social adjustment scale-self-report. The psychiatric profile of the patients was also assessed. Of 73 patients initially enrolled, 62 performed the initial inclusion visit (M-2) and the 2 postoperative visits (M+3, M+6). For these 62 patients (52% male), the overall mean age was 59 ± 6.13 years, and the mean disease duration was 9.44 ± 3.62 years. No specific differences were observed for social adjustment between the groups or visits (M-2, M+3, M+6); however, an interaction was found in the cognitive restructuration group at M+6 for the family dimension of the social adjustment scale-self-report. Our results suggest that even if no overall increase in the social adjustment score was observed, patients with Parkinson's disease eligible for neurosurgery should undergo preoperative psychosocial therapy to define their expectations and help them in their psychological restructuration. This type of therapy, complementary to psychoeducation, could represent an opportunity to prevent postoperative deception and social maladjustment.

Factores asociados al riesgo cardiovascular y enfermedad cardiovascular y renal en el estudio IBERICAN (Identificación de la poBlación Española de RIesgo CArdiovascular y reNal): resultados definitivos

ObjectiveTo analyse the prevalence in clinical practice of cardiovascular risk factors (CVRF) and cardiovascular disease (CVD), as well as their causal relationship, in the study inclusion visit. Material and methodsCross-sectional analysis of the study inclusion visit of 8,066 patients of 18 to 85years of age included in the IBERICAN study. By reviewing the medical history, analytics and medical visits, the patient's physician has collected socio-demographic information, personal and family history and prevalence of CVRF and CVD and renal disease. A multivariate analysis was carried out using a logistic regression that included the autonomous region variable as a random effect variable, in order to analyse the impact of certain variables on the development of each CVRF, metabolic syndrome, subclinical organ damage, renal disease, and CVD. ResultsDyslipidaemia was 2.4 times more frequent in diabetics, and the risk was increased by 59% in hypertensive patients. Arterial hypertension was twice as frequent in diabetics, and increased 94% in hyperuricaemic patients and 62.1% in dyslipidaemia patients. Diabetes mellitus was 2.5 times higher in dyslipidaemia patients, and 2.2 times higher in hypertensive patients. CVD was four times more frequent in patients with a family history, and the risk in women was increased by 90.8% and by 53.8% in patients with renal disease. ConclusionsThe Spanish population seen in Primary Care that were analysed in the IBERICAN study had a high prevalence of CVRF and CVD, which gives it a high CVR. The multivariate analysis performed shows a close causal relationship between the CVRF with each other, and with renal disease and CVD.