scholarly journals Association of Polygenic Liability for Alcohol Dependence and EEG Connectivity in Adolescence and Young Adulthood

2019 ◽  
Vol 9 (10) ◽  
pp. 280 ◽  
Author(s):  
Jacquelyn L. Meyers ◽  
David B. Chorlian ◽  
Emma C. Johnson ◽  
Ashwini K. Pandey ◽  
Chella Kamarajan ◽  
...  
Keyword(s):  
Alcohol Dependence ◽  
Large Scale ◽  
Collaborative Study ◽  
Adolescent And Young Adult ◽  
Risk Scores ◽  
Neurocognitive Performance ◽  
Opioid Use ◽  
Increased Risk ◽  
Eeg Connectivity ◽  
Use Behavior

Differences in the connectivity of large-scale functional brain networks among individuals with alcohol use disorders (AUD), as well as those at risk for AUD, point to dysfunctional neural communication and related cognitive impairments. In this study, we examined how polygenic risk scores (PRS), derived from a recent GWAS of DSM-IV Alcohol Dependence (AD) conducted by the Psychiatric Genomics Consortium, relate to longitudinal measures of interhemispheric and intrahemispheric EEG connectivity (alpha, theta, and beta frequencies) in adolescent and young adult offspring from the Collaborative Study on the Genetics of Alcoholism (COGA) assessed between ages 12 and 31. Our findings indicate that AD PRS (p-threshold < 0.001) was associated with increased fronto-central, tempo-parietal, centro-parietal, and parietal-occipital interhemispheric theta and alpha connectivity in males only from ages 18–31 (beta coefficients ranged from 0.02–0.06, p-values ranged from 10−6–10−12), but not in females. Individuals with higher AD PRS also demonstrated more performance deficits on neuropsychological tasks (Tower of London task, visual span test) as well as increased risk for lifetime DSM-5 alcohol and opioid use disorders. We conclude that measures of neural connectivity, together with neurocognitive performance and substance use behavior, can be used to further understanding of how genetic risk variants from large GWAS of AUD may influence brain function. In addition, these data indicate the importance of examining sex and developmental effects, which otherwise may be masked. Understanding of neural mechanisms linking genetic variants emerging from GWAS to risk for AUD throughout development may help to identify specific points when neurocognitive prevention and intervention efforts may be most effective.

scholarly journals Brain ageing in schizophrenia: evidence from 26 international cohorts via the ENIGMA Schizophrenia consortium

2022 ◽  
Author(s):  
Constantinos Constantinides ◽  
Laura KM Han ◽  
Clara Alloza ◽  
Linda Antonucci ◽  
Celso Arango ◽  
...  
Keyword(s):  
Clinical Characteristics ◽  
Large Scale ◽  
Age Of Onset ◽  
Collaborative Study ◽  
Brain Magnetic Resonance Imaging ◽  
Age Difference ◽  
Intracranial Volume ◽  
Age Related ◽  
Brain Ageing ◽  
Increased Risk

Schizophrenia (SZ) is associated with an increased risk of life-long cognitive impairments, age-related chronic disease, and premature mortality. We investigated evidence for advanced brain ageing in adult SZ patients, and whether this was associated with clinical characteristics in a prospective meta-analytic study conducted by the ENIGMA Schizophrenia Working Group. The study included data from 26 cohorts worldwide, with a total of 2803 SZ patients (mean age 34.2 years; range 18-72 years; 67% male) and 2598 healthy controls (mean age 33.8 years, range 18-73 years, 55% male). Brain-predicted age was individually estimated using a model trained on independent data based on 68 measures of cortical thickness and surface area, 7 subcortical volumes, lateral ventricular volumes and total intracranial volume, all derived from T1-weighted brain magnetic resonance imaging (MRI) scans. Deviations from a healthy brain ageing trajectory were assessed by the difference between brain-predicted age and chronological age (brain-predicted age difference [brain-PAD]). On average, SZ patients showed a higher brain-PAD of +3.64 years (95% CI: 3.01, 4.26; I2 = 55.28%) compared to controls, after adjusting for age and sex (Cohen's d = 0.50). Among SZ patients, brain-PAD was not associated with specific clinical characteristics (age of onset, duration of illness, symptom severity, or antipsychotic use and dose). This large-scale collaborative study suggests advanced structural brain ageing in SZ. Longitudinal studies of SZ and a range of mental and somatic health outcomes will help to further evaluate the clinical implications of increased brain-PAD and its ability to be influenced by interventions.

Biomarkers Associated with Bleeding Risk in the Setting of Atrial Fibrillation

2019 ◽  
Vol 26 (5) ◽  
pp. 824-836 ◽  
Author(s):  
Skevos Sideris ◽  
Stefanos Archontakis ◽  
George Latsios ◽  
George Lazaros ◽  
Konstantinos Toutouzas ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Large Scale ◽  
Oral Anticoagulants ◽  
Significant Risk ◽  
Bleeding Risk ◽  
Hepatic Function ◽  
Risk Scores ◽  
Current Evidence ◽  
Prognostic Impact ◽  
Increased Risk

Background: Prevention of thromboembolic disease, mainly stroke, with oral anticoagulants remains a major therapeutic goal in patients with atrial fibrillation. Unfortunately, despite the high efficacy, anticoagulant therapy is associated with a significant risk of, frequently catastrophic, and hemorrhagic complications. Among different clinical and laboratory parameters related to an increased risk of bleeding, several biological markers have been recognized and various risk scores for bleeding have been developed. Objectives/Methods: The aim of the present study is to review current evidence regarding the different biomarkers associated with raised bleeding risk in atrial fibrillation. Results: Data originating from large cohorts or the recent large-scale trials of atrial fibrillation have linked numerous individual biomarkers to an increased bleeding risk. Such a relation was revealed for markers of cardiac physiology, such as troponin, BNP and NT-proBNP, markers of renal function, such as GFR and Cystatin or hepatic function, markers involving the system of coagulation, such as D-dimer and Von Willebrand factor, hematologic markers, such as low haemoglobin or low platelets, inflammatory markers, such as interleukin-6, other factors such as GDF-15 and vitamin-E and finally genetic polymorphisms. Many such biomarkers are incorporated in the bleeding risk schemata developed for the prediction of the hemorrhagic risk. Conclusions: Biomarkers were introduced in clinical practice in order to better estimate the potential risk of haemorrhage in these patients and increase the prognostic impact of clinical risk scores. In the last years this concept is gaining significant importance.

scholarly journals Polygenic contributions to alcohol use and alcohol use disorders across population-based and clinically ascertained samples

2020 ◽  
pp. 1-10 ◽  
Author(s):  
Emma C. Johnson ◽  
Sandra Sanchez-Roige ◽  
Laura Acion ◽  
Mark J. Adams ◽  
Kathleen K. Bucholz ◽  
...  
Keyword(s):  
Alcohol Use ◽  
Alcohol Dependence ◽  
Problem Drinking ◽  
Alcohol Use Disorders ◽  
Collaborative Study ◽  
Population Based ◽  
Risk Scores ◽  
Parents And Children ◽  
Generation Scotland ◽  
The Uk

Abstract Background Studies suggest that alcohol consumption and alcohol use disorders have distinct genetic backgrounds. Methods We examined whether polygenic risk scores (PRS) for consumption and problem subscales of the Alcohol Use Disorders Identification Test (AUDIT-C, AUDIT-P) in the UK Biobank (UKB; N = 121 630) correlate with alcohol outcomes in four independent samples: an ascertained cohort, the Collaborative Study on the Genetics of Alcoholism (COGA; N = 6850), and population-based cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC; N = 5911), Generation Scotland (GS; N = 17 461), and an independent subset of UKB (N = 245 947). Regression models and survival analyses tested whether the PRS were associated with the alcohol-related outcomes. Results In COGA, AUDIT-P PRS was associated with alcohol dependence, AUD symptom count, maximum drinks (R2 = 0.47–0.68%, p = 2.0 × 10−8–1.0 × 10−10), and increased likelihood of onset of alcohol dependence (hazard ratio = 1.15, p = 4.7 × 10−8); AUDIT-C PRS was not an independent predictor of any phenotype. In ALSPAC, the AUDIT-C PRS was associated with alcohol dependence (R2 = 0.96%, p = 4.8 × 10−6). In GS, AUDIT-C PRS was a better predictor of weekly alcohol use (R2 = 0.27%, p = 5.5 × 10−11), while AUDIT-P PRS was more associated with problem drinking (R2 = 0.40%, p = 9.0 × 10−7). Lastly, AUDIT-P PRS was associated with ICD-based alcohol-related disorders in the UKB subset (R2 = 0.18%, p < 2.0 × 10−16). Conclusions AUDIT-P PRS was associated with a range of alcohol-related phenotypes across population-based and ascertained cohorts, while AUDIT-C PRS showed less utility in the ascertained cohort. We show that AUDIT-P is genetically correlated with both use and misuse and demonstrate the influence of ascertainment schemes on PRS analyses.

scholarly journals Polygenic Prediction of Substance Use Disorders in Clinical and Population Samples

2019 ◽  
Author(s):  
Peter B. Barr ◽  
Albert Ksinan ◽  
Jinni Su ◽  
Emma C. Johnson ◽  
Jacquelyn L. Meyers ◽  
...  
Keyword(s):  
Substance Use ◽  
Association Studies ◽  
Collaborative Study ◽  
Risky Behaviors ◽  
Alcohol Problems ◽  
Risk Scores ◽  
Genome Wide Association Studies ◽  
Current Form ◽  
Genome Wide ◽  
Increased Risk

AbstractGenome-wide, polygenic risk scores (PRS) have emerged as a useful way to characterize genetic liability using genotypic data. There is growing evidence that PRS may prove useful to identify those at increased risk for developing certain diseases. The current utility of PRS in relation to alcohol use disorders (AUD) remains an open question. Using data from both a population-based sample [the FinnTwin12 (FT12) study] and a high risk sample [the Collaborative Study on the Genetics of Alcoholism (COGA)], we examined the association between PRSs derived from genome-wide association studies (GWASs) of 1) alcohol dependence/alcohol problems, 2) alcohol consumption, and 3) risky behaviors with AUD and other substance use disorder (SUD) symptoms. Individuals in the top 20%, 10%, and 5% of PRSs had increasingly greater odds of having an AUD compared to the lower end of the continuum in both COGA (80th% OR = 1.95; 90th% OR = 2.03; 95th% OR = 2.13) and FT12 (80th% OR = 1.77; 90th% OR = 2.27; 95th% OR = 2.39). Those in the top 5% reported greater levels of licit (alcohol and nicotine) and illicit (cannabis) SUD symptoms. PRSs can predict elevated risk for SUD in independent samples. However, clinical utility of these scores in their current form is modest. As these scores become more predictive of SUD, they may become useful to practitioners. Improvement in predictive ability will likely be dependent on increasing the size of well-phenotyped discovery samples.

Ongoing randomized clinical trials for the treatment of thrombosis in the antiphospholipid syndrome

2001 ◽  
Vol 21 (02) ◽  
pp. 77-81 ◽  
Author(s):  
G. Finazzi
Keyword(s):  
Clinical Trials ◽  
Large Scale ◽  
Low Dose ◽  
Randomized Clinical Trials ◽  
Oral Anticoagulants ◽  
Collaborative Study ◽  
Clinical Problem ◽  
Vascular Events ◽  
Dose Oral ◽  
Adverse Pregnancy

SummaryThrombotic events are a major clinical problem for patients with antiphospholipid antibodies (APA). However, current recommendations for their prevention and treatment are still based on retrospective studies. Data from large scale, prospective clinical trials are required to ultimately identify the optimal management of these patients. To date, at least four randomized studies are underway. The WAPS and PAPRE clinical trials are aimed to establish the correct duration and intensity of oral anticoagulation in APA patients with major arterial or venous thrombosis. The WARSS-APASS is a collaborative study to evaluate the efficacy and safety of aspirin or low-dose oral anticoagulants in preventing the recurrence of ischemic stroke. The recently announced UK Trial compares low-dose aspirin with or without low-intensity anticoagulation for the primary prevention of vascular events in APA-positive patients with SLE or adverse pregnancy history, but still thrombosis-free. It is hoped that the results of these trials will be available soon since clinicians urgently need more powerful data to treat their patients with the APA syndrome.

Four-Corner Arthrodesis versus Proximal Row Carpectomy: Risk Factors and Complications Associated with Prolonged Postoperative Opioid Use

2020 ◽  
Author(s):  
Neill Y. Li ◽  
Alexander S. Kuczmarski ◽  
Andrew M. Hresko ◽  
Avi D. Goodman ◽  
Joseph A. Gil ◽  
...  
Keyword(s):  
Risk Factors ◽  
International Classification Of Diseases ◽  
Opioid Use ◽  
Proximal Row Carpectomy ◽  
Use Patterns ◽  
Patient Demographics ◽  
Implant Complications ◽  
Increased Risk ◽  
Classification Of Diseases

Abstract Introduction This article compares opioid use patterns following four-corner arthrodesis (FCA) and proximal row carpectomy (PRC) and identifies risk factors and complications associated with prolonged opioid consumption. Materials and Methods The PearlDiver Research Program was used to identify patients undergoing primary FCA (Current Procedural Terminology [CPT] codes 25820, 25825) or PRC (CPT 25215) from 2007 to 2017. Patient demographics, comorbidities, perioperative opioid use, and postoperative complications were assessed. Opioids were identified through generic drug codes while complications were defined by International Classification of Diseases, Ninth and Tenth Revisions, Clinical Modification codes. Multivariable logistic regressions were performed with p < 0.05 considered statistically significant. Results A total of 888 patients underwent FCA and 835 underwent PRC. Three months postoperatively, more FCA patients (18.0%) continued to use opioids than PRC patients (14.7%) (p = 0.033). Preoperative opioid use was the strongest risk factor for prolonged opioid use for both FCA (odds ratio [OR]: 4.91; p < 0.001) and PRC (OR: 6.33; p < 0.001). Prolonged opioid use was associated with an increased risk of implant complications (OR: 4.96; p < 0.001) and conversion to total wrist arthrodesis (OR: 3.55; p < 0.001) following FCA. Conclusion Prolonged postoperative opioid use is more frequent in patients undergoing FCA than PRC. Understanding the prevalence, risk factors, and complications associated with prolonged postoperative opioid use after these procedures may help physicians counsel patients and implement opioid minimization strategies preoperatively.

Study of Biochemical and Clinical Markers in Steatohepatitis Related to Obesity

2018 ◽  
Vol 69 (6) ◽  
pp. 1501-1505
Author(s):  
Roxana Maria Livadariu ◽  
Radu Danila ◽  
Lidia Ionescu ◽  
Delia Ciobanu ◽  
Daniel Timofte
Keyword(s):  
Liver Disease ◽  
Liver Biopsy ◽  
Large Scale ◽  
Biological Data ◽  
Obese Patients ◽  
Clinical Markers ◽  
Mean Values ◽  
Nonalcoholic Fatty Liver ◽  
Obstructive Sleep ◽  
Increased Risk

Nonalcoholic fatty liver disease (NAFLD) is highly associated to obesity and comprises several liver diseases, from simple steatosis to steatohepatitis (NASH) with increased risk of developing progressive liver fibrosis, cirrhosis and hepatocellular carcinoma. Liver biopsy is the gold standard in diagnosing the disease, but it cannot be used in a large scale. The aim of the study was the assessment of some non-invasive clinical and biological markers in relation to the progressive forms of NAFLD. We performed a prospective study on 64 obese patients successively hospitalised for bariatric surgery in our Surgical Unit. Patients with history of alcohol consumption, chronic hepatitis B or C, other chronic liver disease or patients undergoing hepatotoxic drug use were excluded. All patients underwent liver biopsy during sleeve gastrectomy. NAFLD was present in 100% of the patients: hepatic steatosis (38%), NASH with the two forms: with fibrosis (31%) and without fibrosis (20%), cumulating 51%; 7 patients had NASH with vanished steatosis. NASH with fibrosis statistically correlated with metabolic syndrome (p = 0.036), DM II (p = 0.01) and obstructive sleep apnea (p = 0.02). Waist circumference was significantly higher in the steatohepatitis groups (both with and without fibrosis), each 10 cm increase increasing the risk of steatohepatitis (p = 0.007). The mean values of serum fibrinogen and CRP were significantly higher in patients having the progressive forms of NAFLD. Simple clinical and biological data available to the practitioner in medicine can be used to identify obese patients at high risk of NASH, aiming to direct them to specialized medical centers.

Should all Hypertensive Patients be Screened for Primary Aldosteronism?

2019 ◽  
Vol 15 (1) ◽  
pp. 54-56
Author(s):  
Stelina Alkagiet ◽  
Konstantinos Tziomalos
Keyword(s):  
Resistant Hypertension ◽  
Primary Aldosteronism ◽  
Large Scale ◽  
Controlled Trial ◽  
The Other ◽  
Limited Data ◽  
Hypertensive Patients ◽  
Randomized Controlled ◽  
Increased Risk ◽  
Prospective Randomized Controlled Trial

Primary aldosteronism (PA) is not only a leading cause of secondary and resistant hypertension, but is also quite frequent in unselected hypertensive patients. Moreover, PA is associated with increased cardiovascular risk, which is disproportionate to BP levels. In addition, timely diagnosis of PA and prompt initiation of treatment attenuate this increased risk. On the other hand, there are limited data regarding the usefulness of screening for PA in all asymptomatic or normokalemic hypertensive patients. More importantly, until now, no well-organized, large-scale, prospective, randomized controlled trial has proved the effectiveness of screening for PA for improving clinical outcome. Accordingly, until more relevant data are available, screening for PA should be considered in hypertensive patients with spontaneous or diuretic-induced hypokalemia as well as in those with resistant hypertension. However, screening for PA in all hypertensive patients cannot be currently recommended.

scholarly journals Perceived Health among Adolescent and Young Adult Survivors of Childhood Cancer

2021 ◽  
Vol 28 (1) ◽  
pp. 825-836
Author(s):  
Morgan Young-Speirs ◽  
Caitlin Forbes ◽  
Michaela Patton ◽  
K. Brooke Russell ◽  
Mehak Stokoe ◽  
...  
Keyword(s):  
Childhood Cancer ◽  
Health Resources ◽  
Adult Survivors ◽  
Perceived Health ◽  
Good Health ◽  
Adolescent And Young Adult ◽  
Control Group ◽  
Increased Risk ◽  
Patient Reported ◽  
Survivors Of Childhood Cancer

Survivors of childhood cancer (SCCs) are at increased risk of late effects, which are cancer- and treatment-related side-effects that are experienced months to years post-treatment and encapsulate a range of physical, cognitive and emotional problems including secondary malignancies. Perceived health can serve as an indicator of overall health. This study aims to (1) understand how a patient reported outcome (PRO) of perceived health of SCCs compares to controls who have not had a cancer diagnosis and (2) examine the relationships between perceived health and demographic and clinical variables, and health behavior. A total of 209 SCCs (n = 113 (54.10%) males; median age at diagnosis = 6.50 years; median time off treatment = 11.10 years; mean age at study = 19.00 years) were included. SCCs completed annual assessments as part of Long-Term Survivor Clinic appointments, including a question on perceived health answered on a five-point Likert scale. Data were collected retrospectively from medical charts. Perceived health of SCCs was compared to a control group (n = 836) using data from the 2014 Canadian Community Health Survey. Most SCCs (67%) reported excellent or very good health. The mean perceived health of SCCs (2.15 ± 0.91) was not statistically different from population controls (2.10 ± 0.87). Pain (B = 0.35; p < 0.001), physical activity (B = −0.39; p = 0.013) and concerns related to health resources (B = 0.59; p = 0.002) were significant predictors of perceived health. Factors shown to influence SCCs’ perceived health may inform interventions. Exploration into how SCCs develop their conception of health may be warranted.

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