Multidimensional evaluation of the pain profile as prognostic factor in individuals with hip or knee osteoarthritis receiving total joint replacement:protocol of a 2-year longitudinal prognostic cohort study

INTRODUCTION: Knee and hip osteoarthritis are two highly prevalent musculoskeletal pain conditions. Unsuccessful rates after hip/knee replacement range from 10% to 20%. Subjects with sensitisation manifestations are vulnerable to worse clinical outcomes. Most studies have analysed outcomes up to 1 year after surgery. The aim of this 2-year longitudinal study will be to evaluate sensory-related, psychological and psychophysical pain sensitisation manifestations and a potential epigenetic biomarker as prognostic clinical outcomes for the development of chronic postoperative pain after knee or hip replacement.METHODS AND ANALYSIS: A prospective longitudinal study with a 2-year follow-up period will be conducted. The prognostic variables will include pain, function, related-disability, anxiety, depression, quality of life, sensitisation-associated symptoms, kinesiophobia, neuropathic pain and catastrophising, and expectative of the intervention will be assessed before surgery. We will also evaluate the presence of the Val158Met polymorphism as a possible epigenetic marker. Clinical outcomes including pain, related-disability and self-perceived satisfaction, sensitisation-associated symptoms and neuropathic pain will be assessed 3, 6, 12, 18 and 24 months after surgery. These variables will be used to construct three prediction models: (1) pain and function, (2) sensitisation-associated symptomatology and (3) neuropathic pain features classifying those patients in responders and non-responders. Data from knee or hip osteoarthritis will be analysed separately. Statistical analyses will be conducted with logistic regressions.ETHICS AND DISSEMINATION: The study has been approved by the Ethics Committee of both institutions involved (Hospital Universitario Fundación Alcorcón (HUFA) 19-141 and Universidad Rey Juan Carlos (URJC) 0312201917319). Participants will sign the written informed consent before their inclusion. Study results will be disseminated through peer-reviewed publications and presentations at scientific meetings.</p

Genetic variants associated with fasting glucose and insulin concentrations in an ethnically diverse population: results from the Population Architecture using Genomics and Epidemiology (PAGE) study

Background: Multiple genome-wide association studies (GWAS) within European populations have implicated common genetic variants associated with insulin and glucose concentrations. In contrast, few studies have been conducted within minority groups, which carry the highest burden of impaired glucose homeostasis and type 2 diabetes in the U.S. Methods: As part of the 'Population Architecture using Genomics and Epidemiology (PAGE) Consortium, we investigated the association of up to 10 GWAS-identified single nucleotide polymorphisms (SNPs) in 8 genetic regions with glucose or insulin concentrations in up to 36,579 non-diabetic subjects including 23,323 European Americans (EA) and 7,526 African Americans (AA), 3,140 Hispanics, 1,779 American Indians (AI), and 811 Asians. We estimated the association between each SNP and fasting glucose or log-transformed fasting insulin, followed by meta-analysis to combine results across PAGE sites. Results: Overall, our results show that 9/9 GWAS SNPs are associated with glucose in EA (p = 0.04 to 9 × 10-15), versus 3/9 in AA (p= 0.03 to 6 × 10-5), 3/4 SNPs in Hispanics, 2/4 SNPs in AI, and 1/2 SNPs in Asians. For insulin we observed a significant association with rs780094/GCKR in EA, Hispanics and AI only. Conclusions: Generalization of results across multiple racial/ethnic groups helps confirm the relevance of some of these loci for glucose and insulin metabolism. Lack of association in non-EA groups may be due to insufficient power, or to unique patterns of linkage disequilibrium

Genetic Determinants of Lipid Traits in Diverse Populations from the Population Architecture using Genomics and Epidemiology (PAGE) Study

For the past five years, genome-wide association studies (GWAS) have identified hundreds of common variants associated with human diseases and traits, including high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) levels. Approximately 95 loci associated with lipid levels have been identified primarily among populations of European ancestry. The Population Architecture using Genomics and Epidemiology (PAGE) study was established in 2008 to characterize GWAS–identified variants in diverse population-based studies. We genotyped 49 GWAS–identified SNPs associated with one or more lipid traits in at least two PAGE studies and across six racial/ethnic groups. We performed a meta-analysis testing for SNP associations with fasting HDL-C, LDL-C, and ln(TG) levels in self-identified European American (∼20,000), African American (∼9,000), American Indian (∼6,000), Mexican American/Hispanic (∼2,500), Japanese/East Asian (∼690), and Pacific Islander/Native Hawaiian (∼175) adults, regardless of lipid-lowering medication use. We replicated 55 of 60 (92%) SNP associations tested in European Americans at p<0.05. Despite sufficient power, we were unable to replicate ABCA1 rs4149268 and rs1883025, CETP rs1864163, and TTC39B rs471364 previously associated with HDL-C and MAFB rs6102059 previously associated with LDL-C. Based on significance (p<0.05) and consistent direction of effect, a majority of replicated genotype-phentoype associations for HDL-C, LDL-C, and ln(TG) in European Americans generalized to African Americans (48%, 61%, and 57%), American Indians (45%, 64%, and 77%), and Mexican Americans/Hispanics (57%, 56%, and 86%). Overall, 16 associations generalized across all three populations. For the associations that did not generalize, differences in effect sizes, allele frequencies, and linkage disequilibrium offer clues to the next generation of association studies for these traits

No evidence of interaction between known lipid-associated genetic variants and smoking in the multi-ethnic PAGE population

Genome-wide association studies (GWAS) have identified many variants that influence high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and/or triglycerides. However, environmental modifiers, such as smoking, of these known genotype–phenotype associations are just recently emerging in the literature. We have tested for interactions between smoking and 49 GWAS-identified variants in over 41,000 racially/ethnically diverse samples with lipid levels from the Population Architecture Using Genomics and Epidemiology (PAGE) study. Despite their biological plausibility, we were unable to detect significant SNP × smoking interactions

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Rapid detection of identity-by-descent tracts for mega-scale datasets

Traditional methods to identify genomic regions identical-by-descent (IBD) do not scale well to biobank-level datasets. Here, the authors describe a new IBD algorithm, iLASH, which uses LocAlity-Sensitive Hashing to provide rapid IBD estimation when applied to the PAGE and UK Biobank datasets

Psychometric Properties of the Hospital Anxiety and Depression Scale (HADS) in Previously Hospitalized COVID-19 Patients.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus is associated with psychological/emotional disturbances. This study aimed to assess internal consistency, reliability, and construct validity of the Hospital Anxiety and Depressive Scale (HADS), as a patient-reported outcome measure (PROM) for evaluating emotional consequences of SARS-CoV-2 in hospitalized COVID-19 survivors with long COVID. The LONG-COVID-EXP-CM is a multicenter cohort study including patients hospitalized by COVID-19 during the first wave of the pandemic in five hospitals in Madrid. A total of 1969 (age: 61 ± 16 years, 46.5% women) COVID-19 survivors experiencing post-COVID symptoms a mean of 8.4 ± 1.5 months after hospital discharge completed HADS. Internal consistency (Cronbach α), reliability (item-internal consistency, item-discriminant validity), construct validity (confirmatory factor analysis), and floor effect and ceiling effect were calculated. The mean time for fulfilling HADS was 65 ± 12 s. A ceiling effect ranging from 1.99% to 13.74% and a floor effect ranging from 43.05% to 77.77% was observed. Based on the item-scale correlation coefficients, the Cronbach's alpha values reflecting the internal consistency reliability were 0.890 for the anxiety scale (HADS-A) and 0.856 for the depressive scale (HADS-D) The correlation coefficient between HADS-A and HADS-D scores was excellent (r: 0.878). The confirmatory factor analysis revealed that five out of the seven fitness indexes were excellent: CFI = 0.969, NNFI = 0.963; TLI = 0.963; AGFI = 0.951; GFI = 0.972), supporting good construct validity. In conclusion, this study indicates that both anxiety and depressive symptoms scales of HADS had overall good psychometric properties to be used for assessing psychological and emotional stress in COVID-19 survivors with long COVID

Psychometric Properties of the Hospital Anxiety and Depression Scale (HADS) in Previously Hospitalized COVID-19 Patients

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus is associated with psychological/emotional disturbances. This study aimed to assess internal consistency, reliability, and construct validity of the Hospital Anxiety and Depressive Scale (HADS), as a patient-reported outcome measure (PROM) for evaluating emotional consequences of SARS-CoV-2 in hospitalized COVID-19 survivors with long COVID. The LONG-COVID-EXP-CM is a multicenter cohort study including patients hospitalized by COVID-19 during the first wave of the pandemic in five hospitals in Madrid. A total of 1969 (age: 61 &plusmn; 16 years, 46.5% women) COVID-19 survivors experiencing post-COVID symptoms a mean of 8.4 &plusmn; 1.5 months after hospital discharge completed HADS. Internal consistency (Cronbach &alpha;), reliability (item-internal consistency, item-discriminant validity), construct validity (confirmatory factor analysis), and floor effect and ceiling effect were calculated. The mean time for fulfilling HADS was 65 &plusmn; 12 s. A ceiling effect ranging from 1.99% to 13.74% and a floor effect ranging from 43.05% to 77.77% was observed. Based on the item-scale correlation coefficients, the Cronbach&rsquo;s alpha values reflecting the internal consistency reliability were 0.890 for the anxiety scale (HADS-A) and 0.856 for the depressive scale (HADS-D) The correlation coefficient between HADS-A and HADS-D scores was excellent (r: 0.878). The confirmatory factor analysis revealed that five out of the seven fitness indexes were excellent: CFI = 0.969, NNFI = 0.963; TLI = 0.963; AGFI = 0.951; GFI = 0.972), supporting good construct validity. In conclusion, this study indicates that both anxiety and depressive symptoms scales of HADS had overall good psychometric properties to be used for assessing psychological and emotional stress in COVID-19 survivors with long COVID