Patients' Expectations before and Satisfaction after Ultrasound Guided Foam Sclerotherapy for Varicose Veins

AbstractObjectivesUltrasound guided foam sclerotherapy (UGFS) is a minimally invasive treatment for varicose veins (VV) whose clinical and cost-effectiveness remains incompletely defined. The aim of the current study was to examine patients' expectations before and satisfaction after UGFS for VV in terms of relief of lower limb symptoms, improvement in appearance, and beneficial effect on life-style.MethodsA consecutive series of 351 patients (464 limbs) undergoing UGFS for VV completed questionnaires one week prior to and six months after treatment.ResultsPre and post-treatment response rates were 80%; 60% returned both questionnaires. Virtually all patients were expecting improvement in lower limb symptoms; these were exceeded in a third. Most patients expected cosmetic improvement and these were largely met. Two-thirds of patients expected significant life-style (clothes, work, social) benefits and outcomes were slightly less than expected. A quarter expected improvement in their interpersonal relationships. This benefit was greater than expected occurring in one-third of patients. Overall, a quarter of patients had their expectations exceeded and 10% (appearance and relationships) to 25% (clothing, work and social and leisure activities) were left with unmet expectations.DiscussionWhen specifically asked most patients admit to having a wide range of expectations in relation to their VV treatment, many of them probably unanticipated by the clinician. However, present data indicate that UGFS is usually able to meet, and often exceeds, these physical and psychosocial needs and expectations. UGFS is, therefore, a highly effective treatment for VV from the patients' perspective

Explaining motivation in language learning: a framework for evaluation and research

Researching motivation in language learning is complex and multi-faceted. Various models of learner motivation have been proposed in the literature, but no one model supplies a complex and coherent framework for investigating a range of motivational characteristics. Building on previous models I propose such a methodological framework, based on a complex dynamic systems perspective, which re-conceptualises the investigation of motivation in SLA in qualitative and mixed method approaches by offering one flexible tool for case study approaches. This new framework has been tried and tested in three locations in England and reported as case studies. The study aimed to address the following research questions: (1) in what ways does CLIL impact on learner motivation? (2) what are the main elements of CLIL that enhance motivation? Overall analysis of the results found that where expectations of success were high and where the teaching was effective, CLIL had a positive impact on motivation and progress. The framework is designed to be flexible enough to be used to investigate language learning in a range of national contexts. It is hoped that the proposed framework, reported here together with exemplification and commentary from the English study, will enable researchers in a wide range of language learning contexts to investigate learner motivation in a systematic and in-depth manner

Comprehensive analysis of epigenetic clocks reveals associations between disproportionate biological ageing and hippocampal volume

The concept of age acceleration, the difference between biological age and chronological age, is of growing interest, particularly with respect to age-related disorders, such as Alzheimer’s Disease (AD). Whilst studies have reported associations with AD risk and related phenotypes, there remains a lack of consensus on these associations. Here we aimed to comprehensively investigate the relationship between five recognised measures of age acceleration, based on DNA methylation patterns (DNAm age), and cross-sectional and longitudinal cognition and AD-related neuroimaging phenotypes (volumetric MRI and Amyloid-β PET) in the Australian Imaging, Biomarkers and Lifestyle (AIBL) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Significant associations were observed between age acceleration using the Hannum epigenetic clock and cross-sectional hippocampal volume in AIBL and replicated in ADNI. In AIBL, several other findings were observed cross-sectionally, including a significant association between hippocampal volume and the Hannum and Phenoage epigenetic clocks. Further, significant associations were also observed between hippocampal volume and the Zhang and Phenoage epigenetic clocks within Amyloid-β positive individuals. However, these were not validated within the ADNI cohort. No associations between age acceleration and other Alzheimer’s disease-related phenotypes, including measures of cognition or brain Amyloid-β burden, were observed, and there was no association with longitudinal change in any phenotype. This study presents a link between age acceleration, as determined using DNA methylation, and hippocampal volume that was statistically significant across two highly characterised cohorts. The results presented in this study contribute to a growing literature that supports the role of epigenetic modifications in ageing and AD-related phenotypes

Global surveillance of cancer survival 1995-2009: analysis of individual data for 25,676,887 patients from 279 population-based registries in 67 countries (CONCORD-2)

BACKGROUND: Worldwide data for cancer survival are scarce. We aimed to initiate worldwide surveillance of cancer survival by central analysis of population-based registry data, as a metric of the effectiveness of health systems, and to inform global policy on cancer control. METHODS: Individual tumour records were submitted by 279 population-based cancer registries in 67 countries for 25·7 million adults (age 15-99 years) and 75,000 children (age 0-14 years) diagnosed with cancer during 1995-2009 and followed up to Dec 31, 2009, or later. We looked at cancers of the stomach, colon, rectum, liver, lung, breast (women), cervix, ovary, and prostate in adults, and adult and childhood leukaemia. Standardised quality control procedures were applied; errors were corrected by the registry concerned. We estimated 5-year net survival, adjusted for background mortality in every country or region by age (single year), sex, and calendar year, and by race or ethnic origin in some countries. Estimates were age-standardised with the International Cancer Survival Standard weights. FINDINGS: 5-year survival from colon, rectal, and breast cancers has increased steadily in most developed countries. For patients diagnosed during 2005-09, survival for colon and rectal cancer reached 60% or more in 22 countries around the world; for breast cancer, 5-year survival rose to 85% or higher in 17 countries worldwide. Liver and lung cancer remain lethal in all nations: for both cancers, 5-year survival is below 20% everywhere in Europe, in the range 15-19% in North America, and as low as 7-9% in Mongolia and Thailand. Striking rises in 5-year survival from prostate cancer have occurred in many countries: survival rose by 10-20% between 1995-99 and 2005-09 in 22 countries in South America, Asia, and Europe, but survival still varies widely around the world, from less than 60% in Bulgaria and Thailand to 95% or more in Brazil, Puerto Rico, and the USA. For cervical cancer, national estimates of 5-year survival range from less than 50% to more than 70%; regional variations are much wider, and improvements between 1995-99 and 2005-09 have generally been slight. For women diagnosed with ovarian cancer in 2005-09, 5-year survival was 40% or higher only in Ecuador, the USA, and 17 countries in Asia and Europe. 5-year survival for stomach cancer in 2005-09 was high (54-58%) in Japan and South Korea, compared with less than 40% in other countries. By contrast, 5-year survival from adult leukaemia in Japan and South Korea (18-23%) is lower than in most other countries. 5-year survival from childhood acute lymphoblastic leukaemia is less than 60% in several countries, but as high as 90% in Canada and four European countries, which suggests major deficiencies in the management of a largely curable disease. INTERPRETATION: International comparison of survival trends reveals very wide differences that are likely to be attributable to differences in access to early diagnosis and optimum treatment. Continuous worldwide surveillance of cancer survival should become an indispensable source of information for cancer patients and researchers and a stimulus for politicians to improve health policy and health-care systems

Polygenic transcriptome risk scores for COPD and lung function improve cross-ethnic portability of prediction in the NHLBI TOPMed program

While polygenic risk scores (PRSs) enable early identification of genetic risk for chronic obstructive pulmonary disease (COPD), predictive performance is limited when the discovery and target populations are not well matched. Hypothesizing that the biological mechanisms of disease are shared across ancestry groups, we introduce a PrediXcan-derived polygenic transcriptome risk score (PTRS) to improve cross-ethnic portability of risk prediction. We constructed the PTRS using summary statistics from application of PrediXcan on large-scale GWASs of lung function (forced expiratory volume in 1 s [FEV1] and its ratio to forced vital capacity [FEV1/FVC]) in the UK Biobank. We examined prediction performance and cross-ethnic portability of PTRS through smoking-stratified analyses both on 29,381 multi-ethnic participants from TOPMed population/family-based cohorts and on 11,771 multi-ethnic participants from TOPMed COPD-enriched studies. Analyses were carried out for two dichotomous COPD traits (moderate-to-severe and severe COPD) and two quantitative lung function traits (FEV1 and FEV1/FVC). While the proposed PTRS showed weaker associations with disease than PRS for European ancestry, the PTRS showed stronger association with COPD than PRS for African Americans (e.g., odds ratio [OR] = 1.24 [95% confidence interval [CI]: 1.08–1.43] for PTRS versus 1.10 [0.96–1.26] for PRS among heavy smokers with ≥ 40 pack-years of smoking) for moderate-to-severe COPD. Cross-ethnic portability of the PTRS was significantly higher than the PRS (paired t test p < 2.2 × 10−16 with portability gains ranging from 5% to 28%) for both dichotomous COPD traits and across all smoking strata. Our study demonstrates the value of PTRS for improved cross-ethnic portability compared to PRS in predicting COPD risk

Whole genome sequence analysis of pulmonary function and COPD in 19,996 multi-ethnic participants

Chronic obstructive pulmonary disease (COPD), diagnosed by reduced lung function, is a leading cause of morbidity and mortality. We performed whole genome sequence (WGS) analysis of lung function and COPD in a multi-ethnic sample of 11,497 participants from population- and family-based studies, and 8499 individuals from COPD-enriched studies in the NHLBI Trans-Omics for Precision Medicine (TOPMed) Program. We identify at genome-wide significance 10 known GWAS loci and 22 distinct, previously unreported loci, including two common variant signals from stratified analysis of African Americans. Four novel common variants within the regions of PIAS1, RGN (two variants) and FTO show evidence of replication in the UK Biobank (European ancestry n ~ 320,000), while colocalization analyses leveraging multi-omic data from GTEx and TOPMed identify potential molecular mechanisms underlying four of the 22 novel loci. Our study demonstrates the value of performing WGS analyses and multi-omic follow-up in cohorts of diverse ancestry

Editorial Statement About JCCAP’s 2023 Special Issue on Informant Discrepancies in Youth Mental Health Assessments: Observations, Guidelines, and Future Directions Grounded in 60 Years of Research

Issue 1 of the 2011 Volume of the Journal of Clinical Child and Adolescent Psychology (JCCAP) included a Special Section about the use of multi-informant approaches to measure child and adolescent (i.e., hereafter referred to collectively as “youth”) mental health (De Los Reyes, 2011). Researchers collect reports from multiple informants or sources (e.g., parent and peer, youth and teacher) to estimate a given youth’s mental health. The 2011 JCCAP Special Section focused on the most common outcome of these approaches, namely the significant discrepancies that arise when comparing estimates from any two informant’s reports (i.e., informant discrepancies). These discrepancies appear in assessments conducted across the lifespan (Achenbach, 2020). That said, JCCAP dedicated space to understanding informant discrepancies, because they have been a focus of scholarship in youth mental health for over 60 years (e.g., Achenbach et al., 1987; De Los Reyes & Kazdin, 2005; Glennon & Weisz, 1978; Kazdin et al., 1983; Kraemer et al., 2003; Lapouse & Monk, 1958; Quay et al., 1966; Richters, 1992; Rutter et al., 1970; van der Ende et al., 2012). Thus, we have a thorough understanding of the areas of research for which they reliably appear when clinically assessing youth. For instance, intervention researchers observe informant discrepancies in estimates of intervention effects within randomized controlled trials (e.g., Casey & Berman, 1985; Weisz et al., 2017). Service providers observe informant discrepancies when working with individual clients, most notably when making decisions about treatment planning (e.g., Hawley & Weisz, 2003; Hoffman & Chu, 2015). Scholars in developmental psychopathology observe these discrepancies when seeking to understand risk and protective factors linked to youth mental health concerns (e.g., Hawker & Boulton, 2000; Hou et al., 2020; Ivanova et al., 2022). Thus, the 2011 JCCAP Special Section posed a question: Might these informant discrepancies contain data relevant to understanding youth mental health? Suppose none of the work in youth mental health is immune from these discrepancies. In that case, the answer to this question strikes at the core of what we produce―from the interventions we develop and implement, to the developmental psychopathology research that informs intervention development

Rare genetic variants explain missing heritability in smoking

Common genetic variants explain less variation in complex phenotypes than inferred from family-based studies, and there is a debate on the source of this ‘missing heritability’. We investigated the contribution of rare genetic variants to tobacco use with whole-genome sequences from up to 26,257 unrelated individuals of European ancestries and 11,743 individuals of African ancestries. Across four smoking traits, single-nucleotide-polymorphism-based heritability (hSNP2) was estimated from 0.13 to 0.28 (s.e., 0.10–0.13) in European ancestries, with 35–74% of it attributable to rare variants with minor allele frequencies between 0.01% and 1%. These heritability estimates are 1.5–4 times higher than past estimates based on common variants alone and accounted for 60% to 100% of our pedigree-based estimates of narrow-sense heritability (hped2, 0.18–0.34). In the African ancestry samples, hSNP2 was estimated from 0.03 to 0.33 (s.e., 0.09–0.14) across the four smoking traits. These results suggest that rare variants are important contributors to the heritability of smoking