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Purpose This study investigated the impact of body mass index (BMI) on improvement in patient outcomes (pain, function, joint awareness, general health and satisfaction) following total knee arthroplasty (TKA). Methods Data were obtained for primary TKAs performed at a single centre over a 12-month period. Data were collected pre-operatively and 12-month postoperatively with the Oxford Knee Score (OKS) measuring pain and function, the EQ-5D-3L measuring general health status, the Forgotten Joint Score-12 (FJS-12) measuring joint awareness and a single question on treatment satisfaction. Change in scores following surgery was compared across the BMI categories identified by the World Health Organization (< 25.0, 25.0–29.9, 30.0–34.9, 35.0–39.9 and ≥ 40.0). Differences in postoperative improvement between the BMI groups were analysed with an overall Kruskal–Wallis test, with post hoc pairwise comparisons between BMI groups with Mann–Whitney tests. Results Of 402 patients [mean age 70.7 (SD 9.2); 55.2% women] 15.7% were normal weight (BMI < 25.0), 33.1% were overweight (BMI 25.0–29.9), 28.2% had class I obesity (BMI 30.0–34.9), 16.2% had class II obesity (BMI 35.0–39.9), and 7.0% had class III obesity (BMI ≥ 40.0). Postoperative change in OKS (n.s.) and EQ-5D-3L (n.s.) was not associated with BMI. Higher BMI group was associated with less improvement in FJS-12 scores ( p  = 0.010), reflecting a greater awareness of the operated joint during activity in the most obese patients. Treatment satisfaction was associated with BMI category ( p  = 0.029), with obese patients reporting less satisfaction. Conclusions In TKA patients, outcome parameters are influenced differently by BMI. Our study showed a negative impact of BMI on postoperative improvement in joint awareness and satisfaction scores, but there was no influence on pain, function or general health scores. This information may be useful in terms of setting expectations expectation in obese patients planning to undergo TKA. Level of evidence Level 1.

Background Joint awareness was recently introduced as a new concept for outcome assessment after total knee arthroplasty (TKA). Findings from qualitative and psychometric studies suggest that joint awareness is a distinct concept especially relevant to patients with good surgical outcome and patients at late follow-up time points. The aim of this study was to improve the understanding of the concept of joint awareness by identifying situations in which patients are aware of their artificial knee joint and to investigate what bodily sensations and psychological factors raise a patient’s awareness of her/his knee. In addition, we evaluated the relative importance of patient-reported outcome parameters that are commonly assessed in orthopaedics. Methods Qualitative interviews were conducted with patients being at least 12 months after TKA. The interviews focused on when, where and for what reasons patients were aware of their artificial knee joint. To evaluate the relative importance of ‘joint awareness’ after TKA among nine commonly assessed outcome parameters (e.g. pain or stiffness), we collected importance ratings (‘0’ indicating no importance at all and ‘10’ indicating high importance). Results We conducted interviews with 40 TKA patients (mean age 69.0 years; 65.0% female). Joint awareness was found to be frequently triggered by kneeling on the floor (30%), climbing stairs (25%), and starting up after resting (25%). Patients reported joint awareness to be related to activities of daily living (68%), specific movements (60%), or meteoropathy (18%). Sensations causing joint awareness included pain (45%) or stiffness (15%). Psychological factors raising a patient’s awareness of his/her knee comprised for example feelings of insecurity (15%), and fears related to revision surgeries, inflammations or recurring pain (8%). Patients’ importance ratings of outcome parameters were generally high and did not allow differentiating clearly among them. Conclusions We have identified a wide range of situations, activities, movements and psychological factors contributing to patients’ awareness of their artificial knee joints. This improves the understanding of the concept of joint awareness and of a patient’s perception of his/her artificial knee joint. The diversity of sensations and factors raising patient’s awareness of their joint encourages taking a broader perspective on outcome after TKA.

IntroductionSingle-item questions assessing patient satisfaction following total hip or knee arthroplasty (THA/TKA) provide immediate and comprehensible information. However, they have limited reliability as satisfaction as a concept is influenced by factors unrelated to surgery. The aim of this retrospective study was to evaluate variation in pain, function and joint awareness relative to the patients’ satisfaction response following THA/TKA.MethodsWe analysed absolute and improvement scores on the Oxford Knee or Hip score (OKS or OHS) and the Forgotten Joint Score-12 (FJS-12) across satisfaction groups. Patient-reported outcome measures were assessed prior to surgery and at 12-month follow-up. Postoperative satisfaction was assessed using a 5-point Likert scale single-item question.ResultsWe analysed data from 434 TKA patients (mean age 70.4 ± 9.2 years; 54.8% female) and 247 THA patients (mean age 67.3 ± 11.8 years; 57.5% female). Satisfied or very satisfied patients showed higher absolute scores and better improvement in function, pain and joint awareness at 12 months (both, p < 0.001). 13.4% of (very) satisfied THA patients scored equally or worse on the FJS-12 than before surgery. On the OHS, this percentage was 2.8%. In TKAs, these percentages were 7.0% on the FJS-12 and 3.2% on the OKS.ConclusionsWhile higher satisfaction is associated with better patient-reported outcomes and stronger postoperative improvement, a certain percentage of patients score poorly while reporting a high satisfaction. Our results highlight the difficulty in interpreting the meaning of a single satisfaction question, as this provides limited information on patients’ treatment outcome and may be biased by factors unrelated to the intervention.

The development of the comprehension of relational terms \"more,\" \"less,\" and \"same\" were investigated for a broad range of concept areas commonly used in conservation and seriation research: number, weight, proportion, volume, length, area, distance, and substance. Ss were 192 Dutch children from kindergarten divided into three age levels; mean ages, respectively, 54, 62, and 72 months. The results showed ceiling effects in all concept areas except volume for age levels 2 and 3. The asymmetry phenomenon (i.e., \"more\" is easier than \"less\") was not evident in kindergarten age level 1. No clear sequence of mastering was observed for either the terms \"more\" and \"same\" or the terms \"less\" and \"same\" in the majority of the concept areas. Analysis of the incorrect responses did not reveal the synonymity phenomenon (i.e., \"less\" was interpreted as \"more\"). However, another synonymity phenomenon was observed: \"more\" and \"less\" were interpreted as \"same,\" and \"same\" was interpreted as \"more.\" This is a noteworthy finding because it cannot be attributed only to guessing since multiple-choice tasks were used.

An increasing number of large-scale multi-modal research initiatives has been conducted in the typically developing population, e.g. Dev. Cogn. Neur. 32:43-54, 2018; PLoS Med. 12(3):e1001779, 2015; Elam and Van Essen, Enc. Comp. Neur., 2013, as well as in psychiatric cohorts, e.g. Trans. Psych. 10(1):100, 2020; Mol. Psych. 19:659–667, 2014; Mol. Aut. 8:24, 2017; Eur. Child and Adol. Psych. 24(3):265–281, 2015. Missing data is a common problem in such datasets due to the difficulty of assessing multiple measures on a large number of participants. The consequences of missing data accumulate when researchers aim to integrate relationships across multiple measures. Here we aim to evaluate different imputation strategies to fill in missing values in clinical data from a large (total N  = 764) and deeply phenotyped (i.e. range of clinical and cognitive instruments administered) sample of N  = 453 autistic individuals and N  = 311 control individuals recruited as part of the EU-AIMS Longitudinal European Autism Project (LEAP) consortium. In particular, we consider a total of 160 clinical measures divided in 15 overlapping subsets of participants. We use two simple but common univariate strategies—mean and median imputation—as well as a Round Robin regression approach involving four independent multivariate regression models including Bayesian Ridge regression, as well as several non-linear models: Decision Trees (Extra Trees., and Nearest Neighbours regression. We evaluate the models using the traditional mean square error towards removed available data, and also consider the Kullback–Leibler divergence between the observed and the imputed distributions. We show that all of the multivariate approaches tested provide a substantial improvement compared to typical univariate approaches. Further, our analyses reveal that across all 15 data-subsets tested, an Extra Trees regression approach provided the best global results. This not only allows the selection of a unique model to impute missing data for the LEAP project and delivers a fixed set of imputed clinical data to be used by researchers working with the LEAP dataset in the future, but provides more general guidelines for data imputation in large scale epidemiological studies.

Abstract Rationale Chronic obstructive pulmonary disease (COPD) is a common, complex multisystem disease in the elderly with multiple comorbidities that significantly impact morbidity and mortality. Although cerebral small-vessel disease is an important cause of cognitive decline and age-related disability, it is a poorly investigated potential systemic manifestation of patients with COPD. Objectives To examine whether COPD relates to the development and location of cerebral microbleeds, a novel marker of cerebral small-vessel disease. Methods Cross-sectional and longitudinal analyses were part of the Rotterdam Study, a prospective population-based cohort study in subjects aged greater than or equal to 55 years. Diagnosis of COPD was confirmed by spirometry. Cerebral microbleeds were detected using high-resolution magnetic resonance imaging (MRI). Measurements and Main Results Subjects with COPD (n = 165) had a higher prevalence of cerebral microbleeds compared with subjects with normal lung function (n = 645) independent of age, sex, smoking status, atherosclerotic macroangiopathy, antithrombotic use, total cholesterol, triglycerides, and serum creatinin (odds ratio [OR], 1.7; 95% confidence interval [CI], 1.15–2.47; P = 0.007). Regarding the specific microbleed location, subjects with COPD had a significantly higher prevalence of microbleeds in deep or infratentorial locations (OR, 3.3; 95% CI, 1.97–5.53; P < 0.001), which increased with severity of airflow limitation and are suggestive of hypertensive or arteriolosclerotic microangiopathy. Furthermore, in longitudinal analysis restricted to subjects without microbleed at baseline, COPD was an independent predictor of incident cerebral microbleeds in deep or infratentorial locations (OR, 7.1; 95% CI, 2.1–24.5; P = 0.002). Conclusions Our findings are compatible with COPD causing an increased risk of the development of cerebral microbleeds in deep or infratentorial locations.

Neurodevelopmental disorders such as fragile X syndrome (FXS) result in lifelong cognitive and behavioural deficits and represent a major public health burden. FXS is the most frequent monogenic form of intellectual disability and autism, and the underlying pathophysiology linked to its causal gene, FMR1, has been the focus of intense research. Key alterations in synaptic function thought to underlie this neurodevelopmental disorder have been characterized and rescued in animal models of FXS using genetic and pharmacological approaches. These robust preclinical findings have led to the implementation of the most comprehensive drug development programme undertaken thus far for a genetically defined neurodevelopmental disorder, including phase IIb trials of metabotropic glutamate receptor 5 (mGluR5) antagonists and a phase III trial of a GABAB receptor agonist. However, none of the trials has been able to unambiguously demonstrate efficacy, and they have also highlighted the extent of the knowledge gaps in drug development for FXS and other neurodevelopmental disorders. In this Review, we examine potential issues in the previous studies and future directions for preclinical and clinical trials. FXS is at the forefront of efforts to develop drugs for neurodevelopmental disorders, and lessons learned in the process will also be important for such disorders.

Qualitative EEG abnormalities are common in Autism Spectrum Disorder (ASD) and hypothesized to reflect disrupted excitation/inhibition (E/I) balance. To test this, we recently introduced a functional measure of network-level E/I ratio (fE/I). Here, we applied fE/I and other EEG measures to alpha oscillations from source-reconstructed data in the EU-AIMS dataset (267 ASD, 209 controls). We analyzed these measures alongside qualitative EEG abnormalities ranging from slowing of activity to epileptiform patterns, aiming to replicate the findings from the SPACE-BAMBI study. Contrary to our previous report, we did not observe increased fE/I variability in ASD compared to controls. EEG abnormalities were rare in adults and could not be statistically assessed. ASD children-adolescents with EEG abnormalities exhibited lower relative alpha power and fE/I compared to those without. However, EEG-abnormality scoring did not stratify the behavioral heterogeneity of ASD using clinical measures. Surprisingly, several controls also exhibited qualitative EEG abnormalities with a strikingly similar anatomical distribution of reduced fE/I, reflecting inhibition-dominated network dynamics in sensory processing regions. The robustness of this association between EEG abnormalities and reduced fE/I was further supported by re-analysis of the SPACE-BAMBI study in source space. Stratification by the presence of EEG abnormalities and their effects on network activity may help understand neurodevelopmental physiological heterogeneity and the difficulties in implementing E/I targeting treatments in unselected cohorts.