We introduce two novel methods for multivariate genome-wide-association meta-analysis (GWAMA) of related traits that correct for sample overlap. A broad range of simulation scenarios supports the added value of our multivariate methods relative to univariate GWAMA. We applied the novel methods to life satisfaction, positive affect, neuroticism, and depressive symptoms, collectively referred to as the well-being spectrum (Nobs = 2,370,390), and found 304 significant independent signals. Our multivariate approaches resulted in a 26% increase in the number of independent signals relative to the four univariate GWAMAs and in an ~57% increase in the predictive power of polygenic risk scores. Supporting transcriptome- and methylome-wide analyses (TWAS and MWAS, respectively) uncovered an additional 17 and 75 independent loci, respectively. Bioinformatic analyses, based on gene expression in brain tissues and cells, showed that genes differentially expressed in the subiculum and GABAergic interneurons are enriched in their effect on the well-being spectrum.
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Objective The evaluation of voice quality is a major component of voice assessment. The aim of the present study was to develop a new multivariate acoustic model for the evaluation of breathiness. Method Concatenated voice samples of continuous speech and the sustained vowel [a:] from 970 subjects with dysphonia and 88 vocally healthy subjects were perceptually judged for breathiness severity. Acoustic analyses were conducted on the same concatenated voice samples after removal of the non-voiced segments of the continuous speech sample. The development of an acoustic model for breathiness was based on stepwise multiple linear regression analysis. Concurrent validity, diagnostic accuracy, and cross validation were statistically verified on the basis of the Spearman rank-order correlation coefficient (rs), several estimates of the receiver operating characteristics plus the likelihood ratio, and iterated internal cross correlations. Results Ratings of breathiness from four experts with moderate reliability were used. Stepwise multiple regression analysis yielded a nine-variable acoustic model for the multiparametric measurement of breathiness (Acoustic Breathiness Index [ABI]). A strong correlation was found between ABI and auditory-perceptual rating (rs = 0.840, P = 0.000). The cross correlations confirmed a comparably high degree of association. Additionally, the receiver operating characteristics and likelihood ratio results showed the best diagnostic outcome at a threshold of ABI = 3.44 with a sensitivity of 82.4% and a specificity of 92.9%. Conclusions This study developed a new acoustic multivariate correlate for the evaluation of breathiness in voice. The ABI model showed valid and robust results and is therefore proposed as a new acoustic index for the evaluation of breathiness.
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Objective: To predict mortality by disability in a sample of 479 Dutch community-dwelling people aged 75 years or older. Methods: A longitudinal study was carried out using a follow-up of seven years. The Groningen Activity Restriction Scale (GARS), a self-reported questionnaire with good psychometric properties, was used for data collection about total disability, disability in activities in daily living (ADL) and disability in instrumental activities in daily living (IADL). The mortality dates were provided by the municipality of Roosendaal (a city in the Netherlands). For analyses of survival, we used Kaplan–Meier analyses and Cox regression analyses to calculate hazard ratios (HR) with 95% confidence intervals (CI). Results: All three disability variables (total, ADL and IADL) predicted mortality, unadjusted and adjusted for age and gender. The unadjusted HRs for total, ADL and IADL disability were 1.054 (95%-CI: [1.039;1.069]), 1.091 (95%-CI: [1.062;1.121]) and 1.106 (95%-CI: [1.077;1.135]) with p-values <0.001, respectively. The AUCs were <0.7, ranging from 0.630 (ADL) to 0.668 (IADL). Multivariate analyses including all 18 disability items revealed that only “Do the shopping” predicted mortality. In addition, multivariate analyses focusing on 11 ADL items and 7 IADL items separately showed that only the ADL item “Get around in the house” and the IADL item “Do the shopping” significantly predicted mortality. Conclusion: Disability predicted mortality in a seven years follow-up among Dutch community-dwelling older people. It is important that healthcare professionals are aware of disability at early stages, so they can intervene swiftly, efficiently and effectively, to maintain or enhance the quality of life of older people.
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A previous study found a variety of unusual sexual interests to cluster in a five-factor structure, namely submission/masochism, forbidden sexual activities, dominance / sadism, mysophilia, and fetishism (Schippers et al., 2021). The current study was an empirical replication to examine whether these findings generalized to a representative population sample. An online, anonymous sample (N = 256) representative of the Dutch adult male population rated 32 unusual sexual interests on a scale from 1 (very unappealing) to 7 (very appealing). An exploratory factor analysis assessed whether similar factors would emerge as in the original study. A subsequent confirmatory factor analysis served to confirm the factor structure. Four slightly different factors of sexual interest were found: extreme, illegal and mysophilic sexual activities; light BDSM without real pain or suffering; heavy BDSM that may include pain or suffering; and illegal but lower-sentenced and fetishistic sexual activities. The model fit was acceptable. The representative replication sample was more sexually conservative and showed less sexual engagement than the original convenience sample. On a fundamental level, sexual interest in light BDSM activities and extreme, forbidden, and mysophilic activities seem to be relatively separate constructs.
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Rationale: Patients with cancer of the upper gastrointestinal tract or lung are more likely to present with malnutrition at diagnosis than, for instance, patients with melanoma. Low muscle mass is an indicator of malnutrition and can be determined by computed tomography (CT) analysis of the skeletal muscle index (SMI) at the 3rd lumbar vertebra (L3) level. However, CT images at L3 are not always available. At each vertebra level, we determined if type of cancer, i.e., head and neck cancer (HNC), oesophageal cancer (OC) or lung cancer (LC) vs. melanoma (ME) was associated with lower SMI. Methods: CT images from adult patients with HNC, OC, LC or ME were included and analyzed. Scans were performed in the patient’s initial staging after diagnosis. MIM software version 7.0.1 was used to contour the muscle areas for all vertebra levels. Skeletal muscle area was corrected for stature to calculate SMI (cm2/m2). We tested for the association of HNC, OC, or LC diagnosis vs ME with SMI by univariate and multivariate linear regression analyses. In the multivariate analyses, age (years), sex, and body mass index (BMI; kg/m2) were included. Betas (B;95%CI) were calculated and statistical significance was set at p
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The aim of this study was to understand the motives for using the Internet, and its associations with users' attitudes, social values, and relational involvement. Also, this study attempted to crossculturally compare the difference in the pattern of motives and the associations among three countries ' the US, the Netherlands, and S. Korea. The design of methods was based on examination and revision of uses and gratification approach toward Internet users. Findings from factor analysis revealed that information seeking and Self-Improvement were the dominant and common reasons for using the Internet across three countries. The differences in the composition of motives in each country were also reported. Strong correlations across countries were found between all the motives and satisfaction of the Internet. Expectation and positive evaluation of the Internet were also important attitudes associated with Internet use motives. Postmaterialist value showed strong association with motives of information seeking and Self-Improvement. Community involvement was significantly associated with Internet use motives in Korean users.
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Abstract Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), has challenged healthcare globally. An acute increase in the number of hospitalized patients has neces‑ sitated a rigorous reorganization of hospital care, thereby creating circumstances that previously have been identifed as facilitating prescribing errors (PEs), e.g. a demanding work environment, a high turnover of doctors, and prescrib‑ ing beyond expertise. Hospitalized COVID-19 patients may be at risk of PEs, potentially resulting in patient harm. We determined the prevalence, severity, and risk factors for PEs in post–COVID-19 patients, hospitalized during the frst wave of COVID-19 in the Netherlands, 3months after discharge. Methods: This prospective observational cohort study recruited patients who visited a post-COVID-19 outpatient clinic of an academic hospital in the Netherlands, 3months after COVID-19 hospitalization, between June 1 and October 1 2020. All patients with appointments were eligible for inclusion. The prevalence and severity of PEs were assessed in a multidisciplinary consensus meeting. Odds ratios (ORs) were calculated by univariate and multivariate analysis to identify independent risk factors for PEs. Results: Ninety-eight patients were included, of whom 92% had ≥1 PE and 8% experienced medication-related harm requiring an immediate change in medication therapy to prevent detoriation. Overall, 68% of all identifed PEs were made during or after the COVID-19 related hospitalization. Multivariate analyses identifed ICU admission (OR 6.08, 95% CI 2.16–17.09) and a medical history of COPD / asthma (OR 5.36, 95% CI 1.34–21.5) as independent risk fac‑ tors for PEs. Conclusions: PEs occurred frequently during the SARS-CoV-2 pandemic. Patients admitted to an ICU during COVID19 hospitalization or who had a medical history of COPD / asthma were at risk of PEs. These risk factors can be used to identify high-risk patients and to implement targeted interventions. Awareness of prescribing safely is crucial to prevent harm in this new patient population.
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Abstract The aim of this cross-sectional study was to develop a Frailty at Risk Scale (FARS) incorporating ten well-known determinants of frailty: age, sex, marital status, ethnicity, education, income, lifestyle, multimorbidity, life events, and home living environment. In addition, a second aim was to develop an online calculator that can easily support healthcare professionals in determining the risk of frailty among community-dwelling older people. The FARS was developed using data of 373 people aged ≥ 75 years. The Tilburg Frailty Indicator (TFI) was used for assessing frailty. Multivariate logistic regression analysis showed that the determinants multimorbidity, unhealthy lifestyle, and ethnicity (ethnic minority) were the most important predictors. The area under the curve (AUC) of the model was 0.811 (optimism 0.019, 95% bootstrap CI = −0.029; 0.064). The FARS is offered on a Web site, so that it can be easily used by healthcare professionals, allowing quick intervention in promoting quality of life among community-dwelling older people.
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BACKGROUND: In critically ill patients, muscle loss is associated with adverse outcomes. Raw bioelectrical impedance analysis (BIA) parameters (eg, phase angle [PA] and impedance ratio [IR]) have received attention as potential markers of muscularity, nutrition status, and clinical outcomes. Our objective was to test whether PA and IR could be used to assess low muscularity and predict clinical outcomes.METHODS: Patients (≥18 years) having an abdominal computed tomography (CT) scan and admitted to intensive care underwent multifrequency BIA within 72 hours of scan. CT scans were landmarked at the third lumbar vertebra and analyzed for skeletal muscle cross-sectional area (CSA). CSA ≤170 cm(2) for males and ≤110 cm(2) for females defined low muscularity. The relationship between PA (and IR) and CT muscle CSA was evaluated using multivariate regression and included adjustments for age, sex, body mass index, Charlson Comorbidity Index, and admission type. PA and IR were also evaluated for predicting discharge status using dual-energy X-ray absorptiometry-derived cut-points for low fat-free mass index.RESULTS: Of 171 potentially eligible patients, 71 had BIA and CT scans within 72 hours. Area under the receiver operating characteristic (c-index) curve to predict CT-defined low muscularity was 0.67 (P ≤ .05) for both PA and IR. With covariates added to logistic regression models, PA and IR c-indexes were 0.78 and 0.76 (P < .05), respectively. Low PA and high IR predicted time to live ICU discharge.CONCLUSION: Our study highlights the potential utility of PA and IR as markers to identify patients with low muscularity who may benefit from early and rigorous intervention.
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Objective: To predict mortality by disability in a sample of 479 Dutch community-dwelling people aged 75 years or older. Methods: A longitudinal study was carried out using a follow-up of seven years. The Groningen Activity Restriction Scale (GARS), a self-reported questionnaire with good psychometric properties, was used for data collection about total disability, disability in activities in daily living (ADL) and disability in instrumental activities in daily living (IADL). The mortality dates were provided by the municipality of Roosendaal (a city in the Netherlands). For analyses of survival, we used Kaplan–Meier analyses and Cox regression analyses to calculate hazard ratios (HR) with 95% confidence intervals (CI). Results: All three disability variables (total, ADL and IADL) predicted mortality, unadjusted and adjusted for age and gender. The unadjusted HRs for total, ADL and IADL disability were 1.054 (95%-CI: [1.039;1.069]), 1.091 (95%-CI: [1.062;1.121]) and 1.106 (95%-CI: [1.077;1.135]) with p-values <0.001, respectively. The AUCs were <0.7, ranging from 0.630 (ADL) to 0.668 (IADL). Multivariate analyses including all 18 disability items revealed that only “Do the shopping” predicted mortality. In addition, multivariate analyses focusing on 11 ADL items and 7 IADL items separately showed that only the ADL item “Get around in the house” and the IADL item “Do the shopping” significantly predicted mortality. Conclusion: Disability predicted mortality in a seven years follow-up among Dutch community-dwelling older people. It is important that healthcare professionals are aware of disability at early stages, so they can intervene swiftly, efficiently and effectively, to maintain or enhance the quality of life of older people.
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