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Showing papers by "Public Health Research Institute published in 2019"


Journal ArticleDOI
TL;DR: An emphasis is placed on low muscle strength as a key characteristic of sarcopenia, uses detection of low muscle quantity and quality to confirm the sarc Openia diagnosis, and provides clear cut-off points for measurements of variables that identify and characterise sarc openia.
Abstract: Background in 2010, the European Working Group on Sarcopenia in Older People (EWGSOP) published a sarcopenia definition that aimed to foster advances in identifying and caring for people with sarcopenia. In early 2018, the Working Group met again (EWGSOP2) to update the original definition in order to reflect scientific and clinical evidence that has built over the last decade. This paper presents our updated findings. Objectives to increase consistency of research design, clinical diagnoses and ultimately, care for people with sarcopenia. Recommendations sarcopenia is a muscle disease (muscle failure) rooted in adverse muscle changes that accrue across a lifetime; sarcopenia is common among adults of older age but can also occur earlier in life. In this updated consensus paper on sarcopenia, EWGSOP2: (1) focuses on low muscle strength as a key characteristic of sarcopenia, uses detection of low muscle quantity and quality to confirm the sarcopenia diagnosis, and identifies poor physical performance as indicative of severe sarcopenia; (2) updates the clinical algorithm that can be used for sarcopenia case-finding, diagnosis and confirmation, and severity determination and (3) provides clear cut-off points for measurements of variables that identify and characterise sarcopenia. Conclusions EWGSOP2's updated recommendations aim to increase awareness of sarcopenia and its risk. With these new recommendations, EWGSOP2 calls for healthcare professionals who treat patients at risk for sarcopenia to take actions that will promote early detection and treatment. We also encourage more research in the field of sarcopenia in order to prevent or delay adverse health outcomes that incur a heavy burden for patients and healthcare systems.

6,250 citations


Journal ArticleDOI
TL;DR: Efforts are required to avoid poor calibration when developing prediction models, to evaluate calibration when validating models, and to update models when indicated to optimize the utility of predictive analytics for shared decision-making and patient counseling.
Abstract: The assessment of calibration performance of risk prediction models based on regression or more flexible machine learning algorithms receives little attention. Herein, we argue that this needs to change immediately because poorly calibrated algorithms can be misleading and potentially harmful for clinical decision-making. We summarize how to avoid poor calibration at algorithm development and how to assess calibration at algorithm validation, emphasizing balance between model complexity and the available sample size. At external validation, calibration curves require sufficiently large samples. Algorithm updating should be considered for appropriate support of clinical practice. Efforts are required to avoid poor calibration when developing prediction models, to evaluate calibration when validating models, and to update models when indicated. The ultimate aim is to optimize the utility of predictive analytics for shared decision-making and patient counseling.

635 citations


Journal ArticleDOI
TL;DR: It is still unknown whether therapies work through common or specific factors, or both, and proponents of the common factors model often point to meta-analyses of comparative outcome studies that show all therapies have comparable effects.
Abstract: Psychotherapies may work through techniques that are specific to each therapy or through factors that all therapies have in common. Proponents of the common factors model often point to meta-analyses of comparative outcome studies that show all therapies have comparable effects. However, not all meta-analyses support the common factors model; the included studies often have several methodological problems; and there are alternative explanations for finding comparable outcomes. To date, research on the working mechanisms and mediators of therapies has always been correlational, and in order to establish that a mediator is indeed a causal factor in the recovery process of a patient, studies must show a temporal relationship between the mediator and an outcome, a dose-response association, evidence that no third variable causes changes in the mediator and the outcome, supportive experimental research, and have a strong theoretical framework. Currently, no common or specific factor meets these criteria and can be considered an empirically validated working mechanism. Therefore, it is still unknown whether therapies work through common or specific factors, or both.

349 citations


Journal ArticleDOI
TL;DR: The efficacy of app‐supported smartphone interventions for common mental health problems was confirmed and the potential of apps to serve as a cost‐effective, easily accessible, and low intensity intervention for those who cannot receive standard psychological treatment was highlighted.

331 citations


Journal ArticleDOI
TL;DR: An expanded GWAS of birth weight and subsequent analysis using structural equation modeling and Mendelian randomization decomposes maternal and fetal genetic contributions and causal links between birth weight, blood pressure and glycemic traits.
Abstract: Birth weight variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. In expanded genome-wide association analyses of own birth weight (n = 321,223) and offspring birth weight (n = 230,069 mothers), we identified 190 independent association signals (129 of which are novel). We used structural equation modeling to decompose the contributions of direct fetal and indirect maternal genetic effects, then applied Mendelian randomization to illuminate causal pathways. For example, both indirect maternal and direct fetal genetic effects drive the observational relationship between lower birth weight and higher later blood pressure: maternal blood pressure-raising alleles reduce offspring birth weight, but only direct fetal effects of these alleles, once inherited, increase later offspring blood pressure. Using maternal birth weight-lowering genotypes to proxy for an adverse intrauterine environment provided no evidence that it causally raises offspring blood pressure, indicating that the inverse birth weight-blood pressure association is attributable to genetic effects, and not to intrauterine programming.

323 citations


Journal ArticleDOI
LifeCycle Project-Maternal Obesity1, Ellis Voerman1, Susana Santos2, Susana Santos3, Hazel Inskip, Pilar Amiano4, Henrique Barros5, Henrique Barros6, Marie-Aline Charles7, Marie-Aline Charles8, Marie-Aline Charles9, Leda Chatzi10, George P. Chrousos11, Eva Corpeleijn3, Sarah Crozier12, Myriam Doyon13, Merete Eggesbø14, Maria Pia Fantini, Sara Farchi, Francesco Forastiere7, Vagelis Georgiu14, Davide Gori15, Wojciech Hanke16, Irva Hertz-Picciotto6, Irva Hertz-Picciotto5, Barbara Heude17, Barbara Heude12, Marie-France Hivert18, D. Hryhorczuk19, Carmen Iñiguez20, Anne M. Karvonen, Leanne K. Küpers21, Hanna Lagström22, Debbie A Lawlor23, Irina Lehmann13, Per Magnus24, Renata Majewska25, Johanna Mäkelä26, Yannis Manios27, Monique Mommers28, Monique Mommers29, Camilla Schmidt Morgen30, George Moschonis28, Ellen A. Nohr29, Anne-Marie Nybo Andersen17, Emily Oken24, Agnieszka Pac13, Eleni Papadopoulou31, Eleni Papadopoulou20, Juha Pekkanen32, Costanza Pizzi15, Kinga Polańska, Daniela Porta32, Lorenzo Richiardi17, Sheryl L. Rifas-Shiman33, Nel Roeleveld34, L. Ronfani4, Ana Cristina Santos, M. Standl13, Hein Stigum35, Hein Stigum13, Camilla Stoltenberg36, E. Thiering27, Carel Thijs, Maties Torrent37, Tomas Trnovec33, Marleen M.H.J. van Gelder38, Lenie van Rossem, Andrea von Berg39, Martine Vrijheid, Alet H. Wijga, Oleksandr Zvinchuk29, Thorkild I. A. Sørensen3, Thorkild I. A. Sørensen2, Keith M. Godfrey1, Vincent W. V. Jaddoe1, Romy Gaillard1 
07 May 2019-JAMA
TL;DR: In this meta-analysis of pooled individual participant data from 25 cohort studies, the risk for adverse maternal and infant outcomes varied by gestational weight gain and across the range of prepregnancy weights, however, the optimal gestations weight gain ranges had limited predictive value for the outcomes assessed.
Abstract: Importance Both low and high gestational weight gain have been associated with adverse maternal and infant outcomes, but optimal gestational weight gain remains uncertain and not well defined for all prepregnancy weight ranges. Objectives To examine the association of ranges of gestational weight gain with risk of adverse maternal and infant outcomes and estimate optimal gestational weight gain ranges across prepregnancy body mass index categories. Design, Setting, and Participants Individual participant-level meta-analysis using data from 196 670 participants within 25 cohort studies from Europe and North America (main study sample). Optimal gestational weight gain ranges were estimated for each prepregnancy body mass index (BMI) category by selecting the range of gestational weight gain that was associated with lower risk for any adverse outcome. Individual participant-level data from 3505 participants within 4 separate hospital-based cohorts were used as a validation sample. Data were collected between 1989 and 2015. The final date of follow-up was December 2015. Exposures Gestational weight gain. Main Outcomes and Measures The main outcome termedany adverse outcomewas defined as the presence of 1 or more of the following outcomes: preeclampsia, gestational hypertension, gestational diabetes, cesarean delivery, preterm birth, and small or large size for gestational age at birth. Results Of the 196 670 women (median age, 30.0 years [quartile 1 and 3, 27.0 and 33.0 years] and 40 937 were white) included in the main sample, 7809 (4.0%) were categorized at baseline as underweight (BMI Conclusions and Relevance In this meta-analysis of pooled individual participant data from 25 cohort studies, the risk for adverse maternal and infant outcomes varied by gestational weight gain and across the range of prepregnancy weights. The estimates of optimal gestational weight gain may inform prenatal counseling; however, the optimal gestational weight gain ranges had limited predictive value for the outcomes assessed.

286 citations


Journal ArticleDOI
TL;DR: There is strong evidence for beneficial effects of PA on maths performance, and recommendations focus on adequate control groups and sample size, the use of valid and reliable measurement instruments for physical activity and cognitive performance, measurement of compliance and data analysis.
Abstract: Objective To summarise the current evidence on the effects of physical activity (PA) interventions on cognitive and academic performance in children, and formulate research priorities and recommendations. Design Systematic review (following PRISMA guidelines) with a methodological quality assessment and an international expert panel. We based the evaluation of the consistency of the scientific evidence on the findings reported in studies rated as of high methodological quality. Data sources PubMed, PsycINFO, Cochrane Central, Web of Science, ERIC, and SPORTDiscus. Eligibility criteria for selecting studies PA-intervention studies in children with at least one cognitive or academic performance assessment. Results Eleven (19%) of 58 included intervention studies received a high-quality rating for methodological quality: four assessed effects of PA interventions on cognitive performance, six assessed effects on academic performance, and one on both. All high-quality studies contrasted the effects of additional/adapted PA activities with regular curriculum activities. For cognitive performance 10 of 21 (48%) constructs analysed showed statistically significant beneficial intervention effects of PA, while for academic performance, 15 of 25 (60%) analyses found a significant beneficial effect of PA. Across all five studies assessing PA effects on mathematics, beneficial effects were reported in six out of seven (86%) outcomes. Experts put forward 46 research questions. The most pressing research priority cluster concerned the causality of the relationship between PA and cognitive/academic performance. The remaining clusters pertained to PA characteristics, moderators and mechanisms governing the ‘PA–performance’ relationship and miscellaneous topics. Conclusion There is currently inconclusive evidence for the beneficial effects of PA interventions on cognitive and overall academic performance in children. We conclude that there is strong evidence for beneficial effects of PA on maths performance. The expert panel confirmed that more ‘high-quality’ research is warranted. By prioritising the most important research questions and formulating recommendations we aim to guide researchers in generating high-quality evidence. Our recommendations focus on adequate control groups and sample size, the use of valid and reliable measurement instruments for physical activity and cognitive performance, measurement of compliance and data analysis. PROSPERO registration number CRD42017082505.

277 citations


Journal ArticleDOI
Ellis Voerman1, Susana Santos1, Bernadeta Patro Golab2, Bernadeta Patro Golab1, Pilar Amiano, Ferran Ballester3, Henrique Barros4, Anna Bergström5, Marie-Aline Charles6, Marie-Aline Charles7, Leda Chatzi8, Leda Chatzi9, Leda Chatzi10, Cécile Chevrier11, George P. Chrousos12, Eva Corpeleijn13, Nathalie Costet11, Sarah Crozier14, Graham Devereux15, Merete Eggesbø16, Sandra Ekström17, Maria Pia Fantini18, Sara Farchi, Francesco Forastiere, Vagelis Georgiu8, Keith M. Godfrey19, Keith M. Godfrey14, Davide Gori18, Veit Grote20, Wojciech Hanke21, Irva Hertz-Picciotto22, Barbara Heude6, Barbara Heude7, Daniel O. Hryhorczuk23, Rae-Chi Huang24, Hazel Inskip14, Hazel Inskip19, Nina Iszatt16, Anne M. Karvonen25, Louise C. Kenny26, Berthold Koletzko20, Leanne K. Küpers27, Hanna Lagström28, Irina Lehmann29, Per Magnus16, Renata Majewska30, Johanna Mäkelä31, Yannis Manios32, Fionnuala M. McAuliffe33, Sheila McDonald34, John Mehegan33, Monique Mommers35, Camilla Schmidt Morgen36, Camilla Schmidt Morgen37, Trevor A. Mori24, George Moschonis38, Deirdre M. Murray26, Carol Ní Chaoimh26, Ellen A. Nohr37, Anne-Marie Nybo Andersen36, Emily Oken39, Adriette J. J. M. Oostvogels35, Agnieszka Pac30, Eleni Papadopoulou16, Juha Pekkanen40, Costanza Pizzi41, Kinga Polańska21, Daniela Porta, Lorenzo Richiardi41, Sheryl L. Rifas-Shiman39, Luca Ronfani42, Ana Cristina Santos4, Marie Standl, Camilla Stoltenberg43, Elisabeth Thiering20, Carel Thijs35, Maties Torrent, Suzanne Tough34, Tomas Trnovec44, Steve Turner45, Lenie van Rossem46, Andrea von Berg, Martine Vrijheid47, Tanja G. M. Vrijkotte35, Jane West48, Alet H. Wijga, John Wright48, Oleksandr Zvinchuk, Thorkild I. A. Sørensen36, Debbie A Lawlor27, Romy Gaillard1, Vincent W. V. Jaddoe1 
TL;DR: In this article, the authors conducted an individual participant data meta-analysis of data from 162,129 mothers and children from 37 pregnancy and birth cohort studies from Europe, North-America and Australia, using multilevel binary logistic regression models with a random intercept at cohort level adjusted for maternal socio-demographic and life style related characteristics.
Abstract: Background: Maternal obesity and excessive gestational weight gain may have persistent effects on offspring fat development. However, it remains unclear whether these risks differ by severity of obesity, and whether these effects are restricted to the extremes of maternal body mass index (BMI) and gestational weight gain. We aimed to assess the separate and combined associations of maternal BMI and gestational weight gain with the risk of overweight/obesity throughout childhood, and their population impact. Methods and Findings: We conducted an individual participant data meta-analysis of data from 162,129 mothers and children from 37 pregnancy and birth cohort studies from Europe, North-America and Australia. We assessed the individual and combined associations of maternal pre-pregnancy BMI and gestational weight gain, both in clinical categories and across their full ranges with the risks of overweight/obesity in early- (2.0-5.0 years), mid- (5.0-10.0 years) and late childhood (10.0-18.0 years), using multilevel binary logistic regression models with a random intercept at cohort level adjusted for maternal socio-demographic and life style related characteristics. We observed that a higher maternal pre-pregnancy BMI and gestational weight gain both in clinical categories and across their full ranges were associated with higher risks of childhood overweight/obesity, with the strongest effects in late childhood (Odds Ratios (OR) for overweight/obesity in early-, mid- and late childhood, respectively: 1.66 (95% Confidence Interval (CI): 1.56, 1.78), OR 1.91 (95% CI: 1.85, 1.98), and OR 2.28 (95% CI: 2.08, 2.50) for maternal overweight, OR 2.43 (95% CI: 2.24, 2.64), OR 3.12 (95% CI: 2.98, 3.27), and OR 4.47 (95% CI: 3.99, 5.23) for maternal obesity, and OR 1.39 (95% CI: 1.30, 1.49), OR 1.55 (95% CI: 1.49, 1.60), and 1.72 (95% CI: 1.56, 1.91) for excessive gestational weight gain. The proportions of childhood overweight/obesity prevalence attributable to maternal overweight, maternal obesity and excessive gestational weight gain ranged from 10.2 to 21.6%. Relative to the effect of maternal BMI, excessive gestational weight gain only slightly increased the risk of childhood overweight/obesity within each clinical BMI category (P-values for interactions of maternal BMI with gestational weight gain: p=0.038, p<0.001 and p=0.637, in early-, mid- and late childhood, respectively). Limitations of this study include the self-report of maternal BMI and gestational weight gain for some of the cohorts, and the potential of residual confounding. Also, as this study only included participants from Europe, North-America and Australia, results need to be interpreted with caution with respect to other populations. Conclusions: In this study, higher maternal pre-pregnancy BMI and gestational weight gain were associated with an increased risk of childhood overweight/obesity, with the strongest effects at later ages. The additional effect of gestational weight gain in women who are overweight or obese before pregnancy is small. Given the large population impact, future intervention trials aiming to reduce the prevalence of childhood overweight and obesity should focus on maternal weight status before pregnancy, in addition to weight gain during pregnancy.

248 citations


Journal ArticleDOI
02 Dec 2019
TL;DR: Although some trials showed potential of apps targeting mental health symptoms, using smartphone apps as standalone psychological interventions cannot be recommended based on the current level of evidence.
Abstract: While smartphone usage is ubiquitous, and the app market for smartphone apps targeted at mental health is growing rapidly, the evidence of standalone apps for treating mental health symptoms is still unclear. This meta-analysis investigated the efficacy of standalone smartphone apps for mental health. A comprehensive literature search was conducted in February 2018 on randomized controlled trials investigating the effects of standalone apps for mental health in adults with heightened symptom severity, compared to a control group. A random-effects model was employed. When insufficient comparisons were available, data was presented in a narrative synthesis. Outcomes included assessments of mental health disorder symptom severity specifically targeted at by the app. In total, 5945 records were identified and 165 full-text articles were screened for inclusion by two independent researchers. Nineteen trials with 3681 participants were included in the analysis: depression (k = 6), anxiety (k = 4), substance use (k = 5), self-injurious thoughts and behaviors (k = 4), PTSD (k = 2), and sleep problems (k = 2). Effects on depression (Hedges’ g = 0.33, 95%CI 0.10–0.57, P = 0.005, NNT = 5.43, I2 = 59%) and on smoking behavior (g = 0.39, 95%CI 0.21–0.57, NNT = 4.59, P ≤ 0.001, I2 = 0%) were significant. No significant pooled effects were found for anxiety, suicidal ideation, self-injury, or alcohol use (g = −0.14 to 0.18). Effect sizes for single trials ranged from g = −0.05 to 0.14 for PTSD and g = 0.72 to 0.84 for insomnia. Although some trials showed potential of apps targeting mental health symptoms, using smartphone apps as standalone psychological interventions cannot be recommended based on the current level of evidence.

248 citations


Journal ArticleDOI
TL;DR: An overview of different methods available and applicable in clinical settings and the use of grip strength to measure muscle strength and theUse of 4-m gait speed or the Short Physical Performance Battery test to measure physical performance in daily practice are proposed.
Abstract: It is well recognized that poor muscle function and poor physical performance are strong predictors of clinically relevant adverse events in older people. Given the large number of approaches to measure muscle function and physical performance, clinicians often struggle to choose a tool that is appropriate and validated for the population of older people they deal with. In this paper, an overview of different methods available and applicable in clinical settings is proposed. This paper is based on literature reviews performed by members of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) working group on frailty and sarcopenia. Face-to-face meetings were organized afterwards where the whole group could amend and discuss the recommendations further. Several characteristics should be considered when choosing a tool: (1) purpose of the assessment (intervention, screening, diagnosis); (2) patient characteristics (population, settings, functional ability, etc.); (3) psychometric properties of the tool (test–retest reliability, inter-rater reliability, responsiveness, floor and ceiling effects, etc.); (4) applicability of the tool in clinical settings (overall cost, time required for the examination, level of training, equipment, patient acceptance, etc.); (5) prognostic reliability for relevant clinical outcomes. Based on these criteria and the available evidence, the expert group advises the use of grip strength to measure muscle strength and the use of 4-m gait speed or the Short Physical Performance Battery test to measure physical performance in daily practice. The tools proposed are relevant for the assessment of muscle weakness and physical performance. Subjects with low values should receive additional diagnostic workups to achieve a full diagnosis of the underlying condition responsible (sarcopenia, frailty or other).

239 citations



Journal ArticleDOI
TL;DR: For acute symptoms of depression, group, telephone, and guidedSelf-help treatment formats appeared to be effective interventions, which may be considered as alternatives to individual CBT; although there were few indications of significant differences in efficacy between treatments with human support, guided self-help CBT may be less acceptable for patients than individual, Group, or telephone formats.
Abstract: Importance Cognitive behavior therapy (CBT) has been shown to be effective in the treatment of acute depression. However, whether CBT can be effectively delivered in individual, group, telephone-administered, guided self-help, and unguided self-help formats remains unclear. Objective To examine the most effective delivery format for CBT via a network meta-analysis. Data Sources A database updated yearly from PubMed, PsycINFO, Embase, and the Cochrane Library. Literature search dates encompassed January 1, 1966, to January 1, 2018. Study Selection Randomized clinical trials of CBT for adult depression. The 5 treatment formats were compared with each other and the control conditions (waiting list, care as usual, and pill placebo). Data Extraction and Synthesis PRISMA guidelines were used when extracting data and assessing data quality. Data were pooled using a random-effects model. Pairwise and network meta-analyses were conducted. Main Outcomes and Measures Severity of depression and acceptability of the treatment formats. Results A total of 155 trials with 15 191 participants compared 5 CBT delivery formats with 2 control conditions. In half of the studies (78 [50.3%]), patients met the criteria for a depressive disorder; in the other half (77 [49.7%]), participants scored above the cutoff point on a self-report measure. The effectiveness of individual, group, telephone, and guided self-help CBT did not differ statistically significantly from each other. These formats were statistically significantly more effective than the waiting list (standardized mean differences [SMDs], 0.87-1.02) and care as usual (SMDs, 0.47-0.72) control conditions as well as the unguided self-help CBT (SMDs, 0.34-0.59). In terms of acceptability (dropout for any reason), individual (relative risk [RR] = 1.44; 95% CI, 1.09-1.89) and group (RR = 1.38; 95% CI, 1.06-1.80) CBT were significantly better than guided self-help. Guided self-help was also less acceptable than being on a waiting list (RR = 0.63; 95% CI, 0.52-0.75) and care as usual (RR = 0.72; 95% CI, 0.57-0.90). Sensitivity analyses supported the overall findings. Conclusions and Relevance For acute symptoms of depression, group, telephone, and guided self-help treatment formats appeared to be effective interventions, which may be considered as alternatives to individual CBT; although there were few indications of significant differences in efficacy between treatments with human support, guided self-help CBT may be less acceptable for patients than individual, group, or telephone formats.

Journal ArticleDOI
Adrienne Tin1, Jonathan Marten2, Victoria L. Halperin Kuhns3, Yong Li4  +248 moreInstitutions (77)
TL;DR: A trans-ancestry genome-wide association study of serum urate levels identifies 183 loci that improve the prediction of gout in an independent cohort of 334,880 individuals, and implicates the kidney and liver as key target organs and prioritize potential causal genes.
Abstract: Elevated serum urate levels cause gout and correlate with cardiometabolic diseases via poorly understood mechanisms. We performed a trans-ancestry genome-wide association study of serum urate in 457,690 individuals, identifying 183 loci (147 previously unknown) that improve the prediction of gout in an independent cohort of 334,880 individuals. Serum urate showed significant genetic correlations with many cardiometabolic traits, with genetic causality analyses supporting a substantial role for pleiotropy. Enrichment analysis, fine-mapping of urate-associated loci and colocalization with gene expression in 47 tissues implicated the kidney and liver as the main target organs and prioritized potentially causal genes and variants, including the transcriptional master regulators in the liver and kidney, HNF1A and HNF4A. Experimental validation showed that HNF4A transactivated the promoter of ABCG2, encoding a major urate transporter, in kidney cells, and that HNF4A p.Thr139Ile is a functional variant. Transcriptional coregulation within and across organs may be a general mechanism underlying the observed pleiotropy between urate and cardiometabolic traits.

Journal ArticleDOI
TL;DR: Two novel methods for multivariate genome-wide-association meta-analysis of related traits that correct for sample overlap are introduced and it is shown that genes differentially expressed in the subiculum and GABAergic interneurons are enriched in their effect on the well-being spectrum.
Abstract: 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.

Journal ArticleDOI
TL;DR: The relationship between multimorbidity and QoL or health-related quality of life (HRQoL) through systematic literature review is understood and the strength of this association is explored by conducting the first meta-analysis on the subject.

Journal ArticleDOI
20 Aug 2019-JAMA
TL;DR: Among pregnant women without overt thyroid disease, subclinical hypothyroidism, isolated hypothyroxinemia, and TPO antibody positivity were significantly associated with higher risk of preterm birth, providing insights toward optimizing clinical decision-making strategies.
Abstract: Importance: Maternal hypothyroidism and hyperthyroidism are risk factors for preterm birth. Milder thyroid function test abnormalities and thyroid autoimmunity are more prevalent, but it remains controversial if these are associated with preterm birth. Objective: To study if maternal thyroid function test abnormalities and thyroid autoimmunity are risk factors for preterm birth. Data Sources and Study Selection: Studies were identified through a search of the Ovid MEDLINE, EMBASE, Web of Science, the Cochrane Central Register of Controlled Trials, and Google Scholar databases from inception to March 18, 2018, and by publishing open invitations in relevant journals. Data sets from published and unpublished prospective cohort studies with data on thyroid function tests (thyrotropin [often referred to as thyroid-stimulating hormone or TSH] and free thyroxine [FT4] concentrations) or thyroid peroxidase (TPO) antibody measurements and gestational age at birth were screened for eligibility by 2 independent reviewers. Studies in which participants received treatment based on abnormal thyroid function tests were excluded. Data Extraction and Synthesis: The primary authors provided individual participant data that were analyzed using mixed-effects models. Main Outcomes and Measures: The primary outcome was preterm birth (<37 weeks' gestational age). Results: From 2526 published reports, 35 cohorts were invited to participate. After the addition of 5 unpublished data sets, a total of 19 cohorts were included. The study population included 47045 pregnant women (mean age, 29 years; median gestational age at blood sampling, 12.9 weeks), of whom 1234 (3.1%) had subclinical hypothyroidism (increased thyrotropin concentration with normal FT4 concentration), 904 (2.2%) had isolated hypothyroxinemia (decreased FT4 concentration with normal thyrotropin concentration), and 3043 (7.5%) were TPO antibody positive; 2357 (5.0%) had a preterm birth. The risk of preterm birth was higher for women with subclinical hypothyroidism than euthyroid women (6.1% vs 5.0%, respectively; absolute risk difference, 1.4% [95% CI, 0%-3.2%]; odds ratio [OR], 1.29 [95% CI, 1.01-1.64]). Among women with isolated hypothyroxinemia, the risk of preterm birth was 7.1% vs 5.0% in euthyroid women (absolute risk difference, 2.3% [95% CI, 0.6%-4.5%]; OR, 1.46 [95% CI, 1.12-1.90]). In continuous analyses, each 1-SD higher maternal thyrotropin concentration was associated with a higher risk of preterm birth (absolute risk difference, 0.2% [95% CI, 0%-0.4%] per 1 SD; OR, 1.04 [95% CI, 1.00-1.09] per 1 SD). Thyroid peroxidase antibody-positive women had a higher risk of preterm birth vs TPO antibody-negative women (6.6% vs 4.9%, respectively; absolute risk difference, 1.6% [95% CI, 0.7%-2.8%]; OR, 1.33 [95% CI, 1.15-1.56]). Conclusions and Relevance: Among pregnant women without overt thyroid disease, subclinical hypothyroidism, isolated hypothyroxinemia, and TPO antibody positivity were significantly associated with higher risk of preterm birth. These results provide insights toward optimizing clinical decision-making strategies that should consider the potential harms and benefits of screening programs and levothyroxine treatment during pregnancy.

Journal ArticleDOI
TL;DR: Human islet 3D chromatin architecture provides a framework for interpretation of T2D genome-wide association study (GWAS) signals and identifies more than 1,300 three-dimensional regulatory hubs, linking diabetes-associated enhancers to their target genes.
Abstract: Genetic studies promise to provide insight into the molecular mechanisms underlying type 2 diabetes (T2D). Variants associated with T2D are often located in tissue-specific enhancer clusters or super-enhancers. So far, such domains have been defined through clustering of enhancers in linear genome maps rather than in three-dimensional (3D) space. Furthermore, their target genes are often unknown. We have created promoter capture Hi-C maps in human pancreatic islets. This linked diabetes-associated enhancers to their target genes, often located hundreds of kilobases away. It also revealed >1,300 groups of islet enhancers, super-enhancers and active promoters that form 3D hubs, some of which show coordinated glucose-dependent activity. We demonstrate that genetic variation in hubs impacts insulin secretion heritability, and show that hub annotations can be used for polygenic scores that predict T2D risk driven by islet regulatory variants. Human islet 3D chromatin architecture, therefore, provides a framework for interpretation of T2D genome-wide association study (GWAS) signals.


Journal ArticleDOI
TL;DR: It is found that food fussiness is a barrier to acceptance, whereas green eating behavior and higher educational attainment are facilitators to older adults’ acceptance to eat protein from alternative, more sustainable sources.
Abstract: Protein-energy malnutrition (PEM) is a growing concern on account of an aging population and its negative health consequences. While dietary protein plays a key role in the prevention of PEM, it also plays a pivotal role in the environmental impact of the human diet. In search for sustainable dietary strategies to increase protein intake in older adults, this study investigated the readiness of older adults to accept the consumption of the following alternative, more sustainable protein sources: plant-based protein, insects, single-cell protein, and in vitro meat. Using ordinal logistic regression modeling, the associations of different food-related attitudes and behavior and sociodemographics with older adults’ acceptance to consume such protein sources were assessed. Results were obtained through a consumer survey among 1825 community-dwelling older adults aged 65 years or above in five EU countries (United Kingdom, the Netherlands, Poland, Spain, and Finland). Dairy-based protein was generally the most accepted protein source in food products (75% of the respondents found its consumption acceptable or very acceptable). Plant-based protein was the most accepted alternative, more sustainable protein source (58%) followed by single-cell protein (20%), insect-based protein (9%), and in vitro meat-based protein (6%). We found that food fussiness is a barrier to acceptance, whereas green eating behavior and higher educational attainment are facilitators to older adults’ acceptance to eat protein from alternative, more sustainable sources. Health, sensory appeal, and price as food choice motives, as well as gender and country of residence were found to influence acceptance, although not consistently across all the protein sources. Findings suggest that there is a window of opportunity to increase older adults’ acceptance of alternative, more sustainable protein sources and in turn increase protein intake in an environmentally sustainable way in EU older adults.

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TL;DR: Current approaches and evidence regarding malnutrition treatment are described and relevant knowledge gaps that need to be addressed and research methodology should be harmonised to allow for the comparability of studies.
Abstract: Malnutrition is widespread in older people and represents a major geriatric syndrome with multifactorial etiology and severe consequences for health outcomes and quality of life. The aim of the present paper is to describe current approaches and evidence regarding malnutrition treatment and to highlight relevant knowledge gaps that need to be addressed. Recently published guidelines of the European Society for Clinical Nutrition and Metabolism (ESPEN) provide a summary of the available evidence and highlight the wide range of different measures that can be taken—from the identification and elimination of potential causes to enteral and parenteral nutrition—depending on the patient’s abilities and needs. However, more than half of the recommendations therein are based on expert consensus because of a lack of evidence, and only three are concern patient-centred outcomes. Future research should further clarify the etiology of malnutrition and identify the most relevant causes in order to prevent malnutrition. Based on limited and partly conflicting evidence and the limitations of existing studies, it remains unclear which interventions are most effective in which patient groups, and if specific situations, diseases or etiologies of malnutrition require specific approaches. Patient-relevant outcomes such as functionality and quality of life need more attention, and research methodology should be harmonised to allow for the comparability of studies.

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TL;DR: Although mental disorders and suicidal thoughts‐behaviors (suicidal thoughts and behaviors) are common among university students, the majority of students with these problems remain untreated.
Abstract: CITATION: Ebert, D. D., et al. 2019. Barriers of mental health treatment utilization among first-year college students: First cross-national results from the WHO World Mental Health International College Student Initiative. International Journal of Methods in Psychiatric Research, 8(2):e1782, doi:10.1002/mpr.1782.

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TL;DR: The prevalence of high malnutrition risk in European older adults varies widely between countries and across health-care settings, and the use of one preferred malnutrition screening tool per setting is strongly recommended.

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TL;DR: Findings are consistent enough for hypothesising causation (at least for cardiovascular-related outcomes), further studies are needed to clarify the role of potential confounding factors.
Abstract: The aim of this study was to provide a comprehensive evaluation of current evidence on fruit and vegetable consumption and health outcomes. A systematic search for quantitative syntheses was performed. Several criteria, including study design, dose-response relationship, heterogeneity and agreement of results over time, and identification of potential confounding factors, were used to assess the level of evidence. The strongest (probable) evidence was found for cardiovascular disease protection; possible evidence for decreased risk of colon cancer, depression and pancreatic diseases was found for fruit intake; and colon and rectal cancer, hip fracture, stroke, depression and pancreatic diseases was found for vegetable intake. Suggestive and rather limited associations with other outcomes have been found. Evidence of potential confounding by sex and geographical localisation has been reported. Despite findings are consistent enough for hypothesising causation (at least for cardiovascular-related outcomes), further studies are needed to clarify the role of potential confounding factors.

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08 Mar 2019-PLOS ONE
TL;DR: QoL can be expressed in a number of domains and related subthemes that are important for older adults living at home, and the results showed that although different domains can be distinguished, these are also strongly connected.
Abstract: Background Consideration of older adults' quality of life (QoL) is becoming increasingly important in the evaluation, quality improvement and allocation of health and social care services. While numerous definitions and theories of QoL have been proposed, an overall synthesis of the perspective of older adults themselves is lacking. Methods Qualitative studies were identified in PubMed, Ebsco/Psycinfo and Ebsco/CINAHL, through a search on 28 November 2018. Articles needed to meet all of the following criteria: (i) focus on perceptions of QoL, (ii) older adults living at home as main participants, (iii) use of qualitative methodology, (iv) conducted in a Western country and (v) published in English (vi) not focused on specific patient groups. A thematic synthesis was conducted of the selected studies, using the complete 'findings/results' sections from the papers. Results We included 48 qualitative studies representing the views of more than 3,400 older adults living at home in 11 Western countries. The QoL aspects identified in the synthesis were categorized into nine QoL domains: Autonomy, role and activity, health perception, relationships, attitude and adaptation, emotional comfort, spirituality, home and neighbourhood, and financial security. The results showed that although different domains can be distinguished, these are also strongly connected. Conclusion QoL can be expressed in a number of domains and related subthemes that are important for older adults living at home. The findings further support that the concept of QoL should be seen as a dynamic web of intertwined domains.

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TL;DR: In comparison to AlereLAM, FujiLAM offers superior diagnostic sensitivity, while maintaining specificity, and could transform rapid point-of-care tuberculosis diagnosis for hospital inpatients with HIV.
Abstract: Summary Background Most tuberculosis-related deaths in people with HIV could be prevented with earlier diagnosis and treatment. The only commercially available tuberculosis point-of-care test (Alere Determine TB LAM Ag [AlereLAM]) has suboptimal sensitivity, which restricts its use in clinical practice. The novel Fujifilm SILVAMP TB LAM (FujiLAM) assay has been developed to improve the sensitivity of AlereLAM. We assessed the diagnostic accuracy of the FujiLAM assay for the detection of tuberculosis in hospital inpatients with HIV compared with the AlereLAM assay. Methods For this diagnostic accuracy study, we assessed biobanked urine samples obtained from the FIND Specimen Bank and the University of Cape Town Biobank, which had been collected from hospital inpatients (aged ≥18 years) with HIV during three independent prospective cohort studies done at two South African hospitals. Urine samples were tested using FujiLAM and AlereLAM assays. The conduct and reporting of each test was done blind to other test results. The primary objective was to assess the diagnostic accuracy of FujiLAM compared with AlereLAM, against microbiological and composite reference standards (including clinical diagnoses). Findings Between April 18, 2018, and May 3, 2018, urine samples from 968 hospital inpatients with HIV were evaluated. The prevalence of microbiologically-confirmed tuberculosis was 62% and the median CD4 count was 86 cells per μL. Using the microbiological reference standard, the estimated sensitivity of FujiLAM was 70·4% (95% CI 53·0 to 83·1) compared with 42·3% (31·7 to 51·8) for AlereLAM (difference 28·1%) and the estimated specificity of FujiLAM was 90·8% (86·0 to 94·4) and 95·0% (87·7–98·8) for AlereLAM (difference −4·2%). Against the composite reference standard, the specificity of both assays was higher (95·7% [92·0 to 98·0] for FujiLAM vs 98·2% [95·7 to 99·6] for AlereLAM; difference −2·5%), but the sensitivity of both assays was lower (64·9% [50·1 to 76·7] for FujiLAM vs 38·2% [28·1 to 47·3] for AlereLAM; difference 26·7%). Interpretation In comparison to AlereLAM, FujiLAM offers superior diagnostic sensitivity, while maintaining specificity, and could transform rapid point-of-care tuberculosis diagnosis for hospital inpatients with HIV. The applicability of FujiLAM for settings of intended use requires prospective assessment. Funding Global Health Innovative Technology Fund, UK Department for International Development, Dutch Ministry of Foreign Affairs, Bill & Melinda Gates Foundation, German Federal Ministry of Education and Research, Australian Department of Foreign Affairs and Trade, Wellcome Trust, Department of Science and Technology and National Research Foundation of South Africa, and South African Medical Research Council.

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TL;DR: It is concluded that the full HPSF is effective in promoting children’s health behaviours at T1 and T2 compared with control schools and focusing on both nutrition and PA components seems to be more effective in promote healthy behaviours.
Abstract: Schools can help to improve children’s health. The ‘Healthy Primary School of the Future’ (HPSF) aims to sustainably integrate health and well-being into the school system. This study examined the effects of HPSF on children’s dietary and physical activity (PA) behaviours after 1 and 2 years’ follow-up. The study (n = 1676 children) has a quasi-experimental design with four intervention schools, i.e., two full HPSF (focus: nutrition and PA) and two partial HPSF (focus: PA), and four control schools. Accelerometers and child- and parent-reported questionnaires were used at baseline, after 1 (T1) and 2 (T2) years. Mixed-model analyses showed significant favourable effects for the full HPSF versus control schools for, among others, school water consumption (effect size (ES) = 1.03 (T1), 1.14 (T2)), lunch intake of vegetables (odds ratio (OR) = 3.17 (T1), 4.39 (T2)) and dairy products (OR = 4.43 (T1), 4.52 (T2)), sedentary time (ES = −0.23 (T2)) and light PA (ES = 0.22 (T2)). Almost no significant favourable effects were found for partial HPSF compared to control schools. We conclude that the full HPSF is effective in promoting children’s health behaviours at T1 and T2 compared with control schools. Focusing on both nutrition and PA components seems to be more effective in promoting healthy behaviours than focusing exclusively on PA.

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TL;DR: This work systematically synthesized recent literature on determinants of weight loss maintenance for individuals with overweight and obesity to arrive at a consensus on the importance of diet and exercise in maintaining weight loss.
Abstract: Background Discerning the determinants of weight loss maintenance is important in the planning of future interventions and policies regarding overweight and obesity. We have therefore systematically synthesized recent literature on determinants of weight loss maintenance for individuals with overweight and obesity. Methods With the use of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, prospective studies were identified from searches in PubMed and PsycINFO from 2006 to 2016. We included articles investigating adults with overweight and obesity undergoing weight loss without surgery or medication. Included articles were scored on their methodological quality, and a best-evidence synthesis was applied to summarize the results. Results Our search resulted in 8,222 articles of which 67 articles were selected. In total, 124 determinants were identified of which 5 were demographic, 59 were behavioural, 51 were psychological/cognitive and 9 were social and physical environmental determinants. We found consistent evidence that demographic determinants were not predictive of weight loss maintenance. Behavioural and cognitive determinants that promote a reduction in energy intake, an increase in energy expenditure and monitoring of this balance are predictive determinants. Conclusion This review identifies key determinants in weight loss maintenance. However, more research regarding cognitive and environmental determinants of weight loss maintenance is needed to advance our knowledge on determinants of weight loss maintenance.

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TL;DR: Psychological therapies are effective in the treatment of depression in primary care, have longer lasting effects than drugs, are preferred by the majority of patients, and can be applied flexibly with different formats and across different target groups.
Abstract: We give an overview of recent developments on psychological treatments of depression in primary care. In recent years, it has become clear that psychotherapies can effectively be delivered through e-health applications. Furthermore, several studies in low and middle income countries have shown that lay health counselors can effectively deliver psychological therapies. Behavioral activation, a relatively simple form of therapy, has been found to be as effective as cognitive behavior therapy. Treatment of subthreshold depression has been found to not only reduce depressive symptoms but also prevent the onset of major depression. In addition, therapies are effective in older adults, patients with general medical disorders and in perinatal depression. Psychological therapies are effective in the treatment of depression in primary care, have longer lasting effects than drugs, are preferred by the majority of patients, and can be applied flexibly with different formats and across different target groups.

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Leanne K. Küpers, Claire Monnereau1, Gemma C Sharp2, Paul Yousefi2  +148 moreInstitutions (58)
TL;DR: In this article, a meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium was conducted, and the authors found that DNA methylation in neonatal blood is associated with birthweight at 914 sites, with a difference in birthweight ranging from -183 to 178 grams per 10% increase in methylation.
Abstract: Birthweight is associated with health outcomes across the life course, DNA methylation may be an underlying mechanism. In this meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, we find that DNA methylation in neonatal blood is associated with birthweight at 914 sites, with a difference in birthweight ranging from -183 to 178 grams per 10% increase in methylation (PBonferroni < 1.06 x 10-7). In additional analyses in 7,278 participants, <1.3% of birthweight-associated differential methylation is also observed in childhood and adolescence, but not adulthood. Birthweight-related CpGs overlap with some Bonferroni-significant CpGs that were previously reported to be related to maternal smoking (55/914, p = 6.12 x 10-74) and BMI in pregnancy (3/914, p = 1.13x10-3), but not with those related to folate levels in pregnancy. Whether the associations that we observe are causal or explained by confounding or fetal growth influencing DNA methylation (i.e. reverse causality) requires further research.

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TL;DR: It is found that breastfeeding duration in early life and pre-school dietary lifestyle correlated with the composition and functional competences of the gut microbiota in the children at school age and underscore enterotype-specific links between the host metabolic phenotypes and dietary patterns.
Abstract: The gut microbiota evolves from birth and is in early life influenced by events such as birth mode, type of infant feeding, and maternal and infant antibiotics use. However, we still have a gap in our understanding of gut microbiota development in older children, and to what extent early events and pre-school lifestyle modulate the composition of the gut microbiota, and how this impinges on whole body metabolic regulation in school-age children. Taking advantage of the KOALA Birth Cohort Study, a long-term prospective birth cohort in the Netherlands with extensive collection of high-quality host metadata, we applied shotgun metagenomics sequencing and systematically investigated the gut microbiota of children at 6–9 years of age. We demonstrated an overall adult-like gut microbiota in the 281 Dutch school-age children and identified 3 enterotypes dominated by the genera Bacteroides, Prevotella, and Bifidobacterium, respectively. Importantly, we found that breastfeeding duration in early life and pre-school dietary lifestyle correlated with the composition and functional competences of the gut microbiota in the children at school age. The correlations between pre-school dietary lifestyle and metabolic phenotypes exhibited a striking enterotype dependency. Thus, an inverse correlation between high dietary fiber consumption and low plasma insulin levels was only observed in individuals with the Bacteroides and Prevotella enterotypes, but not in Bifidobacterium enterotype individuals in whom the gut microbiota displayed overall lower microbial gene richness, alpha-diversity, functional potential for complex carbohydrate fermentation, and butyrate and succinate production. High total fat consumption and elevated plasma free fatty acid levels in the Bifidobacterium enterotype are associated with the co-occurrence of Streptococcus. Our work highlights the persistent effects of breastfeeding duration and pre-school dietary lifestyle in affecting the gut microbiota in school-age children and reveals distinct compositional and functional potential in children according to enterotypes. The findings underscore enterotype-specific links between the host metabolic phenotypes and dietary patterns, emphasizing the importance of microbiome-based stratification when investigating metabolic responses to diets. Future diet intervention studies are clearly warranted to examine gut microbe-diet-host relationships to promote knowledge-based recommendations in relation to improving metabolic health in children.