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المكتبة البحثية18 results

Peer-reviewed works with DOI and abstract, discovered from MEDLINE-indexed literature. Candidates: no tier, no stated finding, not yet read.

Wong SY, Yip BH, Mak WW, Mercer S, Cheung EY, Ling CY, Lui WW, Tang WK, Lo HH, Wu JC, Lee TM, Gao T, Griffiths SM, Chan PH, Ma HS. (2016)MEDLINE-indexed journal, not yet read by usThe British journal of psychiatry : the journal of mental science · randomised controlled trial

Mindfulness-based cognitive therapy v. group psychoeducation for people with generalised anxiety disorder: randomised controlled trial.

Background: Research suggests that an 8-week mindfulness-based cognitive therapy (MBCT) course may be effective for generalised anxiety disorder (GAD). Aims: To compare changes in anxiety levels among participants with GAD randomly assigned to MBCT, cognitive-behavioural therapy-based psychoeducation and usual care. Method: In total, 182 participants with GAD were recruited (trial registration number: CUHK_CCT00267) and assigned to the three groups and followed for 5 months after baseline assessment with the two intervention groups followed for an additional 6 months. Primary outcomes were anxiety and worry levels. Results: Linear mixed models demonstrated significant group × time interaction (F(4,148) = 5.10, P = 0.001) effects for decreased anxiety for both the intervention groups relative to usual care. Significant group × time interaction effects were observed for worry and depressive symptoms and mental health-related quality of life for the psychoeducation group only. Conclusions: These results suggest that both of the interventions appear to be superior to usual care for the reduction of anxiety symptoms.

The British journal of psychiatry : the journal of mental science · randomised controlled trial · 47 citationsread the source →

Lang IA, Llewellyn DJ, Langa KM, Wallace RB, Melzer D. (2008)MEDLINE-indexed journal, not yet read by usAge and ageing

Neighbourhood deprivation and incident mobility disability in older adults.

Objective: to assess whether incident mobility disability and neighbourhood deprivation in older people are associated independent of the effects of individual socio-economic status, health behaviours and health status. Methods: prospective cohort study with a 2-year follow-up. Setting: the English Longitudinal Study of Ageing (ELSA), a national probability sample of non-institutionalised older people. Participants: 4,148 participants aged 60 years and over. Measurements: exposure was a census-based index of neighbourhood deprivation [the Index of Multiple Deprivation (IMD)]; outcomes were measured and self-reported incident mobility difficulties. Results: neighbourhood deprivation had a statistically significant effect on physical function following adjustment for individual socio-economic factors, health behaviours and health status. Compared to those living in the least deprived 20% of neighbourhoods, those in the most deprived neighbourhoods had a risk ratio (RR) of incident self-reported mobility difficulties of 1.75 (95% CI 1.14-2.70) and RR of incident-impaired gait speed of 1.63 (95% CI 1.01-2.62). In adjusted models, 4.0 per 100 (95% CI 3.0-5.4) older adults in neighbourhoods in the least deprived 20% had incident mobility difficulties over a 2-year period, whereas 13.6 per 100 (95% CI 10.5-17.4) older adults had incident mobility difficulties in neighbourhoods in the most deprived 20%. Conclusions: older people living in deprived neighbourhoods are significantly more likely to experience incident mobility difficulties than those in less-deprived neighbourhoods. The mechanisms underlying this relationship are unclear and research to identify mechanisms and appropriate interventions is needed.

Age and ageing · 42 citationsread the source →

Kwok JYY, Jiang D, Yeung DY, Choi NG, Ho RTH, Warner LM, Chou KL. (2024)MEDLINE-indexed journal, not yet read by usJAMA network open · randomised controlled trial

Layperson-Delivered Telephone-Based Behavioral Activation Among Low-Income Older Adults During the COVID-19 Pandemic: The HEAL-HOA Randomized Clinical Trial.

Importance: Older adults are particularly vulnerable to loneliness and its physical and psychosocial sequelae, but scalable interventions are lacking, especially during disasters such as pandemics. Objective: To compare the effects of layperson-delivered, telephone-based behavioral activation and mindfulness interventions vs telephone-based befriending on loneliness among at-risk older adults. Design, setting, and participants: This assessor-blinded, 3-arm randomized clinical trial screened Chinese older adults through household visits and community referrals from April 1, 2021, to April 30, 2023, in Hong Kong. Eligible participants (≥65 years of age) who were lonely, digitally excluded, living alone, and living below the poverty line and provided consent to participate were randomized into behavioral activation, mindfulness, and befriending groups. Assessments were conducted at baseline, 1 month, and 3 months. Intervention: As part of the Helping Alleviate Loneliness in Hong Kong Older Adults (HEAL-HOA) dual randomized clinical trial, 148 older laypersons were trained to deliver a twice-weekly 30-minute intervention via telephone for 4 weeks. Main outcomes and measures: The primary outcome was loneliness measured by the UCLA Loneliness Scale (range, 20-80) and the De Jong Gierveld Loneliness Scale (range, 0-6), with higher scores on both scales indicating greater loneliness. Secondary outcomes were depression, perceived stress, life satisfaction, psychological well-being, sleep quality, perceived social support, and social network. Results: A total of 1151 participants (mean [SD] age, 76.6 [7.8] years; 843 [73.2%] female) were randomized to the behavioral activation (n = 335), mindfulness (n = 460) or befriending (n = 356) group. Most were widowed or divorced (932 [81.0%]), had primary education or below (782 [67.9%]), and had 3 or more chronic diseases (505 [43.9%]). Following intention-to-treat principles, linear mixed-effects regression model analyses showed that loneliness measured by the UCLA Loneliness Scale was significantly reduced in the behavioral activation group (mean difference [MD], -1.96 [95% CI, -3.16 to -0.77] points; P < .001]) and in the mindfulness group (MD, -1.49 [95% CI, -2.60 to -0.37] points; P = .004) at 3 months compared with befriending. Loneliness measured by the De Jong Gierveld Loneliness Scale was not significantly reduced at 3 months in the behavioral activation group (MD, -0.06 [95% CI, -0.26 to 0.13] points; P > .99]) but was in the mindfulness group (MD, 0.22 [95% CI, 0.03 to 0.40] points; P = .01) at 3 months compared with befriending. In the behavioral activation and mindfulness groups, sleep quality improved compared with befriending, but perceived stress increased. Psychological well-being and perceived social support improved in the behavioral activation group. No statistically significant between-group differences were observed in depression, life satisfaction, or social network. Conclusion and relevance: In this randomized clinical trial, scalable psychosocial interventions delivered remotely by older laypersons appeared promising in reducing later life loneliness and addressing the pressing mental health challenges faced by aging populations and professional geriatric mental health workforce shortages. Further research should explore ways to maximize the clinical relevance and cost-effectiveness of these interventions. Trial registration: Chinese Clinical Trial Registry Identifier: ChiCTR2300072909.

JAMA network open · randomised controlled trial · 17 citationsread the source →

Xu HG, Eley R, Kynoch K, Tuckett A. (2022)MEDLINE-indexed journal, not yet read by usEmergency medicine Australasia : EMA · randomised controlled trial

Effects of mobile mindfulness on emergency department work stress: A randomised controlled trial.

Objective: High-occupational stress among ED staff has a detrimental impact on both staff wellness and patient care. The objective of the study is to determine whether 4 weeks of smartphone app-guided mindfulness practice reduces stress levels of ED staff. Methods: This two-arm randomised controlled trial was conducted in two Australian EDs in 2019-2020. Eligible participants were randomly assigned (1:1) to either an App group or a Wait to Treat group to practice daily 10 min app-guided mindfulness for 4 weeks. Online surveys were collected for both groups at three time periods: before (T1), immediately after (T2) and 3 months after cessation (T3). Then the Wait to Treat group received the same intervention, followed by surveys immediately after the intervention (T4) and 3 months later (T5). Primary outcome was measured using the Perceived Stress Scale. Secondary outcomes were measured using the Maslach Burnout Inventory (three subscales: emotional exhaustion, depersonalisation and personal accomplishment), Mindfulness Attention Awareness Scale and Warwick-Edinburgh Mental Well-being Scale. Both intention-to-treat and per-protocol analysis were performed. Repeated measurement data were analysed by the linear mixed model. Results: Of 148 enrolled participants 98 completed all the surveys, but only half (48%) reported continuous use of the app. Based on the results of the intention-to-treat analysis, there was a statistically significant improvement of perceived stress levels (F = 15.70, P < 0.001), all three components of burnout (emotional exhaustion [F = 14.22, P < 0.001], depersonalisation [F = 3.62, P = 0.030], personal accomplishment [F = 7.51, P < 0.001]), mindfulness (F = 8.83, P < 0.001) and wellbeing levels (F = 10.71, P < 0.001) from pre-intervention to 3 months later with small effect sizes. Conclusion: Results of the present study demonstrate that brief mindfulness training via innovative digital technology had a small positive effect in improving emergency staff stress, burnout, mindfulness and wellbeing.

Emergency medicine Australasia : EMA · randomised controlled trial · 21 citationsread the source →

Mazurek MO, Parker RA, Chan J, Kuhlthau K, Sohl K, ECHO Autism Collaborative. (2020)MEDLINE-indexed journal, not yet read by usJAMA pediatrics · randomised controlled trial

Effectiveness of the Extension for Community Health Outcomes Model as Applied to Primary Care for Autism: A Partial Stepped-Wedge Randomized Clinical Trial.

Importance: The Extension for Community Health Outcomes (ECHO) model is a widely adopted technology-based model for training primary care physicians and practitioners (PCPs) to care for patients with complex conditions. Despite its popularity, to our knowledge, direct effects of ECHO on clinical practice have not been tested in a large-scale study. Objective: To test the effectiveness of the ECHO model as applied to primary care for autism and whether it resulted in improved clinical practice, knowledge, and self-efficacy regarding autism screening and comorbidity management. Design, setting, and participants: Primary care physicians and practitioners were recruited to participate in a 6-month ECHO Autism program delivered by 1 of 10 academic medical center sites. A sequential, staggered rollout of ECHO Autism was delivered to 5 cohorts of participants (15 per site; 2 sites per cohort). Sites were randomized after recruitment to cohort/start time. Cohorts launched every 3 months. The ECHO Autism program used videoconferencing technology to connect community-based PCPs with interdisciplinary expert teams at academic medical centers. There were 148 participants (PCPs [family practice physicians, pediatricians, nurse practitioners, and physician assistants] providing outpatient services to underserved children) studied between December 2016 and November 2018. Interventions: The 6-month ECHO Autism program included twelve 2-hour sessions connecting PCP participants with an interdisciplinary expert team. Sessions included didactics, case-based learning, guided practice, and discussion. Main outcomes and measures: Coprimary outcomes were autism screening practices and comorbidity management (assessed by medical record review). Secondary outcomes were knowledge (assessed by direct testing) and self-efficacy (assessed by self-report survey). Assessments were conducted at baseline, mid-ECHO, post-ECHO, and follow-up (3 months after ECHO). Results: Ten sites were randomized to 1 of 5 cohorts. Participants were 82% female (n = 108), 76% white (n = 100), and 6% Hispanic or Latino (n = 8); the median age was 46 years (interquartile range, 37-55 years). Significant changes in autism screening and treatment of comorbidities in children with autism were not observed. Participants demonstrated significant improvements in knowledge (9%; 95% CI, 4-13; P < .001) and self-efficacy (29%; 95% CI, 25-32; P < .001). Conclusions and relevance: The ECHO model was developed to increase access to high-quality health care for underserved patients with complex conditions. Study results provide support for the model in improving clinician knowledge and confidence but little support for achieving practice change. Trial registration: ClinicalTrials.gov Identifier: NCT03677089.

JAMA pediatrics · randomised controlled trial · 63 citationsread the source →

Putensen C, Theuerkauf N, Zinserling J, Wrigge H, Pelosi P. (2009)MEDLINE-indexed journal, not yet read by usAnnals of internal medicine · meta-analysis

Meta-analysis: ventilation strategies and outcomes of the acute respiratory distress syndrome and acute lung injury.

Background: Trials have provided conflicting results regarding the effect of different ventilatory strategies on the outcomes of patients with the acute respiratory distress syndrome (ARDS) and acute lung injury. Purpose: To determine whether ventilation with low tidal volume (Vt) and limited airway pressure or higher positive end-expiratory pressure (PEEP) improves outcomes for patients with ARDS or acute lung injury. Data sources: Multiple computerized databases (through March 2009), reference lists of identified articles, and queries of principal investigators. No language restrictions were applied. Study selection: Randomized, controlled trials (RCTs) reporting mortality and comparing lower versus higher Vt ventilation, lower versus higher PEEP, or a combination of both in adults with ARDS or acute lung injury. Data extraction: Using a standard protocol, 2 reviewer teams assessed trial eligibility and abstracted data on quality of study design and conduct, population characteristics, intervention, co-interventions, and confounding variables. Data synthesis: 4 RCTs tested lower versus higher Vt ventilation at similar PEEP in 1149 patients, 3 RCTs compared lower versus higher PEEP at low Vt ventilation in 2299 patients, and 2 RCTs compared a combination of higher Vt and lower PEEP ventilation versus lower Vt and higher PEEP ventilation in 148 patients. Lower Vt ventilation reduced hospital mortality (odds ratio, 0.75 [95% CI, 0.58 to 0.96]; P = 0.02) compared with higher Vt ventilation at similar PEEP. Higher PEEP did not reduce hospital mortality (odds ratio, 0.86 [CI, 0.72 to 1.02]; P = 0.08) compared with lower PEEP using low Vt ventilation. Higher PEEP reduced the need for rescue therapy to prevent life-threatening hypoxemia (odds ratio, 0.51 [CI, 0.36 to 0.71]; P < 0.001) and death (odds ratio, 0.51 [CI, 0.36 to 0.71]; P < 0.001) in patients receiving rescue therapies. Limitations: Pooling according to similar ventilatory strategies resulted in few RCTs analyzed in each group. The benefit of low Vt is derived from only 1 study. Conclusion: Available evidence from a limited number of RCTs shows better outcomes with routine use of low Vt but not high PEEP ventilation in unselected patients with ARDS or acute lung injury. High PEEP may help to prevent life-threatening hypoxemia in selected patients.

Annals of internal medicine · meta-analysis · 245 citationsread the source →

Kessler D, Lewis G, Kaur S, Wiles N, King M, Weich S, Sharp DJ, Araya R, Hollinghurst S, Peters TJ. (2009)MEDLINE-indexed journal, not yet read by usLancet (London, England) · randomised controlled trial

Therapist-delivered Internet psychotherapy for depression in primary care: a randomised controlled trial.

Background: Despite strong evidence for its effectiveness, cognitive-behavioural therapy (CBT) remains difficult to access. Computerised programs have been developed to improve accessibility, but whether these interventions are responsive to individual needs is unknown. We investigated the effectiveness of CBT delivered online in real time by a therapist for patients with depression in primary care. Methods: In this multicentre, randomised controlled trial, 297 individuals with a score of 14 or more on the Beck depression inventory (BDI) and a confirmed diagnosis of depression were recruited from 55 general practices in Bristol, London, and Warwickshire, UK. Participants were randomly assigned, by a computer-generated code, to online CBT in addition to usual care (intervention; n=149) or to usual care from their general practitioner while on an 8-month waiting list for online CBT (control; n=148). Participants, researchers involved in recruitment, and therapists were masked in advance to allocation. The primary outcome was recovery from depression (BDI score <10) at 4 months. Analysis was by intention to treat. This trial is registered, number ISRCTN 45444578. Findings: 113 participants in the intervention group and 97 in the control group completed 4-month follow-up. 43 (38%) patients recovered from depression (BDI score <10) in the intervention group versus 23 (24%) in the control group at 4 months (odds ratio 2.39, 95% CI 1.23-4.67; p=0.011), and 46 (42%) versus 26 (26%) at 8 months (2.07, 1.11-3.87; p=0.023). Interpretation: CBT seems to be effective when delivered online in real time by a therapist, with benefits maintained over 8 months. This method of delivery could broaden access to CBT. Funding: BUPA Foundation.

Lancet (London, England) · randomised controlled trial · 214 citationsread the source →

Prevalence, determinants, and effect on quality of life of freezing of gait in Parkinson disease.

Importance: Freezing of gait (FOG) is a common axial symptom of Parkinson disease (PD). Objective: To determine the prevalence of FOG in a large group of PD patients, assess its relationship with quality of life and clinical and pharmacological factors, and explore its changes from the off to on conditions in patients with motor fluctuations. Design, setting, and participants: Cross-sectional survey of 683 patients with idiopathic PD. Scores for FOG were missing in 11 patients who were not included in the analysis. Patients were recruited from referral centers and general neurology clinics in public or private institutions in France. Exposure: Patients with FOG were identified as those with a score of 1 or greater on item 14 of the Unified Parkinson's Disease Rating Scale (UPDRS) in the on condition. Item 14 scores for FOG in the off condition were also collected in patients with fluctuating motor symptoms. Main outcomes and measures: Quality of life (measured by the 39-item Parkinson's Disease Questionnaire and 36-Item Short Form Health Survey), anxiety and depression (Hospital Anxiety and Depression Scale), clinical features (UPDRS), and drug consumption. Results: Of 672 PD patients, 257 reported FOG during the onstate (38.2%), which was significantly related to lower quality of life scores (P < .01). Freezing of gait was also correlated with longer PD duration (odds ratio, 1.92 [95% CI, 1.28-2.86]), higher UPDRS parts II and III scores (4.67 [3.21-6.78]), the presence of apathy (UPDRS item 4) (1.94 [1.33-2.82]), a higher levodopa equivalent daily dose (1.63 [1.09-2.43]), and more frequent exposure to antimuscarinics (3.07 [1.35-6.97]) (logistic regression). The FOG score improved from the off to on states in 148 of 174 patients with motor fluctuations (85.1%) and showed no change in 13.8%. The FOG score improved by more than 50% in 43.7% of patients. Greater improvement in the on state was observed in younger patients (r = -0.25; P < .01) with lower UPDRS II and III scores (r = -0.50; P < .01) and no antimuscarinic use (r = -0.21; P < .01). Conclusions and relevance: Freezing of gait in PD patients correlates with poor quality of life, disease severity, apathy, and exposure to antimuscarinics. Dopaminergic therapy improved FOG in most patients with motor fluctuations, especially younger ones with less severe disease and no antimuscarinic use. This finding suggests that quality of life is impaired in PD patients with FOG and that optimizing dopaminergic therapy and avoiding antimuscarinics should be considered.

JAMA neurology · cohort or longitudinal · 254 citationsread the source →

Goldstein BI, Velyvis VP, Parikh SV. (2006)MEDLINE-indexed journal, not yet read by usThe Journal of clinical psychiatry · cohort or longitudinal

The association between moderate alcohol use and illness severity in bipolar disorder: a preliminary report.

Objective: To examine the association of alcohol consumption with symptoms, illness course, and health care utilization among non-alcoholic patients with bipolar disorder. Method: Subjects were 148 patients with bipolar I or II disorder enrolled in a longitudinal study of cognitive-behavioral therapy versus psychoeducation. Subjects were 18 to 60 years old, in full or partial remission, and non-heavy drinkers with no history of substance use disorders. At least 4 weeks of consistent naturalistic treatment with mood stabilizer was required for enrollment. Measures included the Structured Clinical Interview for DSM-IV, the Hamilton Rating Scale for Depression, the Clinician-Administered Rating Scale for Mania, and the Khavari Alcohol Test. Data were gathered from July 2002 to December 2004. Results: Mean weekly alcoholic beverage consumption was minimal among both men (3.8 standard drinks, SD = 8.9) and women (1.2 standard drinks, SD = 1.9). Nonetheless, total alcohol consumption among men was associated with lifetime manic episodes (F = 10.2, df = 1, p = .003) and emergency department visits (F = 4.3, df = 1, p = .046). Spirits consumption among men was strongly associated with lifetime manic episodes (F = 81.8, df = 1, p < .001) and emergency department visits (F = 14.0, df = 1, p < .001). Among women, the frequency of alcohol consumption was associated with lifetime episodes of depression (F = 15.5, df = 1, p < .001) and hypomania (F = 4.8, df = 1, p < .03). Wine consumption among women was associated with lifetime hypomanic episodes (F = 13.6, df = 1, p < .001) and current manic symptoms (F = 4.0, df = 1, p < .05). Conclusion: Despite low volumes of consumption, alcohol was associated with measures of illness severity in bipolar disorder among both men and women. The adverse effects of alcohol on bipolar disorder may occur over a range of consumption, rather than being confined to heavy drinkers.

The Journal of clinical psychiatry · cohort or longitudinal · 48 citationsread the source →

Precision medicine for suicidality: from universality to subtypes and personalization.

Suicide remains a clear, present and increasing public health problem, despite being a potentially preventable tragedy. Its incidence is particularly high in people with overt or un(der)diagnosed psychiatric disorders. Objective and precise identification of individuals at risk, ways of monitoring response to treatments and novel preventive therapeutics need to be discovered, employed and widely deployed. We sought to investigate whether blood gene expression biomarkers for suicide (that is, a 'liquid biopsy' approach) can be identified that are more universal in nature, working across psychiatric diagnoses and genders, using larger cohorts than in previous studies. Such markers may reflect and/or be a proxy for the core biology of suicide. We were successful in this endeavor, using a comprehensive stepwise approach, leading to a wealth of findings. Steps 1, 2 and 3 were discovery, prioritization and validation for tracking suicidality, resulting in a Top Dozen list of candidate biomarkers comprising the top biomarkers from each step, as well as a larger list of 148 candidate biomarkers that survived Bonferroni correction in the validation step. Step 4 was testing the Top Dozen list and Bonferroni biomarker list for predictive ability for suicidal ideation (SI) and for future hospitalizations for suicidality in independent cohorts, leading to the identification of completely novel predictive biomarkers (such as CLN5 and AK2), as well as reinforcement of ours and others previous findings in the field (such as SLC4A4 and SKA2). Additionally, we examined whether subtypes of suicidality can be identified based on mental state at the time of high SI and identified four potential subtypes: high anxiety, low mood, combined and non-affective (psychotic). Such subtypes may delineate groups of individuals that are more homogenous in terms of suicidality biology and behavior. We also studied a more personalized approach, by psychiatric diagnosis and gender, with a focus on bipolar males, the highest risk group. Such a personalized approach may be more sensitive to gender differences and to the impact of psychiatric co-morbidities and medications. We compared testing the universal biomarkers in everybody versus testing by subtypes versus personalized by gender and diagnosis, and show that the subtype and personalized approaches permit enhanced precision of predictions for different universal biomarkers. In particular, LHFP appears to be a strong predictor for suicidality in males with depression. We also directly examined whether biomarkers discovered using male bipolars only are better predictors in a male bipolar independent cohort than universal biomarkers and show evidence for a possible advantage of personalization. We identified completely novel biomarkers (such as SPTBN1 and C7orf73), and reinforced previously known biomarkers (such as PTEN and SAT1). For diagnostic ability testing purposes, we also examined as predictors phenotypic measures as apps (for suicide risk (CFI-S, Convergent Functional Information for Suicidality) and for anxiety and mood (SASS, Simplified Affective State Scale)) by themselves, as well as in combination with the top biomarkers (the combination being our a priori primary endpoint), to provide context and enhance precision of predictions. We obtained area under the curves of 90% for SI and 77% for future hospitalizations in independent cohorts. Step 5 was to look for mechanistic understanding, starting with examining evidence for the Top Dozen and Bonferroni biomarkers for involvement in other psychiatric and non-psychiatric disorders, as a mechanism for biological predisposition and vulnerability. The biomarkers we identified also provide a window towards understanding the biology of suicide, implicating biological pathways related to neurogenesis, programmed cell death and insulin signaling from the universal biomarkers, as well as mTOR signaling from the male bipolar biomarkers. In particular, HTR2A increase coupled with ARRB1 and GSK3B decreases in expression in suicidality may provide a synergistic mechanistical corrective target, as do SLC4A4 increase coupled with AHCYL1 and AHCYL2 decrease. Step 6 was to move beyond diagnostics and mechanistical risk assessment, towards providing a foundation for personalized therapeutics. Items scored positive in the CFI-S and subtypes identified by SASS in different individuals provide targets for personalized (psycho)therapy. Some individual biomarkers are targets of existing drugs used to treat mood disorders and suicidality (lithium, clozapine and omega-3 fatty acids), providing a means toward pharmacogenomics stratification of patients and monitoring of response to treatment. Such biomarkers merit evaluation in clinical trials. Bioinformatics drug repurposing analyses with the gene expression biosignatures of the Top Dozen and Bonferroni-validated universal biomarkers identified novel potential therapeutics for suicidality, such as ebselen (a lithium mimetic), piracetam (a nootropic), chlorogenic acid (a polyphenol) and metformin (an antidiabetic and possible longevity promoting drug). Finally, based on the totality of our data and of the evidence in the field to date, a convergent functional evidence score prioritizing biomarkers that have all around evidence (track suicidality, predict it, are reflective of biological predisposition and are potential drug targets) brought to the fore APOE and IL6 from among the universal biomarkers, suggesting an inflammatory/accelerated aging component that may be a targetable common denominator.

Molecular psychiatry · 75 citationsread the source →

Marcos Nadal; Martin Skov (2018)MEDLINE-indexed journal, not yet read by usProceedings of the Royal Society B Biological Sciences · editorial or comment

The pleasure of art as a matter of fact

You have accessMoreSectionsView PDF ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InRedditEmail Cite this article Nadal Marcos and Skov Martin 2018The pleasure of art as a matter of factProc. R. Soc. B.2852017225220172252http://doi.org/10.1098/rspb.2017.2252SectionYou have accessCommentThe pleasure of art as a matter of fact Marcos Nadal Marcos Nadal http://orcid.org/0000-0002-9341-4688 Department of Psychology, University of the Balearic Islands, Palma de Mallorca 07122, Spain [email protected] Google Scholar Find this author on PubMed Search for more papers by this author and Martin Skov Martin Skov Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital Hvidovre, Copenhagen 2650, Denmark Center for Decision Neuroscience, Copenhagen Business School, Copenhagen 2000, Denmark Google Scholar Find this author on PubMed Search for more papers by this author Marcos Nadal Marcos Nadal http://orcid.org/0000-0002-9341-4688 Department of Psychology, University of the Balearic Islands, Palma de Mallorca 07122, Spain [email protected] Google Scholar Find this author on PubMed and Martin Skov Martin Skov Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital Hvidovre, Copenhagen 2650, Denmark Center for Decision Neuroscience, Copenhagen Business School, Copenhagen 2000, Denmark Google Scholar Find this author on PubMed Published:21 March 2018https://doi.org/10.1098/rspb.2017.2252All other forms of perception divide a man, because they are exclusively based either on the sensuous or on the intellectual part of his being; only the perception of the Beautiful makes something whole of him, because both his natures must accord with it.— Schiller, 1793–1795, Letters on the Aesthetic Education of Man, p. 138, Letter 27Can art make us better people? Better members of society? In her recent article, 'Pleasure junkies all around! Why it matters and why "the arts" might be the answer: a biopsychological perspective', Christensen [1] claims that engaging with art can promote healthy choices, choices that balance short-term pleasure goals with long-term general well-being. She suggests that many modern life conveniences, such as social media, computer games or online shopping, have the potential to turn us into 'pleasure junkies' because they maximize short-term pleasures. But art, Christensen argues, is a safe choice and a means to remedy this unhealthy addiction to pleasure. Christensen's argument is grounded on three claims about the sort of pleasure we get from art. First, in contrast to low-level pleasure, which Christensen conceives as 'a mere perceptual stimulation leading to a rewarding sensation (food, sex, etc.)' ([1], p. 2), pleasure from art is presented as a kind of higher-order pleasure that engages 'broader neural networks implied in the attribution of meaning' (p. 2), presumably leading to 'long-term maintenance of healthy bodily function' (p. 2). Second, 'the arts do not induce states of craving without fulfilment—as do activities with reinforcement schedules which are prone to create habits and addictions such as intermittent variable ratio or interval reinforcement schedules (e.g. social media, gambling, football, extreme sports, drugs' (p. 4). Third, 'the arts do not search for a perceptual "Bliss point" […]. They do not just repeat over and over again a sensory stimulus that excites the senses and induces craving for more of a "pleasurable itch" (e.g. sugar, sexualized body displays, certain musical lyrics, tones; i.e. a perceptual "bliss point")' (p. 4).The claim, in a nutshell, is that the pleasure induced by art is different to the pleasure induced by food, sex, sports or drugs, because it is related to the balanced activation of brain systems related to short-term pleasure and long-term wellbeing goals, because it does not induce craving, and because it is not aimed at a perceptual 'bliss point'. This distinct sort of pleasure, according to Christensen, makes it possible for the arts to thwart the pernicious effects that the unhealthy urges and cravings licensed by 'today's mainstream acceptance of pleasure-seeking behaviour' (p. 5) have on individuals' lives and on societies. Such sweeping statements about art, food, sex, sports and society as a whole merit close examination. Christensen's primary claim that the pleasure induced by art is of a special kind, different to the pleasure induced by other activities is not supported by current understanding of what pleasure is. It is, moreover, contradicted by abundant empirical evidence. This evidence shows that pleasures, whatever their source, owe to activity in the same mesocorticolimbic circuit [2] and are encoded as a common neural currency [3]. As Kent Berridge and Morten Kringelbach put it: 'the brain mechanisms involved in fundamental pleasures (food and sexual pleasures) overlap with those for higher-order pleasures (e.g. monetary, artistic, musical, altruistic and transcendent pleasures) […] From sensory pleasures and drugs of abuse […] to monetary, aesthetic and musical delights, all pleasures seem to involve the same hedonic brain systems' ([4], p. 481). Thus, there is no evidence for specific brain regions or neural circuits related to the pleasure from art. Rather, the appreciation of art relies on brain mechanisms that evolved to appraise the value of biologically relevant objects in relation to internal homeostatic states [5]: 'Emotional reactions to music, further, activate the same cortical, subcortical and autonomic circuits, which are considered as the essential survival circuits of biological organisms in general' ([6], p. 6). In sum, the evidence shows that pleasure elicited by music and other art forms is no different in genesis and function to the pleasure induced by food, drugs and sex [7,8]. This is a matter of fact, not opinion. What supports Christensen's argument if not empirical evidence? In our view, her argument for the distinctness of art-induced pleasure seems based upon an oversimplified and devaluing conception of the pleasures of sex, food and sports, and a very narrow notion of art and its function. Christensen presents food, sex and sports as meaningless low-level sources of pleasure, and the arts as privileged vehicles for meaningful experiences. It is the personal and meaningful engagement with art—Christensen suggests—that fosters a balanced activation of brain systems related to short-term pleasure and long-term well-being goals. However, rarely—if ever—are food, sex and sports meaningless rewarding sensations. Contrary to Christensen's definition on page 2 of her article, pleasure—even sensory pleasure—is not simply reward, and never simply a sensation [4]. Indulging in food, sex or sports are meaningful and personally significant experiences that are not a matter of mere physical sensation. The experience of pleasure from food and sex is shaped by context, knowledge, expectations, anticipations, attitudes and beliefs that bring meaning to them [9–11]. Sex can be meaningful because it signifies physical connection with one's loved one, because it is cheating on someone, or deemed a sin. Likewise, eating is not about obtaining low-level pleasure. What we eat, the way we eat, what we believe about what we eat, where and whom we eat with, imbue eating with individual and social meaning, and shape the actual pleasure of eating [12]. On the other hand, encounters with art are not necessarily meaningful [13,14]. Actually, there is nothing intrinsically meaningful about engaging with art. Many laypeople lack the knowledge schemata required to engage meaningfully with abstract, cubist or contemporary art [15,16]. There are plenty of artworks people do not find meaningful or pleasant. Meaning making is not a special feature of art; it is a general feature of our species's cognition [17,18]. We can endow virtually any aspect of reality with meaning: sex, food, sports, a urinal, the shape of a cloud, an averted glance, someone's absence. Christensen's argument also rests on a historically and culturally narrow conception of art and its function. Art is presented as a circumscribed category of activities that elicit a unique sort of pleasant experiences: — The arts are set of activities of a special kind that share certain defining features distinguishing them from other activities: 'the arts push boundaries, surprise, reveal and excite both artist and spectator' ([1], p. 4).— Art encounters are positive, leading to 'pleasurable chills' and pleasurable experiences of understanding: 'The moment of meaning-assignation, also called "mastering" or "understanding" an artwork, is therefore a pleasurable experience' ([1], p. 4).— The pleasure elicited by art is special, because it does not involve craving for intense peaks: 'The arts do not search for a perceptual "bliss point" […] They do not just repeat over and over a sensory stimulus that excites the senses and induces craving for more of a "pleasurable itch"' ([1], p. 4).This characterization of the arts substantially overlaps with the notion of 'fine arts'. The core features of this characterization were instituted in the eighteenth century, after European intellectuals grouped certain activities into a distinct and autonomous collection, labelled 'fine arts'. To make sense of and promote this grouping, it became imperative to identify a common essence setting art apart from other activities [19,20,21]. One of the most popular proposals was that only art could produce a special sort of pleasure, sophisticated and polite [19,21]—a conception stemming not from any understanding of physiology, but from mere speculation. This limited historical and cultural scope renders this conception of the arts unfit for behavioural or neuroscientific research [19]. The category 'the arts' should not be mistaken for a natural kind. It is a historical convention, and has no direct biological correspondence. Moreover, this conception of art that Christensen espouses does not apply to art as practised in non-Western societies [19,22]. It does not even apply to Western art before the eighteenth century or after the nineteenth century [19,20,21]. First, art does not necessarily evoke pleasurable experiences. There are abundant artworks intended to arouse negative emotions [19,23], and to portray physical and moral ugliness [24]. Understanding art is not necessarily a pleasant experience: it can be an angering, disgusting or upsetting one [25]. Second, many artworks actually exploit repetition, bliss points and craving [26]. Repetition is a fundamental design feature of music and other performance arts [27]: In Relation in Space (1976) Marina Abramovic and Ulay ran into each other repeatedly for an hour; Ravel's Bolero is a 17 min-long instance of melodic and rhythmic repetitiveness. Anticipation and craving for bliss points are also essential to music [28]. In fact, the enjoyment of music is linked to intense feelings of anticipation and expectation caused by dopamine activity in the caudate nucleus (also involved in the rewarding aspect of food) [29,30], and peak pleasure states (bliss points) [31], caused by the release of dopamine and opioids in the brain's reward system (also involved in cocaine induced euphoria) [29,30]. Given the available evidence, therefore, there is no reason to believe that the pleasure from art is special or unique [32].In sum, Christensen's claim for the distinctiveness of pleasure from art is contradicted by empirical evidence, and her argument for the beneficial effects of art rests upon disputed foundations. Art's capacity to promote healthier choices and make us better people that can contribute to a better society remains as unconfirmed today as it was when Schiller speculated on art's power to harmonize human's conflicting sensuous and formal impulses. Christensen's argument is problematic even if intended to highlight hypothetical possibilities. Arguments about hypothetical possibilities should still rely on valid premises, and scientific hypotheses should be grounded on evidence, or at least in line with it. Otherwise, they are merely unfounded speculations. Scientific aesthetics is only just finding its footing and its place within cognitive neuroscience [33,34]. If evidence is ignored or rejected because it does not fit preconceived notions about art and its function, scientific aesthetics will become only an arena to promote and legitimize personally appealing notions of art by applying a scientific gloss over them. A proper scientific study of art needs to be grounded on empirical evidence and strong arguments that follow from solid premises [35,36]. 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(doi:10.1016/j.plrev.2017.06.013) PubMed, ISI, Google Scholar Previous ArticleNext Article VIEW FULL TEXT DOWNLOAD PDF FiguresRelatedReferencesDetailsCited by Clemente A, Pearce M, Skov M and Nadal M (2021) Evaluative judgment across domains: Liking balance, contour, symmetry and complexity in melodies and visual designs, Brain and Cognition, 10.1016/j.bandc.2021.105729, 151, (105729), Online publication date: 1-Jul-2021. Chuan-Peng H, Huang Y, Eickhoff S, Peng K and Sui J (2020) Seeking the "Beauty Center" in the Brain: A Meta-Analysis of fMRI Studies of Beautiful Human Faces and Visual Art, Cognitive, Affective, & Behavioral Neuroscience, 10.3758/s13415-020-00827-z, 20:6, (1200-1215), Online publication date: 1-Dec-2020. Skov M and Nadal M (2020) A Farewell to Art: Aesthetics as a Topic in Psychology and Neuroscience, Perspectives on Psychological Science, 10.1177/1745691619897963, 15:3, (630-642), Online publication date: 1-May-2020. 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Proceedings of the Royal Society B Biological Sciences · editorial or comment · 24 citationsread the source →

Miller JW, Garrod MG, Allen LH, Haan MN, Green R. (2009)MEDLINE-indexed journal, not yet read by usThe American journal of clinical nutrition

Metabolic evidence of vitamin B-12 deficiency, including high homocysteine and methylmalonic acid and low holotranscobalamin, is more pronounced in older adults with elevated plasma folate.

Background: An analysis of data from the National Health and Nutrition Examination Survey indicated that in older adults exposed to folic acid fortification, the combination of low serum vitamin B-12 and elevated folate is associated with higher concentrations of homocysteine and methylmalonic acid and higher odds ratios for cognitive impairment and anemia than the combination of low vitamin B-12 and nonelevated folate. These findings await confirmation in other populations. Objective: The purpose was to compare metabolic indicators of vitamin B-12 status, cognitive function, and depressive symptoms among elderly Latinos with elevated and nonelevated plasma folate. Design: Cross-sectional data were analyzed for 1535 subjects (age: >or=60 y) from the Sacramento Area Latino Study on Aging. Subjects were divided into 4 groups on the basis of plasma vitamin B-12 (< or >or=148 pmol/L) and folate (<or= or >45.3 nmol/L). Homocysteine, methylmalonic acid, holotranscobalamin, ratio of holotranscobalamin to vitamin B-12, Modified Mini-Mental State Examination, delayed recall, and depressive symptom scores were compared between the groups. Results: Individuals with low vitamin B-12 and elevated folate (n = 22) had the highest concentrations of homocysteine and methylmalonic acid and the lowest concentration of holotranscobalamin and ratio of holotranscobalamin to vitamin B-12 when compared with all other groups (P <or= 0.003). No differences in Modified Mini-Mental State Examination, delayed recall, and depressive symptom scores were observed between the low vitamin B-12 and elevated-folate group compared with other groups. Conclusions: Low vitamin B-12 is associated with more pronounced metabolic evidence of vitamin B-12 deficiency when folate is elevated than when folate is not elevated. These data should be considered when assessing the potential costs, risks, and benefits of folic acid and vitamin B-12 fortification programs.

The American journal of clinical nutrition · 81 citationsread the source →

Sluiter F, Incollingo Rodriguez AC, Nephew BC, Cali R, Murgatroyd C, Santos HP. (2020)MEDLINE-indexed journal, not yet read by usNeurobiology of stress

Pregnancy associated epigenetic markers of inflammation predict depression and anxiety symptoms in response to discrimination.

Latina mothers, who have one of the highest fertility rates among ethnic groups in the United States (US), often experience discrimination. Psychosocial influences during pregnancy, such as discrimination stress, promotes inflammation. However, the role of epigenetic markers of inflammation as a mediator between, and predictor of, maternal discrimination stress and neuropsychiatric outcomes has not been extensively studied. The current study investigates the role of DNA methylation at FOXP3 Treg-cell-specific demethylated region (TSDR), as a marker of regulatory T (Treg) cells that are important negative regulators of inflammation, and the promoter of tumour necrosis factor-alpha (TNF-α) gene, an important pro-inflammatory cytokine, in relation to discrimination stress during pregnancy and depression and anxiety symptomatology. A sample of 148 Latina women residing in the US (mean age 27.6 years) were assessed prenatally at 24-32 weeks' gestation and 4-6 weeks postnatally for perceived discrimination exposure (Everyday Discrimination Scale, EDS), emotional distress (depression, anxiety, perinatal-specific depression), acculturation, and acculturative stress. DNA methylation levels at the FOXP3 and TNFα promoter regions from blood samples collected at the prenatal stage were assessed by bisulphite pyrosequencing. Regression analyses showed that prenatal EDS associated with postnatal emotional distress, depression and anxiety symptoms only in those individuals with higher than mean levels of FOXP3 TSDR and TNFα promoter methylation; no such significant associations were found in those with lower than mean levels of methylation for either. We further found that these relationships were mediated by TNFα only in those with high FOXP3 TSDR methylation, implying that immunosuppression via TNFα promoter methylation buffers the impact of discrimination stress on postpartum symptomatology. These results indicate that epigenetic markers of immunosuppression and inflammation play an important role in resilience or sensitivity, respectively, to prenatal stress.

Neurobiology of stress · 26 citationsread the source →

Robinson SM, Crozier SR, Harvey NC, Barton BD, Law CM, Godfrey KM, Cooper C, Inskip HM. (2015)MEDLINE-indexed journal, not yet read by usThe American journal of clinical nutrition

Modifiable early-life risk factors for childhood adiposity and overweight: an analysis of their combined impact and potential for prevention.

Background: Early life may be a "critical period" when appetite and regulation of energy balance are programmed, with lifelong consequences for obesity risk. Insight into the potential impact of modifying early-life risk factors on later obesity can be gained by evaluating their combined effects. Objective: The objective was to examine the relation between the number of early-life risk factors and obesity outcomes among children in a prospective birth cohort (Southampton Women's Survey). Design: Five risk factors were defined: maternal obesity [prepregnant body mass index (BMI; in kg/m(2)) >30], excess gestational weight gain (Institute of Medicine, 2009), smoking during pregnancy, low maternal vitamin D status (<64 nmol/L), and short duration of breastfeeding (none or <1 mo). Obesity outcomes examined when the children were aged 4 and 6 y were BMI, dual-energy X-ray absorptiometry-assessed fat mass, overweight, or obesity (International Obesity Task Force). Data were available for 991 mother-child pairs, with children born between 1998 and 2003. Results: Of the children, 148 (15%) had no early-life risk factors, 330 (33%) had 1, 296 (30%) had 2, 160 (16%) had 3, and 57 (6%) had 4 or 5. At both 4 and 6 y, there were positive graded associations between number of early-life risk factors and each obesity outcome (all P < 0.001). After taking account of confounders, the relative risk of being overweight or obese for children who had 4 or 5 risk factors was 3.99 (95% CI: 1.83, 8.67) at 4 y and 4.65 (95% CI: 2.29, 9.43) at 6 y compared with children who had none (both P < 0.001). Conclusions: Having a greater number of early-life risk factors was associated with large differences in adiposity and risk of overweight and obesity in later childhood. These findings suggest that early intervention to change these modifiable risk factors could make a significant contribution to the prevention of childhood obesity.

The American journal of clinical nutrition · 85 citationsread the source →

Efficacy and Safety of Deep Brain Stimulation in Tourette Syndrome: The International Tourette Syndrome Deep Brain Stimulation Public Database and Registry.

Importance: Collective evidence has strongly suggested that deep brain stimulation (DBS) is a promising therapy for Tourette syndrome. Objective: To assess the efficacy and safety of DBS in a multinational cohort of patients with Tourette syndrome. Design, setting, and participants: The prospective International Deep Brain Stimulation Database and Registry included 185 patients with medically refractory Tourette syndrome who underwent DBS implantation from January 1, 2012, to December 31, 2016, at 31 institutions in 10 countries worldwide. Exposures: Patients with medically refractory symptoms received DBS implantation in the centromedian thalamic region (93 of 163 [57.1%]), the anterior globus pallidus internus (41 of 163 [25.2%]), the posterior globus pallidus internus (25 of 163 [15.3%]), and the anterior limb of the internal capsule (4 of 163 [2.5%]). Main outcomes and measures: Scores on the Yale Global Tic Severity Scale and adverse events. Results: The International Deep Brain Stimulation Database and Registry enrolled 185 patients (of 171 with available data, 37 females and 134 males; mean [SD] age at surgery, 29.1 [10.8] years [range, 13-58 years]). Symptoms of obsessive-compulsive disorder were present in 97 of 151 patients (64.2%) and 32 of 148 (21.6%) had a history of self-injurious behavior. The mean (SD) total Yale Global Tic Severity Scale score improved from 75.01 (18.36) at baseline to 41.19 (20.00) at 1 year after DBS implantation (P < .001). The mean (SD) motor tic subscore improved from 21.00 (3.72) at baseline to 12.91 (5.78) after 1 year (P < .001), and the mean (SD) phonic tic subscore improved from 16.82 (6.56) at baseline to 9.63 (6.99) at 1 year (P < .001). The overall adverse event rate was 35.4% (56 of 158 patients), with intracranial hemorrhage occurring in 2 patients (1.3%), infection in 4 patients with 5 events (3.2%), and lead explantation in 1 patient (0.6%). The most common stimulation-induced adverse effects were dysarthria (10 [6.3%]) and paresthesia (13 [8.2%]). Conclusions and relevance: Deep brain stimulation was associated with symptomatic improvement in patients with Tourette syndrome but also with important adverse events. A publicly available website on outcomes of DBS in patients with Tourette syndrome has been provided.

JAMA neurology · 173 citationsread the source →

Jansen WJ, Janssen O, Tijms BM, Vos SJB, Ossenkoppele R, Visser PJ, Amyloid Biomarker Study Group, Aarsland D, Alcolea D, Altomare D, von Arnim C, Baiardi S, Baldeiras I, Barthel H, Bateman RJ, Van Berckel B, Binette AP, Blennow K, Boada M, Boecker H, Bottlaender M, den Braber A, Brooks DJ, Van Buchem MA, Camus V, Carill JM, Cerman J, Chen K, Chételat G, Chipi E, Cohen AD, Daniels A, Delarue M, Didic M, Drzezga A, Dubois B, Eckerström M, Ekblad LL, Engelborghs S, Epelbaum S, Fagan AM, Fan Y, Fladby T, Fleisher AS, Van der Flier WM, Förster S, Fortea J, Frederiksen KS, Freund-Levi Y, Frings L, Frisoni GB, Fröhlich L, Gabryelewicz T, Gertz HJ, Gill KD, Gkatzima O, Gómez-Tortosa E, Grimmer T, Guedj E, Habeck CG, Hampel H, Handels R, Hansson O, Hausner L, Hellwig S, Heneka MT, Herukka SK, Hildebrandt H, Hodges J, Hort J, Huang CC, Iriondo AJ, Itoh Y, Ivanoiu A, Jagust WJ, Jessen F, Johannsen P, Johnson KA, Kandimalla R, Kapaki EN, Kern S, Kilander L, Klimkowicz-Mrowiec A, Klunk WE, Koglin N, Kornhuber J, Kramberger MG, Kuo HC, Van Laere K, Landau SM, Landeau B, Lee DY, de Leon M, Leyton CE, Lin KJ, Lleó A, Löwenmark M, Madsen K, Maier W, Marcusson J, Marquié M, Martinez-Lage P, Maserejian N, Mattsson N, de Mendonça A, Meyer PT, Miller BL, Minatani S, Mintun MA, Mok VCT, Molinuevo JL, Morbelli SD, Morris JC, Mroczko B, Na DL, Newberg A, Nobili F, Nordberg A, Olde Rikkert MGM, de Oliveira CR, Olivieri P, Orellana A, Paraskevas G, Parchi P, Pardini M, Parnetti L, Peters O, Poirier J, Popp J, Prabhakar S, Rabinovici GD, Ramakers IH, Rami L, Reiman EM, Rinne JO, Rodrigue KM, Rodríguez-Rodriguez E, Roe CM, Rosa-Neto P, Rosen HJ, Rot U, Rowe CC, Rüther E, Ruiz A, Sabri O, Sakhardande J, Sánchez-Juan P, Sando SB, Santana I, Sarazin M, Scheltens P, Schröder J, Selnes P, Seo SW, Silva D, Skoog I, Snyder PJ, Soininen H, Sollberger M, Sperling RA, Spiru L, Stern Y, Stomrud E, Takeda A, Teichmann M, Teunissen CE, Thompson LI, Tomassen J, Tsolaki M, Vandenberghe R, Verbeek MM, Verhey FRJ, Villemagne V, Villeneuve S, Vogelgsang J, Waldemar G, Wallin A, Wallin ÅK, Wiltfang J, Wolk DA, Yen TC, Zboch M, Zetterberg H. (2022)MEDLINE-indexed journal, not yet read by usJAMA neurology

Prevalence Estimates of Amyloid Abnormality Across the Alzheimer Disease Clinical Spectrum.

Importance: One characteristic histopathological event in Alzheimer disease (AD) is cerebral amyloid aggregation, which can be detected by biomarkers in cerebrospinal fluid (CSF) and on positron emission tomography (PET) scans. Prevalence estimates of amyloid pathology are important for health care planning and clinical trial design. Objective: To estimate the prevalence of amyloid abnormality in persons with normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia and to examine the potential implications of cutoff methods, biomarker modality (CSF or PET), age, sex, APOE genotype, educational level, geographical region, and dementia severity for these estimates. Design, setting, and participants: This cross-sectional, individual-participant pooled study included participants from 85 Amyloid Biomarker Study cohorts. Data collection was performed from January 1, 2013, to December 31, 2020. Participants had normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia. Normal cognition and subjective cognitive decline were defined by normal scores on cognitive tests, with the presence of cognitive complaints defining subjective cognitive decline. Mild cognitive impairment and clinical AD dementia were diagnosed according to published criteria. Exposures: Alzheimer disease biomarkers detected on PET or in CSF. Main outcomes and measures: Amyloid measurements were dichotomized as normal or abnormal using cohort-provided cutoffs for CSF or PET or by visual reading for PET. Adjusted data-driven cutoffs for abnormal amyloid were calculated using gaussian mixture modeling. Prevalence of amyloid abnormality was estimated according to age, sex, cognitive status, biomarker modality, APOE carrier status, educational level, geographical location, and dementia severity using generalized estimating equations. Results: Among the 19 097 participants (mean [SD] age, 69.1 [9.8] years; 10 148 women [53.1%]) included, 10 139 (53.1%) underwent an amyloid PET scan and 8958 (46.9%) had an amyloid CSF measurement. Using cohort-provided cutoffs, amyloid abnormality prevalences were similar to 2015 estimates for individuals without dementia and were similar across PET- and CSF-based estimates (24%; 95% CI, 21%-28%) in participants with normal cognition, 27% (95% CI, 21%-33%) in participants with subjective cognitive decline, and 51% (95% CI, 46%-56%) in participants with mild cognitive impairment, whereas for clinical AD dementia the estimates were higher for PET than CSF (87% vs 79%; mean difference, 8%; 95% CI, 0%-16%; P = .04). Gaussian mixture modeling-based cutoffs for amyloid measures on PET scans were similar to cohort-provided cutoffs and were not adjusted. Adjusted CSF cutoffs resulted in a 10% higher amyloid abnormality prevalence than PET-based estimates in persons with normal cognition (mean difference, 9%; 95% CI, 3%-15%; P = .004), subjective cognitive decline (9%; 95% CI, 3%-15%; P = .005), and mild cognitive impairment (10%; 95% CI, 3%-17%; P = .004), whereas the estimates were comparable in persons with clinical AD dementia (mean difference, 4%; 95% CI, -2% to 9%; P = .18). Conclusions and relevance: This study found that CSF-based estimates using adjusted data-driven cutoffs were up to 10% higher than PET-based estimates in people without dementia, whereas the results were similar among people with dementia. This finding suggests that preclinical and prodromal AD may be more prevalent than previously estimated, which has important implications for clinical trial recruitment strategies and health care planning policies.

JAMA neurology · 243 citationsread the source →

Kuper LE, Stewart S, Preston S, Lau M, Lopez X. (2020)MEDLINE-indexed journal, not yet read by usPediatrics

Body Dissatisfaction and Mental Health Outcomes of Youth on Gender-Affirming Hormone Therapy.

Objectives: Our first aim was to examine baseline differences in body dissatisfaction, depression, and anxiety symptoms by gender, age, and Tanner (ie, pubertal) stage. Our second aim was to test for changes in youth symptoms over the first year of receiving gender-affirming hormone therapy. Our third aim was to examine potential differences in change over time by demographic and treatment characteristics. Youth experiences of suicidal ideation, suicide attempt, and nonsuicidal self-injury (NSSI) are also reported. Methods: Participants (n = 148; ages 9-18 years; mean age 14.9 years) were receiving gender-affirming hormone therapy at a multidisciplinary program in Dallas, Texas (n = 25 puberty suppression only; n = 123 feminizing or masculinizing hormone therapy). Participants completed surveys assessing body dissatisfaction (Body Image Scale), depression (Quick Inventory of Depressive Symptoms), and anxiety (Screen for Child Anxiety Related Emotional Disorders) at initial presentation to the clinic and at follow-up. Clinicians completed the Quick Inventory of Depressive Symptoms and collected information on youth experiences of suicidal ideation, suicide attempt, and NSSI. Results: Affirmed males reported greater depression and anxiety at baseline, but these differences were small (P < .01). Youth reported large improvements in body dissatisfaction (P < .001), small to moderate improvements in self-report of depressive symptoms (P < .001), and small improvements in total anxiety symptoms (P < .01). No demographic or treatment-related characteristics were associated with change over time. Lifetime and follow-up rates were 81% and 39% for suicidal ideation, 16% and 4% for suicide attempt, and 52% and 18% for NSSI, respectively. Conclusions: Results provide further evidence of the critical role of gender-affirming hormone therapy in reducing body dissatisfaction. Modest initial improvements in mental health were also evident.

Pediatrics · 155 citationsread the source →

Friedman J, Reed P, Sharplin P, Kelly P. (2012)MEDLINE-indexed journal, not yet read by usChild abuse & neglect

Primary prevention of pediatric abusive head trauma: a cost audit and cost-utility analysis.

Objectives: To obtain comprehensive, reliable data on the direct cost of pediatric abusive head trauma in New Zealand, and to use this data to evaluate the possible cost-benefit of a national primary prevention program. Methods: A 5 year cohort of infants with abusive head trauma admitted to hospital in Auckland, New Zealand was reviewed. We determined the direct costs of hospital care (from hospital and Ministry of Health financial records), community rehabilitation (from the Accident Compensation Corporation), special education (from the Ministry of Education), investigation and child protection (from the Police and Child Protective Services), criminal trials (from the Police, prosecution and defence), punishment of offenders (from the Department of Corrections) and life-time care for moderate or severe disability (from the Accident Compensation Corporation). Analysis of the possible cost-utility of a national primary prevention program was undertaken, using the costs established in our cohort, recent New Zealand national data on the incidence of pediatric abusive head trauma, international data on quality of life after head trauma, and published international literature on prevention programs. Results: There were 52 cases of abusive head trauma in the sample. Hospital costs totaled $NZ2,433,340, child protection $NZ1,560,123, police investigation $NZ1,842,237, criminal trials $NZ3,214,020, punishment of offenders $NZ4,411,852 and community rehabilitation $NZ2,895,848. Projected education costs for disabled survivors were $NZ2,452,148, and the cost of projected lifetime care was $NZ33,624,297. Total costs were $NZ52,433,864, averaging $NZ1,008,344 per child. Cost-utility analysis resulted in a strongly positive economic argument for primary prevention, with expected case scenarios showing lowered net costs with improved health outcomes. Conclusions: Pediatric abusive head trauma is very expensive, and on a conservative estimate the costs of acute hospitalization represent no more than 4% of lifetime direct costs. If shaken baby prevention programs are effective, there is likely to be a strong economic argument for their implementation. This study also provides robust data for future cost-benefit analysis in the field of abusive head trauma prevention.

Child abuse & neglect · 31 citationsread the source →