Association of sugar intake from different sources with cardiovascular disease incidence in the prospective cohort of UK Biobank participants.

BACKGROUND: The relation between incident cardiovascular disease (CVD) and sugar might not only depend on the quantity consumed but also on its source. This study aims to assess the association between various sources of dietary sugars and CVD incidence in the prospective population-based UK Biobank cohort. METHODS: A total of 176,352 participants from the UK Biobank with at least one web-based dietary questionnaire (Oxford WebQ) for assessment of sugar intake were included in this study. Mean follow-up lasted 10.9 years (standard deviation 2.0), with 12,355 incident cases of CVD. To determine the association of free sugar (FS) and intrinsic sugar intake with incident CVD, hazard ratios (HR) were calculated using Cox proportional hazard regression models. FS intake from beverages and beverage subtypes, i.e., soda/fruit drinks, juice, milk-based drinks, and tea/coffee, as well as from solid foods and solids subtypes, i.e., treats, cereals, toppings, and sauces, was included as penalised cubic splines. RESULTS: FS intake showed a J-shaped relationship with CVD risk, reaching the lowest HR (HR-nadir) at 9 %E, while intrinsic sugars displayed a non-linear descending association, with the HR-nadir at 14 %E. FS in beverages demonstrated a significant linear relationship with CVD with the HR-nadir at 3 %E, while FS in solids exhibited a significant non-linear U-shaped relationship with the HR-nadir at 7 %E. Within the beverage subtypes, soda/fruit drinks displayed a linear relationship, as did to a lesser extent FS in milk-based drinks and tea/coffee. Juice, however, showed a significant U-shaped relationship with CVD risk. Among solid foods subtypes, FS in treats had a J-shaped relation with the HR-nadir at 5 %E, and FS in cereals showed a linear association. In comparison, FS in toppings and sauces exhibited a U-shaped pattern with HR-nadir at 3 %E and 0.5 %E, respectively. All major results remained similar in various sensitivity analyses and were more robust for ischemic heart disease compared to stroke. CONCLUSIONS: Only some sources of FS exhibit a robust positive association with CVD incidence. Public health efforts aiming at the reduction of CVD risk should prioritise the reduction of sugary beverages with an emphasis on soda/fruit drinks.

Randomized controlled trial of individualized arousal-biofeedback for children and adolescents with disruptive behavior disorders (DBD).

Disruptive behavior disorders [including conduct disorder (CD) and oppositional defiant disorder (ODD)] are common childhood and adolescent psychiatric conditions often linked to altered arousal. The recommended first-line treatment is multi-modal therapy and includes psychosocial and behavioral interventions. Their modest effect sizes along with clinically and biologically heterogeneous phenotypes emphasize the need for innovative personalized treatment targeting impaired functions such as arousal dysregulation. A total of 37 children aged 8-14 years diagnosed with ODD/CD were randomized to 20 sessions of individualized arousal biofeedback using skin conductance levels (SCL-BF) or active treatment as usual (TAU) including psychoeducation and cognitive-behavioral elements. The primary outcome was the change in parents´ ratings of aggressive behavior measured by the Modified Overt Aggression Scale. Secondary outcome measures were subscales from the Child Behavior Checklist, the Inventory of Callous-Unemotional traits, and the Reactive-Proactive Aggression Questionnaire. The SCL-BF treatment was neither superior nor inferior to the active TAU. Both groups showed reduced aggression after treatment with small effects for the primary outcome and large effects for some secondary outcomes. Importantly, successful learning of SCL self-regulation was related to reduced aggression at post-assessment. Individualized SCL-BF was not inferior to active TAU for any treatment outcome with improvements in aggression. Further, participants were on average able to self-regulate their SCL, and those who best learned self-regulation showed the highest clinical improvement, pointing to specificity of SCL-BF regulation for improving aggression. Further studies with larger samples and improved methods, for example by developing BF for mobile use in ecologically more valid settings are warranted.

[Gut Microbiota and Autism Spectrum Disorders: An Overview of Correlations and Potential Implications for Therapeutic Interventions]. / Darmmikrobiota und Autismus-Spektrum-Störungen: Ein Überblick zu Zusammenhängen und möglichen Implikationen für therapeutische Interventionen.

Gut Microbiota and Autism Spectrum Disorders: An Overview of Correlations and Potential Implications for Therapeutic Interventions Abstract: At the beginning of research on microbiota, researchers focused mainly on the role of microbiota dysbiosis in the development of gastrointestinal diseases. However, over the last years, researchers have also identified correlations with other physical processes and neuropsychiatric diseases such as autism spectrum disorder. These correlations are believed to be at least partly mediated through the brain-gut-microbiome axis. An altered composition of microbiota in patients with autism spectrum disorder was detected compared to healthy controls. Today, the discussion centers around a possible systemic impact of the metabolites of some microbiota or microbiota-induced chronic inflammatory processes on the brain (mediated through the brain-gut-microbiome axis) as an underlying mechanism. Still, the specific underlying mechanisms remain largely unknown, so conclusions on therapeutic implications are difficult to determine. Here, we describe some promising approaches to improving autistic behavior through dietary changes, the use of prebiotics and probiotics, stool transplantation from healthy controls, and restricted absorbance of certain metabolites. We need further clinical studies of high quality to fully understand the pathophysiology of autism spectrum disorder and to improve diagnostic and therapeutic strategies.

[Beyond NICE: Updated Systematic Review on the Current Evidence of Using Puberty Blocking Pharmacological Agents and Cross-Sex-Hormones in Minors with Gender Dysphoria]. / Beyond NICE: Aktualisierte systematische Übersicht zur Evidenzlage der Pubertätsblockade und Hormongabe bei Minderjährigen mit Geschlechtsdysphorie.

Beyond NICE: Updated Systematic Review on the Current Evidence of Using Puberty Blocking Pharmacological Agents and Cross-Sex-Hormones in Minors with Gender Dysphoria Abstract: Objective: The suppression of physiological puberty using puberty-blocking pharmacological agents (PB) and prescribing cross-sex hormones (CSH) to minors with gender dysphoria (GD) is a current matter of discussion, and in some cases, PB and CSH are used in clinical practice for this particular population. Two systematic reviews (one on PB, one on CSH treatment) by the British National Institute for Clinical Excellence (NICE) from 2020 indicated no clear clinical benefit of such treatments regarding critical outcome variables. In particular, these two systematic NICE reviews on the use of PB and CSH in minors with GD detected no clear improvements of GD symptoms. Moreover, the overall scientific quality of the available evidence, as discussed within the above-mentioned two NICE reviews, was classified as "very low certainty" regarding modified GRADE criteria. Method: The present systematic review presents an updated literature search on this particular topic (use of PB and CSH in minors with GD) following NICE principles and PICO criteria for all relevant new original research studies published since the release of the two above-mentioned NICE reviews (updated literature search period was July 2020-August 2023). Results: The newly conducted literature search revealed no newly published original studies targeting NICE-defined critical and important outcomes and the related use of PB in minors with GD following PICO criteria. For CSH treatment, we found two new studies that met PICO criteria, but these particular two studies had low participant numbers, yielded no significant additional clear evidence for specific and clearly beneficial effects of CSH in minors with GD, and could be classified as "low certainty" tfollowing modified GRADE criteria. Conclusions: The currently available studies on the use of PB and CSH in minors with GD have significant conceptual and methodological flaws. The available evidence on the use of PB and CSH in minors with GD is very limited and based on only a few studies with small numbers, and these studies have problematic methodology and quality. There also is a lack of adequate and meaningful long-term studies. Current evidence doesn't suggest that GD symptoms and mental health significantly improve when PB or CSH are used in minors with GD. Psychotherapeutic interventions to address and reduce the experienced burden can become relevant in children and adolescents with GD. If the decision to use PB and/or CSH is made on an individual case-by-case basis and after a complete and thorough mental health assessment, potential treatment of possibly co-occurring mental health problems as well as after a thoroughly conducted and carefully executed individual risk-benefit evaluation, doing so as part of clinical studies or research projects, as currently done in England, can be of value in terms of generation of new research data. The electronic supplement (ESM) 1 is an adapted and abreviated English version of this work.

Processing of social and monetary rewards in autism spectrum disorders.

BACKGROUND: Reward processing has been proposed to underpin the atypical social feature of autism spectrum disorder (ASD). However, previous neuroimaging studies have yielded inconsistent results regarding the specificity of atypicalities for social reward processing in ASD. AIMS: Utilising a large sample, we aimed to assess reward processing in response to reward type (social, monetary) and reward phase (anticipation, delivery) in ASD. METHOD: Functional magnetic resonance imaging during social and monetary reward anticipation and delivery was performed in 212 individuals with ASD (7.6-30.6 years of age) and 181 typically developing participants (7.6-30.8 years of age). RESULTS: Across social and monetary reward anticipation, whole-brain analyses showed hypoactivation of the right ventral striatum in participants with ASD compared with typically developing participants. Further, region of interest analysis across both reward types yielded ASD-related hypoactivation in both the left and right ventral striatum. Across delivery of social and monetary reward, hyperactivation of the ventral striatum in individuals with ASD did not survive correction for multiple comparisons. Dimensional analyses of autism and attention-deficit hyperactivity disorder (ADHD) scores were not significant. In categorical analyses, post hoc comparisons showed that ASD effects were most pronounced in participants with ASD without co-occurring ADHD. CONCLUSIONS: Our results do not support current theories linking atypical social interaction in ASD to specific alterations in social reward processing. Instead, they point towards a generalised hypoactivity of ventral striatum in ASD during anticipation of both social and monetary rewards. We suggest this indicates attenuated reward seeking in ASD independent of social content and that elevated ADHD symptoms may attenuate altered reward seeking in ASD.

Placebo and nocebo responses in randomised, controlled trials of medications for ADHD: a systematic review and meta-analysis.

The nature and magnitude of placebo and nocebo responses to ADHD medications and the extent to which response to active medications and placebo are inter-correlated is unclear. To assess the magnitude of placebo and nocebo responses to ADHD and their association with active treatment response. We searched literature until June 26, 2019, for published/unpublished double-blind, randomised placebo-controlled trials (RCTs) of ADHD medication. Authors were contacted for additional data. We assessed placebo effects on efficacy and nocebo effects on tolerability using random effects meta-analysis. We assessed the association of study design and patient features with placebo/nocebo response. We analysed 128 RCTs (10,578 children/adolescents and 9175 adults) and found significant and heterogenous placebo effects for all efficacy outcomes, with no publication bias. The placebo effect was greatest for clinician compared with other raters. We found nocebo effects on tolerability outcomes. Efficacy outcomes from most raters showed significant positive correlations between the baseline to endpoint placebo effects and the baseline to endpoint drug effects. Placebo and nocebo effects did not differ among drugs. Baseline severity and type of rating scale influenced the findings. Shared non-specific factors influence response to both placebo and active medication. Although ADHD medications are superior to placebo, and placebo treatment in clinical practice is not feasible, clinicians should attempt to incorporate factors associated with placebo effects into clinical care. Future studies should explore how such effects influence response to medication treatment. Upon publication, data will be available in Mendeley Data: PROSPERO (CRD42019130292).

Association of alcohol types, coffee and tea intake with mortality: prospective cohort study of UK Biobank participants.

The present study examines how alcohol intake from wine and non-wine alcoholic beverages (non-wine) in g/d, as well as cups of coffee and tea included as continuous covariates and mutually adjusted are associated with all-cause, cancer, non-cancer and CVD mortality. Consumption was assessed in 354 386 participants of the UK Biobank cohort who drank alcohol at least occasionally and survived at least 2 years after baseline with 20 201 deaths occurring over 4·2 million person-years. Hazard ratios (HR) for mortality were assessed with Cox proportional hazard regression models and beverage intake fitted as penalised cubic splines. A significant U-shaped association was detected between wine consumption and all-cause, non-cancer and CVD mortality. Wine consumption with lowest risk of death (nadir) ranged from 19 to 23 g alcohol/d in all participants and both sexes separately. In contrast, non-wine intake was significantly and positively associated in a dose-dependent manner with all mortality types studied except for CVD in females and with the nadir between 0 and 12 g alcohol/d. In all participants, the nadir for all-cause mortality was 2 cups coffee/d with non-coffee drinkers showing a slightly increased risk of death. Tea consumption was significantly and negatively associated with all mortality types in both sexes. Taken together, light to moderate consumption of wine but not non-wine is associated with decreased all-cause and non-cancer mortality. A minor negative association of coffee consumption with mortality cannot be excluded whereas tea intake is associated with a consistently decreased risk of all mortality types studied.

Association of all-cause mortality with sugar intake from different sources in the prospective cohort of UK Biobank participants.

The present study elucidates the association of intrinsic sugars and free sugars (FS) from all relevant sources with all-cause mortality in the prospective UK Biobank cohort. Sugar intake was assessed in 186 811 UK Biobank participants who completed at least one web-based 24-h dietary recall (Oxford WebQ). Cox proportional hazard regression models for all-cause mortality were used with sugar intake from different sources included as penalised cubic splines to allow non-linear predictor effects. Over a mean follow-up of 12·3 years, 8576 (4·6 %) deaths occurred. FS but not intrinsic sugars were significantly and dose-dependently associated with hazard ratio (HR) for all-cause mortality. The association with all-cause mortality was significant and dose dependent for FS in beverages, but not in solids with the mean (CI) HR at 50 g/d v. 0 g/d consumption at 1·10, 95 % CI (1·07, 1·14) and 1·01, 95 % CI (0·98, 1·03), respectively. Within the beverages subcategories, a significant dose-dependent association with mortality was detected for FS in soda/fruit drinks and milk-based drinks whereas this relation was NS for FS in pure juice and tea/coffee. FS in four different subtypes of solids, i.e. treats, cereals, toppings and sauces, were not positively associated with all-cause mortality. Major findings were robust in sensitivity analyses. In conclusion, only some FS sources were associated with all-cause mortality. Interventions targeting FS subtypes might be most effective concerning mortality if focused on the reduction of soda/fruit drinks and milk-based sugary drinks; however, the present results need to be confirmed by independent studies.

Association of sugar intake from different sources with incident depression in the prospective cohort of UK Biobank participants.

PURPOSE: To elucidate the association of different sources of free sugars (FS) and intrinsic sugars with depression risk in the prospective population-based UK Biobank cohort. METHODS: Sugar consumption was assessed in 188,426 participants (age range: 39-72 years, 54.4% female) with at least one web-based dietary questionnaire (Oxford WebQ). The hazard ratios (HR) for incident depression were assessed with Cox proportional hazard regression models including sugar intake from different sources as penalized cubic splines to allow non-linear predictor effects. Over a mean follow-up of 12.3 (standard deviation 1.8) years, 5410 incident depression cases occurred. RESULTS: FS intake was significantly associated with depression risk in an ascending approximately linear way with the lowest HR observed at 9% total energy (%E). In contrast, consumption of intrinsic sugars was not significantly related with incident depression. FS in beverages were significantly associated with depression risk in an ascending approximately linear way with the lowest HR at 4%E whereas no association was found for FS in solids. Concerning beverage types, FS in soda/fruit drinks, milk-based drinks, and tea/coffee were significantly and positively related to depression risk whereas the association was U-shaped for juice. Major findings were robust in sensitivity analyses. CONCLUSION: Only some sources of FS are positively associated with incident depression. Public health initiatives targeting FS subtypes might be most effective concerning depression risk if focused on the reduction of sugary beverages and more specifically soda/fruit drinks, milk-based drinks, and tea/coffee.

Mapping Research Domain Criteria using a transdiagnostic mini-RDoC assessment in mental disorders: a confirmatory factor analysis.

This study aimed to build on the relationship of well-established self-report and behavioral assessments to the latent constructs positive (PVS) and negative valence systems (NVS), cognitive systems (CS), and social processes (SP) of the Research Domain Criteria (RDoC) framework in a large transnosological population which cuts across DSM/ICD-10 disorder criteria categories. One thousand four hundred and thirty one participants (42.1% suffering from anxiety/fear-related, 18.2% from depressive, 7.9% from schizophrenia spectrum, 7.5% from bipolar, 3.4% from autism spectrum, 2.2% from other disorders, 18.4% healthy controls, and 0.2% with no diagnosis specified) recruited in studies within the German research network for mental disorders for the Phenotypic, Diagnostic and Clinical Domain Assessment Network Germany (PD-CAN) were examined with a Mini-RDoC-Assessment including behavioral and self-report measures. The respective data was analyzed with confirmatory factor analysis (CFA) to delineate the underlying latent RDoC-structure. A revised four-factor model reflecting the core domains positive and negative valence systems as well as cognitive systems and social processes showed a good fit across this sample and showed significantly better fit compared to a one factor solution. The connections between the domains PVS, NVS and SP could be substantiated, indicating a universal latent structure spanning across known nosological entities. This study is the first to give an impression on the latent structure and intercorrelations between four core Research Domain Criteria in a transnosological sample. We emphasize the possibility of using already existing and well validated self-report and behavioral measurements to capture aspects of the latent structure informed by the RDoC matrix.

Association of sugar intake from different sources with incident dementia in the prospective cohort of UK Biobank participants.

BACKGROUND: Dementia is a common disease with around 55 million cases worldwide. Therefore, dietary changes and lifestyle interventions are important approaches to delay the progress of a decline in cognitive function. The study aims to explore the association of various sources of free sugars (FS) and intrinsic sugars with dementia risk in the prospective population-based UK Biobank cohort. METHODS: Sugar consumption was assessed in 186,622 UK Biobank participants with at least one web-based dietary questionnaire (Oxford WebQ). Over a mean follow-up of 10.6 (standard deviation 1.1) years, 1498 incident dementia cases occurred. The hazard ratios (HR) for incident dementia were assessed with Cox proportional hazard regression models including sugar intake from different sources as penalized cubic splines to allow for non-linear predictor effects. RESULTS: The intake of FS and intrinsic sugar was significantly associated with dementia risk in a J-shaped fashion with the HR-nadir observed at 9% and 8% total energy (%E), respectively. FS in beverages were significantly associated with dementia risk in an ascending approximately linear way, whereas no significant association was found for FS in solids. Assessing beverage subtypes, FS in soda/fruit drinks, milk-based drinks and to a lesser extent in juice were significantly and positively related to dementia risk, whereas no association was found for FS in tea/coffee. The association between sugar subtype consumption and dementia risk remained consistent in most sensitivity analyses but changed from a J-shape to a more linear shape when the analysis was restricted to participants with at least two Oxford WebQs. CONCLUSIONS: A linear-shaped association between sugar subtype intake and dementia risk is most consistently found for FS in beverages and more specifically for FS in soda/fruit drinks, as well as in milk-based drinks.

Personalized at-home neurofeedback compared to long-acting methylphenidate in children with ADHD: NEWROFEED, a European randomized noninferiority trial.

BACKGROUND: Neurofeedback is considered a promising intervention for the treatment of attention-deficit hyperactivity disorder (ADHD). NEWROFEED is a prospective, multicentre, randomized (3:2), reference drug-controlled trial in children with ADHD aged between 7 and 13 years. The main objective of NEWROFEED was to demonstrate the noninferiority of personalized at-home neurofeedback (NF) training versus methylphenidate in the treatment of children with ADHD. METHODS: The NF group (n = 111) underwent eight visits and two treatment phases of 16 to 20 at-home sessions with down-training of the theta/beta ratio (TBR) for children with high TBR and enhancing the sensorimotor rhythm (SMR) for the others. The control group (n = 67) received optimally titrated long-acting methylphenidate. The primary endpoint was the change between baseline and endpoint in the Clinician ADHD-RS-IV total score in the per-protocol population (90 NF/59 controls). TRIAL REGISTRATION: US National Institute of Health, ClinicalTrials.gov #NCT02778360. RESULTS: Our study failed to demonstrate noninferiority of NF versus methylphenidate (mean between-group difference 8.09 90% CI [8.09; 10.56]). However, both treatment groups showed significant pre-post improvements in core ADHD symptoms and in a broader range of problems. Reduction in the Clinician ADHD-RS-IV total score between baseline and final visit (D90) was 26.7% (SMD = 0.89) in the NF and 46.9% (SMD = 2.03) in the control group. NF effects increased whereas those of methylphenidate were stable between intermediate and final visit. CONCLUSIONS: Based on clinicians' reports, the effects of at-home NF were inferior to those of methylphenidate as a stand-alone treatment.

Lifespan adversities affect neural correlates of behavioral inhibition in adults.

Introduction: Growing evidence suggests that adverse experiences have long-term effects on executive functioning and underlying neural circuits. Previous work has identified functional abnormalities during inhibitory control in frontal brain regions in individuals exposed to adversities. However, these findings were mostly limited to specific adversity types such as maltreatment and prenatal substance abuse. Methods: We used data from a longitudinal birth cohort study (n = 121, 70 females) to investigate the association between adversities and brain responses during inhibitory control. At the age of 33 years, all participants completed a stop-signal task during fMRI and an Adult Self-Report scale. We collected seven prenatal and postnatal adversity measures across development and performed a principal component analysis to capture common variations across those adversities, which resulted in a three-factor solution. Multiple regression analysis was performed to identify links between adversities and brain responses during inhibitory control using the identified adversity factors to show the common effect and single adversity measures to show the specific contribution of each adversity. To find neural correlates of current psychopathology during inhibitory control, we performed additional regression analyses using Adult Self-Report subscales. Results: The first adversity factor reflecting prenatal maternal smoking and postnatal psychosocial adversities was related to higher activation during inhibitory control in bilateral inferior frontal gyri, insula, anterior cingulate cortex, and middle temporal gyri. Similar results were found for the specific contribution of the adversities linked to the first adversity factor. In contrast, we did not identify any significant association between brain responses during inhibitory control and the second adversity factor reflecting prenatal maternal stress and obstetric risk or the third adversity factor reflecting lower maternal sensitivity. Higher current depressive symptoms were associated with higher activation in the bilateral insula and anterior cingulate cortex during inhibitory control. Conclusion: Our findings extended previous work and showed that early adverse experiences have a long-term effect on the neural circuitry of inhibitory control in adulthood. Furthermore, the overlap between neural correlates of adversity and depressive symptomatology suggests that adverse experiences might increase vulnerability via neural alterations, which needs to be investigated by future longitudinal research.

Association of Maternal Smoking during Pregnancy with Neurophysiological and ADHD-Related Outcomes in School-Aged Children.

Data of a longitudinal cohort study were analyzed to investigate the association between prenatal tobacco exposure and electroencephalographical (EEG) power spectrum in healthy, school-aged children as well as its relationship with attention deficit hyperactivity disorder (ADHD)-related symptoms. Group comparisons (exposed, non-exposed) were performed to test whether prenatal tobacco exposure was associated with brain activity and ADHD symptoms, with adjustments made for covariates including child's sex, child's age, maternal age, maternal smoking habit before pregnancy, alcohol consumption during pregnancy, gestation age, and maternal psychopathology. Tobacco-exposed children showed higher brain activity in the delta and theta frequency bands. This effect was independent of the considered covariates. However, the effects on hyperactivity were found to significantly depend on maternal age and alcohol consumption during pregnancy, but not on the amount of exposure. In summary, smoking during pregnancy significantly affected the resting-state brain activity in children, independent of socio-demographic factors, indicating potential long-lasting effects on brain development. Its impact on ADHD-related behavior was shown to be influenced by socio-demographic confounding factors, such as maternal alcohol consumption and the age of the mother.

The importance of high quality real-life social interactions during the COVID-19 pandemic.

The coronavirus pandemic has brought about dramatic restrictions to real-life social interactions and a shift towards more online social encounters. Positive social interactions have been highlighted as an important protective factor, with previous studies suggesting an involvement of the amygdala in the relationship between social embeddedness and well-being. The present study investigated the effect of the quality of real-life and online social interactions on mood, and explored whether this association is affected by an individual's amygdala activity. Sixty-two participants of a longitudinal study took part in a one-week ecological momentary assessment (EMA) during the first lockdown, reporting their momentary well-being and their engagement in real-life and online social interactions eight times per day (N ~ 3000 observations). Amygdala activity was assessed before the pandemic during an emotion-processing task. Mixed models were calculated to estimate the association between social interactions and well-being, including two-way interactions to test for the moderating effect of amygdala activity. We found a positive relationship between real-life interactions and momentary well-being. In contrast, online interactions had no effect on well-being. Moreover, positive real-life social interactions augmented this social affective benefit, especially in individuals with higher amygdala being more sensitive to the interaction quality. Our findings demonstrate a mood-lifting effect of positive real-life social interactions during the pandemic, which was dependent on amygdala activity before the pandemic. As no corresponding effect was found between online social interactions and well-being, it can be concluded that increased online social interactions may not compensate for the absence of real-life social interactions.

Association of Proton Pump Inhibitor Use With Risk of Acquiring Drug-Resistant Enterobacterales.

Importance: Proton-pump inhibitors (PPIs) have been associated with the risk of colonization with drug-resistant bacteria; however, possible confounding by lifestyle-associated factors and disease severity casts doubt on this association, and whether the risk is dose dependent is not known. Objectives: To assess the association between PPI use and the risk of acquiring drug-resistant Enterobacterales and to examine interactions with possible microbiome-altering agents. Design, Setting, and Participants: This nested case-control study involved 2239 hospitalized adult (aged ≥18 years) patients identified from the microbiology laboratory database of Amsterdam University Medical Centers between December 31, 2018, and January 6, 2021. Patients in the case group had newly detected extended-spectrum ß-lactamase (ESBL)- or carbapenemase-producing Enterobacterales (identified by clinical specimens). Risk-set sampling was used to assign patients with negative results for ESBL- and carbapenemase-producing Enterobacterales to the control group, who were then matched on a 5:1 ratio with patients in the case group by age and culture date. A second validation case-control study included matched pairs (1:1 ratio; 94 in each group) of patients who were prospectively enrolled. Exposures: Proton pump inhibitor use and clinical data at 30 days (primary exposure) and 90 days (secondary exposure) before the date of culture. Main Outcomes and Measures: Adjusted incidence rate ratios (aIRRs) of ESBL- or carbapenemase-producing Enterobacterales acquisition by PPI dose and time risk windows (30 days for the primary outcome and 90 days for the secondary outcome) were estimated using conditional logistic regression models. Results: Among 2239 hospitalized patients (51.1% male; mean [SD] age, 60.9 [16.7] years), 374 were in the case group (51.6% male; mean [SD] age, 61.1 [16.5] years) and 1865 were in the matched control group (51.0% male; mean [SD] age, 60.9 [16.7] years). The aIRR for PPI use overall was 1.48 (95% CI, 1.15-1.91) at 30 days. Sensitivity analyses and the analysis of the pair-matched study with prospectively enrolled patients (aIRR, 2.96, 95% CI, 1.14-7.74) yielded similar results; findings were consistent in subgroups and corroborated by a negative-control exposure analysis. No association with microbiome-disturbing agents was found; laxatives and antibiotics were independently associated with a more than 2-fold increase in the risk of acquisition (antibiotics: aIRR, 2.78 [95% CI, 2.14-3.59]; laxatives: aIRR, 2.26 [95% CI. 1.73-2.94]). Conclusions and Relevance: In this study, after careful control for confounding and sensitivity analyses, PPI use was associated with increases in the risk of acquiring ESBL- or carbapenemase-producing Enterobacterales among adult hospitalized patients. These findings emphasize the need for judicious use of PPIs.

Limited usefulness of neurocognitive functioning indices as predictive markers for treatment response to methylphenidate or neurofeedback@home in children and adolescents with ADHD.

Introduction: Earlier studies exploring the value of executive functioning (EF) indices for assessing treatment effectiveness and predicting treatment response in attention-deficit/hyperactivity disorder (ADHD) mainly focused on pharmacological treatment options and revealed rather heterogeneous results. Envisioning the long-term goal of personalized treatment selection and intervention planning, this study comparing methylphenidate treatment (MPH) and a home-based neurofeedback intervention (NF@Home) aimed to expand previous findings by assessing objective as well as subjectively reported EF indices and by analyzing their value as treatment and predictive markers. Methods: Children and adolescents (n = 146 in the per protocol sample) aged 7-13 years with a formal diagnosis of an inattentive or combined presentation of ADHD were examined. We explored the EF performance profile using the Conners Continuous Performance Task (CPT) and the BRIEF self-report questionnaire within our prospective, multicenter, randomized, reference drug-controlled NEWROFEED study with sites in five European countries (France, Spain, Switzerland, Germany, and Belgium). As primary outcome for treatment response, the clinician-rated ADHD Rating Scale-IV was used. Patients participating in this non-inferiority trial were randomized to either NF@home (34-40 sessions of TBR or SMR NF depending on the pre-assessed individual alpha peak frequency) or MPH treatment (ratio: 3:2). Within a mixed-effects model framework, analyses of change were calculated to explore the predictive value of neurocognitive indices for ADHD symptom-related treatment response. Results: For a variety of neurocognitive indices, we found a significant pre-post change during treatment, mainly in the MPH group. However, the results of the current study reveal a rather limited prognostic value of neurocognitive indices for treatment response to either NF@Home or MPH treatment. Some significant effects emerged for parent-ratings only. Discussion: Current findings indicate a potential value of self-report (BRIEF global score) and some objectively measured neurocognitive indices (CPT commission errors and hit reaction time variability) as treatment markers (of change) for MPH. However, we found a rather limited prognostic value with regard to predicting treatment response not (yet) allowing recommendation for clinical use. Baseline symptom severity was revealed as the most relevant predictor, replicating robust findings from previous studies.

Association of Alcohol Types, Coffee, and Tea Intake with Risk of Dementia: Prospective Cohort Study of UK Biobank Participants.

The prevalence of dementia is increasing globally and is linked to obesity and unfavorable dietary habits. The present study analyses the association of alcohol intake from wine and non-wine alcoholic beverages (non-wine) in g/d, as well as coffee and tea in cups/d, with incident dementia. Over 4.2 million person-years, 4270 dementia cases occurred in 351,436 UK Biobank participants. Hazard ratios (HRs) for incident dementia were defined with Cox proportional hazard regression models in which beverage intake was fitted as penalized cubic splines. Wine intake showed a significant U-shaped association with the lowest risk for incident dementia (nadir) ranging from 21 to 23 g alcohol/d in all participants and in males. In contrast, non-wine consumption was significantly and dose-dependently associated with incident dementia, and the nadir was found at 0 g alcohol/d. Coffee consumption was not related to dementia risk, while moderate-to-high tea intake was negatively associated with incident dementia. Taken together, the current study shows on a population level that moderate consumption of wine and moderate-to-high tea intake is associated with a decreased risk of incident dementia. In contrast, non-wine is positively related to dementia risk in a linear fashion, and no clear association is found for coffee.

Neurostructural traces of early life adversities: A meta-analysis exploring age- and adversity-specific effects.

Early life adversities (ELAs) are associated with an increased risk of psychopathology, with studies suggesting a relation to structural brain alterations. Given the recently growing evidence of ELA effects on brain structure, an updated summary is highly warranted. Therefore, anatomical likelihood estimation was used to conduct a coordinate-based meta-analysis of gray matter volume (GMV) alterations associated with ELAs, including sub-analyses for different age groups and maltreatment as specific ELA-type. The analyses uncovered a convergence of pooled ELA-effects on GMV in the right hippocampus and amygdala and the left inferior frontal gyrus, age-specific effects for the right amygdala and hippocampus in children and adolescents, and maltreatment-specific effects for the right perigenual anterior cingulate cortex in adults. These results reveal a possible underlying commonality in the impact of adversity and also point to specific age and maltreatment effects. They suggest neural markers of ELAs in regions involved in socio-emotional functioning and stress regulation, with the potential to be used as targets for interventions designed to buffer or reverse harmful ELA-effects.

Exploring psychophysiological indices of disruptive behavior disorders and their subtypes of aggression.

BACKGROUND: Psychophysiological measures of arousal are often considered as potential biomarkers for disruptive behavior disorder (DBD). Nevertheless, the evidence is mixed, possibly reflecting the heterogeneity of DBD and different subtypes of aggression. Additionally, arousal measures of the central nervous system (e.g. electroencephalogram: EEG) are underrepresented compared to peripheral ones (heart rate: HR; skin conductance: SC). METHODS: We recorded HR, SC, and EEG (frequency band power at three electrodes Fz, Cz, Pz) in 49 participants with DBD, and 15 typically developing peers during two resting state and an emotional task condition. Group differences were assessed by a repeated measure ANOVA and regression analyses were applied to evaluate subtype-specific patterns. RESULTS: Our results showed higher mean HR activity in DBD participants, which was however driven by medicated participants and no significant group differences were found for SC. Interestingly, a significant group x frequency band interaction emerged for the EEG. DBD youth showed lower alpha activity. Regression analyses showed that higher theta and lower alpha band activity were related to more general aggression scores and higher delta and lower beta activity predicted proactive aggression. CONCLUSIONS: The lack of robust and significant differences for peripheral measurements (HR and SC) fits with previous mixed findings for externalizing disorders. Our results suggest that EEG measurements might be more sensitive to detect group differences and higher delta and lower beta activity might represent an index of a proactive subtype of aggression.