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The heterogeneity of chronic post-COVID neuropsychiatric symptoms (PCNPS), especially after infection by the Omicron strain, has not been adequately explored.
Aims
To explore the clustering pattern of chronic PCNPS in a cohort of patients having their first COVID infection during the ‘Omicron wave’ and discover phenotypes of patients based on their symptoms’ patterns using a pre-registered protocol.
Method
We assessed 1205 eligible subjects in Hong Kong using app-based questionnaires and cognitive tasks.
Results
Partial network analysis of chronic PCNPS in this cohort produced two major symptom clusters (cognitive complaint–fatigue and anxiety–depression) and a minor headache–dizziness cluster, like our pre-Omicron cohort. Participants with high numbers of symptoms could be further grouped into two distinct phenotypes: a cognitive complaint–fatigue predominant phenotype and another with symptoms across multiple clusters. Multiple logistic regression showed that both phenotypes were predicted by the level of pre-infection deprivation (adjusted P-values of 0.025 and 0.0054, respectively). The severity of acute COVID (adjusted P = 0.023) and the number of pre-existing medical conditions predicted only the cognitive complaint–fatigue predominant phenotype (adjusted P = 0.003), and past suicidal ideas predicted only the symptoms across multiple clusters phenotype (adjusted P < 0.001). Pre-infection vaccination status did not predict either phenotype.
Conclusions
Our findings suggest that we should pursue a phenotype-driven approach with holistic biopsychosocial perspectives in disentangling the heterogeneity under the umbrella of chronic PCNPS. Management of patients complaining of chronic PCNPS should be stratified according to their phenotypes. Clinicians should recognise that depression and anxiety cannot explain all chronic post-COVID cognitive symptoms.
New Zealand and Australian governments rely heavily on voluntary industry initiatives to improve population nutrition, such as voluntary front-of-pack nutrition labelling (Health Star Rating [HSR]), industry-led food advertising standards, and optional food reformulation programmes. Research in both countries has shown that food companies vary considerably in their policies and practices on nutrition(1). We aimed to determine if a tailored nutrition support programme for food companies improved their nutrition policies and practices compared with control companies who were not offered the programme. REFORM was a 24-month, two-country, cluster-randomised controlled trial. 132 major packaged food/drink manufacturers (n=96) and fast-food companies (n=36) were randomly assigned (2:1 ratio) to receive a 12-month tailored support programme or to the control group (no intervention). The intervention group was offered a programme designed and delivered by public health academics comprising regular meetings, tailored company reports, and recommendations and resources to improve product composition (e.g., reducing nutrients of concern through reformulation), nutrition labelling (e.g., adoption of HSR labels), marketing to children (reducing the exposure of children to unhealthy products and brands) and improved nutrition policy and corporate sustainability reporting. The primary outcome was the nutrient profile (measured using HSR) of company food and drink products at 24 months. Secondary outcomes were the nutrient content (energy, sodium, total sugar, and saturated fat) of company products, display of HSR labels on packaged products, company nutrition-related policies and commitments, and engagement with the intervention. Eighty-eight eligible intervention companies (9,235 products at baseline) were invited to participate, of whom 21 accepted and were enrolled in the REFORM programme (delivered between September 2021 and December 2022). Forty-four companies (3,551 products at baseline) were randomised to the control arm. At 24 months, the model-adjusted mean HSR of intervention company products was 2.58 compared to 2.68 for control companies, with no significant difference between groups (mean difference -0.10, 95% CI -0.40 to 0.21, p-value 0.53). A per protocol analysis of intervention companies who enrolled in the programme compared to control companies with no major protocol violation also found no significant difference (2.93 vs 2.64, mean difference 0.29, 95% CI -0.13 to 0.72, p-value 0.18). We found no significant differences between the intervention and control groups in any secondary outcome, except in total sugar (g/100g) where the sugar content of intervention company products was higher than that of control companies (12.32 vs 6.98, mean difference 5.34, 95% CI 1.73 to 8.96, p-value 0.004). The per-protocol analysis for sugar did not show a significant difference (10.47 vs 7.44, mean difference 3.03, 95% CI -0.48 to 6.53, p-value 0.09).In conclusion, a 12-month tailored nutrition support for food companies did not improve the nutrient profile of company products.
Existing panel studies on the relationships between cognition and depressive symptoms did not systematically separate between- and within-person components, with measurement time lags that are too long for precise assessment of dynamic within-person relationships.
Aims
To investigate the bidirectional relationships between cognition and depressive symptoms and examine the effects of sociodemographic characteristics and lifestyle factors via random-intercept, cross-lagged panel modelling (RI-CLPM) in middle-aged and older adults.
Method
The sample comprised 24 425 community-based residents aged 45 years or above, recruited via five waves of the China Health and Retirement Longitudinal Study (2011–2020). Cognition was evaluated using the Telephone Interview of Cognition Status, and depressive symptoms were assessed by the ten-item Center for Epidemiologic Studies Depression Scale. RI-CLPM included sociodemographic and lifestyle factors as time-invariant and -varying covariates. Subgroup analysis was conducted across gender, age groups and urban/rural regions.
Results
RI-CLPM showed a superior fit to cross-lagged panel models. Male, higher education, married, urban region, non-smoking, currently working and participation in social activities were linked with better cognition and fewer depressive symptoms. Overall, cognition and depressive symptoms showed significant and negative bidirectional cross-lagged effects over time. Despite similar cross-lagged effects across gender, subgroup analysis across urbanicity found that cross-lagged effects were not significant in urban regions.
Conclusions
The present study provided nuanced results on negative bidirectional relationships between cognition and depressive symptoms in Chinese middle-aged and older adults. Our results highlight the health disparities in cognitive and emotional health across urbanicity and age groups.
Interfacility patient transfers contribute to the regional spread of multidrug-resistant organisms (MDROs). We evaluated whether transfer patterns of inpatients with similar characteristics to carbapenem-resistant Enterobacterales (CRE) case-patients (CRE surrogates) better reflect hospital-level CRE burden than traditionally used populations.
Design:
We determined the risk factors for subsequent hospital admission using demographic and clinical information from Tennessee Department of Health tracked CRE case-patients from July 2015 to September 2019. Risk factors were used to identify CRE surrogates among inpatients in the 2018 Tennessee Hospital Discharge Data System (HDDS). Transfer networks of CRE surrogates, Medicare/TennCare beneficiaries, and all-inpatients with ≤365 days of intervening community stays were compared with the transfer networks of CRE case-patients in 2019. The associations between hospital-level CRE prevalence and hospitals’ incoming transfer volumes from each network were assessed using negative binomial regression models.
Results:
Eight risk factors for subsequent hospital admission were identified from 2,518 CRE case-patients, which were used to match CRE case-patients with HDDS inpatients, resulting in 10,069 surrogate patients. CRE surrogate network showed more structural similarities with the CRE case-patient network than with the all-inpatient and Medicare/TennCare networks. A 33% increase in hospitals’ CRE prevalence in 2019 was associated with each doubling of incoming transfer of CRE surrogates in 2018 (adjusted Risk Ratio [aRR] 1.33, 95%CI: 1.1, 1.59), higher than all-inpatient (aRR 1.27, 95% CI: 1.08, 1.51) and Medicare/TennCare networks (aRR 1.21, 95% CI: 1.02, 1.44).
Conclusions:
Surrogate transfer patterns were associated with hospital-level CRE prevalence, highlighting their value in MDRO containment and prevention.
It remains unclear which individuals with subthreshold depression benefit most from psychological intervention, and what long-term effects this has on symptom deterioration, response and remission.
Aims
To synthesise psychological intervention benefits in adults with subthreshold depression up to 2 years, and explore participant-level effect-modifiers.
Method
Randomised trials comparing psychological intervention with inactive control were identified via systematic search. Authors were contacted to obtain individual participant data (IPD), analysed using Bayesian one-stage meta-analysis. Treatment–covariate interactions were added to examine moderators. Hierarchical-additive models were used to explore treatment benefits conditional on baseline Patient Health Questionnaire 9 (PHQ-9) values.
Results
IPD of 10 671 individuals (50 studies) could be included. We found significant effects on depressive symptom severity up to 12 months (standardised mean-difference [s.m.d.] = −0.48 to −0.27). Effects could not be ascertained up to 24 months (s.m.d. = −0.18). Similar findings emerged for 50% symptom reduction (relative risk = 1.27–2.79), reliable improvement (relative risk = 1.38–3.17), deterioration (relative risk = 0.67–0.54) and close-to-symptom-free status (relative risk = 1.41–2.80). Among participant-level moderators, only initial depression and anxiety severity were highly credible (P > 0.99). Predicted treatment benefits decreased with lower symptom severity but remained minimally important even for very mild symptoms (s.m.d. = −0.33 for PHQ-9 = 5).
Conclusions
Psychological intervention reduces the symptom burden in individuals with subthreshold depression up to 1 year, and protects against symptom deterioration. Benefits up to 2 years are less certain. We find strong support for intervention in subthreshold depression, particularly with PHQ-9 scores ≥ 10. For very mild symptoms, scalable treatments could be an attractive option.
When conducting a systematic review, screening the vast body of literature to identify the small set of relevant studies is a labour-intensive and error-prone process. Although there is an increasing number of fully automated tools for screening, their performance is suboptimal and varies substantially across review topic areas. Many of these tools are only trained on small datasets, and most are not tested on a wide range of review topic areas. This study presents two systematic review datasets compiled from more than 8600 systematic reviews and more than 540000 abstracts covering 51 research topic areas in health and medical research. These datasets are the largest of their kinds to date. We demonstrate their utility in training and evaluating language models for title and abstract screening. Our dataset includes detailed metadata of each review, including title, background, objectives and selection criteria. We demonstrated that a small language model trained on this dataset with additional metadata has excellent performance with an average recall above 95% and specificity over 70% across a wide range of review topic areas. Future research can build on our dataset to further improve the performance of fully automated tools for systematic review title and abstract screening.
The negative predictive value of blaCTX-M on BCID2 for ceftriaxone resistance in E. coli and K. pneumoniae group was 97% and 94%, respectively. Creation of a genotypic antibiogram led to updated local guidance for clinicians to utilize for empiric treatment of Enterobacterales bloodstream infections identified via rapid diagnostics.
Future events can spring to mind unbidden in the form of involuntary mental images also known as ‘flashforwards’, which are deemed important for understanding and treating emotional distress. However, there has been little exploration of this form of imagery in youth, and even less so in those with high psychopathology vulnerabilities (e.g. due to developmental differences associated with neurodiversity or maltreatment).
Aims:
We aimed to test whether flashforwards are heightened (e.g. more frequent and emotional) in autistic and maltreatment-exposed adolescents relative to typically developing adolescents. We also explored their associations with anxiety/depression symptoms.
Method:
A survey including measures of flashforward imagery and mental health was completed by a group of adolescents (n=87) aged 10–16 (and one of their caregivers) who met one of the following criteria: (i) had a diagnosis of autism spectrum disorder; (ii) a history of maltreatment; or (ii) no autism/maltreatment.
Results:
Flashforwards (i) were often of positive events and related to career, education and/or learning; with phenomenological properties (e.g. frequency and emotionality) that were (ii) not significantly different between groups; but nevertheless (iii) associated with symptoms of anxiety across groups (particularly for imagery emotionality), even after accounting for general trait (non-future) imagery vividness.
Conclusions:
As a modifiable cognitive risk factor, flashforward imagery warrants further consideration for understanding and improving mental health in young people. This implication may extend to range of developmental backgrounds, including autism and maltreatment.
Many preoperative urine cultures are of low value and may even lead to patient harms. This study sought to understand practices around ordering preoperative urine cultures and prescribing antibiotic treatment.
We interviewed participants using a qualitative semi-structured interview guide. Collected data was coded inductively and with the Dual Process Model (DPM) using MAXQDA software. Data in the “Testing Decision-Making” code was further reviewed using the concept of perceived risk as a sensitizing concept.
Results:
We identified themes relating to surgeons’ concerns about de-implementing preoperative urine cultures to detect asymptomatic bacteriuria (ASB) in patients undergoing non-urological procedures: (1) anxiety and uncertainty surrounding missing infection signs spanned surgical specialties, (2) there were perceived risks of negative consequences associated with omitting urine cultures and treatment prior to specific procedure sites and types, and additionally, (3) participants suggested potential routes for adjusting these perceived risks to facilitate de-implementation acceptance. Notably, participants suggested that leadership support and peer engagement could help improve surgeon buy-in.
Conclusions:
Concerns about perceived risks sometimes outweigh the evidence against routine preoperative urine cultures to detect ASB. Evidence from trusted peers may improve openness to de-implementing preoperative urine cultures.
Auditory verbal hallucinations (AVHs) in schizophrenia have been suggested to arise from failure of corollary discharge mechanisms to correctly predict and suppress self-initiated inner speech. However, it is unclear whether such dysfunction is related to motor preparation of inner speech during which sensorimotor predictions are formed. The contingent negative variation (CNV) is a slow-going negative event-related potential that occurs prior to executing an action. A recent meta-analysis has revealed a large effect for CNV blunting in schizophrenia. Given that inner speech, similar to overt speech, has been shown to be preceded by a CNV, the present study tested the notion that AVHs are associated with inner speech-specific motor preparation deficits.
Objectives
The present study aimed to provide a useful framework for directly testing the long-held idea that AVHs may be related to inner speech-specific CNV blunting in patients with schizophrenia. This may hold promise for a reliable biomarker of AVHs.
Methods
Hallucinating (n=52) and non-hallucinating (n=45) patients with schizophrenia, along with matched healthy controls (n=42), participated in a novel electroencephalographic (EEG) paradigm. In the Active condition, they were asked to imagine a single phoneme at a cue moment while, precisely at the same time, being presented with an auditory probe. In the Passive condition, they were asked to passively listen to the auditory probes. The amplitude of the CNV preceding the production of inner speech was examined.
Results
Healthy controls showed a larger CNV amplitude (p = .002, d = .50) in the Active compared to the Passive condition, replicating previous results of a CNV preceding inner speech. However, both patient groups did not show a difference between the two conditions (p > .05). Importantly, a repeated measure ANOVA revealed a significant interaction effect (p = .007, ηp2 = .05). Follow-up contrasts showed that healthy controls exhibited a larger CNV amplitude in the Active condition than both the hallucinating (p = .013, d = .52) and non-hallucinating patients (p < .001, d = .88). No difference was found between the two patient groups (p = .320, d = .20).
Conclusions
The results indicated that motor preparation of inner speech in schizophrenia was disrupted. While the production of inner speech resulted in a larger CNV than passive listening in healthy controls, which was indicative of the involvement of motor planning, patients exhibited markedly blunted motor preparatory activity to inner speech. This may reflect dysfunction in the formation of corollary discharges. Interestingly, the deficits did not differ between hallucinating and non-hallucinating patients. Future work is needed to elucidate the specificity of inner speech-specific motor preparation deficits with AVHs. Overall, this study provides evidence in support of atypical inner speech monitoring in schizophrenia.
The negative impact of adverse childhood experiences (ACEs) on mental health has been well documented. While most of the evidence comes from samples of adolescents and young adults, few studies have investigated whether ACEs contribute to poorer mental health among older adults. In particular, depressive symptoms are common in old age, and they display heterogeneous patterns of development across individuals. Therefore, it is important to examine if ACEs are predictive of distinct trajectories of depressive symptoms among older adults.
Objectives
Using longitudinal data from the English Longitudinal Study of Ageing (ELSA), we aimed to examine if ACEs could differentiate between distinct trajectories of depressive symptoms over eight years in community-dwelling older adults.
Methods
Participants from ELSA aged 60 or above who reported no psychiatric diagnoses and completed the items of ACEs at baseline (wave 3) were included in the current study. Nine items of ACEs were subject to a principal component analysis to identify the underlying subtypes. Data of depressive symptoms from waves 3 to 7 (2-year apart), assessed with the 8-item Centre for Epidemiological Studies Depression Scale, were extracted for modelling the distinct trajectories using latent class growth analysis. The trajectories were predicted by subtypes of ACEs using multinomial logistic regression, adjusting for childhood socioeconomic status, sex, age and ethnicity.
Results
The final sample consisted of 4057 participants (54.4% female, mean age= 71.34 (SD= 8.14)). We identified five trajectories of depressive symptoms (Figure 1): ‘low stable’ (73.4%), ‘increasing then decreasing’ (9.9%), ‘high decreasing’ (7.1%), ‘high stable’ (5.7%) and ‘moderate increasing’ (4.0%). Four subtypes of ACEs (i.e., sexual abuse, separation from natural parents, family dysfunction and physical assault) were evident. Compared to the ‘low stable’ group, higher levels of family dysfunction were reported in the ‘increasing then decreasing’ (aOR = 1.35, 95% CI [1.10 - 1.66], p = .012), ‘high stable’ (aOR = 1.59, 95% CI [1.30 - 1.96], p < .001) and ‘moderate increasing’ (aOR = 1.55, 95% CI [1.18 - 2.04], p = .011) groups. The ‘high stable’ group also reported a higher level of separation from natural parents than the ‘low stable’ group (aOR = 1.34, 95% CI [1.04 - 1.72], p = .047). Sexual abuse and physical assault did not predict any group differences.
Image:
Conclusions
Distinct trajectories of depressive symptoms among older adults were predicted by family dysfunction in childhood. Our findings suggested that the negative impact of ACEs on mental health may extend beyond adolescence and young adulthood into the old age.
Adolescents with depression have distinct affective reactions to daily events, but current research is controversial. The emotional context insensitivity theory suggests blunted reactivity in depression, whereas the hypotheses of negative potentiation and mood brightening effect suggest otherwise. While nonlinear associations between depression severity and affective reactivity have been observed, studies with a separate subclinical group remain rare. Subthreshold depression (SD), defined by two to four symptoms lasting for two weeks or more, provides a dimensional view to the underpinnings of affective reactivity. In this study, we compared positive affect (PA) and negative affect (NA) reactivity to positive and negative daily events (uplifts and stress) among adolescents with Major Depressive Disorder (MDD), SD and healthy controls (HC) using experience sampling methods (ESM).
Objectives
We hypothesized a stepped difference in affective reactivity along the depression spectrum: the MDD group will have the strongest reactivity of PA and NA to uplifts and stress, followed by SD and HC.
Methods
Three groups (MDD, SD, and HC) of adolescents were recruited from an epidemiologic sample entitled ‘Hong Kong Child and Adolescent Psychiatric Epidemiologic Survey: Age 6 to 17’. Group status was determined by the Diagnostic Interview Schedule for Children Version 5. They completed an experience sampling diary on smartphone for 14 consecutive days, with 5-10 entries per day. Momentary levels of PA (happy, relaxed, contented), NA (irritated, low, nervous), uplifts and stress experienced before the entry were measured on a 1-7 Likert scale.
Results
The sample consisted of 19 adolescents with MDD, 30 with SD, and 59 HC. The M:F ratio was 17:19. The age range was 12-18 with a mean of 14.8. The overall ESM completion rate was 46%. The MDD group had the highest levels of stress and NA, and the lowest levels of uplifts and PA, followed by the SD and HC groups respectively (p<0.01). Across groups, levels of PA were positively associated with uplifts and negatively associated with stress, whereas levels of NA were positively associated with stress and negatively associated with uplifts. The Group x Uplift interaction effect on PA was significant, with greater PA reactivity in SD (p<0.01) and MDD (p=0.07) when compared with HC. The Group x Uplift interaction effect on NA was significant, with greater NA reactivity in SD than HC (p<0.01). The Group x Stress interaction effect on PA was significant, with greater PA reactivity in SD than HC (p<0.01) and MDD (p<0.01). The Group x Stress interaction effect with NA is non-significant.
Conclusions
Contrary to our hypothesis, adolescents with SD experienced strongest PA and NA reactivity in uplifts and PA reactivity in stress. It provides evidence towards a nonlinear relationship between severity of depression and affective reactivity.
We aimed to study predictive factors for burnout (BO) among healthcare workers in a tertiary hospital in Singapore.
Objectives
We hypothesized that burnout would be assoiciated with singles, females, and foreign born staff recently moved into this country, unaccompanied by family members.
We further hypothesised that BO would be associated with those scoring less on resilience. Recognising that social support mitigated against stress and burnout, we hypothesized that those who perceived less support would be more prone to BO.
Methods
The study questionnaire was sent via corporate email to all staff with email access. We stressed that data would be fully anonymised. No financial rewards were given for participation which was carried out on a voluntary basis.
The following instruments were used, viz. F-SozU K-6, a brief form of the perceived social support questionnaire; Connor Davidson Resilience Scale; Oldenburg Burnout Inventory; Patient Health Questionnaire-4 item; Demand Control Support Questionnaire and Leisure Time Satisfaction Scale. Ethics approval for the study was sought from the SingHealth Centralised Institutional Review Board, which granted exemption of participant consent.
Analyses were performed using Stata version 17.0 (StataCorp. 2021), with statistical significance set as 2-sided 5% (p<0.05). The reliability and internal consistency of the scales used were assessed using Cronbach Alphas and Confirmatory Factor Analysis (CFA).
Results
Neither males nor females were more at risk for BO. And contrary to what we hypothesised those who recently moved to this nation were not at greater risk for BO (p>0.05). Multivariate analyses showed that younger workers displayed higher burnout scores (p < 0.001).The psychological demand sub-score was positively associated with burnout [ 0.61 (95% CI 0.45 to 0.77), p < 0.001)]. Conversely, decision latitude [-0.33 (95% CI -0.44 to -0.21), p < 0.001)] and support [-0.47 (95% CI -0.60 to -0.35), p < 0.001] were negatively associated with BO.
Those who experienced anxiety or depressive symptoms were respectively more likely to experience burnout [0.30 (95% CI 0.02 to 0.58), p = 0.035 and 0.72 (95% CI 0.41 to 1.02), p < 0.001], with a clear association between higher PHQ-4 scores and risk for burnout (r = 0.619).
Moreover, satisfaction with utilisation of leisure time was inversely related to BO [-0.55 (95% CI -0.68 to –0.41; p < 0.001)]. We could not find any association between number of years worked, profession, marital status and perceived social support and BO, on multivariate anbalysis (p>0.05).
Conclusions
Strress reduction interventions should be made available for all staff, especially addressing those at highest risk for burnout.
Serotonin syndrome is a potentially life-threatening condition that is precipitated by the use of serotonergic medications, Selective Serotonin Reuptake Inhibitors (SSRIs) and Monoamine Oxidase Inhibitors (MAOIs). It usually occurs when high doses of serotonergic drugs are prescribed. It is a medical emergency that requires prompt recognition, cessation of offending drugs and supportive therapy.
Objectives
We present a case of serotonin syndrome that occurred in a patient who was prescribed a low dose of sertraline, and aim to highlight the importance of early detection of this severe condition.
Methods
Details of the case were described. Information was gathered based on medical records.
Results
Patient M was a 29-year-old Malay male with a history of major depressive disorder, who was previously trialed on fluvoxamine 100mg every night but subsequently switched to and maintained on sertraline 75mg every night in 2020. He then defaulted follow up appointments. In 2023, he presented to the emergency services for a suicide attempt and was diagnosed with major depressive disorder with psychotic features. He was restarted on sertraline 50mg every night and risperidone 0.5mg every night was newly started. Two days later, sertraline was increased to 100mg every night. Two days following this increase, he was noted to have altered mental state, fever of 39.3-degree celcius, tachycardia of 120 beats per minute, ocular clonus and generalized hyperreflexia. Sertraline and risperidone were immediately stopped. Blood tests including creatine kinase, lumbar puncture and magnetic resonance imaging (MRI) of the brain did not show any abnormalities. After stopping of the medications, the patient’s symptoms resolved within 24 hours. Based on clinical symptoms and a normal creatine kinase level, neuroleptic malignant syndrome (NMS) was ruled out. Subsequently, he was restarted on risperidone 0.5mg and mirtazapine 7.5mg every night. He developed symptoms of serotonin syndrome with a low dose of sertraline. Symptoms resolved after the discontinuation of the SSRI.
Conclusions
In this case, differential diagnoses of serotonin syndrome were also considered, such as NMS, encephalitis, meningitis and thyroid storm. NMS was less likely due to the rapid onset of onset and resolution of symptoms. Encephalitis and meningitis were unlikely in view of normal MRI brain and lumbar puncture findings.
There have been case reports of serotonin syndrome developing with lower doses of an SSRI in the pediatric population. There is, however, a lack of literature describing serotonin syndrome with low doses of SSRI in the adult population. To avoid a missed diagnosis, clinicians should monitor closely for SSRI toxicity, including serotonin syndrome, even when low doses of serotonergic drugs are used.
There is growing concern regarding teratogenic effect of antipsychotics. Previous research assessing association between antipsychotics and congenital malformations (CMs) yielded mixed results and were all derived from Western countries. We aimed to examine risk of major and organ/system-specific CMs associated with prenatal antipsychotic exposure in Hong Kong.
Methods
This population-based study identified women aged 15–50 years who delivered their first/singleton child between 2003–2018 from public healthcare service database. Propensity score (PS)-weighted logistic-regression analyses were performed to examine risk of CMs following first-trimester exposure to antipsychotic classes (second- and first-generation antipsychotic; SGA and FGA) and six most frequently-prescribed individual antipsychotics.
Results
Of 465,069 women, 419 and 420 redeemed ≥1 prescription of SGA and FGA during first-trimester, respectively. Prevalence of any CMs was 4.9% (95%CI:4.9–5.0%) in unexposed-infants, 9.1% (6.7–12.3%) in SGA-exposed infants, and 6.2% (4.3–9.0%) in FGA-exposed infants. SGA exposure (adjusted-odds-ratio: 2.11 [95%CI:1.19–3.86]) was associated with increased risk of CMs. This finding was consistent with sensitivity analyses addressing exposure misclassification and confounding by treatment indication, but not with PS-matched sensitivity analysis. Elevated risk of CMs was observed in infants exposed to high-dose olanzapine (7.50 [1.65–36.13]) and high-dose quetiapine (15.03 [4.86–56.72]), but with wide-CIs. Organ/system-specific malformations were not associated with SGA, FGA or individual antipsychotics.
Conclusion
We observed a small increased risk of major malformations associated with SGA, but was not consistently affirmed in sensitivity analyses, precluding firm conclusions. Research with large sample size clarifying comparative safety of individual antipsychotics on specific malformations is warranted.
Although the link between alcohol involvement and behavioral phenotypes (e.g. impulsivity, negative affect, executive function [EF]) is well-established, the directionality of these associations, specificity to stages of alcohol involvement, and extent of shared genetic liability remain unclear. We estimate longitudinal associations between transitions among alcohol milestones, behavioral phenotypes, and indices of genetic risk.
Methods
Data came from the Collaborative Study on the Genetics of Alcoholism (n = 3681; ages 11–36). Alcohol transitions (first: drink, intoxication, alcohol use disorder [AUD] symptom, AUD diagnosis), internalizing, and externalizing phenotypes came from the Semi-Structured Assessment for the Genetics of Alcoholism. EF was measured with the Tower of London and Visual Span Tasks. Polygenic scores (PGS) were computed for alcohol-related and behavioral phenotypes. Cox models estimated associations among PGS, behavior, and alcohol milestones.
Results
Externalizing phenotypes (e.g. conduct disorder symptoms) were associated with future initiation and drinking problems (hazard ratio (HR)⩾1.16). Internalizing (e.g. social anxiety) was associated with hazards for progression from first drink to severe AUD (HR⩾1.55). Initiation and AUD were associated with increased hazards for later depressive symptoms and suicidal ideation (HR⩾1.38), and initiation was associated with increased hazards for future conduct symptoms (HR = 1.60). EF was not associated with alcohol transitions. Drinks per week PGS was linked with increased hazards for alcohol transitions (HR⩾1.06). Problematic alcohol use PGS increased hazards for suicidal ideation (HR = 1.20).
Conclusions
Behavioral markers of addiction vulnerability precede and follow alcohol transitions, highlighting dynamic, bidirectional relationships between behavior and emerging addiction.
Unhealthy food environments are major drivers of obesity and diet-related diseases(1). Improving the healthiness of food environments requires a widespread organised response from governments, civil society, and industry(2). However, current actions often rely on voluntary participation by industry, such as opt-in nutrition labelling schemes, school/workplace food guidelines, and food reformulation programmes. The aim of the REFORM study is to determine the effects of the provision of tailored support to companies on their nutrition-related policies and practices, compared to food companies that are not offered the programme (the control). REFORM is a two-country, parallel cluster randomised controlled trial. 150 food companies were randomly assigned (2:1 ratio) to receive either a tailored support intervention programme or no intervention. Randomisation was stratified by country (Australia, New Zealand), industry sector (fast food, other packaged food/beverage companies), and company size. The primary outcome is the nutrient profile (measured using Health Star Rating [HSR]) of foods and drinks produced by participating companies at 24 months post-baseline. Secondary outcomes include company nutrition policies and commitments, the nutrient content (sodium, sugar, saturated fat) of products produced by participating companies, display of HSR labels, and engagement with the intervention. Eighty-three eligible intervention companies were invited to take part in the REFORM programme and 21 (25%) accepted and were enrolled. Over 100 meetings were held with company representatives between September 2021 and December 2022. Resources and tailored reports were developed for 6 touchpoints covering product composition and benchmarking, nutrition labelling, consumer insights, nutrition policies, and incentives for companies to act on nutrition. Detailed information on programme resources and preliminary 12-month findings will be presented at the conference. The REFORM programme will assess if provision of tailored support to companies on their nutrition-related policies and practices incentivises the food industry to improve their nutrition policies and actions.
Simple equations are presented which allow double-layer potentials of clays to be derived from co-ion exclusion measurements in monovalent and divalent electrolyte solutions. These equations have been used to re-interpret earlier results for illite and montmorillonite. The potentials derived follow the lyotropic series for the various homoionic modification of each clay. We have demonstrated that the Schofield equation, which assumes high double-layer potentials, cannot be applied to co-ion exclusion in clay systems. Re-analysis of earlier measurements has shown that for a given homoionic clay the potentials are almost independent of concentration over the range 0.3 to 0.003 molar. Thus, clay surfaces appear to behave more like constant-potential than constant-charge surfaces.
Population-wide restrictions during the COVID-19 pandemic may create barriers to mental health diagnosis. This study aims to examine changes in the number of incident cases and the incidence rates of mental health diagnoses during the COVID-19 pandemic.
Methods
By using electronic health records from France, Germany, Italy, South Korea and the UK and claims data from the US, this study conducted interrupted time-series analyses to compare the monthly incident cases and the incidence of depressive disorders, anxiety disorders, alcohol misuse or dependence, substance misuse or dependence, bipolar disorders, personality disorders and psychoses diagnoses before (January 2017 to February 2020) and after (April 2020 to the latest available date of each database [up to November 2021]) the introduction of COVID-related restrictions.
Results
A total of 629,712,954 individuals were enrolled across nine databases. Following the introduction of restrictions, an immediate decline was observed in the number of incident cases of all mental health diagnoses in the US (rate ratios (RRs) ranged from 0.005 to 0.677) and in the incidence of all conditions in France, Germany, Italy and the US (RRs ranged from 0.002 to 0.422). In the UK, significant reductions were only observed in common mental illnesses. The number of incident cases and the incidence began to return to or exceed pre-pandemic levels in most countries from mid-2020 through 2021.
Conclusions
Healthcare providers should be prepared to deliver service adaptations to mitigate burdens directly or indirectly caused by delays in the diagnosis and treatment of mental health conditions.