Engineering Clock Transitions in Molecular Lanthanide Complexes.

Molecular lanthanide (Ln) complexes are promising candidates for the development of next-generation quantum technologies. High-symmetry structures incorporating integer spin Ln ions can give rise to well-isolated crystal field quasi-doublet ground states, i.e., quantum two-level systems that may serve as the basis for magnetic qubits. Recent work has shown that symmetry lowering of the coordination environment around the Ln ion can produce an avoided crossing or clock transition within the ground doublet, leading to significantly enhanced coherence. Here, we employ single-crystal high-frequency electron paramagnetic resonance spectroscopy and high-level ab initio calculations to carry out a detailed investigation of the nine-coordinate complexes, [HoIIIL1L2], where L1 = 1,4,7,10-tetrakis(2-pyridylmethyl)-1,4,7,10-tetraaza-cyclododecane and L2 = F- (1) or [MeCN]0 (2). The pseudo-4-fold symmetry imposed by the neutral organic ligand scaffold (L1) and the apical anionic fluoride ion generates a strong axial anisotropy with an mJ = ±8 ground-state quasi-doublet in 1, where mJ denotes the projection of the J = 8 spin-orbital moment onto the ∼C4 axis. Meanwhile, off-diagonal crystal field interactions give rise to a giant 116.4 ± 1.0 GHz clock transition within this doublet. We then demonstrate targeted crystal field engineering of the clock transition by replacing F- with neutral MeCN (2), resulting in an increase in the clock transition frequency by a factor of 2.2. The experimental results are in broad agreement with quantum chemical calculations. This tunability is highly desirable because decoherence caused by second-order sensitivity to magnetic noise scales inversely with the clock transition frequency.

Estimating demand for potential disease-modifying therapies for Alzheimer's disease in the UK.

BACKGROUND: Phase three trials of the monoclonal antibodies lecanemab and donanemab, which target brain amyloid, have reported statistically significant differences in clinical end-points in early Alzheimer's disease. These drugs are already in use in some countries and are going through the regulatory approval process for use in the UK. Concerns have been raised about the ability of healthcare systems, including those in the UK, to deliver these treatments, considering the resources required for their administration and monitoring. AIMS: To estimate the scale of real-world demand for monoclonal antibodies for Alzheimer's disease in the UK. METHOD: We used anonymised patient record databases from two National Health Service trusts for the year 2019 to collect clinical, demographic, cognitive and neuroimaging data for these cohorts. Eligibility for treatment was assessed using the inclusion criteria from the clinical trials of donanemab and lecanemab, with consideration given to diagnosis, cognitive performance, cerebrovascular disease and willingness to receive treatment. RESULTS: We examined the records of 82 386 people referred to services covering around 2.2 million people. After applying the trial criteria, we estimate that a maximum of 906 people per year would start treatment with monoclonal antibodies in the two services, equating to 30 200 people if extrapolated nationally. CONCLUSIONS: Monoclonal antibody treatments for Alzheimer's disease are likely to present a significant challenge for healthcare services to deliver in terms of the neuroimaging and treatment delivery. The data provided here allows health services to understand the potential demand and plan accordingly.

An investigation of neuropsychiatric symptoms, contextual factors, and antidepressant treatment as risk factors for dementia development in people with mild cognitive impairment.

BACKGROUND: While some people with mild cognitive impairment (MCI) progress to dementia, many others show no progression. The aim of this study was to identify factors associated with risk of dementia development in this population. METHOD: A large naturalistic retrospective cohort study was assembled from mental healthcare records in a south London catchment. Patients were selected at first recorded diagnosis of MCI and subsequent dementia diagnosis was ascertained from case notes or death certificate, excluding those with dementia diagnoses and deaths within 6 months of MCI diagnosis. A range of demographic and clinical characteristics were ascertained around MCI diagnosis and Cox proportional hazards models were used to investigate independent predictors of dementia, focussing on neuropsychiatric symptoms, contextual factors, and antidepressant treatment. RESULTS: Of 2250 patients with MCI, 236 (10.5%) developed dementia at least 6 months after MCI diagnosis. Aside from older age, lower cognitive function, and activities of daily living impairment, impaired social relationships and recorded loneliness were associated with a higher risk of developing dementia. Patients of Black (compared to White) ethnicity were at a lower risk. For depression and antidepressant receipt, only tricyclic use compared to no antidepressant use was associated with an increased dementia risk. CONCLUSIONS: No evidence was found for co-morbid affective disorders or different antidepressant classes as risk factors for dementia development following MCI diagnosis, but loneliness and social impairment were independent predictors and would be worth evaluating as targets for interventions to delay progression.

Associations between recorded loneliness and adverse mental health outcomes among patients receiving mental healthcare in South London: a retrospective cohort study.

PURPOSE: Loneliness disproportionately affects people with mental disorders, but associations with mental health outcomes in groups affected remain less well understood. METHOD: A cohort of patients receiving mental healthcare on 30th June 2012 was assembled from a large mental health records database covering a south London catchment area. Recorded loneliness within the preceding 2 years was extracted using natural language processing and outcomes were measured between 30th June 2012 until 30th December 2019, except for survival which applied a censoring point of 6th December 2020 according to data available at the time of extraction. The following mental healthcare outcomes: (i) time to first crisis episode; (ii) time to first emergency presentation; (iii) all-cause mortality; (iv) days active to service per year; and (v) face-to-face contacts per year. RESULTS: Loneliness was recorded in 4,483 (16.7%) patients in the study population and fully adjusted models showed associations with subsequent crisis episode (HR 1.17, 95% CI 1.07-1.29), emergency presentation (HR 1.30, 1.21-1.40), days active per year (IRR 1.04, 1.03-1.05), and face-to-face contacts per year (IRR 1.28, 1.27-1.30). Recorded loneliness in patients with substance misuse problems was particularly strongly associated with adverse outcomes, including risk of emergency presentation (HR 1.68, 1.29-2.18) and mortality (HR 1.29, 1.01-1.65). CONCLUSION: Patients receiving mental healthcare who are recorded as lonely have a higher risk of several adverse outcomes which may require a need for higher service input.

Understanding social and clinical associations with unemployment for people with schizophrenia and bipolar disorders: large-scale health records study.

PURPOSE: People with severe mental illness (SMI) experience high levels of unemployment. We aimed to better understand the associations between clinical, social, and demographic inequality indicators and unemployment. METHODS: Data were extracted from de-identified health records of people with SMI in contact with secondary mental health services in south London, UK. A Natural Language Processing text-mining application was applied to extract information on unemployment in the health records. Multivariable logistic regression was used to assess associations with unemployment, in people with SMI. RESULTS: Records from 19,768 service users were used for analysis, 84.9% (n = 16,778) had experienced unemployment. In fully adjusted models, Black Caribbean and Black African service users were more likely to experience unemployment compared with White British service users (Black Caribbean: aOR 1.62, 95% CI 1.45-1.80; Black African: 1.32, 1.15-1.51). Although men were more likely to have experienced unemployment relative to women in unadjusted models (OR 1.36, 95% CI 1.26-1.47), differences were no longer apparent in the fully adjusted models (aOR 1.05, 95% CI 0.97-1.15). The presence of a non-affective (compared to affective) diagnosis (1.24, 1.13-1.35), comorbid substance use (2.02, 1.76-2.33), previous inpatient admissions (4.18, 3.71-4.70), longer inpatient stays (78 + days: 7.78, 6.34-9.54), and compulsory admissions (3.45, 3.04-3.92) were associated with unemployment, in fully adjusted models. CONCLUSION: People with SMI experience high levels of unemployment, and we found that unemployment was associated with several clinical and social factors. Interventions to address low employment may need to also address these broader inequalities.

Maternal asthma and asthma exacerbation during pregnancy and attention-deficit/hyperactivity disorder in offspring: a population-based cohort study.

The link between inflammatory disorders, such as asthma, and attention deficit hyperactivity disorder (ADHD) is attracting increasing attention but few studies have examined cross-generational associations. We sought to examine associations of maternal asthma and asthma exacerbation during pregnancy, as well as paternal asthma, with the risk of ADHD in children. This population-based cohort study used data from the Taiwan National Health Insurance Research Database from 2004 to 2017. Cox regression models compared the risk of ADHD in children of parents with and without asthma, adjusting for parental sociodemographic, physical, and mental health conditions, as well as the child's birth weight, and number of births. A sibling control approach was employed to compensate for unmeasured confounders of asthma exacerbation during pregnancy. In the fully adjusted models, maternal and paternal asthma were both significantly associated with an increased risk of ADHD in offspring, with hazard ratios (HRs) of 1.36 (1.31-1.40) and 1.10 (1.05-1.14), respectively. Acute asthma exacerbation during pregnancy was not associated with the risk of further offspring ADHD (adjusted HR 1.00, 95% CI: 0.75-1.34). Both maternal and paternal asthma are associated with an increased risk of ADHD in offspring. The risk was higher from maternal asthma. However, no such association was found with maternal asthma exacerbation during pregnancy of sibling comparison.

3D VSP Imaging Using DAS Recording of P- and S-Waves in Vertical and Lateral Well Sections in West Texas.

A 3D vertical seismic profiling (VSP) survey was acquired using a distributed acoustic sensing (DAS) system in the Permian Basin, West Texas. In total, 682 shot points from a pair of vibroseis units were recorded using optical fibers installed in a 9000 ft (2743 m) vertical part and 5000 ft (1524 m) horizontal reach of a well. Transmitted and reflected P, S, and converted waves were evident in the DAS data. From first-break P and S arrivals, we found average P-wave velocities of approximately 14,000 ft/s (4570 m/s) and S-wave velocities of 8800 ft/s (3000 m/s) in the deep section. We modified the conventional geophone VSP processing workflow and produced P-P reflection and P-S volumes derived from the well's vertical section. The Wolfcamp formation can be seen in two 3D volumes (P-P and P-S) from the vertical section of the well. They cover an area of 3000 ft (914 m) in the north-south direction and 1500 ft (460 m) in the west-east direction. Time slices showed coherent reflections, especially at 1.7 s (~11,000 ft), which was interpreted as the bottom of the Wolfcamp formation. Vp/Vs values from 2300 ft (701 m) -8800 ft (2682 m) interval range were between 1.7 and 2.0. These first data provide baseline images to compare to follow-up surveys after hydraulic fracturing as well as potential usefulness in extracting elastic properties and providing further indications of fractured volumes.

Investigating time-dependent COVID-19 pandemic mental health data: Challenges and opportunities of using panel data analysis.

Mariana Pinto da Costa and Robert Stewart provide commentary on a large prospective panel survey of mental health during the pandemic and consider the implications of such data science initiatives.

Recording of intellectual disability in general hospitals in England 2006-2019: Cohort study using linked datasets.

BACKGROUND: Accurate recognition and recording of intellectual disability in those who are admitted to general hospitals is necessary for making reasonable adjustments, ensuring equitable access, and monitoring quality of care. In this study, we determined the rate of recording of intellectual disability in those with the condition who were admitted to hospital and factors associated with the condition being unrecorded. METHODS AND FINDINGS: Retrospective cohort study using 2 linked datasets of routinely collected clinical data in England. We identified adults with diagnosed intellectual disability in a large secondary mental healthcare database and used general hospital records to investigate recording of intellectual disability when people were admitted to general hospitals between 2006 and 2019. Trends over time and factors associated with intellectual disability being unrecorded were investigated. We obtained data on 2,477 adults with intellectual disability who were admitted to a general hospital in England at least once during the study period (total number of admissions = 27,314; median number of admissions = 5). People with intellectual disability were accurately recorded as having the condition during 2.9% (95% CI 2.7% to 3.1%) of their admissions. Broadening the criteria to include a nonspecific code of learning difficulty increased recording to 27.7% (95% CI 27.2% to 28.3%) of all admissions. In analyses adjusted for age, sex, ethnicity, and socioeconomic deprivation, having a mild intellectual disability and being married were associated with increased odds of the intellectual disability being unrecorded in hospital records. We had no measure of quality of hospital care received and could not relate this to the presence or absence of a record of intellectual disability in the patient record. CONCLUSIONS: Recognition and recording of intellectual disability in adults admitted to English general hospitals needs to be improved. Staff awareness training, screening at the point of admission, and data sharing between health and social care services could improve care for people with intellectual disability.

Antidepressant drug prescription and incidence of COVID-19 in mental health outpatients: a retrospective cohort study.

BACKGROUND: Currently, the main pharmaceutical intervention for COVID-19 is vaccination. While antidepressant (AD) drugs have shown some efficacy in treatment of symptomatic COVID-19, their preventative potential remains largely unexplored. Analysis of association between prescription of ADs and COVID-19 incidence in the population would be beneficial for assessing the utility of ADs in COVID-19 prevention. METHODS: Retrospective study of association between AD prescription and COVID-19 diagnosis was performed in a cohort of community-dwelling adult mental health outpatients during the 1st wave of COVID-19 pandemic in the UK. Clinical record interactive search (CRIS) was performed for mentions of ADs within 3 months preceding admission to inpatient care of the South London and Maudsley (SLaM) NHS Foundation Trust. Incidence of positive COVID-19 tests upon admission and during inpatient treatment was the primary outcome measure. RESULTS: AD mention was associated with approximately 40% lower incidence of positive COVID-19 test results when adjusted for socioeconomic parameters and physical health. This association was also observed for prescription of ADs of the selective serotonin reuptake inhibitor (SSRI) class. CONCLUSIONS: This preliminary study suggests that ADs, and SSRIs in particular, may be of benefit for preventing COVID-19 infection spread in the community. The key limitations of the study are its retrospective nature and the focus on a mental health patient cohort. A more definitive assessment of AD and SSRI preventative potential warrants prospective studies in the wider demographic.

Bulls fed a high-gain diet decrease blastocyst formation after in vitro fertilization.

In brief: Paternal high-gain diet reduces blastocyst development following in vitro fertilization and embryo culture but does not affect gene expression or cellular allocation of resultant blastocysts. Abstract: Bulls used in cattle production are often overfed to induce rapid growth, early puberty, and increase sale price. While the negative consequences of undernutrition on bull sperm quality are known, it is unclear how a high-gain diet influences embryo development. We hypothesized that semen collected from bulls fed a high-gain diet would have a reduced capacity to produce blastocysts following in vitro fertilization. Eight mature bulls were stratified by body weight and fed the same diet for 67 days at either a maintenance level (0.5% body weight per day; n = 4) or a high-gain rate (1.25% body weight per day; n = 4). Semen was collected by electroejaculation at the end of the feeding regimen and subjected to sperm analysis, frozen, and used for in vitro fertilization. The high-gain diet increased body weight, average daily gain, and subcutaneous fat thickness compared to the maintenance diet. Sperm of high-gain bulls tended to have increased early necrosis and had increased post-thaw acrosome damage compared with maintenance bulls, but diet did not affect sperm motility or morphology. Semen of high-gain bulls reduced the percentage of cleaved oocytes that developed to blastocyst stage embryos. Paternal diet had no effect on the number of total or CDX2-positive cells of blastocysts, or blastocysts gene expression for markers associated with developmental capacity. Feeding bulls a high-gain diet did not affect sperm morphology or motility, but increased adiposity and reduced the ability of sperm to generate blastocyst-stage embryos.

Severe mental illness, race/ethnicity, multimorbidity and mortality following COVID-19 infection: nationally representative cohort study.

BACKGROUND: The association of COVID-19 with death in people with severe mental illness (SMI), and associations with multimorbidity and ethnicity, are unclear. AIMS: To determine all-cause mortality in people with SMI following COVID-19 infection, and assess whether excess mortality is affected by multimorbidity or ethnicity. METHOD: This was a retrospective cohort study using primary care data from the Clinical Practice Research Database, from February 2020 to April 2021. Cox proportional hazards regression was used to estimate the effect of SMI on all-cause mortality during the first two waves of the COVID-19 pandemic. RESULTS: Among 7146 people with SMI (56% female), there was a higher prevalence of multimorbidity compared with the non-SMI control group (n = 653 024, 55% female). Following COVID-19 infection, the SMI group experienced a greater risk of death compared with controls (adjusted hazard ratio (aHR) 1.53, 95% CI 1.39-1.68). Black Caribbean/Black African people were more likely to die from COVID-19 compared with White people (aHR = 1.22, 95% CI 1.12-1.34), with similar associations in the SMI group and non-SMI group (P for interaction = 0.73). Following infection with COVID-19, for every additional multimorbidity condition, the aHR for death was 1.06 (95% CI 1.01-1.10) in the SMI stratum and 1.16 (95% CI 1.15-1.17) in the non-SMI stratum (P for interaction = 0.001). CONCLUSIONS: Following COVID-19 infection, patients with SMI were at an elevated risk of death, further magnified by multimorbidity. Black Caribbean/Black African people had a higher risk of death from COVID-19 than White people, and this inequity was similar for the SMI group and the control group.

A marginal structural model to estimate the effect of antidepressant medication treatment on major cardiovascular events among people with post-traumatic stress disorder.

BACKGROUND: Previous evidence on antidepressant medication and cardiovascular disease (CVD) among patients with posttraumatic stress disorder (PTSD) has been inconclusive. We estimated the association between antidepressant medication and CVD by applying a marginal structural model. METHODS: We analyzed medical utilization records of 27 170 people with PTSD without prior major cardiovascular events in the Korean National Health Insurance Database (NHID). PTSD and CVD were defined in accordance with the recorded ICD-10 diagnostic codes. We acquired information on antidepressant use from the NHID and categorized them by medication type. A composite major adverse cardiovascular events (MACE) outcome was defined as coronary artery disease with revascularization, ischaemic stroke, and/or haemorrhagic stroke. We used inverse probability of treatment weighting to estimate the parameters of a marginal structural discrete-time survival analysis regression model, comparing the resulting estimates to those derived from traditional time-fixed and time-varying Cox proportional hazards regression. We calculated cumulative daily defined doses to test for a dose-response relationship. RESULTS: People exposed to antidepressants showed a higher hazard of MACE [hazard ratio (HR) 1.34, 95% confidence interval (CI) 1.18-1.53]. The estimated effects were strongest for selective serotonin reuptake inhibitors (HR 1.24, 95% CI 1.08-1.44) and TCAs (HR 1.33, 95% CI 1.13-1.56). Exposure to serotonin-norepinephrine reuptake inhibitors did not appear to increase the risk of MACE. People exposed to higher doses of antidepressants showed higher risk of MACE. CONCLUSIONS: In a national cohort of people with PTSD, exposure to antidepressant medications increased the risk of MACE in a dose-response fashion.

Multimorbidity clusters among people with serious mental illness: a representative primary and secondary data linkage cohort study.

BACKGROUND: People with serious mental illness (SMI) experience higher mortality partially attributable to higher long-term condition (LTC) prevalence. However, little is known about multiple LTCs (MLTCs) clustering in this population. METHODS: People from South London with SMI and two or more existing LTCs aged 18+ at diagnosis were included using linked primary and mental healthcare records, 2012-2020. Latent class analysis (LCA) determined MLTC classes and multinominal logistic regression examined associations between demographic/clinical characteristics and latent class membership. RESULTS: The sample included 1924 patients (mean (s.d.) age 48.2 (17.3) years). Five latent classes were identified: 'substance related' (24.9%), 'atopic' (24.2%), 'pure affective' (30.4%), 'cardiovascular' (14.1%), and 'complex multimorbidity' (6.4%). Patients had on average 7-9 LTCs in each cluster. Males were at increased odds of MLTCs in all four clusters, compared to the 'pure affective'. Compared to the largest cluster ('pure affective'), the 'substance related' and the 'atopic' clusters were younger [odds ratios (OR) per year increase 0.99 (95% CI 0.98-1.00) and 0.96 (0.95-0.97) respectively], and the 'cardiovascular' and 'complex multimorbidity' clusters were older (ORs 1.09 (1.07-1.10) and 1.16 (1.14-1.18) respectively). The 'substance related' cluster was more likely to be White, the 'cardiovascular' cluster more likely to be Black (compared to White; OR 1.75, 95% CI 1.10-2.79), and both more likely to have schizophrenia, compared to other clusters. CONCLUSION: The current study identified five latent class MLTC clusters among patients with SMI. An integrated care model for treating MLTCs in this population is recommended to improve multimorbidity care.

Life expectancy, mortality risks and cause of death in patients with serious mental illness in South East London: a comparison between 2008-2012 and 2013-2017.

BACKGROUND: People with serious mental illness (SMI) have a significantly shorter life expectancy than the general population. This study investigates whether the mortality rate in this group has changed over the last decade. METHODS: Using Clinical Record Interactive Search software, we extracted data from a large electronic database of patients in South East London. All patients with schizophrenia, schizoaffective disorder or bipolar disorder from 2008 to 2012 and/or 2013 to 2017 were included. Estimates of life expectancy at birth, standardised mortality ratios and causes of death were obtained for each cohort according to diagnosis and gender. Comparisons were made between cohorts and with the general population using data obtained from the UK Office of National Statistics. RESULTS: In total, 26 005 patients were included. In men, life expectancy was greater in 2013-2017 (64.9 years; 95% CI 63.6-66.3) than in 2008-2012 (63.2 years; 95% CI 61.5-64.9). Similarly, in women, life expectancy was greater in 2013-2017 (69.1 years; 95% CI 67.5-70.7) than in 2008-2012 (68.1 years; 95% CI 66.2-69.9). The difference with general population life expectancy fell by 0.9 years between cohorts in men, and 0.5 years in women. In the 2013-2017 cohorts, cancer accounted for a similar proportion of deaths as cardiovascular disease. CONCLUSIONS: Relative to the general population, life expectancy for people with SMI is still much worse, though it appears to be improving. The increased cancer-related mortality suggests that physical health monitoring should consider including cancer as well.

Multiple serum biomarkers for predicting suicidal behaviours in depressive patients receiving pharmacotherapy.

BACKGROUND: Predictive values of multiple serum biomarkers for suicidal behaviours (SBs) have rarely been tested. This study sought to evaluate and develop a panel of multiple serum biomarkers for predicting SBs in outpatients receiving a 12-month pharmacotherapy programme for depressive disorders. METHODS: At baseline, 14 serum biomarkers and socio-demographic/clinical characteristics including previous suicidal attempt and present suicidal severity were evaluated in 1094 patients with depressive disorders without a bipolar diagnosis. Of these, 884 were followed for increased suicidal severity and fatal/non-fatal suicide attempt outcomes over a 12-month treatment period. Individual and combined effects of serum biomarkers on these two prospective SBs were estimated using logistic regression analysis after adjustment for relevant covariates. RESULTS: Increased suicidal severity and fatal/non-fatal suicide attempt during the 12-month pharmacotherapy were present in 155 (17.5%) and 38 (4.3%) participants, respectively. Combined cortisol, total cholesterol, and folate serum biomarkers predicted fatal/non-fatal suicide attempt, and these with interleukin-1 beta and homocysteine additionally predicted increased suicidal severity, with clear gradients robust to adjustment (p values < 0.001). CONCLUSIONS: Application of multiple serum biomarkers could considerably improve the predictability of SBs during the outpatient treatment of depressive disorders, potentially highlighting the need for more frequent monitoring and risk appraisal.

Catatonia: demographic, clinical and laboratory associations.

BACKGROUND: Catatonia, a severe neuropsychiatric syndrome, has few studies of sufficient scale to clarify its epidemiology or pathophysiology. We aimed to characterise demographic associations, peripheral inflammatory markers and outcome of catatonia. METHODS: Electronic healthcare records were searched for validated clinical diagnoses of catatonia. In a case-control study, demographics and inflammatory markers were compared in psychiatric inpatients with and without catatonia. In a cohort study, the two groups were compared in terms of their duration of admission and mortality. RESULTS: We identified 1456 patients with catatonia (of whom 25.1% had two or more episodes) and 24 956 psychiatric inpatients without catatonia. Incidence was 10.6 episodes of catatonia per 100 000 person-years. Patients with and without catatonia were similar in sex, younger and more likely to be of Black ethnicity. Serum iron was reduced in patients with catatonia [11.6 v. 14.2 µmol/L, odds ratio (OR) 0.65 (95% confidence interval (CI) 0.45-0.95), p = 0.03] and creatine kinase was raised [2545 v. 459 IU/L, OR 1.53 (95% CI 1.29-1.81), p < 0.001], but there was no difference in C-reactive protein or white cell count. N-Methyl-d-aspartate receptor antibodies were significantly associated with catatonia, but there were small numbers of positive results. Duration of hospitalisation was greater in the catatonia group (median: 43 v. 25 days), but there was no difference in mortality after adjustment. CONCLUSIONS: In the largest clinical study of catatonia, we found catatonia occurred in approximately 1 per 10 000 person-years. Evidence for a proinflammatory state was mixed. Catatonia was associated with prolonged inpatient admission but not with increased mortality.

Association between depression diagnosis and educational attainment trajectories: an historical cohort study using linked data.

BACKGROUND: Depression symptoms are thought to be associated with lower educational attainment, but patterns of change in attainment among those who receive a clinical diagnosis of depression at any point during childhood and adolescence remain unclear. METHODS: We conducted a secondary analysis of an existing data linkage between a national educational dataset (National Pupil Database) and pseudonymised electronic health records (Clinical Record Interactive Search) from a large mental healthcare provider in London, United Kingdom (2007 to 2013). A cohort of 222,027 pupils were included. We used Growth Mixture Modelling (GMM) and stakeholder input to estimate trajectories of standardised educational attainment over School Years 2, 6 and 11. Multinomial logistic regression analyses were then used to investigate the association between resulting educational attainment trajectory membership (outcome) and depression diagnosis any time before age 18 (exposure). RESULTS: A five-trajectory GMM solution for attainment was derived: (1) average/high-stable, (2) average-modest declining, (3) average-steep declining, (4) low-improving and (5) low-stable. After adjusting for clinical and sociodemographic covariates, having a depression diagnosis before age 18 was associated with occupying the average-modest declining trajectory (RRR = 2.80, 95% CI 2.36-3.32, p < .001) or the average-steep declining trajectory (RRR = 3.54, 95% CI 3.10-4.04, p < .001), as compared to the average/high-stable trajectory. CONCLUSIONS: Receiving a diagnosis of depression before age 18 was associated with a relative decline in attainment throughout school. While these findings cannot support a causal direction, they nonetheless suggest a need for timely mental health and educational support among pupils struggling with depression.

Impact of pre-existing mental health disorders on the receipt of guideline recommended cancer treatments: A systematic review.

OBJECTIVE: Disparities in cancer outcomes for individuals with pre-existing mental health disorders have already been identified, particularly for cancer screening and mortality. We aimed to systematically review the influence on the time from cancer diagnosis to cancer treatment, treatment adherence, and differences in receipt of guideline recommended cancer treatment. METHODS: We included international studies published in English from 1 January 1995 to 23 May 2022 by searching MEDLINE, Embase, and APA PsycInfo. RESULTS: This review identified 29 studies with 27 being published in the past decade. Most studies focused on breast, non-small cell lung and colorectal cancer and were of high or medium quality as assessed by the Newcastle Ottawa Scale. All studies were from high-income countries, and mostly included patients enrolled in national health insurance systems. Five assessed the impact on treatment delay or adherence, and 25 focused on the receipt of guideline recommended treatment. 20/25 studies demonstrated evidence that patients with pre-existing mental health disorders were less likely to receive guideline recommended therapies such as surgery or radiotherapy. In addition, there was a greater likelihood of receiving less intensive or modified treatment including systemic therapy. CONCLUSIONS: Across different cancer types and treatment modalities there is evidence of a clear disparity in the receipt of guideline recommended cancer treatment for patients with pre-existing mental health disorders. The effect of pre-existing mental health disorders on treatment delay or adherence is under-researched. Future research needs to include low- and middle-income countries as well as qualitative investigations to understand the reasons for disparities in cancer treatment.

Prognostic factors for mental wellbeing in prostate cancer: A systematic review and meta-analysis.

OBJECTIVES: To evaluate the evidence base for patient, oncological, and treatment prognostic factors associated with multiple mental wellbeing outcomes in prostate cancer patients. METHODS: We performed a literature search of MEDLINE, EMBASE, and CINAHL databases including studies evaluating patient, oncological, or treatment factors against one of five mental wellbeing outcomes; depression, anxiety, fear of cancer recurrence, masculinity, and body image perception. Data synthesis included a random effects meta-analysis for the prognostic effect of individual factors if sufficient homogenous data was available, with a structured narrative synthesis where this was not possible. RESULTS: A final 62 articles were included. Older age was associated with a reducing odds of depression (OR 0.97, p = 0.04), with little evidence of effect for other outcomes. Additionally, baseline mental health status was related to depression and increasing time since diagnosis was associated with reducing fear of recurrence, albeith with low certainty of evidence. However, few other patient or oncological factors demonstrated any coherent relationship with any wellbeing outcome. Androgen deprivation therapy was associated with increased depression (HR 1.65, 95% CI 1.41-1.92, p < 0.01) and anxiety, however, little difference was seen between other treatment options. Overall, whilst numerous factors were identified, most were evaluated by single studies with few evaluating masculinity and body image outcomes. CONCLUSION: We highlight the existing evidence for prognostic factors in mental wellbeing outcomes in prostate cancer, allowing us to consider high-risk groups of patients for preventative and treatment measures. However, the current evidence is heterogenous with further work required exploring less conclusive factors and outcomes.