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Accurate diagnosis of bipolar disorder (BPD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A depressive episode often precedes the first manic episode, making it difficult to distinguish BPD from unipolar major depressive disorder (MDD).
Aims
We use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores (PRS) that may aid early differential diagnosis.
Method
Based on individual genotypes from case–control cohorts of BPD and MDD shared through the Psychiatric Genomics Consortium, we compile case–case–control cohorts, applying a careful quality control procedure. In a resulting cohort of 51 149 individuals (15 532 BPD patients, 12 920 MDD patients and 22 697 controls), we perform a variety of GWAS and PRS analyses.
Results
Although our GWAS is not well powered to identify genome-wide significant loci, we find significant chip heritability and demonstrate the ability of the resulting PRS to distinguish BPD from MDD, including BPD cases with depressive onset (BPD-D). We replicate our PRS findings in an independent Danish cohort (iPSYCH 2015, N = 25 966). We observe strong genetic correlation between our case–case GWAS and that of case–control BPD.
Conclusions
We find that MDD and BPD, including BPD-D are genetically distinct. Our findings support that controls, MDD and BPD patients primarily lie on a continuum of genetic risk. Future studies with larger and richer samples will likely yield a better understanding of these findings and enable the development of better genetic predictors distinguishing BPD and, importantly, BPD-D from MDD.
In-farm livestock production vaccinations are commonly delivered intramuscularly using needles. While there are alternative strategies these have been subject to little attention and limited commercialisation. One such alternative is needle-free vaccines and studies have focused on the immune response few have addressed the welfare implications. This study aims to compare the impact of intradermal needle-free vaccination and intramuscular injection in terms of the welfare of the piglets. A total of 179 piglets were divided into two treatments: intradermal needle-free delivery and intramuscular delivery of a vaccine. Measures of health and welfare included, vocalisations, behavioural observations, papule formation, and weight. Piglets vaccinated via the needle-free intradermal route vocalised less and displayed no significant behavioural differences but showed increased weight compared to piglets vaccinated intramuscularly. The use of a needle-free device to deliver a vaccine through an intradermal route revealed no adverse effects on piglet welfare and supports the use of alternative strategies to vaccinate livestock.
Seclusion is a restrictive practice that many healthcare services are trying to reduce. Previous studies have sought to identify predictors of seclusion initiation, but few have investigated factors associated with adverse outcomes after seclusion termination.
Aims
To assess the factors that predict an adverse outcome within 24 h of seclusion termination.
Method
In a cohort study of individuals secluded in psychiatric intensive care units, we investigated factors associated with any of the following outcomes: actual violence, attempted violence, or reinitiation of seclusion within 24 h of seclusion termination. Among the seclusion episodes that were initiated between 29 March 2018 and 4 March 2019, we investigated the exposures of medication cooperation, seclusion duration, termination out of working hours, involvement of medical staff in the final seclusion review, lack of insight, and agitation or irritability. In a mixed-effects logistic regression model, associations between each exposure and the outcome were calculated. Odds ratios were calculated unadjusted and adjusted for demographic and clinical variables.
Results
We identified 254 seclusion episodes from 122 individuals (40 female, 82 male), of which 106 (41.7%) had an adverse outcome within 24 h of seclusion termination. Agitation or irritability was associated with an adverse outcome, odds ratio 1.92 (95% CI 1.03 to 3.56, P = 0.04), but there was no statistically significant association with any of the other exposures, although confidence intervals were broad.
Conclusions
Agitation or irritability in the hours preceding termination of seclusion may predict an adverse outcome. The study was not powered to detect other potentially clinically significant factors.
NHS Scotland, one of the keystone healthcare providers in the UK, have recently set a wide variety of sustainability targets in an effort to mitigate waste and the intensive energy demands of healthcare. Medical garment production, management and design is an area in which design researchers can explore and offer solutions. This paper presents a series of co-design explorations to examine design alternatives to single-use theatre caps, the majority of which are currently disposed of routinely. Using a series of probes, major insights into how theatre cap design may be improved is presented.
Marine litter poses a complex challenge in Indonesia, necessitating a well-informed and coordinated strategy for effective mitigation. This study investigates the seasonality of plastic concentrations around Sulawesi Island in central Indonesia during monsoon-driven wet and dry seasons. By using open data and methodologies including the HYCOM and Parcels models, we simulated the dispersal of plastic waste over 3 months during both the southwest and northeast monsoons. Our research extended beyond data analysis, as we actively engaged with local communities, researchers and policymakers through a range of outreach initiatives, including the development of a web application to visualize model results. Our findings underscore the substantial influence of monsoon-driven currents on surface plastic concentrations, highlighting the seasonal variation in the risk to different regional seas. This study adds to the evidence provided by coarser resolution regional ocean modelling studies, emphasizing that seasonality is a key driver of plastic pollution within the Indonesian archipelago. Inclusive international collaboration and a community-oriented approach were integral to our project, and we recommend that future initiatives similarly engage researchers, local communities and decision-makers in marine litter modelling results. This study aims to support the application of model results in solutions to the marine litter problem.
Dementia is a common and progressive condition whose prevalence is growing worldwide. It is challenging for healthcare systems to provide continuity in clinical services for all patients from diagnosis to death.
Aims
To test whether individuals who are most likely to need enhanced care later in the disease course can be identified at the point of diagnosis, thus allowing the targeted intervention.
Method
We used clinical information collected routinely in de-identified electronic patient records from two UK National Health Service (NHS) trusts to identify at diagnosis which individuals were at increased risk of needing enhanced care (psychiatric in-patient or intensive (crisis) community care).
Results
We examined the records of a total of 25 326 patients with dementia. A minority (16% in the Cambridgeshire trust and 2.4% in the London trust) needed enhanced care. Patients who needed enhanced care differed from those who did not in age, cognitive test scores and Health of the Nation Outcome Scale scores. Logistic regression discriminated risk, with an area under the receiver operating characteristic curve (AUROC) of up to 0.78 after 1 year and 0.74 after 4 years. We were able to confirm the validity of the approach in two trusts that differed widely in the populations they serve.
Conclusions
It is possible to identify, at the time of diagnosis of dementia, individuals most likely to need enhanced care later in the disease course. This permits the development of targeted clinical interventions for this high-risk group.
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.
Three-dimensional (3D) food printing is a rapidly emerging technology offering unprecedented potential for customised food design and personalised nutrition. Here, we evaluate the technological advances in extrusion-based 3D food printing and its possibilities to promote healthy and sustainable eating. We consider the challenges in implementing the technology in real-world applications. We propose viable applications for 3D food printing in health care, health promotion and food waste upcycling. Finally, we outline future work on 3D food printing in food safety, acceptability and economics, ethics and regulations.
Jews from France settled in England in the wake of the Norman Conquest. Their fortunes oscillated until, finally taxed out of economic utility, they were expelled by Edward I in 1290. From the start of the Iberian Inquisition in 1492 tiny numbers of Jews found their way to England, living in London and Bristol as ostensible Christians. At the petition of Rabbi Manasseh Ben Israel of Amsterdam, Jews were effectively readmitted with the concurrence of Oliver Cromwell in the closing years of the Commonwealth. From the 1660s they came gradually and in small numbers from many lands in western and eastern Europe, some fleeing persecution and all in search of a better life. Predominantly poor, many eked out an existence as hawkers and pedlars, gradually settling as shopkeepers and merchants and into a variety of occupations. Over time they established synagogues, schools and institutions.
Antisemitic laws enacted in Czarist Russia in 1882 triggered an epoch of emigration from eastern Europe which continued until the start of the First World War. By 1914 there were some 250,000–300,000 Jews in Britain. Through patriotism and military service, the leadership of the Jewish community was anxious to discharge what many Jews saw as their debt of gratitude to Britain for its acceptance of them: ‘England has been all she could be to Jews. Jews will be all they can be to England’ was the prominent banner hung outside the offices of the weekly Jewish Chronicle throughout the war. Some 50,000 Jews from Britain and the empire served in the First World War. Around 2,500 lost their lives, 6,500 were wounded and five Victoria Crosses were won. Partially in response to rising post-war antisemitism, the Jewish military contribution was memorialized in various ways, including an annual service of Remembrance at the Cenotaph in London which, now embracing the Second World War, continues to this day. In the 1930s Jews were foremost amongst those who fought Oswald Mosley's British Union of Fascists at the legendary ‘Battle of Cable Street’ in London in 1936 and in numerous other encounters. By 1939 there were some 350,000 Jews in Britain, including around 55,000 recent refugees from Germany, Austria, Czechoslovakia and elsewhere in Europe.
Jewish integration into British life was gradual and undramatic. This is the basic thesis of the leading contemporary historians of British Jewry, Todd Endelman and David Feldman.
Progress towards understanding the aetiology of major depression is compromised by its clinical heterogeneity. The variety of contexts underlying the development of a major depressive episode may contribute to such heterogeneity.
Aims
To compare risk factor profiles for three subgroups of major depression according to episode context.
Method
Using self-report questionnaires and administrative records from the UK Biobank, we characterised three contextual subgroups of major depression: postpartum depression (3581 cases), depression following diagnosis of a chronic disease (409 cases) and a more typical (named heterogeneous) major depression phenotype excluding the two other contexts (34 699 cases). Controls with the same exposure were also defined. We tested each subgroup for association with the polygenic risk scores (PRS) for major depression and with other risk factors previously associated with major depression (bipolar disorder PRS, neuroticism, reported trauma in childhood and adulthood, socioeconomic status, family history of depression, education).
Results
Major depression PRS was associated with all subgroups, but postpartum depression cases had higher PRS than heterogeneous major depression cases (OR = 1.06, 95% CI 1.02–1.10). Relative to heterogeneous depression, postpartum depression was more weakly associated with adulthood trauma and neuroticism. Depression following diagnosis of a chronic disease had weaker association with neuroticism and reported trauma in adulthood and childhood relative to heterogeneous depression.
Conclusions
The observed differences in risk factor profiles according to the context of a major depressive episode help provide insight into the heterogeneity of depression. Future studies dissecting such heterogeneity could help reveal more refined aetiological insights.
A terrestrial (lacustrine and fluvial) palaeoclimate record from Hoxne (Suffolk, UK) shows two temperate phases separated by a cold episode, correlated with MIS 11 subdivisions corresponding to isotopic events 11.3 (Hoxnian interglacial period), 11.24 (Stratum C cold interval), and 11.23 (warm interval with evidence of human presence). A robust, reproducible multiproxy consensus approach validates and combines quantitative palaeotemperature reconstructions from three invertebrate groups (beetles, chironomids, and ostracods) and plant indicator taxa with qualitative implications of molluscs and small vertebrates. Compared with the present, interglacial mean monthly air temperatures were similar or up to 4.0°C higher in summer, but similar or as much as 3.0°C lower in winter; the Stratum C cold interval, following prolonged nondeposition or erosion of the lake bed, experienced summers 2.5°C cooler and winters between 5°C and 10°C cooler than at present. Possible reworking of fossils into Stratum C from underlying interglacial assemblages is taken into account. Oxygen and carbon isotopes from ostracod shells indicate evaporatively enriched lake water during Stratum C deposition. Comparative evaluation shows that proxy-based palaeoclimate reconstruction methods are best tested against each other and, if validated, can be used to generate more refined and robust results through multiproxy consensus.
The antipsychotic clozapine is known to have immune-modulating effects. Clozapine treatment has been reported to be associated with increased risk of COVID-19 infection. However, it remains unclear whether this is because of increased testing of this patient group, who are closely monitored. We linked anonymised health records from mental health services in Cambridgeshire (UK), for patients taking antipsychotic medication, with data from the local COVID-19 testing hub. Patients receiving clozapine were more likely to be tested for COVID-19, but not to test positive. Increased testing in patients receiving clozapine suggests prudent judgement by clinicians, considering the overall health vulnerabilities of this group.
Wetland sediments are valuable archives of environmental change but can be challenging to date. Terrestrial macrofossils are often sparse, resulting in radiocarbon (14C) dating of less desirable organic fractions. An alternative approach for capturing changes in atmospheric 14C is the use of terrestrial microfossils. We 14C date pollen microfossils from two Australian wetland sediment sequences and compare these to ages from other sediment fractions (n = 56). For the Holocene Lake Werri Berri record, pollen 14C ages are consistent with 14C ages on bulk sediment and humic acids (n = 14), whilst Stable Polycyclic Aromatic Carbon (SPAC) 14C ages (n = 4) are significantly younger. For Welsby Lagoon, pollen concentrate 14C ages (n = 21) provide a stratigraphically coherent sequence back to 50 ka BP. 14C ages from humic acid and >100 µm fractions (n = 13) are inconsistent, and often substantially younger than pollen ages. Our comparison of Bayesian age-depth models, developed in Oxcal, Bacon and Undatable, highlight the strengths and weaknesses of the different programs for straightforward and more complex chrono-stratigraphic records. All models display broad similarities but differences in modeled age-uncertainty, particularly when age constraints are sparse. Intensive dating of wetland sequences improves the identification of outliers and generation of robust age models, regardless of program used.
There is evidence that the COVID-19 pandemic has negatively affected mental health, but most studies have been conducted in the general population.
Aims
To identify factors associated with mental health during the COVID-19 pandemic in individuals with pre-existing mental illness.
Method
Participants (N = 2869, 78% women, ages 18–94 years) from a UK cohort (the National Centre for Mental Health) with a history of mental illness completed a cross-sectional online survey in June to August 2020. Mental health assessments were the GAD-7 (anxiety), PHQ-9 (depression) and WHO-5 (well-being) questionnaires, and a self-report question on whether their mental health had changed during the pandemic. Regressions examined associations between mental health outcomes and hypothesised risk factors. Secondary analyses examined associations between specific mental health diagnoses and mental health.
Results
A total of 60% of participants reported that mental health had worsened during the pandemic. Younger age, difficulty accessing mental health services, low income, income affected by COVID-19, worry about COVID-19, reduced sleep and increased alcohol/drug use were associated with increased depression and anxiety symptoms and reduced well-being. Feeling socially supported by friends/family/services was associated with better mental health and well-being. Participants with a history of anxiety, depression, post-traumatic stress disorder or eating disorder were more likely to report that mental health had worsened during the pandemic than individuals without a history of these diagnoses.
Conclusions
We identified factors associated with worse mental health during the COVID-19 pandemic in individuals with pre-existing mental illness, in addition to specific groups potentially at elevated risk of poor mental health during the pandemic.
Mood disorders are characterised by pronounced symptom heterogeneity, which presents a substantial challenge both to clinical practice and research. Identification of subgroups of individuals with homogeneous symptom profiles that cut across current diagnostic categories could provide insights in to the transdiagnostic relevance of individual symptoms, which current categorical diagnostic systems cannot impart.
Aims
To identify groups of people with homogeneous clinical characteristics, using symptoms of manic and/or irritable mood, and explore differences between groups in diagnoses, functional outcomes and genetic liability.
Method
We used latent class analysis on eight binary self-reported symptoms of manic and irritable mood in the UK Biobank and PROTECT studies, to investigate how individuals formed latent subgroups. We tested associations between the latent classes and diagnoses of psychiatric disorders, sociodemographic characteristics and polygenic risk scores.
Results
Five latent classes were derived in UK Biobank (N = 42 183) and were replicated in the independent PROTECT cohort (N = 4445), including ‘minimally affected’, ‘inactive restless’, active restless’, ‘focused creative’ and ‘extensively affected’ individuals. These classes differed in disorder risk, polygenic risk score and functional outcomes. One class that experienced disruptive episodes of mostly irritable mood largely comprised cases of depression/anxiety, and a class of individuals with increased confidence/creativity reported comparatively lower disruptiveness and functional impairment.
Conclusions
Findings suggest that data-driven investigations of psychopathological symptoms that include sub-diagnostic threshold conditions can complement research of clinical diagnoses. Improved classification systems of psychopathology could investigate a weighted approach to symptoms, toward a more dimensional classification of mood disorders.
Lithium is viewed as the first-line long-term treatment for prevention of relapse in people with bipolar disorder.
Aims
This study examined factors associated with the likelihood of maintaining serum lithium levels within the recommended range and explored whether the monitoring interval could be extended in some cases.
Method
We included 46 555 lithium rest requests in 3371 individuals over 7 years from three UK centres. Using lithium results in four categories (<0.4 mmol/L; 0.40–0.79 mmol/L; 0.80–0.99 mmol/L; ≥1.0 mmol/L), we determined the proportion of instances where lithium results remained stable or switched category on subsequent testing, considering the effects of age, duration of lithium therapy and testing history.
Results
For tests within the recommended range (0.40–0.99 mmol/L categories), 84.5% of subsequent tests remained within this range. Overall, 3 monthly testing was associated with 90% of lithium results remaining within range, compared with 85% at 6 monthly intervals. In cases where the lithium level in the previous 12 months was on target (0.40–0.79 mmol/L; British National Formulary/National Institute for Health and Care Excellence criteria), 90% remained within the target range at 6 months. Neither age nor duration of lithium therapy had any significant effect on lithium level stability. Levels within the 0.80–0.99 mmol/L category were linked to a higher probability of moving to the ≥1.0 mmol/L category (10%) compared with those in the 0.4–0.79 mmol/L group (2%), irrespective of testing frequency.
Conclusion
We propose that for those who achieve 12 months of lithium tests within the 0.40–0.79 mmol/L range, the interval between tests could increase to 6 months, irrespective of age. Where lithium levels are 0.80–0.99 mmol/L, the test interval should remain at 3 months. This could reduce lithium test numbers by 15% and costs by ~$0.4 m p.a.
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.
Persisting symptoms and dysfunction after SARS-CoV-2 infection have frequently been observed. However, information on the aftermath of COVID-19 is inadequate. We followed up people with severe mental illness (SMI) infected with SARS-CoV-2, and evaluated their longer-term mortality, using data from Cambridgeshire and Peterborough NHS Foundation Trust, UK. We examined the time course and duration of mortality risk from the point of diagnosis. After SARS-CoV-2 infection, people with SMI had a substantially higher risk of death (hazard ratio (HR) = 5.16, 95% confidence interval (CI) 1.56–17.03; P = 0.007) during the first 28 days and during the following 28–60 days (HR = 2.96, 95% CI 1.21–7.26; P = 0.018) than those without infection, but after 60 days the additional risk of death was no longer significant (HR = 2.33, 95% CI 0.83–6.53; P = 0.107).
We present five cases of pediatric drug-resistant epilepsy (DRE) that failed management using high cannabidiol (CBD) doses, but had significant reduction in seizure frequency with reintroduction or increasing doses of tetrahydrocannabinol (THC). There is growing evidence supporting the use of whole-plant CBD-rich extracts (containing THC and other cannabinoids) in the treatment of pediatric DRE. Based on our experiences and reports in the literature, we propose that, in patients who fail management with an initial trial of high-dose CBD-focused therapy, there may be a role for add-on THC-focused formulations.