Temporal trends in population attributable fractions of modifiable risk factors for dementia: a time-series study of the English Longitudinal Study of Ageing (2004-2019).

BACKGROUND: Interest in modifiable risk factors (MRFs) for dementia is high, given the personal, social, and economic impact of the disorder, especially in ageing societies such as the United Kingdom. Exploring the population attributable fraction (PAF) of dementia attributable to MRFs and how this may have changed over time remains unclear. Unravelling the temporal dynamics of MRFs is crucial for informing the development of evidence-based and effective public health policies. This investigation examined the temporal trajectories of MRFs for dementia in England. METHODS: We used data from the English Longitudinal Study of Ageing, a panel study over eight waves collected between 2004 and 2019 (76,904 interviews in total). We calculated the PAFs for twelve MRFs (including six early- to mid-life factors and six late-life factors), as recommended by the Lancet Commission, and the individual weighted PAFs (IW-PAFs) for each risk factor. Temporal trends were analysed to understand the changes in the overall PAF and IW-PAF over the study period. Subgroup analyses were conducted by sex and socioeconomic status (SES). RESULTS: The overall PAF for dementia MRFs changed from 46.73% in 2004/2005 to 36.79% in 2018/2019, though this trend was not statistically significant. During 2004-2019, hypertension, with an average IW-PAF of 8.21%, was the primary modifiable determinant of dementia, followed by obesity (6.16%), social isolation (5.61%), hearing loss (4.81%), depression (4.72%), low education (4.63%), physical inactivity (3.26%), diabetes mellitus (2.49%), smoking (2.0%), excessive alcohol consumption (1.16%), air pollution (0.42%), and traumatic brain injury (TBI) (0.26%). During 2004-2019, only IW-PAFs of low education, social isolation, and smoking showed significant decreasing trends, while IW-PAFs of other factors either did not change significantly or increased (including TBI, diabetes mellitus, and air pollution). Upon sex-specific disaggregation, a higher overall PAF for MRFs was found among women, predominantly associated with later-life risk factors, most notably social isolation, depression, and physical inactivity. Additionally, hearing loss, classified as an early- to mid-life factor, played a supplementary role in the identified sex disparity. A comparable discrepancy was evident upon PAF evaluation by SES, with lower income groups experiencing a higher dementia risk, largely tied to later-life factors such as social isolation, physical inactivity, depression, and smoking. Early- to mid-life factors, in particular, low education and obesity, were also observed to contribute to the SES-associated divergence in dementia risk. Temporal PAF and IW-PAF trends, stratified by sex and SES, revealed that MRF PAF gaps across sex or SES categories have persisted or increased. CONCLUSIONS: In England, there was little change over time in the proportion of dementia attributable to known modifiable risk factors. The observed trends underscore the continuing relevance of these risk factors and the need for targeted public health strategies to address them.

Predicting patients with dementia most at risk of needing psychiatric in-patient or enhanced community care using routinely collected clinical data: retrospective multi-site cohort study.

BACKGROUND: 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.

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.

Long-term impact of the COVID-19 pandemic on the quality of life of people with dementia and their family carers.

INTRODUCTION: Few studies have longitudinally mapped quality of life (QoL) trajectories of newly diagnosed people with dementia and their carers, particularly during coronavirus disease-2019 (COVID-19). METHODS: In a UK cohort study, 261 newly diagnosed people with dementia and 206 family carers were assessed prior to the pandemic (July 2019-March 2020), followed up after the first lockdown (July-October 2020) and then again a year and 2 years later. Latent growth curve modelling examined the level and change of QoL over the four time-points using dementia-specific QoL measures (DEMQOL and C-DEMQOL). RESULTS: Despite variations in individual change scores, our results suggest that generally people with dementia maintained their QoL during the pandemic and experienced some increase towards the end of the period. This contrasted with carers who reported a general deterioration in their QoL over the same period. 'Confidence in future' and 'Feeling supported' were the only carer QoL subscales to show some recovery post-pandemic. DISCUSSION: It is positive that even during a period of global disruption, decline in QoL is not inevitable following the onset of dementia. However, it is of concern that carer QoL declined during this same period even after COVID-19 restrictions had been lifted. Carers play an invaluable role in the lives of people with dementia and wider society, and our findings suggest that, post-pandemic, they may require greater support to maintain their QoL.

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.

Markers for the detection of Lewy body disease versus Alzheimer's disease in mild cognitive impairment: a systematic review and meta-analysis.

BACKGROUND: Mild cognitive impairment (MCI) may evolve into dementia. Early recognition of possible evolution to Alzheimer's disease (AD) and dementia with Lewy Bodies (DLB) is of importance, but actual diagnostic criteria have some limitations. In this systematic review and meta-analysis, we aimed to find the most accurate markers that can discriminate patients with DLB versus AD, in MCI stage. METHODS: We searched several databases up to 17 August 2023 including studies comparing markers that may distinguish DLB-MCI from AD-MCI. We reported data regarding sensitivity, specificity, and the area under the curves (AUCs) with their 95% confidence intervals (CIs). RESULTS: Among 2219 articles initially screened, eight case-control studies and one cohort study were included for a total of 832 outpatients with MCI. The accuracy of cerebrospinal fluid (CSF) markers was the highest among the markers considered (AUC > 0.90 for the CSF markers), with the AUC of CSF Aß42/Aß40 of 0.94. The accuracy for clinical symptom scales was very good (AUC = 0.93), as evaluated in three studies. Although limited to one study, the accuracy of FDG-PET (cingulate island sign ratio) was very good (AUC = 0.95) in discriminating DLB from AD in MCI, while the accuracy of SPECT markers and EEG frequencies was variable. CONCLUSIONS: Few studies have assessed the accuracy of biomarkers and clinical tools to distinguish DLB from AD at the MCI stage. While results are promising for CSF markers, FDG-PET and clinical symptoms scales, more studies, particularly with a prospective design, are needed to evaluate their accuracy and clinical usefulness. CLINICAL TRIAL REGISTRATION: Prospero (CRD42023422600).

Rates of venous thromboembolism associated with acute psychiatric admission: A retrospective cohort study.

The present study aimed to identify rates of venous thromboembolism (VTE) amongst patients treated in inpatient mental health units using linked primary care and mental health care records. Patients resident in the London Borough of Lambeth admitted to mental health units in Southeast London between January 2008 and March 2019 were included, as well as a control group of patients being treated in the community for mental illness. The primary outcome measure was a diagnosis of VTE being recorded in GP records during or within 3 months of an admission to a mental health unit. For 7,198 psychiatric inpatient admissions, 11 episodes of VTE (1.5/1,000 admissions) were identified, with no VTE cases identified in 4,561 patients being treated in the community for mental illness during an equivalent window. This finding indicates that VTE rates following psychiatric inpatient admission might be similar to those following unselected acute medical admission. Larger scale studies are required to confirm the estimated incidence of VTE in patients with mental health conditions and the contribution of acute psychiatry hospitalisation to VTE risk.

Gigantic biatrial myxoma in a young female with an atrial septal defect: a case report.

Background: Myxomas are uncommon and benign cardiac neoplasms that can present with various cardiac, systemic, embolic, or without symptoms depending on their location and size. Very few cases of large, truly biatrial, or tumours connected via the cardiac atria have been reported throughout the years. Case summary: We present an unusual case of an apparently healthy 25-year-old French woman, who presented with dyspnoea at Munich's Octoberfest. Echocardiography and computed tomography identified gigantic masses in left and right atrium, which were connected through an atrial septal defect. They were successfully removed by emergent cardiac surgery. Discussion: This case describes an uncommon tumour and highlights the importance of a quick diagnosis and prompt surgery. We describe the management and surgery for atrial myxomas as well as demonstrating pre- and intraoperative pictures.

A Blinded Evaluation of Brain Morphometry for Differential Diagnosis of Atypical Parkinsonism.

BACKGROUND: Advanced imaging techniques have been studied for differential diagnosis between PD, MSA, and PSP. OBJECTIVES: This study aims to validate the utility of individual voxel-based morphometry techniques for atypical parkinsonism in a blinded fashion. METHODS: Forty-eight healthy controls (HC) T1-WI were used to develop a referential dataset and fit a general linear model after segmentation into gray matter (GM) and white matter (WM) compartments. Segmented GM and WM with PD (n = 96), MSA (n = 18), and PSP (n = 20) were transformed into z-scores using the statistics of referential HC and individual voxel-based z-score maps were generated. An imaging diagnosis was assigned by two independent raters (trained and untrained) blinded to clinical information and final diagnosis. Furthermore, we developed an observer-independent index for ROI-based automated differentiation. RESULTS: The diagnostic performance using voxel-based z-score maps by rater 1 and rater 2 for MSA yielded sensitivities: 0.89, 0.94 (95% CI: 0.74-1.00, 0.84-1.00), specificities: 0.94, 0.80 (0.90-0.98, 0.73-0.87); for PSP, sensitivities: 0.85, 0.90 (0.69-1.00, 0.77-1.00), specificities: 0.98, 0.94 (0.96-1.00, 0.90-0.98). Interrater agreement was good for MSA (Cohen's kappa: 0.61), and excellent for PSP (0.84). Receiver operating characteristic analysis using the ROI-based new index showed an area under the curve (AUC): 0.89 (0.77-1.00) for MSA, and 0.99 (0.98-1.00) for PSP. CONCLUSIONS: These evaluations provide support for the utility of this imaging technique in the differential diagnosis of atypical parkinsonism demonstrating a remarkably high differentiation accuracy for PSP, suggesting potential use in clinical settings in the future.

Probiotics' Effects in the Treatment of Anxiety and Depression: A Comprehensive Review of 2014-2023 Clinical Trials.

Changes in the gut microbiome can affect cognitive and psychological functions via the microbiota-gut-brain (MGB) axis. Probiotic supplements are thought to have largely positive effects on mental health when taken in sufficient amounts; however, despite extensive research having been conducted, there is a lack of consistent findings on the effects of probiotics on anxiety and depression and the associated microbiome alterations. The aim of our study is to systematically review the most recent literature of the last 10 years in order to clarify whether probiotics could actually improve depression and anxiety symptoms. Our results indicate that the majority of the most recent literature suggests a beneficial role of probiotics in the treatment of depression and anxiety, despite the existence of a substantial number of less positive findings. Given probiotics' potential to offer novel, personalized treatment options for mood disorders, further, better targeted research in psychiatric populations is needed to address concerns about the exact mechanisms of probiotics, dosing, timing of treatment, and possible differences in outcomes depending on the severity of anxiety and depression.

BioPrint meets the AI age: development of artificial intelligence-based ADMET models for the drug-discovery platform SAFIRE.

Background: To prioritize compounds with a higher likelihood of success, artificial intelligence models can be used to predict absorption, distribution, metabolism, excretion and toxicity (ADMET) properties of molecules quickly and efficiently. Methods: Models were trained with BioPrint database proprietary data along with public datasets to predict various ADMET end points for the SAFIRE platform. Results: SAFIRE models performed at or above 75% accuracy and 0.4 Matthew's correlation coefficient with validation sets. Training with both proprietary and public data improved model performance and expanded the chemical space on which the models were trained. The platform features scoring functionality to guide user decision-making. Conclusion: High-quality datasets along with chemical space considerations yielded ADMET models performing favorably with utility in the drug discovery process.

Mid-Term Outcome after Extracorporeal Life Support in Postcardiotomy Cardiogenic Shock: Recovery and Quality of Life.

Background: Extracorporeal life support (ECLS) therapy for refractory postcardiotomy cardiogenic shock (rPCS) is associated with high early mortality rates. This study aimed to identify negative predictors of mid-term survival and to assess health-related quality of life (HRQoL) and recovery of the survivors. Methods: Between 2017 and 2020, 142 consecutive patients received ECLS therapy following cardiac surgery. The median age was 66.0 [57.0-73.0] years, 67.6% were male and the median EuroSCORE II was 10.5% [4.2-21.3]. In 48 patients, HRQoL was examined using the 36-Item Short Form Survey (SF-36) and the modified Rankin-Scale (mRS) at a median follow-up time of 2.2 [1.9-3.2] years. Results: Estimated survival rates at 3, 12, 24 and 36 months were 47%, 46%, 43% and 43% (SE: 4%). Multivariable Cox Proportional Hazard regression analysis revealed preoperative EuroSCORE II (p = 0.013), impaired renal function (p = 0.010), cardiopulmonary bypass duration (p = 0.015) and pre-ECLS lactate levels (p = 0.004) as independent predictors of mid-term mortality. At the time of follow-up, 83.3% of the survivors were free of moderate to severe disability (mRS < 3). SF-36 analysis showed a physical component summary of 45.5 ± 10.2 and a mental component summary of 50.6 ± 12.5. Conclusions: Considering the disease to be treated, ECLS for rPCS is associated with acceptable mid-term survival, health-related quality of life and functional status. Preoperative EuroSCORE II, impaired renal function, cardiopulmonary bypass duration and lactate levels prior to ECLS implantation were identified as negative predictors and should be included in the decision-making process.

Failure of Surgical Aortic Valve Prostheses: An Analysis of Heart Team Decisions and Postoperative Outcomes.

Objectives: To analyze Heart Team decisions and outcomes following failure of surgical aortic valve replacement (SAVR) prostheses. Methods: Patients undergoing re-operations following index SAVR (Redo-SAVR) and those undergoing valve-in-valve transcatheter aortic valve replacement (ViV-TAVR) following SAVR were included in this study. Patients who underwent index SAVR and/or Redo-SAVR for endocarditis were excluded. Data are presented as medians and 25th-75th percentiles, or absolute numbers and percentages. Outcomes were analyzed in accordance to the VARC-3 criteria. Results: Between 01/2015 and 03/2021, 53 patients underwent Redo-SAVR, 103 patients ViV-TAVR. Mean EuroSCORE II was 5.7% (3.5-8.5) in the Redo-SAVR group and 9.2% (5.4-13.6) in the ViV group. In the Redo-SAVR group, 12 patients received aortic root enlargement (22.6%). Length of hospital and ICU stay was longer in the Redo-SAVR group (p < 0.001; p < 0.001), PGmax and PGmean were lower in the Redo-SAVR group as compared to the ViV-TAVR group (18 mmHg (10-30) vs. 26 mmHg (19-38), p < 0.001) (9 mmHg (6-15) vs. 15 mmHg (9-21), p < 0.001). A higher rate of paravalvular leakage was seen in the ViV-TAVR group (p = 0.013). VARC-3 Early Safety were comparable between the two populations (p = 0.343). Survival at 1 year and 5 years was 82% and 36% in the ViV-TAVR cohort and 84% and 77% in the Redo-SAVR cohort. The variables were patient age (OR 1.061; [95% CI 1.020-1.104], p = 0.004), coronary heart disease (OR 2.648; [95% CI 1.160-6.048], p = 0.021), and chronic renal insufficiency (OR 2.711; [95% CI 1.160-6.048], p = 0.021) showed a significant correlation to ViV-TAVR. Conclusions: Heart Team decisions are crucial in the treatment of patients with degenerated aortic bioprostheses and lead to a low mortality in both treatment paths thanks to patient-specific therapy planning. ViV-TAVR offers a treatment for elderly or intermediate-risk profile patients with comparable short-term mortality. However, this therapy is associated with increased pressure gradients and a high prevalence of paravalvular leakage. Redo-SAVR enables the surgical treatment of concomitant cardiac pathologies and allows anticipation for later VIV-TAVR by implanting the largest possible valve prostheses.

Influence of donor age and donor-recipient age difference on intimal hyperplasia in pediatric patients with young and adult donors vs. adult patients after heart transplantation.

AIM: Optimal selection and allocation of donor hearts is a relevant aspect in transplantation medicine. Donor age and cardiac allograft vasculopathy (CAV) affect post-transplant mortality. To what extent donor age impacts intimal hyperplasia (CAVIH) in pediatric and adult patients after heart transplantation (HTx) is understudied. METHODS: In a cohort of 98 HTx patients, 58 pediatric (24.1% with adult donors) and 40 adult patients, we assessed the effect of donor age and donor-recipient age difference (D-R) on the continuous parameter of maximal intima thickness (mIT) in optical coherence tomography. We evaluated their predictive value regarding higher mIT and the prevalence of CAVIH, defined as mIT > 0.3 mm, and compared it to established CAV risk factors. RESULTS: In the overall population, donor age correlated with mIT (p < 0.001), while in the pediatric subpopulation, both donor age and D-R correlated with mIT (p < 0.001 and p = 0.002, respectively). In the overall population, donor age was a main predictor of higher mIT and CAVIH (p = 0.001 and p = 0.01, respectively) in addition to post-transplant interval, arterial hypertension, and dyslipidemia. In the pediatric patients, dyslipidemia remained a main predictor of both higher mIT and CAVIH (p = 0.004 and p = 0.040, respectively), while donor age and D-R were not. CONCLUSION: While there was an effect of the non-modifiable parameter of donor age regarding maximal intimal thickness, a stronger association was seen between the modifiable risk factor dyslipidemia and higher maximal intimal thickness and CAVIH in both the overall population and the pediatric subpopulation.

The SLICE-3D dataset: 400,000 skin lesion image crops extracted from 3D TBP for skin cancer detection.

AI image classification algorithms have shown promising results when applied to skin cancer detection. Most public skin cancer image datasets are comprised of dermoscopic photos and are limited by selection bias, lack of standardization, and lend themselves to development of algorithms that can only be used by skilled clinicians. The SLICE-3D ("Skin Lesion Image Crops Extracted from 3D TBP") dataset described here addresses those concerns and contains images of over 400,000 distinct skin lesions from seven dermatologic centers from around the world. De-identified images were systematically extracted from sensitive 3D Total Body Photographs and are comparable in optical resolution to smartphone images. Algorithms trained on lower quality images could improve clinical workflows and detect skin cancers earlier if deployed in primary care or non-clinical settings, where photos are captured by non-expert physicians or patients. Such a tool could prompt individuals to visit a specialized dermatologist. This dataset circumvents many inherent limitations of prior datasets and may be used to build upon previous applications of skin imaging for cancer detection.

Case report: Paracorporeal lung assist device for 215 days as a bridge-to-lung transplantation in a patient with bronchopulmonary dysplasia and severe pulmonary hypertension.

Pulmonary hypertension (PH) is a known and life limiting complication of preterm born young adults with bronchopulmonary dysplasia (BPD), ultimately leading to progressive right ventricular (RV) failure. Prognosis remains poor, especially in patients unresponsive to modern vasoactive pharmacotherapy. Therefore, lung transplantation presents the treatment of choice to avert cardiac failure. With limited donor organ availability and long waiting times, the implantation of a paracorporeal lung assist device (PLAD) is a way to bridge the patient as an alternative to veno-arterial ECMO. Herein, we present the case of a prematurely born 23-year-old female, who developed severe PH due to BPD and consequently experienced therapy refractory RV failure. Urgent PLAD implantation was performed and the patient successfully underwent double-lung transplantation after 215 days of PLAD support. No major PLAD-associated complications occurred and full recovery of RV function could be observed after double-lung transplantation.