MEG in MRI-Negative Patients with Focal Epilepsy.

OBJECTIVES: To review the evidence on the clinical value of magnetic source imaging (MSI) in patients with refractory focal epilepsy without evidence for an epileptogenic lesion on magnetic resonance imaging ("MRI-negative" or "non-lesional MRI"). METHODS: We conducted a systematic literature search on PUBMED, which was extended by researchrabbit.ai using predefined criteria to identify studies that applied MSI in MRI-negative patients with epilepsy. We extracted data on patient characteristics, MSI methods, localization results, surgical outcomes, and correlation with other modalities. RESULTS: We included 23 studies with a total of 512 non-lesional epilepsy patients who underwent MSI. Most studies used equivalent current dipole (ECD) models to estimate the sources of interictal epileptic discharges (IEDs). MEG detected IEDs in 32-100% of patients. MSI results were concordant with other modalities, such as EEG, PET, and SPECT, in 3892% of cases. If MSI concordant surgery was performed, 52-89% of patients achieved seizure freedom. MSI contributed to the decision-making process in 28-75% of cases and altered the surgical plan in 5-33% of cases. CONCLUSIONS: MSI is a valuable diagnostic tool for MRI-negative patients with epilepsy, as it can detect and localize IEDs with high accuracy and sensitivity, and provides useful information for surgical planning and predicts outcomes. MSI can also complement and refine the results of other modalities, such as EEG and PET, and optimize the use of invasive recordings. MSI should be considered as part of the presurgical evaluation, especially in patients with non-lesional refractory epilepsy.

The role of finerenone in the management of CKD in T2D -Practical considerations for primary care.

The prevalence of diabetes and chronic kidney disease (CKD) is increasing worldwide. Diabetic kidney disease is a chronic condition characterized by a gradual increase in urinary albumin excretion, blood pressure, cardiovascular risk, and a decline in glomerular filtration rate (GFR) that can progress to end-stage kidney disease (ESKD). Individuals with diabetes should be screened for CKD annually. Screening should include both measurement of albuminuria and estimation of GFR (eGFR). The structural changes in diabetic kidney disease in individuals with type 1 diabetes are rather uniform, but the histological picture in those with type 2 diabetes and CKD is on the contrary a mix of changes ranging from minor abnormalities to severe glomerulosclerosis, tubulointerstitial fibrosis, and arteriolohyalinosis. Scarring of the kidneys is closely related to the kidney function. Individuals with diabetes often require multiple therapies to prevent progression of CKD and its associated comorbidities and mortality. Management of cardiorenal risk factors, including lifestyle modification, control of blood glucose, blood pressure, and lipids, use of renin-angiotensin-aldosterone system (RAAS) blockers, use of sodium-glucose co-transporter 2 (SGLT2) inhibitors, and the non-steroidal mineralocorticoid receptor antagonist finerenone in individuals with T2D are the cornerstones of therapy. Primary care physicians (PCPs) play a critical role in identifying individuals with CKD, managing early stages of CKD, and referring those with moderate to severe CKD or rapidly declining kidney function to a nephrologist. Referral to a nephrologist should be considered when certain thresholds for eGFR, albuminuria, proteinuria, hematuria, or hypertension are exceeded. This review summarizes current guidelines for the management of CKD and its complications and highlights the role of PCPs in the care of individuals with CKD.

Frailty indices predict mortality, complications and functional improvements in supratentorial meningioma patients over 80 years of age.

PURPOSE: To assess whether the Modified 5 (mFI-5) and 11 (mFI-11) Factor Frailty Indices associate with postoperative mortality, complications, and functional benefit in supratentorial meningioma patients aged over 80 years. METHODS: Baseline characteristics were collected from eight centers. Based on the patients' preoperative status and comorbidities, frailty was assessed by the mFI-5 and mFI-11. The collected scores were categorized as "robust (mFI=0)", "pre-frail (mFI=1)", "frail (mFI=2)", and "significantly frail (mFI≥3)". Outcome was assessed by the Karnofsky Performance Scale (KPS); functional benefit was defined as improved KPS score. Additionally, we evaluated the patients' functional independence (KPS≥70) after surgery. RESULTS: The study population consisted of 262 patients (median age 83 years) with a median preoperative KPS of 70 (range 20 to 100). The 90-day and 1-year mortality were 9.0% and 13.2%; we recorded surgery-associated complications in 111 (42.4%) patients. At last follow-up within the postoperative first year, 101 (38.5%) patients showed an improved KPS, and 183 (69.8%) either gained or maintained functional independence. "Severely frail" patients were at an increased risk of death at 90 days (OR 16.3 (CI95% 1.7-158.7)) and one year (OR 11.7 (CI95% 1.9-71.7)); nine (42.9%) of severely frail patients died within the first year after surgery. The "severely frail" cohort had increased odds of suffering from surgery-associated complications (OR 3.9 (CI 95%) 1.3-11.3)), but also had a high chance for postoperative functional improvements by KPS≥20 (OR 6.6 (CI95% 1.2-36.2)). CONCLUSION: The mFI-5 and mFI-11 associate with postoperative mortality, complications, and functional benefit. Even though "severely frail" patients had the highest risk morbidity and mortality, they had the highest chance for functional improvement.

Dysglycaemia screening and its prognostic impact in patients with coronary artery disease: experiences from the EUROASPIRE IV and V cohort studies.

BACKGROUND: Glucose perturbations can be detected by fasting plasma glucose (FPG), HbA1c, and the oral glucose tolerance test (OGTT). The highest yield is provided by OGTT. HbA1c is considered more practical. We compare the diagnostic and predictive performance of these glycaemic indicators based on combined data from the EUROASPIRE IV (EAIV) and V (EAV) studies. METHODS: This cohort study was conducted in 79 centres in 24 European countries (EAIV) and 131 centres in 27 European countries (EAV). Eligible patients were aged 18-80 years, did not have diabetes, and were diagnosed with coronary artery disease 6-36 months (EAIV) or 6-24 months (EAV) before the investigation. Patients were investigated with OGTT (FPG and 2 h post-load glucose [2-hPG]) and HbA1c. Follow-up of subsequent cardiovascular events was done by means of a questionnaire at least 1 year after the baseline investigation. Analyses were done in patients with both OGTT and HbA1c data available. Outcome analysis in these patients was restricted to those with valid follow-up data available. FINDINGS: 16 259 patients were interviewed in EAIV (2012-13) and EAV (2016-17). 8364 patients had both OGTT and HbA1C data and were included in the analysis population (3932 in EAIV and 4432 in EAV). Information on cardiovascular events was available in 7892 patients. Follow-up was for a median 1·6 years (IQR 1·2-2·0). The average patient age was 63·3 years (SD 9·8), and 6346 (75·9%) of 8364 patients were men. At baseline, 1856 (22·5%) of 8263 patients were determined to have newly detected type 2 diabetes using OGTT alone, compared with 346 (4·2%) using HbA1c alone. New dysglycaemia, defined as newly detected type 2 diabetes or impaired glucose tolerance (IGT), was present in 3896 (47·1%) of the patients according to 2hPG. 2hPG 9 mmol/L or greater (162 mg/dL, adjusted hazard ratio [aHR] 1·58; 95% CI 1·27-1·95, p<0·0001), and HbA1c 5·9% or greater (41 mmol/mol, aHR 1·48, 1·19-1·84; p=0·0010) were the strongest predictors of cardiovascular events, while FPG did not predict. A multivariable model showed that the effect of HbA1c on cardiovascular events was mainly explained by 2hPG (aHR for 1 unit increase in HbA1c 1·13, 0·98-1·30; p=0·11; and aHR for 1 unit increase in Ln[2hPG] 1·37, 1·08-1·74; p=0·0042). INTERPRETATION: 2hPG appears better than HbA1c in detecting dysglycaemia and predicting its impact on future cardiovascular events in patients with coronary artery disease and should be recommended as the primary screening tool. FUNDING: Swedish Heart-Lung Foundation, Region Stockholm (ALF), the Erling Persson Foundation, the Baltic Child Foundation.

The oncological role of resection in newly diagnosed diffuse adult-type glioma defined by the WHO 2021 classification: a Review by the RANO resect group.

Glioma resection is associated with prolonged survival, but neuro-oncological trials have frequently refrained from quantifying the extent of resection. The Response Assessment in Neuro-Oncology (RANO) resect group is an international, multidisciplinary group that aims to standardise research practice by delineating the oncological role of surgery in diffuse adult-type gliomas as defined per WHO 2021 classification. Favourable survival effects of more extensive resection unfold over months to decades depending on the molecular tumour profile. In tumours with a more aggressive natural history, supramaximal resection might correlate with additional survival benefit. Weighing the expected survival benefits of resection as dictated by molecular tumour profiles against clinical factors, including the introduction of neurological deficits, we propose an algorithm to estimate the oncological effects of surgery for newly diagnosed gliomas. The algorithm serves to select patients who might benefit most from extensive resection and to emphasise the relevance of quantifying the extent of resection in clinical trials.

Characteristics of Nocturnal Hypoglycaemic Events and Their Impact on Glycaemia.

BACKGROUND: Nocturnal hypoglycaemia is a burden for people with diabetes, particularly when treated with multiple daily injections (MDI) therapy. However, the characteristics of nocturnal hypoglycaemic events in this patient group are only poorly described in the literature. METHOD: Continuous glucose monitoring (CGM) data from 185 study participants with type 1 diabetes using MDI therapy were collected under everyday conditions for up to 13 weeks. Hypoglycaemic events were identified as episodes of consecutive CGM readings <70 mg/dl or <54 mg/dl for at least 15 minutes. Subsequently, the time <54 mg/dl (TB54), time below range (TBR), time in range (TIR), time above range (TAR), glucose coefficient of variation (CV), and incidence of hypoglycaemic events were calculated for diurnal and nocturnal periods. Furthermore, the effect of nocturnal hypoglycaemic events on glucose levels the following day was assessed. RESULTS: The incidence of hypoglycaemic events <70 mg/dl was significantly lower during the night compared to the day, with 0.8 and 3.8 events per week, respectively, while the TBR, TB54, and incidence of events with CGM readings <54 mg/dl was not significantly different. Nocturnal hypoglycaemic events <70 mg/dl were significantly longer (60 vs 35 minutes) and enveloped by less rapidly changing glucose levels. On days following nights containing hypoglycaemic events, there was a decrease in TAR, mean CGM glucose level and morning glucose levels and an increase in TB54, TBR, and CV. CONCLUSIONS: The results showed that nocturnal hypoglycaemic events are a common occurrence in persons with type 1 diabetes using MDI with significant differences between the characteristics of nocturnal and diurnal events.

Nocturnal Hypoglycemia in the Era of Continuous Glucose Monitoring.

Nocturnal hypoglycemia is a common acute complication of people with diabetes on insulin therapy. In particular, the inability to control glucose levels during sleep, the impact of external factors such as exercise, or alcohol and the influence of hormones are the main causes. Nocturnal hypoglycemia has several negative somatic, psychological, and social effects for people with diabetes, which are summarized in this article. With the advent of continuous glucose monitoring (CGM), it has been shown that the number of nocturnal hypoglycemic events was significantly underestimated when traditional blood glucose monitoring was used. The CGM can reduce the number of nocturnal hypoglycemia episodes with the help of alarms, trend arrows, and evaluation routines. In combination with CGM with an insulin pump and an algorithm, automatic glucose adjustment (AID) systems have their particular strength in nocturnal glucose regulation and the prevention of nocturnal hypoglycemia. Nevertheless, the problem of nocturnal hypoglycemia has not yet been solved completely with the technologies currently available. The CGM systems that use predictive models to warn of hypoglycemia, improved AID systems that recognize hypoglycemia patterns even better, and the increasing integration of artificial intelligence methods are promising approaches in the future to significantly minimize the risk of a side effect of insulin therapy that is burdensome for people with diabetes.

Rapid phagosome isolation enables unbiased multiomic analysis of human microglial phagosomes.

Microglia are the resident macrophages of the central nervous system (CNS). Their phagocytic activity is central during brain development and homeostasis-and in a plethora of brain pathologies. However, little is known about the composition, dynamics, and function of human microglial phagosomes under homeostatic and pathological conditions. Here, we developed a method for rapid isolation of pure and intact phagosomes from human pluripotent stem cell-derived microglia under various in vitro conditions, and from human brain biopsies, for unbiased multiomic analysis. Phagosome profiling revealed that microglial phagosomes were equipped to sense minute changes in their environment and were highly dynamic. We detected proteins involved in synapse homeostasis, or implicated in brain pathologies, and identified the phagosome as the site where quinolinic acid was stored and metabolized for de novo nicotinamide adenine dinucleotide (NAD+) generation in the cytoplasm. Our findings highlight the central role of phagosomes in microglial functioning in the healthy and diseased brain.

Comprehensive multimodal deep learning survival prediction enabled by a transformer architecture: A multicenter study in glioblastoma.

Background: This research aims to improve glioblastoma survival prediction by integrating MR images, clinical, and molecular-pathologic data in a transformer-based deep learning model, addressing data heterogeneity and performance generalizability. Methods: We propose and evaluate a transformer-based nonlinear and nonproportional survival prediction model. The model employs self-supervised learning techniques to effectively encode the high-dimensional MRI input for integration with nonimaging data using cross-attention. To demonstrate model generalizability, the model is assessed with the time-dependent concordance index (Cdt) in 2 training setups using 3 independent public test sets: UPenn-GBM, UCSF-PDGM, and Rio Hortega University Hospital (RHUH)-GBM, each comprising 378, 366, and 36 cases, respectively. Results: The proposed transformer model achieved a promising performance for imaging as well as nonimaging data, effectively integrating both modalities for enhanced performance (UCSF-PDGM test-set, imaging Cdt 0.578, multimodal Cdt 0.672) while outperforming state-of-the-art late-fusion 3D-CNN-based models. Consistent performance was observed across the 3 independent multicenter test sets with Cdt values of 0.707 (UPenn-GBM, internal test set), 0.672 (UCSF-PDGM, first external test set), and 0.618 (RHUH-GBM, second external test set). The model achieved significant discrimination between patients with favorable and unfavorable survival for all 3 datasets (log-rank P 1.9 × 10-8, 9.7 × 10-3, and 1.2 × 10-2). Comparable results were obtained in the second setup using UCSF-PDGM for training/internal testing and UPenn-GBM and RHUH-GBM for external testing (Cdt 0.670, 0.638, and 0.621). Conclusions: The proposed transformer-based survival prediction model integrates complementary information from diverse input modalities, contributing to improved glioblastoma survival prediction compared to state-of-the-art methods. Consistent performance was observed across institutions supporting model generalizability.

Comprehensive genetic profiling and molecularly guided treatment for patients with primary CNS tumors.

Despite major advances in molecular profiling and classification of primary brain tumors, personalized treatment remains limited for most patients. Here, we explored the feasibility of individual molecular profiling and the efficacy of biomarker-guided therapy for adult patients with primary brain cancers in the real-world setting within the molecular tumor board Freiburg, Germany. We analyzed genetic profiles, personalized treatment recommendations, and clinical outcomes of 102 patients with 21 brain tumor types. Alterations in the cell cycle, BRAF, and mTOR pathways most frequently led to personalized treatment recommendations. Molecularly informed therapies were recommended in 71% and implemented in 32% of patients with completed molecular diagnostics. The disease control rate following targeted treatment was 50% and the overall response rate was 30%, with a progression-free survival 2/1 ratio of at least 1.3 in 31% of patients. This study highlights the efficacy of molecularly guided treatment and the need for biomarker-stratified trials in brain cancers.

Inferring histology-associated gene expression gradients in spatial transcriptomic studies.

Spatially resolved transcriptomics has revolutionized RNA studies by aligning RNA abundance with tissue structure, enabling direct comparisons between histology and gene expression. Traditional approaches to identifying signature genes often involve preliminary data grouping, which can overlook subtle expression patterns in complex tissues. We present Spatial Gradient Screening, an algorithm which facilitates the supervised detection of histology-associated gene expression patterns without prior data grouping. Utilizing spatial transcriptomic data along with single-cell deconvolution from injured mouse cortex, and TCR-seq data from brain tumors, we compare our methodology to standard differential gene expression analysis. Our findings illustrate both the advantages and limitations of cluster-free detection of gene expression, offering more profound insights into the spatial architecture of transcriptomes. The algorithm is embedded in SPATA2, an open-source framework written in R, which provides a comprehensive set of tools for investigating gene expression within tissue.

Topographical anatomy of the septum verum and its white matter connections.

The human septum verum represents a small but clinically important region of the brain. Based on the results of animal experiments, the stimulation of its medial part was recently proposed with various indications like epilepsy or cognitive impairment after traumatic brain injury. The aim of our study was to present the anatomical relationships of the human septum verum using fiber dissection and histological analysis to support its research and provide essential information for future deep brain stimulation therapies. 16 human cadaveric brains were dissected according to Klingler's method. To validate our macroscopical findings, 12 samples obtained from the dissected brains and 2 additional specimens from unfrozen brains were prepared for histological examinations. We identified the following white matter connections of the septum verum: (1) the precommissural fibers of the fornix; (2) the inferior fascicle of the septum pellucidum; (3) the cingulum; (4) the medial olfactory stria; (5) the ventral amygdalofugal pathway; (6) the stria medullaris of the thalamus and (7) the stria terminalis. Moreover, we could distinguish a less-known fiber bundle connecting the postcommissural column of the fornix to the stria medullaris of the thalamus and the anterior thalamic nuclei. In this study we present valuable anatomical information about this region to promote safe and effective deep brain stimulation therapies in the future.

The role of incretin receptor agonists in the treatment of obesity.

INTRODRODUCTION: Obesity and its associated metabolic conditions have become a significant global health problem in recent years, with many people living with obesity fulfilling criteria for pharmacological treatment. The development of the glucagon-like peptide-1 receptor agonists for chronic weight management has triggered new interest in the incretins and other hormones as targets for obesity, and investigations into dual and triple co-agonists. METHODS: The objective of this narrative review was to summarize the available data on approved and emerging incretin-based agents for the treatment of obesity. RESULTS: In clinical trials of currently available agents in people with overweight or obesity, weight loss of between 6% and 21% of baseline body weight has been observed, with between 23% and 94% of participants achieving 10% or higher weight loss, depending on the study and the agent used. Favourable outcomes have also been seen with regard to cardiovascular risk and outcomes, diabetes prevention, metabolic dysfunction-associated steatotic liver disease/steatohepatitis and prevention of weight regain after metabolic surgery. Limitations associated with these agents include high costs, the potential for weight regain once treatment is stopped, the potential loss of lean body mass and gastrointestinal adverse events; potential issues with respect to gallbladder and biliary diseases require further investigation. CONCLUSIONS: Many dual and triple co-agonists are still in development, and more data are needed to assess the efficacy, safety and tolerability of these emerging therapies versus the established incretin-based therapies; however, data are promising, and further results are eagerly awaited.

Localization of protoporphyrin IX during glioma-resection surgery via paired stimulated Raman histology and fluorescence microscopy.

The most widely used fluorophore in glioma-resection surgery, 5-aminolevulinic acid (5-ALA), is thought to cause the selective accumulation of fluorescent protoporphyrin IX (PpIX) in tumour cells. Here we show that the clinical detection of PpIX can be improved via a microscope that performs paired stimulated Raman histology and two-photon excitation fluorescence microscopy (TPEF). We validated the technique in fresh tumour specimens from 115 patients with high-grade gliomas across four medical institutions. We found a weak negative correlation between tissue cellularity and the fluorescence intensity of PpIX across all imaged specimens. Semi-supervised clustering of the TPEF images revealed five distinct patterns of PpIX fluorescence, and spatial transcriptomic analyses of the imaged tissue showed that myeloid cells predominate in areas where PpIX accumulates in the intracellular space. Further analysis of external spatially resolved metabolomics, transcriptomics and RNA-sequencing datasets from glioblastoma specimens confirmed that myeloid cells preferentially accumulate and metabolize PpIX. Our findings question 5-ALA-induced fluorescence in glioma cells and show how 5-ALA and TPEF imaging can provide a window into the immune microenvironment of gliomas.

Undetected permanent dental inflammation as a possible trigger for brain abscesses? A retrospective analysis over the last 2 decades.

BACKGROUND: Recently, there is increasing evidence that the proportion of odontogenic brain abscesses is greater than previously known. In this study, we aim to differentiate the oral infections as triggers more precisely and to classify them in the clinical setting. METHODS: For analysis, we conducted a retrospective single center study. We reviewed patients with brain abscesses who have undergone treatment in the University Hospital of Freiburg, Germany in the period between 2000-2021. Inclusion required two main criteria: 1. The brain abscess must not have an other focus than odontogenic. 2. The microbial spectrum identified in the brain abscess must be consistent with an odontogenic origin. RESULTS: Of 217 brain abscess patients, 26 met the inclusion criteria. 42% (11 patients) suffered from immunosuppressive conditions. Odontogenic foci were diagnosed in 18 cases (69%). Neurologic deficits included vigilance reduction and hemiparesis. Pathogens of the Streptococcus anginosus group were the most frequent causative agent (21 cases, 81%). Metronidazole (54%) and ceftriaxone (42%) were part of the targeted antibiotic therapy. All brain abscesses were surgically treated. Teeth were extracted in 14 of 17 cases for focus control. 18 cases (72%) showed complete or partial resolution of neurologic symptoms and 3 cases were fatal. CONCLUSION: Apparently silent or chronic oral infections are sufficient to cause bacterial colonization of the brain, especially in immunocompromised patients. Therefore, special care should be taken to maintain good oral health. An interdisciplinary management should become a standard to prevent and treat the occurrence of brain abscesses.

Effects of tumor treating fields (TTFields) on human mesenchymal stromal cells.

PURPOSE: Mesenchymal stromal cells (MSCs) within the glioblastoma microenvironment have been shown to promote tumor progression. Tumor Treating Fields (TTFields) are alternating electric fields with low intensity and intermediate frequency that exhibit anti-tumorigenic effects. While the effects of TTFields on glioblastoma cells have been studied previously, nothing is known about the influence of TTFields on MSCs. METHODS: Single-cell RNA sequencing and immunofluorescence staining were employed to identify glioblastoma-associated MSCs in patient samples. Proliferation and clonogenic survival of human bone marrow-derived MSCs were assessed after TTFields in vitro. MSC' characteristic surface marker expression was determined using flow cytometry, while multi-lineage differentiation potential was examined with immunohistochemistry. Apoptosis was quantified based on caspase-3 and annexin-V/7-AAD levels in flow cytometry, and senescence was assessed with ß-galactosidase staining. MSCs' migratory potential was evaluated with Boyden chamber assays. RESULTS: Single-cell RNA sequencing and immunofluorescence showed the presence of glioblastoma-associated MSCs in patient samples. TTFields significantly reduced proliferation and clonogenic survival of human bone marrow-derived MSCs by up to 60% and 90%, respectively. While the characteristic surface marker expression and differentiation capacity were intact after TTFields, treatment resulted in increased apoptosis and senescence. Furthermore, TTFields significantly reduced MSCs' migratory capacity. CONCLUSION: We could demonstrate the presence of tumor-associated MSCs in glioblastoma patients, providing a rationale to study the impact of TTFields on MSCs. TTFields considerably increase apoptosis and senescence in MSCs, resulting in impaired survival and migration. The results provide a basis for further analyses on the role of MSCs in glioblastoma patients receiving TTFields.

Current Practice of Podiatrists in Testing for Diabetic Polyneuropathy and Implementing Foot Care (PROTECT Study Survey 2).

AIMS: Podiatrists constitute a key member of a multidisciplinary foot care team, but their services remain underutilized. We sought to gain insights into the daily practice of podiatrists focusing on screening for and monitoring of diabetic sensorimotor polyneuropathy (DSPN) as well as foot management. METHODS: This cross-sectional survey included 125 podiatrists from 12 federal states across Germany who responded to an online questionnaire. RESULTS: The majority of patients treated in podiatry practices were referred by general practitioners and diabetologists. Screening for or follow-up of DSPN was performed by 36% of the respondents at least once a year, by 28% only at initial examination, by 21% only at suspicion, and by 10% basically at each treatment visit. Instruments to assess vibration, touch/pressure, and temperature sensation were used by 81% to 94% of the podiatrists. Previously undiagnosed DSPN and foot ulcers were detected frequently/very frequently (≥6 cases/mo) by 24.0 and 18.4% of the podiatrists, respectively. Almost all podiatrists advised daily self-monitoring of feet and appropriate foot care and >50% gave advice on medical treatment. CONCLUSIONS: Podiatrists play an important role in the detection, monitoring, and management of both DSPN and diabetic foot ulcers, suggesting that the utilization of their services should be fostered.

Towards the standardisation of adult person-reported outcome domains in diabetes research: A Consensus Statement development panel.

Diabetes is unique among chronic diseases because clinical outcomes are intimately tied to how the person living with diabetes reacts to and implements treatment recommendations. It is further characterised by widespread social stigma, judgement and paternalism. This physical, social and psychological burden collectively influences self-management behaviours. It is widely recognised that the individual's perspective about the impact of trying to manage the disease and the burden that self-management confers must be addressed to achieve optimal health outcomes. Standardised, rigorous assessment of mental and behavioural health status, in interaction with physical health outcomes is crucial to aid understanding of person-reported outcomes (PROs). Whilst tempting to conceptualise PROs as an issue of perceived quality of life (QoL), in fact health-related QoL is multi-dimensional and covers indicators of physical or functional health status, psychological and social well-being. This complexity is illuminated by the large number of person reported outcome measures (PROMs) that have been developed across multiple psychosocial domains. Often measures are used inappropriately or because they have been used in the scientific literature rather than based on methodological or outcome assessment rigour. Given the broad nature of psychosocial functioning/mental health, it is important to broadly define PROs that are evaluated in the context of therapeutic interventions, real-life and observational studies. This report summarises the central themes and lessons derived in the assessment and use of PROMs amongst adults with diabetes. Effective assessment of PROMs routinely in clinical research is crucial to understanding the true impact of any intervention. Selecting appropriate measures, relevant to the specific factors of PROs important in the research study will provide valuable data alongside physical health data.

Dual-pathway Inhibition with Low-dose Aspirin and Rivaroxaban versus Aspirin Monotherapy in Patients with Coronary Artery Disease and Peripheral Artery Disease: Systematic Literature Review and Meta-analysis.

Background: Low-dose aspirin lowers cardiovascular event risk; dual-pathway inhibition (DPI) using low-dose aspirin with low-dose rivaroxaban may reduce this risk further. A systematic literature review and meta-analysis compared the efficacy, safety and net clinical benefit (NCB) of DPI with aspirin. Methods: PubMed and Embase were searched for randomised controlled trials reporting clinical efficacy, safety and NCB of DPI compared with aspirin alone in patients with coronary artery disease (CAD) and/or peripheral artery disease. Six articles representing four trials were included. Results: DPI versus aspirin alone significantly reduced major adverse cardiovascular events (HR 0.77; 95% CI [0.69-0.87]; p<0.01), increased International Society on Thrombosis and Haemostasis major bleeding events (HR 1.67; 95% CI [1.37-2.02]; p<0.01) and resulted in a significant NCB (HR 0.79; 95% CI [0.70-0.90]; p<0.01). Conclusion: These results underscore the potential benefit of DPI in patients with CAD, including those in the immediate post-acute coronary syndrome stage and with established CAD, as well as patients with peripheral artery disease.