Search

Objective: Cardiovascular disease (CVD) is the leading cause of death across Europe. We estimated lost earnings (productivity losses) associated with premature mortality due to CVD, and separately for its main sub-categories of coronary heart disease and cerebrovascular disease, across 54 country members of the European Society of Cardiology (ESC)., Methods and Results: We used a standardized approach to estimate working years and earnings lost due to premature death resulting from CVD across the 54 ESC member countries in 2018. Our population-based approach was based on national data on the number of deaths, employment rates, and earnings by age group and sex. We discounted future working years and earnings lost to present values using a 3.5% annual rate. In 2018, there were 4.4 million deaths due to CVD across the 54 countries, with 7.1 million working years lost. This represented productivity losses due to premature death of €62 billion in 2018. Deaths due to coronary heart disease accounted for 47% (€29 billion) of all CVD costs, and cerebrovascular disease accounted for 18% (€11 billion). Approximately 60% (€37 billion) of all productivity losses occurred in the 28 European Union member states, despite accounting for only 42% (1.8 million) of deaths and 21% (1.5 million) of working years lost across the 54 countries., Conclusion: Our study provides a snapshot of the economic consequences posed by premature mortality due to CVD across 54 countries in 2018. The considerable variation across countries highlights the potential gains from policies targeting prevention and care of cardiovascular diseases., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Acute aortic dissection (AAD) is a life-threatening medical condition with high early fatality. Therefore, a prompt and precise diagnosis, which can be achieved through invasive and non-invasive techniques is vital. Echocardiography, unlike MRI and CT, is accessible in emergency units and bedside-compatible. The recommended echocardiographic techniques for AAD are transthoracic and transoesophageal echocardiography (TTE and TOE). Therefore, our review compares their diagnostic roles in AAD., Methods: Studies relevant to our topic were attained through a database search and manual scrutiny of references lists of articles obtained from the electronic databases. The Quality Assessment of Diagnostic Accuracy Studies tool (QUADAS-2) has been used for quality assessment. All quantitative analyses were performed using either STATA 16 or Comprehensive Meta-Analyst software., Results: The search strategy yielded 1,798 articles, of which only 11 were eligible for inclusion. Our subgroup analysis showed that conventional TTE had a sensitivity and specificity of 85.35% and 84.51% for the diagnosis of Stanford type A AAD and was 45.89% sensitive and 87.05% specific for the diagnosis of type B AAD. However, the subgroup analysis shows that contrast-enhancement of TTE results in a sensitivity and specificity of 93.30% and 97.60% for diagnosis of type A AAD, and 83.60% and 94.50% for diagnosis of type B AAD, respectively. On the other hand, conventional TOE was 93.64% sensitive and 95.50% specific for the diagnosis of type A AAD, 99.80% sensitive and 99.87% specific for the diagnosis of type B AAD. Moreover, our analyses show that TTE has pooled false negative and positive rates of 28.6% and 18.6%, while TOE has shown false negative and positive rates of 2.4% and 4.3%, respectively., Conclusion: TOE is the more favorable diagnostic tool for AAD diagnosis than TTE. However, it cannot be used as a stand-alone diagnostic tool since misdiagnosis cases are being reported. Contrast-enhanced TTE can also diagnose AAD since it provides similar results to conventional TOE., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Zaki, Albaroudi, Shaban, Alkahlout, Yigit, Elnabawy, Basharat, Almarri and Azad.)

Background: Pre-injury frailty is associated with adverse in-hospital outcomes in older trauma patients, but the association with longer term survival and recovery is unclear. We aimed to investigate post discharge survival and health-related quality of life (HRQoL) in older frail patients at six months after Major Trauma Centre (MTC) admission., Methods: This was a multi-centre study of patients aged ≥ 65 years admitted to five MTCs. Data were collected via questionnaire at hospital discharge and six months later. The primary outcome was patient-reported HRQoL at follow up using Euroqol EQ5D-5 L visual analogue scale (VAS). Secondary outcomes included health status according to EQ5D dimensions and care requirements at follow up. Multivariable linear regression analysis was conducted to evaluate the association between predictor variables and EQ-5D-5 L VAS at follow up., Results: Fifty-four patients died in the follow up period, of which two-third (64%) had been categorised as frail pre-injury, compared to 21 (16%) of the 133 survivors. There was no difference in self-reported HRQoL between frail and not-frail patients at discharge (Mean EQ-VAS: Frail 55.8 vs. Not-frail 64.1, p = 0.137) however at follow-up HRQoL had improved for the not-frail group but deteriorated for frail patients (Mean EQ-VAS: Frail: 50.0 vs. Not-frail: 65.8, p = 0.009). There was a two-fold increase in poor quality of life at six months (VAS ≤ 50) for frail patients (Frail: 65% vs. Not-frail: 30% p < 0.009). Frailty (β-13.741 [95% CI -25.377, 2.105], p = 0.02), increased age (β -1.064 [95% CI [-1.705, -0.423] p = 0.00) and non-home discharge (β -12.017 [95% CI [118.403, 207.203], p = 0.04) were associated with worse HRQoL at follow up. Requirements for professional carers increased five-fold in frail patients at follow-up (Frail: 25% vs. Not-frail: 4%, p = 0.01)., Conclusions: Frailty is associated with increased mortality post trauma discharge and frail older trauma survivors had worse HRQoL and increased care needs at six months post-discharge. Pre-injury frailty is a predictor of poor longer-term HRQoL after trauma and recognition should enable early specialist pathways and discharge planning., (© 2024. The Author(s).)

In April 2021, the use of the Johnson & Johnson COVID-19 vaccine was paused to investigate whether it had caused serious blood clots to a small number of women (six out of 6.8 million Americans who had been administered that vaccine). As these events were unfolding, we surveyed a sample of Americans (N = 625) to assess their reactions to this news, whether they supported the pausing of the vaccine, and potential psychological factors underlying their decision. In addition, we employed automated text analyses as a supporting method to more classical quantitative measures. Results showed that political ideology influenced the support for the pausing of the vaccine; liberals were more likely to oppose it than conservatives. In addition, the effect of political ideology was mediated by the difference between perceived benefit and risk and the language style used to produce reasons in support (or against) the decision to pause the vaccine. Liberals perceived the benefit of vaccines higher than the risk, used a more analytic language style when stating their reasons, and had a more positive attitude toward the vaccine. We discuss the implications of our findings considering vaccine hesitancy and risk perception during the COVID-19 pandemic., (© 2023 The Authors. Risk Analysis published by Wiley Periodicals LLC on behalf of Society for Risk Analysis.)

Background: Despite increasing evidence that Epstein-Barr virus (EBV) plays a causal role in MS, no treatments have been shown to reduce EBV turnover. We studied the effect of famciclovir on salivary EBV shedding in people with MS (NCT05283551) in a pilot, proof-of-concept study., Methods: People with MS receiving natalizumab provided weekly saliva samples for 12 weeks before starting famciclovir 500 mg twice daily for 12 weeks. Twelve saliva samples were provided on treatment and 12 following treatment. A real-time qPCR Taqman assay was used to detect EBV DNA in saliva. The proportion of saliva samples containing EBV DNA was compared using the Friedman test., Results: Of 30 participants (19 F; mean age 41 years; median EDSS 3.5), 29 received famciclovir, and 24 completed the 12-week course. Twenty-one participants provided at least one usable saliva sample in all epochs. Ten of the 21 had shedding in at least one sample pre-drug; 7/21 when taking famciclovir (not significant). No difference in EBV DNA copy number was seen. There were no drug-related serious adverse events., Conclusion: No significant effect of famciclovir on EBV shedding was seen in this small pilot study. Given the low numbers, a small effect of famciclovir cannot be excluded. Salivary EBV shedding in this natalizumab-treated cohort was lower than in previous studies, which requires replication., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: R.D. has received payments to her institution, including grants from Biogen, Merck, Celgene, National MS Society, MS Society UK, Horne Family Trust, and the BMA Foundation; honoraria from Biogen, Janssen, Merck, Novartis, Roche, Sanofi, and Teva; participated on an advisory board for Biogen, Janssen, Merck, Novartis, and Roche; and received support for attending meetings or travel from Biogen, Janssen, Merck, Novartis, Roche, and Sanofi. G.G. has received consulting or speaker fees from AbbVie, Aslan, Atara Bio, Biogen, Bristol Myers Squibb–Celgene, GlaxoSmithKline, GW Pharma, Janssen–Actelion, Japanese Tobacco, Jazz Pharmaceuticals, LifNano, Merck & Co, Merck KGaA–EMD Serono, Moderna, Novartis, Sanofi Genzyme, Roche-Genentech, and Teva Pharmaceuticals. The remaining authors had nothing to declare.

In the UK, most adults with hypertension are managed in Primary Care. Referrals to Secondary Care Hypertension Specialists are targeted to patients in whom further investigations are likely to change management decisions. In this position statement the British and Irish Hypertension Society provide clinicians with a framework for referring patients to Hypertension Specialists. Additional therapeutic advice is provided to optimise patient management whilst awaiting specialist review. Our aim is to ensure that referral criteria to Hypertension Specialists are consistent across the UK and Ireland to ensure equitable access for all patients., (© 2024. The Author(s).)

Background: There is increasing interest in self-referral and direct access as alternatives pathways to care to improve patient access to specialist services. The impact of these pathways on health inequalities is unknown., Objectives: The purpose of this systematic review is to explore the impact of self-referral and direct access pathways on inequalities in health care use., Design: Three databases (Ovid Medline, Embase, Web of Science) and grey literature were systematically searched for articles from January 2000 to February 2023, reporting on self-referral and direct access pathways to care. Title and abstracts were screened against eligibility criteria to identify studies that evaluated the impact on health inequalities. Data were extracted from eligible studies after full text review and a quality assessment was performed using the ROBINS-I tool., Results: The search strategy identified 2948 articles. Nineteen records were included, covering seven countries and six healthcare services. The impact of self-referral and direct access on inequalities was mixed, suggesting that the relationship is dependent on patient and system factors. Typically self-referral pathways and direct access pathways tend to widen health inequalities. White, younger, educated women from less deprived backgrounds are more likely to self-refer, exacerbating existing health inequalities., Conclusions: Self-referral pathways risk widening health inequalities. Further research is required to understand the context-dependent mechanisms by which this can occur, explore ways to mitigate this and even narrow health inequalities, as well as understand the impact on the wider healthcare system., Competing Interests: Declarations of Competing Interest None., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: In adults with an intellectual disability, health-related quality of life (HRQoL) is often measured by proxy report. This cross-sectional study investigated whether the mental health of proxy raters impacts the way they rate HRQoL., Methods: In this study, 110 carers of adults with an intellectual disability completed measures of psychological distress (Kessler-6) and HRQoL (EQ-5D-3L) about their own HRQoL and that of the care recipient. Differences between HRQoL scores as rated by the carer about themselves and the care recipient were calculated (convergence scores) and multiple regression models were fitted to estimate the association between proxy psychological distress and convergence scores for subjective/objective HRQoL controlling for support needs of the care recipient, carer age and gender of care recipient., Results: There was a significant association between psychological distress and subjective HRQoL convergence scores (r = .92; P = 0.03; 95%; CI: -1.76 to -0.09). There was no association between psychological distress and objective HRQoL convergence scores (r = .01; CI -0.02 to 0.001; P = 0.08). The association between psychological distress and HRQoL scores was no longer present when models did not include convergence scores., Conclusions: Carers experiencing more psychological distress tended to rate their own and the care recipients' subjective HRQoL more similarly. Objective HRQoL measures did not show this convergence in scores with increasing carer psychological distress. Findings differed when the analysis approach was changed, suggesting the results above require replication in future studies., (© 2023 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.)

Introduction: Interventions promoting exclusive breastfeeding (EBF) may benefit infant health outcomes, but evidence is inconsistent. The objective of this review was to assess the effect of interventions promoting EBF on health outcomes in infants and children under 7 years of age., Methods: A literature search was conducted using EMBASE, MEDLINE, CINAHL, Cochrane Central, Cochrane Database of Systematic Reviews, and WHO International Clinical Trials Registry Platform from inception to April 2022. Inclusion criteria were randomized or cluster-randomized controlled trials aiming to increase EBF that reported effects on offspring growth, morbidity, and/or mortality up to age 7 years. The primary outcome was infant/child growth. Secondary outcomes were infant morbidity and mortality and EBF rates. Data were pooled using a random-effects model., Results: Thirty-two studies (40 papers) were identified. No effect on infant/child growth was observed. EBF promotion interventions significantly improved EBF rates up to 6 months (n = 25; OR 3.15; 95% CI: 2.36, 4.19) and significantly reduced the odds of respiratory illness at 0-3 months by 59% (n = 2; OR 0.41; 95% CI: 0.20, 0.84) but not at later time-points. A borderline significant effect was observed for diarrhea (n = 12; OR 0.84; 95% CI: 0.70, 1.00). Effects on hospitalizations or mortality were not significant., Discussion/conclusion: EBF promotion interventions improve EBF rates and might yield modest reductions in infant morbidity without affecting infant/child growth. Future studies should investigate the cost-effectiveness of these interventions and examine potential benefits on other health outcomes., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Hypertension, defined as persistently elevated systolic blood pressure (SBP) >140 mmHg and/or diastolic blood pressure (DBP) at least 90 mmHg (International Society of Hypertension guidelines), affects over 1.5 billion people worldwide. Hypertension is associated with increased risk of cardiovascular disease (CVD) events (e.g. coronary heart disease, heart failure and stroke) and death. An international panel of experts convened by the International Society of Hypertension College of Experts compiled lifestyle management recommendations as first-line strategy to prevent and control hypertension in adulthood. We also recommend that lifestyle changes be continued even when blood pressure-lowering medications are prescribed. Specific recommendations based on literature evidence are summarized with advice to start these measures early in life, including maintaining a healthy body weight, increased levels of different types of physical activity, healthy eating and drinking, avoidance and cessation of smoking and alcohol use, management of stress and sleep levels. We also discuss the relevance of specific approaches including consumption of sodium, potassium, sugar, fibre, coffee, tea, intermittent fasting as well as integrated strategies to implement these recommendations using, for example, behaviour change-related technologies and digital tools., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Alongside the lack of homogeneity among international guidelines and consensus documents on primary hyperaldosteronism, the National UK guidelines on hypertension do not provide extensive recommendations regarding the diagnosis and management of this condition. Local guidelines vary from area to area, and this is reflected in the current clinical practice in the UK. In an attempt to provide support to the clinicians involved in the screening of subjects with hypertension and clinical management of suspected cases of primary hyperaldosteronism the following document has been prepared on the behalf of the BIHS Guidelines and Information Service Standing Committee. Through remote video conferences, the authors of this document reviewed an initial draft which was then circulated among the BIHS Executive members for feedback. A survey among members of the BIHS was carried out in 2022 to assess screening strategies and clinical management of primary hyperaldosteronism in the different regions of the UK. Feedback and results of the survey were then discussed and incorporated in the final document which was approved by the panel after consensus was achieved considering critical review of existing literature and expert opinions. Grading of recommendations was not performed in light of the limited available data from properly designed randomized controlled trials., (© 2023. The Author(s).)

Background: Multiple sclerosis is a leading cause of non-traumatic neurological disability among young adults worldwide. Prior studies have identified modifiable risk factors for multiple sclerosis in cohorts of White ethnicity, such as infectious mononucleosis, smoking, and obesity during adolescence/early adulthood. It is unknown whether modifiable exposures for multiple sclerosis have a consistent impact on risk across ethnic groups., Aim: To determine whether modifiable risk factors for multiple sclerosis have similar effects across diverse ethnic backgrounds., Methods: We conducted a nested case-control study using data from the UK Clinical Practice Research Datalink. Multiple sclerosis cases diagnosed from 2001 until 2022 were identified from electronic healthcare records and matched to unaffected controls based on year of birth. We used stratified logistic regression models and formal statistical interaction tests to determine whether the effect of modifiable risk factors for multiple sclerosis differed by ethnicity., Results: We included 9662 multiple sclerosis cases and 118,914 age-matched controls. The cohort was ethnically diverse (MS: 277 South Asian [2.9%], 251 Black [2.6%]; Controls: 5043 South Asian [5.7%], 4019 Black [4.5%]). The age at MS diagnosis was earlier in the Black (40.5 [SD 10.9]) and Asian (37.2 [SD 10.0]) groups compared with White cohort (46.1 [SD 12.2]). There was a female predominance in all ethnic groups; however, the relative proportion of males was higher in the South Asian population (proportion of women 60.3% vs 71% [White] and 75.7% [Black]). Established modifiable risk factors for multiple sclerosis-smoking, obesity, infectious mononucleosis, low vitamin D, and head injury-were consistently associated with multiple sclerosis in the Black and South Asian cohorts. The magnitude and direction of these effects were broadly similar across all ethnic groups examined. There was no evidence of statistical interaction between ethnicity and any tested exposure, and no evidence to suggest that differences in area-level deprivation modifies these risk factor-disease associations. These findings were robust to a range of sensitivity analyses., Conclusions and Relevance: Established modifiable risk factors for multiple sclerosis are applicable across diverse ethnic backgrounds. Efforts to reduce the population incidence of multiple sclerosis by tackling these risk factors need to be inclusive of people from diverse ethnicities., (© 2023. The Author(s).)

Isolation of live cells from the tumor microenvironment (TME) has represented a challenge, particularly from metastatic nodules that need to be identified within the entire metastatic tissue. Cherry-niche, an in vivo labelling technique, allows the isolation of all the different cell populations in the TME without needing to visually locate the metastatic cancer cell colonies. Therefore, neighboring TME cells can be isolated even from the early stages of cancer cell seeding and colonization in the metastatic tissue. Here, we show how to use Cherry-niche to identify and isolate neutrophils from the lung metastatic niche. We also provide examples of downstream analyses to characterize freshly isolated neutrophils ex vivo, such as Giemsa staining, reactive oxygen species (ROS) detection, and phagocytosis assays. Similar strategies can be used to isolate other immune and non-immune cells from the metastatic TME., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Sleep quality may affect symptom experience in irritable bowel syndrome (IBS). Our aim was to investigate the relationship between sleep quality and gastrointestinal (GI) symptoms using actigraphy and the experience sampling method., Methods: Patients with IBS were recruited from a tertiary Neurogastroenterology clinic and the community. GI symptoms and mood were recorded on a smartphone application, 10 times per day, over 7 consecutive days. Subjective sleep quality was recorded every morning to reflect the night before. Objective measures of sleep quality were estimated from wrist-worn actigraphy. Cross-lagged structural equation models were built to assess the directionality of sleep-symptom relationships over time., Results: Eighty patients with IBS completed the study (mean age: 37 years [range 20-68], 89% female, 78% community). Approximately 66% had a Pittsburgh Sleep Quality Index score ≥ 8, indicating a clinically significant sleep disturbance. Approximately 82% (95% CI: 72-90) screened positive for a sleep disorder, most commonly insomnia. In cross-lagged analysis, poor subjective sleep quality predicted next-day abdominal pain (0.036 < P < 0.040) and lower GI symptoms (0.030 < P < 0.032), but not vice versa. No significant relationship with GI symptoms was found for any objective sleep measure using actigraphy., Discussion: Poor subjective sleep quality was associated with higher next-day lower GI symptom levels, but not vice versa. Objective sleep measures did not predict next-day abdominal symptoms, potentially supporting the conclusion that it is the perception of sleep quality that is most influential. This study may be used to guide future research into the effect of sleep interventions on GI symptoms., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Background: Despite the popularity of the Twin Block (TB) and the Hanks Herbst (HH) functional appliances, there is limited prospective research comparing these removable and fixed designs, respectively., Objectives: To evaluate and compare the skeletal and dental effects associated with TB and HH functional appliances as well as to detect factors that might influence the success or failure of treatment in adolescents with Class II malocclusion., Design and Setting: A parallel-group randomized controlled trial was undertaken in a single-centre hospital in the United Kingdom., Methods: A total of 80 participants (aged 10-14 years) with overjet of 7 mm or more were randomized to receive either the HH or TB appliance. Cephalometric radiographs were collected at the start of the study and immediately after the withdrawal of the functional appliances and measured using Pancherz analysis. Participants were allocated to the TB or HH group, based on an electronic randomization, stratified for gender and allocation concealed. Blinding to the allocated arm was not possible. However, all data were coded and anonymized to ensure that assessors were blinded to the group allocation. The main outcome was the anterior-posterior skeletal and dento-alveolar changes at the end of the functional phase., Results: Fifteen (37.5%) participants from the TB group and 7 (15.5%) from HH failed to achieve full overjet reduction (<4 mm) after 12 months of treatment. Overjet reduction was 2 mm greater with HH compared to TB (P = .05; 95% CI: 0.2, 3.2). No significant differences regarding skeletal and dental changes were reported, with the exception that participants in HH group experienced greater lower molar protraction (P = .002; 95% CI: -2.8, -0.8) and mandibular incisors advancement (P = .001; 95% CI: -2.9, -1), indicating greater dental than skeletal effects., Conclusion: The TB appliance was associated with a higher rate of treatment discontinuation. No significant clinical differences were observed in the skeletal and dental effects, although the HH may be associated with more pronounced effects on the mandibular dentition., Clinical Trial Registration: The protocol was registered online before the start of the trial (ISRCTN11717011)., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: International guidelines for neuroprotection following out-of-hospital cardiac arrest (OHCA) recommend fever prevention ahead of routine temperature management. This study aimed to identify any effect of changing from targeted temperature management to fever prevention on neurological outcome following OHCA., Methods: A retrospective observational cohort study was conducted of consecutive admissions to an ICU at a tertiary OHCA centre. Comparison was made between a period of protocolised targeted temperature management (TTM) to 36 °C and a period of fever prevention., Results: Data were available for 183 patients. Active temperature management was administered in 86/118 (72%) of the TTM cohort and 20/65 (31%) of the fever prevention group. The median highest temperature prior to the start of temperature management was significantly lower in the TTM group at 35.6 (IQR 34.9-36.2) compared to 37.9 °C (IQR 37.7-38.2) in the fever prevention group (adjusted p < 0.001).There was no difference in the proportion of patients discharged with Cerebral Performance Category 1 or 2 between the groups (42% vs. 40%, p = 0.88). Patients in the fever prevention group required a reduced duration of noradrenaline (36 vs. 46 h, p = 0.03) and a trend towards a reduced duration of propofol (37 vs. 56 h, p = 0.06).In unadjusted analysis, use of active temperature management (irrespective of group) appeared to be associated with decreased risk of poor outcome (OR = 0.43, 95% CI 0.23-0.78) but after adjustment for patient age, presenting rhythm, witnessed arrest and duration of CPR, this was no longer significant (OR = 0.93, 95% CI 0.37-2.31, p = 0.88)., Conclusion: Switching from TTM to fever prevention following OHCA was associated with similar rates of neurological outcomes, with a possible decrease in sedation and vasopressor requirements., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [AP is funded by a Medical Research Council Clinical Academic Research Partnership Award (Ref:MR/W03011X/1) and the Barts Charity. All other authors declare no conflict of interest.]., (© 2023 The Author(s).)

Aims: Clinical likelihood (CL) models are designed based on a reference of coronary stenosis in patients with suspected obstructive coronary artery disease. However, a reference standard for myocardial perfusion defects (MPDs) could be more appropriate. We aimed to investigate the ability of the 2019 European Society of Cardiology pre-test probability (ESC-PTP), the risk-factor-weighted (RF-CL) model, and coronary artery calcium score-weighted (CACS-CL) model to diagnose MPDs., Methods and Results: Symptomatic stable de novo chest pain patients (n = 3374) underwent coronary computed tomography angiography and subsequent myocardial perfusion imaging by single-photon emission computed tomography, positron emission tomography, or cardiac magnetic resonance. For all modalities, MPD was defined as coronary computed tomography angiography with suspected stenosis and stress-perfusion abnormality in ≥2 segments. The ESC-PTP was calculated based on age, sex, and symptom typicality, and the RF-CL and CACS-CL additionally included a number of risk factors and CACS. In total, 219/3374 (6.5%) patients had an MPD. Both the RF-CL and the CACS-CL classified substantially more patients to low CL (<5%) of obstructive coronary artery disease compared with the ESC-PTP (32.5 and 54.1 vs. 12.0%, P < 0.001) with preserved low prevalences of MPD (<2% for all models). Compared with the ESC-PTP [area under the receiver-operating characteristic curve (AUC) 0.74 (0.71-0.78)], the discrimination of having an MPD was higher for the CACS-CL model [AUC 0.88 (0.86-0.91), P < 0.001], while it was similar for the RF-CL model [AUC 0.73 (0.70-0.76), P = 0.32]., Conclusion: Compared with basic CL models, the RF-CL and CACS-CL models improve down classification of patients to a very low-risk group with a low prevalence of MPD., Competing Interests: Conflict of interest: L.D.R. acknowledges support from the Danish Cardiovascular Academy (grant number PD5Y-2023001-DCA), which is funded by the Novo Nordisk Foundation (grant number NNF20SA0067242) and The Danish Heart Foundation. S.W. acknowledges support from the Novo Nordisk Foundation Clinical Emerging Investigator grant (NNF21OC0066981). S.E.P. provides consultancy to Circle Cardiovascular Imaging Inc. M.B. discloses advisory board participation for Novo Nordisk, Astra-Zeneca, Pfizer, Boeringer Ingelheim, Bayer, Sanofi, Novartis, Amgen, CLS-Behring Acarix, and MEDtrace. All other authors declare no conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Context: Quality of life (QoL) has been inconsistently reported in children and young people (CYP) with congenital adrenal hyperplasia (CAH)., Objective: Assess QoL in CYP with CAH in the UK alongside biometric and androgen profiles., Design: To define the evidence base for health care delivery, we conducted a cross-sectional study in CYP with CAH in the UK. Questionnaire results were compared with normative data and between groups, and modelled for association with sex, height, weight, body mass index, or steroid biomarkers of CAH control., Setting: Tertiary care in 14 UK centers., Patients: Results from 104 patients, 55% female, mean age 12.7 years (SD 3.0), paired responses from parents., Interventions: Strengths and Difficulties questionnaire (SDQ) and pediatric QoL questionnaire., Main Outcome Measure: Total QoL scores as assessed by SDQ and a pediatric QoL questionnaire in comparison to normative data., Results: Total scores were worse in parents than normative data, but similar in patients. Patient QoL was rated better in social functioning but worse in emotional, school, and peer domains by patients, and worse in total scores and domains of peer problems, and psychosocial, emotional, and school functioning by parents. Parents consistently scored QoL of their children lower than their child. Larger height-SD score and lower weight-SD score were associated with better QoL. Girls with lower steroid biomarkers had worse SDQ scores., Conclusions: In CYP with CAH, reduced height, increased weight, and hormonal biomarkers consistent with overtreatment were associated with worse QoL; addressing these problems should be prioritized in clinical management.Clinical Trials Registration Number: SCH/15/088., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Aims: Emery-Dreifuss muscular dystrophy (EDMD) is caused by variants in EMD (EDMD1) and LMNA (EDMD2). Cardiac conduction defects and atrial arrhythmia are common to both, but LMNA variants also cause end-stage heart failure (ESHF) and malignant ventricular arrhythmia (MVA). This study aimed to better characterize the cardiac complications of EMD variants., Methods: Consecutively referred EMD variant-carriers were retrospectively recruited from 12 international cardiomyopathy units. MVA and ESHF incidences in male and female variant-carriers were determined. Male EMD variant-carriers with a cardiac phenotype at baseline (EMDCARDIAC) were compared with consecutively recruited male LMNA variant-carriers with a cardiac phenotype at baseline (LMNACARDIAC)., Results: Longitudinal follow-up data were available for 38 male and 21 female EMD variant-carriers [mean (SD) ages 33.4 (13.3) and 43.3 (16.8) years, respectively]. Nine (23.7%) males developed MVA and five (13.2%) developed ESHF during a median (inter-quartile range) follow-up of 65.0 (24.3-109.5) months. No female EMD variant-carrier had MVA or ESHF, but nine (42.8%) developed a cardiac phenotype at a median (inter-quartile range) age of 58.6 (53.2-60.4) years. Incidence rates for MVA were similar for EMDCARDIAC and LMNACARDIAC (4.8 and 6.6 per 100 person-years, respectively; log-rank P = .49). Incidence rates for ESHF were 2.4 and 5.9 per 100 person-years for EMDCARDIAC and LMNACARDIAC, respectively (log-rank P = .09)., Conclusions: Male EMD variant-carriers have a risk of progressive heart failure and ventricular arrhythmias similar to that of male LMNA variant-carriers. Early implantable cardioverter defibrillator implantation and heart failure drug therapy should be considered in male EMD variant-carriers with cardiac disease., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Given the expansion of remote digital dermatology services from the National Health Service, particularly during the COVID-19 pandemic, there is a need for methods that identify patients at risk of digital exclusion to guide equitable representation in service co-design processes and tailor remote services to the needs of their patient population., Objective: This quality improvement project aims to inform the redesign of remote services to optimally support the ongoing needs of patients with chronic skin diseases, ensuring that the services are tailored to patients' digital health literacy requirements., Methods: We profiled the digital health literacy of 123 people with chronic skin conditions who require long-term surveillance in 2 specialist clinics (London, United Kingdom) using the Multidimensional Readiness and Enablement Index for Health Technology (READHY) questionnaire alongside the Optimizing Health Literacy and Access (Ophelia) process for hierarchical cluster analysis., Results: The cluster analysis of READHY dimensions in responding participants (n=116) revealed 7 groups with distinct digital and health literacy characteristics. High READHY scores in groups 1 (n=22, 19%) and 2 (n=20, 17.2%) represent those who are confident with managing their health and using technology, whereas the lower-scoring groups, 6 (n=4, 3.4%) and 7 (n=12, 10.3%), depended on traditional services. Groups 3 (n=27, 23.3%), 4 (n=23, 19.8%), and 5 (n=8, 6.9%) had varying digital skills, access, and engagement, highlighting a population that may benefit from a co-designed dermatology service., Conclusions: By identifying patient groups with distinguishable patterns of digital access and health literacy, our method demonstrates that 63.8% (n=74) of people attending specialist clinics in our center require support in order to optimize remote follow-up or need an alternative approach. Future efforts should streamline the READHY question profile to improve its practicality and use focus groups to elicit strategies for engaging patients with digital services., (©Serena Ramjee, Hanen Mohamedthani, Aditya Umeshkumar Patel, Rebeca Goiriz, Catherine A Harwood, Richard H Osborne, Christina Cheng, Zeeshaan-ul Hasan. Originally published in JMIR Dermatology (http://derma.jmir.org), 08.12.2023.)

DNA Topoisomerase IIA (Topo IIA) is an enzyme that alters the topological state of DNA and is essential for the separation of replicated sister chromatids and the integrity of cell division. Topo IIA dysfunction activates cell cycle checkpoints, resulting in arrest in either the G2-phase or metaphase of mitosis, ultimately triggering the abscission checkpoint if non-disjunction persists. These events, which directly or indirectly monitor the activity of Topo IIA, have become of major interest as many cancers have deficiencies in Topoisomerase checkpoints, leading to genome instability. Recent studies into how cells sense Topo IIA dysfunction and respond by regulating cell cycle progression demonstrate that the Topo IIA G2 checkpoint is distinct from the G2-DNA damage checkpoint. Likewise, in mitosis, the metaphase Topo IIA checkpoint is separate from the spindle assembly checkpoint. Here, we integrate mechanistic knowledge of Topo IIA checkpoints with the current understanding of how cells regulate progression through the cell cycle to accomplish faithful genome transmission and discuss the opportunities this offers for therapy., (© 2023 Soliman et al.)

Psychodermatology is a subspecialty of dermatology that is of increasing interest to dermatologists and patients. The case for the provision of at least regional psychodermatology services across Europe is robust. Psychodermatology services have been shown to have better, quicker and more cost-efficient clinical outcomes for patients with psychodermatological conditions. Despite this, psychodermatology services are not uniformly available across Europe. In fact many countries have yet to establish dedicated psychodermatology services. In other countries psychodermatology services are in development. Even in countries where psychodermatolgy units have been established, the services are not available across the whole country. This is especially true for the provision of paediatric psychodermatology services. Also whilst most states across Europe are keen to develop psychodermatology services, the rate at which this development is being implemented is very slow. Our paper maps the current provision of psychodermatology services across Europe and indicates that there is still very much more work to be done in order to develop the comprehensive psychodermatology services across Europe, which are so crucial for our patients., (© 2023 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Background: In KEYNOTE-119 (ClinicalTrials.gov, NCT02555657), overall survival (primary end-point) was similar between pembrolizumab and chemotherapy in patients with previously treated metastatic triple-negative breast cancer (TNBC), although the pembrolizumab treatment effect increased with tumour PD-L1 expression. We report results of prespecified health-related quality of life (HRQoL) analyses from KEYNOTE-119., Methods: Eligible patients were randomised 1:1 to pembrolizumab 200 mg Q3W intravenously for up to 35 cycles or treatment of physician's choice per local/country guidelines. Prespecified exploratory end-points were the change from baseline in HRQoL (EORTC QLQ-C30, QLQ-BR23) and to characterise utilities (EQ-5D-3L). Time to deterioration (TTD) was the time from start of treatment to first onset of a ≥10-point worsening from baseline., Results: HRQoL analyses included 187 patients with tumour PD-L1 combined positive score (CPS) ≥10. Changes from baseline at 6 weeks (primary analysis time point) were directionally better with pembrolizumab versus chemotherapy for QLQ-C30 GHS/QoL (between-group difference in least-squares mean scores of 4.21 [95% CI, -1.38 to 9.80]), QLQ-C30 functional scales (physical, role, cognitive, social), QLQ-C30 symptom scales/items (fatigue, nausea/vomiting, dyspnoea, appetite loss), and QLQ-BR23 symptom scales/items (systemic therapy side-effects, upset by hair loss). Median TTD was directionally longer for pembrolizumab versus chemotherapy for QLQ-C30 QHS/QoL (4.3 versus 1.7 months), QLQ-C30 nausea/vomiting (7.7 versus 4.8 months), and QLQ-BR23 systemic therapy side-effects (6.1 versus 3.4 months). Minimal treatment differences were observed for other HRQoL end-points., Conclusions: HRQoL results were consistent with clinical outcomes and appeared to be driven by results for patients with tumour PD-L1 CPS ≥10., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Peter Schmid: Consultant/Honoraria: AstraZeneca, Bayer, Boehringer Ingelheim, Celgene, Eisai, Merck Sharp, and Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Novartis, Pfizer, Puma, and Roche; grant funding to institution: Astellas, AstraZeneca, Genentech, Medivation, Novartis, Oncogenex, and Roche. Oleg Lipatov: Nothing to disclose. Seock-Ah Im: consulting/advisory role: AstraZeneca, Novartis, Roche/Genentech, Pfizer, Amgen, Hanmi, Lilly, GlaxoSmithKline, Merck Sharp and Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Daiichi Sankyo, Idience Co. Ltd., and Bertis; research funding to institution: AstraZeneca, Pfizer, Roche/Genentech, Daewoong Pharmaceutical, Eisai Korea, and Boryung Pharm. Anthony Goncalves: Nonfinancial support/consultant (compensated to hospital): AstraZeneca, Novartis, Astellas, Pfizer, Merck Sharp and Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Lilly, Mylan, Parexel, and Roche. Eva Muñoz-Couselo: Nothing to disclose. Keun Seok Lee: Consultant: Lilly, Novartis, Pfizer, Merck Sharp and Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Bixink, Everest Medicine, Daiichi Sankyo, and Roche; drug supplies: Dong-A Pharm. Kenji Tamura: Nothing to disclose. Laura Testa: Funding for the current trial conduct, provision of study materials, medical writing, and article processing charges: Merck Sharp and Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA; research grant: Novartis; payment or honoraria for medical education: Lilly, Novartis, Pfizer, AstraZeneca, Daiichi-Sankyo, and Merck Sharp and Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA; support for attending meetings and/or travel: Roche, Gilead, and AstraZeneca; Data Safety Monitoring/Advisory board: AstraZeneca, Lilly, Novartis, Merck Sharp, and Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Daichi-Sankyo, and Pfizer; steering committee for trials: AstraZeneca and Lilly. Isabell Witzel: Research funding to institution: Merck Sharp and Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA; personal fees: Daiichi Sankyo, Merck Sharp, and Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Novartis, Pfizer, and Roche. Shoichiro Ohtani: Lecture fees: AstraZeneca, Chugai, Lilly, and Pfizer. Nicholas Turner: Advisory board honoraria: AstraZeneca, Lilly, Pfizer, Roche/Genentech, Novartis, GlaxoSmithKline, Repare Therapeutics, Relay Therapeutics, Zentalis, Gilead, Inivata, Guardant, and Exact Sciences; research funding: AstraZeneca, Pfizer, Roche/Genentech, Merck Sharp and Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Guardant Health, Invitae, Inivata, Personalis, and Natera. Stefania Zambelli: Nothing to disclose. Nadia Harbeck: Consulting/Lecture fees: AstraZeneca, Daiichi Sankyo, Lilly, Merck Sharp, and Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Novartis, Pfizer, Pierre Fabre, Roche, Sandoz, and Seattle Genetics. Fabrice Andre: Research grants to institution: AstraZeneca, Daiichi Sankyo, Lilly, Novartis, Pfizer, and Roche; Advisory board or speaker (compensation to institution): AstraZeneca, Daiichi Sankyo, Roche, Lilly, Pfizer, Owkin, Novartis, and Guardant Health; and personal fees (advisory board): Lilly. Rebecca Dent: Advisory board: AstraZeneca, Eisai, Eli Lilly and Company, Genentech, Merck Sharp and Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Novartis, and Pfizer; Consultant: Genentech; Travel: Genentech, Merck Sharp and Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, and Pfizer. Jaime A. Mejia: employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA; owns stock in Merck & Co., Inc., Rahway, NJ, USA. Xuan Zhou: Employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA; owns stock in Merck & Co., Inc., Rahway, NJ, USA. Amin Haiderali: employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA; owns stock in Merck & Co., Inc., Rahway, NJ, USA. Allison Martin Nguyen: Employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA; owns stock in Merck & Co., Inc., Rahway, NJ, USA. Javier Cortes: Consulting fees: AstraZeneca, Athenex, Bioasis, BioInvent, Boehringer Ingelheim, Celgene, Cellestia, Clovis Oncology, Daiichi Sankyo, Ellipses, Erytech, Gemoab, Gilead, GSK, Hibercell, Leuko, Lilly, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Polyphor, Roche, and Seattle Genetics; fees for non-CME services received directly from commercial interest or their agents (e.g., speakers' bureaus): Celgene, Daiichi Sankyo, Eisai, Lilly, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Novartis, Pfizer, Roche, and Samsung Bioepis; contracted research: Ariad Pharmaceuticals, AstraZeneca, Baxalta GMBH/Servier Affaires, Bayer Healthcare, Eisai, F. Hoffman-La Roche, Guardant Health, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Pfizer, Piqur Therapeutics, Puma, Queen Mary University of London, and Roche; Ownership interest (stock, stock options, or other ownership interest excluding diversified mutual funds): MedSIR; Travel/Accommodation: Daiichi Sankyo, Eisai, Novartis, Pfizer, and Roche; Patent: HER2 as a predictor of response to dual HER2 blockade in the absence of cytotoxic therapy. Eric P. Winer: Advisory board member: LEAP; Consultant: G1 Therapeutics, Garrick Therapeutics, Genomic Health, GlaxoSmithKline, Jounce, Lilly, Novartis, Roche Genentech, Seattle Genetics, and Syros., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background and Aims: Cardiovascular disease (CVD) impacts significantly health and social care systems as well as society through premature mortality and disability, with patients requiring care from relatives. Previous pan-European estimates of the economic burden of CVD are now outdated. This study aims to provide novel, up-to-date evidence on the economic burden across the 27 European Union (EU) countries in 2021., Methods: Aggregate country-specific resource use data on morbidity, mortality, and health, social and informal care were obtained from international sources, such as the Statistical Office of the European Communities, enhanced by data from the European Society of Cardiology Atlas programme and patient-level data from the Survey of Health, Ageing and Retirement in Europe. Country-specific unit costs were used, with cost estimates reported on a per capita basis, after adjustment for price differentials., Results: CVD is estimated to cost the EU €282 billion annually, with health and long-term care accounting for €155 billion (55%), equalling 11% of EU-health expenditure. Productivity losses accounted for 17% (€48 billion), whereas informal care costs were €79 billion (28%). CVD represented a cost of €630 per person, ranging from €381 in Cyprus to €903 in Germany. Coronary heart disease accounted for 27% (€77 billion) and cerebrovascular diseases for 27% (€76 billion) of CVD costs., Conclusions: This study provides contemporary estimates of the wide-ranging impact of CVD on all aspects of the economy. The data help inform evidence-based policies to reduce the impact of CVD, promoting care access and better health outcomes and economic sustainability., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

There is a lack of published guidelines on the management of patients with multiple sclerosis (MS) undergoing procedures that require anaesthesia and respective advice is largely based on retrospective studies or case reports. The aim of this paper is to provide recommendations for anaesthetists and neurologists for the management of patients with MS requiring anaesthesia. This review covers issues related to the anaesthetic management of patients with MS, with a focus on preoperative assessment, choice of anaesthetic techniques and agents, side-effects of drugs used during anaesthesia and their potential impact on the disease evolution, drug interactions that may occur, and the need to use monitoring devices. A systematic PubMed research was performed to retrieve relevant articles., Competing Interests: Declaration of Competing Interest Oriane de Maere has no disclosure. Nicolas Dubuisson was an ECTRIMS fellow, which is unrelated to the contents of this publication. He has received travel costs from Pfizer, Merck-Serono and Genzyme unrelated to the context of this publication. Monica Marta has received honoraria and travel costs from Genzyme, AbbVie, Roche and Novartis, unrelated to the context of this publication. Sharmilee Gnanapavan has received honoraria and meeting support from Biogen, Novartis, Teva, Genzyme and research funds from Genzyme, which is unrelated to the contents of this publication. Benjamin Turner has received honoraria from Roche, Teva, Novartis, Merck-Serono, Sanofi-Genzyme and Biogen, unrelated to the context of this publication. David Baker is a founder and consultant to Canbex therapeutics and has received research funds from Canbex therapeutics, Sanofi-Genzyme and Takeda in the past 3 years. This is unrelated to the context of this publication. Klaus Schmierer has received research support from Biogen, Merck, and Novartis; speaking honoraria from, and/or served in an advisory role for, Amgen-Gensenta, Biogen, EMD Serono, Merck, Novartis, Roche, Sanofi, and Teva; and remuneration for teaching activities from AcadeMe, Medscape, and the Neurology Academy.This is unrelated to the context of this publication. Gavin Giovannoni has received fees for participation in advisory board for AbbVie Biotherapeutics, Biogen, Canbex, Ironwood, Novartis, Merck, Merck Serono, Roche, Sanofi Genzyme, Synthon, Teva and Vertex; speaker fees from AbbVie, Biogen, Bayer HealthCare,Genzyme, Merck Serono, Sanofi-Aventis and Teva. Research support from Biogen, Genzyme, Ironwood, Merck, Merck Serono and Novartis. This is unrelated to the context of this publication. Vishwajit Verma: no disclosure. Marie-Agnès Docquier: no disclosure., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Snakebite-related fatalities disproportionately affect populations in impoverished socio-economic regions, marked by limited access to adequate healthcare and constrained antivenom availability. Early medical intervention is pivotal in mitigating mortality and morbidity associated with snakebite envenoming (SBE). While clinical assessment remains fundamental in treating SBE, this review aims to spotlight objective parameters that could also affect outcomes. Selected studies that identify factors associated with poor outcomes are predominantly region-specific, single-site, and observational, yet collectively reveal similar findings. They consistently report factors such as treatment delays, susceptibility in vulnerable groups such as children and pregnant women, as well as various biochemical and haematological abnormalities. Acute kidney injury (AKI), low platelets, leucocytosis, abnormal coagulation, and elevated creatine kinase (CK) all show an association with poor outcomes. Furthermore, recognising rare and unusual SBE presentations such as adrenal insufficiency, severe hypertension, intracranial haemorrhage, acute angle closure glaucoma, and bowel ischaemia also has a bearing on outcomes. Despite the integration of these parameters into clinical decision tools and guidelines, the validation of this evidence is limited. This review underscores the imperative for high-quality, multi-centre studies aligned with consensus-driven Core Outcome Sets (COS) and Patient-Reported Outcome Measures (PROMS) to validate and strengthen the current evidence.

The number of patients at the intersection of cancer and cardiovascular disease (CVD) is increasing, reflecting ageing global populations, rising burden of shared cardiometabolic risk factors, and improved cancer survival. Many cancer treatments carry a risk of cardiotoxicity. Baseline cardiovascular risk assessment is recommended in all patients with cancer and requires consideration of individual patient risk and the cardiotoxicity profile of proposed anticancer therapies. Patients with pre-existing CVD are potentially at high or very high risk of cancer-therapy related cardiovascular toxicity. The detection of pre-existing CVD should prompt cardiac optimisation and planning of surveillance during cancer treatment. In patients with severe CVD, the risk of certain cancer therapies may be prohibitively high. Such decisions require multidisciplinary discussion with consideration of alternative anti-cancer therapies, risk-benefit assessment, and patient preference. Current practice is primarily guided by expert opinion and data from select clinical cohorts. There is need for development of a stronger evidence base to guide clinical practice in cardio-oncology. The establishment of multicentre international registries and national-level healthcare data linkage projects are important steps towards facilitating enrichment of cardio-oncology research programmes. In this narrative review, we consider epidemiological trends of cancer and CVD comorbidities and the impact of their co-occurrence on clinical outcomes, current approach to supporting cancer patients with pre-existing CVD and gaps in existing knowledge., Competing Interests: Competing interests: MAM is an International Advisory Board Member of Heart. RKC is an Associate Editor for Heart., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Patients with intermediate-risk prostate cancer are faced with the decision of whether to undergo radical treatment. Decision-making aids, such as Predict Prostate, can empower both clinicians and patients to make treatment decisions with personalised information, but their impact on multi-disciplinary team (MDT) decision-making and uptake of radical treatment remains unknown., Objective: The objective of this study is to assess the utilisation and utility of Predict Prostate in informing treatment decisions for patients with intermediate-risk prostate cancer., Patients and Methods: A retrospective cohort study was conducted in Cambridge University Hospitals (CUH) of patients referred to the prostate cancer specialist multi-disciplinary team (pcSMDT) and robotic prostatectomy clinic (ROPD) between September 2019 and August 2021 for consideration of radical prostatectomy (RARP). Data on patient characteristics, use of PredictProstate and management decisions were collected from the Epic electronic medical record (EMR) of 839 patients, of whom 386 had intermediate-risk prostate cancer., Results: The use of Predict Prostate at the pcSMDT increased in the second half of the study period (34.5% vs. 23.8%, p  < 0.001). The use of Predict Prostate was associated with an increased likelihood of attending ROPD for men with CPG2 prostate cancer (OR = 2.155, 95% CI = 1.158-4.013, p  = 0.015) but a reduced likelihood of proceeding with RARP for men with CPG2 (OR = 0.397, 95% CI = 0.209-0.753, p  = 0.005) and CPG3 (OR = 0.305, 95% CI = 0.108-0.861, p  = 0.025) prostate cancer., Conclusion: Our study showed that the use of Predict Prostate for patients with intermediate-risk prostate cancer is associated with increased attendance at specialist surgical clinic and a reduced chance of undergoing radical prostate surgery., Competing Interests: MP, IP, LW, LG, OS, JT, and NS have none to declare. BWL has previously received honoraria from Astra Zeneca for speaking about the use of predict prostate. VG received honoraria from Janssen speaking about risk and prognosis in prostate cancer and use of Predict Prostate and Cambridge Prognostic Groups., (© 2023 The Authors. BJUI Compass published by John Wiley & Sons Ltd on behalf of BJU International Company.)

Background: Conventional systemic drugs are used to treat children and young people (CYP) with severe atopic dermatitis (AD) worldwide, but no robust randomized controlled trial (RCT) evidence exists regarding their efficacy and safety in this population. While novel therapies have expanded therapeutic options, their high cost means traditional agents remain important, especially in lower-resource settings., Objectives: To compare the safety and efficacy of ciclosporin (CyA) with methotrexate (MTX) in CYP with severe AD in the TREatment of severe Atopic Eczema Trial (TREAT) trial., Methods: We conducted a parallel group assessor-blinded RCT in 13 UK and Irish centres. Eligible participants aged 2-16 years and unresponsive to potent topical treatment were randomized to either oral CyA (4 mg kg-1 daily) or MTX (0.4 mg kg-1 weekly) for 36 weeks and followed-up for 24 weeks. Co-primary outcomes were change from baseline to 12 weeks in Objective Severity Scoring of Atopic Dermatitis (o-SCORAD) and time to first significant flare (relapse) after treatment cessation. Secondary outcomes included change in quality of life (QoL) from baseline to 60 weeks; number of participant-reported flares following treatment cessation; proportion of participants achieving ≥ 50% improvement in Eczema Area and Severity Index (EASI 50) and ≥ 75% improvement in EASI (EASI 75); and stratification of outcomes by filaggrin status., Results: In total, 103 participants were randomized (May 2016-February 2019): 52 to CyA and 51 to MTX. CyA showed greater improvement in disease severity by 12 weeks [mean difference in o-SCORAD -5.69, 97.5% confidence interval (CI) -10.81 to -0.57 (P = 0.01)]. More participants achieved ≥ 50% improvement in o-SCORAD (o-SCORAD 50) at 12 weeks in the CyA arm vs. the MTX arm [odds ratio (OR) 2.60, 95% CI 1.23-5.49; P = 0.01]. By 60 weeks MTX was superior (OR 0.33, 95% CI 0.13-0.85; P = 0.02), a trend also seen for ≥ 75% improvement in o-SCORAD (o-SCORAD 75), EASI 50 and EASI 75. Participant-reported flares post-treatment were higher in the CyA arm (OR 3.22, 95% CI 0.42-6.01; P = 0.02). QoL improved with both treatments and was sustained after treatment cessation. Filaggrin status did not affect outcomes. The frequency of adverse events (AEs) was comparable between both treatments. Five (10%) participants on CyA and seven (14%) on MTX experienced a serious AE., Conclusions: Both CyA and MTX proved effective in CYP with severe AD over 36 weeks. Participants who received CyA showed a more rapid response to treatment, while MTX induced more sustained disease control after discontinuation., Competing Interests: Conflicts of interest C.F. is Chief Investigator of the UK National Institute for Health Research-funded TREAT (ISRCTN15837754) and SOFTER (ClinicalTrials.gov: NCT03270566) trials, as well as the UK–Irish Atopic eczema Systemic Therapy Register (A-STAR; ISRCTN11210918) and a Principal Investigator in the European Union (EU) Horizon 2020-funded BIOMAP Consortium (http://www.biomap-imi.eu). He also leads the EU Trans-Foods consortium. His department has received investigator-led funding from Sanofi-Genzyme and Pfizer for microbiome work. D.O’K. has received funding for advisory board participation with Sanofi-Genzyme. M.W. is a steering committee member of A-STAR (ISRCTN11210918). T.M. has received funding for advisory boards and teaching from Sanofi-Genzyme, AbbVie and Pfizer. M.J.C. has received investigator-led funding from Hyphens Pharma, Johnson & Johnson, Sanofi, L’Oréal, LEO Pharma, ACO Nordic, Pfizer, Regeneron and Sanofi-Genzyme, as well as funding for advisory board participation with Menlo. He has also received consultant fees from Boots, Eli Lilly and Procter & Gamble. S.J.B. is a medical advisor to the Ichthyosis Support Group and Eczema Outreach Support and has received funding from the Wellcome Trust. A.D.I. has received consulting fees from Area, Almirall, AbbVie, Pfizer, Eli Lilly and Sanofi-Regeneron, and is the Director of the International Eczema Council. A.R.-H., A.P.J., B.R.T., C.S., M.-L.L., E. Hilger, M.D.S., F.A., F.B., D.G., P.B., B.E., J.E.G., S.A., S.B., P.R.W., L.S.T., R.H., T.H.S., E. Howard, J.R. and L.S. declare no conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Background: Methylation levels may be associated with and serve as markers to predict risk of progression of precancerous cervical lesions. We conducted an epigenome-wide association study (EWAS) of CpG methylation and progression to high-grade cervical intraepithelial neoplasia (CIN2 +) following an abnormal screening test., Methods: A prospective US cohort of 289 colposcopy patients with normal or CIN1 enrollment histology was assessed. Baseline cervical sample DNA was analyzed using Illumina HumanMethylation 450K (n = 76) or EPIC 850K (n = 213) arrays. Participants returned at provider-recommended intervals and were followed up to 5 years via medical records. We assessed continuous CpG M values for 9 cervical cancer-associated genes and time-to-progression to CIN2+. We estimated CpG-specific time-to-event ratios (TTER) and hazard ratios using adjusted, interval-censored Weibull accelerated failure time models. We also conducted an exploratory EWAS to identify novel CpGs with false discovery rate (FDR) < 0.05., Results: At enrollment, median age was 29.2 years; 64.0% were high-risk HPV-positive, and 54.3% were non-white. During follow-up (median 24.4 months), 15 participants progressed to CIN2+. Greater methylation levels were associated with a shorter time-to-CIN2+ for CADM1 cg03505501 (TTER = 0.28; 95%CI 0.12, 0.63; FDR = 0.03) and RARB Cluster 1 (TTER = 0.46; 95% CI 0.29, 0.71; FDR = 0.01). There was evidence of similar trends for DAPK1 cg14286732, PAX1 cg07213060, and PAX1 Cluster 1. The EWAS detected 336 novel progression-associated CpGs, including those located in CpG islands associated with genes FGF22, TOX, COL18A1, GPM6A, XAB2, TIMP2, GSPT1, NR4A2, and APBB1IP., Conclusions: Using prospective time-to-event data, we detected associations between CADM1-, DAPK1-, PAX1-, and RARB-related CpGs and cervical disease progression, and we identified novel progression-associated CpGs., Impact: Methylation levels at novel CpG sites may help identify individuals with ≤CIN1 histology at higher risk of progression to CIN2+ and inform risk-based cervical cancer screening guidelines., (© 2023. The Author(s).)

Objectives: This study interviewed adult patients presenting to the emergency department (ED) for various pain conditions enquiring about their preferred tool for reporting pain severity and preferred time interval between initial assessment and subsequent pain reassessments., Methods: A prospective observational (cross-sectional) study was conducted in adult patients with acute pain in a tertiary care hospital ED setting. Patients' initial pain score was recorded using NRS (numerical rating scale) pain scale, and appropriate analgesia offered. Once the patient had been evaluated by an attending physician, a research team member interviewed the patient regarding the pain reassessment time and preferred pain assessment tool. The pain assessment tools evaluated in this study were NRS, PS (picture scale or face pain scale), VRS (verbal rating scale), and VAS (visual analogue scale). The patients were presented with the four pain assessment tools (in their primary language) through an audio-visual on an electronic tablet display., Results: 200 (138 male, mean age 36.5 ± 11.17) patients participated in the study. With increasing age, pain reassessment interval increased by 0.19 min (95% CI 0.03-0.36 min). Males requested pain reassessment 6.7 min (95% CI 2.2-10.8) faster than females. In this study, the preferred interval for pain reassessment was reported as a mean of 22.8 (SD + -13.6) minutes. There was no relationship reported between time reassessment and pain severity (P = 0.22). Out of 200 subjects, irrespective of the initial pain scores, 100 preferred NRS. NRS was preferred by patients with mild to moderated pain due to the perception of being faster. However, patients with severe pain choose a non-NRS scale to prioritize accuracy., Conclusion: There was no influence found between the initial pain severity scores and the desired frequency of pain reassessment. However, associations were identified between the time for pain reassessment interval and age, sex, and geographical region. Patients with severe pain preferred PS or VRS while patients with mild/moderate pain preferred the NRS., Competing Interests: Declaration of Competing Interest No conflicts of Interest are declared., (Copyright © 2023 Elsevier Inc. All rights reserved.)

This Review provides an epidemiological overview of global mortality from acute coronary syndromes (ACS). Across the regions of the world where data are available, mortality from ACS - including premature (age <70 years) mortality from ACS - was higher in men than in women. In both sexes, age-standardized mortality rates (ASMRs) for ACS in 2020 were highest in lower-income global regions. However, 20 years earlier, ASMRs for ACS were highest in higher-income global regions, including Europe, Northern America and Oceania. These higher-income regions have seen progressive reductions in mortality from ACS during the past 20 years, which is in contrast to the more stable levels of mortality from ACS in Asia and in Latin America and the Caribbean. In the seven African countries with data available, a small upwards trend in ASMRs for ACS was observed, reflecting an epidemiological transition that is already well advanced in these regions. Consistent with these changes during the past 20 years were >50% reductions in ASMRs for ACS in the high-income countries of the world compared with <15% reductions in lower-middle-income countries. Policymakers need more complete epidemiological data across and within global regions to identify those countries in which the burden of death from ACS is greatest and the need to implement preventive strategies is most pressing., (© 2023. Springer Nature Limited.)

Background & Aims: Chronic liver disease (CLD) is associated with increased cardiovascular disease (CVD) risk. We investigated whether early signs of liver disease (measured by iron-corrected T1-mapping [cT1]) were associated with an increased risk of major CVD events., Methods: Liver disease activity (cT1) and fat (proton density fat fraction [PDFF]) were measured using LiverMultiScan® between January 2016 and February 2020 in the UK Biobank imaging sub-study. Using multivariable Cox regression, we explored associations between liver cT1 (MRI) and primary CVD (coronary artery disease, atrial fibrillation [AF], embolism/vascular events, heart failure [HF] and stroke), and CVD hospitalisation and all-cause mortality. Liver blood biomarkers, general metabolism biomarkers, and demographics were also included. Subgroup analysis was conducted in those without metabolic syndrome (defined as at least three of: a large waist, high triglycerides, low high-density lipoprotein cholesterol, increased systolic blood pressure, or elevated haemoglobin A1c)., Results: A total of 33,616 participants (mean age 65 years, mean BMI 26 kg/m 2 , mean haemoglobin A1c 35 mmol/mol) had complete MRI liver data with linked clinical outcomes (median time to major CVD event onset: 1.4 years [range: 0.002-5.1]; follow-up: 2.5 years [range: 1.1-5.2]). Liver disease activity (cT1), but not liver fat (PDFF), was associated with higher risk of any major CVD event (hazard ratio 1.14; 95% CI 1.03-1.26; p = 0.008), AF (1.30; 1.12-1.51; p <0.001); HF (1.30; 1.09-1.56; p= 0.004); CVD hospitalisation (1.27; 1.18-1.37; p <0.001) and all-cause mortality (1.19; 1.02-1.38; p = 0.026). FIB-4 index was associated with HF (1.06; 1.01-1.10; p = 0.007). Risk of CVD hospitalisation was independently associated with cT1 in individuals without metabolic syndrome (1.26; 1.13-1.4; p <0.001)., Conclusion: Liver disease activity, by cT1, was independently associated with a higher risk of incident CVD and all-cause mortality, independent of pre-existing metabolic syndrome, liver fibrosis or fat., Impact and Implications: Chronic liver disease (CLD) is associated with a twofold greater incidence of cardiovascular disease. Our work shows that early liver disease on iron-corrected T1 mapping was associated with a higher risk of major cardiovascular disease (14%), cardiovascular disease hospitalisation (27%) and all-cause mortality (19%). These findings highlight the prognostic relevance of a comprehensive evaluation of liver health in populations at risk of CVD and/or CLD, even in the absence of clinical manifestations or metabolic syndrome, when there is an opportunity to modify/address risk factors and prevent disease progression. As such, they are relevant to patients, carers, clinicians, and policymakers., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

In the last decade there has been a proliferation of research on misinformation. One important aspect of this work that receives less attention than it should is exactly why misinformation is a problem. To adequately address this question, we must first look to its speculated causes and effects. We examined different disciplines (computer science, economics, history, information science, journalism, law, media, politics, philosophy, psychology, sociology) that investigate misinformation. The consensus view points to advancements in information technology (e.g., the Internet, social media) as a main cause of the proliferation and increasing impact of misinformation, with a variety of illustrations of the effects. We critically analyzed both issues. As to the effects, misbehaviors are not yet reliably demonstrated empirically to be the outcome of misinformation; correlation as causation may have a hand in that perception. As to the cause, advancements in information technologies enable, as well as reveal, multitudes of interactions that represent significant deviations from ground truths through people's new way of knowing (intersubjectivity). This, we argue, is illusionary when understood in light of historical epistemology. Both doubts we raise are used to consider the cost to established norms of liberal democracy that come from efforts to target the problem of misinformation.

Background: Concerns about the housing of migrants and asylum seekers have escalated since the COVID-19 pandemic. From the use of quasi-detention facilities and so-called contingency accommodation to outbreaks of diphtheria in processing centres, there is a worrying trend to normalise potentially damaging conditions. The aim of this study was to assess the health risks posed by contingency housing for asylum seekers in the UK., Methods: In this cross-sectional survey, a 10-point online questionnaire was sent to professional networks working with refugees and asylum seekers within the UK. Responses were collected between March 4, and April 11, 2022, using a mixture of convenience and snowballing sampling approach. The objectives of the survey were (1) to identify and document unmet needs, (2) to offer practical support, and (3) to map out services and organisation. The survey was designed by six medical professionals with experience of working with migrants and validated by three doctors who had experience running out-reach medical clinics for asylum seekers within contingency accommodation. Background details of geographical location and occupation were collected, and a combination of closed and open questions were used to collect information across five domains (medical, legal social, integration, and basic essentials) using a social determinants of health framework. A code book thematic analysis using a deductive/inductive hybrid approach was used to identify health and social needs as well as specific rights being denied., Findings: There were 68 responses from around the UK, of which 30 (44%) were health-care professionals, and 38 (56%) were from the wider voluntary sector. 45 (67%) had visited an accommodation site, and 21 (33%) had worked with those living in contingency accommodation in other respects. Respondents reported observations regarding sites across most parts of the UK. Major themes of access to health-care, access to other services, barriers to access, and safeguarding were identified, with subthemes on access to primary care, maternity, and mental health services (eg, "Vast unmet need in mental health provision, several suicide attempts"); access to basic essential services (eg, "Food was not fit for purpose" "[c]hildren often did not receive breakfast"); education, and legal support; and frequent moving and communication., Interpretation: Through several themes we highlight the substantial impact of structural isolation of asylum seekers through contingency housing, its major effects on wellbeing and the exacerbation of health inequities. We are using these results to work with asylum seekers and local non-governmental organisations to campaign for improved housing conditions. Study limitations include sampling bias, and a lack of voices of those with lived experience., Funding: None., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Post-mortem computed tomography (CT) can provide useful insights into coronial and forensic pathological investigation of the fire-damage victim. Understanding the pathological changes that can occur in fatalities caused by fire, particularly in relation to fire damage to the body, is paramount in attempting to distinguish ante-mortem and peri-mortem blunt traumatic injuries from fire-related damage to the body. Understanding the fire-damage features on post-mortem CT may also assist in determining cause of the fire and associated fire-damage. Although the requirements of radiological evaluation in post-mortem imaging are very different to those of day-to-day clinical ante-mortem imaging, foremost is a high-resolution CT protocol of the entire body in order to fulfil the requirements and expectations of such imaging and radiological interpretation., (Copyright © 2023 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Aims: Cardiovascular disease (CVD) is the leading cause of mortality and morbidity in type 1 (T1D) and type 2 diabetes (T2D). Despite diabetes affects the myocardium, risk prediction models do not include myocardial function parameters. Myocardial performance index (MPI) reflects left ventricular function. The prognostic value of MPI has not been evaluated in large-scale diabetes populations., Methods and Results: We evaluated two prospective cohort studies: Thousand&1 (1093 individuals with T1D) and Thousand&2 (1030 individuals with T2D). Clinical data, including echocardiography, were collected at baseline. We collected follow-up data from national registries. We defined major adverse cardiovascular events (MACE) as incident events of hospital admission for acute coronary syndrome, heart failure, stroke, or all-cause mortality. For included individuals (56% male, 54 ± 15 years, MPI 0.51 ± 0.1, 63% T1D), follow-up was 100% after median of 5.3 years (range: 4.8-6.3). MPI was associated with MACE (HR 1.2, 95%CI 1.0-1.3, P = 0.012, per 0.10-unit increase) and heart failure (HR 1.3, 95%CI 1.1-1.6, P = 0.005, per 0.10-unit increase) after adjusting for clinical and echocardiographic variables. MPI predicted MACE and heart failure better in T1D than T2D (P = 0.031 for interaction). MPI added discriminatory power to the Steno T1 Risk Engine, based on clinical characteristics, in predicting MACE [area under the curve (AUC) from 0.77 to 0.79, P = 0.030] and heart failure (AUC from 0.77 to 0.83, P = 0.009) in T1D., Conclusion: MPI is independently associated with MACE and heart failure in T1D but not T2D and improves prediction in T1D. Echocardiographic assessment in T1D may enhance risk prediction., Competing Interests: Conflict of interest: P.G.J. reports lecture fees from Astra Zeneca. U.D. has been an invited speaker for and received research grants from Bayer. T.B.-S. reports grants to his institution from Amgen, AstraZeneca, Boehringer, GE Healthcare, Novo Nordisk, and Sanofi Pasteur; has been on the advisory board of Amgen, GSK, and Sanofi Pasteur; and has received honoraria from Bayer, GSK, Novartis, and Sanofi Pasteur. P.R. reports grants to his institution from Astra Zeneca, Bayer, and Novo Nordisk and has received honoraria from Abbott, Astellas, Astra Zeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, and Sanofi (all fees to the institution). M.T.J. has been a consultant, on advisory boards, or invited speaker for Astra Zeneca, GE, Novo Nordisk, and Novartis. All other authors have declared no conflict of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Hypertension is a key modifiable risk factor for cardiovascular disease - the leading cause of death in the UK. Good blood pressure (BP) control reduces mortality. However, health inequities may lead to variability in hypertension monitoring and control., Aim: To investigate health inequities related to ethnicity, sex, age, and socioeconomic status in the monitoring, treatment, and control of BP in a large cohort of adult patients with hypertension., Design and Setting: A cross-sectional cohort study of adults with hypertension registered with general practices in North East London on 1 April 2019., Method: Multivariable logistic regression was used to estimate associations of demographics and treatment intensity for the following hypertension management indicators: a) BP recording in past 12 months; b) BP on age- adjusted target; and c) BP on age-adjusted target and BP recorded in past 12 months., Results: In total, 156 296 adults were included. The Black ethnicity group was less likely to have controlled BP than the White ethnicity group (odds ratio [OR] 0.87, 95% [confidence interval] CI = 0.84 to 0.91). The Asian ethnicity group was more likely to have controlled BP (OR 1.28, 95% CI = 1.23 to 1.32). Ethnicity differences in control could not be explained by the likelihood of having a recent BP recording, nor by treatment intensity differences. Older adults (aged ≥50 years) were more likely to have controlled hypertension than younger patients., Conclusion: Individuals of Black ethnicity and younger people are less likely to have controlled hypertension and may warrant targeted interventions. Possible explanations for these findings are presented but further research is needed about reasons for ethnic differences., (© The Authors.)

Long-term adverse experiences following psychedelic use can persist for weeks, months, or even years, and are relatively unexplored in psychedelic research. Our convergent mixed-method study gained quantitative and qualitative data from 608 participants who reported extended difficulties following psychedelic experiences. Data was gathered on the context of use, the nature and duration of the challenges they experienced (including a written description of these), plus a range of possible risk factors and perceived causes. The most common forms of extended difficulty were feelings of anxiety and fear, existential struggle, social disconnection, depersonalization and derealization. For approximately one-third of the participants, problems persisted for over a year, and for a sixth, they endured for more than three years. It was found that a shorter duration of difficulties was predicted by knowledge of dose, drug type and lower levels of difficulty reported during the psychoactive experience, while a narrower range of difficulties was predicted by taking the drug in a guided setting. Implications for psychedelic harm reduction are discussed., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Evans et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Genome-wide association studies for glycemic traits have identified hundreds of loci associated with these biomarkers of glucose homeostasis. Despite this success, the challenge remains to link variant associations to genes, and underlying biological pathways., Methods: To identify coding variant associations which may pinpoint effector genes at both novel and previously established genome-wide association loci, we performed meta-analyses of exome-array studies for four glycemic traits: glycated hemoglobin (HbA1c, up to 144,060 participants), fasting glucose (FG, up to 129,665 participants), fasting insulin (FI, up to 104,140) and 2hr glucose post-oral glucose challenge (2hGlu, up to 57,878). In addition, we performed network and pathway analyses., Results: Single-variant and gene-based association analyses identified coding variant associations at more than 60 genes, which when combined with other datasets may be useful to nominate effector genes. Network and pathway analyses identified pathways related to insulin secretion, zinc transport and fatty acid metabolism. HbA1c associations were strongly enriched in pathways related to blood cell biology., Conclusions: Our results provided novel glycemic trait associations and highlighted pathways implicated in glycemic regulation. Exome-array summary statistic results are being made available to the scientific community to enable further discoveries., Competing Interests: Competing interests: Rebecca S. Fine: Rebecca S. Fine is currently employed by Vertex Pharmaceuticals Incorporated. Audrey Y Chu: Currently employed by GlaxoSmithkline. Dennis O. Mook-Kanamori: Dennis Mook-Kanamori is working as a part-time clinical research consultant for Metabolon, Inc. Paul W. Franks: PWF has been a paid consultant for Eli Lilly and Sanofi Aventis and has received research support from several pharmaceutical companies as part of a European Union Innovative Medicines Initiative (IMI) project. Mike A. Nalls: Dr. Mike A. Nalls is supported by a consulting contract between Data Tecnica International LLC and the National Institute on Aging (NIA), National Institutes of Health (NIH), Bethesda, MD, USA. Dr. Nalls also consults for Illumina Inc., the Michael J. Fox Foundation, and the University of California Healthcare. Mark J. Caulfield: MJC is Chief Scientist for Genomics England, a UK government company. Joel N. Hirschhorn: JHN is on the scientific advisory board of Camp4 Therapeutics. Erik Ingelsson: Erik Ingelsson is now an employee of GlaxoSmithKline. Anubha Mahajan: Anubha Mahajan is an employee of Genentech since January 2020, and a holder of Roche stock. Mark I McCarthy: The views expressed in this article are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health. MMcC has served on advisory panels for Pfizer, NovoNordisk and Zoe Global, has received honoraria from Merck, Pfizer, Novo Nordisk and Eli Lilly, and research funding from Abbvie, Astra Zeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, NovoNordisk, Pfizer, Roche, Sanofi Aventis, Servier, and Takeda. As of June 2019, MMcC is an employee of Genentech, and a holder of Roche stock. Inês Barroso: IB and spouse declare stock ownership in GlaxoSmithkline and Incyte Ltd. James B. Meigs: JBM serves as an Academic Associate for Quest Diagnostics R&D Bruce M Psaty serves on the Steering Committee of the Yale Open Data Access Project funded by Johnson & Johnson. Dr. Sander W. van der Laan has received Roche funding for unrelated work. Matthias Blüher received honoraria as a consultant and speaker from Amgen, AstraZeneca, Bayer, Boehringer-Ingelheim, Lilly, Novo Nordisk, Novartis, Pfizer and Sanofi. Vinicius Tragante: VT became an employee of deCODE genetics/Amgen Inc. after the conclusion of this work Dr Franco is employed by ErasmusAGE, a center for aging research across the life course funded by Nestlé Nutrition (Nestec Ltd.) and Metagenics., (Copyright: © 2023 Willems SM et al.)

Introduction: We aimed to investigate ethnic differences in the associations of potentially modifiable risk factors with dementia., Methods: We used anonymised data from English electronic primary care records for adults aged 65 and older between 1997 and 2018. We used Cox regression to investigate main effects for each risk factor and interaction effects between each risk factor and ethnicity., Results: We included 865,674 people with 8,479,973 person years of follow up. Hypertension, dyslipidaemia, obesity and diabetes were more common in people from minority ethnic groups than White people. The impact of hypertension, obesity, diabetes, low HDL and sleep disorders on dementia risk was increased in South Asian people compared to White people. The impact of hypertension was greater in Black compared to White people., Discussion: Dementia prevention efforts should be targeted towards people from minority ethnic groups and tailored to risk factors of particular importance., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Mukadam et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Variations in cardiovascular disease (CVD) burden between West and South European countries are rarely reported. To address this knowledge gap, The Lancet Regional Health-Europe convened experts from a broad range of countries to assess the current state of knowledge of cardiovascular disease inequalities across Europe. This Review is specifically focused on West and South European countries. Mortality, risk factor and economic data for nine West European and six South European countries were sourced from the World Health Organisation, the Global Burden of Disease study and the World Bank. Healthcare data were collected by survey of participating countries. A key finding was of declines in age-standardised mortality rates (ASMRs) across all countries since 1990. In 2019 rates per 100,000 were lower in West European countries in males (279.7 (264.1-335.9) vs 337.2 (323.7-367.2)) and females (196.2 (183.3-228.8) vs 247.3 (232.2-268.3)). Differences in risk factor exposures were small, with the exception of physical activity and dietary factors, but across all countries the prevalence of obesity has increased, affecting >20% of adults in 2019. Healthcare delivery in 2019 showed inequalities with cardiovascular procedure rates lower in South compared with West European countries. Further declines in ASMRs in West and South European countries will require population strategies to reduce obesity and address inequalities in physical activity and dietary factors. Reducing the gap in procedure rates is unlikely to match the beneficial effects of population strategies for reducing CVD burden in South European countries., Competing Interests: Timmis owns stock in HD Clinical (Electronic health record systems) and RE-COGNITION Health (Dementia care). Torbica has a consulting contract with the European Society of Cardiology. Aboyans has an unpaid leadership role in the European Heart Health Institute and has received consulting fees from Bayer, Amarin, Boehringer-Ingelheim and NovoNordisk. Vardas has received consulting fees from Hygeia Hospital Group., (© 2023 The Author(s).)

Background: Temporal trends of the impact of social determinants on cardiovascular outcomes of cancer patients has not been previously studied., Objectives: This study examined social disparities in cardiovascular mortality of people with and without cancer in the US population between 1999 and 2019., Methods: Primary cardiovascular deaths were identified from the Multiple Cause of Death database and grouped by cancer status. The cancer cohort was subcategorized into breast, lung, prostate, colorectal, and haematological. The number of cardiovascular deaths, crude cardiovascular mortality rate, cardiovascular age-adjusted mortality rate (AAMR), and percentage change in cardiovascular AAMR were calculated by cancer status and cancer type, and stratified by sex, race, ethnicity, and urban-rural setting., Results: 17.9 million cardiovascular deaths were analysed. Of these, 572,222 occurred in patients with a record of cancer. The cancer cohort were older and included more men and White racial groups. Regardless of cancer status, cardiovascular AAMR was higher in men, rural settings, and Black or African American races. Cardiovascular AAMR declined over time, with greater reduction in those with cancer (-51.6% vs -38.3%); the greatest reductions were in colorectal (-68.4%), prostate (-60.0%), and breast (-58.8%) cancers. Sex, race, and ethnic disparities reduced over time, with greater narrowing in the cancer cohort. There was increase in urban-rural disparities, which appeared greater in those with cancer., Conclusions: While most social disparities narrowed over time, urban-rural disparities widened, with greater increase in those with cancer. Healthcare plans should incorporate strategies for reduction of health inequality equitable access to cardio-oncology services., (© 2023 The Authors. Published by Elsevier B.V.)

Background: Cardiac dysfunction (CD) has emerged as a key contributor to delayed organ failure and late mortality in patients surviving the initial traumatic hemorrhagic response. Inflammatory processes are implicated in the initial stages of this CD; however, downstream pathways leading to a characteristic rapid fall in stroke volume and cardiac output are not yet fully defined. Currently, no cardioprotective treatments are available. We investigated the role of myocardial oxidative stress in the pathogenesis of CD associated to traumatic hemorrhagic injury, and its related metabolomic profile., Methods: Ex vivo tissue from a 3-hour murine model of pressure-controlled trauma hemorrhagic shock (THS) was analyzed. Animals were randomized to echocardiography-guided crystalloid fluid resuscitation or a control group (sham: cannulation and anesthesia only, or naïve: no intervention). Trauma hemorrhagic shock and naïve samples were assessed by immunohistochemistry for nuclear 8-hydroxy-2'-deoxyguanosine expression as a marker of oxidative stress. Metabolomic analysis of THS and sham group tissue was performed by LC-MS., Results: 8-Hydroxy-2'-deoxyguanosine expression across the myocardium was significantly higher following THS injury compared to naïve group (33.01 ± 14.40% vs. 15.08 ± 3.96%, p < 0.05). Trauma hemorrhagic shock injury significantly increased lysine ( p = 0.022), and decreased aconitate ( p = 0.016) and glutamate ( p = 0.047) in the myocardium, indicating activation of a catabolic metabolism and oxidative stress response., Conclusion: We confirm the acute development of oxidative stress lesions and altered cardiac energy metabolism following traumatic hemorrhage injury, providing insight into the relationship between inflammatory damage and impaired cardiac contractility. These findings may provide targets for development of novel cardioprotective therapeutics aiming to decrease late mortality from trauma., (Copyright © 2023 American Association for the Surgery of Trauma.)

Objective: To develop a core outcome set for heavy menstrual bleeding (HMB)., Design: Core outcome set (COS) development methodology described by the COMET initiative., Setting: University hospital gynaecology department, online international survey and web-based international consensus meetings., Population or Sample: An international collaboration of stakeholders (clinicians, patients, academics, guideline developers) from 20 countries and 6 continents., Methods: Phase 1: Systematic review of previously reported outcomes to identify potential core outcomes. Phase 2: Qualitative studies with patients to identify outcomes most important to them. Phase 3: Online two-round Delphi survey to achieve consensus about which outcomes are most important. Phase 4: A consensus meeting to finalise the COS., Main Outcome Measures: Outcome importance was assessed in the Delphi survey on a 9-point scale., Results: From the 'long list' of 114, 10 outcomes were included in the final COS: subjective blood loss; flooding; menstrual cycle metrics; severity of dysmenorrhoea; number of days with dysmenorrhoea; quality of life; adverse events; patient satisfaction; number of patients going on to have further treatment for HMB and haemoglobin level., Conclusions: The final COS includes variables that are feasible for use in clinical trials in all resource settings and apply to all known underlying causes of the symptom of HMB. These outcomes should be reported in all future trials of interventions, their systematic reviews, and clinical guidelines to underpin policy., (© 2023 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)