Hazard characterization of Alternaria toxins to identify data gaps and improve risk assessment for human health.

Fungi of the genus Alternaria are ubiquitous plant pathogens and saprophytes which are able to grow under varying temperature and moisture conditions as well as on a large range of substrates. A spectrum of structurally diverse secondary metabolites with toxic potential has been identified, but occurrence and relative proportion of the different metabolites in complex mixtures depend on strain, substrate, and growth conditions. This review compiles the available knowledge on hazard identification and characterization of Alternaria toxins. Alternariol (AOH), its monomethylether AME and the perylene quinones altertoxin I (ATX-I), ATX-II, ATX-III, alterperylenol (ALP), and stemphyltoxin III (STTX-III) showed in vitro genotoxic and mutagenic properties. Of all identified Alternaria toxins, the epoxide-bearing analogs ATX-II, ATX-III, and STTX-III show the highest cytotoxic, genotoxic, and mutagenic potential in vitro. Under hormone-sensitive conditions, AOH and AME act as moderate xenoestrogens, but in silico modeling predicts further Alternaria toxins as potential estrogenic factors. Recent studies indicate also an immunosuppressive role of AOH and ATX-II; however, no data are available for the majority of Alternaria toxins. Overall, hazard characterization of Alternaria toxins focused, so far, primarily on the commercially available dibenzo-α-pyrones AOH and AME and tenuazonic acid (TeA). Limited data sets are available for altersetin (ALS), altenuene (ALT), and tentoxin (TEN). The occurrence and toxicological relevance of perylene quinone-based Alternaria toxins still remain to be fully elucidated. We identified data gaps on hazard identification and characterization crucial to improve risk assessment of Alternaria mycotoxins for consumers and occupationally exposed workers.

Global perspectives on heart disease rehabilitation and secondary prevention: a scientific statement from the Association of Cardiovascular Nursing and Allied Professions, European Association of Preventive Cardiology, and International Council of Cardiovascular Prevention and Rehabilitation.

Cardiovascular disease is a leading cause of death, morbidity, disability, and reduced health-related quality of life, as well as economic burden worldwide, with some 80% of disease burden occurring in the low- and middle-income country (LMIC) settings. With increasing numbers of people living longer with symptomatic disease, the effectiveness and accessibility of secondary preventative and rehabilitative health services have never been more important. Whilst LMICs experience the highest prevalence and mortality rates, the global approach to secondary prevention and cardiac rehabilitation, which mitigates this burden, has traditionally been driven from clinical guidelines emanating from high-income settings. This state-of-the art review provides a contemporary global perspective on cardiac rehabilitation and secondary prevention, contrasting the challenges of and opportunities for high vs. lower income settings. Actionable solutions to overcome system, clinician, programme, and patient level barriers to cardiac rehabilitation access in LMICs are provided.

Placing patient-reported outcomes at the centre of cardiovascular clinical practice: implications for quality of care and management.

Patient-reported outcomes (PROs) provide important insights into patients' own perspectives about their health and medical condition, and there is evidence that their use can lead to improvements in the quality of care and to better-informed clinical decisions. Their application in cardiovascular populations has grown over the past decades. This statement describes what PROs are, and it provides an inventory of disease-specific and domain-specific PROs that have been developed for cardiovascular populations. International standards and quality indices have been published, which can guide the selection of PROs for clinical practice and in clinical trials and research; patients as well as experts in psychometrics should be involved in choosing which are most appropriate. Collaborations are needed to define criteria for using PROs to guide regulatory decisions, and the utility of PROs for comparing and monitoring the quality of care and for allocating resources should be evaluated. New sources for recording PROs include wearable digital health devices, medical registries, and electronic health record. Advice is given for the optimal use of PROs in shared clinical decision-making in cardiovascular medicine, and concerning future directions for their wider application.

Multimodal Analgesic Effectiveness on Acute Postoperative Pain Management After Adult Cardiac Surgery: Protocol for a Systematic Review.

BACKGROUND: Many patients report moderate to severe pain in the acute postoperative period. Enhanced recovery protocols recommend multimodal analgesics, but the optimal combination of these is unknown. PURPOSE: The aim of this study was to synthesize the best available evidence about effectiveness of multimodal analgesics on pain after adult cardiac surgery. METHODS: A systematic review to determine the effect of multimodal postoperative analgesics is proposed (International Prospective Register of Systematic Reviews Registration CRD42022355834). Multiple databases including the Cochrane Library, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, American Psychological Association, the Education Resources Information Centre, the Excerpta Medica database, the Medical Literature Analysis and Retrieval System Online, Scopus, Web of Science, and clinical trials databases will be searched. Screening in Covidence and quality assessment will be conducted by 2 authors. A grading of recommendations, assessment, development, and evaluation summary of findings will be presented if meta-analysis is possible.

Potassium Supplementation and Prevention of Atrial Fibrillation After Cardiac Surgery: The TIGHT K Randomized Clinical Trial.

IMPORTANCE: Supplementing potassium in an effort to maintain high-normal serum concentrations is a widespread strategy used to prevent atrial fibrillation after cardiac surgery (AFACS), but is not evidence-based, carries risks, and is costly. OBJECTIVE: To determine whether a lower serum potassium concentration trigger for supplementation is noninferior to a high-normal trigger. DESIGN, SETTING, AND PARTICIPANTS: This open-label, noninferiority, randomized clinical trial was conducted at 23 cardiac surgical centers in the United Kingdom and Germany. Between October 20, 2020, and November 16, 2023, patients with no history of atrial dysrhythmias scheduled for isolated coronary artery bypass grafting (CABG) surgery were enrolled. The last study patient was discharged from the hospital on December 11, 2023. INTERVENTIONS: Patients were randomly assigned to a strategy of tight or relaxed potassium control (only supplementing if serum potassium concentration fell below 4.5 mEq/L or 3.6 mEq/L, respectively). Patients wore an ambulatory heart rhythm monitor, which was analyzed by a core laboratory masked to treatment assignment. MAIN OUTCOMES AND MEASURES: The prespecified primary end point was clinically detected and electrocardiographically confirmed new-onset AFACS in the first 120 hours after CABG surgery or until hospital discharge, whichever occurred first. All primary outcome events were validated by an event validation committee, which was masked to treatment assignment. Noninferiority of relaxed potassium control was defined as a risk difference for new-onset AFACS with associated upper bound of a 1-sided 97.5% CI of less than 10%. Secondary outcomes included other heart rhythm-related events, clinical outcomes, and cost related to the intervention. RESULTS: A total of 1690 patients (mean age, 65 years; 256 [15%] females) were randomized. The primary end point occurred in 26.2% of patients (n = 219) in the tight group and 27.8% of patients (n = 231) in the relaxed group, which is a risk difference of 1.7% (95% CI, -2.6% to 5.9%). There was no difference between the groups in the incidence of at least 1 AFACS episode detected by any means or by ambulatory heart rhythm monitor alone, non-AFACS dysrhythmias, in-patient mortality, or length of stay. Per-patient cost for purchasing and administering potassium was significantly lower in the relaxed group (mean difference, $111.89 [95% CI, $103.60-$120.19]; P <.001). CONCLUSIONS AND RELEVANCE: For AFACS prophylaxis, supplementation only when serum potassium concentration fell below 3.6 mEq/L was noninferior to the current widespread practice of supplementing potassium to maintain a serum potassium concentration greater than or equal to 4.5 mEq/L. The lower threshold of supplementation was not associated with any increase in dysrhythmias or adverse clinical outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04053816.

Self-Management and Glycemic Targets in Adult Haitian Immigrants With Type 2 Diabetes: Research Protocol.

BACKGROUND: Type 2 diabetes (T2D) is a chronic condition affecting more than 34.2 million U.S. adults, and people of African descent have a disproportionate burden. Haitian immigrants' unique cultural and biological factors put them at elevated risk for T2D-related complications. Despite prior research highlighting the success of multimethod approaches to T2D self-management behaviors on glycemic targets, a dearth of studies have used these methods to improve diabetes self-management in this marginalized population. OBJECTIVES: This article describes a repeated-measures design protocol of a going study about self-management behaviors among adult Haitian immigrants with T2D and characterizing their barriers to T2D self-management. METHODS: We will enroll 100 Haitian immigrants aged 18-64 years who have lived with T2D for at least 1 year. Using multiple recruitment methods and Research Electronic Data Capture, subjective and objective data on T2D self-management practices, glucose variability via continuous glucose monitor, and a comprehensive view of physical activity via actigraphy are collected. RESULTS: Data analysis will follow a two-part approach mirroring the two primary study objectives. DISCUSSION: Findings from the study will guide the development and testing of a culturally tailored diabetes self-management education program that will contribute essential information about best practices for this population and break barriers that may impede research on unique individuals and subsequent effective self-management.

Effectiveness of cognitive interventions for adult surgical patients after general anaesthesia to improve cognitive functioning: A systematic review.

AIMS AND OBJECTIVES: To examine the effectiveness of cognitive interventions after general anaesthesia to improve cognitive functioning. BACKGROUND: The number of surgical procedures performed worldwide is large and growing. Postoperative cognitive dysfunction is a common complication associated with poor postoperative outcomes. A variety of cognitive interventions have been developed to maintain or improve cognitive function in one or more cognitive domains. Cognitive interventions have shown to be effective in healthy older populations, those with mild cognitive impairment, and those with heart failure. The impact of cognitive interventions in surgical patients after general anaesthesia is a relatively new focus of research and is therefore less well established. METHODS: Seven bibliographic databases were searched in relation to 'surgery' and 'cognitive interventions'; no date or language limits were imposed. Studies including adult patients who were scheduled for, or who had undergone surgery under general anaesthesia, had a baseline cognitive assessment using a validated measurement, and had engaged with any cognition-based intervention were included. Full-text review for inclusion, quality assessment and data extraction were undertaken independently by two authors. This study is reported in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. RESULTS: A total of 550 papers were identified for possible inclusion, of which nine met the inclusion criteria and were included in the review. The majority were randomised controlled trials (RCTs) (n = 6 [66.7%]). Four studies used computerised cognitive interventions, while five used traditional cognitive interventions. Most of the studies used multi-domain cognitive training focusing on two or more domains (n = 7 [77.8%]) while two studies used single-domain cognitive training. Memory (n = 7 [77.8%]) and attention (n = 5 [55.6%]) were the cognitive domains most often targeted during the intervention. CONCLUSIONS: The use of cognitive interventions demonstrated some efficacy in improving cognitive function after general anaesthesia, particularly those targeting memory. RELEVANCE FOR CLINICAL PRACTICE: The findings of this review suggest that cognitive interventions show promise at improving cognitive performance in patients with POCD and could be usefully implemented in clinical practice to improve patient outcomes.

Impact of experimental design factors on the potency of genotoxicants in in vitro tests.

Previous studies have shown that differences in experimental design factors may alter the potency of genotoxic compounds in in vitro genotoxicity tests. Most of these studies used traditional statistical methods based on the lowest observed genotoxic effect levels, whereas more appropriate methods, such as the benchmark dose (BMD) approach, are now available to compare genotoxic potencies under different test conditions. We therefore investigated the influence of two parameters, i.e. cell type and exposure duration, on the potencies of two known genotoxicants [aflatoxin B1 and ethyl methanesulfonate (EMS)] in the in vitro micronucleus (MN) assay and comet assay (CA). Both compounds were tested in the two assays using two cell types (i.e. CHO-K1 and TK6 cells). To evaluate the effect of exposure duration, the genotoxicity of EMS was assessed after 3 and 24 h of exposure. Results were analyzed using the BMD covariate approach, also referred to as BMD potency ranking, and the outcome was compared with that of more traditional statistical methods based on lowest observed genotoxic effect levels. When comparing the in vitro MN results obtained in both cell lines with the BMD covariate approach, a difference in potency was detected only when EMS exposures were conducted for 24 h, with TK6 cells being more sensitive. No difference was observed in the potency of both EMS and aflatoxin B1 in the in vitro CA using both cell lines. In contrast, EMS was more potent after 24 h exposure compared with a 3 h exposure under all tested conditions, i.e. in the in vitro MN assay and CA in both cell lines. Importantly, for several of the investigated factors, the BMD covariate method could not be used to confirm the differences in potencies detected with the traditional statistical methods, thus highlighting the need to evaluate the impact of experimental design factors with adequate approaches.

Predictors of health-related quality of life after cardiac surgery: a systematic review.

BACKGROUND: Health-related quality of life (HRQoL) is important in determining surgical success, particularly from the patients' perspective. AIMS: To identify predictors for HRQoL outcome after cardiac surgery in order to identify potentially modifiable factors where interventions to improve patient outcomes could be targeted. METHODS: Electronic databases (including MEDLINE, CINAHL, Embase) were searched between January 2001 and December 2020 for studies determining predictors of HRQoL (using a recognised and validated tool) in adult patients undergoing cardiac surgery. Data extraction and quality assessments were undertaken and data was summarised using descriptive statistics and narrative synthesis, as appropriate. RESULTS: Overall, 3924 papers were screened with 41 papers included in the review. Considerable methodological heterogeneity between studies was observed. Most were single-centre (75.6%) prospective observational studies (73.2%) conducted in patients undergoing coronary artery bypass graft (CABG) (n = 51.2%) using a version of the SF-36 (n = 63.4%). Overall, 103 independent predictors (62 pre-operative, five intra-operative and 36 post-operative) were identified, where 34 (33.0%) were reported in more than one study. Potential pre-operative modifiable predictors include alcohol use, BMI/weight, depression, pre-operative quality of life and smoking while in the post-operative period pain and strategies to reduce post-operative complications and intensive care and hospital length of stay are potential therapeutic targets. CONCLUSION: Despite a lack of consistency across studies, several potentially modifiable predictors were identified that could be targeted in interventions to improve patient or treatment outcomes. This may contribute to delivering more person-centred care involving shared decision-making to improve patient HRQoL after cardiac surgery.

Maintenance of Serum Potassium Levels ≥3.6 mEq/L Versus ≥4.5 mEq/L After Isolated Elective Coronary Artery Bypass Grafting and the Incidence of New-Onset Atrial Fibrillation: Pilot and Feasibility Study Results.

OBJECTIVE: Serum potassium levels frequently are maintained at high levels (≥4.5 mEq/L) to prevent atrial fibrillation after cardiac surgery (AFACS), with limited evidence. Before undertaking a noninferiority randomized controlled trial to investigate the noninferiority of maintaining levels ≥3.6 mEq/L compared with this strategy, the authors wanted to assess the feasibility, acceptability, and safety of recruiting for such a trial. DESIGN: Pilot and feasibility study of full trial protocol. SETTING: Two university tertiary-care hospitals. PARTICIPANTS: A total of 160 individuals undergoing first-time elective isolated coronary artery bypass grafting. INTERVENTIONS: Randomization (1:1) to protocols aiming to maintain serum potassium at either ≥3.6 mEq/L or ≥4.5 mEq/L after arrival in the postoperative care facility and for 120 hours or until discharge from the hospital or AFACS occurred, whichever happened first. MEASUREMENTS AND MAIN RESULTS: Primary outcomes: (1) whether it was possible to recruit and randomize 160 patients for six months (estimated 20% of those eligible); (2) maintaining supplementation protocol violation rate ≤10% (defined as potassium supplementation being inappropriately administered or withheld according to treatment allocation after a serum potassium measurement); and (3) retaining 28-day follow-up rates ≥90% after surgery. Between August 2017 and April 2018, 723 patients were screened and 160 (22%) were recruited. Potassium protocol violation rate = 9.8%. Follow-up rate at 28 days = 94.3%. Data on planned outcomes for the full trial also were collected. CONCLUSIONS: It is feasible to recruit and randomize patients to a study assessing the impact of maintaining serum potassium concentrations at either ≥3.6 mEq/L or ≥4.5 mEq/L on the incidence of AFACS.

Embedding post-doctoral clinical academic careers in practice: The St Bartholomew's Hospital model.

AIMS AND OBJECTIVES: In order to retain and develop pre-doctoral and doctoral staff, we sought to establish and implement a model for supporting postdoctoral clinical academic careers at our hospital. BACKGROUND: Doctorally-prepared nurses can raise clinical practice standards, but there is a deficit of career opportunities and post-doctoral positions. This will inevitably impact delivering the evidence for improving patient outcomes and service delivery. It is therefore imperative that post-doctoral nursing and allied professional post-doctoral clinical academic career opportunities are developed and embedded in practice. DESIGN: We describe the development and implementation of a model to provide and embed post-doctoral clinical academic roles at our hospital. METHODS: A multidisciplinary group devised the model which was approved by the Hospital Executive Board. RESULTS: The model includes having a bespoke plan for each individual, planning the post-doctoral role at time of PhD planning, providing 1 day a week protected research time for a minimum of 12 months after PhD completion, having an appropriate honorary academic contract at a partner University, and providing integrated clinical and academic supervision throughout. Other key components include senior clinical and Executive Board support and an existing vibrant research culture at our organisation. CONCLUSIONS: The St Bartholomew's Hospital model, focusing on individualised posts integrating clinical and academic roles to address service needs, offers a novel approach to supporting post-doctoral clinical academic careers in a clinical setting. RELEVANCE TO CLINICAL PRACTICE: Since doctorally-prepared nurses can raise clinical practice standards we developed a sustainable infrastructure to increase our postdoctoral nursing and allied professional workforce. This model could provide a framework for other hospitals to embed postdoctoral clinical academic careers in practice.

A blinded clinical study using a subepidermal moisture biocapacitance measurement device for early detection of pressure injuries.

This study aimed to evaluate the sensitivity and specificity of subepidermal moisture (SEM), a biomarker employed for early detection of pressure injuries (PI), compared to the "Gold Standard" of clinical skin and tissue assessment (STA), and to characterize the timing of SEM changes relative to the diagnosis of a PI. This blinded, longitudinal, prospective clinical study enrolled 189 patients (n = 182 in intent-to-treat [ITT]) at acute and post-acute sites (9 USA, 3 UK). Data were collected from patients' heels and sacrums using a biocapacitance measurement device beginning at admission and continuing for a minimum of 6 days to: (a) the patient developing a PI, (b) discharge from care, or (c) a maximum of 21 days. Standard of care clinical interventions prevailed, uninterrupted. Principal investigators oversaw the study at each site. Blinded Generalists gathered SEM data, and blinded Specialists diagnosed the presence or absence of PIs. Of the ITT population, 26.4% developed a PI during the study; 66.7% classified as Stage 1 injuries, 23% deep tissue injuries, the remaining being Stage 2 or Unstageable. Sensitivity was 87.5% (95% CI: 74.8%-95.3%) and specificity was 32.9% (95% CI: 28.3%-37.8%). Area under the receiver operating characteristic curve (AUC) was 0.6713 (95% CI 0.5969-0.7457, P < .001). SEM changes were observed 4.7 (± 2.4 days) earlier than diagnosis of a PI via STA alone. Latency between the SEM biomarker and later onset of a PI, in combination with standard of care interventions administered to at-risk patients, may have confounded specificity. Aggregate SEM sensitivity and specificity and 67.13% AUC exceeded that of clinical judgment alone. While acknowledging specificity limitations, these data suggest that SEM biocapacitance measures can complement STAs, facilitate earlier identification of the risk of specific anatomies developing PIs, and inform earlier anatomy-specific intervention decisions than STAs alone. Future work should include cost-consequence analyses of SEM informed interventions.

A case of delayed methotrexate clearance following administration of a complementary medication containing chlorophyll.

A 54-year-old male with relapsed primary cerebral lymphoma and normal renal function was treated with methotrexate (MTX) 3 g/m(2) monthly by intravenous infusion. Throughout treatment the patient self-administered a complementary medicine (Jason Winter's chlorophyll®), which he was advised to cease during methotrexate treatment due to the potential for unknown interactions. For the first four cycles, chlorophyll was ceased two days prior to commencement of methotrexate and withheld until clearance. These cycles were administered without complication, and the methotrexate level reduced to <0.05 µmol/L within three days of each dose. Prior to cycle 5, chlorophyll was not ceased and there were no changes to concomitant medications. A literature search found no documented interactions between methotrexate and chlorophyll and the chemotherapy was administered without a delay in treatment. The methotrexate level three days post-administration was 0.36 µmol/L and did not reduce to <0.05 µmol/L until day 10. Consequently, from cycles 6 to 12, the methotrexate dose was halved, and the patient ceased chlorophyll 48 h prior to methotrexate administration until clearance. There were no further episodes of delayed methotrexate clearance. No impurities were detected in a sample of Jason Winter's chlorophyll®. It is therefore likely that the patient's delayed methotrexate clearance was due to an interaction with chlorophyll. It is recommended that such chlorophyll containing preparations be avoided in patients treated with methotrexate.

Factors affecting women's participation in cardiovascular research: a scoping review.

AIMS: Women are underrepresented in cardiovascular trials. We sought to explore the proportional representation of women in contemporary cardiovascular research and the factors (barriers and enablers) that affect their participation in cardiovascular studies. METHODS AND RESULTS: Multiple electronic databases were searched between January 2011 and September 2021 to identify papers that defined underrepresentation of women in cardiovascular research and/or reported sex-based differences in participating in cardiovascular research and/or barriers for women to participate in cardiovascular research. Data extraction was undertaken independently by two authors using a standardised data collection form. Results were summarised using descriptive statistics and narrative synthesis as appropriate.From 548 identified papers, 10 papers were included. Of those, four were conducted prospectively and six were retrospective studies. Five of the retrospective studies involved secondary analysis of trial data including over 780 trials in over 1.1 million participants. Overall, women were reported to be underrepresented in heart failure, coronary disease, myocardial infarction, and arrhythmia trials, compared to men. Barriers to participation included lack of information and understanding of the research, trial-related procedures, the perceived health status of the participant, and patient-specific factors including travel, childcare availability, and cost. A significantly higher likelihood of research participation was reported by women following a patient educational intervention. CONCLUSION: This review has highlighted the underrepresentation of women in a range of cardiovascular trials. Several barriers to women's participation in cardiovascular studies were identified. Researchers could mitigate against these in future trial planning and delivery to increase women's participation in cardiovascular research. REGISTRATION: The protocol was published on the public Open Science Framework platform on 13th August 2021 (no registration reference provided) and can be accessed at https://osf.io/ny4fd/.

Correction: Impact of maintaining serum potassium concentration ≥ 3.6mEq/L versus ≥ 4.5mEq/L for 120 hours after isolated coronary artery bypass graft surgery on incidence of new onset atrial fibrillation: Protocol for a randomized non-inferiority trial.

[This corrects the article DOI: 10.1371/journal.pone.0296525.].

Impact of maintaining serum potassium concentration ≥ 3.6mEq/L versus ≥ 4.5mEq/L for 120 hours after isolated coronary artery bypass graft surgery on incidence of new onset atrial fibrillation: Protocol for a randomized non-inferiority trial.

BACKGROUND: Atrial Fibrillation After Cardiac Surgery (AFACS) occurs in about one in three patients following Coronary Artery Bypass Grafting (CABG). It is associated with increased short- and long-term morbidity, mortality and costs. To reduce AFACS incidence, efforts are often made to maintain serum potassium in the high-normal range (≥ 4.5mEq/L). However, there is no evidence that this strategy is efficacious. Furthermore, the approach is costly, often unpleasant for patients, and risks causing harm. We describe the protocol of a planned randomized non-inferiority trial to investigate the impact of intervening to maintain serum potassium ≥ 3.6 mEq/L vs ≥ 4.5 mEq/L on incidence of new-onset AFACS after isolated elective CABG. METHODS: Patients undergoing isolated CABG at sites in the UK and Germany will be recruited, randomized 1:1 and stratified by site to protocols maintaining serum potassium at either ≥ 3.6 mEq/L or ≥ 4.5 mEq/L. Participants will not be blind to treatment allocation. The primary endpoint is AFACS, defined as an episode of atrial fibrillation, flutter or tachycardia lasting ≥ 30 seconds until hour 120 after surgery, which is both clinically detected and electrocardiographically confirmed. Assuming a 35% incidence of AFACS in the 'tight control group', and allowing for a 10% loss to follow-up, 1684 participants are required to provide 90% certainty that the upper limit of a one-sided 97.5% confidence interval (CI) will exclude a > 10% difference in favour of tight potassium control. Secondary endpoints include mortality, use of hospital resources and incidence of dysrhythmias not meeting the primary endpoint (detected using continuous heart rhythm monitoring). DISCUSSION: The Tight K Trial will assess whether a protocol to maintain serum potassium ≥ 3.6 mEq/L is non inferior to maintaining serum potassium ≥ 4.5 mEq/L in preventing new-onset AFACS after isolated CABG. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04053816. Registered on 13 August 2019. Last update 7 January 2021.

Association of a sequence variant in DAB2IP with coronary heart disease.

AIMS: A sequence variant, rs7025486[A], in DAB2IP on chromosome 9q33 has recently been associated with coronary heart disease (CHD). We sought to replicate this finding and to investigate associations with a panel of inflammatory and haemostatic biomarkers. We also sought to examine whether this variant, in combination with a chromosome 9p21 CHD variant (rs10757278) and the Framingham risk score (FRS), could improve the prediction of events compared with the FRS alone. METHODS AND RESULTS: rs7025486 was genotyped in 1386 CHD cases and 3532 controls and was associated with CHD [odds ratio (OR) of 1.16, 95% confidence interval (CI) 1.05-1.29, P= 0.003]. Meta-analysis, using data from the original report and from genome-wide association studies in both the Wellcome Trust Case Control Consortium and the Cardiovascular Health Study, comprising 9968 cases and 20 048 controls, confirmed the association (OR of 1.10, 95% CI 1.06-1.14, P= 3.2 × 10(-6)). There was no association with a panel of CHD biomarkers, including any lipid, inflammation, or coagulation trait, nor with telomere length. Addition to the FRS of this variant plus rs10757278 on chromosome 9p21 improved the area under the receiver-operating characteristic curve (A(ROC)) from 0.61 to 0.64 (P= 0.03) as well as improving the reclassification (net reclassification index = 11.1%, P= 0.007). CONCLUSION: This study replicates a previous association of a variant in DAB2IP with CHD. Addition of multiple variants improves the performance of predictive models based upon classical cardiovascular risk factors.

Health-related quality of life in cardiac sarcoidosis: a systematic review.

People living with cardiac sarcoidosis (CS) are likely to have worse clinical outcomes and greater impairment on health-related quality of life (HRQoL) than other sarcoidosis manifestations. CS can result in a constellation of intrusive symptoms (such as palpitations, dizziness, syncope/pre-syncope, chest pain, dyspnoea, orthopnoea, or peripheral oedema) and/or life-threatening episodes, requiring consideration of invasive cardiac procedures for diagnosis and for the management of acute events. Additionally, the presence of multisystemic involvement and persistent non-specific sarcoidosis symptoms negatively affect HRQoL. A systematic review was undertaken to explore the impact of CS on HRQoL in adults with CS. Multiple bibliographic databases were searched for studies with HRQoL as primary or secondary outcomes in CS (PROSPERO registration: CRD42019119752). Data extraction and quality assessments were undertaken independently by two authors. From the initial 1609 identified records, only 11 studies included CS patients but none specifically reported HRQoL scores for CS patients. The average representation of CS patients was 14.5% within these cohorts (range 2-22%). The majority (73%) was conducted in single-centre tertiary care settings, and only one study (9%) included longitudinal HRQoL data. CS patients were among those sarcoidosis patients with impaired HRQoL and worse outcomes, requiring higher doses of sarcoidosis-specific therapy which contribute to further deterioration of HRQoL. Sarcoidosis studies do not incorporate stratified HRQoL scores for CS patients. While there is a need for longitudinal and multicentre studies assessing HRQoL outcomes in CS cohorts, the development of CS-specific tools is also needed.