Syndrome Registry Research Articles

Less frequent skin ulcers among patients with Werner syndrome treated with pioglitazone: findings from the Japanese Werner Syndrome Registry.

Werner syndrome (WS) is an autosomal recessive, adult-onset, progeroid syndrome caused by WRN mutations. As refractory skin ulcers significantly affect the quality of life of patients with WS, this study identified ulcer risk factors and assessed prevention methods. We analyzed the data of 51 patients with WS enrolled in the Japanese Werner Syndrome Registry between 2016 and 2022. A cross-sectional analysis was performed to determine the association with skin ulcers at baseline. Statistical analyses were conducted, including Welch's and Pearson's chi-square tests. Age was adjusted using a logistic regression model. The mean patient age was 48.8±7.6 years, and 66.7% of patients presented with skin ulcers. Univariate analysis showed that patients with skin ulcers were older than those without ulcers. Systolic blood pressure (SBP) was higher in patients with skin ulcers. Patients without skin ulcers received metformin and pioglitazone treatment significantly more often than those with ulcers. Logistic regression analysis adjusted for age showed that higher SBP remained a significant risk factor for skin ulcers. Patients administered pioglitazone had lower ulcer morbidity. Age and SBP are risk factors for skin ulcers in patients with WS. Moreover, pioglitazone treatment may prevent skin ulcers.

Stability of symptom-based subtypes in Sjogren’s disease

ObjectivesThe Newcastle Sjogren’s Stratification Tool (NSST) stratifies Sjogren’s disease patients into four subtypes. Understanding the stability of the subtypes is vital if symptom-based stratification is to be more broadly adopted....

Clinico-demographical differences and seven years management performance of acute coronary syndrome in Bali, Indonesia

BackgroundThe geographical diversity and clinical presentation differences of acute coronary syndrome (ACS) patients in Bali significantly influence the management performance and intervention outcomes. Bali, an island with varied geography, presents unique challenges for timely access to percutaneous coronary intervention (PCI) facilities, which are concentrated in South Bali. This study aims to describe annually the clinical characteristics of ACS patients in Bali, focusing on geographical factors and management performance. MethodsThe regional data from the Indonesia Acute Coronary Syndrome Registry (One ACS) were utilized in this study. The study population consisted of patients aged over 18 years who were treated for ACS from 2017 to 2023 at Prof. Dr. I.G.N.G Ngoerah Central General Hospital in Denpasar, Bali. Several outcomes were described, including baseline characteristics, transfer time, door-to-balloon time (DTB), door-to-wire time (DTW), ambulance transport time, patient transport time, and major adverse cardiac event (MACE) outcomes. ResultsA total of 4588 ACS patients based in Bali were included from 2017 to 2023. The majority of ACS patients originated from Denpasar city (44.1 %), followed by Badung (19.2 %) and Gianyar (8.5 %). More than half of the patients (57.9 %) were referred from primary healthcare, with a mean transfer time of 247.45 ± 698.26 min. Mortality rates were high, with significant numbers of cardiac arrests, heart failure, and cardiogenic shock. On multivariate analysis, shortness of breath, chest pain during light activity, patients seeking first medical contact (FMC) in Karangasem, and self-admission to the hospital were independently associated with mortality. ConclusionsThe geographical challenges of Bali, particularly the limited distribution of PCI-capable facilities, contribute to delays in treatment and varied outcomes for ACS patients. Improvements in healthcare systems across Bali are required to conform with current guidelines and enhance intervention outcomes.

Acute coronary syndrome and Khat consumption in Yemeni women admitted to Coronary Care and Intensive Care in major hospital in Yemen

Background: There is a significant percent of normal coronaries in patients with a history of documented myocardial infarction among Yemeni patients who have undergone diagnostic coronary angiogram, and they theoretically attributed that to the effect of Khat as a vasoconstrictor to the coronary artery. Also, unadjusted comparisons of mortality and major morbidity after acute myocardial infarction have generally indicated that women have a poorer outcome than men. Methods: Data was collected prospectively from 15 hospitals in 8 governorates with acute coronary syndrome registry in the Gulf countries. All female patients who were admitted in any monitored bed in Coronary Care Units (CCU) or Intensive Care Units (ICU) with a provisional diagnosis of acute coronary syndrome (ACS) were included in the study. The presentations with khat chewing were compared with all other known and documented risk factor outcomes among women using multiple logistic regressions. Results There were 50.5% regular khat chewers of female patients at presentations to the general emergency department with an attack of acute coronary syndrome; 14.4% of all female patients have no other risk factors except khat. These patients were relatively younger and had a lower body mass index (BMI) when compared with the incidence of acute events in other populations. They had no significantly worse outcome during hospitalization in comparison to the males of the same age group. Conclusions It seems likely that there is at most only an intermediate association between Khat and the development of acute coronary syndrome in females, with less mortality and morbidity after suspected acute myocardial infarction. However, a larger study is needed, with more complete adjustment for coexisting risk factors, to determine whether the female has a worse outcome, which increases with khat.

Impact of different P2Y12 inhibitors in acute coronary syndrome patients with severe chronic kidney disease: insights from the CORALYS registry

Abstract Background The impact of the most potent P2Y12i ticagrelor and prasugrel after acute coronary syndrome in patients with chronic kidney disease (CKD) remains unclear. Most evidence on dual antiplatelet therapy (DAPT) comes from real-world study but is limited to glomerular filtration rate (GFR) under 60 ml/min whereas no data are available regarding patients with severe CKD (stages IV-V) Methods Consecutive patients with acute coronary syndrome (ACS) treated with percutaneous coronary intervention (PCI) and severe CKD defined as GFR under 30 ml/min not on dialysis from the CORALYS (Incidence and Predictors of Heart Failure After Acute Coronary Syndrome) registry were included. Incidence of Net Adverse Clinical Events (NACE) defined as major adverse cardiac events (MACE, a composite of cardiovascular death, myocardial infarction and unplanned revascularizations) in addition to major bleedings (classified as BARC scale 3 to 5) was our primary endpoint. Overall MACE and their single components, all bleedings, major bleedings and hospitalizations for heart failure were the secondary ones. Results Of 14699 patients in the CORALYS registry, 257 presented with severe CKD not on dialysis and had available data on antiplatelet regimen at discharge. Patients were divided into two groups according to the type of P2Y12i prescribed at discharge: 193 (75.1%) were given clopidogrel while 64 (24.9%) with ticagrelor or prasugrel. Our populaiton was predominantly male (153, 59.5%) with an average age 75.8 ± 10.9 years old. Average GFR was 21.8 ± 6.3 ml/min. Over a median follow-up of 459 days, Ticagrelor and Prasugrel were associated to lower rates of NACE compared to Clopidogrel (39.9% vs 25.0%, p=0.036). This was mainly driven by an excess of both CV mortality (31.1% vs 6.3%) and myocardial infarction (20.7% vs 9.4%) reported in the clopidogrel group. No difference was reported regarding overall bleeding events (5.7% vs 4.6% with clopidogrel and new P2Y12i respectively, p=0.81) and major bleedings (1.7% vs 4.6% with clopidogrel and new P2Y12i respectively, p=0.15). At multivariate Cox regression analysis DAPT with Ticagrelor/Prasugrel resulted independently associated with a lower risk of NACE (Adj Hr 0.41, 95%CI 0.23-0.74, p=0.003) whereas left main involvement or multivessel coronary disease led to higher risk of NACE (Adj HR 1.96 95%CI 1.21-3.18, p=0.006) Conclusions In ACS patients treated with PCI with severe CKD ticagrelor and prasugrel were associated to lower risk of NACE, MACE, CV death and myocardial infarction compared to clopidogrel. No significative difference was reported in overall and major bleedings despite a relative increase of major bleedings in the group treated with Ticagrelor or Prasugrel.

Evaluating MCMC Convergence in a Bayesian Model of ST-Elevation Myocardial Infarction Female Patients in Malaysia

The majority of research that looked at the Bayesian Markov Chain Monte Carlo (MCMC) approach for prognostic modelling of cardiovascular disease only focused on the use of the Bayesian approach in variable selection, model selection, and prior distribution selection. But very few of this research has looked at the Markov chains' convergence in the model. In this study, convergence diagnostics were carried out to evaluate the convergence of Markov chains using both visual inspection and additional diagnostics. The National Cardiovascular Disease Database-Acute Coronary Syndrome (NCVD-ACS) registry, which included 1248 female patients with ST-Elevation Myocardial Infarction (STEMI) between 2006 and 2013, was used for this study's analysis. The multivariate Bayesian model identified six significant variables: dyslipidaemia, myocardial infarction, smoking, renal disease, Killip class, and age group. The trace plots did not reveal any distinctive patterns based on these significant variables, and the model's MCMC mixing is typically good. While for the autocorrelation plots, mild autocorrelations for age group, Killip IV, as well as the intercept term in the model. Since there were only mild autocorrelations, no thinning is needed. Also, the Geweke diagnostic showed that the chain is divided into two windows containing a set fraction of the first and last iterations which produced standard Z-scores. The Geweke diagnostic did not provide evidence of non-convergence, as none of the Z-scores fell in the extreme tails of the N (0,1). In this study, a number of plots and additional diagnostic tools showed that the Markov chains have reached convergence, which is relevant to the general use of the MCMC approach.

Low remission rates and high incidence of adverse events in a prospective VEXAS syndrome registry.

We aimed to gather real-world clinical evidence of detailed disease activity, treatments, remission rates, and adverse events (AEs) associated with vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome in a prospective study. Patients in Japan suspected of having VEXAS syndrome were enrolled in a registry study. A novel disease activity measure (VEXASCAF) assessing 11 symptoms associated with VEXAS syndrome was evaluated at enrolment and after 3 months. AEs, survival, CRP levels, and treatments were also recorded at enrolment and 3 months after enrolment. All exons of UBA1 were sequenced using a next-generation sequencer to determine the variant allele frequencies of pathogenic variants in the peripheral blood of all patients. Of the 55 registered patients, 30 patients were confirmed to have pathogenic variants of UBA1. All patients were male, with a median age of 73.5 years. VEXASCAF and CRP levels decreased significantly at 3 months post-enrolment, but the oral prednisolone dose did not change. Only two patients achieved complete remission according to FRENVEX at 3 months after enrolment. During the observation period of 6 months, 28 AEs were observed, including 3 deaths, 4 malignancies from two cases, 2 thromboses, and 13 infections (including 4 mycobacterial infections). Inflammation of the lung and cervical region (i.e. parotid and submandibular gland swelling, tonsillitis, cervical swelling, and pain) were the most common AEs. Patients with VEXAS syndrome required high-dose glucocorticoids to achieve remission, and complications-such as malignancy, thrombosis, and infection-occurred frequently within a short observation period.

Association between sleep disturbances and challenging behavior in children and adolescents with Angelman syndrome

Angelman Syndrome (AS) is a neurodevelopmental disorder with severe symptoms and associated comorbidities. It is caused by the inactivity or lack of the UBE3a gene. Symptoms of the syndrome include intellectual disability and developmental delay.The current study investigated sleep disturbances (SD) in children and adolescents with AS, associations between SD and possible predictors of SD. Variables examined included age, gender, newborn and infancy history, challenging behavior, type of therapy received, genetic type of AS, and seizures. The sample included data from 109 participants with a mean age of 8.21, accessed via the Global Angelman Syndrome Registry. Chi-square tests were carried out to assess the associations between the variables and a logistical regression was carried out to assess the possible predictors of SD. Associations were found between SD and certain repetitive behaviors: slapping walls, focal hand movements, and agitation at new situations. From these associations, a regression formed a predictive model for sleep disturbances. The findings of this research demonstrated the importance of investigating the relationship between sleep disturbances and challenging behavior in children and adolescents with AS and the need for further research in this area.

Baseline Characteristics of Adult Patients Treated and Never Treated with Teduglutide in a Multinational Short Bowel Syndrome and Intestinal Failure Registry.

The Short Bowel Syndrome (SBS) Registry (NCT01990040) is a multinational real-world study evaluating the long-term safety of teduglutide in patients with SBS and intestinal failure (SBS-IF) in routine clinical practice. This paper describes the study methodology and baseline characteristics of adult patients who have (ever-treated) or have never (never-treated) received teduglutide. A total of 1411 adult patients (679 ever-treated; 732 never-treated) were enrolled at 124 sites across 17 countries. The mean (standard deviation [SD]) age at enrollment was 55.4 (15.46) years, and 60.2% of patients were women. Crohn's disease was the most common cause of major intestinal resection in both ever-treated (34.1%) and never-treated patients (20.4%). A similar proportion of ever-treated and never-treated patients had a prior history of colorectal polyps (2.7% vs. 3.6%), whereas proportionally fewer ever-treated patients reported a history of colorectal cancer (1.8% vs. 6.2%) or any malignancy (17.7% vs. 30.0%) than never-treated patients. Never-treated patients received a numerically greater mean (SD) volume of parenteral nutrition and/or intravenous fluids than ever-treated patients (12.4 [8.02] vs. 10.1 [6.64] L/week). Ever-treated patients received a mean teduglutide dosage of 0.05 mg/kg/day. This is the first report of patient baseline characteristics from the SBS Registry, and the largest cohort of patients with SBS-IF to date. Overall, ever-treated and never-treated patients had similar baseline characteristics. Differences between treatment groups may reflect variations in patient selection and degree of monitoring.

Genetic and clinical characteristics of catecholaminergic polymorphic ventricular tachycardia in a Taiwanese nationwide cohort

BackgroundCatecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare and lethal arrhythmia. Ryanodine receptor 2 (RYR2) mutation accounts for ∼60% of CPVT patients which is inherited in an autosomal dominant pattern. ObjectiveThis study aimed to identify CPVT-related mutations and clinical characteristics among Taiwanese CPVT patients and compare to other cohorts worldwide. MethodsClinical and genetic data were obtained from the Sudden Arrhythmia Death Syndrome Registry in Taiwan (SADS-TW). Forty clinically diagnosed Taiwanese CPVT patients were included. ResultsThis is the first nationwide CPVT cohort in Taiwan. Among the 29 Taiwanese patients with CPVT-related gene mutations, 55% had RYR2 mutations, a rate similar to other ethnicities. Three out of 12 RYR2 variants were unreported. Exercise-induced symptoms including syncope and cardiac arrest were more frequent in East Asian cohorts (Taiwanese 79%, Japanese 91%), compared to Caucasian cohorts (59%) (p = 0.002). ConclusionThe discovery of diverse RYR2 mutations in the Taiwanese CVPT population demonstrates the importance of genetic testing in different ethnicities.

Type 2 Myocardial Infarction in a Sub-Saharan Africa Population: Challenging the Current Concepts-Data From REACTIV.

From a large observational acute coronary syndrome registry in Côte d'Ivoire, we aimed to assess incidence, clinical presentation, management, and in-hospital outcomes for type 2 myocardial infarction (T2MI) compared with type 1 MI. We conducted a cross-sectional monocentric study using data from REACTIV (Registre des Infarctus de Côte d'Ivoire) at the Abidjan Heart Institute. All patients hospitalized with MI between 2018 and 2022 who underwent coronary angiography were included. For each patient, sociodemographic data, cardiovascular risk factors and history, and clinical and paraclinical presentation were collected at admission. In-hospital outcomes, including major adverse cardiovascular events and mortality, were reported. Among 541 consecutive patients hospitalized with MI, 441 met the definition of type 1 MI or T2MI. T2MI accounted for 14.1% of cases. Patients with T2MI showed a trend toward slightly younger age (54 versus 58 years, P=0.09). Patients with T2MI seemed to have less severe coronary artery disease, with less frequent multivessel disease (P<0.001). Main triggering factors for T2MI were coronary embolism (24.2%), severe hypertension with or without left ventricular hypertrophy (22.6%), and tachyarrhythmia (16.1%). In-hospital event rates were low in both MI types. Although the difference was nonsignificant, death rates for patients with type 1 MI tended to be higher than for patients with T2MI, as well as occurrence of major adverse cardiovascular events. Our study revealed disparities in clinical characteristics, angiographic features, cause, and in-hospital outcomes in T2MI in our population compared with Western populations. These results suggest the heterogeneity of T2MI and the potential causative and demographic variability depending on geographical area.

The Rationale and Design of the KOSovan Acute Coronary Syndrome (KOS-ACS) Registry.

The KOSovan Acute Coronary Syndrome (KOS-ACS) Registry is established as a prospective, continuous, nationwide, web-based registry that is operated online. The KOS-ACS registry is designed with the following objectives: (1) to obtain data on the demographic, clinical, and laboratory characteristics of ACS patients treated in Kosovo; (2) to create a national database with information on health care in ACS patients treated in Kosovo; (3) to identify the national features of associations between ACS characteristics and clinical outcomes, including mortality, complications, the length of hospital stay, and the quality of clinical care; and (4) to propose a practical guide for improving the quality and efficiency of ACS treatment in Kosovo. The Kosovo Society of Cardiology and University of Prishtina will be responsible for the development of the KOS-ACS registry and centralized data analysis at the national level. The KOS-ACS Registry will enroll all patients admitted, at any of the registered clinical centers, with the diagnosis of ACS and who will be clinically managed at any of the Kosovo hospitals. Data on patient demographics, clinical characteristics, previous and hospital drug treatment, and reperfusion therapy will be collected. The type of ACS (unstable angina, NSTEMI, or STEMI) will also be clearly defined. The time from first medical contact to balloon inflation (FMC-to-balloon) and door-to-ballon time will be registered. In-hospital death and complications will be registered. Data on the post-hospital primary outcome (MACE: cardiac death, all-cause mortality, hospitalization, stroke, need for coronary revascularization) of patients, at 30 days and 1 year, will be included in the registry.

Exploring the Clinical and Genetic Landscape of Angelman Syndrome: Patient-Reported Insights from an Italian Registry.

Background: The Angelman Syndrome Registry (RISA) was developed as a retrospective study with the following objectives: to evaluate the clinical history of individuals with Angelman Syndrome (AS) in Italy and compare it with the existing literature; to investigate the feasibility of gathering data by directly involving participants in the data collection process; and to explore the relationship between different symptoms and genotypes. Methods: Established in 2018, RISA enrolled a total of 82 participants, with 62 (75.6%) providing complete data. Demographic, clinical, and genetic information was collected using electronic case report forms. Descriptive statistics characterized the sample, while associations between genotype and clinical characteristics were examined. Results: Descriptive analysis revealed a median participant age of 8.0 years, with males comprising 48.8% of the sample. Deletion (58.1%) was the most common genotype. The majority (82.2%) experienced epilepsy, with seizures typically onset before 3 years of age. Most patients (86.2%) required multiple anti-epileptic drugs for control, with generalized tonic-clonic seizures and atypical absence seizures being most prevalent. The deletion group exhibited more severe developmental delays and a trend towards higher seizure severity. Sleep problems affected 69.4% of participants, characterized by difficulties in sleep onset and maintenance. Conclusions: This study offers valuable insights into the clinical history and genetic characteristics of AS in Italy, consistent with the prior literature. Additionally, it underscores the efficacy of patient registries in capturing comprehensive data on rare diseases such as AS, highlighting their potential to advance research and enhance patient care.

Association Between Challenging Behaviour and Sleep Problems in Adults Enrolled in the Global Angelman Syndrome Registry.

Angelman Syndrome (AS) is a rare genetic disorder that impacts 1:20,000 people. Challenging behaviour, such as severe injurious behaviour, aggression and frequent unprovoked episodes of laughter are a significant problem among adults with AS that adversely impacts an individual's quality of life. This study, for the first time, aims understand the characteristic of challenging behaviour, its frequency, and the factors associated with it in adults with AS. Data from participants with AS (N = 37; aged 18-46 years) registered with the Global Angelman Registry, were divided into challenging behaviour and non-challenging behaviour groups based on the presence or absence of 50% of the behaviours recorded in the registry. Descriptive statistics, chi-squared and t-test analysis were conducted to assess the impact of variables on challenging behaviour. Multiple regressions were conducted to investigate the predictors of challenging behaviour. 56% of the sample presented with challenging behaviour. Disorders of arousal, self-injury, behaviour dysregulation, repetitive behaviour, and the lack of physical therapy accounted for 59% of the variance of challenging behaviour in this population. It was found that challenging behaviour was very common in this population. A significant association was found between challenging behaviour and both sleep arousal and the lack of physical therapy. Sleep arousal and the lack of physical therapy were the key factors associated with challenging behaviour in this study. Targeted interventions are needed to decrease challenging behaviour and future research should focus on sleep interventions and increased opportunities for physical therapy.

P153 Exploring the relationships between objective and subjective clinical measures in Sjogren's Syndrome

Abstract Background/Aims Patient Reported Outcome Measures (PROMs) are standardised, validated questionnaires designed to measure the patient’s perception of their disease. Discordance between the patient’s perspective and objective clinical measures (clinical scores, laboratory data) has led to increased interest in PROMs in Sjogren’s syndrome (SS). Initial concern about the subjectivity of PROMs has given way to methodological rigour and clear guidance for the development of PROMs. Several studies have now used PROMs for symptom-based stratification, and recently researchers have developed composite disease assessment tools incorporating PROMs and objective clinical measures to create more clinically meaningful endpoints for SS trials. With the advent of PROM-based stratification tools and composite endpoints, it is vital to better understand the relationship between clinical measures in SS. In this project we performed network analysis with data from a large cohort of well-characterised SS patient to improve our understanding of the relationship between objectively measured parameters and PROMs. Methods The UK Primary Sjogren’s Syndrome Registry (UKPSSR) is a nationwide observational cohort of primary SS patients who fulfil the 2002 American European Consensus Group classification criteria. The UKPSSR holds detailed clinical and laboratory data that is collected prospectively, including patient-reported outcomes collected using standardized questionnaires. To assess concordance between clinical measures we used the ARACNE algorithm, which calculates mutual information between the variables of a multidimensional dataset to construct a network of shared information. Statistical analysis was performed in R-v4.1.3 and JMP Pro-v15 and network visualisation in Cytoscape-v3.8.2. Results The ARACNE network highlights key areas of concordance and discordance between PROMs, clinician-based and laboratory-based measurements. Providing assurance to this approach, multi-domain PROMs and ESSDAI (EULAR Sjögren's syndrome disease activity index) subdomains are strongly associated with their component scores and different PROMs measuring the same symptoms were also correlated. In contrast, there is a clear separation between PROMs, clinician-based and laboratory-based measurements each forming their own sub-networks. Furthermore, most laboratory measurements do not have strong relationship with clinician-based disease activity score or PROMs. EQ-5D utility and HADS (Hospital Anxiety and Depression Scale) values provide the primary link between ESSPRI (EULAR Sjogren's Syndrome Patient Reported Index) and ESSDAI subdomain scores and both ESSDAI and ESSPRI are important contributors to quality-of-life. Conclusion The dissociation between PROMs and objective clinical measures is important for clinical management and trial design. Whilst it complicates clinical management of SS including any treat-to-target strategy; it highlights the importance of PROMs in supporting clinician assessment and laboratory measurements to better capture all aspects of SS and give a more individualised, meaningful assessment. Finally, it supports the dual-target strategy of systemically pursuing two targets in the design of clinical trials: one focused on the disease activity and another focused on the symptoms and impact. Disclosure J.S. Berry: None. J. Tarn: None. D. Lendrem: None. J. Casement: None. W. Ng: Consultancies; Expert advice in the area of Sjogren’s syndrome to GlaxoSmithKline, MedImmune, UCB, Abbvie, Roche, Eli Lilly, Takeda, Resolves Therapeutics, Sanofi, Novartis and BMS.

Evaluation of the Relationship between QT Interval in ECG and GRACE Score Amount of Hospitalized Patients with NSTEMI.

Non-ST-elevation myocardial infarction (NSTEMI) is a significant component of acute coronary syndrome (ACS) and typically exhibits a relative incidence that is more than double that of ST-segment elevation myocardial infarction (STEMI). Data obtained from the International Long QT Syndrome Registry indicate that the risk of developing malignant arrhythmias in individuals with long QT syndrome is exponentially associated with the duration of the QTc interval. Therefore, the aim of this study was to assess the potential inclusion of prolonged QTc as a prognostic risk factor in NSTEMI patients. A cross-sectional study was conducted on patients with NSTEMI diagnosis admitted to the Bu-Ali Hospital of Qazvin between April 2021 and September 2021 by census method. The QT interval was measured in the electrocardiogram at admission. The documented grace score was calculated and its relationship with the corrected QTc interval was estimated using the Hodges formula. Finally, the relationship between QTc and GRACE score was investigated as a prognostic factor in ACS patients. Relationships were assessed by using both the T-test and the chi-square test. A total of 60 patients (31.7% females, 63.8% males) with a mean age of 63 ± 12.7 years were evaluated. Most of the patients (68.3%) were at low risk regarding the Grace score category. In evaluating the relationship between QTc in the electrocardiogram at admission with total GRACE score, the Pearson correlation results were significant and there was a positive relationship between these two factors (r = 0.497, P < 0.001). This study revealed a significant relationship between the QTc interval of patients and the GRACE Score. It was shown patients' QTc can be a predictive factor of patients' mortality.

Prescribing Trends of Renin-Angiotensin System Inhibitors and Mortality among Acute Coronary Syndrome Patients: Insights from the Malaysian National Cardiovascular Disease Registry.

Despite guideline recommendations, suboptimal prescription rates of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have been observed in patients with acute coronary syndrome. This study aimed to examine the temporal trends, variations, and mortality outcomes among acute coronary syndrome patients prescribed ACEIs/ARBs in the multi-ethnic population of Malaysia. This retrospective study utilized data from the Malaysian National Cardiovascular Disease-Acute Coronary Syndrome registry, encompassing consecutive patient records from 2008 to 2017 (N = 60,854). Ten-year temporal trends of on-discharge ACEIs/ARBs prescription were examined. Demographics, clinical characteristics and 1-year all-cause mortality outcomes were compared between patients prescribed and not prescribed ACEIs/ARBs. The 10-year prescription rate of on-discharge ACEIs/ARBs was 52.8% (n = 32,140), with a significant decline over the years [linear trend test, P = 0.008; SD = 0.03; SE = 0.001; 95% CI = 0.55-0.64]. Patients aged ≥65 years (aOR = 0.79; 95% CI = 0.73-0.86) were less likely to be prescribed ACEIs/ARBs than those aged <65 years. In addition, patients with comorbid diabetes mellitus (DM) (aOR = 0.85; 95% CI = 0.79-0.92) and chronic kidney disease (CKD) (aOR = 0.34; 95% CI = 0.30-0.40) were significantly less likely to receive ACEIs/ARBs. IPW-adjusted survival analysis revealed a 38% lower 1-year all-cause mortality rate in patients prescribed on-discharge ACEIs/ARBs (HR = 0.62; 95% CI = 0.56-0.69; P < 0.001). Acute coronary syndrome patients with concomitant DM and CKD were less likely to receive on-discharge ACEIs/ARBs in Malaysia. Suboptimal prescription rates of ACEIs/ARBs persisted over the 10-year period, despite improved 1-year survival in ACS patients prescribed ACEIs/ARBs.

Factors associated with sleep disturbances in children and adolescents with Angelman Syndrome

BackgroundAngelman Syndrome (AS) is a rare genetic disorder characterised by hyperactivity, overexcitability, developmental delays, and lack of speech. MethodsThis study used secondary data analysis to investigate sleep disturbances in children and adolescents (n = 212) who are enrolled in the Global Angelman Syndrome Registry. Participants were divided into two groups based on the presence or absence of sleep disturbance. The cut-off score of 40 on the Sleep Disturbance Scale for Children was used to indicate the presence or absence of sleep disturbances. Sleep disturbances and their association with co-occurring conditions were examined regarding challenging behaviour, language and communication, infancy history, gastrointestinal symptoms, and epilepsy. Multiple regression was then conducted to investigate possible predictors for sleep disturbances. ResultsChildren and adolescents with AS, with and without sleep disturbances, differed considerably regarding anxiety. Sleep disturbances were significantly associated with an ability to use spoken words and computerised communication devices, and anxiety was a predictor of sleep disturbances. ConclusionFuture research is necessary to replicate this novel research, and to advance the clinical treatment of sleep disturbances in children and adolescents with AS.

Predictive Value of Artificial Intelligence-Enabled Electrocardiography in Patients With Takotsubo Cardiomyopathy.

Recent studies have indicated high rates of future major adverse cardiovascular events in patients with Takotsubo cardiomyopathy (TC), but there is no well-established tool for risk stratification. This study sought to evaluate the prognostic value of several artificial intelligence-augmented ECG (AI-ECG) algorithms in patients with TC. This study examined consecutive patients in the prospective and observational Mayo Clinic Takotsubo syndrome registry. Several previously validated AI-ECG algorithms were used for the estimation of ECG- age, probability of low ejection fraction, and probability of atrial fibrillation. Multivariable models were constructed to evaluate the association of AI-ECG and other clinical characteristics with major adverse cardiac events, defined as cardiovascular death, recurrence of TC, nonfatal myocardial infarction, hospitalization for congestive heart failure, and stroke. In the final analysis, 305 patients with TC were studied over a median follow-up of 4.8 years. Patients with future major adverse cardiac events were more likely to be older, have a history of hypertension, congestive heart failure, worse renal function, as well as high-risk AI-ECG findings compared with those without. Multivariable Cox proportional hazards analysis indicated that the presence of 2 or 3 high-risk findings detected by AI-ECG remained a significant predictor of major adverse cardiac events in patients with TC after adjustment by conventional risk factors (hazard ratio, 4.419 [95% CI, 1.833-10.66], P=0.001). The combined use of AI-ECG algorithms derived from a single 12-lead ECG might detect subtle underlying patterns associated with worse outcomes in patients with TC. This approach might be beneficial for stratifying high-risk patients with TC.

The comprehensive English National Lynch Syndrome Registry: development and description of a new genomics data resource

Lynch Syndrome (LS) is a cancer predisposition syndrome caused by constitutional pathogenic variants in the mismatch repair (MMR) genes. To date, fragmentation of clinical and genomic data has restricted understanding of national LS ascertainment and outcomes, and precluded evaluation of NICE guidance on testing and management. To address this, via collaboration between researchers, the National Disease Registration Service (NDRS), NHS Genomic Medicine Service Alliances (GMSAs), and NHS Regional Clinical Genetics Services, a comprehensive registry of LS carriers in England has been established. For comprehensive ascertainment of retrospectively identified MMR pathogenic variant (PV) carriers (diagnosed prior to January 1, 2023), information was retrieved from all clinical genetics services across England, then restructured, amalgamated, and validated via a team of trained experts in NDRS. An online submission portal was established for prospective ascertainment from January 1, 2023. The resulting data, stored in a secure database in NDRS, were used to investigate the demographic and genetic characteristics of the cohort, censored at July 25, 2023. Cancer outcomes were investigated via linkage to the National Cancer Registration Dataset (NCRD). A total of 11,722 retrospective and 570 prospective data submissions were received, resulting in a comprehensive English National Lynch Syndrome Registry (ENLSR) comprising 9030 unique individuals. The most frequently identified pathogenic MMR genes were MSH2 and MLH1 at 37.2% (n=3362) and 29.1% (n=2624), respectively. 35.9% (n=3239) of the ENLSR cohort received their LS diagnosis before their first cancer diagnosis (presumptive predictive germline test). Of these, 6.3% (n=204) developed colorectal cancer, at a median age of initial diagnosis of 51 (IQR 40-62), compared to 73 years (IQR 64-80) in the general population (p<0.0001). The ENLSR represents the first comprehensive national registry of PV carriers in England and one of the largest cohorts of MMR PV carriers worldwide. The establishment of a secure, centralised infrastructure and mechanism for routine registration of newly identified carriers ensures sustainability of the data resource. This work was funded by the Wellcome Trust, Cancer Research UK and Bowel Cancer UK. The funder of this study had no role in study design, data collection, data analysis, data interpretation, or writing of the report.