A novel tool for arrhythmic risk stratification in desmoplakin gene variant carriers.

BACKGROUND AND AIMS: Pathogenic desmoplakin (DSP) gene variants are associated with the development of a distinct form of arrhythmogenic cardiomyopathy known as DSP cardiomyopathy. Patients harbouring these variants are at high risk for sustained ventricular arrhythmia (VA), but existing tools for individualized arrhythmic risk assessment have proven unreliable in this population. METHODS: Patients from the multi-national DSP-ERADOS (Desmoplakin SPecific Effort for a RAre Disease Outcome Study) Network patient registry who had pathogenic or likely pathogenic DSP variants and no sustained VA prior to enrolment were followed longitudinally for the development of first sustained VA event. Clinically guided, step-wise Cox regression analysis was used to develop a novel clinical tool predicting the development of incident VA. Model performance was assessed by c-statistic in both the model development cohort (n = 385) and in an external validation cohort (n = 86). RESULTS: In total, 471 DSP patients [mean age 37.8 years, 65.6% women, 38.6% probands, 26% with left ventricular ejection fraction (LVEF) < 50%] were followed for a median of 4.0 (interquartile range: 1.6-7.3) years; 71 experienced first sustained VA events {2.6% [95% confidence interval (CI): 2.0, 3.5] events/year}. Within the development cohort, five readily available clinical parameters were identified as independent predictors of VA and included in a novel DSP risk score: female sex [hazard ratio (HR) 1.9 (95% CI: 1.1-3.4)], history of non-sustained ventricular tachycardia [HR 1.7 (95% CI: 1.1-2.8)], natural logarithm of 24-h premature ventricular contraction burden [HR 1.3 (95% CI: 1.1-1.4)], LVEF < 50% [HR 1.5 (95% CI: .95-2.5)], and presence of moderate to severe right ventricular systolic dysfunction [HR 6.0 (95% CI: 2.9-12.5)]. The model demonstrated good risk discrimination within both the development [c-statistic .782 (95% CI: .77-.80)] and external validation [c-statistic .791 (95% CI: .75-.83)] cohorts. The negative predictive value for DSP patients in the external validation cohort deemed to be at low risk for VA (<5% at 5 years; n = 26) was 100%. CONCLUSIONS: The DSP risk score is a novel model that leverages readily available clinical parameters to provide individualized VA risk assessment for DSP patients. This tool may help guide decision-making for primary prevention implantable cardioverter-defibrillator placement in this high-risk population and supports a gene-first risk stratification approach.

Effects of Electronic Nicotine Delivery Systems Substitution on Body Weight Status: Protocol for a Systematic Review and Meta-Analysis.

BACKGROUND: Weight gain following smoking cessation is a well-documented concern, often attributed to the absence of nicotine's metabolic influence. The adoption of Electronic Nicotine Delivery Systems (ENDS) has been used to achieve smoking cessation, with claims of aiding weight control. However, existing reviews present conflicting conclusions on ENDS' impact on weight status, necessitating a rigorous evaluation. OBJECTIVE: We aim to conduct a systematic review with meta-analysis to assess the actual impact of ENDS on weight status in individuals who have ceased or reduced conventional smoking. The primary goal is to provide clinicians with evidence-based insights into the potential effects of ENDS use as a smoking substitute on weight control. METHODS: Adhering to PRISMA-P (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols) guidelines, our systematic review will analyze randomized and nonrandomized controlled trials, clinical trials (quasi-experimental), and prospective or retrospective cohort studies on the weight status effects of ENDS among individuals who have either quit or reduced smoking. Searches will include PubMed, Scopus, and Cochrane Library, covering the period from 2010 to January 2024. A gray literature search and supplementary searches will be performed. Data will be extracted independently by 2 reviewers and quality assessments will be conducted concurrently. Quality assessments will use Joanna Briggs Institute tools, 2020 version, along with bias assessments for internal validity and reporting bias based on the Catalogue of Bias. The included studies will be examined for any internal data reporting discrepancies by using Puljak's checklist. Meta-analysis and subgroup analyses (ie, general ENDS usage, ENDS use coupled with a reduction in smoking exceeding 50%, and exclusive ENDS use for achieving smoking cessation) are planned. Certainty of evidence will be evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. RESULTS: The protocol has been registered in PROSPERO (CRD42023494974) and the entire systematic review is expected to be completed by April 2024. The main goal of this review is to retrieve all current human research studies investigating the influence of ENDS on weight management among individuals who have quit or reduced smoking. Furthermore, the review will assess the quality of these studies and examine potential biases to identify the most dependable evidence available. Dissemination strategies will include traditional journal publications, social media announcements, and a white paper. The latter, available for download and distributed at conferences, aims to reach a broad audience, including clinicians and ENDS users. CONCLUSIONS: The review will address the importance of informing health care professionals and patients about the current and robust evidence regarding the effects of transitioning to ENDS for smoking cessation on weight status. TRIAL REGISTRATION: PROSPERO CRD42023494974; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=494974. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/56324.

The Impact of Calcium and Vitamin D Supplementation Prior to Thyroidectomy on Mitigating Postoperative Hypocalcemia.

Background Hypocalcemia remains the most frequent complication after thyroidectomy. It can either be transient or permanent, and patients often find it unpleasant due to its association with prolonged hospitalization. The objective of this study was to determine the role of preoperative calcium and vitamin D supplementation in preventing hypocalcemia after subtotal/total thyroidectomy. Material and methods This quasi-experimental study was conducted at the Department of General Surgery, Ayub Teaching Hospital, Abbottabad, Pakistan, from January 2023 to July 2023. We utilized non-probability purposive sampling. Patients undergoing total thyroidectomy were recruited and followed until discharge to ascertain outcomes. They were divided into two groups: Group A received vitamin D (200,000 IU) one week preoperatively as single intramuscular dose and calcium (1 gm) orally two times daily for one week preoperatively, while Group B served as the control. Venous blood samples were taken post-surgery, on the second and seventh day and at day 30 to assess hypocalcemia. Chi-square test was employed, comparing hypocalcemia in both groups with a p-value ≤0.05 considered significant. Results One hundred thirty-two patients underwent subtotal/total thyroidectomy, with 46.2% (n = 61) being male and 53.8% (n = 71) female. The mean age of these patients was 37.12 ± 6.22 years, ranging from 20 to 50 years, and 57.6% (n = 76) were aged over 35 years. More than half (55.3%, n = 73) hailed from rural areas, while 4.7% (n = 59) resided in urban locales. Among the patients, 15.9% (n = 21) had a history of diabetes, and 24.2% (n = 32) were hypertensive. The mean body mass index (BMI) was 23.32 ± 2.41 kg/m2, with 7.6% (n = 10) classified as obese. The mean preoperative serum calcium level was 9.87 ± 1.07 mg/dL. Postoperatively, the mean serum calcium level was 8.74 ± 0.83 mg/dL. Both Group A (preoperative vitamin D and calcium supplementation) and Group B (control) demonstrated comparable baseline characteristics before undergoing thyroidectomy. The incidence of postoperative hypocalcemia was notably lower in Group A, with only 4.5% (n = 3) experiencing this complication. By contrast, 24.2% (n = 16) of patients in Group B, the control group, developed hypocalcemia (P = 0.001). Conclusion Our study supports the use of preoperative calcium and vitamin D supplementation in patients undergoing thyroidectomy to combat hypocalcemia. The treated group showed significantly lower hypocalcemia compared to the untreated group B. We recommend preoperative calcium and vitamin D supplementation for all thyroidectomy patients to reduce related morbidities and hospitalization duration.

Adult perceptions of cigarettes and e-cigarettes: A Pakistan focus group study.

Objective: Evidence suggests that the popularity of Reduced Risk Products' (RRPs) is growing globally, and they are being considered as effective aids for tobacco cessation. To explore different policy options for reducing disease burden, this qualitative study investigates the perceptions of the urban adult population regarding the use of e-cigarettes (EC), combustible cigarettes, or both, and the factors influencing their choices. Methods: Twelve focus group discussions (FGDs), involving 132 participants, (68 male, 64 female), aged 18-60, were conducted from August to October 2022 in three metropolitan cities of Pakistan. Thematic analyses were conducted using the NVivo software. The Standards for Reporting Qualitative Research were employed for reporting and conducting purposes. Results: The findings indicate that while all participants discussed the health risks associated with combustible cigarettes and EC and expressed intensions to quit, many continued to smoke or vape. Reasons cited included perceived stress relief, alleviation of medical issues, or addiction hindering cessation efforts. Among the youth, EC use gained popularity due to its social acceptability and the inclusion of appealing flavours and fragrances. Additionally, participants managed the higher costs of ECs by sharing and pooling expenses. Some users of combustible cigarettes transitioned to ECs with the expectation of achieving better health outcomes. Conclusion: This study establishes a foundation for undertaking quantitative research to identify pathways for assisting policymakers in mitigating the growing disease burden. Additionally, it aims to contribute to the achievement of Sustainable Development Goals 3a and 3.4 for Pakistan.

Respiratory health effects of e-cigarette substitution for tobacco cigarettes: a systematic review.

BACKGROUND: E-cigarettes (electronic nicotine delivery system, ENDS) have been presented as a harm reduction strategy for people who smoke tobacco cigarettes but who cannot achieve abstinence, or for those who wish to continue to enjoy nicotine and the habit of smoking. What are the health effects of the substitution of ENDS for tobacco cigarettes? This systematic review evaluates the evidence of human clinical tests on the respiratory effects of ENDS use in participants who smoke tobacco cigarettes. METHODS: A registered and published protocol was developed conforming to PRISMA 2020 and AMSTAR2 standards. The literature search was conducted in PubMed, Scopus, and the CENTRAL Cochrane Library and updated to May 2022. Three supplementary searches and a grey literature search were performed. Studies were evaluated with the JBI quality tools and the Oxford Catalogue of Bias. Due to the heterogeneity (diversity) of the studies, a narrative data synthesis was performed on the test findings plus three sub-group analyses. RESULTS: The review consists of sixteen studies and twenty publications. Spirometry tests comprised the majority of the data. In total, 66 respiratory test measurements were reported, out of which 43 (65%) were not significant. Statistically significant findings were mixed, with 9 tests showing improvements and 14 measuring declines, none of which was clinically relevant. Ten studies were rated at a high risk of bias, and six had some concerns primarily due to inadequate research designs and the conduct of the studies. Reporting bias was documented in thirteen studies. CONCLUSIONS: Most of the studies showed no difference in respiratory parameters. This indicates that ENDS substitution for smoking likely does not result in additional harm to respiratory health. Due to the low quality of the studies, confidence in the conclusions is rated as low. Robust studies with a longer duration and sufficient power are required to validate any potential benefits or possible harms of ENDS substitution. Registration PROSPERO #CRD42021239094, International Registered Report Identifier (IRRID): DERR1-10.2196/29084.

Novel Biomarkers and the Multiple-Marker Approach in Early Detection, Prognosis, and Risk Stratification of Cardiac Diseases: A Narrative Review.

Cardiac diseases are a primary cause of mortality worldwide, underscoring the importance of early identification and risk stratification to enhance patient outcomes. Biomarkers have become important tools for the risk assessment of cardiovascular disease and monitoring disease progression. This narrative review focuses on the multiple-marker approach, which involves simultaneously evaluating several biomarkers for the early detection and risk stratification of heart diseases. The review covers the clinical applications of novel biomarkers, such as high-sensitivity troponin, galectin-3, source of tumorigenicity 2, B-type natriuretic peptide and N-terminal pro-B-type natriuretic peptide, growth differentiation factor 15, myeloperoxidase, fatty acid-binding protein, C-reactive protein, lipoprotein-associated phospholipase A2, microRNAs, circulating endothelial cells, and ischemia-modified albumin. These biomarkers have demonstrated potential in identifying people who are at high risk for developing heart disease and in providing prognostic data. Given the complexity of cardiac illnesses, the multiple-marker approach to risk assessment is extremely beneficial. Implementing the multiple-marker strategy can improve risk stratification, diagnostic accuracy, and patient care in heart disease patients.

Murphy's Law and Ophthalmic Complications in a Patient With Type 1 Diabetes Mellitus.

Diabetes can lead to various acute clinical complications, although the occurrence of ophthalmic signs and symptoms is uncommon. Neovascular glaucoma (NG), a rare complication associated with diabetes mellitus, is one such condition. Additionally, anti-vascular endothelial growth factor (VEGF)-induced toxic anterior segment syndrome (TASS) is a rare complication of intravitreal bevacizumab. In this case report, we present a unique case of a patient with juvenile diabetes (type 1 diabetes mellitus) who presented to the emergency room (ER) with typical features of diabetic ketoacidosis (DKA) accompanied by bilateral ocular pain. Subsequent investigation revealed secondary angle-closure neovascular glaucoma as the underlying cause. The patient received management for DKA in the ER and subsequent medicine ward. Various interventions were performed for glaucoma in the right eye, including addressing cataracts, which ultimately resulted in TASS. The patient was successfully treated with cryo-diode laser therapy.

Clinical testing of the cardiovascular effects of e-cigarette substitution for smoking: a living systematic review.

Some persons who smoke have substituted e-cigarettes for tobacco cigarettes, either completely or partially. What effect does this have on cardiovascular functioning? We conducted a living systematic review on human clinical studies measuring the cardiovascular effects of e-cigarette substitution for smoking. The Scopus, PubMed, and CENTRAL Cochrane Library databases were searched on January 31 and April 29, 2021. Three secondary searches and a grey literature search were conducted. Included study designs were randomized controlled trials, quasi-experimental clinical trials, and cohort studies. Risk of bias and study quality were evaluated with the JBI Critical Appraisal tools and the Oxford Catalogue of Bias. The systematic review covered 25 studies comprising 1810 participants who smoked. Twenty studies were rated at high risk of bias, and five as some concerns. A tabular synthesis by direction of effect was conducted due to heterogeneity in the data. Nearly two-thirds of the test analyses indicated that e-cigarette use had no significance difference compared with tobacco cigarettes on heart rate, blood pressure, and in other cardiovascular tests. In two studies, participants with hypertension experienced a clinically relevant reduction in systolic blood pressure after 1 year of e-cigarette use. E-cigarette substitution incurs no additional cardiovascular risks, and some possible benefits may be obtained, but the evidence is of low to very low certainty. An update search on May 30, 2022 retrieved five studies that did not alter our conclusion.Registration PROSPERO #CRD42021239094.

Loss-of-Function FLNC Variants Are Associated With Arrhythmogenic Cardiomyopathy Phenotypes When Identified Through Exome Sequencing of a General Clinical Population.

BACKGROUND: The FLNC gene has recently garnered attention as a likely cause of arrhythmogenic cardiomyopathy, which is considered an actionable genetic condition. However, the association with disease in an unselected clinical population is unknown. We hypothesized that individuals with loss-of-function variants in FLNC (FLNCLOF) would have increased odds for arrhythmogenic cardiomyopathy-associated phenotypes versus variant-negative controls in the Geisinger MyCode cohort. METHODS: We identified rare, putative FLNCLOF among 171 948 individuals with exome sequencing linked to health records. Associations with arrhythmogenic cardiomyopathy phenotypes from available diagnoses and cardiac evaluations were investigated. RESULTS: Sixty individuals (0.03%; median age 58 years [47-70 interquartile range], 43% male) harbored 27 unique FLNCLOF. These individuals had significantly increased odds ratios for dilated cardiomyopathy (odds ratio, 4.9 [95% CI, 2.6-7.6]; P<0.001), supraventricular tachycardia (odds ratio, 3.2 [95% CI, 1.1-5.6]; P=0.048), and left-dominant arrhythmogenic cardiomyopathy (odds ratio, 4.2 [95% CI, 1.4-7.9]; P=0.03). Echocardiography revealed reduced left ventricular ejection fraction (52±13% versus 57±9%; P=0.001) associated with FLNCLOF. Overall, at least 9% of FLNCLOF patients demonstrated evidence of penetrant disease. CONCLUSIONS: FLNCLOF variants are associated with increased odds of ventricular arrhythmia and dysfunction in an unselected clinical population. These findings support genomic screening of FLNC for actionable secondary findings.

Self-assessment and deep learning-based coronavirus detection and medical diagnosis systems for healthcare.

Coronavirus is one of the serious threat and challenge for existing healthcare systems. Several prevention methods and precautions have been proposed by medical specialists to treat the virus and secure infected patients. Deep learning methods have been adopted for disease detection, especially for medical image classification. In this paper, we proposed a deep learning-based medical image classification for COVID-19 patients namely deep learning model for coronavirus (DLM-COVID-19). The proposed model improves the medical image classification and optimization for better disease diagnosis. This paper also proposes a mobile application for COVID-19 patient detection using a self-assessment test combined with medical expertise and diagnose and prevent the virus using the online system. The proposed deep learning model is evaluated with existing algorithms where it shows better performance in terms of sensitivity, specificity, and accuracy. Whereas the proposed application also helps to overcome the virus risk and spread.

Nature-inspired solution for coronavirus disease detection and its impact on existing healthcare systems.

Coronavirus is an infectious life-threatening disease and is mainly transmitted through infected person coughs, sneezes, or exhales. This disease is a global challenge that demands advanced solutions to address multiple dimensions of this pandemic for health and wellbeing.  Different types of medical and technological-based solutions have been proposed to control and treat COVID-19. Machine learning is one of the technologies used in Magnetic Resonance Imaging (MRI) classification whereas nature-inspired algorithms are also adopted for image optimization. In this paper, we combined the machine learning and nature-inspired algorithm for brain MRI images of COVID-19 patients namely Machine Learning and Nature Inspired Model for Coronavirus (MLNI-COVID-19). This model improves the MRI image classification and optimization for better diagnosis. This model will improve the overall performance especially the area of brain images that is neglected due to the unavailability of the dataset. COVID-19 has a serious impact on the patient brain. The proposed model will help to improve the diagnosis process for better medical decisions and performance. The proposed model is evaluated with existing algorithms and achieved better performance in terms of sensitivity, specificity, and accuracy.

Respiratory and Cardiovascular Health Effects of e-Cigarette Substitution: Protocol for Two Living Systematic Reviews.

BACKGROUND: Despite the clear risks of tobacco use, millions of people continue to smoke. Electronic nicotine delivery systems (ENDS), commonly called e-cigarettes, have been proposed as a substitute for those who are unwilling or unable to quit. Current systematic and narrative reviews on the health effects of ENDS use, particularly respiratory and cardiovascular effects, have come to differing conclusions. OBJECTIVE: We conducted two systematic reviews to critically assess and synthesize available human studies on the respiratory and cardiovascular health effects of ENDS substitution for people who smoke. The primary goal is to provide clinicians with evidence on the health effects of ENDS substitution to inform their treatment recommendations and plans. The twin goal of the reviews is to promote health literacy in ENDS users with facts on the health effects of ENDS. METHODS: These two reviews will be living systematic reviews. The systematic reviews will be initiated through a baseline review. Studies will be evaluated using the JBI quality assessment tools and a checklist of biases drawn from the Centre for Evidence Based Medicine Catalogue of Bias. A narrative synthesis is planned because of the heterogeneity of data. A search for recently published studies will be conducted every 3 months, and an updated review will be published every 6 months for the duration of the project or possibly longer. RESULTS: The baseline and updated reviews will be published in a peer-reviewed journal. The findings of the reviews will be reported in a white paper for clinicians and a fact sheet for people who use ENDS. CONCLUSIONS: The substitution of ENDS for cigarettes is one way to potentially reduce the risks of smoking. Clinicians and their patients need to understand the potential benefits and possible risks of substituting ENDS for cigarettes. Our living systematic reviews seek to highlight the best and most up-to-date evidence in this highly contentious and fast-moving field of research. TRIAL REGISTRATION: PROSPERO CRD42021239094; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=239094. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/29084.

Clinical Outcomes of Selective Versus Nonselective His Bundle Pacing.

OBJECTIVES: The aim of the study was to evaluate the clinical outcomes of nonselective (NS) His bundle pacing (HBP) compared with selective (S) HBP. BACKGROUND: HBP is the most physiologic form of ventricular pacing. NS-HBP results in right ventricular septal pre-excitation due to fusion with myocardial capture in addition to His bundle capture resulting in widened QRS duration compared with S-HBP wherein there is exclusive His bundle capture and conduction. METHODS: The Geisinger and Rush University HBP registries comprise 640 patients who underwent successful HBP. Our study population included 350 consecutive patients treated with HBP for bradyarrhythmic indications who demonstrated ≥20% ventricular pacing burden 3 months post-implantation. Patients were categorized into S-HBP or NS-HBP based on QRS morphology (NS-HBP n = 232; S-HBP n = 118) at the programmed output at the 3-month follow-up. The primary analysis outcome was a combined endpoint of all-cause mortality or heart failure hospitalization. RESULTS: The NS-HBP group had a higher number of men (64% vs. 50%; p = 0.01), higher incidence of infranodal atrioventricular block (40% vs. 9%; p < 0.01), ischemic cardiomyopathy (24% vs. 14%; p = 0.03), and permanent atrial fibrillation (18% vs. 8%; p = 0.01). The primary endpoint occurred in 81 of 232 patients (35%) in the NS-HBP group compared with 23 of 118 patients (19%) in the S-HBP group (hazard ratio: 1.38; 95% confidence interval: 0.87 to 2.20; p = 0.17). Subgroup analyses of patients at greatest risk (higher pacing burden or lower left ventricular ejection fraction) revealed no incremental risk with NS-HBP. CONCLUSIONS: NS-HBP was associated with similar outcomes of death or heart failure hospitalization when compared with S-HBP. Multicenter risk-matched clinical studies are needed to confirm these findings.

Thematic analysis of psychiatric patients' perceptions of nursing staff.

Therapeutic and informal interactions with nurses are integral to the quality of care that psychiatric patients receive. How well these interactions are performed, and their impact on the experience and outcomes of inpatient care, have not been subject to systematic evaluation. The aim of the present study was to examine patients' perceptions of the personal and professional qualities of nursing staff and how these contribute to the ward environment. Patients (n = 119) from 16 acute psychiatric wards were interviewed using a schedule developed by a service-user researcher. Transcriptions of interviews were coded and organized into six themes: staff duties, staff disposition, control, communication and engagement, therapeutic ward environment, and consistency. Patients recognized that nurses have a difficult and stressful job, but frequently expressed feelings of anger, frustration, and hopelessness about their experience of the wards. Patients frequently felt that nursing staff did not understand issues from their perspective or attempt to empathize with them. The findings indicate poorly-communicated and inconsistent care. Initiatives to improve patients' experiences of acute psychiatric wards are urgently needed.

An intermediate care unit for older people with both physical and psychiatric disorders: naturalistic outcome study.

BACKGROUND: An intermediate care unit opened in 2008 aiming to relieve pressure on beds in the local general hospital. Its goal was to provide rehabilitation for people recovering from physical illness who had coexisting psychiatric symptoms, including from delirium, but for whom assessment suggested that discharge home might be achieved. As an experimental unit, it warranted evaluation. We aimed to identify clinical factors associated with higher rates of discharge of the patients to their own homes. METHODS: A naturalistic retrospective exploratory cohort study of 100 consecutive admissions to the intermediate care unit. A backward logistic regression analysis was performed. RESULTS: Discharge home was associated with better scores on the Barthel Index of Activities of Daily Living at the time of discharge, a shorter duration of stay, and a psychiatric diagnosis other than delirium. CONCLUSIONS: At the time of pre-admission assessment, clinical factors which were likely to predict discharge home were unclear, suggesting a need for further studies to determine who might best benefit from this sort of intermediate care placement.