Beta blockers are one of the commonest prescription drugs in medicine and they have been thought to revolutionize the treatment of heart failure (HF) with reduced ejection fraction (HFrEF) in the last century. In addition to HFrEF, they are prescribed for a variety of diseases in cardiology from hypertension to HF, angina, and stable coronary artery disease (CAD). The increased prescription of beta blockers in conditions like HF with preserved ejection fraction (HFpEF), and stable CAD may be doing more harm than good as per the data we have so far. The available data shows that beta blockers are associated with increased stroke risk and atrial fibrillation (AF) in hypertension and in patients with HFpEF, they have been associated with decreased exercise capacity. In patients with stable CAD and patients with myocardial infarction with normal systolic functions, beta blockers don’t offer any mortality benefit. In this article, we critically review the common indications and the uses of beta blockers in patients with HFpEF, CAD, hypertension and AF and we propose that beta blockers are overprescribed under the shadow of their beneficial effects in patients with HFrEF.

Introduction: Children with learning difficulties (LD) have poorer oral health compared to those without LD due to barriers in maintaining oral care. However, the scarcity of data for this population in Malaysia has left a huge gap in understanding their problems and how to overcome those barriers. Therefore, this study was conducted to evaluate the unmet dental needs and barriers to care perceived by the guardians of children with learning difficulties (CWLD) attending the Special Education Integrated Programmes of a mainstream primary school, in comparison to children without learning difficulties. Methods: This cross-sectional study surveyed the guardians of CWLD (case) and those without LD (control), aged 6-12 years old. A total of 225 questionnaires were distributed to the guardians with a response rate of 40.4% (N=91). Unmet dental needs and barriers in both groups were analysed using the chi-square test. Barriers with significant Chi-square results were further tested with logistic regression to investigate possible confounders. Results: Unmet dental needs of 23.1% of CWLD were found. Most of the guardians agreed that regular dental check-ups were the most needed dental treatment (27.1%) compared to other treatments. The child’s behaviour and the unwillingness of the dentists to treat were among the significant barriers to dental care within the CWLD group. Conclusion: Despite regular dental visits, guardians of CWLD perceived that their children had the most unmet dental needs compared to other children without LD, with significant barriers in terms of accessing professional dental services.

Background/Aims: This study aimed to develop a diagnostic tool using machine learning to apply functional luminal imaging probe (FLIP) panometry data to determine the probability of esophagogastric junction (EGJ) obstruction as determined using the Chicago Classification version 4.0 (CCv4.0) and high-resolution manometry (HRM). Methods: Five hundred and fifty-seven adult patients that completed FLIP and HRM (with a conclusive CCv4.0 assessment of EGJ outflow) and 35 asymptomatic volunteers (“controls”) were included. EGJ opening was evaluated with 16-cm FLIP performed during sedated endoscopy via EGJ-distensibility index and maximum EGJ diameter. HRM was classified according to the CCv4.0 as conclusive disorders of EGJ outflow or normal EGJ outflow (timed barium esophagram applied when required and available). The probability tool utilized Bayesian additive regression treesBART, which were evaluated using a leave-one-out approach and a holdout test set. Results: Per HRM and CCv4.0, 243 patients had a conclusive disorder of EGJ outflow while 314 patients (and all 35 controls) had normal EGJ outflow. The model accuracy to predict EGJ obstruction (based on leave-one-out/holdout test set, respectively) was 89%/90%, with 87%/85% sensitivity, 92%/97% specificity, and an area under the receiver operating characteristic curve of 0.95/0.97. A free, opensource tool to calculate probability for EGJ obstruction using FLIP metrics is available at https://www.wklytics.commgi/prob_flip.html. Conclusions Application of FLIP metrics utilizing a probabilistic approach incorporates the diagnostic confidence (or uncertainty) into the clinical interpretation of EGJ obstruction. This tool can provide clinical decision support during application of FLIP Panometry for evaluation of esophageal motility disorders.

Objective. To determine the diagnostic accuracy of self-collected snorted and spit saliva in detecting COVID-19 using RT-PCR (ssRT-PCR) and lateral flow antigen test (ssLFA) versus nasopharyngeal swab RT-PCR (npRT-PCR). Methods. One hundred ninety-seven symptomatic subjects for COVID-19 testing in a tertiary hospital underwent snort-spit saliva self-collection for RT-PCR and antigen testing and nasopharyngeal swab for RT-PCR as reference. Positivity rates, agreement, sensitivity, specificity, and likelihood ratios were estimated. Results. Estimated prevalence of COVID-19 using npRT-PCR was 9% (exact 95% CI of 5.5% - 14.1%). A higher positivity rate of 13% in the ssRT-PCR assay suggested possible higher viral RNA in the snort-spit samples. There was 92.9% agreement between ssRT-PCR and npRT-PCR (exact 95% CI of 88.4% to 96.1%; Cohen’s Kappa of 0.6435). If npRT-PCR will be assumed as reference standard, the estimated Sensitivity was 83.3% (exact 95% CI of 60.8% to 94.2%), Specificity 93.9% (exact 95% CI of 89.3% to 96.5%), Positive predictive value of 57.7% (exact 95% CI of 38.9% to 74.5%), Negative predictive value of 98.2% (exact 95% CI of 95% to 99.4%), positive likelihood ratio of 3.65 (95% CI of 7.37 to 24.9), negative likelihood ratio of 0.178 (95% CI of 0.063 to 0.499). There was 84.84% agreement (95% exact CI of 79.1% to 89.5%; Cohen’s Kappa of 0.2356) between ssLFAvs npRT-PCR, sensitivity of 38.9% (exact 95% CI of 20.3% to 61.4%), specificity of 89.4% (exact 95% CI of 84.1% to 93.1%), PPV of 26.9% (95% CI of 13.7% to 46.1%), NPV of 93.6% (exact 95% CI of 88.8% to 96.4%), LR+ of 3.67 (95% CI of 1.79 - 7.51), LR – of 0.68 (95% CI of 0.47 - 0.99). Conclusion. Our data showed that snort-spit saliva RT-PCR testing had acceptable diagnostic performance characteristics and can potentially be used as an alternative to the standard nasopharyngeal/oropharyngeal swab RT-PCR test for COVID-19 in certain situations. However, our data also showed that snort-spit saliva antigen testing using lateral flow assay did not offer acceptable performance.
Saliva ; SARS-CoV-2 ; Reverse Transcription ; Reverse Transcriptase Polymerase Chain Reaction

Background: This is a rare and challenging case of Wolff–Parkinson–White syndrome due to a posteroseptal acces‑ sory pathway located in the coronary sinus diverticulum. It is often difficult to precisely locate this type of accessory pathway, and the ablation procedure could be associated with collateral damage to the neighbouring coronary arteries.Case Presentation: The patient was a 49-year-old female with Wolff–Parkinson–White syndrome who was referred for catheter ablation. She had had a previous unsuccessful attempt at ablation and had remained symptomatic despite drug therapy. The pre-procedural cardiac computed tomography scan revealed the presence of a diverticu‑ lum in the proximal coronary sinus. Using an advanced three-dimensional cardiac mapping system, the electroana‑ tomic map of the diverticulum was created. The accessory pathway potential was identified within the diverticulum preceding the ventricular insertion. The accessory pathway was then successfully ablated using radiofrequency energy. Conclusion We have demonstrated that the advanced three-dimensional cardiac mapping system plays a very important role in guiding clinicians in order to precisely locate and safely ablate this type of challenging accessory pathway.

Objective: To systematically review studies on canine agenesis prevalence in different populations and continents, based on the jaw, sex, location, and associated dental anomalies. Methods: Electronic and hand searches of English literature in PubMed, Web of Science, Scopus, OpenGrey, and Science Direct were conducted, and the authors were contacted when necessary. Observational studies (population-based, hospital/clinic-based, and cross-sectional) were included. For study appraisal and synthesis, duplicate selection was performed independently by two reviewers. Study quality was assessed using a modified Strengthening the Reporting of Observational Studies in Epidemiology checklist, with main outcome of prevalence of canine agenesis. Results: The global population prevalence of canine agenesis was 0.30% (0.0−4.7%), highest in Asia (0.54%), followed by Africa (0.33%), and the least in Europe and South America (0.19% in both continents). Canine agenesis was more common in the maxilla (88.57%), followed by both maxilla and mandible (8.57%), and the least common was mandible-only presentation (2.86%). The condition was more common in females (female:male ratio = 1.23), except in Asia (female:male ratio = 0.88) and Africa (female:male ratio = 1). In Asia, unilateral agenesis was almost twice as prevalent as bilateral, but in Europe, the bilateral form was more common. Conclusions The overall prevalence of canine agenesis is 0.30%, with the highest prevalence in Asia, followed by Africa, Europe, and South America.The condition is more common in the maxilla than the mandible, and in females than males (except in Asia and Africa), with unilateral agenesis being more common in Asia and the bilateral form showing a greater prevalence in Europe.

In this work, we describe the development of Polar Gini Curve, a method for characterizing cluster markers by analyzing single-cell RNA sequencing (scRNA-seq) data. Polar Gini Curve combines the gene expression and the 2D coordinates ("spatial") information to detect patterns of uniformity in any clustered cells from scRNA-seq data. We demonstrate that Polar Gini Curve can help users characterize the shape and density distribution of cells in a particular cluster, which can be generated during routine scRNA-seq data analysis. To quantify the extent to which a gene is uniformly distributed in a cell cluster space, we combine two polar Gini curves (PGCs)-one drawn upon the cell-points expressing the gene (the "foreground curve") and the other drawn upon all cell-points in the cluster (the "background curve"). We show that genes with highly dissimilar foreground and background curves tend not to uniformly distributed in the cell cluster-thus having spatially divergent gene expression patterns within the cluster. Genes with similar foreground and background curves tend to uniformly distributed in the cell cluster-thus having uniform gene expression patterns within the cluster. Such quantitative attributes of PGCs can be applied to sensitively discover biomarkers across clusters from scRNA-seq data. We demonstrate the performance of the Polar Gini Curve framework in several simulation case studies. Using this framework to analyze a real-world neonatal mouse heart cell dataset, the detected biomarkers may characterize novel subtypes of cardiac muscle cells. The source code and data for Polar Gini Curve could be found at http://discovery.informatics.uab.edu/PGC/ or https://figshare.com/projects/Polar_Gini_Curve/76749.

Objective: To systematically review studies on canine agenesis prevalence in different populations and continents, based on the jaw, sex, location, and associated dental anomalies. Methods: Electronic and hand searches of English literature in PubMed, Web of Science, Scopus, OpenGrey, and Science Direct were conducted, and the authors were contacted when necessary. Observational studies (population-based, hospital/clinic-based, and cross-sectional) were included. For study appraisal and synthesis, duplicate selection was performed independently by two reviewers. Study quality was assessed using a modified Strengthening the Reporting of Observational Studies in Epidemiology checklist, with main outcome of prevalence of canine agenesis. Results: The global population prevalence of canine agenesis was 0.30% (0.0−4.7%), highest in Asia (0.54%), followed by Africa (0.33%), and the least in Europe and South America (0.19% in both continents). Canine agenesis was more common in the maxilla (88.57%), followed by both maxilla and mandible (8.57%), and the least common was mandible-only presentation (2.86%). The condition was more common in females (female:male ratio = 1.23), except in Asia (female:male ratio = 0.88) and Africa (female:male ratio = 1). In Asia, unilateral agenesis was almost twice as prevalent as bilateral, but in Europe, the bilateral form was more common. Conclusions The overall prevalence of canine agenesis is 0.30%, with the highest prevalence in Asia, followed by Africa, Europe, and South America.The condition is more common in the maxilla than the mandible, and in females than males (except in Asia and Africa), with unilateral agenesis being more common in Asia and the bilateral form showing a greater prevalence in Europe.

Background: This is a rare and challenging case of Wolff–Parkinson–White syndrome due to a posteroseptal acces‑ sory pathway located in the coronary sinus diverticulum. It is often difficult to precisely locate this type of accessory pathway, and the ablation procedure could be associated with collateral damage to the neighbouring coronary arteries.Case Presentation: The patient was a 49-year-old female with Wolff–Parkinson–White syndrome who was referred for catheter ablation. She had had a previous unsuccessful attempt at ablation and had remained symptomatic despite drug therapy. The pre-procedural cardiac computed tomography scan revealed the presence of a diverticu‑ lum in the proximal coronary sinus. Using an advanced three-dimensional cardiac mapping system, the electroana‑ tomic map of the diverticulum was created. The accessory pathway potential was identified within the diverticulum preceding the ventricular insertion. The accessory pathway was then successfully ablated using radiofrequency energy. Conclusion We have demonstrated that the advanced three-dimensional cardiac mapping system plays a very important role in guiding clinicians in order to precisely locate and safely ablate this type of challenging accessory pathway.

Background:Missed clinic appointments negatively impact clinic patient flow and health outcomes of people living with HIV (PLHIV).PLHIV likelihood of missing clinic appointments is associated with direct and indirect expenditures made while accessing HIV care.The objective of this study was to examine the relationship between out-of-pocket (OOP) health expenditures and the likelihood of missing appointments.Method:Totally 618 PLHIV older than 18 years attending two HIV care and treatment centres (CTC) in Northern Tanzania were enrolled in the study.Clinic attendance and clinical characteristics were abstracted from medical records.Information on OOP health expenditures,demographics,and socio-economic factors were self-reported by the participants.We used a hurdle model.The first part of the hurdle model assessed the marginal effect of a one Tanzanian Shillings (TZS) increase in OOP health expenditure on the probability of having a missed appointment and the second part assessed the probability of having missed appointments for those who had missed an appointment over the study period.Results:Among these 618 participants,242 (39％) had at least one missed clinic appointment in the past year.OOP expenditure was not significantly associated with the number of missed clinic appointments.The median amount of OOP paid was 5100 TZS per visit,about 7％ of the median monthly income.Participants who were separated from their partners (adjusted odds ratio[AOR]=1.83,95％ confidence interval[CI]:1.11-8.03) and those aged above 50 years (AOR =2.85,95％ CI:1.01-8.03) were significantly associated with missing an appointment.For those who had at least one missed appointment over the study period,the probability of missing a clinic appointment was significantly associated with seeking care in a public CTC (P =0.49,95％ CI:0.88-0.09) and aged between ＞ 25-35 years (P =0.90,95％ CI:0.11-1.69).Conclusion:Interventions focused on improving compliance to clinic appointments should target public CTCs,PLHIV aged between ＞ 25-35 years,above 50 years of age and those who are separated from their partners.