Penicillin allergy de-labeling: Adaptation of risk stratification tool for patients and families.

Penicillin allergy is reported in 10% of the population; however, over 90% of patients are deemed non-allergic upon allergist assessment. The goal of this quality improvement project is to validate a patient-driven assessment tool to safely identify patients at low risk of penicillin allergy and de-label them. Pediatric patients and pregnant women referred to the institution's allergy clinics for penicillin allergy assessment were invited to use the patient tool to complete a self-assessment, resulting in the assignment of a risk category. The risk stratification determined using the patient tool was compared against the allergist's assessment. The patient tool demonstrated agreement with the allergist assessment in 57/84 (67.9%, 95% CI [56.7%,77.4%]) assessments, intra-class correlation (ICC) = 0.618, p < 0.001. In 22/84 (26.2%) assessments, the patient tool determined a higher risk category, primarily due to differences in patients' perceived timing and description of symptoms. Only 5/84 (6.0%) patients were placed in a lower risk category by the patient tool compared to the allergist assessment. The patient tool demonstrates good validity in determining penicillin allergy risk, offering potential as a method of empowering patients to advocate in their care. Iterative changes to the patient tool will be applied to increase agreement.

Activity levels across the intensity spectrum in athletes: a systematic review protocol.

Physical activity (PA) promotes better cardiometabolic health, physical function, brain health and longevity. In contrast, prolonged sedentary behaviour (SB) is a risk factor for many chronic diseases and poor health. Limited research has evaluated or synthesised how competitive sports participation influences PA across the lifespan. Some evidence suggests, ironically, that former competitive athletes may be insufficiently active and current athletes may be highly sedentary away from sport. This study describes the protocol for a systematic review and meta-analysis on activity levels across the intensity spectrum in athletes, addressing the primary research question: is sports participation significantly associated with PA and/or SB among current and former competitive athletes? PubMed, Embase, Cochrane Database of Systematic Reviews, Web of Science and SPORTDiscus databases will be searched. Two reviewers will independently screen titles/abstracts and full texts of selected abstracts. Data will be extracted regarding the study population, sport played, PA measures and protocols, outcomes of interest and findings. Primary outcomes will include step counts, daily activity across the intensity spectrum (ie, sedentary, light, moderate and vigorous PA), metabolic equivalent of task and whole-day energy expenditure. Secondary outcomes will include additional accelerometry measures of PA, activity patterns and self-reported PA. The risk of bias will be assessed using the National Institutes of Health Study Quality Assessment Tools. Extracted data will be presented using narrative synthesis and tabular presentation. Meta-analyses will be conducted to determine outcomes with sufficient data.PROSPERO registration number: CRD42024469267.https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=469267.

Antipsychotics possess anti-glioblastoma activity by disrupting lysosomal function and inhibiting oncogenic signaling by stabilizing PTEN.

The repurposing of medications developed for central nervous system (CNS) disorders, possessing favorable safety profiles and blood-brain barrier permeability, represents a promising strategy for identifying new therapies to combat glioblastoma (GBM). In this study, we investigated the anti-GBM activity of specific antipsychotics and antidepressants in vitro and in vivo. Our results demonstrate that these compounds share a common mechanism of action in GBM, disrupting lysosomal function and subsequently inducing lysosomal membrane rupture and cell death. Notably, PTEN intact GBMs possess an increased sensitivity to these compounds. The inhibition of lysosomal function synergized with inhibitors targeting the EGFR-PI3K-Akt pathway, leading to an energetic and antioxidant collapse. These findings provide a foundation for the potential clinical application of CNS drugs in GBM treatment. Additionally, this work offers critical insights into the mechanisms and determinants of cytotoxicity for drugs currently undergoing clinical trials as repurposing agents for various cancers, including Fluoxetine, Sertraline, Thioridazine, Chlorpromazine, and Fluphenazine.

Detection of rat lungworm (Angiostrongylus cantonensis) infection by real-time PCR from the peripheral blood of animals: a preliminary study.

Rat lungworm disease or neuroangiostrongyliasis is a cerebral parasitic infection that affects humans and animals alike. Its clinical signs and symptoms can range from mild self-resolving to serious life-threatening conditions. Studies suggest therapeutic interventions during the early stages of infection to be more effective than in later stages. However, early diagnosis of infection is usually problematic without the knowledge of exposure and/or detection of the parasite's DNA or antibody against the parasite in the cerebrospinal fluid. This requires a lumbar puncture, which is an invasive procedure that generally requires hospitalization. This study evaluates an affordable and less invasive alternative to detect parasitic DNA by PCR from the peripheral blood of potentially infected animals. Blood samples from 58 animals (55 dogs and 3 cats) with clinical suspicion of infection were submitted to our lab between February 2019 and August 2022 by local, licensed veterinarians. DNA was extracted from whole blood, plasma, serum, and/or packed cells using the Qiagen DNeasy Blood & Tissue Kit as per the manufacturer's protocol. All 58 animals were tested by real-time PCR using the AcanITS1 assay and 32 of these animals (31dogs; 1 cat) were also tested using the AcanR3990 assay. The PCR results for both assays were classified into strongly positive > positive > weakly positive > negative, and equivocal for ambiguous results, based on the strength of the signal. The percent infection detected using the AcanITS1 and AcanR3990 assays was 12.72% (7/55) and 20.68% (6/29), respectively. The overall percent infection detected was 34.37% (11/32), with only two animals testing positive by both assays. The three cats involved in this study tested negative by both assays. These results are promising and warrant further investigations to increase sensitivity including variables that might affect detection in the blood, such as parasite load, and laboratory methodologies.

Robotic Magnetic Sphincter Augmentation Device Removal.

Although most patients with reflux can be managed with medical therapy, some require surgical intervention to manage their disease. Newer technologies, such as magnetic sphincter augmentation (MSA), have been promoted as the replacement of fundoplication. However, as time has elapsed, our institution noticed the need for the removal of MSA devices. Although a few reports have described MSA device removals, we provide a deeper explanation of how to perform a robotic device removal. Our article describes the technical steps and includes a video to demonstrate how to complete the surgery robotically.

Midlife health crisis of former competitive athletes: dissecting their experiences via qualitative study.

Sports participation confers many health benefits yet greatly increases injury risk. Long-term health outcomes in former athletes and transition to life after competitive sports are understudied. Ending a sport may pose physical and psychosocial challenges. The purpose was to determine the lived experiences of former competitive athletes and how their sports participation impacted their long-term health and well-being. Former college varsity athletes participated in semistructured interviews focusing on their experiences, including past and current health, the impact of injuries, activity, exercise, diet and transition to life after competitive sport. Thematic analysis was completed using a collaborative, iterative process. Thirty-one (16 female, 15 male) former college athletes aged 51.3±7.4 years were interviewed. Six themes emerged: (1) lifelong athlete identity; (2) structure, support and challenges of the college athlete experience; (3) a big transition to life beyond competitive sport; (4) impact of competitive sport on long-term health; (5) facilitators and barriers to long-term health after sport and (6) transferable life skills. Continuing sports eased the transition for many but often delayed their postathlete void. Challenges included managing pain and prior injury (eg, If I didn't have my knee injury, I would definitely be more active), reducing energy needs and intake (eg, When I was an athlete, I could eat anything; and unfortunately, that's carried into my regular life), lack of accountability, changed identity and lost resources and social support. Participants suggested a programme, toolkit, mentoring or exit course to facilitate the transition. While former athletes benefit from transferrable life skills and often continue sports and exercise, they face unique challenges such as managing pain and prior injury, staying active, reducing energy intake and changing identity. Future research should develop and evaluate a toolkit, programme and other resources to facilitate life after ending competitive sports under 'normal' conditions (eg, retirement) and after a career-ending injury.

Beta Blockers in Contemporary Cardiology: Is It Better to Cast Them Out?

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 over-prescribed under the shadow of their beneficial effects in patients with HFrEF.

Efficacy of X-Ray Phytosanitary Irradiation on the Infectivity and Reproduction of Angiostrongylus cantonensis in Experimentally Infected Rats.

Angiostrongylus cantonensis is a globally distributed nematode and the leading cause of eosinophilic meningitis in humans. As a global hotspot for this disease, Hawaii's agricultural exports may be contributing to the spread of A. cantonensis. Phytosanitary irradiation doses of 150 or 400 Gy provide quarantine security against multiple insect pests. We evaluated the in vitro and in vivo effects of phytosanitary irradiation on infectious, third-stage, A. cantonensis larvae. In vitro experiments directly exposed larvae to irradiation doses ranging from 200 to 1,000 Gy. Results showed low mortality and no dose response across all treatments 27 days post-irradiation. In vivo studies isolated larvae from wild-caught Parmarion martensi after exposure to x-ray irradiation at doses of 0, 150, and 400 Gy and infected them into laboratory rats. Fourteen rats were assigned to each treatment and infected with 50 larvae from their assigned irradiation dose. Results at 3 and 6 weeks post-infection demonstrated a significant negative dose response in regard to the number of larvae that migrated to the brain and adults found in the pulmonary artery. No irradiated larvae that grew into adults were able to produce eggs. These findings indicate that x-ray irradiation does not result in the direct mortality of A. cantonensis larvae; however, it does affect the infectivity and reproduction of A. cantonensis within its definitive host, the rat. Phytosanitary irradiation at doses ≥150 Gy appears to be an effective means of preventing the establishment of viable populations of A. cantonensis, thus reducing the potential for global spread due to agricultural exports from Hawaii.

PTCH1-mutant human cerebellar organoids exhibit altered neural development and recapitulate early medulloblastoma tumorigenesis.

Patched 1 (PTCH1) is the primary receptor for the sonic hedgehog (SHH) ligand and negatively regulates SHH signalling, an essential pathway in human embryogenesis. Loss-of-function mutations in PTCH1 are associated with altered neuronal development and the malignant brain tumour medulloblastoma. As a result of differences between murine and human development, molecular and cellular perturbations that arise from human PTCH1 mutations remain poorly understood. Here, we used cerebellar organoids differentiated from human induced pluripotent stem cells combined with CRISPR/Cas9 gene editing to investigate the earliest molecular and cellular consequences of PTCH1 mutations on human cerebellar development. Our findings demonstrate that developmental mechanisms in cerebellar organoids reflect in vivo processes of regionalisation and SHH signalling, and offer new insights into early pathophysiological events of medulloblastoma tumorigenesis without the use of animal models.

miRNA-194-3p represses NF-κB in gliomas to attenuate iPSC genes and proneural to mesenchymal transition.

Severe tumor heterogeneity drives the aggressive and treatment refractory nature of glioblastomas (GBMs). While limiting GBM heterogeneity offers promising therapeutic potential, the underlying mechanisms that regulate GBM plasticity remain poorly understood. We utilized 14 patient-derived and four commercially available cell lines to uncover miR-194-3p as a key epigenetic determinant of stemness and transcriptional subtype in GBM. We demonstrate that miR-194-3p degrades TAB2, an important mediator of NF-κB activity, decreasing NF-κB transcriptional activity. The loss in NF-κB activity following miR-194-3p overexpression or TAB2 silencing decreased expression of induced pluripotent stem cell (iPSC) genes, inhibited the oncogenic IL-6/STAT3 signaling axis, suppressed the mesenchymal transcriptional subtype in relation to the proneural subtype, and induced differentiation from the glioma stem cell (GSC) to monolayer (ML) phenotype. miR-194-3p/TAB2/NF-κB signaling axis acts as an epigenetic switch that regulates GBM plasticity and targeting this signaling axis represents a potential strategy to limit transcriptional heterogeneity in GBMs.

Oral Health Needs and Barriers to Care in Children with Learning Difficulties

@#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.

Epidemiological investigation of the COVID-19 outbreak in Vellore district in South India using Geographic Information Surveillance (GIS)

ObjectivesGeographical Information Surveillance (GIS) is an advanced digital technology tool that maps location-based data and helps in epidemiological modeling. We applied GIS to analyze patterns of spread and hotspots of COVID-19 cases in Vellore district in South India. MethodsLaboratory-confirmed COVID-19 cases from the Vellore district and neighboring taluks from March 2020 to June 2021 were geo-coded and spatial maps were generated. Time trends exploring urban-rural burden with an age-sex distribution of cases and other variables were correlated with outcomes. ResultsA total of 45,401 cases of COVID-19 were detected with 20730 cases during the first wave and 24671 cases during the second wave. The overall incidence rates of COVID-19 were 462.8 and 588.6 per 100,000 populations during the first and second waves respectively. The pattern of spread revealed epicenters in densely populated urban areas with radial spread sparing rural areas in the first wave. The case fatality rate was 1.89% and 1.6% during the first and second waves that increased with advancing age. ConclusionsModern surveillance systems like GIS can accurately predict the trends and pattern of spread during future pandemics. A real-time mapping can help design risk mitigation strategies thereby preventing the spread to rural areas.

Hemodynamic changes during exodontia in hypertensive and normotensive patients following injection of local anesthetics with and without epinephrine: a prospective comparative study / Cambios hemodinámicos durante la extracción en pacientes hipertensivos y normotensivos tras la inyección de anestésicos locales con y sin epinefrina: un estudio comparativo prospectivo

Introduction: Hypertensive patients are frequently encountered in routine dental practice and exodontia procedures. Possibility of cardiovascular complications can be anticipated in these patients. This study compares blood pressure, heart rate, and peripheral capillary oxygen saturation, in normotensive and hypertensive patients prior to, during and after dental extractions. Patients and methods: A prospective comparative study was carried out in 100 (N = 100) patients between the age group of 40-70 years. 50 patients diagnosed with Stage I hypertension and 50 patients who were normotensives, requiring extraction of tooth were recruited. They were further divided into four groups namely, A, B, C and D, each consisting of 25 (n = 25). Group A included patients with controlled hypertension who were administered local anesthesia with epinephrine, while Group B had patients with controlled hypertension who were administered local anesthesia without epinephrine. Group C had normotensive patients who were administered local anesthesia with epinephrine and normotensive patients who were administered local anesthesia without epinephrine were under group D. The patients were evaluated at preoperative, intra operatively and post-operative interval for blood pressure, heart rate and peripheral oxygen saturation. (AU)

Introducción: Con frecuencia, en la práctica dental habitual y en los procedimientos de exodoncia se encuentran pacientes hipertensos. En estos pacientes se pueden anticipar posibles complicaciones cardiovasculares. Este estudio compara la presión arterial, la frecuencia cardiaca y la saturación de oxígeno periférico en pacientes normotensos e hipertensos antes, durante y después de las extracciones dentarias. Pacientes y métodos: Se realizó un estudio comparativo prospectivo en 100 pacientes (n = 100) entre un grupo de edad de 40-70 años. Se reclutaron 50 pacientes con diagnóstico de hipertensión en estadio I y 50 pacientes normotensos que requirieron extracción dentaria. Se dividieron además en cuatro grupos, A, B, C y D, cada uno de los cuales constaba de 25 (n = 25). El grupo A incluyó pacientes con hipertensión controlada a los que se les administró anestesia local con epinefrina, mientras que el grupo B tenía pacientes con hipertensión controlada a los que se les administró anestesia local sin epinefrina. El grupo C tenía pacientes normotensos a los que se les administró anestesia local con epinefrina y los pacientes normotensos a los que se les administró anestesia local sin epinefrina estaban en el grupo D. En el intervalo preoperatorio, intraoperatorio y postoperatorio se evaluaron la presión arterial, frecuencia cardiaca y saturación de oxígeno periférico de los pacientes. (AU)

Reconstructing the COVID-19 epidemic in Delhi, India: infection attack rate and reporting of deaths

India reported over 10 million COVID-19 cases and 149,000 deaths in 2020. To estimate exposure and the potential for further spread, we used a SARS-CoV-2 transmission model fit to seroprevalence data from three serosurveys in Delhi and the time-series of reported deaths to reconstruct the epidemic. The cumulative proportion of the population estimated infected was 48.7% (95% CrI 22.1% - 76.8%) by end-September 2020. Using an age-adjusted overall infection fatality ratio (IFR) based on age-specific estimates from mostly high-income countries (HICs), we estimate that 15.0% (95% CrI 9.3% - 34.0%) of COVID-19 deaths were reported. This indicates either under-reporting of COVID-19 deaths and/or a lower age-specific IFR in India compared with HICs. Despite the high attack rate of SARS-CoV-2, a third wave occurred in late 2020, suggesting that herd immunity was not yet reached. Future dynamics will strongly depend on the duration of immunity and protection against new variants.

The global distribution of permanent canine hypodontia: A systematic review / 대한치과교정학회지

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.

The global distribution of permanent canine hypodontia: A systematic review / 대한치과교정학회지

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.

Polar Gini Curve: A Technique to Discover Gene Expression Spatial Patterns from Single-cell RNA-seq Data / 基因组蛋白质组与生物信息学报·英文版

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.

Community prevalence of antibodies to SARS-CoV-2 and correlates of protective immunity in five localities in an Indian metropolitan city

ObjectivesTo assess seroprevalence of anti-SARS-CoV-2 antibodies in a densely populated urban Indian settings and its implications for disease trends and protective immunity. DesignCross-sectional sero-epidemiological survey linked with administrative reporting of COVID-19 testing data. SettingsPune city in western India Main outcome measurePrevalence of anti-SARS-CoV-2 spike protein antibodies were estimated and along with correlates of virus neutralisation and other immune and inflammatory markers. ResultsSeropositivity was extensive (51{middle dot}3%; 95%CI 39{middle dot}9 to 62{middle dot}4) but varied widely in the five localities tested, ranging from 35{middle dot}8% to 66{middle dot}4%. Seropositivity was higher in crowded living conditions in the slums (OR 1{middle dot}91), and was lower in those 65 years or older (OR 0{middle dot}59). The infection-fatality ratio was estimated at 0.21%. Post survey, COVID-19 incidence was lower in areas noted to have higher seroprevalence. Substantial virus-neutralising activity was observed in seropositive individuals, but with considerable heterogeneity in the immune response and possible age-dependent diversity in the antibody repertoire. ConclusionDespite crowded living conditions having facilitated widespread transmission, the variability in seroprevalence in localities that are in geographical proximity indicates a heterogenous spread of infection. Declining infection rates in areas with high seropositivity suggest population-level protection. It is also supported by substantial neutralising activity in asymptomatically infected individuals. This is the first report of a significantly high proportion of protective immune response among asymptomatic individuals in the population. The heterogeneity in antibody levels and neutralisation capacity indicates the existence of immunological sub-groups of functional interest. Trial registrationRegistered with the Clinical Trials Registry of India (CTRI/2020/07/026509)

Pooling RT-PCR or NGS samples has the potential to cost-effectively generate estimates of COVID-19 prevalence in resource limited environments

BackgroundCOVID-19 originated in China and has quickly spread worldwide causing a pandemic. Countries need rapid data on the prevalence of the virus in communities to enable rapid containment. However, the equipment, human and laboratory resources required for conducting individual RT-PCR is prohibitive. One technique to reduce the number of tests required is the pooling of samples for analysis by RT-PCR prior to testing. MethodsWe conducted a mathematical analysis of pooling strategies for infection rate classification using group testing and for the identification of individuals by testing pooled clusters of samples. FindingsOn the basis of the proposed pooled testing strategy we calculate the probability of false alarm, the probability of detection, and the average number of tests required as a function of the pool size. We find that when the sample size is 256, using a maximum pool size of 64, with only 7.3 tests on average, we can distinguish between prevalences of 1% and 5% with a probability of detection of 95% and probability of false alarm of 4%. InterpretationThe pooling of RT-PCR samples is a cost-effective technique for providing much-needed course-grained data on the prevalence of COVID-19. This is a powerful tool in providing countries with information that can facilitate a response to the pandemic that is evidence-based and saves the most lives possible with the resources available. FundingBill & Melinda Gates Foundation Authors contributionsRL and KRN conceived the study. IF, KT, KRN, SB and RL all contributed to the writing of the manuscript and AH and JJ provided comments. KRN and AH conducted the analysis and designed the figures. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSThe pooling of RT-PCR samples has been shown to be effective in screening for HIV, Chlamydia, Malaria, and influenza, among other pathogens in human health. In agriculture, this method has been used to assess the prevalence of many pathogens, including Dichelobacter nodosus, which causes footrot in sheep, postweaning multisystemic wasting syndrome, and antibiotic resistance in swine feces, in addition to the identification of coronaviruses in multiple bat species. In relation to the current pandemic, researchers in multiple countries have begun to employ this technique to investigate samples for COVID-19. Added value of this studyGiven recent interest in this topic, this study provides a mathematical analysis of infection rate classification using group testing and calculates the probability of false alarm, the probability of detection, and the average number of tests required as a function of the pool size. In addition the identification of individuals by pooled cluster testing is evaluated. Implications of all the available evidenceThis research suggests the pooling of RT-PCR samples for testing can provide a cheap and effective way of gathering much needed data on the prevalence of COVID-19 and identifying infected individuals in the community, where it may be infeasible to carry out a high number of tests. This will enable countries to use stretched resources in the most appropriate way possible, providing valuable data that can inform an evidence-based response to the pandemic.

Assessment of clinical and radiographic status of crowned teeth

@#This cross sectional study investigated the clinical and radiographic status of crowned teeth with and without root canal treatment. The study used secondary data from records of patients who received crown treatment at the Faculty of Dentistry, University of Malaya before 2015 and walk-in patients attending the primary care clinic between July - December 2016. The inclusion criterion was crown fitted for more than 12 months. Once identified, the patients were assessed for clinical and radiographic status. Data were entered into and analysed using SPSS Version 20 software. A total of 66 crowns [35 root canal treated (RCT) and 31 non-root canal treated (n-RCT)] were identified. Chi-square test was carried out to determine the health of crowned teeth and for its longevity in the oral cavity. There were 43 crowns (46.5% RCT; 53.5% n-RCT) with plaque accumulation, 15 (66.7% RCT; 33.3% n-RCT) with gingival swelling/recession, 17 (46.5% RCT; 53.5% n-RCT) with widening of the periodontal ligament, 13 (53.8% RCT; 46.2% n-RCT) with bone loss and 5 (60% RCT; 40% n-RCT) crowns with periapical lesion. There was no statistically significant difference except for poorer alveolar bone condition for crowns that have been in the mouth for >10 years. Based on the study, no significant adverse pulpal involvement between crown with RCT and crown without RCT was observed.