Clinical performance of a prefabricated immunofluorescence assay for nasopharyngeal cancer screening.

BACKGROUND: Epstein-Barr virus (EBV) IgA serology for viral capsid antigen (VCA) and early antigen (EA) aids early detection of nasopharyngeal cancer (NPC), resulting in improved survival. We evaluated the diagnostic performance of a prefabricated immunofluorescent assay (IFA) for NPC screening in high-risk individuals. METHODS: Sera from 96 biopsy-proven patients with NPC diagnosed at the outpatient clinic and 96 healthy family members were tested for EBV-VCA IgA and EBV-EA IgA using the prefabricated IFA from EUROIMMUN (EI) and the traditional immunofluorescence method. RESULTS: The AUC of EI EBV-VCA IgA and EBV-EA IgA was 0.907 (95% confidence interval [CI]: 0.894-0.965) and 0.898 (95% CI: 0.848-0.947), respectively. Combined testing with the prefabricated assay at a threshold of VCA ≥1:320 or EA ≥1:10 showed 92.7% sensitivity and 81.2% specificity. Overall, the traditional EBV-EA IgA assay demonstrated the best accuracy (sensitivity 91.7% and specificity 96.9%) at a threshold of ≥1:5. CONCLUSION: While the traditional IFA method was more accurate, the prefabricated IFA test kit can be a useful tool for NPC screening in high-risk populations.

The optimal government size and economic growth: A comparative study between Malaysia and South Korea.

Inspired by the Look East Policy, Malaysia aims to learn from such a successful Asian country as South Korea in order to break through its upper-middle-income trap. Using the dynamic threshold nonlinear approach, this comparative study is therefore timely to compare and contrast the nonlinear correlation between economic growth and government spending between these two nations. When considering two different measures of government size as the threshold variable, namely government operating/real GDP (GS1) and government investment/real GDP (GS2), the practical findings of this research indicate the presence of a threshold effect between government size and economic growth in the contexts of Malaysia and South Korea. Specifically, the BARS curve exists in Malaysia and South Korea when GS1 is set as the threshold variable. However, a U-shaped curve of nonlinear relationship exists in both countries when GS2 serves as the threshold variable. Interestingly, the threshold two-regime regression results show that while government operating expenditures in both Malaysia and South Korea are not found to be overspent and are beneficial for economic growth, the Malaysian government's investment expenditure has not achieved the full potential of accelerating economic growth compared to South Korea.

Lessons learned from the hospital to home community care program in Singapore and the supporting AI multiple readmissions prediction model.

In a prior practice and policy article published in Healthcare Science, we introduced the deployed application of an artificial intelligence (AI) model to predict longer-term inpatient readmissions to guide community care interventions for patients with complex conditions in the context of Singapore's Hospital to Home (H2H) program that has been operating since 2017. In this follow on practice and policy article, we further elaborate on Singapore's H2H program and care model, and its supporting AI model for multiple readmission prediction, in the following ways: (1) by providing updates on the AI and supporting information systems, (2) by reporting on customer engagement and related service delivery outcomes including staff-related time savings and patient benefits in terms of bed days saved, (3) by sharing lessons learned with respect to (i) analytics challenges encountered due to the high degree of heterogeneity and resulting variability of the data set associated with the population of program participants, (ii) balancing competing needs for simpler and stable predictive models versus continuing to further enhance models and add yet more predictive variables, and (iii) the complications of continuing to make model changes when the AI part of the system is highly interlinked with supporting clinical information systems, (4) by highlighting how this H2H effort supported broader Covid-19 response efforts across Singapore's public healthcare system, and finally (5) by commenting on how the experiences and related capabilities acquired from running this H2H program and related community care model and supporting AI prediction model are expected to contribute to the next wave of Singapore's public healthcare efforts from 2023 onwards. For the convenience of the reader, some content that introduces the H2H program and the multiple readmissions AI prediction model that previously appeared in the prior Healthcare Science publication is repeated at the beginning of this article.

Nonlinear threshold approach for asymmetric effects of government size on economic growth in an emerging Asian economy: the Malaysian experience.

This paper discovers the asymmetric relation between government size and economic growth in Malaysia, an emerging Asian economy, by utilising a dynamic threshold nonlinear approach. The study finds empiric evidence that the threshold effect linking government size to economic growth in Malaysia exists when two different proxies of government size are set as the threshold variable. On closer inspection, it is found that an inverted U-shaped Armey curve is present when allowing for endogenous government size threshold proxied by government operating/real GDP. However, a U-shaped curve of nonlinear relationship exists instead when the government investment/real GDP serves as the threshold variable. In general, this paper gives policymakers a real insight into the optimal government size in Malaysia especially when designing an effectual fiscal policy to advance sustainable economic growth to materialise its Shared Prosperity Vision by the year 2030.

Two Singapore public healthcare AI applications for national screening programs and other examples.

This article explains how two AI systems have been incorporated into the everyday operations of two Singapore public healthcare nation-wide screening programs. The first example is embedded within the setting of a national level population health screening program for diabetes related eye diseases, targeting the rapidly increasing number of adults in the country with diabetes. In the second example, the AI assisted screening is done shortly after a person is admitted to one of the public hospitals to identify which inpatients-especially which elderly patients with complex conditions-have a high risk of being readmitted as an inpatient multiple times in the months following discharge. Ways in which healthcare needs and the clinical operations context influenced the approach to designing or deploying the AI systems are highlighted, illustrating the multiplicity of factors that shape the requirements for successful large-scale deployments of AI systems that are deeply embedded within clinical workflows. In the first example, the choice was made to use the system in a semi-automated (vs. fully automated) mode as this was assessed to be more cost-effective, though still offering substantial productivity improvement. In the second example, machine learning algorithm design and model execution trade-offs were made that prioritized key aspects of patient engagement and inclusion over higher levels of predictive accuracy. The article concludes with several lessons learned related to deploying AI systems within healthcare settings, and also lists several other AI efforts already in deployment and in the pipeline for Singapore's public healthcare system.

Chest radiograph-based artificial intelligence predictive model for mortality in community-acquired pneumonia.

BACKGROUND: Chest radiograph (CXR) is a basic diagnostic test in community-acquired pneumonia (CAP) with prognostic value. We developed a CXR-based artificial intelligence (AI) model (CAP AI predictive Engine: CAPE) and prospectively evaluated its discrimination for 30-day mortality. METHODS: Deep-learning model using convolutional neural network (CNN) was trained with a retrospective cohort of 2235 CXRs from 1966 unique adult patients admitted for CAP from 1 January 2019 to 31 December 2019. A single-centre prospective cohort between 11 May 2020 and 15 June 2020 was analysed for model performance. CAPE mortality risk score based on CNN analysis of the first CXR performed for CAP was used to determine the area under the receiver operating characteristic curve (AUC) for 30-day mortality. RESULTS: 315 inpatient episodes for CAP occurred, with 30-day mortality of 19.4% (n=61/315). Non-survivors were older than survivors (mean (SD)age, 80.4 (10.3) vs 69.2 (18.7)); more likely to have dementia (n=27/61 vs n=58/254) and malignancies (n=16/61 vs n=18/254); demonstrate higher serum C reactive protein (mean (SD), 109 mg/L (98.6) vs 59.3 mg/L (69.7)) and serum procalcitonin (mean (SD), 11.3 (27.8) µg/L vs 1.4 (5.9) µg/L). The AUC for CAPE mortality risk score for 30-day mortality was 0.79 (95% CI 0.73 to 0.85, p<0.001); Pneumonia Severity Index (PSI) 0.80 (95% CI 0.74 to 0.86, p<0.001); Confusion of new onset, blood Urea nitrogen, Respiratory rate, Blood pressure, 65 (CURB-65) score 0.76 (95% CI 0.70 to 0.81, p<0.001), respectively. CAPE combined with CURB-65 model has an AUC of 0.83 (95% CI 0.77 to 0.88, p<0.001). The best performing model was CAPE incorporated with PSI, with an AUC of 0.84 (95% CI 0.79 to 0.89, p<0.001). CONCLUSION: CXR-based CAPE mortality risk score was comparable to traditional pneumonia severity scores and improved its discrimination when combined.

Outcomes for emergency department patients with suspected and confirmed COVID-19: An analysis of the Australian experience in 2020 (COVED-5).

OBJECTIVE: The aim of the present study was to describe the characteristics and outcomes of patients presenting to Australian EDs with suspected and confirmed COVID-19 during 2020, and to determine the predictors of in-hospital death for SARS-CoV-2 positive patients. METHODS: This analysis from the COVED Project presents data from 12 sites across four Australian states for the period from 1 April to 30 November 2020. All adult patients who met local criteria for suspected COVID-19 and underwent testing for SARS-CoV-2 in the ED were eligible for inclusion. Study outcomes were mechanical ventilation and in-hospital mortality. RESULTS: Among 24 405 eligible ED presentations over the whole study period, 423 tested positive for SARS-CoV-2. During the 'second wave' from 1 July to 30 September 2020, 26 (6%) of 406 SARS-CoV-2 patients received invasive mechanical ventilation, compared to 175 (2%) of the 9024 SARS-CoV-2 negative patients (odds ratio [OR] 3.5; 95% confidence interval [CI] 2.3-5.2, P < 0.001), and 41 (10%) SARS-CoV-2 positive patients died in hospital compared to 312 (3%) SARS-CoV-2 negative patients (OR 3.2; 95% CI 2.2-4.4, P = 0.001). For SARS-CoV-2 positive patients, the strongest independent predictors of hospital death were age (OR 1.1; 95% CI 1.1-1.1, P < 0.001), higher triage category (OR 3.5; 95% CI 1.3-9.4, P = 0.012), obesity (OR 4.2; 95% CI 1.2-14.3, P = 0.024) and receiving immunosuppressive treatment (OR 8.2; 95% CI 1.8-36.7, P = 0.006). CONCLUSIONS: ED patients who tested positive for SARS-CoV-2 had higher odds of mechanical ventilation and death in hospital. The strongest predictors of death were age, a higher triage category, obesity and receiving immunosuppressive treatment.

Design and Multicenter Clinical Validation of a 3-Dimensionally Printed Nasopharyngeal Swab for SARS-CoV-2 Testing.

Importance: Three-dimensionally printed nasopharyngeal swabs (3DP swabs) have been used to mitigate swab shortages during the coronavirus disease 2019 (COVID-19) pandemic. Clinical validation for diagnostic accuracy and consistency, as well as patient acceptability, is crucial to evaluate the swab's performance. Objective: To determine the accuracy and acceptability of the 3DP swab for identifying severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Design, Setting, and Participants: A diagnostic study was conducted from May to July 2020 at 2 tertiary care centers in Singapore with different reference swabs (FLOQSwab [COPAN Diagnostics] or Dacron swab [Deltalab]) and swab processing techniques (wet or dry) to evaluate the performance of the 3DP swab compared with traditional, standard-of-care nasopharyngeal swabs used in health care institutions. The participants were patients with COVID-19 in the first 2 weeks of illness and controls with acute respiratory illness with negative test results for SARS-CoV-2. Paired nasopharyngeal swabs were obtained from the same nostril and tested for SARS-CoV-2 by reverse-transcriptase polymerase chain reaction. The sequence of swabs was randomized based on odd and even participant numbers. Main Outcomes and Measures: Primary outcome measures were overall agreement (OA), positive percentage agreement (PPA), and negative percentage agreement of the 3DP swab compared with reference swabs. Secondary outcome measures were the correlation of cycle threshold (Ct) values of both swabs. Results: The mean (SD) age of participants was 45.4 (13.1) years, and most participants were men (87 of 89 [97.8%]), in keeping with the epidemiology of the COVID-19 pandemic in Singapore. A total of 79 patients with COVID-19 and 10 controls were recruited. Among the patients with COVID-19, the overall agreement and PPA of the 3DP swab was 91.1% and 93.5%, respectively, compared with reference swabs. The PPA was 100% for patients with COVID-19 who were tested within the first week of illness. All controls tested negative. The reverse-transcriptase polymerase chain reaction Ct values for the ORF1ab and E-gene targets showed a strong correlation (intraclass correlations coefficient, 0.869-0.920) between the 3DP and reference swab on independent testing at each institution despite differences in sample processing. Discordant results for both gene targets were observed only at high Ct values. Conclusions and Relevance: In this diagnostic study of 79 patients with COVID-19 and 10 controls, the 3DP swab performed accurately and consistently across health care institutions and could help mitigate strained resources in the escalating COVID-19 pandemic.

Clinical Diagnostic Study of a Novel Injection Molded Swab for SARS-Cov-2 Testing.

INTRODUCTION: The gold standard for COVID-19 diagnosis is currently a real-time reverse transcriptase polymerase chain reaction (RT-PCR) to detect SARS-CoV-2. This is most commonly performed on respiratory secretions obtained via a nasopharyngeal swab. Due to supply chain limitations and high demand worldwide because of the COVID-19 pandemic, access to commercial nasopharyngeal swabs has not been assured. 3D printing methods have been used to meet the shortfall. For longer-term considerations, 3D printing may not compare well with injection molding as a production method due to the challenging scalability and greater production costs of 3D printing. METHODS: To secure sufficient nasopharyngeal swab availability for our national healthcare system, we designed a novel injection molded nasopharyngeal swab (the IM2 swab). We performed a clinical diagnostic study comparing the IM2 swab to the Copan FLOQSwab. Forty patients with a known diagnosis of COVID-19 and 10 healthy controls were recruited. Paired nasopharyngeal swabs were obtained from the same nostril of each participant and tested for SARS-CoV-2 by RT-PCR. RESULTS: When compared to the Copan FLOQswab, results from the IM2 swab displayed excellent overall agreement and positive percent agreement of 96.0% and 94.9%, respectively. There was no significant difference in mean RT-PCR cycle threshold values for the ORF1ab (28.05 vs. 28.03, p = 0.97) and E-gene (29.72 vs. 29.37, p = 0.64) targets, respectively. We did not observe any significant adverse events and there was no significant difference in patient-reported pain. CONCLUSION: In summary, the IM2 nasopharyngeal swab is a clinically safe, highly accurate option to commercial nasopharyngeal swabs.

Apoptotic and cytostatic actions of maslinic acid in colorectal cancer cells through possible IKK-β inhibition

Objective: To explore the anti-cancer activity of maslinic acid against colorectal cancer (CRC) cell lines and its possible mechanism. Methods: The inhibitory effect of maslinic acid was screened against five CRC cell lines (HT-29, HCT 116, SW480, SW48, and LS 174T) via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Apoptosis and cell cycle analyses were carried out using annexin Ⅴ-FITC/propidium iodide staining and propidium iodide staining, respectively and subjected to fluorescence-activated cell sorting analysis. Protein expression studies of inhibitor of κB kinase-β (IKK-β), checkpoint kinase 1 (Chk1) and cyclin D1 were conducted using the JESS system. Results: Maslinic acid exhibited growth inhibitory effect in a dose- and time-dependent manner in HT-29 and HCT 116 cell lines. A more prominent apoptosis induced by maslinic acid was observed in HCT 116 cell line. However, in HT-29 cell line, maslinic acid induced cell cycle arrest by inhibiting the G1-S transition, which was accompanied by the downregulation of cyclin D1. The expression of unphosphorylated IKK-β protein was increased in both (HT-29 and HCT 116) cell lines after maslinic acid treatment. Conclusions: Maslinic acid inhibits the growth of HT-29 and HCT 116 cells in a different manner, induces cell cycle arrest in HT-29 cells and causes apoptosis in HCT 116 cells partially via NF-κB pathway inhibition.

A comparison of EBV serology and serum cell-free DNA as screening tools for nasopharyngeal cancer: Results of the Singapore NPC screening cohort.

We aimed to evaluate the effectiveness of nasopharyngeal cancer (NPC) screening by comprehensive clinical follow-up and adjunctive Epstein-Barr virus (EBV) testing. In a prospective cohort study, 524 individuals with a first-degree family history of NPC were recruited at a university clinical center in Singapore. The cohort was evaluated at baseline and at 6 monthly intervals, with a complete head and neck examination including nasopharyngeal endoscopy. Blood was taken at baseline and at yearly intervals for EBV Viral Capsid Antigen (VCA) IgA, EBV Early Antigen (EA) IgA serology and serum cell-free EBV DNA. Nasopharyngeal biopsy was performed when any irregularity in the nasopharynx was observed, or when EBV markers were elevated. The mean duration of follow-up was 57.7 months, with an average of 8.6 clinical visits per participant. Five participants (0.96%) were identified to have NPC, giving a prevalence of 199 per 100,000 person-years of screening. Four of the five NPC cases identified had asymptomatic T1 disease, at an earlier stage compared to NPC patients diagnosed in the clinic during the same time period (p = 0.0297). All NPC cases identified had elevated EBV-EA IgA titers ≥1:10, with a specificity of 94.6% and a positive predictive value of 15.2%, outperforming EBV-VCA IgA and serum EBV DNA. Two NPC cases were biopsied only because of elevated EBV serology titers, with increasing EBV-EA IgA titers preceding the diagnosis of NPC. In conclusion, screening for NPC is effective in identifying early-stage disease. Adjunctive EBV-EA IgA testing improved the effectiveness of screening.

Time course and clinical characterization of cisplatin-induced ototoxicity after treatment for nasopharyngeal carcinoma in a South East Asian population.

BACKGROUND: The purpose of this study was to characterize the clinical course of hearing loss in patients with nasopharyngeal carcinoma (NPC) and the clinical factors affecting its severity. METHODS: The time course of hearing loss in patients with NPC was assessed using threshold shift from baseline and Common Terminology Criteria for Adverse Events (CTCAE) grade. RESULTS: In the chemoradiotherapy (CRT) groups, the threshold shift was significantly higher from 3 months at 4 kHz (P = 2.30 × 10-9 , concurrent CRT only) but not within 2 years posttreatment in the radiotherapy (RT) group. The CRT groups had worse CTCAE grades than the RT group (percentage of latest CTCAE grade ≥1: 64.9% vs 29.0%, respectively). Cumulative cisplatin dose and cochlear RT dose significantly affects threshold shifts, especially at high frequencies. CONCLUSION: Although cisplatin led to high frequency hearing impairment from about 3 months posttreatment, RT conferred no significant hearing impairment in the first 2 years.

The Role of Epstein-Barr Virus DNA Load and Serology as Screening Tools for Nasopharyngeal Carcinoma.

OBJECTIVE: Screening for nasopharyngeal carcinoma (NPC) among family members has been advocated in endemic populations in view of significantly increased risks. We aimed to compare the role of Epstein-Barr virus (EBV) DNA load and EBV IgA serology as tools for screening patients with a first-degree family history of NPC. STUDY DESIGN: Case-control study. SETTING: Tertiary referral center. SUBJECTS AND METHODS: Serum samples were compared from 293 newly diagnosed NPC patients and 475 individuals with a first-degree family history of NPC. EBV DNA load was measured by real-time quantitative polymerase chain reaction, while EBV viral capsid antigen (VCA) IgA and EBV early antigen (EA) IgA titers were measured by immunofluorescence assays. RESULTS: NPC patients had a significantly higher median EBV DNA load as compared with unaffected family members (835.4 vs 18.8 copies/mL; P < .001). At 100 copies/mL, EBV DNA load demonstrated a sensitivity of 76.8% and a specificity of 85.6%. A positive EBV-EA IgA titer (≥1:10) gave a sensitivity of 85.0% and a specificity of 96.4%. There was good correlation between EBV DNA load and EBV serology titers (Spearman's ρ = .536 and .594 for EBV-VCA IgA and EBV-EA IgA, respectively; P < .001). Receiver operating characteristic analysis demonstrated that EBV-VCA IgA and EBV-EA IgA were better classifiers than EBV DNA load (areas under the curve: 0.942, 0.926, and 0.880, respectively) in distinguishing NPC patients and unaffected family members. CONCLUSION: EBV DNA load and EBV IgA serology demonstrate good sensitivity and specificity as screening tools. EBV-EA IgA gave the best sensitivity and specificity profile as a screening tool for NPC among high-risk family members.

Baseline measurement of running away among youth in foster care.

The current study evaluated the use of various behavioral measures of running away with regard to (a) the differential utility of interval- versus event-based measures, (b) the differential utility of rate versus duration measures, (c) the utility of correcting for occurrence opportunity, and (d) the influence of unit of analysis (i.e., single-subject vs. grouped data). Seven different baseline measures were calculated for 84 runaways, and a unit-size analysis was conducted by constructing groups of various sizes from the original sample. An expert panel evaluated the suitability of the baseline measures for treatment evaluation. Results demonstrate the utility of evaluating duration-based measures and correcting for occurrence opportunity. Results also indicate that single-subject baselines may often be unacceptable for treatment evaluations, regardless of the type of measure selected for use.

An evaluation of simultaneous and sequential presentation of preferred and nonpreferred food to treat food selectivity.

In the current investigation, we compared two methods of food presentation (simultaneous vs. sequential) to increase consumption of nonpreferred food for 3 children with food selectivity. In the simultaneous condition, preferred foods were presented at the same time as nonpreferred food (e.g., a piece of broccoli was presented on a chip). In the sequential condition, acceptance of the nonpreferred food resulted in presentation of the preferred food. Increases in consumption occurred immediately during the simultaneous condition for 2 of the 3 participants. For 1 participant, increases in consumption occurred in the simultaneous condition relative to the sequential condition, but only after physical guidance and re-presentation were added to treatment. Finally, consumption increased for 1 participant in the sequential condition, but only after several sessions. These results are discussed in terms of possible mechanisms that may alter preferences for food (i.e., establishing operations, flavor-flavor conditioning).