David Michael Allen
Email Address
mdcdma@nus.edu.sg
Organizational Units
MEDICINE
dept
YONG LOO LIN SCH OF MEDICINE
faculty
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Publication Central nervous system histoplasmosis(Ovid Technologies (Wolters Kluwer Health), 2018-03-01) Myint, T; Guo, Y; Kemmer, P; Hage, C; Terry, C; Azar, MM; Riddell, J; Ender, P; Chen, S; Shehab, K; Cleveland, K; Esguerra, E; Johnson, J; Wright, P; Douglas, V; Vergidis, P; Ooi, W; Baddley, J; Bamberger, D; Khairy, R; Vikram, H; Jenny-Avital, E; Sivasubramanian, G; Bowlware, K; Pahud, B; Sarria, J; Tsai, T; Assi, M; Mocherla, S; Prakash, V; Allen, D; Passaretti, C; Huprikar, S; Anderson, A; Dr David Michael Allen; MEDICINE© 2018 the Author(s). Published by Wolters Kluwer Health, Inc. Central nervous system (CNS) involvement occurs in 5 to 10% of individuals with disseminated histoplasmosis. Most experience has been derived from small single center case series, or case report literature reviews. Therefore, a larger study of central nervous system (CNS) histoplasmosis is needed in order to guide the approach to diagnosis, and treatment. A convenience sample of 77 patients with histoplasmosis infection of the CNS was evaluated. Data was collected that focused on recognition of infection, diagnostic techniques, and outcomes of treatment. Twenty nine percent of patients were not immunosuppressed. Histoplasma antigen, or anti-Histoplasma antibodies were detected in the cerebrospinal fluid (CSF) in 75% of patients. One year survival was 75% among patients treated initially with amphotericin B, and was highest with liposomal, or deoxycholate formulations. Mortality was higher in immunocompromised patients, and patients 54 years of age, or older. Six percent of patients relapsed, all of whom had the acquired immunodeficiency syndrome (AIDS), and were poorly adherent with treatment. While CNS histoplasmosis occurred most often in immunocompromised individuals, a significant proportion of patients were previously, healthy. The diagnosis can be established by antigen, and antibody testing of the CSF, and serum, and antigen testing of the urine in most patients. Treatment with liposomal amphotericin B (AMB-L) for at least 1 month; followed by itraconazole for at least 1 year, results in survival among the majority of individuals. Patients should be followed for relapse for at least 1 year, after stopping therapy.Publication Evaluating the onset, severity, and recovery of changes to smell and taste associated with covid-19 infection in a singaporean population (the covosmia-19 trial): Protocol for a prospective case-control study(JMIR Publications Inc., 2020-12-01) Sheen, F; Tan, V; Lim, AJY; Haldar, S; Sengupta, S; Allen, D; Somani, J; Chen, HY; Tambyah, P; Forde, CG; Assoc Prof David Michael Allen; MEDICINEBackground: Sudden loss of smell and/or taste has been suggested to be an early marker of COVID-19 infection, with most findings based on self-reporting of sensory changes at a single time point. Objective: To understand the onset, severity, and recovery of sensory changes associated with COVID-19 infection, this study will longitudinally track changes in chemosensory acuity among people with suspected COVID-19 infection using standardized test stimuli that are self-administered over 28 days. Methods: In a prospective, case-controlled observational study, volunteers will be recruited when they present for COVID-19 screening by respiratory tract polymerase chain reaction test (“swab test”). The volunteers will initially complete a series of questionnaires to record their recent changes in smell and taste ability, followed by a brief standardized smell and taste test. Participants will receive a home-use smell and taste test kit to prospectively complete daily self-assessments of their smell and taste acuity at their place of residence for up to 4 weeks, with all data submitted for collection through web-based software. Results: This study has been approved by the Domain Specific Review Board of the National Healthcare Group, Singapore, and is funded by the Biomedical Research Council Singapore COVID-19 Research Fund. Recruitment began on July 23, 2020, and will continue through to March 31, 2021. As of October 2, 2020, 69 participants had been recruited. Conclusions: To our knowledge, this study will be the first to collect longitudinal data on changes to smell and taste sensitivity related to clinically diagnosed COVID-19 infection, confirmed by PCR swab test, in a population-based cohort. The findings will provide temporal insights on the onset, severity, and recovery of sensory changes with COVID-19 infection, the consistency of symptoms, and the frequency of full smell recovery among patients with COVID-19. This self-administered and cost-effective approach has many advantages over self-report questionnaire-based methods and provides a more objective measure of smell and taste changes associated with COVID-19 infection; this will encourage otherwise asymptomatic individuals who are potential spreaders of the virus to self-isolate and seek formal medical diagnosis if they experience a sudden change in sensory acuity. This broadened case finding can potentially help control the COVID-19 pandemic and reduce the emergence of clusters of infections.Publication Clinical Diagnostic Study of a Novel Injection Molded Swab for SARS-Cov-2 Testing(SPRINGER LONDON LTD, 2021-01-11) Tay, Joshua K; Cross, Gail B; Sun, Louisa; Chia, Alfred; Chee, Jeremy; Loh, Jerold; Lim, Zhenyu; Ngiam, Nicholas; Khang, WenPang; Yeap, Stephanie; Goh, Han Lee; Siow, Chor Hiang; Loh, WoeiShyang; Loh, KwokSeng; Lee, ChunKiat; Yan, Benedict; Chow, Vincent TK; Wang, De Yun; Boey, Freddy; Wong, John EL; Allen, David M; Assoc Prof David Michael Allen; BIOMEDICAL ENGINEERING; MEDICINE; MICROBIOLOGY AND IMMUNOLOGY; OTOLARYNGOLOGYIntroduction: 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.Publication IDentif.AI-Omicron: Harnessing an AI-Derived and Disease-Agnostic Platform to Pinpoint Combinatorial Therapies for Clinically Actionable Anti-SARS-CoV-2 Intervention(AMER CHEMICAL SOC, 2022-08-17) Blasiak, Agata; Truong, Anh TL; Wang, Peter; Hooi, Lissa; Chye, De Hoe; Tan, Shi-Bei; You, Kui; Remus, Alexandria; Allen, David Michael; Chai, Louis Yi Ann; Chan, Conrad EZ; Lye, David CB; Tan, Gek-Yen G; Seah, Shirley GK; Chow, Edward Kai-Hua; Ho, Dean; Assoc Prof David Michael Allen; PHARMACOLOGY; BIOMEDICAL ENGINEERING; MEDICINE; LIFE SCIENCES INSTITUTE; CANCER SCIENCE INSTITUTE OF SINGAPORENanomedicine-based and unmodified drug interventions to address COVID-19 have evolved over the course of the pandemic as more information is gleaned and virus variants continue to emerge. For example, some early therapies (e.g., antibodies) have experienced markedly decreased efficacy. Due to a growing concern of future drug resistant variants, current drug development strategies are seeking to find effective drug combinations. In this study, we used IDentif.AI, an artificial intelligence-derived platform, to investigate the drug-drug and drug-dose interaction space of six promising experimental or currently deployed therapies at various concentrations: EIDD-1931, YH-53, nirmatrelvir, AT-511, favipiravir, and auranofin. The drugs were tested in vitro against a live B.1.1.529 (Omicron) virus first in monotherapy and then in 50 strategic combinations designed to interrogate the interaction space of 729 possible combinations. Key findings and interactions were then further explored and validated in an additional experimental round using an expanded concentration range. Overall, we found that few of the tested drugs showed moderate efficacy as monotherapies in the actionable concentration range, but combinatorial drug testing revealed significant dose-dependent drug-drug interactions, specifically between EIDD-1931 and YH-53, as well as nirmatrelvir and YH-53. Checkerboard validation analysis confirmed these synergistic interactions and also identified an interaction between EIDD-1931 and favipiravir in an expanded range. Based on the platform nature of IDentif.AI, these findings may support further explorations of the dose-dependent drug interactions between different drug classes in further pre-clinical and clinical trials as possible combinatorial therapies consisting of unmodified and nanomedicine-enabled drugs, to combat current and future COVID-19 strains and other emerging pathogens.Publication Detection of hospital environmental contamination during SARS-CoV-2 Omicron predominance using a highly sensitive air sampling device(Frontiers Media SA, 2023-01-10) Tan, Kai Sen; Ang, Alicia Xin Yu; Tay, Douglas Jie Wen; Somani, Jyoti; Ng, Alexander Jet Yue; Peng, Li Lee; Chu, Justin Jang Hann; Tambyah, Paul Anantharajah; Allen, David Michael; Assoc Prof David Michael Allen; MEDICINE; SURGERY; MICROBIOLOGY AND IMMUNOLOGYBackground and objectivesThe high transmissibility of SARS-CoV-2 has exposed weaknesses in our infection control and detection measures, particularly in healthcare settings. Aerial sampling has evolved from passive impact filters to active sampling using negative pressure to expose culture substrate for virus detection. We evaluated the effectiveness of an active air sampling device as a potential surveillance system in detecting hospital pathogens, for augmenting containment measures to prevent nosocomial transmission, using SARS-CoV-2 as a surrogate.MethodsWe conducted air sampling in a hospital environment using the AerosolSenseTM air sampling device and compared it with surface swabs for their capacity to detect SARS-CoV-2.ResultsWhen combined with RT-qPCR detection, we found the device provided consistent SARS-CoV-2 detection, compared to surface sampling, in as little as 2 h of sampling time. The device also showed that it can identify minute quantities of SARS-CoV-2 in designated “clean areas” and through a N95 mask, indicating good surveillance capacity and sensitivity of the device in hospital settings.ConclusionActive air sampling was shown to be a sensitive surveillance system in healthcare settings. Findings from this study can also be applied in an organism agnostic manner for surveillance in the hospital, improving our ability to contain and prevent nosocomial outbreaks.Publication Responding to COVID-19: How an academic infectious diseases division mobilized in Singapore(BioMed Central Ltd, 2020) Archuleta, S.; Cross, G.; Somani, J.; Lum, L.; Santosa, A.; Alagha, R.A.; Allen, D.M.; Ang, A.; Beh, D.; Chai, L.; Chan, S.M.; Lim, S.M.; Olszyna, D.P.; Ong, C.; Oon, J.; Salada, B.M.A.; Smitasin, N.; Sun, L.; Tambyah, P.A.; Tham, S.M.; Yan, G.; Yee, C.H.; Dan, Yock Young; Jureen, R.; Tee, N.; Mahadevan, M.; Yau, Y.W.; Quek, S.C.; Liu, Eugene H.; Sin, C.; Bagdasarian, Natasha; Fisher, D.A.; MEDICINE; SURGERY; ANAESTHESIA; PAEDIATRICS; PATHOLOGYBackground: On January 30, COVID-19 was declared a Public Health Emergency of International Concern - a week after Singapore's first imported case and 5 days before local transmission. The National University Hospital (NUH) is Singapore's third largest hospital with 1200 beds, heavy clinical workloads, and major roles in research and teaching. Main body: With memories of SARS still vivid, there was an urgent requirement for the NUH Division of Infectious Diseases to adapt - undergoing major reorganization to face rapidly changing priorities while ensuring usual essential services and standards. Leveraging on individual strengths, our division mobilized to meet the demands of COVID-19 while engaging in high-level coordination, strategy, and advocacy. We present our experience of the 60 days since the nation's first case. During this time, our hospital has managed 3030 suspect cases, including 1300 inpatients, 37 confirmed cases, and overseen 4384 samples tested for COVID-19. Conclusion: Complex hospital adaptations were supported by an unprecedented number of workflows and coordination channels essential to safe and effective operations. The actions we describe, aligned with international recommendations and emerging evidence-based best practices, may serve as a framework for other divisions and institutions facing the spread of COVID-19 globally. � 2020 The Author(s).Publication The IDentif.AI-x pandemic readiness platform: Rapid prioritization of optimized COVID-19 combination therapy regimens.(Springer Science and Business Media LLC, 2022-06-30) Blasiak, Agata; Truong, Anh TL; Remus, Alexandria; Hooi, Lissa; Seah, Shirley Gek Kheng; Wang, Peter; Chye, De Hoe; Lim, Angeline Pei Chiew; Ng, Kim Tien; Teo, Swee Teng; Tan, Yee-Joo; Allen, David Michael; Chai, Louis Yi Ann; Chng, Wee Joo; Lin, Raymond TP; Lye, David CB; Wong, John Eu-Li; Tan, Gek-Yen Gladys; Chan, Conrad En Zuo; Chow, Edward Kai-Hua; Ho, Dean; Assoc Prof David Michael Allen; PHARMACOLOGY; DEAN'S OFFICE (MEDICINE); MEDICINE; MICROBIOLOGY AND IMMUNOLOGY; LIFE SCIENCES INSTITUTE; CANCER SCIENCE INSTITUTE OF SINGAPORE; COLLEGE OF DESIGN AND ENGINEERING; OFFICE OF THE SR DY PRESIDENT & PROVOSTIDentif.AI-x, a clinically actionable artificial intelligence platform, was used to rapidly pinpoint and prioritize optimal combination therapies against COVID-19 by pairing a prospective, experimental validation of multi-drug efficacy on a SARS-CoV-2 live virus and Vero E6 assay with a quadratic optimization workflow. A starting pool of 12 candidate drugs developed in collaboration with a community of infectious disease clinicians was first narrowed down to a six-drug pool and then interrogated in 50 combination regimens at three dosing levels per drug, representing 729 possible combinations. IDentif.AI-x revealed EIDD-1931 to be a strong candidate upon which multiple drug combinations can be derived, and pinpointed a number of clinically actionable drug interactions, which were further reconfirmed in SARS-CoV-2 variants B.1.351 (Beta) and B.1.617.2 (Delta). IDentif.AI-x prioritized promising drug combinations for clinical translation and can be immediately adjusted and re-executed with a new pool of promising therapies in an actionable path towards rapidly optimizing combination therapy following pandemic emergence.Publication Evaluating the Onset, Severity, and Recovery of Changes to Smell and Taste Associated With COVID-19 Infection in a Singaporean Population (the COVOSMIA-19 Trial): Protocol for a Prospective Case-Control Study (Preprint)(2020) Sheen, Florence; Tan, Vicki; Haldar, Sumanto; Sengupta, Sharmila; Allen, David; Somani, Jyoti; Chen, Hui Yee; Tambyah, Paul; Forde, Ciaran G; Assoc Prof David Michael Allen; MEDICINEBACKGROUNDSudden loss of smell and/or taste has been suggested to be an early marker of COVID-19 infection, with most findings based on self-reporting of sensory changes at a single time point.
OBJECTIVETo understand the onset, severity, and recovery of sensory changes associated with COVID-19 infection, this study will longitudinally track changes in chemosensory acuity among people with suspected COVID-19 infection using standardized test stimuli that are self-administered over 28 days.
METHODSIn a prospective, case-controlled observational study, volunteers will be recruited when they present for COVID-19 screening by respiratory tract polymerase chain reaction test (“swab test”). The volunteers will initially complete a series of questionnaires to record their recent changes in smell and taste ability, followed by a brief standardized smell and taste test. Participants will receive a home-use smell and taste test kit to prospectively complete daily self-assessments of their smell and taste acuity at their place of residence for up to 4 weeks, with all data submitted for collection through web-based software.
RESULTSThis study has been approved by the Domain Specific Review Board of the National Healthcare Group, Singapore, and is funded by the Biomedical Research Council Singapore COVID-19 Research Fund. Recruitment began on July 23, 2020, and will continue through to March 31, 2021. As of October 2, 2020, 69 participants had been recruited.
CONCLUSIONSTo our knowledge, this study will be the first to collect longitudinal data on changes to smell and taste sensitivity related to clinically diagnosed COVID-19 infection, confirmed by PCR swab test, in a population-based cohort. The findings will provide temporal insights on the onset, severity, and recovery of sensory changes with COVID-19 infection, the consistency of symptoms, and the frequency of full smell recovery among patients with COVID-19. This self-administered and cost-effective approach has many advantages over self-report questionnaire–based methods and provides a more objective measure of smell and taste changes associated with COVID-19 infection; this will encourage otherwise asymptomatic individuals who are potential spreaders of the virus to self-isolate and seek formal medical diagnosis if they experience a sudden change in sensory acuity. This broadened case finding can potentially help control the COVID-19 pandemic and reduce the emergence of clusters of infections.
CLINICALTRIALClinicalTrials.gov NCT04492904; https://clinicaltrials.gov/ct2/show/NCT04492904.
INTERNATIONAL REGISTERED REPORTDERR1-10.2196/24797
Publication The COVOSMIA-19 trial: Preliminary application of the Singapore smell and taste test to objectively measure smell and taste function with COVID-19(Elsevier BV, 2022-04-01) Sheen, F; Tan, V; Lim, AJY; Haldar, S; Sengupta, S; Allen, D; Somani, J; Chen, HY; Tambyah, P; Forde, CG; Assoc Prof David Michael Allen; MEDICINE; PHYSIOLOGYSudden loss of smell and/or taste has been identified as an early symptom of SARS-CoV-2 2019 (COVID-19) infection, and presents an effective target for prompt self-isolation and reducing community spread. The current study sought to develop and test a novel, rapid, self-administered test to objectively measure smell and taste losses associated with COVID-19, and administered self-report questionnaires to characterise symptoms associated with COVID-19 in Singapore. Participants (N = 99) completed questionnaires to record recent changes in smell and taste ability. This was followed by the ‘Singapore Smell and Taste Test’ (SSTT), a personal, objective testing kit for daily self-assessment of smell and taste function at their place of residence. Seventy-two recruited participants were confirmed as COVID-19 positive at baseline, of which 58 completed the SSTT at home. Of these, 36.2% had objectively measured smell and/or taste loss. The SSTT measures of smell and taste function were positively associated with participants’ self-reported smell and taste acuity, and rated smell intensity of 6 common household items. This study presents the first application of the SSTT as a rapid, cost-effective, objective tool to self-monitor smell and taste function in a residential setting, and ensures comparability across individuals through the use of standardised stimuli. The SSTT has potential for future application in populations with limited access to formal COVID-19 testing as a self-administered objective method to monitor sudden changes in smell and taste, and to prompt early self-isolation, in order to reduce community transmission of COVID-19.Publication Computed tomography in suspected bacteria meningitis(Singapore Medical Association, 1990) Allen, David Michael; Assoc Prof David Michael Allen; MEDICINE