Financial burden and financial aid for medical students in Singapore: a national survey across all three medical schools.

INTRODUCTION: Singapore has had three medical schools since 2013. We undertook a cross-sectional quantitative national survey to determine the financial impact of medical education on medical students in Singapore. METHODS: All 1,829 medical students in Singapore were invited to participate in this study. Information on demographics, financial aid utilisation and outside work was collected and analysed. RESULTS: 1,241 (67.9%) of 1,829 students participated in the survey. While the overall proportion of students from households with monthly incomes < SGD 3,000 was only 21.2% compared to the national figure of 31.4%, 85.4% of medical students expected to graduate with debts > SGD 75,000. There were significant differences in per capita incomes among the schools, with 54.5%, 23.3% and 7.8% of Duke-NUS Medical School (Duke-NUS), NUS Yong Loo Lin School of Medicine (NUS Medicine) and Lee Kong Chian School of Medicine (LKCMedicine) students, respectively, reporting a per capita income of < SGD 1,000 (p < 0.001). There were significant differences in financial support: 75.0%, 34.1% and 38.8% of Duke-NUS, NUS Medicine and LKCMedicine students, respectively, received financial aid (p < 0.001). The top reasons for not applying for aid included a troublesome application process (21.4%) and the perception that it would be too difficult to obtain (21.0%). CONCLUSION: Students in the three medical schools in Singapore differ in their financial needs and levels of financial support received. A national approach to funding medical education may be needed to ensure that financial burdens do not hamper the optimal training of doctors for Singapore's future.

Review of the role of gastrointestinal multiplex polymerase chain reaction in the management of diarrheal illness.

Acute and chronic diarrheal illness secondary to gastrointestinal infection is a significant cause of morbidity and mortality around the world. A cornerstone of management includes prompt diagnosis and appropriate treatment of culprit pathogens. Timely diagnosis can improve patient care, assist in infection control, and prevent disease outbreaks. Historical methods of diagnosis include traditional culture methods and stool analysis. These are limited by long turnaround time and inability to simultaneously assess multiple pathogens. The advent of multiplexed nucleic acid amplification tests first began with the Food and Drug Administration-approved respiratory virus multiplex polymerase chain reaction (PCR) panel in 2009, followed by gastrointestinal infections in 2013, and neurological infections in 2014. We conducted a review of current literature pertaining to the clinical utility of a gastrointestinal multiplex PCR in management of acute and chronic diarrhea in patients. To date, seven platforms approved by the US Food and Drug Administration are used in detection of various bacterial, viral, and parasitic causative organisms for diagnosis of gastrointestinal infections. The sensitivity and specificity of each assay vary depending on the tested organism. Interpretation of a positive result has to be tailored to the clinical context. Further studies are required to establish the utility of gastrointestinal multiplex PCR from a cost-based perspective, whether specific enteropathogens such as Clostridioides difficile are better assessed with toxin gene detection and whether new parameters such as cycle threshold values can improve clinical application of test results.

A rapid simple point-of-care assay for the detection of SARS-CoV-2 neutralizing antibodies.

Background: Neutralizing antibodies (NAbs) prevent pathogens from infecting host cells. Detection of SARS-CoV-2 NAbs is critical to evaluate herd immunity and monitor vaccine efficacy against SARS-CoV-2, the virus that causes COVID-19. All currently available NAb tests are lab-based and time-intensive. Method: We develop a 10 min cellulose pull-down test to detect NAbs against SARS-CoV-2 from human plasma. The test evaluates the ability of antibodies to disrupt ACE2 receptor-RBD complex formation. The simple, portable, and rapid testing process relies on two key technologies: (i) the vertical-flow paper-based assay format and (ii) the rapid interaction of cellulose binding domain to cellulose paper. Results: Here we show the construction of a cellulose-based vertical-flow test. The developed test gives above 80% sensitivity and specificity and up to 93% accuracy as compared to two current lab-based methods using COVID-19 convalescent plasma. Conclusions: A rapid 10 min cellulose based test has been developed for detection of NAb against SARS-CoV-2. The test demonstrates comparable performance to the lab-based tests and can be used at Point-of-Care. Importantly, the approach used for this test can be easily extended to test RBD variants or to evaluate NAbs against other pathogens.

Persistent Dengue Infection in an Immunosuppressed Patient Reveals the Roles of Humoral and Cellular Immune Responses in Virus Clearance.

Detailed understanding of the roles of humoral and cellular immune responses in sterilizing dengue virus (DENV) infection in humans is required to inform effective vaccine development. We report an unusual case of persistent DENV infection in a lymphopenic renal transplant recipient who was therapeutically immunosuppressed to prevent organ rejection. Following resolution of symptomatic dengue, this patient remained positive for DENV3 RNA in the blood for 4 months and viruric up to 9 months post-infection despite demonstrable levels of serum neutralizing antibodies throughout this period. Full resolution of DENV infection instead coincided with recovery of CD8+ T cell counts during reversal from lymphopenia. Taken collectively, our observations suggest a role for cellular immunity in sterilizing DENV infection in humans. Any dengue vaccine should thus be able to induce both humoral and cellular immunity that respectively prevent symptomatic infection and enable effective viral clearance.

Impact of financial background and student debt on postgraduate residency choices of medical students in Singapore.

INTRODUCTION: Medical school fees are rising globally. Student debt and financial background may affect residency choices, but few studies have been conducted in Asia. This study aimed to explore the relationship between financial background, student debt and postgraduate residency choices among medical students in Singapore. METHODS: An anonymised survey of all medical students in Singapore was conducted and had a response rate of 67.9%. RESULTS: 40.5% of our study population would graduate with debt. Medical students with monthly per capita household income < SGD 1,000 were more likely to graduate with debt (unadjusted odds ratio [OR] 2.0, 95% confidence interval [CI] 1.6-2.7; p < 0.001) and feel burdened by the cost of medical education (unadjusted OR 2.8, 95% CI 2.0-3.9; p < 0.001). Students with monthly per capita household income < SGD 1,000 (unadjusted OR 1.818, 95% CI 1.338-2.470, p < 0.001; adjusted OR 1.692, 95% CI 1.202-2.381, p = 0.003) and those with debt (unadjusted OR 1.623, 95% CI 1.261-2.090, p < 0.001; adjusted OR 1.393, 95% CI 1.048-1.851, p = 0.022) were more likely to rank at least one economic factor as 'very significant' in influencing their postgraduate training choices. CONCLUSION: It is concerning that despite financial aid schemes, the cost of medical education remains a burden to students from lower-income households in Singapore. Student debt and financial background may distort postgraduate career choices, creating an undue push towards high-paying specialties.

Neurology of the H1N1 pandemic in Singapore: a nationwide case series of children and adults.

Neurologic complications have long been associated with influenza. A novel strain of influenza A (H1N1) first described in humans to have outbreak potential in 2009 in Mexico went on to become the first influenza pandemic of this century. We evaluated the neurologic complications of the novel influenza A (H1N1) 2009 in children and adults admitted to all public hospitals in Singapore during the influenza A (H1N1) 2009 pandemic between May 2009 and March 2010. All patients were positive for novel H1N1 infection and presented with neurologic symptoms prior to oseltamivir treatment. Ninety-eight patients (median age 6.6 years, range 0.4-62.6) were identified; 90 % were younger than 18 years; 32 % suffered from preexisting neurological, respiratory, or cardiac disease; and 66 % presented with seizures. Of those presenting with seizures, new onset seizures were the most common manifestation (n = 40, 61.5 %), followed by breakthrough seizures (n = 18, 27.7 %) and status epilepticus (n = 7, 10.8 %). Influenza-associated encephalopathy occurred in 20 %. The majority of children (n = 88) presented with seizures (n = 63, 71.6 %), encephalopathy (n = 19, 21.6 %), and syncope (n = 4, 4.5 %). Among adults, a wider range of neurological conditions were seen, with half of them presenting with an exacerbation of their underlying neurological disease. The neurological symptoms developed at a median of 2 days after the onset of systemic symptoms. The median length of hospital stay was 3 days, and 79 % were monitored in general wards. Neurologic complications associated with the novel influenza A (H1N1) 2009 strain were generally mild and had a good outcome. They occurred more frequently in patients with underlying neurological disorders. Seizures and encephalopathy were the most common manifestations, similar to other influenza virus strains.

The costs of nosocomial resistant gram negative intensive care unit infections among patients with the systemic inflammatory response syndrome- a propensity matched case control study.

BACKGROUND: Infections due to multi-drug resistant gram negative bacilli (RGNB) in critically ill patients have been reported to be associated with increased morbidity and costs and only a few studies have been done in Asia. We examined the financial impact of nosocomial RGNB infections among critically ill patients in Singapore. METHODS: A nested case control study was done for patients at medical and surgical ICUs of a tertiary university hospital (August 2007-December 2011) matched by propensity scores. Two groups of propensity-matched controls were selected for each case patient with nosocomial drug resistant gram negative infection: at-risk patients with no gram negative infection or colonization (Control A) and patients with ICU acquired susceptible gram negative infection (SGNB) (Control B). The costs of the hospital stay, laboratory tests and antibiotics prescribed as well as length of stay were compared using the Wilcoxon matched-pairs signed rank test. RESULTS: Of the 1539 patients included in the analysis, 76 and 65 patients had ICU acquired RGNB and SGNB infection respectively. The median(range) total hospital bill per day for patients with RGNB infection was 1.5 times higher than at-risk patients without GNB infection [Singapore dollars 2637.8 (458.7-20610.3) vs. 1757.4 (179.9-6107.4), p0.0001]. The same trend was observed when compared with SGNB infected patients. The median costs per day of antibiotics and laboratory investigations were also found to be significantly higher for patients with RGNB infection. The length of stay post infection was not found to be different between those infected with RGNB and SGNB. CONCLUSION: The economic burden of RGNB infections to the patients and the hospital is considerable. Efforts need to be taken to prevent their occurrence by cost effective infection control practices.

A prediction tool for nosocomial multi-drug Resistant Gram-Negative Bacilli infections in critically ill patients - prospective observational study.

BACKGROUND: The widespread use of empiric broad spectrum antibiotics has contributed to the global increase of Resistant Gram-Negative Bacilli (RGNB) infections in intensive care units (ICU). The aim of this study was to develop a tool to predict nosocomial RGNB infections among ICU patients for targeted therapy. METHODS: We conducted a prospective observational study from August'07 to December'11. All adult patients who were admitted and stayed for more than 24 hours at the medical and surgical ICU's were included. All patients who developed nosocomial RGNB infections 48 hours after ICU admission were identified. A prediction score was formulated by using independent risk factors obtained from logistic regression analysis. This was prospectively validated with a subsequent cohort of patients admitted to the ICUs during the following time period of January-September 2012. RESULTS: Seventy-six patients with nosocomial RGNB Infection (31bacteremia) were compared with 1398 patients with Systemic Inflammatory Response Syndrome (SIRS) without any gram negative bacterial infection/colonization admitted to the ICUs during the study period. The following independent risk factors were obtained by a multivariable logistic regression analysis - prior isolation of Gram negative organism (coeff: 1.1, 95% CI 0.5-1.7); Surgery during current admission (coeff: 0.69, 95% CI 0.2-1.2); prior Dialysis with end stage renal disease (coeff: 0.7, 95% CI 0.1-1.1); prior use of Carbapenems (coeff: 1.3, 95% CI 0.3-2.3) and Stay in the ICU for more than 5 days (coeff: 2.4, 95% CI 1.6-3.2). It was validated prospectively in a subsequent cohort (n = 408) and the area-under-the-curve (AUC) of the GSDCS score for predicting nosocomial ICU acquired RGNB infection and bacteremia was 0.77 (95% CI 0.68-0.89 and 0.78 (95% CI 0.69-0.89) respectively. The GSDCS (0-4.3) score clearly differentiated the low (0-1.3), medium (1.4-2.3) and high (2.4-4.3) risk patients, both for RGNB infection (p:0.003) and bacteremia (p:0.009). CONCLUSION: GSDCS is a simple bedside clinical score which predicts RGNB infection and bacteremia with high predictive value and differentiates low versus high risk patients. This score will help clinicians to choose appropriate, timely targeted antibiotic therapy and avoid exposure to unnecessary treatment for patients at low risk of nosocomial RGNB infection. This will reduce the selection pressure and help to contain antibiotic resistance in ICUs.

High burden of antimicrobial drug resistance in Asia.

The rapid development of antimicrobial resistance among micro-organisms is a serious public health concern. Moreover, the dissemination of antibiotic-resistant bacteria makes this issue a global problem, and Asia is no exception. For example, since New Delhi metallo-ß-lactamase (NDM)-producing Enterobacteriaceae were identified in India, further spread of NDM has become a worldwide threat. However, the epidemiology of antibiotic-resistant bacteria in Asia may be different to other regions, and clinical condition may be worse than in western countries. Antibiotic-resistant bacteria, including community-acquired and hospital-acquired meticillin-resistant Staphylococcus aureus (MRSA), vancomycin-intermediate S. aureus (VISA), vancomycin-resistant enterococci, macrolide- and penicillin-resistant Streptococcus pneumoniae, extend-spectrum ß-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae, carbapenem-resistant Enterobacteriaceae, and multidrug-resistant Pseudomonas aeruginosa and Acinetobacter spp., are becoming prevalent in many countries in Asia. Moreover, the prevalence of each antibiotic-resistant bacterium in each country is not identical. This review provides useful information regarding the critical condition of antibiotic resistance in Asia and emphasises the importance of continuous surveillance of resistance data.

Risk factors for infection/colonization caused by resistant Gram negative bacilli in critically ill patients (an observational study of 1633 critically ill patients).

OBJECTIVE: The objective of this study is to identify risk factors associated with multi-resistant Gram negative (RGNB) infection and colonization among critically ill patients. METHODS: A prospective cohort study of all patients aged 21-90 admitted for more than 24 hours in Medical and Surgical intensive care units (ICU) at a large teaching hospital in Singapore for the period of Aug '07-Dec '09 was conducted. Patient demographics, comorbidities, antibiotics, invasive devices, and culture results were collected. Forward stepwise logistic regression analyses were done to identify risk factors associated with RGNB infection and colonization. RESULTS: Of the 1373 patients included in the analysis, 13.5% developed RGNB infection. A logistic regression analysis including variables with a p value of <0.2 in the univariate analysis showed that recent surgery (OR 2.1, 95% CI 1.2-3.6), renal impairment (OR 2.9, 95% CI 1.5-5.4), liver disease (OR: 3.8, 95% CI 1.7-8.8), central line (OR 1.8, 95% CI 1.01-3.4) were independently associated with RGNB infection in the ICU. Surgery (OR 3.9, 95% CI 2.7-5.7), third-line antibiotics (carbapenem, vancomycin, linezolid) (OR 1.8, 95% CI 1.2-2.9) were independently associated with RGNB infection during their hospitalization. CONCLUSION: The major risk factors identified for RGNB infection and colonization in the ICU were mainly patient dependent. However, broad spectrum initial antibiotic treatment remains an important independent modifiable risk factor. Interventions aimed at reducing initial broad spectrum antibiotics are clearly needed to help control the spread of these difficult to treat infections.

Neisseria gonorrhoeae paravertebral abscess.

The authors present the case of an isolated gonococcal paravertebral abscess with an epidural component in a 42-year-old man. A primary epidural abscess of the spine is a rare condition and is most commonly caused by Staphylococcus aureus. In this report, the authors present their therapeutic decisions and review the relevant literature on disseminated gonococcal infection in a patient presenting with an epidural abscess. A 42-year-old Indonesian man was admitted with symptoms of neck and upper back pain and bilateral lower-limb weakness. Clinical examination was unremarkable apart from tenderness over the lower cervical spine. Postgadolinium T1-weighted MRI of the cervical and thoracic spine demonstrated an enhancing lesion in the right paraspinal and epidural soft tissue at C-6 to T1-2, in keeping with a spinal epidural abscess. The patient underwent laminectomy of C-7 and T-1 with abscess drainage. Tissue cultures subsequently grew Neisseria gonorrhoeae that was resistant to quinolones by genotyping. Upon further questioning, the patient admitted to unprotected sexual intercourse with commercial sex workers. Further investigations showed that he was negative for other sexually transmitted infections. Postoperatively, he received a course of beta-lactam antibiotics with good recovery. Clinicians should be aware of this unusual disseminated gonococcal infection manifested in any patient with the relevant risk factors.

The ethics of responding to a novel pandemic.

Recent epidemics and pandemics have highlighted a number of ethical concerns about the response to the increasing threat of emerging infectious diseases. Some of these ethical concerns are very fundamental. They include why a pandemic was declared, how much clinical information can be collected for public health without threatening patient confidentiality and how to ensure fairness in the distribution of resources. We discuss these issues and suggest approaches to resolve these dilemmas as we anticipate the next pandemic.

Prospective audit of febrile neutropenia management at a tertiary university hospital in Singapore.

INTRODUCTION: Febrile neutropenia (FN) remains a major cause of morbidity and mortality in Oncology/Haematology units. We launched a new protocol for FN management that incorporates risk stratification at our institute from October 2008. An audit was performed concurrently to evaluate the protocol and to define the epidemiology of FN locally. MATERIALS AND METHODS: Case records of all inpatients with FN between October 2008 and June 2009 were reviewed prospectively. Clinical and microbiological characteristics were collated along with outcomes and programme adherence. Statistical testing was performed using Stata 10.1. RESULTS: There were 178 FN episodes (50 in patients with solid cancers) from 131 patients. Forty-two (23.6%) episodes were classified as high-risk according to MASCC criteria. Initial blood cultures were positive in 49 (27.5%) episodes, of which gram-negative bacilli (GNB) predominated. Overall compliance to the protocol was 56.7%, with the main issue being disinclination to use oral antibiotics as fi rst-line empirical therapy for low-risk episodes. Overall mortality was 7.3% and infection-related mortality was 4.5%. High-risk FN and the presence of central venous catheters were independently associated with bacteraemia on multivariate analysis, but there were no independent predictors of infection-related mortality. CONCLUSIONS: GNB accounted for the majority of bloodstream infections at our institute, unlike data from developed countries. Uptake of the new FN protocol was satisfactory, although the use of oral antibiotics as fi rst-line empirical therapy can be improved. A better method for predicting infections caused by antibiotic-resistant GNB is urgently required, and antibiotic resistance trends should be monitored to enable the implementation of more appropriate antibiotic regimens over time.