INTRODUCTIONFebrile neutropenia (FN) is a significant cause of mortality and morbidity in oncology and haematology units worldwide. The overall mortality in hospital surveys in Singapore surveys on post-chemotherapy FN has ranged between 3.0% and 8.8%. However, recent evidence indicates that outpatient management of patients with low-risk FN is safe and cost-effective.

MATERIALS AND METHODSWe conducted a prospective audit on a cohort of adult patients with post-chemotherapy FN seen at 2 local public sector cancer centres over a 1-year period in order to define their epidemiological characteristics and outcomes, and also to assess the uptake of early discharge/outpatient management strategies for these patients.

RESULTSWe reviewed 306 FN episodes from 248 patients. Patient characteristics and outcomes were similar between both institutions. Eleven (3.7%) FN episodes were managed as outpatient and none developed complications. Overall 30-day mortality was 6.6%, while the median length of stay (LOS) was 7 days (IQR: 4 to 11 days). The only independent risk factor for mortality was severe sepsis (OR:13.19; 95% CI: 1.98 to 87.7; P = 0.008). Factors independently associated with a longer LOS were vancomycin prescription (coefficient: 0.25; 95% CI: 0.08 to 0.41; P = 0.003), longer duration of intravenous antibiotics (coefficient: 0.08; 95% CI: 0.06 to 0.10; P <0.001), and prior review by an infectious diseases physician (coefficient: 0.16; 95% CI: 0.01 to 0.31; P = 0.034).

CONCLUSIONThis audit demonstrated that mortality from FN in our 2 cancer centres is low and comparable to international institutions. It also demonstrates that outpatient management of FN is safe in selected patients, and can be further expanded for right-siting of resources.

Adult ; Anti-Bacterial Agents ; therapeutic use ; Antineoplastic Agents ; adverse effects ; Bacterial Infections ; epidemiology ; Cohort Studies ; Female ; Fever ; epidemiology ; etiology ; Humans ; Male ; Middle Aged ; Mycoses ; epidemiology ; Neoplasms ; complications ; drug therapy ; Neutropenia ; epidemiology ; etiology ; Prospective Studies ; Singapore ; epidemiology

Temozolomide(TMZ)is an anticancer agent used to treat glioblastoma,typically following radiation therapy and/or surgical resection.However,despite its effectiveness,at least 50％of patients do not respond to TMZ,which is associated with repair and/or tolerance of TMZ-induced DNA lesions.Studies have demonstrated that alkyladenine DNA glycosylase(AAG),an enzyme that triggers the base excision repair(BER)pathway by excising TMZ-induced N3-methyladenine(3meA)and N7-methylguanine le-sions,is overexpressed in glioblastoma tissues compared to normal tissues.Therefore,it is essential to develop a rapid and efficient screening method for AAG inhibitors to overcome TMZ resistance in glio-blastomas.Herein,we report a robust time-resolved photoluminescence platform for identifying AAG inhibitors with improved sensitivity compared to conventional steady-state spectroscopic methods.As a proof-of-concept,this assay was used to screen 1440 food and drug administration-approved drugs against AAG,resulting in the repurposing of sunitinib as a potential AAG inhibitor.Sunitinib restored glioblastoma(GBM)cancer cell sensitivity to TMZ,inhibited GBM cell proliferation and stem cell char-acteristics,and induced GBM cell cycle arrest.Overall,this strategy offers a new method for the rapid identification of small-molecule inhibitors of BER enzyme activities that can prevent false negatives due to a fluorescent background.

Background: We evaluated changes in glycemic status, over 1 year, of coronavirus disease 2019 (COVID-19) survivors with dysglycemia in acute COVID-19. Methods: COVID-19 survivors who had dysglycemia (defined by glycosylated hemoglobin [HbA1c] 5.7% to 6.4% or random glucose ≥10.0 mmol/L) in acute COVID-19 were recruited from a major COVID-19 treatment center from September to October 2020. Matched non-COVID controls were recruited from community. The 75-g oral glucose tolerance test (OGTT) were performed at baseline (6 weeks after acute COVID-19) and 1 year after acute COVID-19, with HbA1c, insulin and C-peptide measurements. Progression in glycemic status was defined by progression from normoglycemia to prediabetes/diabetes, or prediabetes to diabetes. Results: Fifty-two COVID-19 survivors were recruited. Compared with non-COVID controls, they had higher C-peptide (P< 0.001) and trend towards higher homeostasis model assessment of insulin resistance (P=0.065). Forty-three COVID-19 survivors attended 1-year reassessment. HbA1c increased from 5.5%±0.3% to 5.7%±0.2% (P<0.001), with increases in glucose on OGTT at fasting (P=0.089), 30-minute (P=0.126), 1-hour (P=0.014), and 2-hour (P=0.165). At baseline, 19 subjects had normoglycemia, 23 had prediabetes, and one had diabetes. Over 1 year, 10 subjects (23.8%; of 42 non-diabetes subjects at baseline) had progression in glycemic status. C-peptide levels remained unchanged (P=0.835). Matsuda index decreased (P=0.007) and there was a trend of body mass index increase from 24.4±2.7 kg/m2 to 25.6±5.2 (P=0.083). Subjects with progression in glycemic status had more severe COVID-19 illness than non-progressors (P=0.030). Reassessment was not performed in the control group. Conclusion Subjects who had dysglycemia in acute COVID-19 were characterized by insulin resistance. Over 1 year, a quarter had progression in glycemic status, especially those with more severe COVID-19. Importantly, there was no significant deterioration in insulin secretory capacity.

PURPOSE: To assess the effectiveness and safety of acupuncture for erectile dysfunction (ED). MATERIALS AND METHODS: We searched six major English and Chinese databases included randomized controlled trials (RCTs) testing acupuncture alone or in combination for ED. Dichotomous data were presented as risk ratio (RR) and continuous data were presented as mean difference (MD) both with 95% confidence interval (CI). The Revman (v.5.3) was used for data analyses. Quality of evidence across studies was assessed by the online GRADEpro tool. RESULTS: We identified 22 RCTs, fourteen of them involving psychogenic ED. Most of the included RCTs had high or unclear risk of bias. There was no difference between electro-acupuncture and sham acupuncture with electrical stimulation on the rate of satisfaction and self-assessment (RR, 1.50; 95% CI, 0.71–3.16; 1 trial). Acupuncture combined with tadalafil appeared to have better effect on increasing cure rate (RR, 1.31; 95% CI, 1.00–1.71; 2 trials), and International Index of Erectile Function-5 scores (MD, 5.38; 95% CI, 4.46–6.29; 2 trials). When acupuncture plus herbal medicine compared with herbal medicine alone, the combination therapy showed significant better improvement in erectile function (RR, 1.68; 95% CI, 1.31–2.15; 7 trials). Only two trials reported facial red and dizziness cases, and needle sticking and pruritus cases in acupuncture group. CONCLUSIONS: Low quality evidence shows beneficial effect of acupuncture as adjunctive treatment for people mainly with psychogenic ED. Safety of acupuncture was insufficiently reported. The findings should be confirmed in large, rigorously designed and well-reported trials.
Acupuncture ; Asian Continental Ancestry Group ; Bias (Epidemiology) ; Dizziness ; Electric Stimulation ; Erectile Dysfunction ; Herbal Medicine ; Humans ; Male ; Needles ; Odds Ratio ; Pruritus ; Self-Assessment ; Statistics as Topic ; Tadalafil

BACKGROUNDProactive infection control management is crucial in preventing the introduction of multiple drug resistant organisms in the healthcare setting. In Hong Kong, where vancomycin-resistant enterococci (VRE) endemicity is not yet established, contact tracing and screening, together with other infection control measures are essential in limiting intra- and inter-hospital transmission. The objective of this study was to illustrate the control measures used to eradicate a VRE outbreak in a hospital network in Hong Kong.

METHODSWe described an outbreak of VRE in a healthcare region in Hong Kong, involving a University affiliated hospital and a convalescent hospital of 1600 and 550 beds respectively. Computer-assisted analysis was utilized to facilitate contact tracing, followed by VRE screening using chromogenic agar. Multi-locus sequence typing (MLST) was performed to assess the clonality of the VRE strains isolated. A case-control study was conducted to identify the risk factors for nosocomial acquisition of VRE.

RESULTSBetween November 26 and December 17, 2011, 11 patients (1 exogenous case and 10 secondary cases) in two hospitals with VRE colonization were detected during our outbreak investigation and screening for 361 contact patients, resulting in a clinical attack rate of 2.8% (10/361). There were 8 males and 3 females with a median age of 78 years (range, 40 - 87 years). MLST confirmed sequence type ST414 in all isolates. Case-control analysis demonstrated that VRE positive cases had a significantly longer cumulative length of stay (P < 0.001), a higher proportion with chronic cerebral and cardiopulmonary conditions (P = 0.001), underlying malignancies (P < 0.001), and presence of urinary catheter (P < 0.001), wound or ulcer (P < 0.001), and a greater proportion of these patients were receiving β-lactam/β-lactamase inhibitors (P = 0.009), carbapenem group (P < 0.001), fluoroquinolones (P = 0.003), or vancomycin (P = 0.001) when compared with the controls.

CONCLUSIONExtensive contact tracing and screening with a "search-and-confine" strategy was a successful tool for outbreak control in our healthcare region.

Aged ; Aged, 80 and over ; Enterococcus faecium ; growth & development ; pathogenicity ; Female ; Gram-Positive Bacterial Infections ; epidemiology ; prevention & control ; Hong Kong ; epidemiology ; Humans ; Male ; Middle Aged ; Vancomycin Resistance

Melioidosis is an infection caused by Burkholderia pseudomallei known to be endemic in large portions of Asia, Sub-Sahara, and North Australia. Despite its endemicity in Malaysia, prompt diagnosis and subsequent treatment remain elusive especially in the more peripheral medical centres. This coupled with increasing risk to the population because of worsening climate crises renders early recognition and treatment more justifiable than ever. Here we present a case of melioidosis septic arthritis with systemic dissemination and discuss the factors involved in disease contraction, worsening prevalence, and diagnostic methods.
Melioidosis ; Arthritis, Infectious ; mviN protein, Burkholderia pseudomallei [Supplementary Concept]

INTRODUCTION: Three doses of SARS-CoV-2 mRNA vaccines have been recommended for cancer patients to reduce the risk of severe disease. Anti-neoplastic treatment, such as chemotherapy, may affect long-term vaccine immunogenicity. METHOD: Patients with solid or haematological cancer were recruited from 2 hospitals between July 2021 and March 2022. Humoral response was evaluated using GenScript cPASS surrogate virus neutralisation assays. Clinical outcomes were obtained from medical records and national mandatory-reporting databases. RESULTS: A total of 273 patients were recruited, with 40 having haematological malignancies and the rest solid tumours. Among the participants, 204 (74.7%) were receiving active cancer therapy, including 98 (35.9%) undergoing systemic chemotherapy and the rest targeted therapy or immunotherapy. All patients were seronegative at baseline. Seroconversion rates after receiving 1, 2 and 3 doses of SARS-CoV-2 mRNA vaccination were 35.2%, 79.4% and 92.4%, respectively. After 3 doses, patients on active treatment for haematological malignancies had lower antibodies (57.3%±46.2) when compared to patients on immunotherapy (94.1%±9.56, P<0.05) and chemotherapy (92.8%±18.1, P<0.05). SARS-CoV-2 infection was reported in 77 (28.2%) patients, of which 18 were severe. No patient receiving a third dose within 90 days of the second dose experienced severe infection. CONCLUSION This study demonstrates the benefit of early administration of the third dose among cancer patients.
Humans ; SARS-CoV-2 ; COVID-19/prevention & control* ; Treatment Outcome ; Neoplasms/drug therapy* ; Hematologic Neoplasms ; Vaccination ; RNA, Messenger ; Antibodies, Viral ; Immunogenicity, Vaccine

INTRODUCTIONWe aimed to evaluate the effectiveness and safety of canagliflozin as compared to sitagliptin in a real-world setting among multiethnic patients with Type 2 diabetes mellitus (T2DM) in Singapore.

METHODSThis was a new-user, active-comparator, single-centre retrospective cohort study. Patients aged 18-69 years with T2DM and estimated glomerular filtration rate ≥ 60 mL/min/1.73 m were eligible for inclusion if they were initiated and maintained on a steady daily dose of canagliflozin 300 mg or sitagliptin 100 mg between 1 May and 31 December 2014, and followed up for 24 weeks.

RESULTSIn total, 57 patients (canagliflozin 300 mg, n = 22; sitagliptin 100 mg, n = 35) were included. The baseline patient characteristics in the two groups were similar, with overall mean glycated haemoglobin (HbA1c) of 9.4% ± 1.4%. The use of canagliflozin 300 mg was associated with greater reductions in HbA1c (least squares [LS] mean change -1.6% vs. -0.4%; p < 0.001), body weight (LS mean change -3.0 kg vs. 0.2 kg; p < 0.001) and systolic blood pressure (LS mean change: -9.7 mmHg vs. 0.4 mmHg; p < 0.001), as compared with sitagliptin 100 mg. About half of the patients on canagliflozin 300 mg reported mild osmotic diuresis-related side effects that did not lead to drug discontinuation.

CONCLUSIONOur findings suggest that canagliflozin was more effective than sitagliptin in reducing HbA1c, body weight and systolic blood pressure in patients with T2DM, although its use was associated with an increased incidence of mild osmotic diuresis-related side effects.

Adolescent ; Adult ; Aged ; Blood Glucose ; drug effects ; Blood Pressure ; Body Mass Index ; Body Weight ; Canagliflozin ; administration & dosage ; Diabetes Mellitus, Type 2 ; drug therapy ; Female ; Glomerular Filtration Rate ; Hemoglobins ; analysis ; Humans ; Hypoglycemic Agents ; administration & dosage ; Least-Squares Analysis ; Male ; Middle Aged ; Osmosis ; Retrospective Studies ; Singapore ; Sitagliptin Phosphate ; administration & dosage ; Systole ; Treatment Outcome ; Young Adult

Objective: To assess the public health risk to Singapore posed by the emergence of artemisinin-resistant (ART-R) malaria in the Greater Mekong Subregion (GMS). Methods: We assessed the likelihood of importation of drug-resistant malaria into Singapore and the impact on public health of its subsequent secondary spread in Singapore. Literature on the epidemiology and contextual factors associated with ART-R malaria was reviewed. The epidemiology of malaria cases in Singapore was analysed. The vulnerability and receptivity of Singapore were examined, including the connectivity with countries reporting ART-R malaria, as well as the preparedness of Singaporean health authorities. Sources of information include international journals, World Health Organization guidelines, data from the Singapore Ministry of Health and National Public Health Laboratory of the National Centre for Infectious Diseases, and the International Air Transport Association. Results: The importation of ART-R malaria into Singapore is possible given the close proximity and significant travel volume between Singapore and the GMS countries reporting artemisinin resistance. Singapore’s vulnerability is further enhanced by the presence of foreign workers from neighbouring endemic countries. Nonetheless, the overall likelihood of such an event is low based on the rarity and decreasing trend of imported malaria incidence. With the presence of Anopheles vectors in Singapore, imported cases of drug-resistant malaria could cause secondary transmission. Nevertheless, the risk of sustained spread is likely to be mitigated by the comprehensive surveillance and control system in place for both infected vectors and human cases. Discussion This risk assessment highlights the need for a continued high degree of vigilance of ART-R malaria locally and globally to minimize the risk and public health impact of drug-resistant malaria in Singapore.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.