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CKD-CHECK toolkit to improve doctors' practice in managing chronic kidney disease rapid progressors: a pilot study in primary care setting

Ang WS, Jamil TR, Kamaludin R, Mustafar R

Med J Malaysia, 2023 Nov;78(6):721-732.
PMID: 38031213

INTRODUCTION: Chronic kidney disease (CKD) rapid progression is associated with higher risk of end-stage kidney disease and higher mortality rate. Monitoring and recognition of CKD rapid progression is still lacking, however interventions have been shown to improve this. Thus, this study aimed to evaluate the acceptability and feasibility of CKD-CHECK toolkit and preliminary measure the outcome of the CKD-CHECK toolkit in assisting primary care doctor to order further tests for CKD rapid progressors and trigger appropriate nephrology referral.
MATERIALS AND METHODS: The CKD-CHECK (CKD-CHECK EGFR Chart in Kidney disease) is a toolkit that was developed to auto-generate patients' eGFR trend using a line graph, displaying the trend visually over a year. It identifies patients with rapid CKD progression, triggers the doctors to order appropriate tests (proteinuria quantification or renal imaging) and helps in decision making (continued monitoring at primary care level or referral to nephrologist). The toolkit was piloted among medical officers practising in a hospital-based primary care clinic treating patients with eGFR<60ml/min/1.73m2 using an interventional before-after study design from February to May 2022. In the preintervention period, the CKD patients were managed based on standard practice. The doctors then used the CKDCHECK toolkit on the same group of CKD patients during the intervention period. The feasibility and acceptability of the toolkit was assessed at the end of the study period using the Acceptability of Intervention Measure (AIM) and Feasibility of Intervention Measure (FIM) questionnaires. All patients' clinical data and referral rate were collected retrospectively through medical files and electronic data systems. Comparison between the pre- and post-intervention group were analysed using paired t-test and McNemar test, with statistical significance p value of <0.05.
RESULTS: A total of 25 medical officers used the toolkit on 60 CKD patients. The medical officers found the CKD-CHECK toolkit to be highly acceptable and feasible in primary care setting. The baseline characteristics of the patients were a mean age of 72 years old, predominantly females and Chinese ethnicity. Majority of the CKD patients had diabetes mellitus, hypertension and dyslipidemia. The numbers of CKD rapid progressors was similar (26.7% in the preintervention group vs 33.3% in the post-intervention group). There were no significant differences in terms of proteinuria assessment and ultrasound kidney for CKD rapid progressors before and after the intervention. However, a significant number of CKD rapid progressors were referred to nephrologists after the use of CKD-CHECK toolkit (p=0.016).
CONCLUSIONS: CKD-CHECK toolkit is acceptable and feasible to be used in primary care. Preliminary findings show that the CKD-CHECK toolkit improved the primary care doctor's referral of rapid CKD progressors to nephrologists.
In vitro antiviral activity of medicinal mushroom Ganoderma neo-japonicum Imazeki against enteroviruses that caused hand, foot and mouth disease

Ang WX, Sarasvathy S, Kuppusamy UR, Sabaratnam V, Tan SH, Wong KT, et al.

Trop Biomed, 2021 Sep 01;38(3):239-247.
PMID: 34362866 DOI: 10.47665/tb.38.3.063

Hand, foot and mouth disease (HFMD) is a highly contagious viral disease that predominantly affects children younger than 5 years old. HFMD is primarily caused by enterovirus A71 (EVA71) and coxsackievirus A16 (CV-A16). However, coxsackievirus A10 (CV-A10) and coxsackievirus A6 (CV-A6) are being increasingly reported as the predominant causative of HFMD outbreaks worldwide since the past decade. To date, there are still no licensed multivalent vaccines or antiviral drugs targeting enteroviruses that cause HFMD, despite HFMD outbreaks are still being frequently reported, especially in Asia-Pacific countries. The high rate of transmission, morbidity and potential neurological complications of HFMD is indeed making the development of broad-spectrum antiviral drugs/agents against these enteroviruses a compelling need. In this study, we have investigated the in vitro antiviral effect of 4 Ganoderma neo-japonicum Imazeki (GNJI) crude extracts (S1-S4) against EV-A71, CV-A16, CV-A10 and CV-A6. GNJI is a medicinal mushroom that can be found growing saprophytically on decaying bamboo clumps in Malaysian forests. The antiviral effects of this medicinal mushroom were determined using cytopathic inhibition and virus titration assays. The S2 (1.25 mg/ml) hot aqueous extract demonstrated the highest broad-spectrum antiviral activity against all tested enteroviruses in human primary oral fibroblast cells. Replication of EV-A71, CV-A16 and CVA10 were effectively inhibited at 2 hours post-infection (hpi) to 72 hpi, except for CV-A6 which was only at 2 hpi. S2 also has virucidal activity against EV-A71. Polysaccharides isolated and purified from crude hot aqueous extract demonstrated similar antiviral activity as S2, suggesting that polysaccharides could be one of the active compounds responsible for the antiviral activity shown by S2. To our knowledge, this study demonstrates for the first time the ability of GNJI to inhibit enterovirus infection and replication. Thus, GNJI is potential to be further developed as an antiviral agent against enteroviruses that caused HFMD.
Antiviral activity of povidone-iodine gargle and mouthwash solution against Enterovirus A71, Coxsackieviruses A16, A10 and A6

Ang WX, Tan SH, Wong KT, Perera D, Kuppusamy UR, Ong KC

Trop Biomed, 2024 Sep 01;41(3):241-250.
PMID: 39548776 DOI: 10.47665/tb.41.3.002

Hand, Foot and Mouth Disease (HFMD), a highly contagious viral disease common among infants and young children, is primarily caused by Enterovirus A71 (EV-A71) and Coxsackievirus A16 (CVA16). Nonetheless, emerging enteroviruses, such as CV-A10 and CV-A6, have also caused widespread outbreaks globally, in part due to the absence of effective antiviral therapies, and the high personto-person transmission rate. Person-to-person transmission is usually through fecal-oral or oral-oral routes, and sometimes via droplets. As the oral cavity is a primary site for early virus infection and replication, controlling oral viral shedding can mitigate the risk of transmission through this route. Povidone-iodine (PVP-I), a widely used antiseptic, has shown broad-spectrum antimicrobial properties but antiviral studies against HFMD-causing enteroviruses are limited, especially for CV-A10 and CVA6. Our study demonstrated that a 1% PVP-I solution (final concentration of 0.5%) exhibited virucidal activity against EV-A71, CV-A16, CV-A10, and CV-A6. All seven EV-A71 isolates and five CV-A16 isolates showed a significant virus titer reduction after a 1-minute incubation, while five CV-A10 isolates and two CV-A6 isolates required a 5-minute incubation to achieve this. The virucidal activity was confirmed through the EN14476:2013+A2:2019 virucidal quantitative suspension test, wherein all four viruses were completely inactivated after a 30-minute incubation with PVP-I at 37°C under both clean and dirty conditions. Western blot analysis suggested that PVP-I could affect the VP1 structural proteins of EV-A71. Our results suggest that PVP-I could serve as a potential virucidal agent to reduce the risk of person-to-person transmission of HFMD.

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