Chin Fang Ngim

This study explored the contribution of viral respiratory infections (VRIs) in dengue-like illness (DLI) patients and their distinguishing clinicolaboratory parameters. Two hundred DLI patients were prospectively recruited (1 July–1 October 2019) from a community clinic in Southern Malaysia. Patients ≥18 years with acute fever and fulfilling the WHO criteria of probable dengue were recruited. They underwent blood testing: blood counts, rapid dengue tests (nonstructural antigen-1/IgM) and polymerase chain reaction (PCR) for dengue, Zika, chikungunya, and Leptospira. Nasopharyngeal swabs (NPSs) were collected for FilmArray^®RP2plus testing. From the 200 NPSs, 58 respiratory viruses (RVs) were detected in 54 patients. Of the 96 dengue-confirmed cases, 86 had dengue mono-infection, and 10 were coinfected with RVs. Of the 104 nondengue, 44 were RV positive and 4 Leptospira positive. Zika and chikungunya virus were not detected. Overall, the etiological diagnosis was confirmed for 72% of patients. Clinicolaboratory parameters were compared between dengue mono-infection and VRI mono-infection. Patients with coinfections were excluded. Multiple logistic regression showed that recent household/neighborhood history of dengue (adjusted odds ratio [aOR]: 5.9, 95% CI = 1.7–20.7), leukopenia (aOR: 12.5, 95% CI = 2.6–61.4) and thrombocytopenia (aOR: 5.5, 95% CI = 1.3–23.0) predicted dengue. Inversely, rhinorrhoea (aOR: 0.1, 95% CI = 0.01–0.3) and cough (aOR: 0.3, 95% CI = 0.1–0.9) favored VRI. Thus, VRIs comprise many infections diagnosed initially as DLIs. Early clinicolaboratory parameters can guide physicians screen patients for further testing.

Background: Due to an ageing population, dengue among older patients is encountered more frequently in many countries. Our study aimed to explore the clinico-laboratory parameters and outcomes among dengue-infected older patients in comparison with younger patients. Methods: This retrospective chart review involved dengue patients with dengue non-structural protein 1 (NS1) antigen positivity admitted to a tertiary hospital in Malaysia from January to July 2015. A comparison was made between older people (aged ≥60 y) and others. Results: Among 406 dengue patients, 43 (10.6%) were older people. Older dengue patients were less likely to present with persistent vomiting (adjusted OR [AOR] 0.247, 95% CI 0.093 to 0.656, p=0.005), while restlessness and confusion were more common at presentation (AOR 3.356, 95% CI 1.024 to 11.003, p=0.046). Older patients had significantly lower albumin upon admission (38 vs 40 g/L, p=0.036) and during hospital stay (35 vs 37 g/L, p=0.015). Compared with younger patients, older patients were more likely to have experienced nadir platelet counts of <50×109/L (AOR 2.897, 95% CI to 1.176 to 7.137, p=0.021). They were also more likely to require an extended hospital stay (AOR 3.547, 95% CI 1.575 to 7.986, p=0.002). Conclusions: Diagnosis of dengue in older people may be challenging because of atypical presentations. Increased vigilance is necessary as there is an increased tendency to develop severe thrombocytopenia, hypoalbuminemia and prolonged hospitalisation in older people.

Background: Dengue fever is the most common mosquito-borne infection worldwide where an expanding surveillance and characterization of this infection are needed to better inform the healthcare system. In this surveillance-based study, we explored the prevalence and distinguishing features of dengue fever amongst febrile patients in a large community-based health facility in southern peninsular Malaysia. Methods: Over six months in 2018, we recruited 368 adults who met the WHO 2009 criteria for probable dengue infection. They underwent the following blood tests: full blood count, dengue virus (DENV) rapid diagnostic test (RDT), ELISA (dengue IgM and IgG), nested RT-PCR for dengue, multiplex qRT-PCR for Zika, Chikungunya and dengue as well as PCR tests for Leptopspira spp., Japanese encephalitis and West Nile virus. Results: Laboratory-confirmed dengue infections (defined by positive tests in NS1, IgM, high-titre IgG or nested RT-PCR) were found in 167 (45.4%) patients. Of these 167 dengue patients, only 104 (62.3%) were positive on rapid diagnostic testing. Dengue infection was significantly associated with the following features: family or neighbours with dengue in the past week (AOR: 3.59, 95% CI:2.14–6.00, p<0.001), cutaneous rash (AOR: 3.58, 95% CI:1.77–7.23, p<0.001), increased temperature (AOR: 1.33, 95% CI:1.04–1.70, p = 0.021), leucopenia (white cell count < 4,000/μL) (AOR: 3.44, 95% CI:1.72–6.89, p<0.001) and thrombocytopenia (platelet count <150,000/μL)(AOR: 4.63, 95% CI:2.33–9.21, p<0.001). Dengue infection was negatively associated with runny nose (AOR: 0.47, 95% CI:0.29–0.78, p = 0.003) and arthralgia (AOR: 0.42, 95% CI:0.24–0.75, p = 0.004). Serotyping by nested RT-PCR revealed mostly mono-infections with DENV-2 (n = 64), DENV-1 (n = 32) and DENV-3 (n = 17); 14 co-infections occurred with DENV-1/DENV-2 (n = 13) and DENV-1/DENV-4 (n = 1). Besides dengue, none of the pathogens above were found in patients’ serum. Conclusions: Acute undifferentiated febrile infections are a diagnostic challenge for community-based clinicians. Rapid diagnostic tests are increasingly used to diagnose dengue infection but negative tests should be interpreted with caution as they fail to detect a considerable proportion of dengue infection. Certain clinical features and haematological parameters are important in the clinical diagnosis of dengue infection.

Background: The Objective Structured Clinical Exam (OSCE) is a useful means of generating meaningful feedback. OSCE feedback may be in various forms (written, face to face and audio or video recordings). Studies on OSCE feedback are uncommon, especially involving Asian medical students. Methods: We compared two methods of OSCE feedback delivered to fourth year medical students in Malaysia: (i) Face to face (FTF) immediate feedback (semester one) (ii) Individualised enhanced written (EW) feedback containing detailed scores in each domain, examiners’ free text comments and the marking rubric (semester two). Both methods were evaluated by students and staff examiners, and students’ responses were compared against their OSCE performance. Results: Of the 116 students who sat for both formative OSCEs, 82.8% (n=96) and 86.2% (n=100) responded to the first and second survey respectively. Most students were comfortable to receive feedback (91.3% in FTF, 96% in EW) with EW feedback associated with higher comfort levels (p=0.022). Distress affected a small number with no differences between either method (13.5% in FTF, 10% in EW, p=0.316). Most students perceived both types of feedback improved their performance (89.6% in FTF, 95% in EW); this perception was significantly stronger for EW feedback (p=0.008). Students who preferred EW feedback had lower OSCE scores compared to those preferring FTF feedback (mean scores ± SD: 43.8 ± 5.3 in EW, 47.2 ± 6.5 in FTF, p=0.049). Students ranked the “marking rubric” to be the most valuable aspect of the EW feedback. Tutors felt both methods of feedback were equally beneficial. Few examiners felt they needed training (21.4% in FTF, 15% in EW) but students perceived this need for tutors’ training differently (53.1% in FTF, 46% in EW) Conclusion: Whilst both methods of OSCE feedback were highly valued, students preferred to receive EW feedback and felt it was more beneficial. Learning cultures of Malaysian students may have influenced this view. Information provided in EW feedback should be tailored accordingly to provide meaningful feedback in OSCE exams.

Background: The Objective Structured Clinical Exam (OSCE) is a useful means of generating meaningful feedback. OSCE feedback may be in various forms (written, face to face and audio or video recordings). Studies on OSCE feedback are uncommon, especially involving Asian medical students. Methods: We compared two methods of OSCE feedback delivered to fourth year medical students in Malaysia: (i) Face to face (FTF) immediate feedback (semester one) (ii) Individualised enhanced written (EW) feedback containing detailed scores in each domain, examiners’ free text comments and the marking rubric (semester two). Both methods were evaluated by students and staff examiners, and students’ responses were compared against their OSCE performance.Results: Of the 116 students who sat for both formative OSCEs, 82.8% (n=96) and 86.2% (n=100) responded to the first and second survey respectively. Most students were comfortable to receive feedback (91.3% in FTF, 96% in EW) with EW feedback associated with higher comfort levels (p=0.022). Distress affected a small number with no differences between either method (13.5% in FTF, 10% in EW, p=0.316). Most students perceived both types of feedback improved their performance (89.6% in FTF, 95% in EW); this perception was significantly stronger for EW feedback (p=0.008). Students who preferred EW feedback had lower OSCE scores compared to those preferring FTF feedback (mean scores ± SD: 43.8 ± 5.3 in EW, 47.2 ± 6.5 in FTF, p=0.049). Students ranked the “marking rubric” to be the most valuable aspect of the EW feedback. Tutors felt both methods of feedback were equally beneficial. Few examiners felt they needed training (21.4% in FTF, 15% in EW) but students perceived this need for tutors’ training differently (53.1% in FTF, 46% in EW)Conclusion: Whilst both methods of OSCE feedback were highly valued, students preferred to receive EW feedback and felt it was more beneficial. Learning cultures of Malaysian students may have influenced this view. Information provided in EW feedback should be tailored accordingly to provide meaningful feedback in OSCE exams.

Background Thalassaemia is a recessively‐inherited blood disorder that leads to anaemia of varying severity. In those affected by the more severe forms, regular blood transfusions are required which may lead to iron overload. Accumulated iron from blood transfusions may be deposited in vital organs including the heart, liver and endocrine organs such as the pituitary glands which can affect growth hormone production. Growth hormone deficiency is one of the factors that can lead to short stature, a common complication in people with thalassaemia. Growth hormone replacement therapy has been used in children with thalassaemia who have short stature and growth hormone deficiency. This review on the role of growth hormone was originally published in September 2017 and updated in April 2020. Objectives To assess the benefits and safety of growth hormone therapy in people with thalassaemia. Search methods We searched the Cochrane Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. Date of latest search: 14 November 2019. We also searched the reference lists of relevant articles, reviews and clinical trial registries. Date of latest search: 06 January 2020. Selection criteria Randomised and quasi‐randomised controlled trials comparing the use of growth hormone therapy to placebo or standard care in people with thalassaemia of any type or severity. Data collection and analysis Two authors independently selected trials for inclusion. Data extraction and assessment of risk of bias were also conducted independently by two authors. The certainty of the evidence was assessed using GRADE criteria. Main results We included one parallel trial conducted in Turkey. The trial recruited 20 children with homozygous beta thalassaemia who had short stature; 10 children received growth hormone therapy administered subcutaneously on a daily basis at a dose of 0.7 IU/kg per week and 10 children received standard care. The overall risk of bias in this trial was low except for the selection criteria and attrition bias which were unclear. The certainty of the evidence for all major outcomes was moderate, the main concern was imprecision of the estimates due to the small sample size leading to wide confidence intervals. Final height (cm) (the review's pre‐specified primary outcome) and change in height were not assessed in the included trial. The trial reported no clear difference between groups in height standard deviation (SD) score after one year, mean difference (MD) ‐0.09 (95% confidence interval (CI) ‐0.33 to 0.15 (moderate‐certainty evidence). However, modest improvements appeared to be observed in the following key outcomes in children receiving growth hormone therapy compared to control (moderate‐certainty evidence): change between baseline and final visit in height SD score, MD 0.26 (95% CI 0.13 to 0.39); height velocity, MD 2.28 cm/year (95% CI 1.76 to 2.80); height velocity SD score, MD 3.31 (95% CI 2.43 to 4.19); and change in height velocity SD score between baseline and final visit, MD 3.41 (95% CI 2.45 to 4.37). No adverse effects of treatment were reported in either group; however, while there was no clear difference between groups in the oral glucose tolerance test at one year, fasting blood glucose was significantly higher in the growth hormone therapy group compared to control, although both results were still within the normal range, MD 6.67 mg/dL (95% CI 2.66 to 10.68). There were no data beyond the one‐year trial period. Authors' conclusions A small single trial contributed evidence of moderate certainty that the use of growth hormone for a year may improve height velocity of children with thalassaemia although height SD score in the treatment group was similar to the control group. There are no randomised controlled trials in adults or trials that address the use of growth hormone therapy over a longer period and assess its effect on final height and quality of life. The optimal dosage of growth hormone and the ideal time to start this therapy remain uncertain. Large well‐designed randomised controlled trials over a longer period with sufficient duration of follow up are needed.

Background: There is an escalation of frequency and magnitude of dengue epidemics in Malaysia, with a concomitant increase in patient hospitalization. Prolonged hospitalization (PH) due to dengue virus (DENV) infections causes considerable socioeconomic burden. Early identification of patients needing PH could optimize resource consumption and reduce health care costs. This study aims to identify clinicopathological factors present on admission that are associated with PH among patients with DENV infections. Methods: This study was conducted in a tertiary referral hospital in Southern Malaysia. Relevant clinical and laboratory data upon admission were retrieved from medical records of 253 consecutive DENV nonstructural protein 1 (NS1) antigen and PCR-positive hospitalized patients. The DENV serotype present in each patient was determined. Patients were stratified based on duration of hospital stay (® SPSS ^® 25.0. Multivariate logistic regression was performed to examine the association between PH and admission parameters. Results: Of 253 DENV hospitalized patients, 95 (37.5%) had PH (≥4 days). The mean duration of hospital stay was 3.43 ± 2.085 days (median = 3 days, interquartile range = 7 days). Diabetes mellitus (adjusted odds ratio [AOR] = 6.261, 95% confidence interval [CI] = 2.130–18.406, p = 0.001), DENV-2 serotype (AOR = 2.581, 95% CI = 1.179–5.650, p = 0.018), duration of fever ≤4 days (AOR = 2.423, 95% CI = 0.872–6.734, p = 0.09), and a shorter preadmission fever duration (AOR = 0.679, 95% CI = 0.481–0.957, p = 0.027) were independently associated with PH. However, PH was not found to be associated with symptoms on admission, secondary DENV infections or platelet count, hematocrit, or liver enzyme levels on admission. Conclusions: Early identification of these factors at presentation may alert clinicians to anticipate and recognize challenges in treating such patients, leading to more focused management plans that may shorten the duration of hospitalization.

Thalassaemia is a public health burden in Malaysia and its prevention faces many challenges. In this study, we aimed to assess the effectiveness of a web-based educational module in improving knowledge and attitudes about thalassaemia prevention amongst Malaysian young adults. We designed an interactive web-based educational module in the Malay language wherein videos were combined with text and pictorial visual cues. Malaysians aged 18-40 years old who underwent the module had their knowledge and attitudes assessed at baseline, post-intervention and at 6-month follow-up using a selfadministered validated questionnaire. Sixty-five participants: 47 Malays (72.3%), 15 Chinese (23.1%), three Indians (4.6%) underwent the module. Questionnaires were completed at baseline (n=65), postintervention (n=65) and at 6-month follow-up (n=60). Out of a total knowledge score of 21, significant changes were recorded across three time-points- median scores were 12 at pre-intervention, 19 at post-intervention and 16 at 6-month follow-up (p<0.001). Post-hoc testing comparing preintervention and 6-month follow-up scores showed significant retention of knowledge (p<0.001). Compared to baseline, attitudes at 6-month follow-up showed an increased acceptance for "marriage avoidance between carriers" (pre-intervention 20%, 6-month follow-up 48.3%, p<0.001) and "prenatal diagnosis" (pre-intervention 73.8%, 6-month follow-up 86.2%, p=0.008). Acceptance for selective termination however, remained low without significant change (pre-intervention 6.2%, 6-month follow-up 16.7%, p=0.109). A web-based educational module appears effective in improving knowledge and attitudes towards thalassaemia prevention and its incorporation in thalassaemia prevention programs is potentially useful in Malaysia and countries with a high internet penetration rate.

We explored the severity and risk factors for cardiac and liver iron overload (IOL) in 69 thalassemia patients who underwent T2* magnetic resonance imaging (T2* MRI) in a Malaysian tertiary hospital from 2011 to 2015. Fifty-three patients (76.8%) had transfusion-dependent thalassemia (TDT) and 16 (23.2%) had non transfusion-dependent thalassemia (NTDT). Median serum ferritin prior to T2* MRI was 3848.0 μg/L (TDT) and 3971.0 μg/L (NTDT). Cardiac IOL was present in 16 (30.2%) TDT patients and two (12.5%) NTDT patients, in whom severe cardiac IOL defined as T2* 15 mgFe/gm dry weight). Serum ferritin showed a significantly strong negative correlation with liver T2* in both TDT (rs = –0.507, p = 0.001) and NTDT (r = –0.762, p = 0.002) but no correlation to cardiac T2* in TDT (r = –0.252, p = 0.099) as well as NTDT (r = –0.457, p = 0.100). For the TDT group, regression analysis showed that cardiac IOL was more severe in males (p = 0.022) and liver IOL was more severe in the Malay ethnic group (p = 0.028) and those with higher serum ferritin levels (p = 0.030). The high prevalence of IOL in our study and the poor correlation between serum ferritin and cardiac T2* underline the need to routinely screen thalassemia patients using T2* MRI to enable the early detection of cardiac IOL.