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Prevalence and Risk Factors for Cardiac and Liver Iron Overload in Adults with Thalassemia in Malaysia

Ngim CF, Lee MY, Othman N, Lim SM, Ng CS, Ramadas A

Hemoglobin, 2019 Mar;43(2):95-100.
PMID: 31179787 DOI: 10.1080/03630269.2019.1599906

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* <10 ms affected six (11.3%) TDT patients. Liver IOL was present in 51 (96.2%) TDT and 16 (100%) NTDT patients, 37 (69.8%) TDT and 13 (81.3%) NTDT patients were in the most severe category (>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.
Music-based Intervention for Improving Sleep Quality of Adults without Sleep Disorder: A Systematic Review and Meta-analysis

Tang YW, Teoh SL, Yeo JHH, Ngim CF, Lai NM, Durrant SJ, et al.

Behav Sleep Med, 2021 Apr 25.
PMID: 33896299 DOI: 10.1080/15402002.2021.1915787

Background: Listening to music is often used as a self-help intervention to improve sleep quality, but its efficacy among individuals without sleep disorder remains unclear.Methods: A search was performed on five databases to identify for studies that examined the use of music-based intervention to improve sleep quality among individuals without sleep disorder. Random-effects meta-analysis was performed, and the certainty of evidence was evaluated using GRADE (Grading of Recommendations Assessment, Development and Evaluation).Results: Twenty-two articles which recruited 1,514 participants were included for review. Meta-analysis of six studies including 424 participants did not find an improvement in sleep quality among recipients of music-based intervention compared to those with standard care (mean difference: -0.80; 95% CI: -2.15 to 0.54, low-quality evidence). Subgroup analysis showed a clear improvement in sleep quality when interventions were administered for at least 3 weeks (-2.09; -3.84 to -0.34, n = 3). No difference in terms of sleep onset latency (standardized mean difference (SMD) -0.32; 95% CI -0.88 to 0.25, n = 4, very-low quality evidence) and sleep efficiency (SMD: -0.59; 95% CI -3.15 to 1.97, n = 2, very-low quality evidence) were observed. The effect of music-based intervention on anxiety, depression and quality of life were mixed with suggestions of possible benefits.Conclusion: Music-based intervention in addition to standard care appears to be a promising strategy to improve sleep quality when delivered for 3 week or longer. However, effects are inconsistent across studies and larger randomized controlled studies reporting long-term outcomes are needed before it can be recommended for routine use.PROSPERO registration: CRD42018081193.
Admission Clinicopathological Factors Associated with Prolonged Hospital Stay Among Hospitalized Patients with Dengue Viral Infections

Willeam Peter SS, Hassan SS, Khei Tan VP, Ngim CF, Azreen Adnan NA, Pong LY, et al.

Vector Borne Zoonotic Dis, 2019 07;19(7):549-552.
PMID: 30668248 DOI: 10.1089/vbz.2018.2379

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 (<4 vs. ≥4 days). Data were analyzed using IBM® 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.
Risk factors and clinical outcome of profound thrombocytopenia in adult patients with DENV infections

Dhanoa A, Rajasekaram G, Hassan SS, Ramadas A, Azreen Adnan NA, Lau CF, et al.

Platelets, 2017 Nov;28(7):724-727.
PMID: 28287000 DOI: 10.1080/09537104.2017.1293802

Severe thrombocytopenia is common in dengue virus (DENV) infections. However, studies focusing on the role of profound thrombocytopenia (PT) (nadir platelet counts ≤ 20 000/mm3) in DENV infections are scarce. This study aims to identify the associated features and outcome of DENV patients with PT. It involves 237 adult hospitalized patients who were DENV PCR positive. The presence of comorbidity (AOR = 4.625; 95% CI = 1.113-19.230), higher admission hematocrit (AOR = 1.213; 95% CI = 1.067-1.379), lower admission albumin (AOR = 0.870; 95% CI = 0.766-0.988) and lower admission platelets (AOR = 0.980; 95% CI = 0.969-0.991) was associated with platelets ≤ 20 000/mm3 in multivariate logistic regression. PT was not affected by DENV serotypes, coinfections and secondary DENV infections. Patients with PT had significantly higher risk of experiencing warning signs (AOR = 3.709, 95% CI = 1.089-12.634) and longer hospital stay (AOR = 1.943, 95% CI = 1.010-3.774). However, severe dengue disease, hemorrhagic manifestations and need for intensive care were not significantly associated with PT.
Fulltext The association between obesity and dengue virus (DENV) infection in hospitalised patients

Tan VPK, Ngim CF, Lee EZ, Ramadas A, Pong LY, Ng JI, et al.

PLoS One, 2018;13(7):e0200698.
PMID: 30016369 DOI: 10.1371/journal.pone.0200698

Both obesity and DENV infections are growing public health concerns that have far-ranging socioeconomic effects, especially in developing countries. Despite the increasing prevalence of these conditions, there is a scarcity of data investigating the potential relationships between these two entities. Our study aims to examine the influence of obesity on various clinical and laboratory parameters amongst patients with DENV infections. A total of 335 hospitalized patients aged >12 years who were DENV non-structural protein 1 (NS1) antigen-positive were enrolled in this study. Clinical and laboratory variables were compared between patients with and without obesity. Multivariate analysis showed that the following admission clinical findings and laboratory results were independently associated with obesity; chills and rigors (AOR:2.653, 95% CI: 1.286-5.474), higher temperature (AOR:1.485, 95% CI: 1.080-2.042), higher systolic BP (AOR:1.057, 95% CI:1.037-1.078), raised haematocrit (AOR: 1.953, 95% CI: 1.010-3.778), elevated creatinine (AOR:3.504, 95% CI:1.351-9.008) and elevated ALT (AOR: 4.146, 95% CI:1.878-9.154). Obesity was found to be significantly associated with hospitalization >3 days (AOR: 1.990, 95% CI: 1.134-3.494) and the presence of increasing haematocrit with decreasing platelets (AOR: 2.134, 95% CI = 1.235-3.688). Serial assessment of laboratory data revealed that peak haematocrit was significantly higher and nadir platelets levels were significantly lower in obese patients. Both peak and admission levels of leukocyte counts, AST, ALT and creatinine were significantly higher in the obese group. Conversely, both admission and nadir albumin levels were lower for the obese group, although only nadir albumin levels achieved statistical significance. These findings support closer clinical monitoring of obese patients who present with DENV infections, as this patient cohort may possess an increased tendency towards developing more severe clinical manifestations of DENV infections as compared to non-obese patients.
Factors associated with ultrasound-guided water enema reduction for pediatric intussusception in resource-limited setting: potential predictive role of thrombocytosis and anemia

Lim RZM, Lee T, Ng JYZ, Quek KF, Abdul Wahab N, Amansah SL, et al.

J Pediatr Surg, 2018 Nov;53(11):2312-2317.
PMID: 29459045 DOI: 10.1016/j.jpedsurg.2018.01.004

BACKGROUND/PURPOSE: Although ultrasound-guided hydrostatic reduction (USGHR) is increasingly used in managing pediatric intussusception, there is limited literature concerning its use in Malaysia. We aim to examine the experience and factors associated with the effectiveness of USGHR using water.
METHODS: This is a single-center retrospective observational study in a Malaysian tertiary referral center. Children with intussusception admitted between year 2012 and 2016 were included and medical records reviewed. Factors associated with success or failure of USGHR were identified using multivariable logistic regression.
RESULTS: Of the 172 cases included, 151 cases (87.8%) underwent USGHR, of whom 129 cases were successfully reduced (success rate of 85.4%). One perforation (0.7%) was reported. Age more than 3years old (aOR=7.16; 95% CI=1.07-47.94; p=0.042), anemia (aOR=10.12; 95% CI=1.12-91.35; p=0.039), thrombocytosis (aOR=11.21; 95% CI=2.06-64.33; p=0.005) and ultrasound findings of free fluid (aOR=9.39; 95% CI=1.62-54.38; p=0.012) and left-sided intussusception (aOR=8.18;95% CI=1.22-54.90, p=0.031) were independently associated with USGHR irreducibility. Symptom duration, blood in stool, vomiting and other clinical presentations, however, showed no association.
CONCLUSIONS: USGHR with water is effective in the non-operative management of pediatric intussusception. Prolonged symptom duration need not necessarily preclude USGHR. The findings of anemia and thrombocytosis as independent predictors of USGHR irreducibility deserve further study.
TYPE OF STUDY: Treatment study LEVEL OF EVIDENCE: III.
Fulltext Impact of dengue virus (DENV) co-infection on clinical manifestations, disease severity and laboratory parameters

Dhanoa A, Hassan SS, Ngim CF, Lau CF, Chan TS, Adnan NA, et al.

BMC Infect Dis, 2016 08 11;16(1):406.
PMID: 27514512 DOI: 10.1186/s12879-016-1731-8

BACKGROUND: The co-circulation of 4 DENV serotypes in geographically expanding area, has resulted in increasing occurrence of DENV co-infections. However, studies assessing the clinical impact of DENV co-infections have been scarce and have involved small number of patients. This study explores the impact of DENV co-infection on clinical manifestations and laboratory parameters.
METHODS: This retrospective study involved consecutive hospitalized patients with non-structural protein 1 (NS1) antigen positivity during an outbreak (Jan to April 2014). Multiplex RT-PCR was performed directly on NS1 positive serum samples to detect and determine the DENV serotypes. All PCR-positive serum samples were inoculated onto C6/36 cells. Multiplex PCR was repeated on the supernatant of the first blind passage of the serum-infected cells. Random samples of supernatant from the first passage of C6/36 infected cells were subjected to whole genome sequencing. Clinical and laboratory variables were compared between patients with and without DENV co-infections.
RESULTS: Of the 290 NS1 positive serum samples, 280 were PCR positive for DENV. Medical notes of 262 patients were available for analysis. All 4 DENV serotypes were identified. Of the 262 patients, forty patients (15.3 %) had DENV co-infections: DENV-1/DENV-2(85 %), DENV-1/DENV-3 (12.5 %) and DENV-2/DENV-3 (2.5 %). Another 222 patients (84.7 %) were infected with single DENV serotype (mono-infection), with DENV- 1 (76.6 %) and DENV- 2 (19.8 %) predominating. Secondary dengue infections occurred in 31.3 % patients. Whole genome sequences of random samples representing DENV-1 and DENV-2 showed heterogeneity amongst the DENVs. Multivariate analysis revealed that pleural effusion and the presence of warning signs were significantly higher in the co-infected group, both in the overall and subgroup analysis. Diarrhoea was negatively associated with co-infection. Additionally, DENV-2 co-infected patients had higher frequency of patients with severe thrombocytopenia (platelet count < 50,000/mm(3)), whereas DENV-2 mono-infections presented more commonly with myalgia. Elevated creatinine levels were more frequent amongst the co-infected patients in univariate analysis. Haemoconcentration and haemorrhagic manifestations were not higher amongst the co-infected patients. Serotypes associated with severe dengue were: DENV-1 (n = 9), DENV-2 (n = 1), DENV-3 (n = 1) in mono-infected patients and DENV-1/DENV-2 (n = 5) and DENV-1/DENV-3 (n = 1) amongst the co-infected patients.
CONCLUSION: DENV co-infections are not uncommon in a hyperendemic region and co-infected patients are skewed towards more severe clinical manifestations compared to mono-infected patients.
Fulltext Contribution of Viral Respiratory Infections to Dengue-Like Illness Presentation at a Community Clinic in Southern Malaysia

Dhanoa A, Ngim CF, Yunos NM, Husain SMT, Pong LY, Ismail WFW, et al.

Am J Trop Med Hyg, 2021 Sep 27;106(1):187-191.
PMID: 34583338 DOI: 10.4269/ajtmh.21-0648

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 (July 1- October 1, 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.
Fulltext Rapid testing requires clinical evaluation for accurate diagnosis of dengue disease: A passive surveillance study in Southern Malaysia

Ngim CF, Husain SMT, Hassan SS, Dhanoa A, Ahmad SAA, Mariapun J, et al.

PLoS Negl Trop Dis, 2021 05;15(5):e0009445.
PMID: 34014983 DOI: 10.1371/journal.pntd.0009445

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.