Burden of pertussis among young infants in Malaysia: A hospital-based surveillance study.

BACKGROUND: The case fatality rate and the risk of complications due to pertussis is very high in infants. Asia has the second highest childhood pertussis burden. The study aimed to assess the prevalence, clinical complications, and mortality rates of pertussis disease requiring hospitalization among young infants in Malaysia. METHODS: The study was a one-year, hospital-based, multi-site surveillance of infants less than six months of age with symptoms consistent with pertussis and a cross-sectional analysis of their mothers for recent pertussis infection. Information was obtained from medical records and interviews with the parents. Pertussis diagnosis was confirmed for all infants through serum anti-PT titration test or PCR test. RESULTS: 441 possible cases of pertussis were included in this study. Of these, 12.7 % had laboratory confirmation of pertussis. Infants with confirmed pertussis had significantly higher rates of cyanosis (37.5 % vs 8.6 %; p < 0.0001) and apnea (12.5 % vs 3.9 %; p = 0.027) than test-negative infants. Most infants from both groups were in recovery/recovered at discharge. Those with confirmed pertussis had higher case fatality rate than test-negative cases (5.4 % vs 1.0 %; p = 0.094), but the difference did not reach significance. The majority of confirmed pertussis cases (89.3 %) occurred in infants too young to be fully vaccinated or under-vaccinated for their age. Both test-negative and confirmed pertussis resulted in work-day losses and incurred costs for both parents. CONCLUSIONS: A high pertussis disease burden persists in infants less than six months of age, especially among those un- and under-vaccinated. Maternal and complete, on-time infant vaccination is important to reduce disease burden.

Differential Regulation of NK Cell Receptors in Acute Lymphoblastic Leukemia.

Cancer immunotherapies are preferred over conventional treatments which are highly cytotoxic to normal cells. Focus has been on T cells but natural killer (NK) cells have equal potential. Concepts in cancer control and influence of sex require further investigation to improve successful mobilization of immune cells in cancer patients. Acute lymphoblastic leukemia (ALL) is a hematological malignancy mainly of B cell (B-ALL) and T cell (T-ALL) subtypes. Influence of ALL on NK cell is still unclear. Targeted next-generation sequencing was conducted on 62 activating/inhibitory receptors, ligands, effector, and exhaustion molecules on T-ALL (6 males) and normal controls (NC) (4 males and 4 females). Quantitative PCR (q-PCR) further investigated copy number variation (CNV), methylation index (MI), and mRNA expression of significant genes in T-ALL (14 males), NC (12 males and 12 females), and B-ALL samples (N = 12 males and 12 females). Bioinformatics revealed unique variants particularly rs2253849 (T>C) in KLRC1 and rs1141715 (A>G) in KLRC2 only among T-ALL (allele frequency 0.8-1.0). Gene amplification was highest in female B-ALL compared to male B-ALL (KLRC2, KLRC4, and NCR3, p < 0.05) and lowest in male T-ALL cumulating in deletion of KLRD1 and CD69. MI was higher in male ALL of both subtypes compared to normal (KIR2DL1-2 and 4 and KIR2DS2 and 4, p < 0.05) as well as to female B-ALL (KIR3DL2 and KIR2DS2, p < 0.05). mRNA expressions were low. Thus, ALL subtypes potentially regulated NK cell suppression by different mechanisms which should be considered in future immunotherapies for ALL.

Forecasting COVID-19 Case Trends Using SARIMA Models during the Third Wave of COVID-19 in Malaysia.

With many countries experiencing a resurgence in COVID-19 cases, it is important to forecast disease trends to enable effective planning and implementation of control measures. This study aims to develop Seasonal Autoregressive Integrated Moving Average (SARIMA) models using 593 data points and smoothened case and covariate time-series data to generate a 28-day forecast of COVID-19 case trends during the third wave in Malaysia. SARIMA models were developed using COVID-19 case data sourced from the Ministry of Health Malaysia's official website. Model training and validation was conducted from 22 January 2020 to 5 September 2021 using daily COVID-19 case data. The SARIMA model with the lowest root mean square error (RMSE), mean absolute percentage error (MAE) and Bayesian information criterion (BIC) was selected to generate forecasts from 6 September to 3 October 2021. The best SARIMA model with a RMSE = 73.374, MAE = 39.716 and BIC = 8.656 showed a downward trend of COVID-19 cases during the forecast period, wherein the observed daily cases were within the forecast range. The majority (89%) of the difference between the forecasted and observed values was well within a deviation range of 25%. Based on this work, we conclude that SARIMA models developed in this paper using 593 data points and smoothened data and sensitive covariates can generate accurate forecast of COVID-19 case trends.

Efficiency and management factors: finding the balance in Thalassaemia care centres.

BACKGROUND: Optimizing efficiency has become increasingly critical with the growing demand for finite healthcare resources driven by population growth and an ageing society. Hence, policymakers are urgently finding more efficient ways to deliver health services. Thalassemia is a complex inherited blood disorder with significant prevalence in Malaysia. The high number of patients put substantial strain on the healthcare system. This study aims to evaluate the technical efficiency of thalassaemia care centres throughout Malaysia and the determinants that affect the efficiency. METHOD: Data from 30 public hospitals with thalassaemia care centres were collected. A double bootstrap data envelopment analysis (DEA) approach is used with the assumption of input-oriented and variable-to-scale DEA models to generate technical efficiency scores. Bootstrap truncated regression was later conducted to identify the factors affecting the efficiency scores. RESULTS: The mean bias-corrected technical efficiency score has improved to 0.75 in 2017 from 0.71 in 2016. In both years, more than 50% of thalassaemia care centres showed good efficiency scores (0.8-1.0). Management factors that affect the efficiency scores include separation of patient management (ß = 0.0653) and budget (ß = 0.0843), where they are found to positively affect the efficiency scores. In contrast, having longer operating hours is found to inversely influence the performance levels (ß = - 0.4023). CONCLUSIONS: The study provides a pioneering framework to evaluate the technical efficiency of thalassaemia treatment centres in public healthcare settings and could provide a useful guide for policymaker and thalassaemia care centre managers to improve efficiency in service delivery to thalassaemia patients and their caregivers without compromising quality of care.

Effectiveness of the movement control measures during the third wave of COVID-19 in Malaysia.

OBJECTIVES: Starting in March 2020, movement control measures were instituted across several phases in Malaysia to break the chain of transmission of coronavirus disease 2019 (COVID-19). In this study, we developed a susceptible-exposed-infected-recovered (SEIR) model to examine the effects of the various phases of movement control measures on disease transmissibility and the trend of cases during the third wave of the COVID-19 pandemic in Malaysia. METHODS: Three SEIR models were developed using the R programming software ODIN interface based on COVID-19 case data from September 1, 2020, to March 29, 2021. The models were validated and subsequently used to provide forecasts of daily cases from October 14, 2020, to March 29, 2021, based on 3 phases of movement control measures. RESULTS: We found that the reproduction rate (R-value) of COVID-19 decreased by 59.1% from an initial high of 2.2 during the nationwide Recovery Movement Control Order (RMCO) to 0.9 during the Movement Control Order (MCO) and Conditional MCO (CMCO) phases. In addition, the observed cumulative and daily highest numbers of cases were much lower than the forecasted cumulative and daily highest numbers of cases (by 64.4-98.9% and 68.8-99.8%, respectively). CONCLUSIONS: The movement control measures progressively reduced the R-value during the COVID-19 pandemic. In addition, more stringent movement control measures such as the MCO and CMCO were effective for further lowering the R-value and case numbers during the third wave of the COVID-19 pandemic in Malaysia due to their higher stringency than the nationwide RMCO.

Economic burden in the management of transfusion-dependent thalassaemia patients in Malaysia from a societal perspective.

BACKGROUND: Transfusion-dependent thalassaemia (TDT) is a hereditary blood disorder in which blood transfusion is the mainstay treatment to prolong survival and improve quality of life. Patients with this disease require blood transfusion at more than 100 ml/kg annually and iron-chelating therapy (ICT) to prevent iron overload (IOL) complications. There are substantial numbers of TDT patients in Malaysia, but limited data are available regarding the economic burden associated with this disease. The purpose of this study was to determine the lifetime cost of TDT from a societal perspective and identify potential factors increasing patient and family expenditures among thalassaemia populations. METHODS: The total lifetime cost per TDT patient (TC1) is the sum of lifetime healthcare cost (TC2) and lifetime patient and family healthcare expenditure (TC3). TC2 was simulated using the Markov model, taking into account all costs subsidized by the government, and TC3 was estimated through a cross-sectional health survey approach. A survey was performed using a two-stage sampling method in 13 thalassaemia centres covering all regions in Malaysia. RESULTS: A TDT patient is expected to incur TC2 of USD 561,208. ICT was the main driver of cost and accounted for 56.9% of the total cost followed by blood transfusion cost at 13.1%. TC3 was estimated to be USD 45,458. Therefore, the estimated TC1 of a TDT patient was USD 606,665. Sensitivity analyses showed that if all patients were prescribed oral ICT deferasirox for their lifetime, the total healthcare cost would increase by approximately 65%. Frequency of visits to health facilities for blood transfusion/routine monitoring and patients who were prescribed desferrioxamine were observed to be factors affecting patient and family monthly expenses. CONCLUSION: The lifetime cost per TDT patient was USD 606,665, and this result may be useful for national health allocation planning. An estimation of the economic burden will provide additional information to decision makers on implementing prevention interventions to reduce the number of new births and medical service reimbursement.

Validity of the Malay EQ-5D-3L in the Malaysian Transfusion-Dependent Thalassemia Population.

OBJECTIVE: The objective of this study was to examine the cross-sectional convergent and known-group validity of the Malay-language EQ-5D-3L instrument in children and adults with transfusion-dependent thalassemia (TDT). METHODS: A cross-sectional health-related quality of life survey involving TDT patients from 12 different treatment centers across Malaysia was conducted using the Malay PedsQL 4.0 Generic Core Scales and the Malay EQ-5D-3L questionnaire. Patients with non-TDT and other hemoglobinopathies were excluded. Convergent, discriminant, and known-group validity of the EQ-5D-3L was assessed against the PedsQL 4.0 Generic Core Scales in children. In the adult population, known-group validity of the EQ-5D-3L was assessed using an a priori hypothesis between patients' demographic characteristics and health outcomes obtained from literature. RESULTS: A total of 370 children and 225 adults were sampled. The mean (standard deviation) EQ-5D-3L scores of the children were 0.892 (0.082) and the adults were 0.887 (0.085). Convergent and discriminant validity was identified when correlated with the PedsQL domain in children. In both groups, known-group validity was evident when comparing groups of patients with reported problems to the group of patients with no reported problems on the EQ-5D-3L domains based on the a priori hypothesis derived from literature. CONCLUSION: This study found convergent, discriminant, and known-group validity of the Malay EQ-5D-3L in a population-based sample of patients with TDT. Hence, the instrument is valid for the assessment of health-related quality of life in children and adults with TDT in Malaysia.

Rurioctocog alfa pegol PK-guided prophylaxis in hemophilia A: results from the phase 3 PROPEL study.

Rurioctocog alfa pegol prophylaxis targeting factor VIII (FVIII) troughs ≥1% has shown to be efficacious with an acceptable safety profile in people with hemophilia A (PwHA). The PROPEL trial compared safety and efficacy of 2 target FVIII troughs in PwHA aged 12 to 65 years, with severe disease, annualized bleeding rate ≥2, and previous FVIII treatment. PwHA were randomized to 12 months' pharmacokinetic (PK)-guided rurioctocog alfa pegol prophylaxis targeting FVIII troughs of 1% to 3% (reference arm) or 8% to 12% (elevated arm); first 6 months was treatment-adjustment period. The primary endpoint was absence of bleeds during the second 6 months, analyzed using multiple imputations (full analysis set [FAS]). In the 1% to 3% and 8% to 12% arms, respectively, point estimates (95% confidence interval) of proportions of PwHA with zero total bleeds were 42% (29% to 55%) and 62% (49% to 75%) in FAS (N = 115; P = .055) and 40% (27% to 55%) and 67% (52% to 81%) in per-protocol analysis set (N = 95; P = .015). Dosing frequency and consumption varied in each arm. Adverse events (AEs) occurred in 70/115 (60.9%) PwHA; serious AEs in 7/115 (6%) PwHA, including 1 treatment-related in 8% to 12% arm (transient anti-FVIII inhibitor). There were no deaths, serious thrombotic events, or AE-related discontinuations. PK-guided prophylaxis was achievable and efficacious in both arms. No new safety signals were observed in the 8% to 12% arm. These results demonstrate elevated FVIII troughs can increase the proportion of PwHA with zero bleeds and emphasize the importance of personalized treatment. This trial was registered at www.clinicaltrials.gov as #NCT02585960.

Health-related quality of life among children with transfusion-dependent thalassemia: A cross-sectional study in Malaysia.

BACKGROUND: The treatment of children with transfusion-dependent thalassemia (TDT) in Malaysia has progressed since 2005. This study provides an updated health-related quality of life (HRQoL) assessment for children with the disorder and the factors affecting the HRQoL. METHODS: A cross-sectional HRQoL survey of Malaysian children with TDT was conducted using the PedsQL™ 4.0 Generic Core Scales. Patients with non-transfusion dependent thalassemia and other haemoglobinopathies were excluded. Parent-proxy and self-reported HRQoL scores were obtained using a multi-stage convenient sampling. The relationship between HRQoL scores and demographic factors were tested using association, correlation and regression analysis. RESULTS: A total of 368 patients were recruited. The mean (SD) Total Summary Score (TSS) was 80.12(13.87). Predictors for a lower TSS was an increasing age group and the use of dual chelating agents (R2 = 0.057, F (4, 359) = 5.40, p = < 0.001). The mean (SD) Physical Health Summary Score (PHSS) was 82.21 (16.82). Predictors of a higher PHSS score was being male, while predictors of a lower score was an increasing age group and parent-proxy reports(R2 = 0.075, F (5,358) = 5.80, p = < 0.001). The mean (SD) Psychosocial Health Summary Score (PCHS) was 79.39 (14.81). Predictors for a lower PCHS was the use of dual chelating agents(R2 = 0.041, F (1, 362) = 15.60, p = < 0.001). The school functioning score had the lowest mean (SD) score of 69.52(20.92) in the psychosocial dimension. CONCLUSION: The HRQoL of TDT children in Malaysia has improved over the last decade owing to the better access in treatment. However, further effort is needed to improve the school functioning dimension.

Association of ABCC2 with levels and toxicity of methotrexate in Malaysian Childhood Acute Lymphoblastic Leukemia (ALL).

Studies had shown that genetic polymorphism plays a significant role in the pharmacokinetics and pharmacodynamics variation of high dose methotrexate (MTX), 5000 mg/m2 regimen. The objective of this study was to investigate the genetic variations associated with the serum level and toxicity of MTX in Malaysian children with acute lymphoblastic leukemia (ALL). Thirty-eight patients were genotyped for rs717620 (ABCC2), rs4948496 (ARID5B), rs1801133 (MTHFR) and rs4149056 (SLCO1B1). Serum levels of MTX at 48 h post 24 h of intravenous infusion were analyzed by high-performance liquid chromatography-mass spectrometry. The ABCC2 genotype was significantly associated with the serum levels of MTX at 48 h after treatment (p = 0.017). Patients with CT and TT of rs717620 (ABCC2) and TC and CC of rs4948496 (ARID5B) were significantly associated with leukopenia grade I-IV (Fisher Exact Test; p = 0.03 and 0.02, respectively). The three most common MTX related toxicities were leukopenia (60.5%), increased alanine aminotransferase enzyme (47.4%), and thrombocytopenia (47.4%). Our results demonstrate that by prescreening of patients for ABCC2 and ARID5B associated with the serum levels and adverse effects of MTX would identify patients at risk and therefore help a pediatric oncologist to personalize chemotherapy drugs for precision health.

Roles of cancer registries in enhancing oncology drug access in the Asia-Pacific region.

Cancer registries help to establish and maintain cancer incidence reporting systems, serve as a resource for investigation of cancer and its causes, and provide information for planning and evaluation of preventive and control programs. However, their wider role in directly enhancing oncology drug access has not been fully explored. We examined the value of cancer registries in oncology drug access in the Asia-Pacific region on three levels: (1) specific registry variable types; (2) macroscopic strategies on the national level; and (3) a regional cancer registry network. Using literature search and proceedings from an expert forum, this paper covers recent cancer registry developments in eight economies in the Asia-Pacific region - Australia, China, Hong Kong, Malaysia, Singapore, South Korea, Taiwan, and Thailand - and the ways they can contribute to oncology drug access. Specific registry variables relating to demographics, tumor characteristics, initial treatment plans, prognostic markers, risk factors, and mortality help to anticipate drug needs, identify high-priority research area and design access programs. On a national level, linking registry data with clinical, drug safety, financial, or drug utilization databases allows analyses of associations between utilization and outcomes. Concurrent efforts should also be channeled into developing and implementing data integrity and stewardship policies, and providing clear avenues to make data available. Less mature registry systems can employ modeling techniques and ad-hoc surveys while increasing coverage. Beyond local settings, a cancer registry network for the Asia-Pacific region would offer cross-learning and research opportunities that can exert leverage through the experiences and capabilities of a highly diverse region.

A case-control study on the association between environmental factors and the occurrence of acute leukemia among children in Klang Valley, Malaysia.

BACKGROUND: In Malaysia, acute leukemia is the most common cancer among children below the age of 15. A case-control study was here conducted for cases from the Klang Valley, Malaysia, who received treatment at the National University of Malaysia Hospital (HUKM) and Kuala Lumpur General Hospital (GHKL). The main objective was to determine any association with environmental factors. METHODS: Case subjects were children aged below 15 years and diagnosed with acute leukemia in HUKM and GHKL between January 1, 2001 and May 30, 2007. Control subjects were children aged below 15 years who were diagnosed with any non-cancerous acute illnesses in these hospitals. A total of 128 case subjects and 128 control subjects were enrolled in this study. The information was collected using a structured questionnaire and a global positioning system (GPS) device. All factors were analyzed using unmatched logistic regression. RESULTS: The analysis showed that the occurrence of acute leukemia among children was strongly determined by the following factors: family income (odds ratio (OR) 0.19, 95% confidence interval (CI): 0.09-0.42), father with higher social contact (OR 7.61, 95% CI: 3.78-15.4), number of elder siblings (OR 0.36, 95% CI: 0.18-0.77), father who smokes (OR 2.78, 95% CI: 1.49-5.16), and the distance of the house from a power line (OR 2.30, 95% CI: 1.18-4.49). CONCLUSIONS: Some socioeconomic, demographic, and environmental factors are strong predictors of the occurrence of acute leukemia among children in Klang Valley, Malaysia. In terms of environmental factors, it is recommended that future housing areas should be developed at least 200 m away from power lines.

Health Related Quality of Life in Malaysian children with thalassaemia.

BACKGROUND: Health Related Quality of Life (HRQoL) studies on children with chronic illness such as thalassaemia are limited. We conducted the first study to investigate if children with thalassaemia have a lower quality of life in the four dimensions as measured using the PedsQL 4.0 generic Scale Score: physical, emotional, social and role (school) functioning compared to the healthy controls allowing for age, gender, ethnicity and household income. METHODS: The PedsQL 4.0 was administered to children receiving blood transfusions and treatments at Hospital Kuala Lumpur, Malaysia using PedsQL 4.0 generic Scale Score. Accordingly, the questionnaire was also administered to a control group of healthy school children. Socio-demographic data were also collected from patients and controls using an interview schedule designed for the study. RESULTS: Of the 96 thalassaemia patients approached, 78 gave consent to be interviewed giving a response rate of 81.3%. Out of 235 healthy controls approached, all agreed to participate giving a response rate of 100%. The mean age for the patients and schoolchildren is 11.9 and 13.2 years respectively. The age range for the patients and the schoolchildren is between 5 to 18 years and 7 to 18 years respectively. After controlling for age and demographic background, the thalassaemia patients reported having significantly lower quality of life than the healthy controls. CONCLUSION: Thalassaemia has a negative impact on perceived physical, emotional, social and school functioning in thalassaemia patients which was also found to be worse than the children's healthy counterparts. Continuing support of free desferal from the Ministry of Health should be given to these patients. More understanding and support especially from health authorities, school authorities and the society is essential to enhance their quality of life.