Obtaining assent for research involving children in Malaysia: a position statement from the Academy of Medicine of Malaysia College of Paediatrics.

The Academy of Medicine of Malaysia College of Paediatrics acknowledges the role of children in research and this position statement explores the ethical considerations in obtaining assent from minors in the Malaysian context. It highlights the importance in respecting children's agency and navigating cultural complexities. The College proposes flexibility in the minimum age for assent of at least nine years old, while emphasising the need for a tailored assent procedure. Addressing language and cultural diversities and expanding local empirical research on a formal assent process are some building blocks in developing a standardised nationwide process in obtaining assent from children.

The effects of N-acetylcysteine on lung alveolar epithelial cells infected with respiratory syncytial virus.

INTRODUCTION: Respiratory syncytial virus (RSV) is one of the most common causes of acute lower respiratory infection in infants and young children. Mucolytic agents, such as acetylcysteine and carbocysteine have reported benefits in alleviating acute upper or lower respiratory infections. Among these, N-acetylcysteine (NAC) has cyto-protective effects when cells are infected with the RSV. MATERIALS AND METHODS: Our study investigated primarily the dose-dependent effects of NAC on respiratory alveolar epithelial (A549) cells when co-cultured with RSV in vitro. Three different concentrations of NAC were used, 0.1 mM, 1 mM, and 10 mM. The cytotoxicity of RSV-infected cells was measured by lactate dehydrogenase and antiviral activity of NAC on cell cultures was evaluated by immunofluorescence. RESULTS: Pre-treatment with the highest dose, 10 mM NAC, resulted in features of cell injury even without RSV infection. The proportion of cells infected by RSV and RSV-induced cell death decreased by more than 3-fold when cells were pre-treated with 1 mM NAC. Pre-treatment at the lowest dose, 0.1 mM, did not show any significant changes. CONCLUSION: A moderate dose of NAC (1 mM) appeared protective of RSV infection to lung alveolar epithelial cells. However, a higher dose of NAC (10 mM) may be relatively toxic and injurious to these cells.

Evaluation of quantitative point-of-care test for measurement of glucose-6-phosphate dehydrogenase enzyme activity in Malaysia.

INTRODUCTION: The treatment of Plasmodium vivax malaria with 8-aminoquinolines is contraindicated in glucose-6-phosphate dehydrogenase (G6PD) deficient individuals due to the risk of acute haemolytic anaemia. Effective G6PD screening is paramount to avoid adverse drug reactions. This study aimed to evaluate the performance of novel quantitative point-of-care (POC) tests as a new screening method for G6PD deficiency in Malaysia. MATERIALS AND METHODS: A total of 153 neonatal cord blood, 99 peripheral blood of older children aged between 1 month to 12-years old, and 62 peripheral adult blood were screened for G6PD deficiency using two quantitative POC tests, CareStartTM biosensor (Carestart) and CareStartTM Biosensor 1 (S1). The results were compared with OSMMR2000D kit as a reference assay. Two statistical analyses were performed in this study to evaluate the POC test performances, the Spearman's correlation test and the Cohen's kappa method. RESULTS: Both Carestart and S1 tests showed significant positive correlations to OSMMRS000D with r2 = 0.7916 and r2 = 0.7467. Their measurement of agreement showed a kappa (κ) value of 0.805 (p<0.001, 95% CI), and 0.795 (p<0.001, 95% CI), respectively. Analysis of the area under the Receiver Operating Curve (ROC) at 60% cut-off illustrated that the Carestart had 90.2% sensitivity, 98.9% specificity, 98.3% positive predictive value (PPV), and 93.8% negative predictive value (NPV). The corresponding values for the S1 were 95.2%, 100%, 100%, and 96.8%, respectively. CONCLUSION: This study showed that the Carestart and S1 biosensors have high-performance reliability for screening of G6PD deficiency, which can guide safe prescriptions of anti-malaria medications and hence, eradication of Plasmodium vivax malaria.

COVID-19 vaccination for children in Malaysia - A position statement by the College of Paediatrics, Academy of Medicine of Malaysia.

The availability of COVID-19 vaccines and mass vaccination programmes in adults have significantly reduced the case attack rates and disease burden. COVID-19 vaccination successfully decreases the population at risk of infection, allowing for the safer re-opening of economies and reducing the pandemic's crippling impact on healthcare systems. However, the rapidly mutating severe acute respiratory syndrome-coronavirus-2 poses challenges in diminishing vaccine-induced immunity and vaccinating a significant proportion of adults to achieve herd immunity. These challenges necessitated adolescent vaccination. With the recent emergence of the highly transmissible Omicron variant and the increasing COVID-19 hospitalisation rates of children below 12 years old, many countries opted to also vaccinate younger children. Phase II/III clinical trials and real-world experience demonstrate that COVID-19 vaccinations are effective and safe for younger children and adolescents. Before Malaysia introduced its national COVID-19 vaccination programme for children 5-11 years old (which ran between March and June 2022), an expert advisory statement was issued by the College of Paediatrics, Academy of Medicine of Malaysia, to highlight the benefits and importance of vaccinating children. The advisory statement included clarifications about vaccine-related side effects such as post-vaccination myocarditis and allergic reactions to encourage informed decision making by healthcare providers and parents. This paper, which was prepared based on the critical appraisal of the current evidence, evaluation of the international experiences and the positive impact of COVID-19 vaccination in children, collectively sums up the rationale to support and ensure the success of the nationwide vaccination programme for children. Hence, the College recommends COVID-19 vaccination for children in Malaysia.

Severe acute respiratory syndrome-Coronavirus-2 infection: A review of the clinical-pathological correlations of Coronavirus disease-19 in children.

The coronavirus disease-19 (COVID-19) has become a global pandemic of acute respiratory disease in just less than a year by the middle of 2020. This disease caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), has resulted in significant mortality especially among the older age population and those with health co-morbidities. In contrast, children are relatively spared of this potentially ravaging disease that culminates in the acute respiratory distress syndrome, multi-organ failure and death. SARS-CoV-2 infection induces exuberant release of pro-inflammatory mediators, causing a "cytokine storm" and hypercoagulable states that underlie these complications. The SARS-CoV-2 infection median incubation is 5.1 days, with most developing symptoms by 11.5 days. It is highly infectious, spreading via the horizontal mode of transmission, but there is yet very limited evidence of vertical transmission to the newborn infant occurring either transplacentally or through breastfeeding. This said, various immune factors during childhood may modulate the expression of COVID-19, with the multisystem inflammatory syndrome in children (MIS-C) at the severe end of the disease spectrum. This article gives an overview of the SARS-CoV-2 infection, clinical presentation and laboratory tests of COVID-19 and correlating with the current understanding of the pathological basis of this disease in the paediatric population.

Correction to 'Genotyping of Malaysian G6PD-deficient neonates by reverse dot blot flow-through hybridisation'.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Genotyping of Malaysian G6PD-deficient neonates by reverse dot blot flow-through hybridisation.

G6PD deficiency is the commonest enzyme deficiency found in humans. Current diagnostic methods lack sensitivity to detect all cases of G6PD deficiency. We evaluated the reverse dot blot flow-through hybridisation assay designed to detect simultaneously multiple known G6PD mutations in a group of Malaysian neonates. Archival DNA samples from 141 G6PD-deficient neonates were subjected to reverse dot blot flow-through hybridisation assay using the GenoArray Diagnostic Kit (Hybribio Limited, Hong Kong) and DNA sequencing. The method involved PCR amplification of 5 G6PD exons using biotinylated primers, hybridisation of amplicons to a membrane containing oligoprobes designed for G6PD mutations known to occur in the Malaysian population and colour detection by enzyme immunoassay. The assay detected 13 of the 14 G6PD mutations and genotyped 133 (94.3%) out of 141 (102 males, 39 females) cases. Among the 39 female G6PD-deficient neonates, there were 7 homozygous and 6 compound heterozygous cases. The commonest alleles were G6PD Viangchan 871G > A (21%) and G6PD Mahidol 487G > A(20%) followed by G6PD Mediterranean 563C > T, (14%), G6PD Vanua Lava 383T > C (12%), G6PD Canton 1376G > T (10%), G6PD Orissa 131C > G (6.3%) G6PD Coimbra 592C > T (5.6%) plus 6 other mutations. DNA sequencing of remaining cases revealed 6 cases of intron 11 nt 93C > T not previously reported in Malaysia and two novel mutations, one case each of nt 1361G > T and nt 1030G > A. We found the reverse dot blot assay easy to perform, rapid, accurate and reproducible, potentially becoming an improved diagnostic test for G6PD deficiency.

Gardnerella vaginalis in perinatology: An overview of the clinicopathological correlation.

Gardnerella vaginalis (GV) is a facultatively anaerobic gram-variable bacillus and is the major organism involved in bacterial vaginosis. GV-associated bacterial vaginosis has been associated with adverse pregnancy outcomes include preterm parturition and subclinical chorioamnionitis. Inflammatory response induced by GV presents paediatric problems as well. Studies had shown that increased levels of proinflammatory cytokines include TNF-α, IL-1ß and IL-6 following fetal inflammatory response syndrome secondary to GV-induced intrauterine infection may result in the development of periventricular leukomalacia and bronchopulmonary dysplasia in the infected fetus. There is increasing evidence that GV-associated BV infection serves as a risk factor for long-term neurological complications, such as cerebral palsy and learning disability. GV is fastidious and could elude conventional detection methods such as bacterial cultures. With current more sophisticated molecular biology detection methods, its role and pathogenic effects have been shown to have a greater impact on intrauterine inflammation and fetal/neonatal infection. This review gives an overview on the characteristics of GV and its virulence properties. Its detrimental role in causing unfavourable GV-related perinatal outcomes, with emphasis on the possible mechanistic pathways is discussed. The discovery of disease mechanisms allows the building of a strong platform where further research on innovative therapies can be based on, for instance, an anti-TLR monoclonal antibody as therapeutic agent to halt inflammation-precipitate adverse perinatal outcomes.

Single-tube tetradecaplex panel of highly polymorphic microsatellite markers < 1 Mb from F8 for simplified preimplantation genetic diagnosis of hemophilia A.

Essentials Preimplantation genetic diagnosis (PGD) of severe hemophilia A relies on linkage analysis. Simultaneous multi-marker screening can simplify selection of informative markers in a couple. We developed a single-tube tetradecaplex panel of polymorphic markers for hemophilia A PGD use. Informative markers can be used for linkage analysis alone or combined with mutation detection. SUMMARY: Background It is currently not possible to perform single-cell preimplantation genetic diagnosis (PGD) to directly detect the common inversion mutations of the factor VIII (F8) gene responsible for severe hemophilia A (HEMA). As such, PGD for such inversion carriers relies on indirect analysis of linked polymorphic markers. Objectives To simplify linkage-based PGD of HEMA, we aimed to develop a panel of highly polymorphic microsatellite markers located near the F8 gene that could be simultaneously genotyped in a multiplex-PCR reaction. Methods We assessed the polymorphism of various microsatellite markers located ≤ 1 Mb from F8 in 177 female subjects. Highly polymorphic markers were selected for co-amplification with the AMELX/Y indel dimorphism in a single-tube reaction. Results Thirteen microsatellite markers located within 0.6 Mb of F8 were successfully co-amplified with AMELX/Y in a single-tube reaction. Observed heterozygosities of component markers ranged from 0.43 to 0.84, and ∼70-80% of individuals were heterozygous for ≥ 5 markers. The tetradecaplex panel successfully identified fully informative markers in a couple interested in PGD for HEMA because of an intragenic F8 point mutation, with haplotype phasing established through a carrier daughter. In-vitro fertilization (IVF)-PGD involved single-tube co-amplification of fully informative markers with AMELX/Y and the mutation-containing F8 amplicon, followed by microsatellite analysis and amplicon mutation-site minisequencing analysis. Conclusions The single-tube multiplex-PCR format of this highly polymorphic microsatellite marker panel simplifies identification and selection of informative markers for linkage-based PGD of HEMA. Informative markers can also be easily co-amplified with mutation-containing F8 amplicons for combined mutation detection and linkage analysis.

ABO incompatibility and glucose-6-phosphate dehydrogenase deficiency presenting as Hydrops Foetalis.

ABO incompatibility and glucose-6-phosphate dehydrogenase deficiency G6PD are common haematological problems affecting the newborn. The resulting haemolytic disease of foetus and newborn (HDFN) caused by either of these pathologies generally follows a benign course. It is typically characterized by mild jaundice without significant anaemia. ABO incompatibility alone as a cause of foetal hydrops is extremely rare. We report a case of a newborn baby girl with an anti-B isoimmunisation and G6PD deficiency manifesting with hydrops foetalis, anaemia and hyperbilirubinaemia, born to a mother with blood group O.

Tracheal agenesis: a rare cause of unsuccessful tracheal intubation during resuscitation.

Tracheal agenesis is a rare congenital airway anomaly that usually results in a fatal outcome. The diagnosis is usually made through post-mortem examination. In the current literature, there has been no reported long-term survival although a few reports claimed prolongation of life of several hours to days. This condition is commonly associated with premature birth, polyhydramnios and a male predominance. In 90% of the cases, it is associated with multiple cardiovascular, gastrointestinal and genitourinary tract anomalies which are incompatible with life. We report a case of a premature newborn with severe respiratory distress, absent cry and cyanosis soon after birth. Attempts at endotracheal intubation failed as it was no possible to negotiate the tube beyond the vocal cords. Needle cricothyrotomy and attempted tracheostomy also failed to secure the airway. The diagnosis was confirmed at post-mortem examination.

Use of magnetic resonance imaging in evaluation of placental invasion.

AIM: To review and describe the magnetic resonance imaging (MRI) features in patients with suspected placental invasion and correlate the findings with surgery and pathology findings. MATERIALS AND METHODS: A retrospective review was undertaken of the MRI images of seven consecutive patients with ultrasound findings suspicious for placental invasion. Two experienced MRI radiologists, blinded to the pathology and surgery findings, reviewed the MRI. The pathology or surgical findings were used as the reference standard to establish accuracy and concordance with the MRI findings. RESULTS: Three MRI features described in an earlier series were consistently present in the patients with placental invasion: lower uterine bulging, heterogeneous placenta, and dark intraplacental linear bands on T2-weighted images. CONCLUSION: MRI features, which were described in patients with placental invasion in an earlier series, were useful in establishing the presence and depth of placental invasion.

A quality assurance study on the administration of medication by nurses in a neonatal intensive care unit.

INTRODUCTION: This study aimed to determine the rates of non-adherence to standard steps of medication administration and medication administration errors committed by registered nurses in a neonatal intensive care unit before and after intervention. METHODS: A baseline assessment of compliance with ten standard medication administration steps by neonatal intensive care unit nurses was carried out over a two-week period. Following this, a re-education programme was launched. Three months later, they were re-assessed similarly. RESULTS: The baseline assessment showed that the nurses did not carry out at least one of the ten standard administrative steps during the administration of 188 medication doses. The most common steps omitted were having another nurse to witness drug administration (95 percent); labelling of individual medication prepared prior to administration (88 percent), checking prescription charts against patients' identification prior to administration (85 percent) and visually inspecting a patient's identification tag (71 percent) . Medication administration errors occurred in 31 percent (59/188) of doses administered, all due to imprecise timing of medication administration. There were no resultant adverse outcomes. Following implementation of remedial measures, there was a significant reduction in non-adherence of seven of the ten medication administration steps and the rate of medication administration errors (p-value is less than 0.001). However, in 94 percent of doses administered, the nurses still did not get a witness to countercheck calculations of drug dosages before administration. CONCLUSION: Non-compliance with the standard practice of medication administration by nurses is common but can be improved by continuing re-education and monitoring, plus the implementation of a standard operating procedure.

Gadolinium-enhanced magnetic resonance angiography in renal artery stenosis: comparison with digital subtraction angiography.

OBJECTIVES: To evaluate the accuracy of gadolinium-enhanced magnetic resonance angiography in assessing renal artery stenosis compared to catheter digital subtraction angiography. DESIGN: Retrospective study. SETTING: Singapore General Hospital. PATIENTS: Records of patients who underwent magnetic resonance angiography as well as digital subtraction angiography for assessment of renal artery stenosis from January 2003 to December 2005 were reviewed. RESULTS: There were 27 patients (14 male, 13 female) with a mean age of 62 (range, 44-77) years. There were 10 patients with renal transplants; their native renal arteries were not evaluated. Each of the two experienced interventional and body magnetic resonance radiologists, who were blinded to the results, reviewed the digital subtraction angiography and magnetic resonance angiography images respectively. Digital subtraction angiography was used as the standard of reference. A total of 39 renal arteries from these 27 patients were evaluated. One of the arteries was previously stented and could not be assessed with magnetic resonance angiography due to severe artefacts. Of the remaining 38 renal arteries, two were graded as normal, seven as having mild stenosis (<50%), eight as having moderate stenosis (> or =50% but <75%), and 21 as having severe stenosis (> or =75%). Magnetic resonance angiography and digital subtraction angiography were concordant in 89% of the arteries; magnetic resonance angiography overestimated the degree of stenosis in 8% and underestimated it in 3% of them. In the evaluation of clinically significant renal artery stenosis (> or =50%) with magnetic resonance angiography, the overall sensitivity, specificity, positive predictive value, and negative predictive value were 97%, 67%, 90%, and 86% respectively. The sensitivity and specificity of magnetic resonance angiography in transplant renal artery stenosis was 100%. CONCLUSION. Our experience suggested that gadolinium-enhanced magnetic resonance angiography is a sensitive non-invasive modality useful in the assessment of clinically significant renal artery stenosis.

Prevalence of significant extracoronary findings on multislice CT coronary angiography examinations and coronary artery calcium scoring examinations.

The purpose of the study was to review the prevalence of significant extracoronary findings in patients who underwent multislice CT coronary angiography examinations and coronary artery calcium scoring examinations. We reviewed the reports of 295 consecutive patients who underwent multislice CT coronary angiography examinations and 140 consecutive patients who had separate coronary calcium scoring examinations from September 2004 to March 2006 in our department's radiology information system. Additional investigations carried out as a result of these findings were also recorded. Fifty-six (19%) out of 295 patients had significant extracoronary findings on coronary CT angiography requiring clinical or radiological follow up. There were 60 significant extracoronary findings. These included 24 patients who had pulmonary abnormalities, 4 who had mediastinal abnormalities, 20 who had upper abdominal abnormalities and 5 who had non-coronary cardiac abnormalities. Three patients had both pulmonary and upper abdominal abnormalities. Eleven (8%) out of 140 patients had significant pulmonary, breast, mediastinal, upper abdominal and cardiac abnormalities on coronary artery calcium scoring examinations, yielding a total of 12 significant findings. In our experience, 19% of the patients who underwent multislice CT coronary angiography and 8% of the patients who underwent coronary artery calcium scoring examinations had significant extracoronary findings requiring follow up. It is therefore imperative for the reporting physician to review the entire examination after the coronary arteries have been assessed. The prevalence of extracoronary findings on these examinations may be of significance, resulting in additional 'hidden costs' if widespread 'screening' is adopted.

Intraperitoneal extravasation of total parental nutrition infusate from an umbilical venous catheter.

A preterm male infant who had an umbilical venous catheter (UVC) in situ for infusion of total parenteral nutrition (TPN) subsequently developed abdominal distension. He was initially diagnosed to have necrotising enterocolitis. However, a diagnostic abdominal paracentesis yielded fluid which biochemical analysis found to be consistent with TPN. TPN is often infused through a UVC, in the first few days of life, for the nutritional support of a premature infant. Various complications have been reported to be associated with this path of delivery, one of which will be illustrated in this case report.

Enterolith formation in the roux limb hepaticojejunostomy.

Enterolith in the Roux limb of Roux-en-Y hepaticojejunostomy is rare. We report a case of a Roux loop enterolith presenting with recurrent cholangitis. Cholescintigraphy and magnetic resonance imaging aided in the preoperative diagnosis. Intraoperatively, a large enterolith was extracted distal to the biliodigestive anastomosis. A kink of the small bowel was also noted distal to the stone. The mechanism for enterolith formation in the Roux loop is discussed.

Endovascular stent graft treatment of leaking thoracic aortic tuberculous pseudoaneurysm.

Mycobacterium tuberculosis infection is one of the leading causes of death from communicable diseases worldwide. However, the incidence of leaking thoracic aortic tuberculous pseudoaneurysms is rare as a complication. Conventional treatment of a leaking tuberculous pseudoaneurysm involves surgery with graft interposition or patch repair. With the emergence of stent graft treatment as a viable option for leaking pseudoaneurysms, we report a 63-year-old man who had his leaking toracic aortic tuberculous pseudoaneurysm treated with endovascular stent grafting.

Coronary subclavian steal syndrome: a rare cause of acute myocardial infarction.

The coronary subclavian steal syndrome (CSSS) leading to an acute myocardial infarction (AMI) post-coronary bypass is a rare occurrence. We describe an 83-year-old Indian man who presented with AMI and was subsequently found to have CSSS. The patient had severe stenosis of his left subclavian artery ostium with retrograde flow up his left internal mammary artery graft. Angiographical steal from the left anterior descending artery was demonstrated during coronary angiogram and was thought to be the main contributing cause of his AMI. Percutaneous transfemoral angioplasty and stent implantation was performed to the left subclavian artery, with resolution of myocardial blood flow steal and anterior ischaemia.