Early Pseudomonas aeruginosa predicts poorer pulmonary function in preschool children with cystic fibrosis.

BACKGROUND: We previously reported relatively normal pulmonary function (2 years of age) and computed tomography (CT, 1 year of age) in cystic fibrosis (CF) newborn screened (NBS) infants. We now report follow up of these children to preschool age. METHODS: 67 NBS children with CF and 41 healthy controls underwent pulmonary function tests in infancy (∼3 months, 1 year and 2 years) and at preschool (3-6 years). Broncho-alveolar lavage (BAL) and CT were undertaken in those with CF at 1 year. Primary outcomes at preschool were lung clearance index (LCI) and forced expired volume (FEV0.75). Risk factors for lung function impairment were identified by regression modelling, emphasising factors that could be identified or measured in the first 2 years of life. RESULTS: At preschool age children with CF had poorer lung function than controls, mean(95% CI) difference in LCI z-score: 1.47(0.96;1.97) and FEV0.75 z-score -0.54(-0.98; -0.10). Isolation of Pseudomonas aeruginosa before 6 months was a highly significant predictor of raised (abnormal) preschool LCI, associated with a mean (95%CI) increase of 1.69(0.43, 2.95) z-scores, compared to those with no Pseudomonas aeruginosa during the first 2 years of life. Including 2 year LCI and 1 year CT data in the predictive model increased the r2 from 13% to 61%. CONCLUSIONS: Lung function deteriorates after 2 years in NBS children with CF. Isolation of Pseudomonas aeruginosa before 6 months and minor abnormalities of infant lung function tests and CT in infancy are associated with higher preschool LCI.

A review of smell and taste dysfunction in COVID-19 patients.

INTRODUCTION: Multiple anecdotal reports suggest that smell and taste loss were early subclinical symptoms of COVID-19 patients. The objective of this review was to identify the incidence of smell and taste dysfunction in COVID-19, determine the onset of their symptoms and the risk factors of anosmia, hyposmia, ageusia or dysgeusia for COVID-19 infection. METHODS: We searched the PubMed and Google Scholar on 15th May 2020, with search terms including SARS-COV-2, coronavirus, COVID-19, hyposmia, anosmia, ageusia and dysgeusia. The articles included were cross sectional studies, observational studies and retrospective or prospective audits, letters to editor and short communications that included a study of a cohort of patients. Case reports, case-series and interventional studies were excluded. DISCUSSION: A total of 16 studies were selected. Incidence of smell and taste dysfunction was higher in Europe (34 to 86%), North America (19 to 71%) and the Middle East (36 to 98%) when compared to the Asian cohorts (11 to 15%) in COVID-19 positive patients. Incidence of smell and taste dysfunction in COVID-19 negative patients was low in comparison (12 to 27%). Total incidence of smell and taste dysfunction from COVID-19 positive and negative patients from seven studies was 20% and 10% respectively. Symptoms may appear just before, concomitantly, or immediately after the onset of the usual symptoms. Occurs predominantly in females. When occurring immediately after the onset of the usual symptoms, the median time of onset was 3.3 to 4.4 days. Symptoms persist for a period of seven to 14 days. Patients with smell and taste dysfunction were reported to have a six to ten-fold odds of having COVID-19. CONCLUSION: Smell and taste dysfunction has a high incidence in Europe, North America, and the Middle East. The incidence was lower in the Asia region. It is a strong risk factor for COVID-19. It may be the only symptom and should be added to the list of symptoms when screening for COVID- 19.

Upper respiratory tract sampling in COVID-19.

INTRODUCTION: To review the present literature on upper respiratory tract sampling in COVID-19 and provide recommendations to improve healthcare practices and directions in future studies. METHODS: Twelve relevant manuscripts were sourced from a total of 7288 search results obtained using PubMed, Medline and Google Scholar. The search keywords used were COVID-19, nasopharyngeal, oropharyngeal, swabs, SARS and CoV2. Original manuscripts were obtained and analysed by all authors. The review included manuscripts which have not undergone rigorous peer-review process in view of the magnitude of the topic discussed. RESULTS: The viral load of SARS-CoV-2 RNA in the upper respiratory tract was significantly higher during the first week and peaked at 4-6 days after onset of symptoms, during which it can be potentially sampled. Nasopharyngeal swab has demonstrated higher viral load than oropharyngeal swab, where the difference in paired samples is best seen at 0-9 days after the onset of illness. Sensitivity of nasopharyngeal swab was higher than oropharyngeal swabs in COVID-19 patients. Patient self-collected throat washing has been shown to contain higher viral load than nasopharyngeal or oropharyngeal swab, with significantly higher sensitivity when compared with paired nasopharyngeal swab. RECOMMENDATIONS: Routine nasopharyngeal swab of suspected COVID-19 infection should take anatomy of the nasal cavity into consideration to increase patient comfort and diagnostic yield. Routine oropharyngeal swab should be replaced by throat washing which has demonstrated better diagnostic accuracy, and it is safe towards others.

Conditioning Regimens for Hematopoietic Cell Transplantation in Primary Immunodeficiency.

PURPOSE OF REVIEW: Hematopoietic cell transplantation (HCT) is an established curative treatment for children with primary immunodeficiencies. This article reviews the latest developments in conditioning regimens for primary immunodeficiency (PID). It focuses on data regarding transplant outcomes according to newer reduced toxicity conditioning regimens used in HCT for PID. RECENT FINDINGS: Conventional myeloablative conditioning regimens are associated with significant acute toxicities, transplant-related mortality, and late effects such as infertility. Reduced toxicity conditioning regimens have had significant positive impacts on HCT outcome, and there are now well-established strategies in children with PID. Treosulfan has emerged as a promising preparative agent. Use of a peripheral stem cell source has been shown to be associated with better donor chimerism in patients receiving reduced toxicity conditioning. Minimal conditioning regimens using monoclonal antibodies are in clinical trials with promising results thus far. Reduced toxicity conditioning has emerged as standard of care for PID and has resulted in improved transplant survival for patients with significant comorbidities.

Body mass index adjustments to increase the validity of body fatness assessment in UK Black African and South Asian children.

BACKGROUND/OBJECTIVES: Body mass index (BMI) (weight per height2) is the most widely used marker of childhood obesity and total body fatness (BF). However, its validity is limited, especially in children of South Asian and Black African origins. We aimed to quantify BMI adjustments needed for UK children of Black African and South Asian origins so that adjusted BMI related to BF in the same way as for White European children. METHODS: We used data from four recent UK studies that made deuterium dilution BF measurements in UK children of White European, South Asian and Black African origins. A height-standardized fat mass index (FMI) was derived to represent BF. Linear regression models were then fitted, separately for boys and girls, to quantify ethnic differences in BMI-FMI relationships and to provide ethnic-specific BMI adjustments. RESULTS: We restricted analyses to 4-12 year olds, to whom a single consistent FMI (fat mass per height5) could be applied. BMI consistently underestimated BF in South Asians, requiring positive BMI adjustments of +1.12 kg m-2 (95% confidence interval (CI): 0.83, 1.41 kg m-2; P<0.0001) for boys and +1.07 kg m-2 (95% CI: 0.74, 1.39 kg m-2; P<0.0001) for girls of all age groups and FMI levels. BMI overestimated BF in Black Africans, requiring negative BMI adjustments for Black African children. However, these were complex because there were statistically significant interactions between Black African ethnicity and FMI (P=0.004 boys; P=0.003 girls) and also between FMI and age group (P<0.0001 for boys and girls). BMI adjustments therefore varied by age group and FMI level (and indirectly BMI); the largest adjustments were in younger children with higher unadjusted BMI and the smallest in older children with lower unadjusted BMI. CONCLUSIONS: BMI underestimated BF in South Asians and overestimated BF in Black Africans. Ethnic-specific adjustments, increasing BMI in South Asians and reducing BMI in Black Africans, can improve the accuracy of BF assessment in these children.

Changes in the incidence, patterns and outcomes of graft failure following hematopoietic stem cell transplantation for Hurler syndrome.

Hematopoietic stem cell transplantation (HSCT) is the standard of care in children with Hurler syndrome (HS) as it is the only therapy that can arrest disease progression. We examined the incidence, patterns and outcomes of graft failure in all HS children undergoing first HSCT at the Royal Manchester Children's Hospital or the University of Minnesota Children's Hospital from 1983 to 2016. Implementation of busulfan pharmacokinetic monitoring started in 2004 in both institutions. Two hundred and forty HS children were included in this analysis (historical era (pre-2004), n=131; current era (post 2004), n=109). The proportion of patients with graft failure was significantly lower in the current era compared with the historical era (37.2% vs 10.1%, respectively). Of 49 patients with graft failure in the historical era, 1 had aplasia and 48 had autologous reconstitution. All the 11 graft failures of the current era occurred in recipients of cord blood transplants (7 aplasia and 4 autologous reconstitution). The outcomes of second transplant in these patients has improved, with 89% of such patients alive and engrafted in the current era compared with 58% in the historical era. The pattern of graft failure has changed from autologous reconstitution, likely secondary to inadequate myelosuppression in the historical era, to aplasia in the current era, likely due to imperfect immunosuppression.

Persistence of long-distance, insect-mediated pollen movement for a tropical canopy tree species in remnant forest patches in an urban landscape.

As deforestation and urbanization continue at rapid rates in tropical regions, urban forest patches are essential repositories of biodiversity. However, almost nothing is known about gene flow of forest-dependent tree species in urban landscapes. In this study, we investigated gene flow in the insect-pollinated, wind-dispersed tropical tree Koompassia malaccensis in and among three remnant forest patches in the urbanized landscape of Singapore. We genotyped the vast majority of adults (N=179) and a large number of recruits (N=2103) with 8 highly polymorphic microsatellite markers. Spatial genetic structure of the recruit and adult cohorts was significant, showing routine gene dispersal distances of ~100-400 m. Parentage analysis showed that 97% of recruits were within 100 m of their mother tree, and a high frequency of relatively short-distance pollen dispersal (median ~143-187 m). Despite routine seed and pollen dispersal distances of within a few hundred meters, interpatch gene flow occurred between all patches and was dominated by pollen movement: parentage analysis showed 76 pollen versus 2 seed interpatch dispersal events, and the seedling neighborhood model estimated ~1-6% seed immigration and ~21-46% pollen immigration rates, depending on patch. In addition, the smallest patch (containing five adult K. malaccensis trees) was entirely surrounded by >2.5 km of 'impervious' substrate, yet had the highest proportional pollen and seed immigration estimates of any patch. Hence, contrary to our hypothesis, insect-mediated gene flow persisted across an urban landscape, and several of our results also parallel key findings from insect-pollinated canopy trees sampled in mixed agricultural-forest landscapes.

A four-point clinical criteria distinguishes immune thrombocytopenia from acute lymphoblastic leukaemia.

Immune thrombocytopenia is the most common diagnosis of isolated thrombocytopenia. The dilemma encountered by paediatricians is missing diagnosis of acute leukaemia in children with isolated thrombocytopenia. We demonstrated childhood ITP could be diagnosed using a four point clinical criteria without missing a diagnosis of acute leukaemia. Hence, bone marrow examination is not necessary in children with typical features compatible with ITP prior to steroid therapy. This can encourage paediatricians to choose steroid therapy, which is cheaper and non-blood product, as first line platelet elevating therapy in children with significant haemorrhage.

Aetiological profile of paediatric stridor in a Malaysian tertiary hospital.

BACKGROUND: Conditions causing stridor in paediatric patients can range from minor illnesses to life-threatening disorders. Proper evaluation and correct diagnosis are essential for timely intervention. The objective of this study was to determine the aetiological profiles and the management of paediatric patients with stridor referred to the Otorhinolaryngology Department of Hospital Serdang. METHODS: Medical records of all paediatric patients presenting with symptom of stridor from January 2010 to February 2015 were reviewed retrospectively. The patients' demographic data, clinical notes, laryngoscope findings, diagnosis and management were retrieved and analysed. RESULTS: Out of the total 137 patients referred for noisy breathing, 121 patients had stridor and were included in this study. There were 73 males and 48 females-most were of Malay ethnicity (77.7%). The age of presentation ranged from newborn to 10 years, with a mean of 4.9 months. Eighteen patients (14.9%) had associated congenital pathologies. The majority were congenital causes (90.9%), in which laryngomalacia was the commonest (78.5%), followed by subglottic stenosis (5.0%), vallecular cyst (2.5%) and congenital vocal fold paralysis (2.5%). Twelve patients (9.9%) had synchronous airway lesion. The majority of the patients were managed conservatively. Thirty-one patients (25.6%) required surgical intervention, of which only one needed tracheostomy. CONCLUSION: Laryngomalacia was the commonest cause of stridor among paediatric patients. A synchronous airway lesion should be considered if the child has persistent or severe symptoms. The majority of the patients were managed conservatively.

The teaching of trauma management in undergraduate medical education.

BACKGROUND: The teaching of trauma in medical schools faces many educational and logistic challenges. Issues on what to teach, how to teach, when to teach, who will teach and whether medical students with insufficient exposure to clinical medicine can benefit from a trauma course are unclear. MATERIALS AND METHODS: A well-designed one day intensive trauma course concentrating on the primary survey was taught to semester seven and semester eight students by a multi-disciplinary team comprising of surgeons, anaesthetists, emergency physicians and trained medical officers. The course comprised of a pre-test of 30 multiple choice questions followed by three hours of lectures, three hours of skill stations and a post-test. The pre-test and posttest scores were analysed using the paired sample t-test and the independent t-test. RESULTS: The pre- and post-test scores showed significant improvement for both semester seven and semester eight students. Semester seven students, who only had a sevenweek posting in Surgery had pre-test and post-test scores of only 4% less than semester eight students who had an additional six weeks in Orthopaedics and two weeks in Accident and Emergency postings. The use of a multidisciplinary team reduced the logistic burden of finding sufficient surgeons to teach trauma management. CONCLUSION: Trauma education can be taught to undergraduates by a multidisciplinary team as early as year three, in semester seven. However, the mean score of semester eight students is only at 66%, suggesting that a refresher course prior to graduation at semester ten will be useful. KEY WORDS.

Retention of Knowledge following training of students in Basic Trauma Life Support.

INTRODUCTION: In the course of their undergraduate training at the International Medical University, students receive a Basic Trauma Life Support course. OBJECTIVE: We wanted to test the long-term retention of knowledge (after 16 months) of third year medical students who had received training in Basic Trauma Life Support Method: To assess the retention of knowledge one cohort of students who received the training course were tested again 16 months later using the same 30 question One Best Answer quiz. RESULTS: Seventy-three students who underwent the course sat for the Retention test. The number of students who passed the Retention test was not significantly different from the test taken immediately after the course. The mean scores, 62.5% and 59.5% respectively, were however significantly different. CONCLUSION: Our study involves a relatively long interval between the course and retention of knowledge test shows encouraging results.

Embryonal rhabdomyosarcoma of the middle ear presenting with aural polyp and facial nerve palsy.

Rhabdomyosarcoma is a rare tumour in the middle ear and mastoid cavity in children and the diagnosis is difficult. Repeated histological examination may be essential to confirm the diagnosis. We report a 6 year old boy with a left aural polyp, otorrhoea and facial nerve palsy who was initially thought to have otitis media and mastoiditis. He had polypectomy and the tissue taken for histopathology suggested an inflammatory condition. Subsequently he had mastoidectomy. Tissue taken during mastoidectomy was however reported as rhabdomyosarcoma. The child developed a cerebral abscess and eventually succumbed. A literature review of the disease, radiological findings, immunohistochemical features and treatment options is described.

Interpretation of pediatric lung function: impact of ethnicity.

RATIONALE: To evaluate the appropriateness of spirometric and plethysmographic reference equations in healthy young children according to ethnic origin. METHODS: Spirometry data were collated in 400 healthy children (214 Black and 186 White) aged 6-12 years. Of these children, 68 Black and 115 White children also undertook plethysmography. Results were expressed as percent predicted according to commonly used equations for spirometry and plethysmography. RESULTS: Black children had lower lung function for a given height compared to White children. The magnitude and direction of these differences varied according to specific outcome. In the studied age range (6-12 years) the ethnic-specific Wang equations were adequate for spirometry (mean results approximating 100% predicted in both ethnic groups). By contrast, significant differences were found between observed and % predicted plethysmographic lung volumes according to published equations derived from White children: Among the Black children, function residual capacity (FRC) and total lung capacity (TLC) were on average, 14 and 6% lower than predicted, whereas mean residual volume (RV) and RV/TLC were 4 and 10% higher. Among White children, the Rosenthal equations gave the best fit, with the exception of FRC which was, on average, 9% lower than predicted. CONCLUSION: Spirometry equations may suffice in Black children; however, interpretation of static lung volumes in Black children is limited due to inappropriate reference equations. More appropriate plethysmographic reference equations that are applicable to all ethnic groups across the entire age range are urgently needed.

Rapid reversal of subclinical hyperthyroidism in patients with large multinodular goitres after thyroidectomy.

A patient is said to have subclinical hyperthyroidism if he has a depressed thyroid stimulating hormone (TSH) level but is clinically euthyroid and has a normal thyroxine (T4) and triiodothyronine (T3) level. The aetiology of this condition is unknown, its progression is uncertain and the value of treatment is doubtful. These 2 cases show a rapid reversal of TSH suppression within a week after thyroidectomy. This suggest an unidentified potent but innocuous suppressor of TSH is produced by some large nodular goitres. Patients with multinodular goitres with subclinical hyperthyroidism can have their anxiety allayed with assurance that their condition is benign and that their TSH suppression is due to the presence of an innocuous substance which is protective in nature. This substance, when isolated, will find a useful place in the prevention and treatment of papillary carcinoma of the thyroid because of its potent effect on the pituitary-thyroid axis without causing any peripheral effects.

Alveolar LCI vs. standard LCI in detecting early CF lung disease.

Multiple breath washout (MBW) is a sensitive technique that detects early airways disease. However in very young children, large equipment and physiological dead space relative to lung volumes may result in a higher Lung Clearance Index (LCI). We investigated whether alveolar LCI (aLCI) is a more sensitive index than standard LCI in children. MBW data-sets from children aged 0.1-10.7 years [97 healthy controls and 93 with cystic fibrosis (CF)] were analysed. LCI is traditionally calculated by dividing the cumulative expired volume (CEV) by functional residual capacity (FRC) after correcting for equipment dead space. aLCI was calculated similarly, but after correcting the CEV and FRC for Langley's physiological dead space. There was a significant correlation between LCI and aLCI in health (r(2): 0.993; p<0.0001) and disease (r(2): 0.984; p<0.0001). Sensitivity of both LCI and aLCI in detecting abnormal lung function in CF was 39% during infancy, which increased to 77% and 83% respectively in older children. However, the difference in sensitivity (aLCI vs. LCI) was not significant (p=0.36). We conclude that LCI is minimally affected by airway deadspace, or relative equipment deadspace, and is an appropriate measure of lung function in infancy.

Nature and severity of lung function abnormalities in extremely pre-term children at 11 years of age.

Advances in neonatal care have resulted in increased survival of children born extremely pre-term (EP). Nevertheless the incidence of bronchopulmonary dysplasia and long-term respiratory morbidity remains high. We investigated the nature of pathophysiological changes at 11 yrs of age to ascertain whether respiratory morbidity in EP children primarily reflects alterations in the lung periphery or more centralised airway function in this population. Spirometry, plethysmography, diffusing capacity, exhaled nitric oxide, multiple-breath washout, skin tests and methacholine challenge were used during laboratory-based assessments in a subgroup of the 1995 EPICure cohort and in controls. Results were obtained in 49 EP and 52 control children. Lung function abnormalities were found in 78% of EP children, with evidence of airway obstruction, ventilation inhomogeneity, gas trapping and airway hyperresponsiveness. Levels of atopy and exhaled nitric oxide were similar between the groups. Prior wheeze was associated with significant reductions in forced flows and volumes. By contrast, abnormalities of the lung periphery appear to be mediated primarily through EP birth per se. The prevalence of lung function abnormalities, which is largely obstructive in nature and likely to have long-term implications, remains high among 11-yr-old children born EP. Spirometry proved an effective means of detecting these persistent abnormalities.

A study of acupuncture in Asian patients: clinical aspects and effects on cortical excitability.

OBJECTIVE: To determine the effect of acupuncture on the phosphene threshold, by transcranial magnetic stimulation (TMS), and the clinical effect of acupuncture on headache frequency, duration and severity. METHODS: Twenty-one patients (16 women; mean age 46 years; range 23-61 years, 17 Chinese, 2 Malays, 2 Indians) underwent 10 acupuncture sessions scheduled twice a week for 5 weeks. The lowest TMS intensity to elicit phosphene perception is defined as the phosphene threshold. TMS was performed before the first and last sessions, and at 2 months' follow-up. RESULTS: Acupuncture resulted in reduction of headache frequency, duration and severity over the course of treatment. However, this was not accompanied by a corresponding increase in the phosphene threshold over a similar time course. The baseline threshold before acupuncture treatment had no predictive value for outcome of treatment. CONCLUSIONS: Although acupuncture was effective in treating migraine, the use of occipital cortex excitability as an adjunctive parameter to evaluate treatment response was not suitable. The relief of migraine with acupuncture may be related to separate neural pathways independent of occipital or visual processes in the human brain.

Reference equations for specific airway resistance in children: the Asthma UK initiative.

Plethysmographic specific airway resistance (sR(aw)) is a useful research method for discriminating lung disease in young children. Its use in clinical management has, however, been limited by lack of consensus regarding equipment, methodology and reference data. The aim of our study was to collate reference data from healthy children (3-10 yrs), document methodological differences, explore the impact of these differences and construct reference equations from the collated dataset. Centres were approached to contribute sR(aw) data as part of the Asthma UK initiative. A random selection of pressure-flow plots were assessed for quality and site visits elucidated data collection and analysis protocols. Five centres contributed 2,872 measurements. Marked variation in methodology and analysis excluded two centres. sR(aw) over-read sheets were developed for quality control. Reference equations and recommendations for recording and reporting both specific effective and total airway resistance (sR(eff) and sR(tot), respectively) were developed for White European children from 1,908 measurements made under similar conditions. Reference sR(aw) data collected from a single centre may be misleading, as methodological differences exist between centres. These preliminary reference equations can only be applied under similar measurement conditions. Given the potential clinical usefulness of sR(aw), particularly with respect to sR(eff), methodological guidelines need to be established and used in prospective data collection.

A pilot study of topiramate dosages for migraine prophylaxis in an Asian population.

Topiramate is known to be efficacious in migraine prophylaxis, but its optimal dose has not been systematically studied in the Asian population. Here, we show that a fixed low dose of topiramate 25 mg/day is efficacious in migraine prophylaxis and also attest to advantages in terms of medication cost savings and more favourable side effect profile.