Iron deficiency in healthy, term infants aged five months, in a pediatric outpatient clinic: a prospective study.

BACKGROUND: Iron deficiency (ID) is prevalent in Malaysian children. The incidence of ID in infants under 6 months of age is unknown. Our aim was to determine the prevalence of iron deficiency (ID) and iron deficiency anemia (IDA) in healthy, term infants aged below 6 months in our hospital population. METHODS: A prospective longitudinal pilot study of mother-infant pairs was conducted on infants receiving routine immunizations in a mother and child clinic at a university hospital, in Kuala Lumpur, Malaysia. Mothers completed standardized questionnaires at 3- and 5-month postnatal visits. Maternal and infant full blood count, ferritin, and C-reactive protein (CRP) levels were measured at 3 months and for the infants repeated at 5 months. Infant anthropometric measurements were obtained at both visits. We conducted a univariate analysis to identify factors associated with ID and IDA. RESULTS: Altogether, 91 mother-infant pairs were enrolled, with 88 completing the study. No infant had ID or IDA at 3 months; the lowest ferritin level was 16.6 µg/L. At 5 months, 5.9% (5/85) of infants had ID, and 2.4% (2/85) had IDA. Median (interquartile range) infant ferritin levels significantly declined from 113.4 (65.0-183.6) µg/L at 3 months to 50.9 (29.2-70.4) µg/L at 5 months, p < 0.001. Exclusive breastfeeding until 3 or 5 months was significantly associated with ID at 5 months (p = 0.020, and p = 0.008, respectively) on univariate analysis. The drop in ferritin between 3-5 months was significantly associated with weight and length gains between 0-3 months (p = 0.018, p = 0.009, respectively). Altogether, 14.3% of infants exclusively breastfed until 5 months developed ID. At 5 months, 3.4% of infants were underweight, 1.1% stunted, and 10.2% wasted. CONCLUSIONS: In exclusively breastfed term infants, ID occurred by 5 months. Early introduction of iron-rich foods should be considered in exclusively breastfed babies. A high prevalence of wasting suggests a calorie deficit in this population and will lead to stunting if not addressed.

Breastfeeding Prevalence and Factors Affecting Breastfeeding Duration Among Urban Multi-ethnic Malaysian Mothers: A Single-Center University Hospital Study.

Breastfeeding rates in urban Malaysian mothers are below World Health Organization (WHO) targets. Our prospective survey identified breastfeeding prevalences at 3, 6, and 12 months of 85.5%, 77%, and 60%, respectively. Combined (direct and expressed) breastfeeding significantly sustained longer-term breastfeeding. Efforts should be focused on mothers of Indian ethnicity and on expression after one month postpartum.

Hyperferritinemia in Severe Dengue Infection: Single-Center Retrospective Cohort Study.

OBJECTIVES: Hyperferritinemia in the critical phase of dengue infections may correlate with severe dengue ( sd ) disease, and our primary objective was to examine the association between ferritin level on day 1 of PICU admission and 2009 World Health Organization (WHO) criteria for sd . Our secondary objective was outcome in relation to care. It is unclear whether immunomodulatory therapy during the critical phase may restore immune homeostasis and mitigate disease severity. DESIGN, SETTING, AND PATIENTS: Retrospective cohort study of children with dengue 1 month to 16 years old with admission ferritin greater than or equal to 500 ng/mL requiring PICU admission. Demographics, clinical, and laboratory parameters, presence of the 2009 WHO sd criteria and outcomes were analyzed. Immunomodulatory therapy was used when there was persistent hyperinflammation beyond the critical phase of plasma leakage. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Fifty-five patients were admitted in the critical phase of dengue with median (interquartile range) ferritin levels of 8,105 ng/mL (2,350-15,765 ng/mL). Patients with at least one WHO sd category had higher ferritin levels compared to those without any sd criteria, with the highest levels in eight patients with all three sd categories. In our cohort of 55, 52 patients (94%) recovered with standard supportive therapy. Recovery was associated with decreased ferritin levels that occurred in parallel with improved circulation and platelet counts; this included 22 of 24 patients with admission ferritin levels greater than or equal to 10,000 ng/mL and two with ferritin greater than 1,00,000 ng/mL. Immunomodulation was used in three patients with unremitting fever, persistent hyperferritinemia, and progressive multiple organ dysfunction beyond the critical phase, of whom two died. CONCLUSIONS: Hyperferritinemia in the critical phase of sd is associated with the number of 2009 WHO sd criteria present. Our data also indicate that many patients with sd recover well with supportive care.

The Prevalence and Determinants of Child Hunger and Its Associations with Early Childhood Nutritional Status among Urban Poverty Households during COVID-19 Pandemic in Petaling District, Malaysia: An Exploratory Cross-Sectional Survey.

Child hunger was prevalent during the COVID-19 pandemic, but the extent, determinants, and impact on pre-school children aged 6 months to 7 years old from Malaysian urban poor households are still unknown. This exploratory cross-sectional study was performed between July 2020 and January 2021 at the Lembah Subang People Housing Project, Petaling. The households' food security status was assessed using the previously validated Radimer/Cornell questionnaire, and the children's anthropometric measurements were taken. Food diversity score was assessed using the World Health Organization Infant and Young Children Feeding (under-2 children) or Food and Agriculture Organization Women's Dietary Diversity (2-year-old-and-above children) systems. Overall, 106 households were recruited. The prevalence of child hunger is 58.4% (95% CI: 50.0, 67.4). Significant differences were found in breastfeeding and sugar-sweetened beverage consumption between under-2 and ≥2-year-old children. There were no significant differences between child hunger and other food-insecure groups in weight-for-age, height-for-age, and weight-for-height z-scores. Only a higher dietary diversity score was significantly protective against child hunger after adjusting for maternal age, paternal employment status, and the number of household children (ORadjusted: 0.637 (95% CI: 0.443, 0.916), p = 0.015)). Proactive strategies are warranted to reduce child hunger during the COVID-19 pandemic by improving childhood dietary diversity.

Early diagnostic indicators of dengue versus other febrile illnesses in Asia and Latin America (IDAMS study): a multicentre, prospective, observational study.

BACKGROUND: Improvements in the early diagnosis of dengue are urgently needed, especially in resource-limited settings where the distinction between dengue and other febrile illnesses is crucial for patient management. METHODS: In this prospective, observational study (IDAMS), we included patients aged 5 years and older with undifferentiated fever at presentation from 26 outpatient facilities in eight countries (Bangladesh, Brazil, Cambodia, El Salvador, Indonesia, Malaysia, Venezuela, and Viet Nam). We used multivariable logistic regression to investigate the association between clinical symptoms and laboratory tests with dengue versus other febrile illnesses between day 2 and day 5 after onset of fever (ie, illness days). We built a set of candidate regression models including clinical and laboratory variables to reflect the need of a comprehensive versus parsimonious approach. We assessed performance of these models via standard measures of diagnostic values. FINDINGS: Between Oct 18, 2011, and Aug 4, 2016, we recruited 7428 patients, of whom 2694 (36%) were diagnosed with laboratory-confirmed dengue and 2495 (34%) with (non-dengue) other febrile illnesses and met inclusion criteria, and were included in the analysis. 2703 (52%) of 5189 included patients were younger than 15 years, 2486 (48%) were aged 15 years or older, 2179 (42%) were female and 3010 (58%) were male. Platelet count, white blood cell count, and the change in these variables from the previous day of illness had a strong association with dengue. Cough and rhinitis had strong associations with other febrile illnesses, whereas bleeding, anorexia, and skin flush were generally associated with dengue. Model performance increased between day 2 and 5 of illness. The comprehensive model (18 clinical and laboratory predictors) had sensitivities of 0·80 to 0·87 and specificities of 0·80 to 0·91, whereas the parsimonious model (eight clinical and laboratory predictors) had sensitivities of 0·80 to 0·88 and specificities of 0·81 to 0·89. A model that includes laboratory markers that are easy to measure (eg, platelet count or white blood cell count) outperformed the models based on clinical variables only. INTERPRETATION: Our results confirm the important role of platelet and white blood cell counts in diagnosing dengue, and the importance of serial measurements over subsequent days. We successfully quantified the performance of clinical and laboratory markers covering the early period of dengue. Resulting algorithms performed better than published schemes for distinction of dengue from other febrile illnesses, and take into account the dynamic changes over time. Our results provide crucial information needed for the update of guidelines, including the Integrated Management of Childhood Illness handbook. FUNDING: EU's Seventh Framework Programme. TRANSLATIONS: For the Bangla, Bahasa Indonesia, Portuguese, Khmer, Spanish and Vietnamese translations of the abstract see Supplementary Materials section.

A Randomized Pilot Trial of Micronutrient Supplementation for Under-5 Children in an Urban Low-Cost Flat Community in Malaysia: A Framework for Community-Based Research Integration.

Early childhood nutritional deficiency has detrimental consequences on physical and cognitive development. We conducted a single-center, single-blind, two-arm pilot randomized no-treatment controlled trial (the Child of Urban Poverty Iron Project (CUPIP); NCT03819530) in a people's housing project locale in Selangor, Malaysia, between September 2019 and February 2020, to assess the trial's general feasibility and preliminary benefits of daily micronutrient supplementation for iron storage and anthropometric outcomes in under-5 children. Those with history of premature births, congenital abnormalities, or baseline hemoglobin <70 g/L were excluded. Participants received baseline deworming and were simply randomized in a 1:1 ratio to either micronutrient (4-month daily micronutrient packets) or control (no micronutrient supplementation) groups. Information on anthropometric, erythrocytic, and iron storage endpoints were collected. Overall, 45 (25 micronutrient and 20 controls) participants were enrolled and completed 4-month endpoint assessments. Micronutrient recipients demonstrated higher median mean corpuscular volume, serum ferritin level with no significant differences in all anthropometric endpoints. In conclusion, this pilot trial was implementable, demonstrating that micronutrient supplementation significantly improved hematological, but not anthropometric, endpoints, of under-5-year-old children living in an underprivileged environment. A definitive well-designed trial with larger sample sizes and greater attrition control should be contemplated in the future.

Outcomes of neonatal congenital diaphragmatic hernia in a non-ECMO center in a middle-income country: a retrospective cohort study.

BACKGROUND: Most studies examining survival of neonates with congenital diaphragmatic hernia (CDH) are in high-income countries. We aimed to describe the management, survival to hospital discharge rate, and factors associated with survival of neonates with unilateral CDH in a middle-income country. METHODS: We retrospectively reviewed the medical notes of neonates with unilateral CDH admitted to a pediatric intensive care unit (PICU) in a tertiary referral center over a 15-year period, from 2003-2017. We described the newborns' respiratory care pathways and then compared baseline demographic, hemodynamic, and respiratory indicators between survivors and non-survivors. The primary outcome measure was survival to hospital discharge. RESULTS: Altogether, 120 neonates were included with 43.3% (52/120) diagnosed antenatally. Stabilization occurred in 38.3% (46/120) with conventional ventilation, 13.3% (16/120) with high-frequency intermittent positive-pressure ventilation, and 22.5% (27/120) with high frequency oscillatory ventilation. Surgical repair was possible in 75.0% (90/120). The overall 30-day survival was 70.8% (85/120) and survival to hospital discharge was 66.7% (80/120). Survival to hospital discharge tended to improve over time (p > 0.05), from 56.0% to 69.5% before and after, respectively, a service reorganization. For those neonates who could be stabilized and operated on, 90.9% (80/88) survived to hospital discharge. The commonest post-operative complication was infection, occurring in 43.3%. The median survivor length of stay was 32.5 (interquartile range 18.8-58.0) days. Multiple logistic regression modelling showed vaginal delivery (odds ratio [OR] = 4.8; 95% confidence interval [CI] [1.1-21.67]; p = 0.041), Apgar score [Formula: see text] 7 at 5 min (OR = 6.7; 95% CI [1.2-36.3]; p = 0.028), and fraction of inspired oxygen (FiO2) < 50% at 24 h (OR = 89.6; 95% CI [10.6-758.6]; p < 0.001) were significantly associated with improved survival to hospital discharge. CONCLUSIONS: We report a survival to hospital discharge rate of 66.7%. Survival tended to improve over time, reflecting a greater critical volume of cases and multi-disciplinary care with early involvement of the respiratory team resulting in improved transitioning from PICU. Vaginal delivery, Apgar score [Formula: see text] 7 at 5 min, and FiO2 < 50% at 24 h increased the likelihood of survival to hospital discharge.

Safety, tolerability and efficacy of LEGA-Kid® mechanical percussion device versus conventional chest physiotherapy in children: a randomised, single-blind controlled study.

INTRODUCTION: Chest physiotherapy (CPT) may benefit children aged below five years who suffer from lower respiratory tract infection (LRTI). However, its effects depend on the technique used. This study aimed to determine whether mechanical CPT using the LEGA-Kid® mechanical percussion device is superior to manual CPT in children with LRTI. METHODS: Children aged five months to five years who were admitted and referred for CPT from January to April 2017 were randomised to either manual CPT or mechanical CPT with LEGA-Kid. Outcomes measured before intervention and two hours after intervention were respiratory rate (RR), oxygen saturation and modified Respiratory Distress Assessment Instrument (mRDAI) score. RESULTS: All 30 enrolled patients showed significant reduction in post-intervention RR and mRDAI scores. There was an 8% reduction in RR for the manual CPT group (p = 0.002) and a 16.5% reduction in the mechanical CPT group (p = 0.0001), with a significantly greater reduction in the latter (p = 0.024). mRDAI scores decreased by 2.96 in the manual group (p = 0.0001) and 3.62 in the mechanical group (p = 0.002), with no significant difference between the groups. There was no significant improvement in oxygen saturation, and no adverse events were observed after CPT. CONCLUSION: Children receiving both manual and mechanical CPT showed improvements in respiratory distress symptoms, with no adverse effects. A combined strategy of nebulised hypertonic saline followed by CPT for LRTI removes airway secretions and results in improvements in moderately severe respiratory distress. The LEGA-Kid mechanical CPT method is superior to manual CPT in reducing the RR.

Evaluation of immature platelet fraction as a marker of dengue fever progression.

OBJECTIVES: Progression of dengue is often associated with thrombocytopenia resulting from viral-induced bone marrow suppression and immune-mediated peripheral platelet consumption. Immature platelet fraction (IPF), which can be measured using a haematology analyser, is a precursor indicating platelet formation in the bone marrow. This study evaluated the trend of IPF as an early recovery indicator of platelets in dengue patients with thrombocytopenia, and its relationship with severe dengue in conjunction with reticulocyte count. METHODS: Hospitalized patients with dengue were enrolled and followed-up daily until discharge. Blood investigations included daily full blood counts and IPF measured using a haematology analyser. RESULTS: In total, 287 patients with confirmed dengue were enrolled in this study, 25 of whom had severe dengue. All patients had a decreasing trend in platelet count in the first week of illness, concomitant with an increasing trend in the percentage of immature platelets to total platelets (IPF%) for more than 3 days prior to platelet recovery. IPF% was significantly increased in patients with severe dengue compared with patients with non-severe dengue on days 3-5 after the onset of fever. Reticulocyte count increased significantly in patients with severe dengue on day 5. CONCLUSIONS: IPF can be utilized as an early recovery indicator of platelets in patients with dengue and thrombocytopenia.

Combination of inflammatory and vascular markers in the febrile phase of dengue is associated with more severe outcomes.

Background: Early identification of severe dengue patients is important regarding patient management and resource allocation. We investigated the association of 10 biomarkers (VCAM-1, SDC-1, Ang-2, IL-8, IP-10, IL-1RA, sCD163, sTREM-1, ferritin, CRP) with the development of severe/moderate dengue (S/MD). Methods: We performed a nested case-control study from a multi-country study. A total of 281 S/MD and 556 uncomplicated dengue cases were included. Results: On days 1-3 from symptom onset, higher levels of any biomarker increased the risk of developing S/MD. When assessing together, SDC-1 and IL-1RA were stable, while IP-10 changed the association from positive to negative; others showed weaker associations. The best combinations associated with S/MD comprised IL-1RA, Ang-2, IL-8, ferritin, IP-10, and SDC-1 for children, and SDC-1, IL-8, ferritin, sTREM-1, IL-1RA, IP-10, and sCD163 for adults. Conclusions: Our findings assist the development of biomarker panels for clinical use and could improve triage and risk prediction in dengue patients. Funding: This study was supported by the EU's Seventh Framework Programme (FP7-281803 IDAMS), the WHO, and the Bill and Melinda Gates Foundation.

Low prevalence of infantile functional gastrointestinal disorders (FGIDs) in a multi-ethnic Asian population.

BACKGROUND: Functional gastrointestinal disorders (FGIDs) are common in children. The prevalence of FGIDs varies across the world but is unknown in Malaysia. We aimed to investigate the prevalence of FGIDs in healthy Malaysian infants. METHODS: This was a cross-sectional study involving healthy infants younger than 12 months of age who attended a well-baby clinic. A universal sampling method was adopted. Children with congenital disorders potentially affecting gastrointestinal functions, chronic debilitating diseases and hypothyroidism were excluded. Rome IV criteria were used to define FGIDs. RESULTS: Of the total 534 infants recruited (54% males), 92% were born at term; 85% had normal birth weight [range 2.5-4.0 kg], and the mean (±S.D.) age at interview was 6.8 (±3.4) months. Thirty-six percent were breastfed, 29% were formula-fed, and 35% had mixed feeding. Prevalence of infant regurgitation and rumination syndrome was 10.5% and 1.7%, respectively. Prevalence of infant colic was 1.9% (3/160) (infant < 5 months old) while infant dyschezia, functional constipation and diarrhoea were 1.3%, 1.1% and 0.3%, respectively. No subjects fulfilled diagnostic criteria for cyclic vomiting syndrome. Breastfed infants were less likely to regurgitate, after adjustment for age, gender, ethnicity, birth weight and gestation (adjusted OR 0.25 [95% CI 0.12-0.54]; p < 0.001). No significant differences among other factors (gender, Malays vs. non-Malays, premature vs. term, and birthweight) were noted for other FGIDs. CONCLUSION: With the exception of the lower prevalence of infant colic and functional constipation, the prevalence rates of other FGIDs observed in the present study were similar to those published in the literature. Breastfeeding protects against infant regurgitation.

Health-related quality of life and developmental outcome of children on home mechanical ventilation in a developing country: A cross-sectional study.

BACKGROUND: Provision of home mechanical ventilation (HMV) to children with chronic respiratory insufficiency enhances growth and quality of life. The hypothesis was that health-related quality of life (HRQoL) and the development of these children were poorer than in healthy children. OBJECTIVES: To determine the HRQoL and developmental outcome of children on HMV. METHODS: This cross-sectional study used the TNO-AZL Preschool children's Quality Of Life (TAPQOL; <5 years old) and Health Utilities Index (HUI) 2/3 (≥5 years old) to assess the quality of life and the Schedule of Growing Skills-II to assess development. Instruments were used on children currently or previously on HMV (≥3 months) and compared with age and sex-matched controls. RESULTS: Sixty-five patients and 130 controls were recruited. Patients' median (interquartile range) age was 3.12 (1.65, 5.81) years. Patients had significantly lower TAPQOL scores in the domains of lung, liveliness, positive mood, social functioning, motor functioning, and communication, and lower HUI 2/3 scores in hearing, sensation, pain, speech, mobility, ambulatory, dexterity, and self-care domains. The developmental outcome of patients was poorer in all domains. However, patients had fewer behavioral problems. Those with respiratory tract disease and without comorbidities had better HRQoL and developmental scores. Having a parent as the primary caregiver was associated with better speech and language skills. CONCLUSIONS: HRQoL and the developmental outcome are lower in children on HMV compared to controls. Children with respiratory tract disease and without comorbidities have a better outcome. Parents play a crucial role in the acquisition of speech.

Assessing dehydration status in dengue patients using urine colourimetry and mobile phone technology.

BACKGROUND: Dengue is a systemic and dynamic disease with symptoms ranging from undifferentiated fever to dengue shock syndrome. Assessment of patients' severity of dehydration is integral to appropriate care and management. Urine colour has been shown to have a high correlation with overall assessment of hydration status. This study tests the feasibility of measuring dehydration severity in dengue fever patients by comparing urine colour captured by mobile phone cameras to established laboratory parameters. METHODOLOGY/PRINCIPAL FINDINGS: Photos of urine samples were taken in a customized photo booth, then processed using Adobe Photoshop to index urine colour into the red, green, and blue (RGB) colour space and assigned a unique RGB value. The RGB values were then correlated with patients' clinical and laboratory hydration indices using Pearson's correlation and multiple linear regression. There were strong correlations between urine osmolality and the RGB of urine colour, with r = -0.701 (red), r = -0.741 (green), and r = -0.761 (blue) (all p-value <0.05). There were strong correlations between urine specific gravity and the RGB of urine colour, with r = -0.759 (red), r = -0.785 (green), and r = -0.820 (blue) (all p-value <0.05). The blue component had the highest correlations with urine specific gravity and urine osmolality. There were moderate correlations between RGB components and serum urea, at r = -0.338 (red), -0.329 (green), -0.360 (blue). In terms of urine biochemical parameters linked to dehydration, multiple linear regression studies showed that the green colourimetry code was predictive of urine osmolality (ß coefficient -0.082, p-value <0.001) while the blue colourimetry code was predictive of urine specific gravity (ß coefficient -2,946.255, p-value 0.007). CONCLUSIONS/SIGNIFICANCE: Urine colourimetry using mobile phones was highly correlated with the hydration status of dengue patients, making it a potentially useful hydration status tool.

Severe dengue categories as research endpoints-Results from a prospective observational study in hospitalised dengue patients.

Severe dengue was perceived as one clinical disease entity until the WHO 2009 classification stratified it into severe vascular leakage, severe bleeding, and severe organ dysfunction. The objectives of this study were to investigate the potential use of severe dengue categories as endpoints for intervention research. 271 patients with severe dengue among 1734 confirmed dengue patients were followed prospectively in this hospital-based observational study in Latin America and Asia. We compared the distribution of severe dengue categories according to gender and age (below/above 15y), and determined the relative frequency and the overlap of severe dengue categories in the same patients. In a next step, we extended the analysis to candidate moderate severity categories, based on recently suggested definitions which were adapted for our purposes. Severe vascular leakage occurred in 244 (90%), severe bleeding in 39 (14%), and severe organ dysfunction in 28 (10%) of 271 severe dengue patients. A higher frequency of severe leakage was seen in children or adolescents (<15y) compared to adults. More than 80% of the severe leakage cases, and 30-50% of the cases with severe bleeding or severe organ dysfunction, were defined as severe on the basis of that feature alone. In 136 out of 213 patients with severe leakage alone, neither moderate bleeding manifestation nor hepatic involvement was recorded. On the other hand, moderate leakage manifestations were detected in 4 out of 12 cases that were classified as severe based on bleeding alone. A major proportion of severe dengue patients exhibited clinical manifestations of severe vascular leakage only, which may constitute a useful endpoint for intervention research or pathophysiology studies. Severe bleeding and severe organ manifestation were recorded less frequently and exhibited a higher degree of overlap with severe leakage. Severe bleeding without leakage may be associated with individual predisposition or the presence of comorbidities. More detailed assessments are needed to explore this hypothesis. Candidate moderate disease endpoints were investigated and need to be further validated.

C-reactive protein as a potential biomarker for disease progression in dengue: a multi-country observational study.

BACKGROUND: Dengue infection can cause a wide spectrum of clinical outcomes. The severe clinical manifestations occur sufficiently late in the disease course, during day 4-6 of illness, to allow a window of opportunity for risk stratification. Markers of inflammation may be useful biomarkers. We investigated the value of C-reactive protein (CRP) measured early on illness days 1-3 to predict dengue disease outcome and the difference in CRP levels between dengue and other febrile illnesses (OFI). METHOD: We performed a nested case-control study using the clinical data and samples collected from the IDAMS-consortium multi-country study. This was a prospective multi-center observational study that enrolled almost 8000 participants presenting with a dengue-like illness to outpatient facilities in 8 countries across Asia and Latin America. Predefined severity definitions of severe and intermediate dengue were used as the primary outcomes. A total of 281 cases with severe/intermediate dengue were compared to 836 uncomplicated dengue patients as controls (ratio 1:3), and also 394 patients with OFI. RESULTS: In patients with confirmed dengue, median (interquartile range) of CRP level within the first 3 days was 30.2 mg/L (12.4-61.2 mg/L) (uncomplicated dengue, 28.6 (10.5-58.9); severe or intermediate dengue, 34.0 (17.4-71.8)). Higher CRP levels in the first 3 days of illness were associated with a higher risk of severe or intermediate outcome (OR 1.17, 95% CI 1.07-1.29), especially in children. Higher CRP levels, exceeding 30 mg/L, also associated with hospitalization (OR 1.37, 95% CI 1.14-1.64) and longer fever clearance time (HR 0.84, 95% CI 0.76-0.93), especially in adults. CRP levels in patients with dengue were higher than patients with potential viral infection but lower than patients with potential bacterial infection, resulting in a quadratic association between dengue diagnosis and CRP, with levels of approximately 30 mg/L associated with the highest risk of having dengue. CRP had a positive correlation with total white cell count and neutrophils and negative correlation with lymphocytes, but did not correlate with liver transaminases, albumin, or platelet nadir. CONCLUSIONS: In summary, CRP measured in the first 3 days of illness could be a useful biomarker for early dengue risk prediction and may assist differentiating dengue from other febrile illnesses.

Predictors and Clinical Outcomes of Poor Platelet Recovery in Adult Dengue With Thrombocytopenia: A Multicenter, Prospective Study.

BACKGROUND: Platelet transfusion is common in dengue patients with thrombocytopenia. We previously showed in a randomized clinical trial that prophylactic platelet transfusion did not reduce clinical bleeding. In this study, we aimed to characterize the predictors and clinical outcomes of poor platelet recovery in transfused and nontransfused participants. METHODS: We analyzed patients from the Adult Dengue Platelet Study with laboratory-confirmed dengue with ≤20 000 platelets/µL and without persistent mild bleeding or any severe bleeding in a post hoc analysis. Poor platelet recovery was defined as a platelet count of ≤20 000/µL on Day 2. We recruited 372 participants from 5 acute care hospitals located in Singapore and Malaysia between 29 April 2010 and 9 December 2014. Of these, 188 were randomly assigned to the transfusion group and 184 to the control group. RESULTS: Of 360 patients, 158 had poor platelet recovery. Age, white cell count, and day of illness at study enrollment were significant predictors of poor platelet recovery after adjustment for baseline characteristics and platelet transfusion. Patients with poor platelet recovery had longer hospitalizations but no significant difference in other clinical outcomes, regardless of transfusion. We found a significant interaction between platelet recovery and transfusion; patients with poor platelet recovery were more likely to bleed if given a prophylactic platelet transfusion (odds ratio 2.34, 95% confidence interval 1.18-4.63). CONCLUSIONS: Dengue patients with thrombocytopenia who were older or presented earlier and with lower white cell counts were more likely to have poor platelet recovery. In patients with poor platelet recovery, platelet transfusion does not improve outcomes and may actually increase the risk of bleeding. The mechanisms of poor platelet recovery need to be determined. CLINICAL TRIALS REGISTRATION: NCT01030211.

Parental concern of feeding difficulty predicts poor growth status in their child.

BACKGROUND: Parents often express concerns about feeding difficulties in their child. We hypothesized that these parental concerns were associated with adverse growth status in early childhood. We aimed to determine the prevalence of such concerns and whether these concerns were associated with adverse growth status in early childhood. METHODS: We performed a cross-sectional study among healthy children aged 12-36 months attending three well-baby clinics in three urban areas in Malaysia and Singapore between December 2016 and February 2017. Parents were interviewed for concerns about their child's feeding and presence of behavioral and organic red flags for feeding difficulties. We defined growth faltering as weight-for-age < 3rd centile and short stature as height-for-age < 3rd centile according to World Health Organization Growth Standards. RESULTS: Of the 303 children studied (boys = 160, 52.8%; mean [± SD] chronological age at interview 21.3 [± 4.0] months), 13% (n = 38/292) had growth faltering and 19.5% (n = 50/256) had short stature. Overall, 36.3% (n = 110) of parents expressed concerns about their child's feeding behavior. Sixty-eight percent (n = 206) of parents reported presence of at least one behavioral and 18.5% (n = 56) had at least one organic red flag for feeding difficulties, respectively. 9.9% (n = 30) had both behavioral and organic red flags for feeding difficulties. Growth faltering was significantly associated with parental concern about feeding (odds ratio [OR] 3.049, p < 0.001), food refusal (OR 4.047, p < 0.001) and presence of at least one organic red flag (OR 2.625, p = 0.012). CONCLUSION: We found that parental concerns about their child's feeding to be common. Presence of parental concern, food refusal in the child and presence of organic red flags for feeding difficulties are associated growth faltering in early childhood.

Using clinical practice guidelines to manage dengue: a qualitative study in a Malaysian hospital.

BACKGROUND: Malaysia has rising dengue incidence. World Health Organization clinical practice guidelines for managing dengue have been adapted by the Ministry of Health in Malaysia, with evidence of good awareness by clinicians. However, dengue mortality has not reduced. This study aimed to explore the challenges of dengue management for Medical Officers, with a particular focus on use of clinical practice guidelines. METHODS: Qualitative study using six focus groups and 14 semi-structured interviews with doctors responsible for dengue management at a large tertiary hospital in Malaysia. RESULTS: Dengue was recognised as difficult to diagnose and manage. Wide awareness and use of both WHO and Ministry of Health guidelines was reported, but several limitations noted in their coverage of particular patient groups. However, the phrase 'guidelines' also referred to local algorithms for fluid management, which were less clinically evidence-based. Where Medical Officers were well trained in the appropriate use of evidence-based guidelines, barriers to use included: the potential for 'following the algorithm' to undermine junior clinicians' claims to clinical expertise; inability to recognise the pattern of clinical progress; and lack of clinical experience. Other reported barriers to improved case management were resource constraints, poor referral practices, and insufficient awareness of the need for timely help seeking. CONCLUSIONS: Awareness of clinical practice guidelines is a necessary, but not sufficient, condition for optimal dengue management. In high prevalence settings, all clinical staff would benefit from regular dengue management training which should include diagnosis, practice in monitoring disease progression and the use of clinical practice guidelines in a range of clinical contexts.