Topical emollient therapy in the management of severe acute malnutrition in children under two: A randomized controlled clinical trial in Bangladesh.
ABSTRACT: Background:Topical emollient therapy can improve neonatal health and growth and potentially provides an additional avenue for augmenting the provision of nutrition to children with severe acute malnutrition (SAM). We hypothesised that topical treatment of hospitalised children with SAM using sunflower seed oil (SSO), in addition to standard-of-care for SAM, would improve skin barrier function and weight gain, reduce risk of infection, and accelerate clinical recovery. Methods:We conducted a randomised, two-arm, controlled, unblinded clinical trial in 212 subjects aged 2 to 24 months who were admitted for care of SAM at the 'Dhaka Hospital' of icddr,b during January 2016 to November 2017. Enrollment was age-stratified into 2 to <6 months and 6 to 24 months age groups in a 1:2 ratio. All children received SAM standard-of-care, and the SSO group was also treated with 3 g of SSO per kg body weight three times daily for 10 days. Primary outcome was rate of weight gain over the 10-day study period. Secondary endpoints included rate of nosocomial infection, time to recovery from acute illness, skin condition score, rate of transepidermal water loss (TEWL) and C-reactive protein (CRP) level. Results:Rate of weight gain was higher in the SSO than the control group (adjusted mean difference, AMD?=?0.90 g/kg/d, 95% confidence interval (CI)?=?-1.22 to 3.03 in the younger age stratum), but did not reach statistical significance. Nosocomial infection rate was significantly lower in the SSO group in the older age stratum (adjusted odds ratio (OR)?=?0.41, 95% CI?=?0.19 to 0.85; P?=?0.017), but was comparable in the younger age stratum and overall. Skin condition score improved (AMD?=?-14.88, 95% CI?=?-24.12 to -5.65, P?=?0.002) and TEWL was reduced overall (AMD?=?-2.59, 95% CI?=?-3.86 to -1.31, P?
Project description:BACKGROUND:Natural vegetable oils are widely used for newborn massage in many low resource settings. Animal models indicated that sunflower seed oil (SSO) can accelerate skin barrier recovery following damage, while other oils, including mustard oil (MO), may cause further skin barrier damage. The objective was to compare the effects of two SSO and MO used for routine massage on skin integrity in premature and full-term neonates. METHODS:This community-based cluster randomized controlled trial included 995 neonates assigned to full body massage with sunflower seed oil (SSO, intervention) or mustard seed oil (MO, standard practice) from July 2012-May 2014 in Sarlahi, Nepal. Skin integrity measures were evaluated over 28?days, including skin condition (erythema, rash, dryness), skin surface pH, stratum corneum (SC) cohesion/protein concentration, and transepidermal water loss (TEWL). Overall means and rates of change in these skin measures were compared between oil groups using bivariate random-effects models. RESULTS:500 and 495 live born neonates received repeated massage with MO and SSO, respectively. Skin pH decreased more quickly for SSO than MO in the first week of life, with a difference in mean daily reductions of 0.02 (95% CI: 0.002-0.040). Erythema, rash and dryness increased (worsened) over days 1-14 then decreased by day 28, with no significant oil group differences. TEWL increased over time, with no significant oil group differences. Gestational age did not modify the effect; the slightly faster decrease in skin pH among SSO infants was similar in magnitude between term and preterm infants. CONCLUSIONS:Oil type may contribute to differences in skin integrity when neonates are massaged regularly. The more rapid acid mantle development observed for SSO may be protective for neonates in lower resource settings. TRIAL REGISTRATION:ClinicalTrials.gov (NCT01177111); registered August 6th, 2010.
Project description:Epidermal ceramides are indispensable lipids that maintain the functions of the stratum corneum. Esterified omega-hydroxyacyl-sphingosine (EOS) ceramide with a linoleate moiety is one of the most important ceramide species for forming cornified lipid envelopes. This linoleate moiety is eventually metabolized to trihydroxy-linoleic acid (triol, 9,10,13-trihydroxy-11E-octadecenoic acid). Thus, we assumed that a decrease of triols might reflect skin barrier dysfunction. Against this background, the purposes of this study were to measure the triols by a simple tape-stripping method and to determine the correlation between the amount of triols and transepidermal water loss (TEWL) as an indicator of barrier dysfunction in atopic dermatitis patients. Twenty Japanese subjects with normal skin and 20 atopic dermatitis patients were enrolled in this study. TEWL was measured and triols of the stratum corneum were analyzed by tape-stripping. The results showed for the first time that triols in the stratum corneum could be simply measured using the tape-stripping method. The triol levels in atopic dermatitis patients were much higher than those in healthy subjects. Moreover, the triol levels correlated with TEWL of non-lesional forearm skin in patients with atopic dermatitis. The results suggest that the assaying of triol levels via non-invasive tape-stripping could be beneficial for monitoring barrier function in atopic dermatitis.
Project description:To determine the effect a novel formulation of fluocinonide cream on skin barrier function in subjects with atopic dermatitis.The authors performed an open-label, investigator-blinded, side-by-side, controlled trial examining skin barrier function before and after a two-week course of a class I, super-potent topical steroid.Outpatient university-based dermatology clinic in Portland, OR.Twenty-five subjects aged 12 or older with a diagnosis of moderate, severe, or very severe AD were recruited for this study.Fluocinonide 0.1% cream, a novel formulation of a class I super-potent topical steroid was applied to all affected areas, except a control site, once daily for two weeks or until clear. The control target site was treated with the vehicle once daily.The study's primary outcome was change in skin barrier function as measured by basal transepidermal water loss (TEWL) in acute lesional skin from baseline as measured at two weeks.TEWL readings significantly decreased (reflecting improved barrier function) in both the active and control target sites. The active target site decreased 14.35+/-16 mg/cm2 per hour; 95 percent confidence interval, P<0.001. The control target site decreased 8.75+/-11.80 mg/cm2 per hour in 25 subjects; 95 percent confidence interval, P<0.001. Skin electrical capacitance also improved significantly, reflecting improved stratum corneum hydration with therapy. Pruritus, clinical severity, and quality of life scores all showed significant improvement by the end of the study.The authors have shown that short-term treatment with a novel formulation of 0.1% fluocinonide led to significantly improved barrier function as measured by basal TEWL in subjects with active moderate to severe AD. These data suggest short-term treatment with AD with a super-potent corticosteroid improves skin barrier function.
Project description:The management of sensitive skin, which affects over 60% of the general population, has been a long-standing challenge for both patients and clinicians. Because defective epidermal permeability barrier is one of the clinical features of sensitive skin, barrier-enhancing products could be an optimal regimen for sensitive skin. In the present study, we evaluated the efficacy and safety of two barrier-enhancing products, i.e., Atopalm (®) Multi-Lamellar Emulsion (MLE) Cream and Physiogel (®) Intensive Cream for sensitive skin.60 patients with sensitive skin, aged 22-40 years old, were randomly assigned to one group treated with Atopalm MLE Cream, and another group treated with Physiogel Intensive Cream twice daily for 4 weeks. Lactic acid stinging test scores (LASTS), stratum hydration (SC) and transepidermal water loss (TEWL) were assessed before, 2 and 4 weeks after the treatment.Atopalm MLE Cream significantly lowered TEWL after 2 and 4 weeks of treatment (p < 0.01). In contrast, Physiogel Intensive Cream significantly increased TEWL after 2 weeks of treatment (p < 0.05) while TEWL significantly decreased after 4-week treatments. Moreover, both Atopalm MLE Cream and Physiogel Intensive Cream significantly increased SC hydration, and improved LASTS after 4 weeks of treatment.Both barrier-enhancing products are effective and safe for improving epidermal functions, including permeability barrier, SC hydration and LASTS, in sensitive skin. These products could be a valuable alternative for management of sensitive skin.Veterans Affairs Medical Center, San Francisco, California, USA, and NeoPharm Co., Ltd., Daejeon, Korea.
Project description:Early identification of children <5 years with severe acute malnutrition (SAM) is a high priority to reduce child mortality and improved health outcomes. Current WHO guidelines for community screening for SAM recommend a Mid-Upper-Arm Circumference (MUAC) of less than 115 mm to identify children with SAM, but this cut-off does not identify a significant number of children with a weight-for-height Z-score <-3. To establish new specific MUAC cut-offs, pooled data was obtained for 25,755 children from 49 SMART recent surveys in Ethiopia (2016-2019). Sensitivity, proportion of false positive, and areas under receiver-operator characteristic curves (AUC) were calculated. MUAC below 115mm alone identified 55% of children with SAM identified with both methodologies. MUAC was worse in identifying older children (21%), those from a pastoral region (42%) and boys (41%). Using current WHO cut-offs, the sensitivity (Se) of MUAC below 115mm to identify the children severly malnourished screened through Weight-for-height below-3 was 16%. Analysing the ROC curve and Youden Index, Se and Specificity (Sp) were maximal at a MUAC < 133 mm cut-off to identify SAM (respectively Se 61.1%, Sp 81.4%). However, given the high proportion of false-positive children, according to gender, region and age groups, a cut-off around 125 mm to screen SAM could be the optimal one. In Ethiopia, implementation of a MUAC-only screening program for the identification of severe acute malnutrition with the actual cut-off of 115 mm would be unethical as it will lead to many children remaining undiagnosed and untreated. In addition, future study on implementation challenge on screening children with a higher cut-off or gender/age sensitive ones should be assessed with the collection of mortality and morbidity data to ensure that the most in need are being taking care of.
Project description:BACKGROUND:Low- and Middle-Income Countries (LMIC) have remained plagued with the burden of severe acute malnutrition (SAM). The decomposition of the educational inequalities in SAM across individual, household and neighbourhood characteristics in LMIC has not been explored. This study aims to decompose educational-related inequalities in the development of SAM among under-five children in LMIC and identify the risk factors that contribute to the inequalities. METHODS:We pooled successive secondary data from the Demographic and Health Survey conducted between 2010 and 2018 in 51 LMIC. We analysed data of 532,680 under-five children nested within 55,823 neighbourhoods. Severe acute malnutrition was the outcome variable while the literacy status of mothers was the main exposure variable. The explanatory variables cut across the individual-, household- and neighbourhood-level factors of the mother-child pair. Oaxaca-Blinder decomposition method was used at p?=?0.05. RESULTS:The proportion of children whose mothers were not educated ranged from 0.1% in Armenia and Kyrgyz Republic to as much as 86.1% in Niger. The overall prevalence of SAM in the group of children whose mothers had no education was 5.8% compared with 4.2% among those whose mothers were educated, this varied within each country. Fourteen countries (Cameroon(p <?0.001), Chad(p <?0.001), Comoro(p =?0.047), Burkina Faso(p <?0.001), Ethiopia(p <?0.001), India(p <?0.001), Kenya(p <?0.001), Mozambique(p =?0.012), Namibia(p =?0.001), Nigeria(p <?0.001), Pakistan(p <?0.001), Senegal(p =?0.003), Togo(p =?0.013), and Timor Leste(p <?0.001) had statistically significant pro-illiterate inequality while no country showed statistically significant pro-literate inequality. We found significant differences in SAM prevalence across child's age (p?<?0.001), child's sex(p?<?0.001), maternal age(p?=?0.001), household wealth quintile(p?=?0.001), mother's access to media(p?=?0.001), birth weight(p?<?0.001) and neighbourhood socioeconomic status disadvantage(p?<?0.001). On the average, neighbourhood socioeconomic status disadvantage, location of residence were the most important factors in most countries. Other contributors to the explanation of educational inequalities are birth weight, maternal age and toilet type. CONCLUSIONS:SAM is prevalent in most LMIC with wide educational inequalities explained by individual, household and community-level factors. Promotion of women education should be strengthened as better education among women will close the gaps and reduce the burden of SAM generally. We recommend further studies of other determinate causes of inequalities in severe acute malnutrition in LMIC.
Project description:Efficacy of high-dose vitamin A (VA) in children suffering from severe acute malnutrition (SAM) has recently been questioned. This study compared the efficacy of a single high-dose (200,000 IU) in addition to daily low-dose (5000 IU) VA in the management of children suffering from SAM with diarrhea and/or acute lower respiratory tract infection (ALRI).In a randomized, double-blind, controlled clinical trial in icddr,b, Bangladesh during 2005-07, children aged 6-59 months with weight-for-height <-3 Z-score and/or bipedal edema (SAM) received either a high-dose VA or placebo on admission day. Both the groups received 5,000 IU/day VA in a multivitamins drop for 15 days and other standard treatment which is similar to WHO guidelines.A total 260 children (130 in each group) were enrolled. All had diarrhea, 54% had concomitant ALRI, 50% had edema, 48.5% were girl with a mean±SD age of 16±10 months. None had clinical signs of VA deficiency. Mean±SD baseline serum retinol was 13.15±9.28 µg/dl, retinol binding protein was 1.27±0.95 mg/dl, and pre-albumin was 7.97±3.96 mg/dl. Median (inter quartile range) of C-reactive protein was 7.8 (2.1, 22.2) mg/L. Children of the two groups did not differ in any baseline characteristic. Over the 15 days treatment period resolution of diarrhea, ALRI, edema, anthropometric changes, and biochemical indicators of VA were similar between the groups. The high-dose VA supplementation in children with SAM did not show any adverse event.Efficacy of daily low-dose VA compared to an additional single high-dose was not observed to be better in the management of children suffering from SAM with other acute illnesses. A single high-dose VA may be given especially where the children with SAM may leave the hospital/treatment center early.ClinicalTrials.gov NCT00388921.
Project description:Severe acute malnutrition (SAM) may affect cardiac structure and function. Cardiac changes in sick children with SAM have received little attention in the literature. Children aged 6-60 months with SAM were cases, and age and sex matched children were controls. Cardiac biomarker levels were measured by the quantitative the Enzyme- linked immunosorbent assay (ELISA) method, and echocardiography was used to assess cardiac changes in all children. The study included 76 children in each group. Children with SAM had less left ventricular mass and increased myocardial performance index as compared with controls (p < 0.0001). Cardiac biomarker levels were increased in children with SAM (p < 0.0001). Cardiac changes and biomarker levels were comparable in children with edema and children without edema except creatine kinase-MB (p = 0.01).
Project description:BACKGROUND:Recent data suggest that case fatality from severe acute malnutrition (SAM) in India may be lower than the 10%-20% estimated by the World Health Organization (WHO). A contemporary quantification of mortality and recovery from acute malnutrition in Indian community settings is essential to inform policy regarding the benefits of scaling up prevention and treatment programmes. METHODS AND FINDINGS:We conducted a cohort study using data collected during a recently completed cluster-randomised controlled trial in 120 geographical clusters with a total population of 121,531 in rural Jharkhand and Odisha, eastern India. Children born between October 1, 2013, and February 10, 2015, and alive at 6 months of age were followed up at 9, 12, and 18 months. We measured the children's anthropometry and asked caregivers whether children had been referred to services for malnutrition in the past 3 months. We determined the incidence and prevalence of moderate acute malnutrition (MAM) and SAM, as well as mortality and recovery at each follow-up. We then used Cox-proportional models to estimate mortality hazard ratios (HRs) for MAM and SAM. In total, 2,869 children were eligible for follow-up at 6 months of age. We knew the vital status of 93% of children (2,669/2,869) at 18 months. There were 2,704 children-years of follow-up time. The incidence of MAM by weight-for-length z score (WLZ) and/or mid-upper arm circumference (MUAC) was 406 (1,098/2,704) per 1,000 children-years. The incidence of SAM by WLZ, MUAC, or oedema was 190 (513/2,704) per 1,000 children-years. There were 36 deaths: 12 among children with MAM and six among children with SAM. Case fatality rates were 1.1% (12/1,098) for MAM and 1.2% (6/513) for SAM. In total, 99% of all children with SAM at 6 months of age (227/230) were alive 3 months later, 40% (92/230) were still SAM, and 18% (41/230) had recovered (WLZ ? -2 standard deviation [SD]; MUAC ? 12.5; no oedema). The adjusted HRs using all anthropometric indicators were 1.43 (95% CI 0.53-3.87, p = 0.480) for MAM and 2.56 (95% CI 0.99-6.70, p = 0.052) for SAM. Both WLZ < -3 and MUAC ? 11.5 and < 12.5 were associated with increased mortality risk (HR: 3.33, 95% CI 1.23-8.99, p = 0.018 and HR: 3.87, 95% CI 1.63-9.18, p = 0.002, respectively). A key limitation of our analysis was missing WLZ or MUAC data at all time points for 2.5% of children, including for two of the 36 children who died. CONCLUSIONS:In rural eastern India, the incidence of acute malnutrition among children older than 6 months was high, but case fatality following SAM was 1.2%, much lower than the 10%-20% estimated by WHO. Case fatality rates below 6% have now been recorded in three other Indian studies. Community treatment using ready-to-use therapeutic food may not avert a substantial number of SAM-related deaths in children aged over 6 months, as mortality in this group is lower than expected. Our findings strengthen the case for prioritising prevention through known health, nutrition, and multisectoral interventions in the first 1,000 days of life, while ensuring access to treatment when prevention fails.
Project description:Patients with atopic dermatitis (AD) are commonly colonized with Staphylococcus aureus (AD S. aureus+), but what differentiates this group from noncolonized AD patients (AD S. aureus-) has not been well studied. To evaluate whether these two groups have unique phenotypic or endotypic features, we performed a multicenter, cross-sectional study enrolling AD S. aureus+ (n = 51) and AD S. aureus- (n = 45) participants defined by the presence or absence of S. aureus by routine culture techniques and nonatopic, noncolonized control individuals (NA S. aureus-) (n = 46). Filaggrin (FLG) genotypes were determined, and disease severity (Eczema Area and Severity Index, Rajka-Langeland Severity Score, Investigator's Global Assessment score, Numerical Rating Scale, and Dermatology Life Quality Index) was captured. Skin physiology was assessed (transepidermal water loss [TEWL], stratum corneum integrity, hydration, and pH), and serum biomarkers were also measured. We found that AD S. aureus+ patients had more severe disease based on all scoring systems except itch (Numerical Rating Scale), and they had higher levels of type 2 biomarkers (eosinophil count, tIgE, CCL17, and periostin). Additionally, AD S. aureus+ patients had significantly greater allergen sensitization (Phadiatop and tIgE), barrier dysfunction (TEWL and stratum corneum integrity), and serum lactate dehydrogenase (LDH) than both the AD S. aureus- and NA S. aureus- groups. FLG mutations did not associate with S. aureus+ colonization. In conclusion, adult patients with AD who are colonized on their skin with S. aureus have more severe disease, greater type 2 immune deviation, allergen sensitization, barrier disruption, and LDH level elevation than noncolonized patients with AD.