Transmethylation and Oxidative Biomarkers in Children with Autism Spectrum Disorder: A Cross Sectional Study.

We aimed to investigate the potential role of biomarkers of transmethylation, oxidative stress, and mitochondrial dysfunction in children with Autism Spectrum Disorder (ASD) by comparing them with that of typically developing children (TDC) controls. We also tried to correlate them with severity of autism, sensory issues, behavioural comorbidities and developmental quotients 119 with ASD and 52 age and sex matched typically developing children (TDC) controls were enrolled excluding those with chronic-illness or on any antioxidant therapy/multivitamins/anti-epileptic drugs. Median levels of biomarkers - serum homocysteine, cysteine, methionine, urine uric acid-to-creatinine ratio, arterial lactate, serum vitamin E, vitamin B12, folate, Nε-carboxymethyllysine, Nω- carboxymethylarginine (CMA), dityrosine and MTHFR C677T polymorphism were calculated. Children with ASD were further characterised using Childhood Autism Rating Scale-2, Childhood behavioural checklist, child sensory profile 2 caregiver questionnaire, Developmental Profile 3 for any correlation with the various biomarker levels. The median level of serum homocysteine in ASD group was 9 µmol/L(Range, 7- 16µmol/L), which was significantly higher than controls 7 µmol/L(Range, 4- 11µmol/L)(p=0.01). The prevalence of hyper-homocystinemia(>15µmol/L) was 13.4% in ASD as compared to 3.8% in controls with a significant difference(p=0.04). Dityrosine level was higher among ASD children when compared to TDC (9.8 vs 2.2 counts per second(cps), p<0.001). No significant correlation was found between prevalence of hyperhomocysteinemia and severity of autism/DQ/behavioural issues. No significant difference was found between the median levels of other biomarkers. Results support possible role of transmethylation defects and oxidative stress in ASD pathogenesis. Further studies are warranted for a better understanding of ASD pathogenesis.

'Remote inhibition' of motor cortex in Epileptic encephalopathy with spike-wave activation in sleep (EE-SWAS): A TMS based cortical excitability study.

OBJECTIVES: The study compared real-time motor cortex excitability using transcranial magnetic stimulation (TMS)-derived parameters between children with epileptic encephalopathy with spike-wave activation in sleep (EE-SWAS) and age-matched neurotypical controls. The EE-SWAS group received steroids as standard of care and were longitudinally followed for three months. MATERIALS & METHODS: Children aged 5-12 years with immunotherapy-naive EE-SWAS (spike-wave-index≥50 %) and neurotypical controls were enrolled. Cognitive and behavioral assessments were performed using valid psychometric tools. Real-time motor cortex excitability was assessed by measuring resting motor threshold (RMT), short intra-cortical inhibition (SICI) and long intra-cortical inhibition (LICI) in both groups. In EE-SWAS group, a follow up evaluation with TMS at 4- and 12-week intervals, EEG, and neurobehavioral assessments at 12-weeks were performed to assess the effect of steroids on cortical excitability and to determine electroclinical outcome. RESULTS: Forty-eight children with suspected EE-SWAS and 26 neurotypical controls were screened; 20 were enrolled in each group. Children with EE-SWAS (mean age: 8.05 ± 1.76 years) had cognitive and behavioral problems (20/20), and ongoing seizures (12/20). At baseline, the dominant motor cortex was significantly inhibited in the EE-SWAS group compared to neurotypical children{RMT(%)[86.3 ± 6.96 vs 58.05 ± 4.71(p < 0.0001)]; LICI(%)[55.05 ± 4.39 vs 73.9 ± 3.75(p < 0.0001)]; SICI(%)[39.2 ± 4.36 vs 55.45 ± 4.78(p < 0.0001)]}. Reversal of motor cortex inhibition was sequentially observed in EE-SWAS group at 4- and 12-week follow-ups{(RMT[4, 12 weeks]: 71.45 ± 9.83, 63.45 ± 8.48); (LICI[4, 12 weeks]: 66.00 ± 6.26, 74.50 ± 5.36); (SICI[4, 12 weeks]: 49.35 ± 6.24, 56.05 ± 5.57)}[repeated-measures ANOVA: p < 0.0001]. CONCLUSION: Motor cortex is remotely inhibited in EE-SWAS, which may contribute to neurobehavioral impairment. Steroids can disinhibit/reverse the epilepsy-induced motor cortex inhibition leading to improvement in neurobehavior.

Disease Damage in Juvenile Idiopathic Arthritis.

OBJECTIVES: To estimate the prevalence and predictors of disease-related damage in children with juvenile idiopathic arthritis (JIA) in a resource-limited setting. METHODS: A single-centre study was conducted from January 2021 - December 2022. Children (≤ 18 y) diagnosed with JIA as per International League of Associations for Rheumatology (ILAR) criteria, with a disease duration of more than one year, were enrolled for this study. The articular and extra-articular damage was assessed using the juvenile arthritis damage index (JADI) and modified JADI scores. Disease activity and disabilities were evaluated using the clinical juvenile arthritis disease activity score (cJADAS) and Childhood Health Assessment Questionnaire (CHAQ). RESULTS: One hundred and five children [44% (n = 42) boys] with JIA were enrolled in the study. The mean (SD) age of children at enrolment was 158 (46.2) mo. The median (IQR) disease duration was 48 (36-72) mo. Articular damage (JADI score ≥ 1) was present in 48.6%, and extra-articular damage (JADI-E ≥ 1) was observed in 21.9% of children. Half of the children (n = 22) with enthesitis-related arthritis (ERA) had joint damage (modified JADI score ≥ 1). Four children had ocular damage due to uveitis. Among the factors associated with articular damage, the odds of articular damage were high in those with positive rheumatoid factor (RF) and/ or anti-cyclic citrullinated peptides (CCPs) [OR: 4.4, 95% CI (1.00-19.60)]. CONCLUSIONS: 48.6% of children with JIA had articular damage, while 21.9% of the children had extra-articular damage. Children with RF and/ or anti-CCP positivity are associated with higher odds of joint damage.

Neuropsychological Rehabilitation for Epilepsy in India: Looking Beyond the Basics.

BACKGROUND: Neuropsychological Rehabilitation (NR) helps manage cognitive deficits in epilepsy. As internationally developed programs have limited applicability to resource-limited countries, we developed a program to bridge this gap. This 6-week caregiver-assisted, culturally suitable program has components of (1) psychoeducation, (2) compensatory training, and, (3) cognitive retraining and is called EMPOWER (Indigenized Home Based Attention and Memory Rehabilitation Program for Adult Patients with Drug Refractory Epilepsy). Its efficacy needs to be determined. METHODS: We carried out an open-label parallel randomized controlled trial. Adults aged 18-45 years with Drug Refractory Epilepsy (DRE), fluency in Hindi and or English, with impaired attention or memory (n = 28) were randomized to Intervention Group (IG) and Control Group (CG). The primary outcomes were objective memory (Auditory Verbal Learning Test), patient and caregiver reported everyday memory difficulties (Everyday Memory Questionnaire-Revised), number of memory aids in use, depression (Hamilton Depression Rating Scale), anxiety (Hamilton Anxiety Rating Scale) and quality of life (Quality of Life in Epilepsy-31). Intention to treat was carried out for group analysis. In the absence of norms necessary for computing Reliable Change Indices (RCIs), a cut-off of +1.0 Standard Deviation (SD) was utilized to identify clinically meaningful changes in the individual analysis of objective memory. A cut-off of 11.8 points was used for quality of life. Feedback and program evaluation responses were noted. RESULTS: The majority of the sample comprised DRE patients with temporal lobe epilepsy who had undergone epilepsy surgery. Group analysis indicated improved learning (p = 0.013), immediate recall (p = 0.001), delayed recall (p < 0.001), long-term retention (p = 0.031), patient-reported everyday memory (p < 0.001), caregiver-reported everyday memory (p < 0.001), anxiety (p = 0.039) and total quality of life (p < 0.001). Individual analysis showed improvement in 50 %, 64 %, 71 %, 57 %, and 64 % of patients on learning, immediate recall, delayed recall, long-term retention, and total quality of life respectively. Despite improvements, themes indicative of a lack of awareness and understanding of cognitive deficits were identified. Overall, the program was rated favorably by patients and caregivers alike. CONCLUSION: NR shows promise for patients with DRE, however larger studies are warranted. The role of cognition in epilepsy needs to be introduced at the time of diagnosis to help lay the foundation for education and acceptance.

Influence of the severity of periodontal disease on the outcome of non-surgical endodontic therapy: A prospective cohort study.

OBJECTIVE: To investigate the influence of severity of periodontal disease on periapical healing after non-surgical endodontic therapy (NSET). MATERIAL AND METHODS: In this prospective study, subjects (n = 45) requiring NSET in a mandibular molar tooth with the diagnosis of pulp necrosis and asymptomatic apical periodontitis exhibiting radiographic periapical index (PAI) score ≥ 3 and concomitant endodontic periodontal lesion (CEPL) without communication were enrolled. After dividing as per the classification of Periodontal and Peri-Implant Diseases and Conditions, subjects were equally allocated into three groups. Group I- only endodontic lesion {control: healthy periodontium (n = 15)}, Group II- CEPL having stage I and II periodontitis (n = 15) and Group III- CEPL having stage III periodontitis (n = 15). Standardized two-visit NSET was performed with 2% chlorhexidine gel as an intracanal medicament. Periodontal therapy was instituted wherever required. Subjects were recalled at 6-and 12-months for clinical and radiographic assessment. Chi-square test was performed to evaluate the difference between the groups. RESULTS: At 12-month follow-up, all teeth in the three study groups were asymptomatic. On radiographic evaluation of the periapical region, healing was observed in 80%, 47% and 50% of teeth in Groups I, Group II and Group III, respectively. However, the difference was not statistically significant between the groups (p = 0.150). CONCLUSION: The severity of periodontal disease had no influence on periapical healing after NSET in teeth with concomitant endodontic periodontal lesions without communication. CLINICAL RELEVANCE: Periodontal disease has significant impact on apical periodontitis however severity of the periodontitis does not negatively impact the apical periodontitis.

Topical Diclofenac for Prevention of Capecitabine-Associated Hand-Foot Syndrome: A Double-Blind Randomized Controlled Trial.

PURPOSE: Hand-foot syndrome (HFS) is a dose-limiting side effect of capecitabine. Celecoxib prevents HFS by inhibiting cyclooxygenase-2 (COX-2) that is upregulated because of the underlying associated inflammation. However, systemic side effects of celecoxib have limited routine prescription. Topical diclofenac inhibits COX-2 locally with minimal risk of systemic adverse events. Therefore, we conducted this study to assess the efficacy of topical diclofenac in the prevention of capecitabine-induced HFS. METHODS: In this single-site phase III randomized double-blind trial, we enrolled patients with breast or GI cancer who were planned to receive capecitabine-based treatment. Participants were randomly assigned in a 1:1 ratio to receive topical diclofenac or placebo gel for 12 weeks or until the development of HFS, whichever occurred earlier. The primary end point was the incidence of grade 2 or 3 HFS (Common Terminology Criteria for Adverse Events version 5), which was compared between the two groups using simple logistic regression. RESULTS: In total, 264 patients were randomly assigned to receive topical diclofenac gel (n = 131) or placebo (n = 133). Grade 2 or 3 HFS was observed in 3.8% of participants in the diclofenac group compared with 15.0% in the placebo group (absolute difference, 11.2%; 95% CI, 4.3 to 18.1; P = .003). Grade 1-3 HFS was lower in the diclofenac group than in the placebo group (6.1% v 18.1%; absolute risk difference, 11.9%; 95% CI, 4.1 to 19.6). Capecitabine dose reductions because of HFS were less frequent in the diclofenac group (3.8%) than in the placebo group (13.5%; absolute risk difference, 9.7%; 95% CI, 3.0 to 16.4). CONCLUSION: Topical diclofenac prevented HFS in patients receiving capecitabine. This trial supports the use of topical diclofenac to prevent capecitabine-associated HFS.

Development and Validation of a Weight Estimation Tool for Acutely Ill Children Who Cannot be Weighed.

OBJECTIVES: To develop and validate weight estimation tools using mid upper arm circumference (MUAC) and body length, and determine accuracy and precision of Broselow tape in children 6 mo to 15 y of age. METHODS: Data of 18,456 children aged 6 mo to 5 y and 1420 children aged 5 to 15 y were used to develop linear regression equations using length and MUAC to estimate weight. These were validated on prospectively enrolled populations of 276 and 312 children, respectively. Accuracy was measured by Bland-Altman bias, median percentage errors, and percentage of predicted weight within 10% of true weight. Broselow tape was tested on the validation population. RESULTS: Gender specific equations were developed which estimated weight within 10% of true weight in 69.9% (64.1-75.2%) and 65.7% (60.1-70.9%) of children aged 6 mo to 5 y, and 5 to 15 y, respectively. Broselow tape predicted weight within 10% of the true weight in 40.5% (34.7-46.6%) and 32.5% (26.7-38.7%) of children aged 6 mo to 5 y and 5 to 15 y, respectively. CONCLUSIONS: The model developed from MUAC and length accurately estimated weight in children aged 6 mo to 15 y, and is potentially useful during emergencies. The Broselow tape frequently overestimated weight in authors' setting.

Elucidating the Role of miRNA-326 Modulating Hedgehog Signaling in Pancreatic Carcinoma.

BACKGROUND AND AIM: Pancreatic ductal adenocarcinoma (PDAC) is one of the lethal malignancies worldwide characterized by poor prognosis. MicroRNAs (miRNAs) function as the key regulators in carcinogenesis and may act as noninvasive biomarkers in various malignancies including PDAC. The present study aimed to elucidate the role of miR-326, a known modulator of hedgehog (Hh) pathway in PDAC. MATERIALS AND METHODS: miR-326 circulating levels were assessed in 105 PDAC patients, 31 with chronic pancreatitis (CP) and 36 healthy controls by quantitative Polymerase chain reaction. The expression of miR-326 and smoothened (SMO) was checked in surgical PDAC tissue. SMO protein expression was analyzed by immunohistochemistry in different groups. Finally, the role of miR-326 as a modulator of Hh pathway was assessed in vitro. RESULTS: Our results demonstrate that miR-326 is downregulated in both blood and tissue of PDAC patients as compared with controls. In contrast, the target gene/protein expression of SMO is upregulated in PDAC. Moreover, the tumor stromal expression of SMO was found to be clinically associated with lymph-node metastasis and vascular encasement in PDAC. Overexpression of miR-326 in Panc1 cell line was found to induce downregulation of SMO suggesting the tumor suppressor role of miR-326 in PDAC. CONCLUSIONS: Taken together, miR-326 acts as a tumor suppressor in PDAC by modulating Hh pathway. It may be a promising target for the development of efficient drug therapies for the treatment of PDAC.

Optimal duration for recording EEG in children and adolescents- a prospective interventional study.

PURPOSE: This study aimed to determine the proportion of EEG recordings yielding diagnostic findings leading to a change in diagnosis beyond a 20-minute recording window, striking a balance between diagnostic yield and clinical practicability. METHODS: At a tertiary care teaching hospital in North India, 225 subjects aged 1 month to 18 years undergoing outpatient EEG were enrolled. Patients with epileptic encephalopathies, nonepileptic phenomena, and breakthrough seizures in the last 24 hours were excluded. Two recording protocols were employed: Category A (n=163, awake recording with activation procedures for 15 minutes followed by an attempt at sleep for 60 minutes) and Category B (n=62, sleep recording for 55 minutes followed by 5 minutes of awake recording for younger children and those with impaired cognition). EEGs were prospectively reported at 20, 30, 40, 50, and 60-minute time points, with no retrospective changes allowed. RESULTS: Among abnormal EEGs, the final diagnosis was changed beyond 20 minutes in 38.9% and 20.4% in categories A and B, respectively. A significant change in the final diagnosis among abnormal EEGs beyond 20 minutes was seen in - those who achieved sleep compared to those who didn't (45% versus 19%, p=0.03) in category A, and - focal compared to generalised seizures (Category A: 26.1% versus 8.3%, p=0.01; Category B: 23.8% versus 0%, p=0.02). CONCLUSION: Forty minutes of awake EEGs with/without sleep and 30 minutes of sleep EEGs achieve a final diagnosis in nearly 90%. Prolonging awake records beyond 20 minutes, incorporating sleep, is particularly beneficial in focal epilepsies.

Nutrition morbidity interactions in pre-school children.

Background & objectives: Research studies in the 1970s reported that in pre-school children, undernutrition increased the risk of infections and infections aggravated undernutrition. Over decades, there has been a reduction in prevalence of undernutrition and improvement in access to healthcare for treatment of infections. A mixed longitudinal study was undertaken to assess whether over time there were any changes from the earlier reported effect of undernutrition prior to infection on the risk of morbidity and effect of morbidity on nutritional status in pre-school children. Methods: Pre-school (0-59 months of age) children from urban low- and middle-income families whose parents were willing to allow their participation in the study were enrolled. Information on sociodemographic profile of the families was collected at enrolment. Weight of all children and length in infants were recorded every month; length/height in children 12-59 months of age was recorded once in three months. Morbidity information was collected through fortnightly visits. Results: 3888 pre-school children were followed up in 74636 home visits. Among these children, underweight and wasting were associated with a small increase in risk of infections. The odds ratio for risk of infection for underweight children was 1.09 (95% CI: 1.02 to 1.16) and for wasting was 1.18 (95% CI: 1.08 to 1.29). The deterioration in Z scores for weight-for-age and body mass index-for-age in children during illness and convalescence was small but significant (P<0.001). Interpretation & conclusions: The increased risk of infections in undernourished children living in overcrowded tenements in areas with poor environmental hygiene was not significant, perhaps because the risk of infection in normally nourished children was also high. The deterioration in nutritional status following infection was small because of the ready access to and utilization of health and nutrition care.

Vitamin D status & bone health in patients with liver cirrhosis.

Background & objectives: Vitamin D plays an important role in bone metabolism, and liver is the intermediary site of vitamin D metabolism. The purpose of this study was to study the prevalence of vitamin D deficiency and bone health in patients with cirrhosis. Methods: Prospectively, serum 25-hydroxy vitamin D [25(OH)D] level were assessed in cirrhotics by chemiluminescence method. Endocrine Society Clinical practice guideline was used to define deficiency and insufficiency of vitamin D. Bone mineral density (BMD) was assessed using dual-energy X-ray absorptiometry and the World Health Organization criteria was used to define osteoporosis and osteopenia. The lowest T score at the left hip neck or lumbar spine was taken as osteoporosis or osteopenia. The Child-Turcotte-Pugh score was used to assess the severity of cirrhosis. Results: Cirrhotics (n=350, male: 278, compensated: 210) were included. Mean serum 25(OH)D level was 8.75 ng/ml. The prevalence of vitamin D deficiency (VDD) and low-BMD (osteopenia and osteoporosis) was 89.4 and 86 per cent, respectively. VDD, insufficiency and osteoporosis was found in 86.7, 11.9 and 33.8 per cent, respectively, in patients with compensated cirrhosis; and 93.6, 3.6 and 40 per cent, respectively, in patients with decompensated cirrhosis. Body mass index of >25 kg/m2 was protective for bone health. Interpretation & conclusions: VDD and low-BMD is prevalent in Indian patients with cirrhosis and should be looked for in patients with cirrhosis for its prevention.

Randomized Controlled Trial of Neoadjuvant Short-Course Radiotherapy Followed by Consolidation Chemotherapy Versus Long-Course Chemoradiotherapy in Locally Advanced Rectal Cancer: Comparison of Overall Response Rates.

BACKGROUND: Management of locally advanced rectal cancer (LARC) is evolving with current emphasis on the addition of chemotherapy to short course radiotherapy (SCRT). We primarily aimed to analyse the difference in overall response rates between SCRT with sequential chemotherapy and standard long-course chemoradiotherapy (LCCRT)in LARC. METHODS: After randomization, patients in arm A received 45 Gy in 25 fractions over 5 weeks with concurrent capecitabine while patients in arm B received 25 Gy in 5 fractions over 1 week followed by 3 cycles of CAPOX (capecitabine and oxaliplatin) chemotherapy. Clinical and radiological response assessment was made after the completion of neoadjuvant treatment, a week prior to surgery. Adjuvant chemotherapy was added to complete 6 months of peri-operative chemotherapy. Surgery was performed between 8 and 10 weeks of completion of radiation treatment in both arms. RESULTS: Of the 33 patients recruited in this study between February 2020 to July 2021, 17 patients were randomized to arm A and 16 to arm B. The rates of complete tumour regression were 23.1% in arm A versus 35.7% in arm B (p-value = 0.683). Pathological complete response (pCR) rate was 20% arm A versus 30% in arm B (0.446). A higher number of patients in arm B experienced grade 3 diarrhoea, whereas acute skin toxicity was seen only in arm A. SCRT had fewer treatment interruptions compared to LCCRT. CONCLUSIONS: SCRT followed by three cycles of CAPOX chemotherapy in the neoadjuvant setting is comparable to LCCRT in terms of tumour response. This may be a better alternative regimen with fewer treatment interruptions in a resource-limited setting.

Socio-cultural Adaptation and Validation of Ages and Stages Questionnaire (ASQ 3) in Indian Children Aged 2 to 24 Months.

OBJECTIVE: To socio-culturally adapt and validate a Hindi language version of ASQ-3 in Indian children aged 2-24 months. METHODS: This cross-sectional study was conducted at a tertiary-care center between March, 2017 and April, 2019. Children "at-risk" for developmental delay of either gender aged 2-24 months. Socio-cultural adaptation was done through interaction among 37 subject experts followed by validation. After piloting in 20 children, modified ASQ-3 was validated in 568 at-risk children (4 age-groups: 2-7, 7-13, 13-19 and 19-24 months). Validation was done against Development assessment scale for Indian infants (DASII). RESULTS: Results: After screening 654 children, 568 were enrolled. Among these, 420 had developmental delay on DASII while 18 failed to be identified on ASQ (4.3%). Overall sensitivity and specificity of Hindi language Indian-adaptation of ASQ-3 in detecting developmental delay were 95.9% (95%CI: 93.6%-97.5%) and 81.7% (95%CI: 74%-87.9%), respectively with a positive predictive value (PPV) of 94.6% (95%CI: 92%-96.5%) and negative predictive value (NPV) of 85.6% (95%CI: 78.2%-92.2%). The sensitivity and specificity for motor delay were 96.1% (93.8%-97.7%) and 92.4% (86.4%-96.3%) [PPV: 97.7% (95.8%-98.9%); NPV: 87.7% (81%-92.7%)]. Sensitivity and specificity for mental delay were 95.5% (93.1%-97.2%)and 95.3% (90.1%-98.3%) [PPV: 98.6% (97%-99.5%); NPV: 85.9% (79.1%-91.2%)]. CONCLUSION: The Hindi language Indian-adaptation of ASQ-3 had good psychometric properties with high sensitivity for developmental delay (95.9%), mental delay (95.5%), and motor delay (96.1%), suggesting it to be a good screening tool for neurodevelopmental delay.

Evaluation of plasma and urine neutrophil gelatinase-associated lipocalin (NGAL) as an early diagnostic marker of acute kidney injury (AKI) in critically ill trauma patients.

Background and Aims: Acute kidney injury (AKI) is a frequent complication of severe trauma associated with high mortality. The aim of this study was to evaluate the diagnostic ability of plasma and urine neutrophil gelatinase-associated lipocalin (NGAL) as an early marker of AKI assessed by RIFLE criteria as reference in trauma patients in intensive care unit (ICU). Material and Methods: This was a prospective observational study. Four hundred and eighteen patients admitted in the trauma ICU with age ≥18 years without known renal diseases were followed-up (serum creatinine, urine output, and estimated glomerular filtration rate) for 5 consecutive days. As per RIFLE criteria, 70 patients were broadly classified as AKI and rest of the patients (n = 348) as non-AKI. Plasma and urine samples of AKI (n = 70) and non-AKI (n = 70) patients were further assessed for 3 consecutive days following admission. Results: Mean plasma NGAL (pNGAL) was significantly elevated in AKI patients as compared with non-AKI patients; on admission: 204.08 versus 93.74 ng/mL (P = 0.01); at 24 h: 216.73 versus 94.63 ng/mL (P = 0.01); and 48 h: 212.77 versus 86.32 ng/mL (P = 0.01). Mean urine NGAL (uNGAL) at 48 h was also significantly elevated: 15.45 ng/mL in AKI patients as compared with 13.48 ng/mL in non-AKI patients (P = 0.01). Plasma and urine NGAL levels were significantly associated with increased mortality. Conclusion: pNGAL had good predictive value on admission (area under the receiver operative characteristic [AUROC] 0.84), at 24 h (AUROC 0.88) and 48 h (AUROC 0.87), while uNGAL had moderate performance at 24 h (AUROC 0.61) and 48 h (AUROC 0.71). pNGAL can be used as an early and potent diagnostic and predictive marker of AKI and mortality in critically ill trauma patients.

Turning the Gaze from Survive to Thrive for Children in India: Learnings from Two Case Studies.

Despite significant efforts and progress made in newborn care programs in India, implementation gaps persist across the continuum of care. The present case studies of two districts in Himachal Pradesh revealed that pathways of care were often fragmented with inconsistent linkages between facility and community due to poor documentation, lack of tiered referral, health system weaknesses, low utilization of primary level institutions, and inadequate post-natal home visits by Accredited Social Health Activists (ASHAs). Involvement of healthcare providers (HCPs) and frontline health workers (FHWs) was low and uneven in generating awareness across the districts with limited participation in supporting care in the community. Ensuring functionality of health centers and first-level care facilities; strengthening referral systems; adequate/trained human resources; strengthening routine health management systems, discharge processes and community-based care with adequate integration with facilities are necessary in closing access gaps.

Evaluation of a paraffin-based moisturizer compared to a ceramide-based moisturizer in children with atopic dermatitis: A double-blind, randomized controlled trial.

BACKGROUND: Moisturizers are first-line therapy for treatment of atopic dermatitis (AD). Although there are multiple types of moisturizers available, head-to-head trials between different moisturizers are limited. OBJECTIVE: To evaluate if a paraffin-based moisturizer is as effective as ceramide-based moisturizer in children with AD. MATERIALS AND METHODS: In this double-blind, randomized comparative trial of pediatric patients with mild to moderate AD, subjects applied either a paraffin-based or ceramide-based moisturizer twice daily. Clinical disease activity using SCOring Atopic Dermatitis (SCORAD), quality of life using Children/Infants Dermatology Life Quality Index (CDLQI/IDLQI), and transepidermal water loss (TEWL) were measured at baseline and at follow-up at 1, 3, and 6 months. RESULTS: Fifty-three patients were recruited (27 ceramide group and 26 paraffin group) with a mean age of 8.2 years and mean disease duration of 60 months. The mean change in SCORAD at 3 months in the ceramide-based and paraffin-based moisturizer groups was 22.1 and 21.4, respectively (p = .37). The change in CDLQI/IDLQI, TEWL over forearm and back, amount and days of topical corticosteroid required, median time to remission and disease-free days at 3 months were similar in both groups. As the 95% confidence interval (CI) of mean change in SCORAD at 3 months in both groups (0.78, 95% CI: -7.21 to 7.52) was not within the predefined margin of equivalence (-4 to +4), the conclusion of equivalence could not be proven. CONCLUSION: Both the paraffin-based and ceramide-based moisturizers were comparable in improving the disease activity in children with mild to moderate AD.

Diagnostic Accuracy of Ocular Ultrasonography in Identifying Raised Intracranial Pressure among Pediatric Population.

INTRODUCTION: Role of CT scan, MRI, ophthalmoscopy, direct monitoring by a transducer probe in identifying raised intracranial pressure (ICP) in emergency department is limited. There are few studies correlating elevated optic nerve sheath diameter (ONSD) measured by point of care ultrasound (POCUS) with raised ICP in pediatrics emergencies. We studied the diagnostic accuracy of ONSD, crescent sign, and optic disc elevation in identifying increased ICP in pediatrics. METHODS: Prospective observational study was done between April 2018 and August 2019 after ethics approval. Out of 125 subjects, 40 patients without clinical features of raised ICP were recruited as external controls and 85 with clinical features of raised ICP as study subjects. Their demographic profile, clinical examination, and ocular ultrasound findings were noted. This was followed by CT scan. Out of 85 patients, 43 had raised ICP (cases) and 42 had normal ICP (disease controls). Diagnostic accuracy of ONSD in identifying raised ICP was evaluated using STATA. RESULTS: The mean ONSD in case group was 5.5 ± 0.6 mm, 4.9 ± 0.5 mm in disease control group and external control group was 4.8 ± 0.3 mm. Cut-off of ONSD for raised ICP at ≥4.5 mm had a sensitivity and specificity of 97.67% and 10.98%, while ≥5.0 mm showed a sensitivity and specificity of 86.05% and 71.95%. Crescent sign and optic disc elevation had good correlation with increased ICP. CONCLUSION: ONSD ≥5 mm by POCUS identified raised ICP in pediatric population. Crescent sign and optic disc elevation may function as additional POCUS signs in identifying raised ICP.

Impact of Topical Cyclosporine-A or Topical Chloroquine on Post-LASIK Ocular Surface Stability - A Randomized Controlled Trial.

PURPOSE: To compare effect of topical cyclosporine-A 0.05% (CsA) and chloroquine phosphate 0.03% (CHQ) as an adjunct to standard therapy in maintaining post-laser assisted in situ keratomileusis (LASIK) ocular surface stability. METHODS: Randomized controlled trial on 100 eyes undergoing femtosecond-LASIK randomized into three groups: 33 eyes in Group I (Standard Treatment group), 34 eyes in Group II (CsA group) and 33 eyes in Group III (CHQ group). Standard treatment included topical moxifloxacin, topical prednisolone and carboxymethyl cellulose. Group II received topical CsA 0.05% twice daily for three months and group III received topical CHQ 0.03% twice daily for three months in addition to standard treatment. Primary outcome measure was change in ocular surface disease index (OSDI) at 6 months. Secondary outcome measures were tear break up time (TBUT), Schirmer-I score, tear film osmolarity, tear film MMP-9 and visual acuity. Follow-up was performed at postoperative 1, 3 and 6 months. RESULTS: At 6 months, OSDI score, MMP-9, tear osmolarity, TBUT and Schirmer score were significantly better in both CsA and CHQ groups as compared with controls (p < 0.001). OSDI, Tear osmolarity, TBUT, MMP-9 levels were comparable in CsA and CHQ group (p > 0.05). In CsA group, tear film MMP-9 levels at 6 months were comparable to preoperative baseline (p = 0.09). There was no significant change in the Schirmer score from baseline in the CsA group; in addition, the Schirmer score was significantly better than the CHQ group at 6 months (p = 0.02). Visual acuity was comparable in all three groups. Adverse effects including burning sensation, stinging, pain and redness were reported by ten patients (CsA group- 3, CHQ group-7; p = 0.28). CONCLUSION: Both CsA and CHQ are useful adjuncts to standard therapy in maintaining ocular surface stability after refractive surgery. Cyclosporine A has more potent and sustained anti-inflammatory effect with less ocular irritative effects.

Ultrasonography of the neck in patients with obstructive sleep apnea.

INTRODUCTION: In resource-limited settings, obstructive sleep apnea (OSA) often goes undiagnosed as polysomnography (PSG) is expensive, time-consuming, and not readily available. Imaging studies of upper airway have been tried as alternatives to PSG to screen for OSA. However, racial differences in upper airway anatomy preclude generalizability of such studies. We sought to test the hypothesis that ultrasonography (USG), an inexpensive, readily available tool to study soft tissue structures of the upper airway, would have predictive value for OSA in South Asian people. METHODS: Adult patients with sleep-related complaints suspicious for OSA were taken for overnight PSG. After the PSG, consecutive patients with and without OSA were studied with submental ultrasonography to measure tongue base thickness (TBT) and lateral pharyngeal wall thickness (LPWT). RESULTS: Among 50 patients with OSA and 25 controls, mean age was 43.9 ± 11.4 years, and 39 were men. Patients with OSA had higher TBT (6.77 ± 0.63 cm vs 6.34 ± 0.54 cm, P value = 0.004) and higher LPWT (2.47 ± 0.60 cm vs 2.12 ± 0.26 cm, P value = 0.006) compared to patients without OSA. On multivariate analysis, TBT, LPWT, and neck circumference were identified as independent factors associated with OSA. These variables could identify patients with severe OSA with a sensitivity of 72% and a specificity of 76%. CONCLUSION: Patients with OSA have higher tongue base thickness and lateral pharyngeal wall thickness proportionate to the severity of the disease, independent of BMI and neck circumference. These findings suggest that sub-mental ultrasonography may be useful to identify patients with severe OSA in resource-limited settings.