Early versus late fortification of breast milk in preterm infants: a systematic review and meta-analysis.

This systematic review and meta-analysis assessed the effects of early fortification (EF) versus late fortification (LF) of breast milk (BM) on growth of preterm infants. Randomized and quasi-randomized controlled trials (RCTs) dealing with the effects of EF versus LF on growth parameters, incidence of adverse events, and duration of hospital stay in preterm infants were included. Data were pooled using the RevMan 5.3 software. Quality of evidence for predefined outcomes was analyzed by GRADE. Available evidence (3 RCTs, 309 preterm infants) showed no statistically significant difference between EF and LF of BM for any of the growth parameters-weight (standardized mean difference (SMD) 0.13; 95% confidence interval (CI) - 0.09, 0.36); length (SMD 0.02; 95% CI - 0.20, 0.25); and head circumference (SMD - 0.10; 95% CI - 0.33, 0.12). Total parenteral nutrition days were similar. Duration of hospital stay was significantly higher with EF (MD 4.29; 95% CI 0.84, 7.75) with a trend of non-significant increase in feed intolerance and necrotizing enterocolitis (NEC).Conclusion: Very low quality evidence did not find any significant difference in growth parameters of preterm infants in association with EF or LF of BM. A significant increase in hospital stay and non-significant increase in feed intolerance and NEC were associated with EF.PROSPERO registration number: CRD42019139235What is Known:• Fortification of breast milk with essential macro- and micronutrients is necessary for optimization of nutrition in preterm infants.• There is no consensus regarding the breast milk feeding volume at which fortification should be initiated.What is New:• Very low quality evidence showed no significant difference between early and late fortification of breast milk on growth parameters of preterm infants.• Early fortification was associated with non-significant increase in feed intolerance and necrotizing enterocolitis and a significant increase in hospital stay.

Biochemical regulation and structural analysis of copper-transporting ATPase in a human hepatoma cell line for Wilson disease.

Hepatic copper levels differ among patients with Wilson disease (WD) and normal individuals depending on the dietary intake, copper bioavailability, and genetic factors. Copper chloride (CuCl2 ) caused dose-dependent reduction in cell viability of human teratocarcinoma (HepG2) cell line, measured using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Cells were exposed to different concentrations of CuCl2 in log doses and maximum cell viability reduction was recorded at 15 µg/mL. Toxic dose of CuCl2 is potent inducer of reactive oxygen species (ROS). Apoptosis as a pattern of cell death was confirmed through sub-G1 fraction and morphological changes such as mitochondrial depolarization, endoplasmic reticulum and lysosomal destabilization, phosphatidylserine translocation, and DNA damage. Our transcriptional and translational results strongly support apoptotic cell death. Using the available data present in dbSNP and bioinformatics tools, three nonsynonymous single nucleotide polymorphisms (nsSNPs) were identified as deleterious, reducing the stability of protein ATP7B. Structural analysis of native and mutant ATP7B proteins was investigated using molecular dynamics simulation (MDS) approach. Mutation in ATP7B gene might disturb the structural conformation and catalytic function of the ATP7B protein may be inducing WD. Hence, excess dietary intake of copper chloride must be avoided for safety of health to prevent from WD.

Effect of Splint Application on the Functional Duration of Peripheral Intravenous Cannulation in Neonates: A Systematic Review and Meta-analysis.

BACKGROUND: The application of splints is one of the most used methods to prolong the life span of peripheral intravenous cannulation (PIVC). OBJECTIVE: To assess the effect of splint application on the functional duration of PIVC in neonates. METHODS: This systematic review and meta-analysis identified, appraised, and synthesized available evidence from randomized and quasi-randomized controlled trials (RCT) related to the effects of splint application compared to no splinting on the functional duration of PIVC and its associated complications in term and preterm neonates. Data were pooled using RevMan 5.4. The quality of evidence for predefined outcomes was analyzed by GRADE. RESULTS: Available evidence (5 RCTs, 826 neonates) showed a significantly lesser functional duration of PIVC in the splint group compared to no-splint [Mean Difference (MD) 95% Confidence Interval (CI) -3.07 (-5.63, -0.51); Low Certainty of Evidence (CoE)]. On gestation-based subgroup analysis, PIVC duration remained significantly lesser in the splint group in preterm neonates [MD (95% CI), -5.09 (-9.53, -0.65), 2 studies, n = 220; Low CoE], whereas it was comparable in the term neonates [MD (95% CI), 3.92 (-4.27, 12.10), 2 studies, n = 89; Very low CoE]. The overall complications were comparable between the groups [Risk Ratio (95% CI), 1.02 (1.00, 1.05), 5 studies, n = 826; Very low CoE]. CONCLUSION: Based on the very low to low CoE found in this systematic review, it is not possible to recommend or refute splint application in neonates. Further well-designed RCTs are needed.

Design, implementation and evaluation of a spiral module combining data science, digital health and evidence-based medicine in the undergraduate medical curriculum: A mixed methods study.

BACKGROUND: Digital health, data science and health informatics are increasingly important in health and healthcare, but largely ignored in undergraduate medical training. METHODS: In a large UK medical school, with staff and students, we co-designed a new, 'spiral' module (with iterative revisiting of content), covering data science, digital health and evidence-based medicine, implementing in September 2019 in all year groups with continuous evaluation and improvement until 2022. RESULTS: In 2018/19, a new module, 'Doctor as Data Scientist', was co-designed by academic staff (n = 14), students (n = 23), and doctors (n = 7). The module involves 22 staff, 120 h (43 sessions: 22 lectures, 15 group and six other) over a 5-year curriculum. Since September 2019, 5,200 students have been taught with good attendance. Module student satisfaction ratings were 92%, 84%, 84% and 81% in 2019, 2020, 2021 and 2022 respectively, compared to the overall course (81%). CONCLUSIONS: We designed, implemented and evaluated a new undergraduate medical curriculum that combined data science and digital health with high student satisfaction ratings.

Pain Assessment and Management Practices via Education & Reinforcement (PAMPER): A Quality Improvement Initiative.

OBJECTIVES: To establish neonatal pain management practices as an essential developmental supportive measure at a tertiary care unit. METHODS: This quality improvement initiative was conducted as per Point-of-Care-Quality-Improvement Model over 6 mo, followed by 2 y of sustenance phase at a Neonatal Intensive Care Unit (NICU) in northern India. Infants of birth weight ≤1800 g were included and assessed for pain. Pain Assessment and Management Practices via Education and Reinforcement (PAMPER) group was created by resident doctors and nursing staff. The Premature Infant Pain Profile score was used for the assessment of pain. Limiting factors were analyzed using a fishbone diagram and interventions were done in multiple Plan-Do-Study-Act cycles. RESULTS: At the end of interventions, 100% of procedures were assessed for pain. The mean (standard deviation) documented pain score for the first seven days was reduced from 12.8 (0.3) in the baseline phase to 7 (2.5). These interventions helped to sustain the practice in >70% of infants in the next 2 y. CONCLUSIONS: Low-cost interventions improved the pain assessment and management policy of authors' NICU with the establishment of a standard protocol. Audits and reinforcement at regular intervals helped in its long-term sustenance.

Does left atrial appendage morphology and dimension differ amongst etiological stroke subtypes in patients without known atrial fibrillation? Results from the left atrial appendage morphology and dimension assessment by TEE in patients with stroke without known atrial fibrillation (LAMDA-STROKE) study.

CONTEXT: Complex left atrial appendage (LAA) morphology is increasingly associated with cryptogenic ischemic stroke as compared to cardioembolic stroke due to atrial fibrillation (AF). However, data on such an association in patients with other etiological stroke subtypes in the absence of AF is limited. AIM: The study aimed to assess the LAA morphology, dimension and other echocardiographic parameters by transesophageal echocardiography (TEE) in patients with embolic stroke of undetermined source (ESUS) and compare it with other etiological stroke subtypes without known AF. METHODS: This was a single-Centre, observational study involving comparison of echocardiographic parameters including LAA morphology and dimension in ESUS patients (group A; n = 30) with other etiological stroke subtypes i.e., TOAST (Trial of Org 10172 in Acute Stroke Treatment) class I-IV without AF (group B; n = 30). RESULTS: Complex LAA morphology was predominant in group A (18 patients in group A versus 5 patients in group B, p-Value = 0.001). Mean LAA orifice diameter (15.3 + 3.5 mm in group A versus 17 + 2.0 mm in group B, p-Value = 0.027) and LAA depth were significantly lower in group A (28.4 + 6.6 mm in group A versus 31.7 + 4.3 mm in group B, p-Value = 0.026). Out of these three parameters only complex LAA morphology was found to be independently associated with ESUS [OR = 6.003, 95% CI {1.225-29.417}, p = 0.027]. CONCLUSION: Complex LAA morphology is a predominant feature in ischemic stroke patients with ESUS and may contribute to an increased risk of stroke in these patients.

Cortical hemodynamic activity and pain perception during insertion of feeding tubes in preterm neonates: a randomized controlled cross-over trial.

OBJECTIVE: The present study evaluated the pain perception in preterm neonates during insertion of orogastric (OG) vs. nasogastric (NG) tube by measuring the cerebral regional oxygen saturation (crSO2) and premature infant pain profile-revised (PIPP-R) score. STUDY DESIGN: Randomized controlled cross-over trial. RESULTS: Fifty infants of mean (SD) gestational age of 31.54(2) and 31.64(2.2) weeks, birth weight of 1362(354) and 1507(365) grams were randomized into OG/NG (n = 25) and NG/OG (n = 25) sequences. Mean post-menstrual age at assessment was 33(2.8) and 33(1.5) weeks, and the difference between two interventions was 1.08(0.5) and 1.12(0.5) days in OG-NG and NG-OG, respectively. Mean crSO2(%) during insertion was significantly lower with NG compared to OG route. Mean PIPP-R score, heart rate variability, time to normalize crSO2, and the duration of cry were also significantly higher with NG insertion. CONCLUSIONS: Compared to OG, NG route of feeding tube insertion was associated with higher fluctuations in crSO2 and higher PIPP-R scores. CLINICAL TRIAL REGISTRY OF INDIA (CTRI) REGISTRATION NO: CTRI/2020/03/023728.

Fortification of Human Milk With Infant Formula for Very Low Birth Weight Preterm Infants: A Systematic Review.

BACKGROUND: Off-label fortification of expressed human milk (HM) with infant milk formula (IMF) is common in developing countries, though its benefits and safety are unclear. OBJECTIVE: To study the effects of IMF fortification of HM on growth of very low birth weight (VLBW) preterm infants. DESIGN: Systematic review and meta-analysis of randomized and quasi-randomized controlled trials (RCTs). DATA SOURCES AND SELECTION CRITERIA: MEDLINE, EMBASE, CINAHL, CENTRAL and other databases were searched for articles published in English language from inception to December 2019, evaluating the effects of HM fortified with IMF as intervention, compared to unfortified HM or HM fortified with human milk fortifier (HMF). PARTICIPANTS: Five RCTs including 423 VLBW preterm infants. INTERVENTION: Feeding with HM fortified with IMF compared to unfortified or HMF-fortified HM. OUTCOME MEASURES: Primary outcome measure was assessment of growth as weight, length and head circumference (HC) gain velocity. Secondary outcome measures were incidences of feed intolerance (FI), necrotizing enterocolitis (NEC), time to reach full feeds, concentration of nutritional biomarkers, duration of hospital-stay and cost of intervention. RESULTS: Of the five studies included in the review, pooled effects regarding weight gain velocity (SMD 0.27 g/day; 95% CI 0.08 to 0.62), length gain (MD 0.07cm/week; 95% CI 0.02 to 0.16) and HC gain (MD 0.05 cm/wk; 95% CI 0.01 to 0.11), were not statistically significant. Sensitivity analysis by pooling studies using unfortified milk as comparator yielded a statistically significant result for all growth parameters. Risk of FI or NEC was comparable. Length of hospitalstay was reduced in the intervention group. CONCLUSIONS: A very-low quality evidence suggested that IMF fortification of HM is superior to unfortified milk and may be a safe alternative for HMF for short term growth of VLBW preterm infants.

Developmentally Supportive Positioning Policy for Preterm Low Birth Weight Infants in a Tertiary Care Neonatal Unit: A Quality Improvement Initiative.

OBJECTIVES: To improve developmentally supportive positioning practices by 50% in neonates weighing <1800 g, admitted in a neonatal intensive care unit over 6 months. METHODS: Infant Position Assessment Tool (IPAT) scores were used for assessment of the ideal position. Proportion of neonates with IPAT score ≥8 and improvement of average IPAT score were the process and the outcome measures, respectively. At baseline, 16.6% of infants had optimum position. After root cause analysis, interventions were done in multiple Plan-Do-Study-Act (PDSA) cycles of educational sessions, positioning audits, use of low-cost nesting aids, and training of mothers. RESULTS: Over 21 weeks, 74 neonates were observed at 714 opportunities. Over 6 months, mean (SD) IPAT score improved from 3.4 (1.4) to 9.2 (2.8). Optimum positioning was maintained in 83.3% neonates during sustenance phase. CONCLUSIONS: Low-cost interventions, awareness regarding standards of optimum positioning and involvement of primary caregiver can effectively improve infant positioning practices.

Agitated saline contrast to delineate central venous catheter position in neonates.

OBJECTIVE: Central venous catheter (CVC) insertion is required for the management of sick neonates. Ultrasonography/targeted neonatal echocardiography (TNE) with/without normal saline (NS) flush is used to identify CVC position. The present study compared the visibility and safety of agitated saline (AS) with normal saline (NS) flush. STUDY DESIGN: This prospective interventional study included 110 CVC insertions, both umbilical venous catheterization (UVC) and peripherally inserted central catheterization (PICC). Catheter position was monitored by real-time TNE. RESULTS: Overall visibility of catheter tip (combined UVC and PICC) was significantly better in AS (n = 55) compared with NS group (n = 55) [48/55 (87.2%) vs. 28/55 (50.9%); p < 0.0001]. Time to detect catheter tip by AS push was significantly less than that of NS push. There was no difference in the amount of saline flush required with either method. No major adverse effect was observed. CONCLUSIONS: AS push can be used as a safe method to delineate CVC position in neonates.

Oral Care with Mother's Own Milk in Sick and Preterm Neonates: A Quality Improvement Initiative.

OBJECTIVE: Oral care with mother's own milk (OC-MOM) in sick and preterm neonates provides immune protection, improves feed tolerance and helps in earlier achievement of full enteral nutrition. This quality improvement (QI) initiative was undertaken when authors documented scanty awareness regarding neonatal oral care practices among care-givers in their neonatal unit. The project aimed to improve the proportion of OC-MOM in sick and preterm neonates from the baseline of 5.9% to 80%. METHODS: The QI project was designed as per Point of Care Quality Improvement (POCQI) model and conducted over 6 mo (January 14, 2019 to July 12, 2019). Preterm and sick term neonates on enteral fasting or gavage feeding were included. Neonates with major congenital malformation and whose MOM was not available were excluded. An OC-MOM team was formed and baseline data were collected. Flow charts and fish-bone diagrams were used to analyse the problem and identify the key issues. Mouth assessment tool (MAT) was customized and adapted as one of the outcome measures. An OC-MOM protocol was designed and implemented as a part of routine neonatal care. RESULTS: Four Plan-Do-Study-Act (PDSA) cycles were conducted to achieve the target. After successful implementation of OC-MOM protocol, proportion of neonates receiving OC-MOM increased to 83.3% from a baseline of 5.9% and proportion of neonates having MAT score "0" improved to 94.4% from a baseline of 24.4%. CONCLUSIONS: This QI initiative using POCQI model resulted in a significant and sustained improvement in the proportion of neonatal oral care with MOM using locally available resources.

Epidemiology of hepatitis B and C viral infections in Ladakh region.

BACKGROUND: Little is known about the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections in Ladakh, a mountainous region with low population density. We, therefore, determined these and tried to identify risk factors associated with these infections. METHODS: Randomly selected residents of Ladakh region were tested for hepatitis B surface antigen (HBsAg), antibodies to hepatitis B core antigen (anti-HBc) and antibodies to HCV (anti-HCV). A subset of HBsAg-positive persons were tested for hepatitis B e-antigen (HBeAg) and HBV DNA and those with anti-HCV for HCV RNA. Viral genotype was also determined. RESULTS: Of the 2674 subjects, 141 (5.3%) tested positive for HBsAg, i.e. had current HBV infection and 339 (12.7%) tested positive for either HBsAg and or anti-HBc, i.e. had either current or past infection with HBV. Anti-HCV antibody was detected in 22 (0.8%) subjects. The HBsAg positivity rate was higher in Kargil district (8.3%) than in Leh district (3.3%). No particular risk factor was identified for either infection. Of the 141 and 22 specimens that contained HBsAg and anti-HCV, respectively (one had both), 74 and none tested positive for HBV DNA and HCV RNA, respectively. Of the 29 specimens that had sufficient HBV DNA for genotyping, 21, 7, and 1 specimens had HBV genotypes D, C, and A, respectively. CONCLUSION: The overall prevalence of HBV infection seems to be higher in Ladakh region, especially the Kargil district. The prevalence of anti-HCV was similar to that in other parts of India. ᅟ ᅟ.