Efficacy of prophylactic phototherapy for prevention of hyperbilirubinemia in very low birth weight newborns

Background: Jaundice is a common clinical condition in newborn occurring in approximately 60% of term and 80% of preterm infants. Unconjugated hyperbilirubinemia is universally common in all preterm infants especially in newborns with very low biLth weight. Low birth weight and premature infants are at major risk for exaggerated hyperbilirubinemia that can lead to bilirubin encephalopathy. Significant heterogeneity in the approach to the treatment of jaundiced neonates exists throughout the world. Phototherapy is the most common treatment for neonatal hyperbilirubinemia and could be most effective in preventing the sequelae of hyperbilirubinemia if initiated prophylactically. This randomized clinical trial has been proposed with the objective of assessing the efficacy of prophylactic photo therapy in preventing significant rise of unconjugated hyperbilirubinemia in premature neonates weighing less than 1500 gram and therefore to decrease the need for exchange transfusion and finally to reduce hospital stay due to hyperbilirubinemia. Methods: This randomized controlled clinical trial enrolled sixty newborns with birth weight less than 1500 gram. They were divided into two groups: 1) Prophylactic group, in whom phototherapy was started within 24 hours of birth and continued for 7 days and 2) Control group in whom therapeutic phototherapy was started considering serum bilirubin level and other clinical condi­tions as per institutional guidelines. Mean value of total serum bilirubin (TSB), duration of phototherapy, the need for exchange transfusion and duration of hospital stay in both groups were analyzed.Results: The maximum mean TSB level in prophylactic group was observed on 7th day and in control group it was observed on 3rd day of life. The total serum bilirubin levels were significantly lower in the 3rd and 5th days of life in the prophylactic group in comparison to control group (P value 0.001). Total serum bilirubin level exceeded therapeutic range in 6 (21 %) and 14 (50 %) newborns of the prophylactic group and control groups respectively (P value 0.026). No documented side effects of prophylactic photo­therapy was observed. Conclusion: The use of prophylactic photo therapy for infants weighing less than 1500 grn is effec­tive and sate when compared to the control group, considering satisfactory maintenance of low total serum bilimbin levels during first 7 days of life

A Knowledge graph representation of baseline characteristics for the Dutch proton therapy research registry

Cancer registries collect multisource data and provide valuable information that can lead to unique research opportunities. In the Netherlands, a registry and model-based approach (MBA) are used for the selection of patients that are eligible for proton therapy. We collected baseline characteristics including demographic, clinical, tumour and treatment information. These data were transformed into a machine readable format using the FAIR (Findable, Accessible, Interoperable, Reusable) data principles and resulted in a knowledge graph with baseline characteristics of proton therapy patients. With this approach, we enable the possibility of linking external data sources and optimal flexibility to easily adapt the data structure of the existing knowledge graph to the needs of the clinic

Transcriptomic profile of adverse neurodevelopmental outcomes after neonatal encephalopathy

A rapid and early diagnostic test to identify the encephalopathic babies at risk of adverse outcome may accelerate the development of neuroprotectants. We examined if a whole blood transcriptomic signature measured soon after birth,predicts adverse neurodevelopmental outcomeeighteenmonths after neonatal encephalopathy.We performed next generation sequencing on whole blood ribonucleic acid obtained within sixhours of birth from the first 47encephalopathic babies recruited to the Hypothermia for Encephalopathy in Low and middle-income countries (HELIX)trial. Two infants with blood culture positive sepsis were excluded, and the data from remaining 45 were analysed. A total of 855genes were significantly differentially expressed between the good and adverse outcome groups, of which RGS1and SMC4 werethe most significant. Biological pathway analysis adjusted for gender, trial randomisation allocation (cooling therapy versus usual care) and estimated blood leukocyte proportions revealed over-representation of genes from pathways related to melatoninand polo-like kinase in babieswith adverse outcome. These preliminary data suggest that transcriptomic profiling may be a promising tool for rapid risk stratification in neonatal encephalopathy. It may provide insights into biological mechanismsand identify novel therapeutic targetsfor neuroprotection

Early and extended erythropoietin monotherapy after hypoxic ischaemic encephalopathy:a multicentre double-blind pilot randomised controlled trial

Objective: To examine the feasibility of early and extended erythropoietin monotherapy after hypoxic ischaemic encephalopathy (HIE). Design: Double-blind pilot randomised controlled trial.Setting: Eight neonatal units in South Asia. Patients: Neonates (≥36 weeks) with moderate or severe HIE admitted between 31 December 2022 and 3 May 2023. Interventions: Erythropoietin (500 U/kg daily) or to the placebo (sham injections using a screen) within 6 hours of birth and continued for 9 days. MRI at 2 weeks of age. Main outcomes and measures: Feasibility of randomisation, drug administration and assessment of brain injury using MRI. Results: Of the 154 neonates screened, 56 were eligible; 6 declined consent and 50 were recruited; 43 (86%) were inborn. Mean (SD) age at first dose was 4.4 (1.2) hours in erythropoietin and 4.1 (1.0) hours in placebo. Overall mortality at hospital discharge occurred in 5 (19%) vs 11 (46%) (p=0.06), and 3 (13%) vs 9 (40.9%) (p=0.04) among those with moderate encephalopathy in the erythropoietin and placebo groups. Moderate or severe injury to basal ganglia, white matter and cortex occurred in 5 (25%) vs 5 (38.5%); 14 (70%) vs 11 (85%); and 6 (30%) vs 2 (15.4%) in the erythropoietin and placebo group, respectively. Sinus venous thrombosis was seen in two (10%) neonates in the erythropoietin group and none in the control group. Conclusions: Brain injury and mortality after moderate or severe HIE are high in South Asia. Evaluation of erythropoietin monotherapy using MRI to examine treatment effects is feasible in these settings. Trial registration number: NCT05395195

Reducing ineffective practice:Challenges in identifying low-value health care using cochrane systematic reviews

Objectives: Despite international agreement that stopping low value practices will increase efficiency, identifying them is difficult and controversial. Opponents of centralized lists of low value practices stress that the actual problem is inappropriate low value use, and better targeting and implementation of treatment thresholds is needed. Our objective was to use Cochrane Reviews to identify low value practices to support local disinvestment decisions. Methods: New or updated reviews were included if the authors concluded that the uncertain effectiveness of an intervention meant it should only be used in research, or that it was ineffective or harmful and should not be used. The reviews go through a production and quality assurance process, and are published as ‘Cochrane Quality and Productivity topics’ through the NHS Evidence website ( http://www.library.nhs.uk/qipp/ ). Results: Over a six-month period, 65 Cochrane reviews were processed by the National Institute for Health and Clinical Excellence (NICE). Of these, 28 identified potentially low value practices in the UK context. This was primarily due to a lack of randomized evidence of effectiveness, rather than robust evidence of a lack of effectiveness, or evidence of harm. Conclusions: Identifying low-value health care practices for local disinvestment (total or partial) is both practically and politically challenging, yet it is necessary to manage health budgets. This project identified that Cochrane Reviews can potentially identify low value health care practices. However, each review has to be reinterpreted for the UK context and additional analysis has to be undertaken to facilitate local implementation. Recommendations to improve the usability of systematic reviews are made. </jats:sec

Disinvestment and value-based purchasing strategies for pharmaceuticals : an international review

Pharmaceutical expenditure has increased rapidly across many OECD countries over the past three decades. This growth is an increasing concern for Governments and other third party payers seeking to provide equitable and comprehensive healthcare within sustainable budgets. In order to create headroom for increasing utilisation, and to fund new high cost therapies there is an active push to ‘disinvest’ from low-value drugs. The aim of this article is to review how reimbursement policy decision makers have sought to partially or completely disinvest from drugs in a range of OECD countries (UK, France, Canada, Australia and New Zealand) where they are publicly funded or subsidised. We employed a systematic literature search strategy and the incorporation of grey literature known to the authorship team. We canvass key policy instruments from each country to outline: key approaches to the identification of candidate drugs for disinvestment assessment (passive approaches versus more active approaches); Methods of disinvestment and value-based purchasing: de-listing, restricting treatment, price or reimbursement rate reductions, encouraging generic prescribing; Lessons learnt from the various approaches; The potential role of coverage with evidence development, and; The need for careful stakeholder management. Dedicated sections are provided with detailed coverage of policy approaches (with drug examples) from each country. Historically countries have relied on ‘passive disinvestment’, however due to (i) the availability of new cost-effectiveness evidence or (ii) ‘leakage’ in drug utilisation or (iii) market failure in terms of price competition, there is an increasing focus towards ‘active disinvestment’. Isolating low-value drugs that would create headroom for innovative new products to enter the market is also motivating disinvestment efforts by multiple parties, including industry. Historically disinvestment has mainly taken the form of price reductions, especially when market failures are perceived to exist, and restricting treatment to sub-populations, particularly when a drug is no longer considered value for money. There is considerable experimentation internationally in mechanisms for disinvestment and the opportunity for countries to learn from each other. Ongoing evaluation of disinvestment strategies is essential, and ought to be reported in the peer-reviewed literature

EVIDENCE INFORMED DECISION MAKING:THE USE OF “COLLOQUIAL EVIDENCE” AT NICE

Objectives: Colloquial evidence (CE) has been described as the informal evidence that helps provide context to other forms of evidence in guidance development. Despite challenges around quality, and the potential biases, the use of CE is becoming increasingly important in assessments where scientific literature is sparse and to also capture the experience of all stakeholders in discussions, including that of experts and patients. We aimed to ascertain how CE was being used at the National Institute for Health and Care Excellence (NICE). Methods: Relevant data corresponding to the use of CE was extracted from all NICE technical and process manuals by two reviewers and quality assured and analyzed by a third reviewer. This was considered in light of the results of a focused literature review and a combined checklist for quality assessment was developed. Results: At NICE, CE is utilised across all guidance producing programmes and at all stages of development. CE could range from information from experts and patient/carers, grey literature (including evidence from websites and policy reports) and testimony from stakeholders through consultation. Six tools for critical appraisal of CE were available from the literature and a combined best practice checklist has been proposed. Conclusions: As decisions often need to be made in areas where there is a lack of published scientific evidence, CE is employed. Therefore to ensure its appropriateness the development of a validated CE data quality check-list to assist decision makers is essential and further research in this area is a priority

Development of spirometry predictive values for Indian population

Single CSV (comma-separated values) file. ## Access ## This dataset is held in the Edinburgh DataVault, directly accessible only to authorised University of Edinburgh users. Academic researchers may request access, and will be required to sign a data sharing agreement.Interpretation of spirometry involves comparing lung function parameters with predicted values to determine the presence/severity of the disease. The Global Lung Function Initiative (GLI) derived reference equations for healthy individuals aged 3–95 years from multiple populations but highlighted India as a ‘particular group’ in whom further data are needed. We aimed to derive predictive equations for spirometry in a rural Western Indian adult population. We used spirometry data previously collected (2008-2012) from 1,258 healthy adults (aged 18 years and over) by the Vadu Health and Demographic Surveillance System. We constructed sex-stratified prediction equations for FEV1, FVC, and FEV1/FVC using the Generalised Additive Model for Location, Scale and Shape (GAMLSS) method to derive the best fitting model of each outcome as a function of age and height. When compared with GLI Ethnicity Codes 1 (White Caucasian) and 5 (Other/Mixed), the Western Indian adult population appears to have lower lung volumes on average, though the FEV1/FVC ratio is comparable. Both age and height were predictive of mean FEV1 and FVC; and for females, the variability of response was also dependent on age. FEV1/FVC appears to have a very strong age effect, highlighting the limitations of using a fixed 0.7 cut-off value. The use of GLI normal values may result in overdiagnosis of lung disease in this population. We recommend that the values and equations generated from this study should be used by physicians in their routine practice for diagnosing disease and its severity in adults from the Western Indian population.Juvekar, Sanjay; Agarwal, Dhiraj; Pinnock, Hilary; Roy, Sudipto; Parker, Richard; Khatavkar, Parag; Salvi, Sundeep; Ghorpade, Deesha. (2020). Development of spirometry predictive values for Indian population, 2008-2012 [dataset]. KEM Hospital Research Centre, Pune and UoE Usher Institute/RESPIRE group. https://doi.org/10.7488/0a527e2b-8dab-40bb-86c2-bbdde75f7b9

An icteric newborn with bad obstetric history

This article has no abstract. The first 100 words appear below: A 34 week preterm baby was admitted with the complaints of respiratory distress soon after birth. The mother had bad obstetric history. She is having the fifth gravida with the first two alive and healthy who were born by the normal vaginal delivery at home. The third child was born with severe jaundice and was treated by exchange transfusion. Subsequently the baby developed bilirubin encephalopathy. Then the baby developed cerebral palsy and ultimately died due to aspiration pneumonia at the age of 2.5 years. Her first three pregnancies were not on any antenatal check-up by the health care provider due to poor socio-economic background and illiteracy