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.

An Infrastructure Framework for Remote Patient Monitoring Interventions and Research.

Remote patient monitoring (RPM) enables clinicians to maintain and adjust their patients' plan of care by using remotely gathered data, such as vital signs, to proactively make medical decisions about a patient's care. RPM interventions have been touted as a means to improve patient care and well-being while reducing costs and resource needs within the health care ecosystem. However, multiple interworking components must be successfully implemented for an RPM intervention to yield the desired outcomes, and the design and key driver of each component can vary depending on the medical context. This viewpoint and perspective paper presents a 4-component RPM infrastructure framework based on a synthesis of existing literature and practice related to RPM. Specifically, these components are identified and considered: (1) data collection, (2) data transmission and storage, (3) data analysis, and (4) information presentation. Interaction points to consider between components include transmission, interoperability, accessibility, workflow integration, and transparency. Within each of the 4 components, questions affecting research and practice emerge that can affect the outcomes of RPM interventions. This framework provides a holistic perspective of the technologies involved in RPM interventions and how these core elements interact to provide an appropriate infrastructure for deploying RPM in health systems. Further, it provides a common vocabulary to compare and contrast RPM solutions across health contexts and may stimulate new research and intervention opportunities.

Exploring film forming ability and improving its bioadhesiveness by thiolation of mucilaginous polysaccharides from Cassia uniflora seeds for drug delivery application.

The objectives of the present work were to explore film forming ability of mucilaginous polysaccharides obtained from Cassia uniflora seeds and improving its bioadhesive potential by thiolation for drug delivery and other applications. Thiolation was achieved by esterification reaction with thioglycolic acid. The modification was confirmed by performing and comparing its zeta potential, DSC, and spectrophotometric characterization by FTIR and NMR with unmodified mucilaginous polysaccharide. The modified mucilaginous polysaccharides FTIR spectra showed an additional absorption band at 2565 cm-1 and new shifts appeared in the 1H (δ 3.24 and at δ 3.44 ppm) and 13C NMR spectra's (21.56 ppm) confirming the esterification of mucilaginous polysaccharides. The prepared films of thiolated and unmodified mucilaginous polysaccharides were evaluated for various parameters like thickness, pH, and weight measurement, The film formulation had a thickness of 0.16 to 0.18 mm, pH in the range of 6.79 to 7.09 and weight uniformity 0.89 to 0.94 mg. The results reveal that the films based on thiolated material improved bioadhesive properties after thiolation. The SEM photographs revealed a smooth surface of film formulations. The diclofenac-loaded film of thiolated mucilaginous polysaccharide also showed >1.5-fold an increase in in-vitro drug release and exhibited non Fickian transport mechanism. These findings could increase the possible applications of chemically modified-thiolated mucilaginous polysaccharides of Cassia uniflora seeds in drug delivery.

Surfactant administration in preterm babies (28-36 weeks) with respiratory distress syndrome: LISA versus InSurE, an open-label randomized controlled trial.

INTRODUCTION: INtubate-SURfactant-Extubate (InSurE) approach is traditional method of surfactant delivery in preterm neonates with respiratory distress syndrome (RDS). Newer, less invasive surfactant administration (LISA) techniques lessen the need for mechanical ventilation and its adverse consequences. Evidence on the favorable effects of LISA can't be extrapolated from developed to developing countries. Aim of study is to compare the effectiveness of InSurE and LISA. OBJECTIVES: Primary outcome was to find need of intubation and mechanical ventilation within 72 h of birth. Neonates were followed until discharge/death for adverse events and complications. MATERIALS AND METHODS: Open-label randomized controlled trial (RCT) was conducted at tertiary neonatal intensive care unit. Preterm neonates with diagnosis of RDS were randomized in two groups (InSurE or LISA) to receive surfactant soon after birth. Nasal intermittent positive pressure ventilation (NIPPV) was used as primary mode of respiratory support. RESULTS: A total of 150 neonates were analyzed (75 in each group). Insignificant statistical difference was seen in the need for intubation and mechanical ventilation within 72 h of birth between the two groups (InSurE, 30 [40%] and LISA, 30 [40%], relative risk 1.0, 95% confidence interval 0.68-1.48). Twelve percent (n = 9, LISA group) and 14.6% (n = 11 InSurE group) had adverse events during the procedure. Also, we observed insignificant statistical difference in the rates of major complications or duration of respiratory support, hospital stay, and mortality. CONCLUSION: LISA and InSurE are equally effectiSpontaneously breathing pretermve for surfactant administration in the treatment of RDS, when NIPPV is the primary mode of respiratory support. More RCTs are required to compare the efficacy and long-term outcomes of LISA with InSurE.

Levetiracetam or Phenobarbitone as a First-Line Anticonvulsant in Asphyxiated Term Newborns? An Open-Label, Single-Center, Randomized, Controlled, Pragmatic Trial.

BACKGROUND AND OBJECTIVE: Neonatal seizures are one of the most challenging problems for experts across the globe. Although there is no consensus on the "ideal" treatment of neonatal seizures, phenobarbitone has been the drug of choice for decades. Unfortunately, although extensively studied in adults and children, levetiracetam lacks rigorous evaluation in the neonatal population, despite its frequent use as an off-label drug. The objective of this open-label, randomized, active-control, single-center, pragmatic trial was to compare the effectiveness of levetiracetam with phenobarbitone for term asphyxiated infants as a first-line drug. METHODS: The participants included in this study were inborn term asphyxiated infants with seizures in the first 48 hours of life. Infants satisfying the inclusion criteria were randomized to receive levetiracetam (20 mg/kg) or phenobarbitone (20 mg/kg). Clinical seizure control was noted. Infants who failed to respond to the primary drug were given the other group drug. RESULTS: Of 103 eligible infants, 82 were randomly assigned (44 levetiracetam group, 38 phenobarbitone group). Clinical seizure control with the primary drug and maintenance of the same for 24 hours was observed in 29 infants (65.9%) in the levetiracetam group and 13 infants (34.2%) in the phenobarbitone group (P < .05, relative risk 0.52, 95% confidence interval 0.32-0.84). Of the infants in the phenobarbitone group who did not respond to the primary drug, 57.8% were controlled after adding levetiracetam. CONCLUSION: Levetiracetam can be used with effectiveness as a first- and second-line drug in asphyxiated term infants. A more extensive study on pharmacokinetics and optimal regimen is required.

Exploring the role of R&D collaborations and non-patent IP policies in government technology transfer performance: Evidence from U.S. federal agencies (1999-2016).

Around the world, governments make substantial investments in public sector research and development (R&D) entities and activities to generate major scientific and technical advances that may catalyze long-term economic growth. Institutions ranging from the Chinese Academy of Sciences to the French National Centre for Scientific Research to the Helmholtz Association of German Research Centers conduct basic and applied R&D to create commercially valuable knowledge that supports the innovation goals of their respective government sponsors. Globally, the single largest public sector R&D sponsor is the U.S. federal government. In 2019 alone, the U.S. government allocated over $14.9 billion to federally funded research and development centers (FFRDCs), also known as national labs. However, little is known about how federal agencies' utilization of FFRDCs, their modes of R&D collaboration, and their adoption of non-patent intellectual property (IP) policies (copyright protection and materials transfer agreements) affect agency-level performance in technology transfer. In particular, the lack of standardized metrics for quantitatively evaluating government entities' effectiveness in managing innovation is a critical unresolved issue. We address this issue by conducting exploratory empirical analyses of federal agencies' innovation management activities using both supply-side (filing ratio, transfer rate, and licensing success rate) and demand-side (licensing income and portfolio exclusivity) outcome metrics. We find economically significant effects of external R&D collaborations and non-patent IP policies on the technology transfer performance of 10 major federal executive branch agencies (fiscal years 1999-2016). We discuss the scholarly, managerial, and policy implications for ongoing and future evaluations of technology transfer at federal labs. We offer new insights and guidance on how critical differences in federal agencies' interpretation and implementation of their R&D management practices in pursuit of their respective missions affect their technology transfer performance outcomes. We generalize key findings to address the broader innovation processes of public sector R&D entities worldwide.

Quality improvement in Kangaroo Mother Care: learning from a teaching hospital.

BACKGROUND: Kangaroo Mother Care (KMC) is a low-resource, evidence-based, high-impact intervention for low-birth weight (LBW) care. Quality improvement in KMC requires meso-level, macro-level and micro-level interventions. Our institution, a public teaching hospital, hosts a level-II/III neonatal intensive care unit (NICU). The average demand for beds typically exceeds available capacity, with 60% occupancy attributed to LBW patients. There was low uptake of KMC practice at our unit. AIM STATEMENT: In the initial phase, we aimed to improve the coverage of KMC in admitted eligible neonates from a baseline of 20%-80% within 15 days. After a period of complacency, we revised the aim statement with a target of improving the percentage of babies receiving 6-hour KMC from 30% to 80% in 12 weeks. METHODS: We report this quasi-experimental time-series study. With the Point of Care Quality Improvement methodology, we performed Plan-Do-Study-Act (PDSA) cycles to improve KMC practice. We involved all the healthcare workers, mothers and caregivers to customise various KMC tools (KMC book format, KMC bag, mother's gown) and minimise interruptions. Feedback from all levels guided our PDSA cycles. RESULTS: The percentage of babies receiving at least 1-hour KMC increased from 20% to 100% within 15 days of August 2017. In the improvement phase, baseline 6-hour KMC coverage of 30% increased to 80% within 12 weeks (October-December 2017). It sustained for more than 2 years (January 2018 till February-2020) at 76.5%±2.49%. CONCLUSIONS: Quality improvement methods helped increase the coverage and percentage of babies receiving 6-hour KMC per day in our NICU. The duration specified KMC coverage should be adopted as the quality indicator of KMC. The training of healthcare workers and KMC provider should include hands-on sessions involving the mother and the baby. Maintaining data and providing suitable KMC tools are necessary elements for improving KMC. Minimising interruption is possible with family support and appropriate scheduling of activities. Having a designated KMC block helps in peer motivation.

Topic modeling revisited: New evidence on algorithm performance and quality metrics.

Topic modeling is a popular technique for exploring large document collections. It has proven useful for this task, but its application poses a number of challenges. First, the comparison of available algorithms is anything but simple, as researchers use many different datasets and criteria for their evaluation. A second challenge is the choice of a suitable metric for evaluating the calculated results. The metrics used so far provide a mixed picture, making it difficult to verify the accuracy of topic modeling outputs. Altogether, the choice of an appropriate algorithm and the evaluation of the results remain unresolved issues. Although many studies have reported promising performance by various topic models, prior research has not yet systematically investigated the validity of the outcomes in a comprehensive manner, that is, using more than a small number of the available algorithms and metrics. Consequently, our study has two main objectives. First, we compare all commonly used, non-application-specific topic modeling algorithms and assess their relative performance. The comparison is made against a known clustering and thus enables an unbiased evaluation of results. Our findings show a clear ranking of the algorithms in terms of accuracy. Secondly, we analyze the relationship between existing metrics and the known clustering, and thus objectively determine under what conditions these algorithms may be utilized effectively. This way, we enable readers to gain a deeper understanding of the performance of topic modeling techniques and the interplay of performance and evaluation metrics.

Cutaneous Mucormycosis in a Patient of Severe COVID-19 Pneumonia: A Rarer than Rare Case Report.

Coronavirus disease-2019 (COVID-19)-associated mucormycosis is on the rise in the Indian subcontinent. We report a unique case of cutaneous mucormycosis in a case of newly diagnosed young diabetic patient with severe COVID-19 pneumonia with post-COVID lung fibrosis. Neither did he have any preceding trauma or wound, nor was there any evidence of any secondary dissemination. Cutaneous mucormycosis without evidence of either is unheard off. Possible risk factors in this case were multiple bacterial secondary infections with the use of higher antibiotics, use of voriconazole for possible aspergillosis, and steroid use. HOW TO CITE THIS ARTICLE: Tambe RR, Hinduja A, Sunil S, Varaiya A, Joshi A. Cutaneous Mucormycosis in a Patient of Severe COVID-19 Pneumonia: A Rarer than Rare Case Report. Indian J Crit Care Med 2021;25(11):1318-1319.

Response to BRAF and MEK1/2 inhibition in a young adult with BRAF V600E mutant epithelioid glioblastoma multiforme: A Case Report and Literature Review.

Epithelioid glioblastoma multiforme (eGBM) is a rare and aggressive variant of glioblastoma multiforme (GBM) that predominantly affects younger patients and can be difficult to distinguish from other gliomas. Data on how patients with eGBM might be best treated are limited, although genomic analyses have shown that almost half of tumours harbour activating BRAF gene mutations. Here we present the case of a young female with BRAF V600E-mutant eGBM who had a prolonged response to targeted therapy with the BRAF and MEK1/2 inhibitors dabrafenib and trametinib. We review current knowledge about eGBM, including the emerging role for BRAF- ± MEK1/2- targeted therapy.

Pharmacological Therapies in Bipolar Disorder: a Review of Current Treatment Options.

BACKGROUND: Bipolar disorder is a mental illness characterised by periods of elevated mood alternating with periods of depression. Long-term relapse prevention in bipolar disorder is challenging, with a significant number of patients relapsing following the initial stabilisation of mood. Initial treatment of the condition is complex and usually occurs in secondary care. Whilst there is no known cure for bipolar disorder, several therapies have been found to be effective in both managing acute episodes and sustaining long-term remission. The key pharmacological therapies in bipolar disorder are lithium salts, antiepileptics and antipsychotics and these will be the focus of this review. AIM: This review seeks to outline the key common pharmacological therapies used in the treatment and relapse prevention of this condition. METHODS: A MEDLINE search was performed, and the available literature was subsequently analysed, including meta-analyses, reviews and original clinical trials. RESULTS: Management strategies can be subdivided into treating acute presentations of mania and depression and maintaining long-term remission. The extensive side effect profile of several antipsychotics means that there are certain patient groups for whom they may be intolerable or contraindicated. Lithium emerges as a highly efficacious maintenance therapy but retains the burden of therapeutic drug monitoring. Antiepileptics play a crucial role in maintaining remission but are linked to serious, albeit rare, side effects. CONCLUSION: Despite the efficacy of the medications discussed in this article, their underlying mechanisms of action remain to be fully elucidated. Nonetheless, these key therapies continue to be essential tools in the management of bipolar disorder.

Selective Serotonin Re-uptake Inhibitors: An overview.

Selective serotonin re-uptake inhibitors (SSRIs) are front-line pharmacotherapies in the treatment of major depressive disorder (MDD), a disorder characterized by a persistent low mood, anhedonia and feelings of worthlessness. Since their formulation over 40 years ago, there have been several conflicting studies exploring the efficacy of these highly prevalent drugs. The nature of their therapeutic effect has also remained elusive, with several hypothesises pertaining to neurotransmitter and endocrine modulation proposed. While the medications are better tolerated than their predecessors, the tricyclic antidepressant family (TCAs), the side effect profile of SSRIs is not insubstantial and novel cases have highlighted adverse effects enduring past the cessation of drug treatment. Data gathered from clinical practice also highlights that the prevalence of these side effects is often underestimated, leading to patient frustration and non-compliance. This report will seek to outline the rise of SSRI usage in the last half century while exploring possible avenues of pharmacotherapeutic action, with a particular focus on the side effect profile of these drugs.