scholarly journals Incidence of Cerebral Palsy, Seizure Disorder and Developmental Delay in Newborns with Hypoxic Ischemic Encephalopathy Following Treatment with Hypothermia

2020 ◽  
Vol 3 ◽  
Author(s):  
Kazeerat Adedokun ◽  
Heather Wolfe
Keyword(s):  
Cerebral Palsy ◽  
Developmental Delay ◽  
Oxygen Deficiency ◽  
Standard Of Care ◽  
The United States ◽  
Seizure Disorder ◽  
Hypoxic Ischemic Encephalopathy ◽  
Current Standard ◽  
Data Set ◽  
Ischemic Encephalopathy

Neonatal Hypoxic ischemic encephalopathy (HIE) is a serious condition that can lead to significant neurological problems, developmental delay, and mortality. Fetal oxygen deficiency decreases cardiac output, leading to reduced cerebral blood flow and brain injury. In 2006 the United States spent over 300 billion dollars in disability related health care expenditure. HIE if left untreated leads to poor quality of life, and survivors end up with lifelong disabilities. Therapeutic hypothermia became standard of care in 2002, and evidence has shown it has neuroprotective benefit. We hypothesize that neonates treated with hypothermia will have lower incidence of cerebral palsy (CP), seizure disorder (SD) and developmental delay (DD), compared to neonates diagnosed with HIE prior to the current standard of care. Compared to healthy neonates, neonates treated with hypothermia will have higher incidence of CP, SD, and DD    Project Methods: A retrospective chart review will be performed using 200 participants with medical records from Lutheran health network neonate intensive care unit. Historical data from prior to the current standard of care (January 2007 to 2011) will be used for newborns with HIE. Another data set from January 2015 to December 2019 will be used for newborns treated with hypothermia and healthy patients as well. The TIMP test will be used to assess motor performance in early infancy. The Bayley Scales of Infant and Toddler Development third edition will be used to measure cognitive, language and motor development. Cerebral palsy will be assessed using the Gross Motor Function Classification System.    Results: We expect that the results of this study will match previous research, which found that neonates treated with hypothermia had better outcomes compared to neonates not treated with hypothermia.    Potential Impact: If found to be effective, this intervention may improve the quality and quantity of a patient’s life and reduce the cost of healthcare spending on disability. 

scholarly journals Mammillary body atrophy and other MRI correlates of school-age outcome following neonatal hypoxic-ischemic encephalopathy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kim V. Annink ◽  
Linda S. de Vries ◽  
Floris Groenendaal ◽  
Rian M. J. C. Eijsermans ◽  
Manouk Mocking ◽  
...  
Keyword(s):  
Therapeutic Hypothermia ◽  
Memory Function ◽  
Neurodevelopmental Outcome ◽  
Standard Of Care ◽  
Hypoxic Ischemic Encephalopathy ◽  
School Age ◽  
Brain Volumes ◽  
Mammillary Bodies ◽  
Memory Problems ◽  
Ischemic Encephalopathy

AbstractThe mammillary bodies (MB) and hippocampi are important for memory function and are often affected following neonatal hypoxic ischemic encephalopathy (HIE). The aim of this study was to assess neurodevelopmental outcome in 10-year-old children with HIE with and without therapeutic hypothermia. Additional aims were to assess the associations between MB atrophy, brain volumes (including the hippocampi), white matter microstructure and neurodevelopmental outcome at school-age. Ten-year-old children with HIE were included, who were treated with therapeutic hypothermia (n = 22) or would have qualified but were born before this became standard of care (n = 28). Children completed a neuropsychological and motor assessment and MRI. Mammillary bodies were scored as normal or atrophic at 10 years. Brain volumes were segmented on childhood MRI and DTI scans were analysed using tract-based spatial statistics. Children with HIE suffered from neurocognitive and memory problems at school-age, irrespective of hypothermia. Hippocampal volumes and MB atrophy were associated with total and performance IQ, processing speed and episodic memory in both groups. Normal MB and larger hippocampi were positively associated with global fractional anisotropy. In conclusion, injury to the MB and hippocampi was associated with neurocognition and memory at school-age in HIE and might be an early biomarker for neurocognitive and memory problems.

scholarly journals Noninvasive Optical, Electrical, and Acoustic Methods of Total Hemoglobin Determination

2008 ◽  
Vol 54 (2) ◽  
pp. 264-272 ◽  
Author(s):  
John W McMurdy ◽  
Gregory D Jay ◽  
Selim Suner ◽  
Gregory Crawford
Keyword(s):  
Diffuse Reflectance Spectroscopy ◽  
Oxygen Deficiency ◽  
Standard Of Care ◽  
Limiting Factors ◽  
Health Concern ◽  
Current Standard ◽  
Total Hemoglobin ◽  
Admittance Plethysmography ◽  
Significant Public Health

Abstract Background: Anemia is an underdiagnosed, significant public health concern afflicting >2 billion people worldwide. The detrimental effects of tissue oxygen deficiency on the cardiovascular system and concurrent appearance of anemia with numerous high-risk disorders highlight the importance of clinical screening. Currently there is no universally accepted, clinically applicable, noninvasive hemoglobin/hematocrit screening tool. The need for such a device has prompted an investigation into a breadth of techniques. Methods: A synopsis of the literature and current directions of research in noninvasive total hemoglobin measurement was collected. Contributions highlighted in this review are limited to those studies conducted with a clinical aspect, and most include in vivo patient studies. Results: The review of potential techniques presented here includes optoacoustic spectroscopy, spectrophotometric imaging, diffuse reflectance spectroscopy, transcutaneous illumination, electrical admittance plethysmography, and photoplethysmography. The technological performance, relative benefits of each approach, potential instrumentation design considerations, and future directions are discussed in each subcategory. Conclusions: Many techniques reviewed here have shown excellent accuracy, sensitivity, and specificity in measuring hemoglobin/hematocrit, thus in the near future a new clinically viable tool for noninvasive hemoglobin/hematocrit monitoring will likely be widely used for patient care. Limiting factors in clinical adoption will likely involve technology integration into the current standard of care in each field routinely dealing with anemia.

scholarly journals New possibilities for neuroprotection in neonatal hypoxic-ischemic encephalopathy

2021 ◽  
Author(s):  
Suresh Victor ◽  
Eridan Rocha-Ferreira ◽  
Ahad Rahim ◽  
Henrik Hagberg ◽  
David Edwards
Keyword(s):  
Clinical Trials ◽  
Animal Models ◽  
Therapeutic Hypothermia ◽  
Treatment Options ◽  
Standard Of Care ◽  
High Income ◽  
Hypoxic Ischemic Encephalopathy ◽  
Pharmacodynamic Modelling ◽  
Dose Ranging ◽  
Ischemic Encephalopathy

AbstractAround 0.75 million babies worldwide suffer from moderate or severe hypoxic-ischemic encephalopathy (HIE) each year resulting in around 400,000 babies with neurodevelopmental impairment. In 2010, neonatal HIE was associated with 2.4% of the total Global Burden of Disease. Therapeutic hypothermia (TH), a treatment that is now standard of care in high-income countries, provides proof of concept that strategies that aim to improve neurodevelopment are not only possible but can also be implemented to clinical practice. While TH is beneficial, neonates with moderate or severe HIE treated with TH still experience devastating complications: 48% (range: 44–53) combined death or moderate/severe disability. There is a concern that TH may not be effective in low- and middle-income countries. Therapies that further improve outcomes are desperately needed, and in high-income countries, they must be tested in conjunction with TH. We have in this review focussed on pharmacological treatment options (e.g. erythropoietin, allopurinol, melatonin, cannabidiol, exendin-4/exenatide). Erythropoietin and allopurinol show promise and are progressing towards the clinic with ongoing definitive phase 3 randomised placebo-controlled trials. However, there remain global challenges for the next decade. Conclusion: There is a need for more optimal animal models, greater industry support/sponsorship, increased use of juvenile toxicology, dose-ranging studies with pharmacokinetic-pharmacodynamic modelling, and well-designed clinical trials to avoid exposure to harmful medications or abandoning putative treatments. What is Known:• Therapeutic hypothermia is beneficial in neonatal hypoxic-ischemic encephalopathy.• Neonates with moderate or severe hypoxic-ischemic encephalopathy treated with therapeutic hypothermia still experience severe sequelae. What is New:• Erythropoietin, allopurinol, melatonin, cannabidiol, and exendin-4/exenatide show promise in conjunction with therapeutic hypothermia.• There is a need for more optimal animal models, greater industry support/sponsorship, increased use of juvenile toxicology, dose-ranging studies with pharmacokinetic-pharmacodynamic modelling, and well-designed clinical trials.

Variants of the OLIG2 Gene are Associated with Cerebral Palsy in Chinese Han Infants with Hypoxic–Ischemic Encephalopathy

2018 ◽  
Vol 21 (1) ◽  
pp. 75-84 ◽  
Author(s):  
Liya Sun ◽  
Lei Xia ◽  
Mingtai Wang ◽  
Dengna Zhu ◽  
Yangong Wang ◽  
...  
Keyword(s):  
Cerebral Palsy ◽  
Hypoxic Ischemic Encephalopathy ◽  
Chinese Han ◽  
Ischemic Encephalopathy

A decision-analytic model of idelalisib in relapsed or refractory patients with follicular lymphoma in the United States.

2014 ◽  
Vol 32 (30_suppl) ◽  
pp. 30-30 ◽  
Author(s):  
Nathaniel Smith ◽  
Alexander Xenakis ◽  
Rachel Beckerman ◽  
Jagpreet Chhatwal ◽  
Stephanie A. Gregory ◽  
...  
Keyword(s):  
Health Outcomes ◽  
Follicular Lymphoma ◽  
Survival Data ◽  
Treatment Options ◽  
Standard Of Care ◽  
The United States ◽  
Sensitivity Analyses ◽  
Decision Analytic Model ◽  
Current Standard ◽  
Utilization Data

30 Background: There are currently few treatment options for relapsed/refractory (RR) indolent non-Hodgkin’s lymphoma (iNHL) patients. Idelalisib (IDELA) is a first-in class PI3Kδ inhibitor with substantial clinical efficacy in iNHL patients refractory to rituximab and an alkylating agent. A single-arm clinical trial (Study 101-09) showed RR iNHL patients treated with IDELA have a median of 11 and 20.3 months of progression-free and overall survival (PFS and OS), respectively. Efficacy was also demonstrated in patients with iNHL subtypes such as follicular lymphoma (FL). The objective of this study was to project the health outcomes of IDELA versus the current standard of care for US FL patients. Methods: A partitioned survival model simulated a cohort of RR FL patients over 10 year time horizon. Patients first received IDELA or an aggregate comparator of current RR iNHL chemotherapy regimens in a progression-free state before transitioning to a progressive-disease state where they received palliative care until death. Survival data was fit and extrapolated from Study 101-09 (IDELA) for FL patients. A real-world database claims analysis provided survival, disease- and treatment-related adverse event (AEs) profiles, and medical resource utilization data for RR iNHL patients for the comparator. All outcomes were discounted at 3%. Results: Claims data predicted a median of 6.16 and 13.04 months of PFS and OS, respectively, for the comparator. Our model suggests that IDELA treatment improved health outcomes over 10 years versus the comparator, increasing life-months (LMs) and progression-free life-months (PFLMs) by 9.94 and 4.63 mos, respectively. Over 1 year, IDELA reduced both AEs and hospitalisations in FL patients by 40.3% and 49.8%, respectively. Deterministic and probabilistic sensitivity analyses demonstrated the model results are robust across different methods of survival extrapolation. Conclusions: IDELA was projected to improve health outcomes in RR FL patients compared to current treatments, largely driven by improved PFS and OS; short-term reductions in AEs and hospitalisation were specifically related to a delayed disease progression.

scholarly journals Long-Term Neuropathological Changes Associated with Cerebral Palsy in a Nonhuman Primate Model of Hypoxic-Ischemic Encephalopathy

2017 ◽  
Vol 39 (1-4) ◽  
pp. 124-140 ◽  
Author(s):  
Ryan M. McAdams ◽  
Bobbi Fleiss ◽  
Christopher Traudt ◽  
Leslie Schwendimann ◽  
Jessica M. Snyder ◽  
...  
Keyword(s):  
Cerebral Palsy ◽  
White Matter ◽  
Cesarean Section ◽  
Nonhuman Primate ◽  
Cortical Neurons ◽  
Macaca Nemestrina ◽  
Hypoxic Ischemic Encephalopathy ◽  
Brainstem Injury ◽  
Ischemic Encephalopathy

Background: Cerebral palsy (CP) is the most common motor disability in childhood, with a worldwide prevalence of 1.5-4/1,000 live births. Hypoxic-ischemic encephalopathy (HIE) contributes to the burden of CP, but the long-term neuropathological findings of this association remain limited. Methodology: Thirty-four term Macaca nemestrina macaques were included in this long-term neuropathological study: 9 control animals delivered by cesarean section and 25 animals with perinatal asphyxia delivered by cesarean section after 15-18 min of umbilical cord occlusion (UCO). UCO animals were randomized to saline (n = 11), therapeutic hypothermia (TH; n = 6), or TH + erythropoietin (Epo; n = 8). Epo was given on days 1, 2, 3, and 7. Animals had serial developmental assessments and underwent magnetic resonance imaging with diffusion tensor imaging at 9 months of age followed by necropsy. Histology and immunohistochemical (IHC) staining of brain and brainstem sections were performed. Results: All UCO animals demonstrated and met the standard diagnostic criteria for human neonates with moderate-to-severe HIE. Four animals developed moderate-to-severe CP (3 UCO and 1 UCO + TH), 9 had mild CP (2 UCO, 3 UCO + TH, 3 UCO + TH + Epo, and 1 control), and 2 UCO animals died. None of the animals treated with TH + Epo died, had moderate-to-severe CP, or demonstrated signs of long-term neuropathological toxicity. Compared to animals grouped together as having no CP (no-CP; controls and mild CP only), animals with CP (moderate and severe) demonstrated decreased fractional anisotropy of multiple white-matter tracts including the corpus callosum and internal capsule, when using Tract-Based Spatial Statistics (TBSS). Animals with CP had decreased staining for cortical neurons and increased brainstem glial scarring compared to animals without CP. The cerebellar cell density of the internal granular layer and white matter was decreased in CP animals compared to that in control animals without CP. Conclusions/Significance: In this nonhuman primate HIE model, animals treated with TH + Epo had less brain pathology noted on TBSS and IHC staining, which supports the long-term safety of TH + Epo in the setting of HIE. Animals that developed CP showed white-matter changes noted on TBSS, subtle histopathological changes in both the white and gray matter, and brainstem injury that correlated with CP severity. This HIE model may lend itself to further study of the relationship between brainstem injury and CP.

Erythropoietin in perinatal hypoxic-ischemic encephalopathy: a systematic review and meta-analysis

2019 ◽  
Vol 47 (4) ◽  
pp. 478-489 ◽  
Author(s):  
Abdul Razak ◽  
Asif Hussain
Keyword(s):  
Systematic Review ◽  
Cerebral Palsy ◽  
Cognitive Impairment ◽  
Brain Injury ◽  
Meta Analysis ◽  
Hypoxic Ischemic Encephalopathy ◽  
Cochrane Central Register ◽  
Risk Of Death ◽  
Ischemic Encephalopathy ◽  
Reduced Risk

Abstract Background Erythropoietin (EPO) appears to confer neuroprotection to the injured brain. Randomized clinical trials (RCTs) have demonstrated its safety in neonates with hypoxic-ischemic encephalopathy (HIE); however, the evidence is unclear. The objective of this study was to examine the role of EPO in perinatal HIE by a systematic review and meta-analysis. Methods Database search included Embase, MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Cochrane Central Register of Controlled Trials (CENTRAL). RCTs reporting a death, neurodevelopmental outcomes or brain injury were included. Two authors extracted the data independently from included studies and assessed the level of evidence (LOE). Results Six RCTs (EPO=5 and darbepoetin α=1) involving 454 neonates were included. A trend toward a lower risk of death was identified in infants treated with EPO [EPO with or without hypothermia: five RCTs, 368 participants, relative risk (RR) 0.74, 95% confidence interval (CI) 0.47–1.19, LOE−low; EPO without hypothermia: four RCTs, 318 participants, RR 0.89, 95% CI 0.49–1.32, LOE−low]. EPO treatment without hypothermia compared to placebo resulted in a reduced risk of cerebral palsy (two RCTs, 230 participants, RR 0.47, 95% CI 0.27–0.80, LOE−moderate) and moderate to severe cognitive impairment (two RCTs, 226 participants, RR 0.49, 95% CI 0.28–0.85, LOE−moderate). A reduced risk of brain injury was identified in EPO treated infants (EPO with or without hypothermia, two RCTs, 148 participants, RR 0.70, 95% CI 0.53–0.92, LOE−moderate). Conclusion EPO administration in neonates with perinatal HIE reduces the risk of brain injury, cerebral palsy and cognitive impairment. The evidence is limited to suggest its role as an adjuvant to hypothermia. Larger powered trials are underway to overcome this limitation.

Locally Advanced Rectal Cancer: Time for Precision Therapeutics

2015 ◽  
pp. e192-e196 ◽  
Author(s):  
Martin R. Weiser ◽  
Zhen Zhang ◽  
Deborah Schrag
Keyword(s):  
Rectal Cancer ◽  
Local Recurrence ◽  
Locally Advanced ◽  
Standard Of Care ◽  
Advanced Rectal Cancer ◽  
The United States ◽  
Locally Advanced Rectal Cancer ◽  
Neoadjuvant Chemoradiation ◽  
Current Standard ◽  
Trimodality Therapy

The year 2015 marks the 30th anniversary of the publication of NSABP-R01, a landmark trial demonstrating the benefit of adding pelvic radiation to the treatment regimen for locally advanced rectal cancer with a resultant decrease in local recurrence from 25% to 16%. These results ushered in the era of multimodal therapy for rectal cancer, heralding modern treatment and changing the standard of care in the United States. We have seen many advances over the past 3 decades, including optimization of the administration and timing of radiation, widespread adoption of total mesorectal excision (TME), and the implementation of more effective systemic chemotherapy. The current standard is neoadjuvant chemoradiation with 5-fluorouracil (5-FU) and a radiosensitizer, TME, and adjuvant chemotherapy including 5-FU and oxaliplatin. The results of this regimen have been impressive, with a reported local recurrence rate of less than 10%. However, the rates of distant relapse remain 30% to 40%, indicating room for improvement. In addition, trimodality therapy is arduous and many patients are unable to complete the full course of treatment. In this article we discuss the current standard of care and alternative strategies that have evolved in an attempt to individualize therapy according to risk of recurrence.

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