104 results on '"Harini C"'
Search Results
2. Toxicological effect of endocrine disrupting insecticide (deltamethrin) on enzymatical, haematological and histopathological changes in the freshwater iridescent shark, Pangasius hypothalamus
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Kumar Reddy, C. Prabhanjan, Manikandavelu, D., Arisekar, Ulaganathan, Ahilan, B., Uma, A., Jayakumar, N., Kim, Woong, Govarthanan, Muthusamy, Harini, C., Vidya, R. Sri, Madhavan, N., and Kumar Reddy, D. Ravindra
- Published
- 2023
- Full Text
- View/download PDF
3. GastroNet: A CNN based system for detection of abnormalities in gastrointestinal tract from wireless capsule endoscopy images.
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Rajkumar, S., Harini, C. S., Giri, Jayant, Sairam, V. A., Ahmad, Naim, Badawy, Ahmed Said, Krithika, G. K., Dhanusha, P., Chandrasekar, G. E., and Sapthagirivasan, V.
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CAPSULE endoscopy , *CONVOLUTIONAL neural networks , *ULCERATIVE colitis , *WEB-based user interfaces , *GASTROINTESTINAL system , *DEEP learning - Abstract
Gastrointestinal disorders are a class of prevalent disorders in the world. Capsule endoscopy is considered an effective diagnostic modality for diagnosing such gastrointestinal disorders, especially in small intestinal regions. The aim of this work is to leverage the potential of deep convolutional neural networks for automated classification of gastrointestinal abnormalities from capsule endoscopy images. This method developed a deep learning architecture, GastroNetV1, an automated classifier, to detect abnormalities in capsule endoscopy images. The gastrointestinal abnormalities considered are ulcerative colitis, polyps, and esophagitis. The curated dataset consists of 6000 images with "ground truth" labeling. The input image is automatically classified as ulcerative colitis, a polyp, esophagitis, or a normal condition by a web-based application designed with the trained algorithm. The classifier produced 99.2% validation accuracy, 99.3% specificity, 99.3% sensitivity, and 0.991 AUC. These results exceed that of the state-of-the-art systems. Hence, the GastroNetV1 could be used to identify the different gastrointestinal abnormalities in the capsule endoscopy images, which will, in turn, improve healthcare quality. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
4. Role of Proteasome-Dependent Protein Degradation in Long-Term Operant Memory in 'Aplysia'
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Lyons, Lisa C., Gardner, Jacob S., Gandour, Catherine E., and Krishnan, Harini C.
- Abstract
We investigated the in vivo role of protein degradation during intermediate (ITM) and long-term memory (LTM) in "Aplysia" using an operant learning paradigm. The proteasome inhibitor MG-132 inhibited the induction and molecular consolidation of LTM with no effect on ITM. Remarkably, maintenance of steady-state protein levels through inhibition of protein synthesis using either anisomycin or rapamycin in conjunction with proteasome inhibition permitted the formation of robust 24 h LTM. Our studies suggest a primary role for proteasomal activity in facilitation of gene transcription for LTM and raise the possibility that synaptic mechanisms are sufficient to sustain 24 h memory.
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- 2017
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5. Chronic sleep deprivation differentially affects short and long-term operant memory in Aplysia
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Krishnan, Harini C., Noakes, Eric J., and Lyons, Lisa C.
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- 2016
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6. Synchrony and Desynchrony in Circadian Clocks: Impacts on Learning and Memory
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Krishnan, Harini C. and Lyons, Lisa C.
- Abstract
Circadian clocks evolved under conditions of environmental variation, primarily alternating light dark cycles, to enable organisms to anticipate daily environmental events and coordinate metabolic, physiological, and behavioral activities. However, modern lifestyle and advances in technology have increased the percentage of individuals working in phases misaligned with natural circadian activity rhythms. Endogenous circadian oscillators modulate alertness, the acquisition of learning, memory formation, and the recall of memory with examples of circadian modulation of memory observed across phyla from invertebrates to humans. Cognitive performance and memory are significantly diminished when occurring out of phase with natural circadian rhythms. Disruptions in circadian regulation can lead to impairment in the formation of memories and manifestation of other cognitive deficits. This review explores the types of interactions through which the circadian clock modulates cognition, highlights recent progress in identifying mechanistic interactions between the circadian system and the processes involved in memory formation, and outlines methods used to remediate circadian perturbations and reinforce circadian adaptation.
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- 2015
- Full Text
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7. ADVANCEMENT IN LOCALIZATION TECHNIQUES USING PRECODERS FOR ULTRA WIDE-BAND SYSTEMS.
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Saravanakumar, C., Rao, Allanki Sanyasi, Harini, C., and Velusamy, Saravanan
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CO-channel interference ,WIRELESS communications ,SIGNAL-to-noise ratio ,QUALITY of service ,ANTENNAS (Electronics) ,INTERNET of things ,TRANSMITTERS (Communication) - Abstract
In the era of rapidly expanding wireless communication systems, the demand for high-performance, low-latency, and energy-efficient solutions is paramount. One technology that has emerged as a transformative force in addressing these requirements is Massive Multiple-Input Multiple-Output (Massive MIMO) precoding. This abstract delves into the key aspects of Massive MIMO precoding, highlighting its role in enhancing spectral efficiency, mitigating interference, and improving the overall performance of wireless networks. Massive MIMO precoding leverages a substantial number of antennas at the transmitter, allowing for the creation of highly focused spatial beams. These beams can be dynamically optimized to cater to the specific requirements of individual users or devices, maximizing the spectral efficiency by spatially multiplexing multiple streams. This technique offers significant advantages in terms of increasing network capacity and achieving higher data rates, especially in dense network scenarios. Furthermore, Massive MIMO precoding excels in interference mitigation. By spatially directing signals toward intended recipients and steering nulls towards interferers, it reduces the impact of co-channel interference, enhancing network reliability and quality of service. This is particularly valuable in scenarios where network congestion and interference pose significant challenges, such as urban environments and crowded event venues. The research delves into the role of Massive MIMO precoding in improving the signal-to-noise ratio, which directly translates to extended coverage areas and reduced power consumption. Additionally, we explore the implications of Massive MIMO precoding in enabling efficient communication in massive Internet of Things (IoT) deployments and its potential for 5G and beyond. Massive MIMO precoding is poised to reshape the wireless communication landscape. It promises to deliver unprecedented gains in spectral efficiency, interference management, and energy efficiency. As the demand for high-speed, reliable, and ubiquitous connectivity continues to surge, this research plays the pivotal role that Massive MIMO precoding plays in meeting these demands, ushering in a new era of wireless communication. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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8. Influence of different feeding rates of polychaete worms, Eulalia viridis (Annelida, Polychaeta), on the gonad development of male Penaeus semisulcatus (Decapoda, Dendrobranchiata) under captive conditions.
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Harini, C., Betsy, C. Judith, Dattatreya, P. Sri, and Sampath Kumar, J. Stephen
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POLYCHAETA , *SHRIMPS , *WHITE spot syndrome virus , *ANNELIDA , *DECAPODA , *GONADS - Abstract
Penaeus semisulcatus is a large growing species, attaining a maximum size of about 250 mm in total length. It is more resistant to white spot syndrome virus (WSSV) than other cultivable penaeid shrimps, which makes it a potential candidate for culture. The present study evaluated the influence of a different feeding rate of polychaete worms on the gonad development of male P. semisulcatus under captive conditions. P. semisulcatus sub-adults were obtained in the wild. The shrimps were fed with three different concentrations of polychaete worms, viz., ad libitum (T1), 5% of body weight (BW) (T2) and 10% BW (T3), and fresh sardines were fed as a Control (C) diet, all for a period of 60 days. Sampling was done once in 15 days and the bio-growth parameters were recorded. The gonads were harvested for histological analysis. The maximum weight gain (10.19 g), mean weight gain percentage (85.20%), mean daily growth rate (DGR) (0.169833) and mean specific growth rate (SGR) (0.45) were found in shrimps fed with the polychaete worm diet at 5% BW. The estimated bio-growth parameter values were statistically significant when analysed using One way ANOVA (P < 0.05). Histological sections of the testis showed variations in the development of the gonad between the treatments with different feeding rates during the 60 days trials. Indeed in all aspects, the development was higher in shrimps fed with polychaete worms at 5% BW. It can be concluded that feeding polychaete worms at 5% BW created a regime able to improve growth rates, gonad maturation, and quality in the development of the captive male brood stock. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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9. Differential role of calpain-dependent protein cleavage in intermediate and long-term operant memory in Aplysia
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Lyons, Lisa C., Gardner, Jacob S., Lentsch, Cassidy T., Gandour, Catherine E., Krishnan, Harini C., and Noakes, Eric J.
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- 2017
- Full Text
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10. Estrogen modulates in vitro T cell responses in a concentration- and receptor-dependent manner: Effects on intracellular molecular targets and antioxidant enzymes
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Priyanka, Hannah P., Krishnan, Harini C., Singh, Ran Vijay, Hima, Lalgi, and ThyagaRajan, Srinivasan
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- 2013
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11. EMPOWERMENT THROUGH EDUCATION: THE WAY FORWARD
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Dr. Harini C
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education, empowerment, gender equality, sustainable goals - Abstract
Sustainable development goals are a set of goals formulated by UN, so as to ensure a sustainable future for the generations to come. It comprises of 17 interconnected goals that must be addressed to achieve the goal of sustainability. One of the goals is to achieve gender equality across the globe. The first step to achieve equality is education. Girls’ education has a specific significance for any society. Educated girls are better in terms of health and general awareness. As today’s girls are the mothers of tomorrow, their increased awareness about life can help in bringing up a healthier and better generation. Educated mothers will be able to direct their children the right way thereby reducing crime rates and violence in the society. Education is the only force that can empower women both in the family as well as in the society. Ban Ki Moon, the former secretary general of UN opined that education of a girl is the best investment that a country can make. This paper specifically examines the challenges of girl’s education in India. In India, access to education is a big problem for women especially from rural India. There is a huge difference in the male literacy rates and female literacy rates in many states especially the BIMARU states. The paper tries to analyse the various obstacles that come across education of girls and the ways to overcome those obstacles.  
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- 2019
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12. Dermatology Life Quality Index in Patients with Psoriasis Treated with Biologic Versus Non-biologic Treatment in Malaysia: A Retrospective Cross-Sectional Study
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Suganthy Robinson, Tang Min Moon, Tey Kwee Eng, Teoh Tze Yuen, Tang Jyh Jong, Latha Selvarajah, Tan Wooi Chiang, Teh Yeon Chiat, John Tiong, Harini Chinthapatla, Shu Kee Eng, and Suganthi Thevarajah
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Therapeutics. Pharmacology ,RM1-950 ,Pharmacy and materia medica ,RS1-441 - Abstract
Abstract Background Psoriasis imposes a substantial burden on patients’ social, emotional, physical, and family life. Although psoriasis has no complete cure, various treatments are available to control its symptoms and improve a patients’ quality of life. Objective We aimed to compare the effectiveness of biologic versus non-biologic treatments on health-related quality of life among patients with psoriasis in Malaysia. Methods This retrospective cross-sectional study evaluated data of adult patients diagnosed with psoriasis during 2007–18 from the Malaysian Psoriasis Registry. Baseline demographics, disease, and treatment characteristics were described. For a subset of patients treated with biologics and non-biologics who had baseline and 6-month follow-up data available, changes in the mean Dermatology Life Quality Index scores and the proportion of patients with a clinically relevant improvement (≥ 4 points) post-treatment were assessed. Results Overall, 15,238 adult patients with psoriasis from the Malaysian Psoriasis Registry were included in the analysis. Patients receiving biologics showed a statistically significant reduction in the mean Dermatology Life Quality Index scores after 6 months compared with those receiving non-biologic treatment (− 5.7 vs − 0.8%; p < 0.001). The proportion of patients who achieved a ≥ 4-point improvement in Dermatology Life Quality Index scores was approximately two times greater in the biologic-treated group versus the non-biologic-treated group (56.4 vs 27.7%). Conclusions Biologic treatment showed a greater reduction in the Dermatology Life Quality Index scores of patients with psoriasis versus non-biologic treatment. These results highlight the importance of early treatment with more efficacious treatment options, such as biologic therapies, to improve the overall health-related quality of life of patients with psoriasis.
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- 2023
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13. Synchrony and desynchrony in circadian clocks: impacts on learning and memory
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Lisa C. Lyons and Harini C. Krishnan
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Aging ,Recall ,Cognitive Neuroscience ,Circadian clock ,Brain ,Endogeny ,Cognition ,Neurodegenerative Diseases ,Review ,Cellular and Molecular Neuroscience ,Alertness ,Neuropsychology and Physiological Psychology ,Memory ,Circadian Clocks ,Animals ,Humans ,Learning ,Effects of sleep deprivation on cognitive performance ,Circadian rhythm ,Adaptation ,Psychology ,Cognitive psychology - Abstract
Circadian clocks evolved under conditions of environmental variation, primarily alternating light dark cycles, to enable organisms to anticipate daily environmental events and coordinate metabolic, physiological, and behavioral activities. However, modern lifestyle and advances in technology have increased the percentage of individuals working in phases misaligned with natural circadian activity rhythms. Endogenous circadian oscillators modulate alertness, the acquisition of learning, memory formation, and the recall of memory with examples of circadian modulation of memory observed across phyla from invertebrates to humans. Cognitive performance and memory are significantly diminished when occurring out of phase with natural circadian rhythms. Disruptions in circadian regulation can lead to impairment in the formation of memories and manifestation of other cognitive deficits. This review explores the types of interactions through which the circadian clock modulates cognition, highlights recent progress in identifying mechanistic interactions between the circadian system and the processes involved in memory formation, and outlines methods used to remediate circadian perturbations and reinforce circadian adaptation.
- Published
- 2015
14. EFFECT OF BIOFLOC TECHNOLOGY ON WATER QUALITY AND GROWTH PERFORMANCE OF BLUE MORPH, PSEUDOTROPHEUS SAULOSI FRY IN OUTDOOR REARING SYSTEM.
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Harini, C., Radhakrishnan, Kalidoss, Dattatreya, P. Sri., Karthy, A., and Rajagopalasamy, C. B. T.
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SHRIMP culture ,WATER quality ,FISH feeds ,FISHERIES ,FISH farming ,AQUACULTURE ,AQUATIC resources - Abstract
The effect of production of blue morph, Pseudotropheus saulosifry in biofloc technology was examined concerning the growth performances and survival rate. Water quality and growth tests were done with fry that was harvested from the biofloc and control. The physicochemical water quality parameters were checked periodically. Of this, the water temperature and nitrite had a statistical significant. The concentration of nitrite was significantly lower in the biofloc (0.08 ± 0.12 mg/L) than the control (3.57 ± 0.23 mg/L)and as similarly ammonia that means 3.56 ± 0.24 mg/L in biofloc and 4.53 ± 0.29 mg/L in control but no statistical significance. The growth performance was affected passively by the biofloc technology and had a statistical significance at 1 percent level. A greater specific growth rate (%/day) of 3.58 was noticed in biofloc, but the lower of 3.35 was in control. This study concludes that the biofloc had better water quality condition as well as improved growth performance when it compared to control. [ABSTRACT FROM AUTHOR]
- Published
- 2018
15. Death With Function and Graft Failure After Kidney Transplantation: Risk Factors at Baseline Suggest New Approaches to Management
- Author
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Massini A. Merzkani, MD, Andrew J. Bentall, MD, Byron H. Smith, PhD, Xiomara Benavides Lopez, MD, Matthew R. D’Costa, MD, Walter D. Park, BS, Walter K. Kremers, PhD, Naim Issa, MD, Andrew D. Rule, MD, Harini Chakkera, MD, Kunam Reddy, MD, Hasan Khamash, MD, Hani M. Wadei, MD, Martin Mai, MD, Mariam P. Alexander, MD, Hatem Amer, MD, Aleksandra Kukla, MD, Mireille El Ters, MD, Carrie A. Schinstock, MD, Manish J. Gandhi, MD, Raymond Heilman, MD, and Mark D. Stegall, MD
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Surgery ,RD1-811 - Abstract
Background. Improving both patient and graft survival after kidney transplantation are major unmet needs. The goal of this study was to assess risk factors for specific causes of graft loss to determine to what extent patients who develop either death with a functioning graft (DWFG) or graft failure (GF) have similar baseline risk factors for graft loss. Methods. We retrospectively studied all solitary renal transplants performed between January 1, 2006, and December 31, 2018, at 3 centers and determined the specific causes of DWFG and GF. We examined outcomes in different subgroups using competing risk estimates and cause-specific Cox models. Results. Of the 5752 kidney transplants, graft loss occurred in 21.6% (1244) patients, including 12.0% (691) DWFG and 9.6% (553) GF. DWFG was most commonly due to malignancy (20.0%), infection (19.7%), cardiac disease (12.6%) with risk factors of older age and pretransplant dialysis, and diabetes as the cause of renal failure. For GF, alloimmunity (38.7%), glomerular diseases (18.6%), and tubular injury (13.9%) were the major causes. Competing risk incidence models identified diabetes and older recipients with higher rates of both DWFG and nonalloimmune GF. Conclusions. These data suggest that at baseline, 2 distinct populations can be identified who are at high risk for renal allograft loss: a younger, nondiabetic patient group who develops GF due to alloimmunity and an older, more commonly diabetic population who develops DWFG and GF due to a mixture of causes—many nonalloimmune. Individualized management is needed to improve long-term renal allograft survival in the latter group.
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- 2022
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16. LENGTH WEIGHT RELATIONSHIP OF GOLDFISH, CARASSIUS AURATUS (LINNAEUS, 1758) YOUNGONES REARED IN BIOFLOC SYSTEM.
- Author
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Faizullah, M. Mohamed, Daniel, N., Lakshmegayathre, V., and Harini, C.
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GOLDFISH ,BODY weight ,AMMONIA ,PROTEINS ,REGRESSION analysis - Abstract
The present study was carried out for a period of 95 days with the aim to evaluate the length weight relationship of goldfish youngoneswhich reared under the clear and biofloc waters. The experimental fishes were stocked at the rate of 500 numbers per tank. Fishes fed to 5% of their body weight with commercial pellet feed containing 32% Crude protein.Biofloc in the water was prepared using the application of C:N ratio at 1:15 by adding sugar as carbon source and ammonia-N as nitrogenous source. At the time of stocking, regression line of length and weight among goldfish in the control and biofloc treatment tank was W=0.0009L
1.936 and the R2 value is 0.6318. However, during the course of experiment, both the regression coefficient were highly significant (P<0.01) among the gold fish reared under the biofloc and with respect to 'b' value, the animals reared under biofloc had higher b value (2.6629) than that of animals reared in the clear water (2.5305). The overall results suggested that biofloc can improve the length and weight of the goldfish, Carassius auratus. Therefore, the biofloc technology can be applied in the culture of goldfish. [ABSTRACT FROM AUTHOR]- Published
- 2017
17. Identifying Patterns of Adverse Events of Solid Organ Transplantation Through Departmental Case Reviews
- Author
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Amit K. Mathur, MD, MS, Cynthia Stemper-Bartkus, MSN, RN, Kevin Engholdt, MS, MBA, Andrea Thorp, MSN, RN, Melissa Dosmann, RN, Hasan Khamash, MD, Kunam S. Reddy, MD, Bashar Aqel, MD, Adyr Moss, MD, Harini Chakkera, MD, D. Eric Steidley, MD, Octavio Pajaro, MD, PhD, Sadia Shah, MD, Elizabeth J. Oakley, MS, and David Douglas, MD
- Subjects
Medicine (General) ,R5-920 - Abstract
The best approach to adverse-event review in solid organ transplantation is unknown. We initiated a departmental case review (DCR) method based on root-cause analysis methods in a high-volume multiorgan transplant center. We aimed to describe this process and its contributions to process improvement. Methods: Using our prospectively maintained transplant center quality portfolio, we performed a retrospective review of a 30-month period (October 26, 2015, to May 14, 2018) after DCR-process initiation at our center. We used univariate statistics to identify counts of adverse events, DCRs, death and graft-loss events, and quality improvement action-plan items identified during case review. We evaluated variation among organ groups in action-plan items, associated phase of transplant care, and quality improvement theme. Results: Over 30 months, we performed 1449 transplant and living donor procedures with a total of 45 deaths and 31 graft losses; 91 DCRs were performed (kidney transplant n=43; liver transplant n=24; pancreas transplant n=10; heart transplant n=6; lung transplant n=3; living donor n=5). Seventy-nine action-plan items were identified across improvement domains, including errors in clinical decision making, communication, compliance, documentation, selection, waitlist management, and administrative processes. Median time to review was 83 days and varied significantly by program. Median time to action-plan item completion was 9 weeks. Clinical decision making in the pretransplant phase was identified as an improvement opportunity in all programs. Conclusions: DCRs provide a robust approach to transplant adverse-event review. Quality improvement targets and domains may vary based on adverse-event profiles.
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- 2019
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18. Design and assessment of pulsatile technology based chronomodulated delivery systems of nifedipine
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Sowjanya Battu, Prasanna Raju Yalavarthi, G.V. Subba Reddy, V. Uma Maheswara Rao, K. Jyothshna Devi, and Harini Chowdary Vadlamudi
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Medicine (General) ,R5-920 ,Science - Abstract
Nifedipine has poor aqueous solubility which limits its oral absorption as unit formulation. This limitation was acted through multiparticulate pulsatile systems for the treatment of angina pectoris. Initially, solid dispersions of nifedipine (NF) using sodium starch glycolate (SSG) and guar gum (GG) in 1:1 and 1:2 ratios were processed by kneading technique. Solution layering technique was employed to coat the solid dispersions on non-pareil sugar spheres (∼450 µm) to obtain immediate (NMP 1 and 2) and controlled release pellets (NMP-3 and 4). Controlled release pellets were further coated with Eudragit L100 and RS100 to achieve pulsatile pellets (NMPP-1 to 5). Pellets were subjected to saturation solubility, FTIR, DSC, micromeritics, SEM, drug content, drug release, pharmacokinetic and stability studies. By means of solid dispersions, solubility of NF was increased by 130-folds due to encompassing ordered interparticle mixing of NF and carriers. Significant interactions between NF and carriers were not demonstrated in FTIR spectra as well as in DSC thermograms. Fluidization process again proved its supremacy in producing defined spherical shaped pellets with desired micromeritics. Solution layering process resulted with high drug content (81–94.2%) and maximum drug was released by end of 12 h with 6 h lag phase. Suitable pharmacokinetic parameters were moderated by immediate (NMP) and pulsatile pellets (NMPP) as Cmax of 820 ng/mL for NMP-2 and 360.8 ng/mL for NMPP-5 at 5 and 16 h respectively. Increased pharmacokinetics and bioavailability were the result of linear increase in solubility of NF with solid dispersions. The pulsatile formulations were physicochemically intact over a period of time. Thus, multiparticulate systems of NF had demonstrated their applicability in chronotherapy of circadian based ailments. Keywords: Angina, Circadian, Multiparticulates, Non-pareil, Solid dispersion, Solution-layering
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- 2018
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19. Analysis of wind turbine driven doubly fed induction generator.
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Harini, C., Kumari, N.K., and Raju, G.S.
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- 2011
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20. LP31: EEG and MEG source localization of the epileptogenic foci in tuberous sclerosis complex: a pediatric case report
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Hunold, A., Haueisen, J., Ahtam, B., Doshi, C., Harini, C., Camposano, S., Warfield, S.K., Grant, P.E., Okada, Y., and Papadelis, C.
- Published
- 2014
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21. Rasmussen's encephalitis presenting as focal cortical dysplasia
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O'Rourke, D.J., Bergin, A., Rotenberg, A., Peters, J., Gorman, M., Poduri, A., Cryan, J., Lidov, H., Madsen, J., and Harini, C.
- Published
- 2014
- Full Text
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22. Characterization of sleep in Aplysia californica.
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Vorster, Albrecht P A, Krishnan, Harini C, Cirelli, Chiara, and Lyons, Lisa C
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- 2014
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23. Investigation of Osmolyte Effects on FolM: Comparison with Other Dihydrofolate Reductases.
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Bhojane, Purva P., Duff, Jr., Michael R., Patel, Harini C., Vogt, Melissa E., and Howell, Elizabeth E.
- Published
- 2014
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24. Process, Physicochemical Characterization and In-Vitro Assessment of Albendazole Microcrystals
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Vandana KR, Prasanna Raju Yalavarthi, Harini Chowdary Vadlamudi, Jagadesh Kumar Yadav Kalluri, and Arun Rasheed
- Subjects
Particle engineering ,Stabilizers ,Adsorption ,Enthalpy ,Dissolution efficiency ,Surface energy ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Purpose: Albendazole is a poorly soluble drug which limits its oral bioavailability. The study was focussed to enhance the solubility by in-situ micronization. Methods: Albendazole microcrystals were prepared by solvent change method using gum karaya and hupu gum as stabilizing agents and the effect of each stabilizer on the prepared microcrystals were studied. FT-IR, DSC, XRD and SEM analysis were performed as a part of characterization studies. The formulations were evaluated for micromeritics, solubility and drug release. The microcrystals that had shown optimized properties were filled into suitable capsules. Results: The formulations showed reduction in particle size with uniform size distribution and three folds increase in drug release. The microcrystals had shown more than 100-folds increase in solubility compared to pure drug. Surface energy, enthalpy and crystalline nature of microcrystals were found to be reduced. Microcrystals containing gum karaya had shown more drug release. The filled-in capsules also showed increase in drug release rate. The solubility enhancement of albendazole microcrystals was mainly due to the surface adsorption of the stabilizing agents that led to reduction in surface energy and crystalline nature as substantiated by the DSC and XRD studies. The type of stabilizing agent had significant effect on dissolution rate. High affinity of albendazole with gum karaya led to faster drug release profiles. Conclusion: The study proved that in-situ micronization is an effective technique to enhance the solubility and dissolution rate of poorly soluble drugs like albendazole.
- Published
- 2017
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25. Pathways to clinical CLARITY: volumetric analysis of irregular, soft, and heterogeneous tissues in development and disease
- Author
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Brian Hsueh, Vanessa M. Burns, Philip Pauerstein, Katherine Holzem, Li Ye, Kristin Engberg, Ai-Chi Wang, Xueying Gu, Harini Chakravarthy, H. Efsun Arda, Gregory Charville, Hannes Vogel, Igor R. Efimov, Seung Kim, and Karl Deisseroth
- Subjects
Medicine ,Science - Abstract
Abstract Three-dimensional tissue-structural relationships are not well captured by typical thin-section histology, posing challenges for the study of tissue physiology and pathology. Moreover, while recent progress has been made with intact methods for clearing, labeling, and imaging whole organs such as the mature brain, these approaches are generally unsuitable for soft, irregular, and heterogeneous tissues that account for the vast majority of clinical samples and biopsies. Here we develop a biphasic hydrogel methodology, which along with automated analysis, provides for high-throughput quantitative volumetric interrogation of spatially-irregular and friable tissue structures. We validate and apply this approach in the examination of a variety of developing and diseased tissues, with specific focus on the dynamics of normal and pathological pancreatic innervation and development, including in clinical samples. Quantitative advantages of the intact-tissue approach were demonstrated compared to conventional thin-section histology, pointing to broad applications in both research and clinical settings.
- Published
- 2017
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26. Potential of microemulsified entacapone drug delivery systems in the management of acute Parkinson's disease
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Harini Chowdary Vadlamudi, Prasanna Raju Yalavarthi, Basaveswara Rao Mandava Venkata, Jyotsna Thanniru, Vandana K.R., and Sundaresan C.R.
- Subjects
Microemulsion ,Reconstitution ,Zeta-potential ,Catecholamine-o-methyl transferase ,Catalepsy ,Medical emergencies. Critical care. Intensive care. First aid ,RC86-88.9 - Abstract
Objective: To design solid self-microemulsifying drug delivery system (S-SMEDDS) of entacapone and evaluate for its anti-Parkinson's potentials. Methods: Solubility studies were performed in various vehicles i.e., oils, surfactants and co-surfactants and pseudo-ternary phase diagrams were plotted to understand the microemulsion formation region. Liquid self-microemulsifying drug delivery systems (SMEDDS) were developed using gingelly and rice bran oil as lipid vehicles, Tween 80 and Span 20 as surfactants and glycerin, propylene glycol as co-surfactants. They were characterized by Fourier transform infrared spectroscopy, pH, viscosity, zeta potential, polydispersibility index and droplet size analysis and evaluated for drug content, in-vitro release, in-vitro diffusion and ex-vivo permeation. Optimized liquid SMEDDS were converted into S-SMEDDS by adsorption and melt granulation procedures. Characterization by differential scanning calorimetry, SEM, micrometrics, reconstitution property, moisture content and evaluation by drug content, drug release kinetics and shelf-life were performed for S-SMEDDS. Parkinsonism was induced and pharmacodynamic potentials of S-SMEDDS were evaluated. Results: S-SMEDDS formulation AG8 had shown the highest drug release of 90.92% within 60 min. Pharmacodynamic studies also proved the efficiency of entacapone S-SMEDDS against Parkinsonism. Conclusions: Entacapone S-SMEDDS is an effective drug delivery system that offers more predictable and extensive drug release with enhanced shelf-life in the treatment of acute Parkinsonism.
- Published
- 2016
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27. Pharmacological profiling of Argemone mexicana for its aphrodisiac potentials in male Wistar rats
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Asuntha G, Prasanna Raju Y, Harini Chowdary V, Vandana KR, Arun Rasheed, and Prasad KVSRG
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Sexual dysfunction ,Testosterone ,Protopine alkaloid ,Flavanoid ,Estrous cycle ,Sexual behavioral parameters ,Medicine - Abstract
Objective: To study the aphrodisiac potentials of ethanol extract of Argemone mexicana L. (A. mexicana) of Papaveraceae family in sexually sluggish male Wistar rats. Methods: The sexually inactive male rats were divided into two groups of 8 rats each. The test group animals were treated with ethanol extract of A. mexicana (EEAM) at 1 g/kg daily oral dose for 28 days. Other group animals were treated with sildenafil citrate at an oral dose of 5 mg/kg. The latencies of mount, intromission, ejaculation; post ejaculatory pause and frequencies of mount, intromission, and ejaculation were measured on 0, 7th, 14th, 21st and 28th days. Serum testosterone levels were estimated using ELISA. Results: The EEAM was nonlethal even at dose of 4.0 g/kg. The oral dosing of EEAM has significantly enhanced the orientation of males towards female by increase in ano-genital investigatory behavior, frequencies of mount, intromission, and ejaculation (P< 0.01). The latencies of mount, intromission and ejaculation were significantly decreased (P
- Published
- 2014
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28. Teaching NeuroImages: Mesial temporal sclerosis after a prolonged unprovoked seizure in an infant.
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Pinto A, Miller-Horn J, Guilhoto L, Harini C, Morrison P, Prabhu SP, Kothare S, and Loddenkemper T
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- 2011
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29. Recovery of suppressed male reproduction in mice exposed to progesterone during embryonic development by testosterone.
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Harini, C., Sainath, S. B., and Reddy, P. Sreenivasula
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MALE reproductive organs ,PROGESTERONE ,EMBRYOLOGY ,TESTOSTERONE ,SPERMATOZOA ,LABORATORY mice - Abstract
The present study aimed to examine whether transplacental exposure to progesterone caused male reproductive abnormalities and whether the changes can be reversed after testosterone administration. Progesterone was injected to mice on day 1, 3, and 7 of pregnancy. The male pups (F1 generation) were allowed to grow for 50 days and assessed for reproductive performance. Gestational exposure to progesterone (7 mg/kg body weight) resulted in significant body weight gain with a decrease in reproductive tissue indices in mice. Total sperm count, viable sperm, and motile sperm decreased in experimental mice. Hypo-osmotic swelling test revealed that experimental mice sperm membrane integrity was severely altered. The activity levels of testicular steroidogenic marker enzymes (hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase cluster (HSD3B) and hydroxysteroid (17-beta) dehydrogenase 1 (HSD17B)) decreased significantly in mice exposed to progesterone during embryonic development when compared with the controls. The levels of serum testosterone decreased with an increase in serum FSH and LH in mice exposed to progesterone during embryonic development. Prenatal exposure to progesterone caused significant reduction in the number of spermatozoa and increase in the lumen of seminiferous tubule. The experimental mice that cohabited with normal females showed fertility reduction. Administration of testosterone (4.16 mg/kg body weight) on postnatal day 20, 30, and 40 to progesterone-exposed prenates resulted in recovery of progesterone-induced suppressed male reproduction. It is suggested that the impairment of male reproduction in mice exposed to progesterone during embryonic development could be mediated through the inhibition of testosterone production. These results also indicate that in utero exposure to progesterone affects male reproduction and that supplementation of testosterone restores the suppressed male reproduction. [ABSTRACT FROM AUTHOR]
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- 2009
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30. A Multicenter Training and Interrater Reliability Study of the BASED Score for Infantile Epileptic Spasms Syndrome.
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Mytinger JR, Albert DVF, Aylward SC, Beatty CW, Bhalla S, Bhatia S, Brock GN, Ciliberto MA, Choudhari PR, Clark DJ, Cohen JM, Czech TM, Fredwall MM, Gonzalez-Giraldo E, Harini C, Hunter SE, Sandoval Karamian AG, Katyayan A, Kistler I, Kulkarni N, Liu VB, McCabe C, Murray T, Neville K, Patel SH, Pavuluri S, Phillips DJ, Samanta D, Sirsi D, Spelbrink EM, Stafstrom CE, Steenari M, Takacs DS, Terrill T, Tran L, Vidaurre J, and Shrey DW
- Abstract
Purpose: The best possible outcomes in infantile epileptic spasms syndrome require electroclinical remission; however, determining electrographic remission is not straightforward. Although the determination of hypsarrhythmia has inadequate interrater reliability (IRR), the Burden of AmplitudeS and Epileptiform Discharges (BASED) score has shown promise for the reliable interictal assessment of infantile epileptic spasms syndrome. Our aim was to develop a BASED training program and assess the IRR among learners. We hypothesized moderate or better IRR for the final BASED score and the presence or absence of epileptic encephalopathy (+/-EE)., Methods: Using a web-based application, 31 learners assessed 12 unmarked EEGs (length 1-6 hours) from children with infantile epileptic spasms syndrome., Results: For all readers, the IRR was good for the final BASED score (intraclass correlation coefficient 0.86) and +/-EE (Marginal Multirater Kappa 0.63). For all readers, the IRR was fair to good for all individual BASED score elements., Conclusions: These findings support the use of our training program to quickly learn the BASED scoring method. The BASED score may be a valuable clinical and research tool. Given that the IRR for the determination of epileptic encephalopathy is not perfect, clinical acumen remains paramount. Additional experience with the BASED scoring technique among learners and advances in collaborative EEG evaluation platforms may improve IRR., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Clinical Neurophysiology Society.)
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- 2024
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31. Comparison of porcine versus bovine surfactant in preterm respiratory distress syndrome: Evidence from real-world data. A multicentre collaboration from Karnataka.
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Aradhya AS, Ghalige SS, Madarkar B, Pruthvishree HV, Venkatagiri P, Urs P, Ngangom D, Rangaiah S, Kumar V, Harini C, Bansal A, and Halkar MP
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- Animals, Retrospective Studies, Cattle, Infant, Newborn, Swine, Humans, Female, Male, Infant, Premature, India, Gestational Age, Treatment Outcome, Respiratory Distress Syndrome, Newborn drug therapy, Pulmonary Surfactants therapeutic use
- Abstract
Background & Objectives: Porcine surfactant (200 mg/kg initial dose) seems to be superior to bovine surfactants (100 mg/kg) in respiratory distress syndrome (RDS). There is limited data on the choice of surfactant from the developing world. Logically, using higher doses of porcine surfactant comes with an additional cost burden. We decided to evaluate the clinical effects of different types of surfactants., Methods: A retrospective analysis was conducted from August 2019 to December 2022 in six tertiary centers. Neonates 24-34 weeks of gestation with RDS requiring either porcine (200 mg/kg) or bovine surfactant (100 mg/kg) were enrolled. The proportion of BPD, redosing, and other morbidities in either group were analyzed. The outcomes in preterm ≥28 and <28 weeks subgroups were analyzed., Results: Of 1149 eligible babies, 302 (26%) received surfactant after stabilization with CPAP. One hundred fifty-eight received porcine, and 144 received bovine surfactant. There was a higher BPD in porcine compared to the bovine group on univariate analysis [24 (15%) vs. 6 (4%); OR: 4; 95% CI: 1.6-10; p = 0.002]. On logistic regression, the gestational age and PDA requiring treatment were independent predictors of BPD, and the type of surfactant and centres did not influence BPD. Redosing [27 (17%) vs. 18 (12%), OR: 1.4; 95% CI: 0.7-2.7; p = 0.2] was not different between both surfactant types. Other morbidities like mortality, air leaks, invasive ventilation, and CPAP duration were also not different between the groups., Conclusion: We could not find a difference in the outcomes of BPD and redosing using porcine surfactant at 200 mg/kg compared to bovine surfactant. Considering the cost burden in the developing world, efficacy needs to be evaluated in randomized clinical trials., (© 2024 Wiley Periodicals LLC.)
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- 2024
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32. The spectrum of movement disorders in young children with ARX-related epilepsy-dyskinesia syndrome.
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Akula SK, Quiroz V, D'Gama AM, Chiu MY, Koh HY, Saffari A, Zaman Z, Tam A, Srouji R, Valentine R, Wiltrout K, Pinto A, Harini C, Pearl PL, Poduri A, and Ebrahimi-Fakhari D
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- Humans, Male, Female, Child, Preschool, Infant, Mutation, Missense, Child, Movement Disorders genetics, Movement Disorders diagnosis, Movement Disorders etiology, Homeodomain Proteins genetics, Transcription Factors genetics
- Abstract
Children with developmental and epileptic encephalopathies often present with co-occurring dyskinesias. Pathogenic variants in ARX cause a pleomorphic syndrome that includes infantile epilepsy with a variety of movement disorders ranging from focal hand dystonia to generalized dystonia with frequent status dystonicus. In this report, we present three patients with severe movement disorders as part of ARX-associated epilepsy-dyskinesia syndrome, including a patient with a novel pathogenic missense variant (p.R371G). These cases illustrate diagnostic and management challenges of ARX-related disorder and shed light on broader challenges concerning epilepsy-dyskinesia syndromes., (© 2024 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)
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- 2024
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33. Diagnostic Yield of CSF Testing in Infants for Disorders of Biogenic Amine Neurotransmitter Metabolism.
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Kessler R, Fung FW, Patel A, Gupta N, McHugh T, Gonzalez AK, Rodan L, Harini C, and Kessler SK
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- Child, Infant, Humans, Cross-Sectional Studies, Seizures, Neurotransmitter Agents, Biogenic Amines, Dopamine metabolism
- Abstract
Background and Objectives: Biochemical testing of CSF for neurotransmitter metabolites and their cofactors is often used in the diagnostic evaluation of infants with neurologic disorders but requires an invasive, labor-intensive procedure with many potential sources of error. Our aim was to determine the diagnostic yield of CSF testing for biogenic amines (serotonin, norepinephrine, epinephrine, and dopamine) and their cofactors in identifying inborn errors of neurotransmitter metabolism among infants., Methods: We evaluated all infants aged 1 year or younger who underwent CSF biogenic amine neurotransmitter (CSFNT) testing at Children's Hospital of Philadelphia (CHOP) and Boston Children's Hospital (BCH) between 2008 and 2017 in this cross-sectional study. The primary outcome was the proportion of individuals who received a diagnostic result from CSFNT testing. Secondary assessments included the proportion of infants who obtained a diagnostic result from other types of diagnostic testing., Results: The cohort included 323 individuals (191 from CHOP and 232 from BCH). The median age at presentation was 110 days (range 36-193). The most common presenting features were seizures (71%), hypotonia (47%), and developmental delay (43%). The diagnostic yield of CSFNT testing was zero. When CSF pyridoxal-5-phosphate level was assayed with CSFNT testing, 1 patient had a diagnostic result. An etiologic diagnosis was identified in 163 patients (50%) of the cohort, with genetic testing having the highest yield (120 individuals, 37%)., Discussion: Our findings support the case for deimplementation of CSFNT testing as a standard diagnostic test of etiology in infants aged 1 year or younger presenting with neurologic disorders.
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- 2024
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34. Initial combination versus early sequential standard therapies for Infantile Epileptic Spasms Syndrome-Feedback from stakeholders.
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Ramani PK, Briscoe Abath C, Donatelli S, Hadjinicolaou A, Vega Toro S, Acevedo K, Astorga KR, Parbhoo K, Singh A, Catenaccio E, Jain P, Sahu JK, Samanta D, and Harini C
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- Humans, Feedback, Syndrome, Spasm, Spasms, Infantile drug therapy
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- 2024
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35. Timing the clinical onset of epileptic spasms in infantile epileptic spasms syndrome: A tertiary health center's experience.
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Hadjinicolaou A, Briscoe Abath C, Singh A, Donatelli S, Salussolia CL, Cohen AL, He J, Gupta N, Merchant S, Zhang B, Olson H, Yuskaitis CJ, Libenson MH, and Harini C
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- Humans, Infant, Retrospective Studies, Age of Onset, Syndrome, Electroencephalography, Seizures, Spasm, Spasms, Infantile diagnosis, Spasms, Infantile drug therapy
- Abstract
Objective: Lead time to treatment (clinical onset of epileptic spasms [ES] to initiation of appropriate treatment) is known to predict outcomes in infantile epileptic spasms syndrome (IESS). Timing the clinical onset of ES is crucial to establish lead time. We investigated how often ES onset could be established to the nearest week. We aimed to (1) ascertain the exact date or estimate the nearest week of ES onset and (2) compare clinical/demographic factors between patients where date of ES onset was determined or estimated to the nearest week and patients whose date of ES onset could not be estimated to the nearest week. Reasons for difficulties in estimating date of ES onset were explored., Methods: Retrospective chart review of new onset IESS patients (January 2019-May 2022) extracted the date or week of the clinical onset of ES. Predictors of difficulty in date of ES onset estimation to the nearest week were examined by regression analysis. Sources contributing to difficulties determining date of ES onset were assessed after grouping into categories (provider-, caregiver-, disease-related)., Results: Among 100 patients, date of ES onset was estimated to the nearest week in 47%. On univariable analysis, age at diagnosis (p = .021), development delay (p = .007), developmental regression/stagnation (p = .021), ES intermixed with other seizures (p = .011), and nonclustered ES at onset (p = .005) were associated with difficulties estimating date of ES onset. On multivariable analysis, failure to establish date of ES onset was related to ES intermixed with other seizures (p = .004) and nonclustered ES at onset (p = .003). Sources contributing to difficulties determining date of ES onset included disease-related factors (ES characteristics, challenges interpreting electroencephalograms) and provider/caregiver-related factors (delayed diagnosis)., Significance: Difficulties with estimation of lead time (due to difficulties timing ES onset) can impact clinical care (prognostication), as even small increments in lead time duration can have adverse developmental consequences., (© 2024 International League Against Epilepsy.)
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- 2024
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36. Delays to care in infantile epileptic spasms syndrome: Racial and ethnic inequities.
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Abath CB, Gupta N, Hadjinicolaou A, Donatelli S, Singh A, Merchant S, Ryan ME, Soby M, Ryan C, Nelson AK, Maldonado Pacheco JE, Zhang B, Williams DN, Yuskaitis CJ, and Harini C
- Subjects
- Humans, Child, United States, Retrospective Studies, Prospective Studies, Ethnicity, Syndrome, Spasm, Epilepsy diagnosis, Spasms, Infantile therapy, Spasms, Infantile drug therapy
- Abstract
Objective: Non-Hispanic (NH) Black children are less likely to receive a standard treatment course for infantile epileptic spasms syndrome (IESS) than White/NH children at pediatric tertiary care epilepsy centers in the United States. However, if inequities exist in time to diagnosis is unknown. Diagnostic delays as little as 1 week can be associated with worse developmental outcomes., Methods: Diagnostic delays were evaluated in a retrospective cohort of 100 children with new onset IESS between January 2019 and May 2022., Results: Children with Black, Indigenous, and People of Color (BIPOC) caregivers were more likely to experience clinically significant delays in referral from first provider to neurologist, when compared to White/NH children, even after controlling for other demographic and clinical variables (odds ratio = 4.98, confidence interval = 1.24-19.94, p = .023)., Significance: Disproportionate diagnostic delays place BIPOC children at risk of adverse developmental and epilepsy outcomes. Further interventional prospective and qualitative studies are needed to address inequities in care., (© 2023 International League Against Epilepsy.)
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- 2024
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37. Influence of extent and age at corpus callosotomy on seizure outcomes. A single center experience.
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Chourasia N, Stone SSD, Tsuboyama M, Madsen JR, Ryan M, Zhang B, Libenson MH, Bolton J, and Harini C
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- Humans, Treatment Outcome, Corpus Callosum surgery, Seizures surgery, Epilepsy, Drug Resistant Epilepsy surgery
- Abstract
Corpus callosotomy (CC) is a palliative treatment for drop seizures in patients with drug-resistant nonlocalizable epilepsy. We compared drop seizure outcomes between patients undergoing anterior CC versus complete CC and examined factors impacting outcomes for drop seizures including age at CC and duration of epilepsy. A retrospective review of patients who underwent CC between 2003 and 2022 with a minimum of 6 months postsurgical follow-up was included. Outcome measure for drop seizures included seizure reduction ≥50% from baseline as well as elimination of drop seizures. Thirty-eight patients were included. Overall, ≥50% reduction in drop seizures occurred in nearly 70% (23 out of 33) patients with complete elimination in 58% (19 out of 33). Compared with anterior CC (n = 13), patients undergoing complete CC (n = 25) had increased likelihood of ≥50% reduction (p = 0.006) or elimination (p = 0.024) of drop seizures. Regression analysis showed that complete CC was the primary predictor for improved drop seizure outcomes (elimination, p = 0.014 or ≥50% reduction, p = 0.006), while age at CC and duration of epilepsy did not impact the outcomes. Compared to anterior CC, complete CC was significantly more likely to lead to improvement/freedom from drop seizures. Age at CC or duration of epilepsy did not influence drop seizure outcomes., (© 2023 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)
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- 2023
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38. Post-zygotic rescue of meiotic errors causes brain mosaicism and focal epilepsy.
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Miller KE, Rivaldi AC, Shinagawa N, Sran S, Navarro JB, Westfall JJ, Miller AR, Roberts RD, Akkari Y, Supinger R, Hester ME, Marhabaie M, Gade M, Lu J, Rodziyevska O, Bhattacharjee MB, Von Allmen GK, Yang E, Lidov HGW, Harini C, Shah MN, Leonard J, Pindrik J, Shaikhouni A, Goldman JE, Pierson CR, Thomas DL, Boué DR, Ostendorf AP, Mardis ER, Poduri A, Koboldt DC, Heinzen EL, and Bedrosian TA
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- Humans, Mouth Mucosa, Mutation, Brain, Mosaicism, Epilepsies, Partial genetics
- Abstract
Somatic mosaicism is a known cause of neurological disorders, including developmental brain malformations and epilepsy. Brain mosaicism is traditionally attributed to post-zygotic genetic alterations arising in fetal development. Here we describe post-zygotic rescue of meiotic errors as an alternate origin of brain mosaicism in patients with focal epilepsy who have mosaic chromosome 1q copy number gains. Genomic analysis showed evidence of an extra parentally derived chromosome 1q allele in the resected brain tissue from five of six patients. This copy number gain is observed only in patient brain tissue, but not in blood or buccal cells, and is strongly enriched in astrocytes. Astrocytes carrying chromosome 1q gains exhibit distinct gene expression signatures and hyaline inclusions, supporting a novel genetic association for astrocytic inclusions in epilepsy. Further, these data demonstrate an alternate mechanism of brain chromosomal mosaicism, with parentally derived copy number gain isolated to brain, reflecting rescue in other tissues during development., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)
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- 2023
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39. Epileptic spasms in CDKL5 deficiency disorder: Delayed treatment and poor response to first-line therapies.
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Olson HE, Demarest S, Pestana-Knight E, Moosa AN, Zhang X, Pérez-Pérez JR, Weisenberg J, O'Connor Prange E, Marsh ED, Rajaraman RR, Suter B, Katyayan A, Haviland I, Daniels C, Zhang B, Greene C, DeLeo M, Swanson L, Love-Nichols J, Benke T, Harini C, and Poduri A
- Subjects
- Infant, Humans, Female, Male, Vigabatrin therapeutic use, Time-to-Treatment, Anticonvulsants therapeutic use, Adrenocorticotropic Hormone therapeutic use, Spasm drug therapy, Adrenal Cortex Hormones therapeutic use, Treatment Outcome, Protein Serine-Threonine Kinases, Spasms, Infantile drug therapy, Spasms, Infantile genetics
- Abstract
Objective: We aimed to assess the treatment response of infantile-onset epileptic spasms (ES) in CDKL5 deficiency disorder (CDD) vs other etiologies., Methods: We evaluated patients with ES from the CDKL5 Centers of Excellence and the National Infantile Spasms Consortium (NISC), with onset from 2 months to 2 years, treated with adrenocorticotropic hormone (ACTH), oral corticosteroids, vigabatrin, and/or the ketogenic diet. We excluded children with tuberous sclerosis complex, trisomy 21, or unknown etiology with normal development because of known differential treatment responses. We compared the two cohorts for time to treatment and ES remission at 14 days and 3 months., Results: We evaluated 59 individuals with CDD (79% female, median ES onset 6 months) and 232 individuals from the NISC database (46% female, median onset 7 months). In the CDD cohort, seizures prior to ES were common (88%), and hypsarrhythmia and its variants were present at ES onset in 34%. Initial treatment with ACTH, oral corticosteroids, or vigabatrin started within 1 month of ES onset in 27 of 59 (46%) of the CDD cohort and 182 of 232 (78%) of the NISC cohort (p < .0001). Fourteen-day clinical remission of ES was lower for the CDD group (26%, 7/27) than for the NISC cohort (58%, 106/182, p = .0002). Sustained ES remission at 3 months occurred in 1 of 27 (4%) of CDD patients vs 96 of 182 (53%) of the NISC cohort (p < .0001). Comparable results were observed with longer lead time (≥1 month) or prior treatment. Ketogenic diet, used within 3 months of ES onset, resulted in ES remission at 1 month, sustained at 3 months, in at least 2 of 13 (15%) individuals with CDD., Significance: Compared to the broad group of infants with ES, children with ES in the setting of CDD often experience longer lead time to treatment and respond poorly to standard treatments. Development of alternative treatments for ES in CDD is needed., (© 2023 International League Against Epilepsy.)
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- 2023
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40. Hospital readmissions in children with new-onset infantile epileptic spasms syndrome.
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Harini C, Yuskaitis CJ, Singh A, McHugh T, Liu S, DeLeo M, Gupta N, Marti C, Zhang B, Libenson MH, and Berry JG
- Subjects
- Male, Humans, Child, Female, Retrospective Studies, Cohort Studies, Syndrome, Spasm, Patient Readmission, Epilepsy
- Abstract
Objective: To describe inpatient resource use in the 2 years following infantile epileptic spasms syndrome (IESS) diagnosis, examine the association between clinical/demographic variables and incidence of readmission, and identify risk factors/reasons for frequent readmissions., Methods: Retrospective cohort analysis of readmissions (scheduled/unscheduled) within the first 2 years following IESS diagnosis, details of readmissions (number/time between rehospitalizations, and length of stay), demographic/clinical variables, and reasons for readmissions were collected. Negative binomial regression analysis evaluated associations between incidence of readmissions (both scheduled/unscheduled and unscheduled alone) and demographic/clinical factors. Logistic regression assessed the risk of having recurrent readmissions (≥5 readmissions)., Results: Among 93 (60% males) new-onset IESS patients, there were 394 readmissions (56% scheduled and 44% unscheduled) within 2-years following IESS diagnosis. Mean length of stay was 3.5 days (SD: 5.9). Readmissions occurred in 82 patients (88%) and 37 (40%) experienced ≥5 readmissions. On multivariate regression analysis, readmissions were increased with use of multiple first-line treatments for IESS (P = 0.006), technology assistance (P ≤ 0.001), and multispecialty care (P = 0.01); seizure freedom (P = 0.015) and known etiology (P = 0.011) lowered the incidence of readmissions. Examining unscheduled readmissions separately, increased readmissions occurred with public insurance (P = 0.013), technology use (P ≤ 0.0.001), and multispecialty care (P = 0.013); seizure freedom decreased unscheduled readmissions (P = 0.006). Technology assistance (G-tube, NG tube, VP shunt, and tracheostomy use) increased the odds (P = 0.007) for recurrent readmissions. Reasons for readmissions included EEG monitoring (protocol driven for verification of IESS remission/characterization of events/EEG surveillance/presurgical monitoring) (51%), acute medical issues (21%), and seizure exacerbation (15%). Protocol-driven readmissions declined an estimated 52% following protocol modification during the study., Significance: In the 2 years following IESS diagnosis, there is substantial inpatient resource use with nearly 40% experiencing ≥5 readmissions (mostly epilepsy related). Since readmissions are increased by intrinsic patient characteristics such as medical complexity (technology use and multispecialty care) or epilepsy-related issues, the preventability of readmissions is uncertain, except for protocol-driven ones., (© 2023 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)
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- 2023
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41. Clinical characteristics of children with infantile epileptic spasms syndrome from a tertiary-care hospital in Dhaka, Bangladesh.
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Abath CB, Chandra Saha N, Hoque SA, Islam A, Chowdhury YS, Ara Begum MS, Davalji Kanjiker TS, Yuskaitis CJ, Harini C, Alam MB, Mohammed QD, and Mazumdar M
- Abstract
Background: We describe patient characteristics and response to initial treatment in a large case series of children presenting with infantile epileptic spasms syndrome to a tertiary-care hospital with a pediatric neurology service in Bangladesh. The purpose of the study was to add to the growing body of literature on infantile epileptic spasms syndrome in low- and middle-income countries., Methods: We enrolled 212 infants with new-onset infantile epileptic spasms syndrome (IESS) at the time of initial presentation to the National Institute of Neurosciences and Hospital (NINS) in Dhaka, Bangladesh, between January 2019 and August 2021. We collected data about seizure type and frequency, etiology, medication dosage, and available neuroimaging., Results: Median age at initial presentation to NINS was 9 months. Developmental delay and regression prior to presentation were found in 83% and 36%, respectively. Prior to their presentation at NINS, 197 (93%) patients had received anti-seizure medication to treat spasms, of whom only 8 (4%) had received standard therapy with ACTH, prednisolone, or vigabatrin. At NINS, 207 (98%) of patients received standard therapy, most frequently ACTH in 154 (73%). Median time between seizure onset to receipt of first-line therapy was 5 months. Of the 169 patients who were seen in follow-up at average of 5 weeks, 92 (54%) reported absence of clinical epileptic spasms. No serious adverse events requiring hospitalization were reported., Conclusions: This study highlights the long lead times to treatment for IESS in a low- and middle-income country, and the need for early referral of children with suspected epileptic spasms to epilepsy care centers., Competing Interests: The authors declare no competing interests., (© 2023 The Authors.)
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- 2023
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42. Temporal trends in the cost and use of first-line treatments for infantile epileptic spasms syndrome.
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Sánchez Fernández I, Amengual-Gual M, Barcia Aguilar C, Romeu A, Sheikh T, Torres A, Chao J, Jonas R, Gaínza-Lein M, Harini C, and Douglass L
- Subjects
- Humans, Male, Infant, Child, Infant, Newborn, Female, Anticonvulsants therapeutic use, Adrenocorticotropic Hormone therapeutic use, Prednisolone therapeutic use, Syndrome, Spasm drug therapy, Treatment Outcome, Vigabatrin therapeutic use, Spasms, Infantile drug therapy
- Abstract
Objective: To describe the temporal trends in the cost and use of adrenocorticotropic hormone (ACTH), oral prednisolone, and vigabatrin, the first-line treatments for infantile epileptic spasms syndrome (IESS)., Methods: Retrospective observational study using the MarketScan Commercial database from 2006 to 2020. We identified patients with IESS diagnosed between birth and 18 months of age who received at least one of the first-line treatments within 60 days of diagnosis. Costs were adjusted for inflation using the Gross Domestic Product Implicit Price Deflator., Results: A total of 1131 patients received at least one first-line treatment (median [p
25 -p75 ] age: 6.3 [4.5-8.3] months, 55% male), of whom 592 patients received ACTH, 363 patients received oral prednisolone, and 355 patients received vigabatrin. After adjusting for inflation, the median average wholesale price of a 14-day course of treatment increased for ACTH from $3718 in 2006 to $100 457 in 2020, ~2700% (by a factor of 27), whereas it decreased for oral prednisolone from $169 in 2006 to $89 in 2020, ~50% (by a factor of 0.5), and increased for vigabatrin from $1206 in 2009 (first year with data on vigabatrin used for IESS) to $4102 in 2020, ~340% (by a factor of 3.4). During the first 60 days after diagnosis, inpatient admission days and costs where higher for ACTH than for oral prednisolone and vigabatrin-5.0 (3.0-8.3) days vs 2.0 (0.0-5.0) days vs 2.0 (0.0-6.0) days, p < .0001; and $32 828 ($14 711-$67 216) vs $16 227 ($0-$35 829) vs $17 844 ($0-$47 642), p < .0001. ACTH use decreased from representing 78% of first-line treatments in 2006 to 18% in 2020 (p < .0001). Sensitivity analyses confirmed the robustness of the results., Significance: The gap between the cost of ACTH and the cost of oral prednisolone or vigabatrin has widened markedly from 2006 to 2020, whereas the relative proportion of ACTH use has decreased., (© 2023 International League Against Epilepsy.)- Published
- 2023
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43. Association of Time to Clinical Remission With Sustained Resolution in Children With New-Onset Infantile Spasms.
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Yuskaitis CJ, Mytinger JR, Baumer FM, Zhang B, Liu S, Samanta D, Hussain SA, Yozawitz EG, Keator CG, Joshi C, Singh RK, Bhatia S, Bhalla S, Shellhaas R, and Harini C
- Subjects
- Humans, Infant, Adrenocorticotropic Hormone therapeutic use, Anticonvulsants therapeutic use, Cognition, Electroencephalography, Treatment Outcome, Vigabatrin therapeutic use, Spasms, Infantile drug therapy
- Abstract
Background and Objectives: Standard therapies (adrenocorticotropic hormone [ACTH], oral steroids, or vigabatrin) fail to control infantile spasms in almost half of children. Early identification of nonresponders could enable rapid initiation of sequential therapy. We aimed to determine the time to clinical remission after appropriate infantile spasms treatment initiation and identify predictors of the time to infantile spasms treatment response., Methods: The National Infantile Spasms Consortium prospectively followed children aged 2-24 months with new-onset infantile spasms at 23 US centers (2012-2018). We included children treated with standard therapy (ACTH, oral steroids, or vigabatrin). Sustained treatment response was defined as having the last clinically recognized infantile spasms on or before treatment day 14, absence of hypsarrhythmia on EEG 2-4 weeks after treatment, and persistence of remission to day 30. We analyzed the time to treatment response and assessed clinical characteristics to predict sustained treatment response., Results: Among 395 infants, clinical infantile spasms remission occurred in 43% (n = 171) within the first 2 weeks of treatment, of which 81% (138/171) responded within the first week of treatment. There was no difference in the median time to response across standard therapies (ACTH: median 4 days, interquartile range [IQR] 3-7; oral steroids: median 3 days, IQR 2-5; vigabatrin: median 3 days, IQR 1-6). Individuals without hypsarrhythmia on the pretreatment EEG (i.e., abnormal but not hypsarrhythmia) were more likely to have early treatment response than infants with hypsarrhythmia at infantile spasms onset (hazard ratio 2.23, 95% CI 1.39-3.57). No other clinical factors predicted early responders to therapy., Discussion: Remission after first infantile spasms treatment can be identified by treatment day 7 in most children. Given the importance of early and effective treatment, these data suggest that children who do not respond to standard infantile spasms therapy within 1 week should be reassessed immediately for additional standard treatment. This approach could optimize outcomes by facilitating early sequential therapy for children with infantile spasms., (© 2022 American Academy of Neurology.)
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- 2022
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44. Interictal Connectivity Revealed by Granger Analysis of Stereoelectroencephalography: Association With Ictal Onset Zone, Resection, and Outcome.
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Stone SSD, Park EH, Bolton J, Harini C, Libenson MH, Rotenberg A, Takeoka M, Tsuboyama M, Pearl PL, and Madsen JR
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- Electroencephalography, Humans, Retrospective Studies, Seizures diagnosis, Seizures surgery, Stereotaxic Techniques, Treatment Outcome, Epilepsies, Partial surgery, Hemispherectomy
- Abstract
Background: Stereoelectroencephalography (sEEG) facilitates electrical sampling and evaluation of complex deep-seated, dispersed, and multifocal locations. Granger causality (GC), previously used to study seizure networks using interictal data from subdural grids, may help identify the seizure-onset zone from interictal sEEG recordings., Objective: To examine whether statistical analysis of interictal sEEG helps identify surgical target sites and whether surgical resection of highly ranked nodes correspond to favorable outcomes., Methods: Ten minutes of extraoperative recordings from sequential patients who underwent sEEG evaluation were analyzed (n = 20). GC maps were compared with clinically defined surgical targets using rank order statistics. Outcomes of patients with focal resection/ablation with median follow-up of 3.6 years were classified as favorable (Engel 1, 2) or poor (Engel 3, 4) to assess their relationship with the removal of highly ranked nodes using the Wilcoxon rank-sum test., Results: In 12 of 20 cases, the rankings of contacts (based on the sum of outward connection weights) mapped to the seizure-onset zone showed higher causal node connectivity than predicted by chance ( P ≤ .02). A very low aggregate probability ( P < 10 -18 , n = 20) suggests that causal node connectivity predicts seizure networks. In 8 of 16 with outcome data, causal connectivity in the resection was significantly greater than in the remaining contacts ( P ≤ .05). We found a significant association between favorable outcome and the presence of highly ranked nodes in the resection ( P < .05)., Conclusion: Granger analysis can identify seizure foci from interictal sEEG and correlates highly ranked nodes with favorable outcome, potentially informing surgical decision-making without reliance on ictal recordings., (Copyright © Congress of Neurological Surgeons 2022. All rights reserved.)
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- 2022
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45. Inequities in Therapy for Infantile Spasms: A Call to Action.
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Baumer FM, Mytinger JR, Neville K, Briscoe Abath C, Gutierrez CA, Numis AL, Harini C, He Z, Hussain SA, Berg AT, Chu CJ, Gaillard WD, Loddenkemper T, Pasupuleti A, Samanta D, Singh RK, Singhal NS, Wusthoff CJ, Wirrell EC, Yozawitz E, Knupp KG, Shellhaas RA, and Grinspan ZM
- Subjects
- Black People, Child, Hispanic or Latino, Humans, Prospective Studies, Vigabatrin therapeutic use, Spasms, Infantile drug therapy
- Abstract
Objective: The aim of this study was to determine whether selection of treatment for children with infantile spasms (IS) varies by race/ethnicity., Methods: The prospective US National Infantile Spasms Consortium database includes children with IS treated from 2012 to 2018. We examined the relationship between race/ethnicity and receipt of standard IS therapy (prednisolone, adrenocorticotropic hormone, vigabatrin), adjusting for demographic and clinical variables using logistic regression. Our primary outcome was treatment course, which considered therapy prescribed for the first and, when needed, the second IS treatment together., Results: Of 555 children, 324 (58%) were non-Hispanic white, 55 (10%) non-Hispanic Black, 24 (4%) non-Hispanic Asian, 80 (14%) Hispanic, and 72 (13%) other/unknown. Most (398, 72%) received a standard treatment course. Insurance type, geographic location, history of prematurity, prior seizures, developmental delay or regression, abnormal head circumference, hypsarrhythmia, and IS etiologies were associated with standard therapy. In adjusted models, non-Hispanic Black children had lower odds of receiving a standard treatment course compared with non-Hispanic white children (odds ratio [OR], 0.42; 95% confidence interval [CI], 0.20-0.89; p = 0.02). Adjusted models also showed that children with public (vs. private) insurance had lower odds of receiving standard therapy for treatment 1 (OR, 0.42; CI, 0.21-0.84; p = 0.01)., Interpretation: Non-Hispanic Black children were more often treated with non-standard IS therapies than non-Hispanic white children. Likewise, children with public (vs. private) insurance were less likely to receive standard therapies. Investigating drivers of inequities, and understanding the impact of racism on treatment decisions, are critical next steps to improve care for patients with IS. ANN NEUROL 2022;92:32-44., (© 2022 American Neurological Association.)
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- 2022
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46. Infantile spasms: Assessing the diagnostic yield of an institutional guideline and the impact of etiology on long-term treatment response.
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Chourasia N, Yuskaitis CJ, Libenson MH, Bergin AM, Liu S, Zhang B, Poduri A, and Harini C
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- Anticonvulsants therapeutic use, Female, Genetic Testing, Humans, Infant, Male, Retrospective Studies, Spasm drug therapy, Treatment Outcome, Spasms, Infantile etiology, Spasms, Infantile genetics
- Abstract
Objective: Neuroimaging and genetic testing have been proposed for diagnostic evaluation of infantile spasms (IS), establishing etiology in ~60% of multicenter IS cohorts. A retrospective analysis of the yield of diagnostic etiology following an institutionally established guideline for investigation/treatment of IS was conducted, and the association between etiological subgroups and sustained response to standard treatment was evaluated., Methods: Etiology of IS, neuroimaging, and genetic results were extracted from clinical records. Etiology was categorized as acquired or nonacquired, the latter including syndromic patients, nonsyndromic patients with confirmed etiology, and unknown cases. Regression analyses, using clinical variables including subtypes of etiology, were conducted to determine which factors correlated with favorable (spasm freedom at last follow-up after two or fewer standard treatments) versus unfavorable treatment outcome (refractory spasms despite two standard treatments or relapse)., Results: We included 127 IS patients (60% males) with a follow-up of 2.4 years (range = .6-5 years). All patients had neuroimaging, and 95% of patients in the nonacquired category (103 of 108 patients) had genetic testing. Etiology was identified in 103 of 127 (81%, 95% confidence interval = .73-.86). At last follow-up, 42 (33%) patients had favorable treatment outcome. No difference in treatment response was observed between acquired and nonacquired etiologies. Among patients with nonacquired etiologies, developmental delay prior to spasms onset increased the odds of unfavorable treatment outcome (p = .014), whereas a clearly recognizable dysmorphic/syndromic etiology was associated with a lower risk for treatment failure (p = .034). In nonacquired etiology without a recognizable dysmorphic/syndrome but with a genetic etiology, unfavorable treatment outcome was more likely (p = .043)., Significance: Rigorous evaluation with neuroimaging and genetic testing yields an etiological diagnosis in most patients with IS. Among patients with a nonacquired etiology, those with recognizable dysmorphic/syndromic diagnosis had a higher likelihood of a favorable treatment outcome, whereas the absence of such a finding, when associated with an identifiable genetic diagnosis, was associated with unfavorable treatment outcomes., (© 2022 International League Against Epilepsy.)
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- 2022
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47. Comparison of Cosyntropin, Vigabatrin, and Combination Therapy in New-Onset Infantile Spasms in a Prospective Randomized Trial.
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Knupp KG, Coryell J, Singh RK, Gaillard WD, Shellhaas RA, Koh S, Mitchell WG, Harini C, Millichap JJ, May A, Dlugos D, Nickels K, Mytinger JR, Keator C, Yozawitz E, Singhal N, Lockrow J, Thomas JF, and Juarez-Colunga E
- Subjects
- Anticonvulsants adverse effects, Child, Cosyntropin therapeutic use, Humans, Prospective Studies, Spasm chemically induced, Spasm complications, Spasm drug therapy, Treatment Outcome, Spasms, Infantile drug therapy, Spasms, Infantile etiology, Vigabatrin adverse effects
- Abstract
Objective: In a randomized trial, we aimed to evaluate the efficacy of cosyntropin injectable suspension, 1 mg/mL, compared to vigabatrin for infantile spasms syndrome. An additional arm was included to assess the efficacy of combination therapy (cosyntropin and vigabatrin) compared with cosyntropin monotherapy. Methods: Children (2 months to 2 years) with new-onset infantile spasms syndrome and hypsarhythmia were randomized into 3 arms: cosyntropin, vigabatrin, and cosyntropin and vigabatrin combined. Daily seizures and adverse events were recorded, and EEG was repeated at day 14 to assess for resolution of hypsarhythmia. The primary outcome measure was the composite of resolution of hypsarhythmia and absence of clinical spasms at day 14. Fisher exact test was used to compare outcomes. Results: 37 children were enrolled and 34 were included in the final efficacy analysis (1 withdrew prior to treatment and 2 did not return seizure diaries). Resolution of both hypsarhythmia and clinical spasms was achieved in in 9 of 12 participants (75%) treated with cosyntropin, 1/9 (11%) vigabatrin, and 5/13 (38%) cosyntropin and vigabatrin combined. The primary comparison of cosyntropin versus vigabatrin was significant (64% [95% confidence interval 21, 82], P < .01). Adverse events were reported in all 3 treatment arms: 31 (86%) had an adverse event, 7 (19%) had a serious adverse event, and 15 (42%) had an adverse event of special interest with no difference between treatment arms. Significance: This randomized trial was underpowered because of incomplete enrollment, yet it demonstrated that cosyntropin was more effective for short-term outcomes than vigabatrin as initial treatment for infantile spasms.
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- 2022
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48. Confirmation of infantile spasms resolution by prolonged outpatient EEGs.
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Yuskaitis CJ, Mysak K, Godlewski B, Zhang B, and Harini C
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- Electroencephalography, Humans, Outpatients, Retrospective Studies, Spasm, Spasms, Infantile diagnosis, Spasms, Infantile drug therapy
- Abstract
Objective: There is no consensus on the type or duration of the posttreatment EEG needed for assessing treatment response for infantile spasms (IS). We assessed whether outpatient electroencephalograms (EEGs) are sufficient to confirm infantile spasms (IS) treatment response., Methods: Three-year retrospective review identified new-onset IS patients. Only presumed responder to IS treatment at 2 weeks with a prolonged (>90 minutes) outpatient EEG to assess treatment response and at least 3-month follow-up were included. Hypsarrhythmia, electroclinical spasms, and sleep were evaluated for the first hour and for the duration of the EEG., Results: We included 37 consecutive patients with new-onset IS and presumed clinical response at 2 weeks posttreatment. Follow-up outpatient prolonged EEGs (median: 150 minutes, range: 90-240 minutes) were obtained 14 days (IQR: 13-17) after treatment initiation. EEGs detected ongoing IS in 11 of 37 (30%) presumed early responders. Prolonged outpatient EEG had a sensitivity of 85% (confidence interval [CI] 55%-98%) for detecting treatment failure. When hypsarrhythmia and/or electroclinical spasms were not seen, EEG had a negative predictive value 92% (CI: 75%-99%) for confirming continued IS resolution. Outpatient EEG combined with clinical assessment, however, identified all treatment failures at 2 weeks. Compared with the entire prolonged EEG, the first-hour recording missed IS in 45% (5/11). While sleep was captured in 95% (35/37) of the full EEG recording, the first hour of recording captured sleep in only 54% (20/37)., Significance: Infantile spasms treatment response can be confirmed with a clinical history of spasm freedom and an outpatient prolonged EEG without evidence for ongoing spasms (hypsarrhythmia/electroclinical spams on EEG). Outpatient prolonged EEG, but not routine EEGs, represents an alternative to inpatient long-term monitoring for IS posttreatment EEG follow-up., (© 2021 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)
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- 2021
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49. Comparative Effectiveness of Initial Treatment for Infantile Spasms in a Contemporary US Cohort.
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Grinspan ZM, Knupp KG, Patel AD, Yozawitz EG, Wusthoff CJ, Wirrell EC, Valencia I, Singhal NS, Nordli DR, Mytinger JR, Mitchell WG, Keator CG, Loddenkemper T, Hussain SA, Harini C, Gaillard WD, Fernandez IS, Coryell J, Chu CJ, Berg AT, and Shellhaas RA
- Abstract
Objective: To compare the effectiveness of initial treatment for infantile spasms., Methods: The National Infantile Spasms Consortium prospectively followed up children with new-onset infantile spasms that began at age 2 to 24 months at 23 US centers (2012-2018). Freedom from treatment failure at 60 days required no second treatment for infantile spasms and no clinical spasms after 30 days of treatment initiation. We managed treatment selection bias with propensity score weighting and within-center correlation with generalized estimating equations., Results: Freedom from treatment failure rates were as follows: adrenocorticotropic hormone (ACTH) 88 of 190 (46%), oral steroids 42 of 95 (44%), vigabatrin 32 of 87 (37%), and nonstandard therapy 4 of 51 (8%). Changing from oral steroids to ACTH was not estimated to affect response (observed 44% estimated to change to 44% [95% confidence interval 34%-54%]). Changing from nonstandard therapy to ACTH would improve response from 8% to 39% (17%-67%), and changing to oral steroids would improve response from 8% to 38% (15%-68%). There were large but not statistically significant estimated effects of changing from vigabatrin to ACTH (29% to 42% [15%-75%]), from vigabatrin to oral steroids (29% to 42% [28%-57%]), and from nonstandard therapy to vigabatrin (8% to 20% [6%-50%]). Among children treated with vigabatrin, those with tuberous sclerosis complex (TSC) responded more often than others (62% vs 29%; p < 0.05)., Discussion: Compared to nonstandard therapy, ACTH and oral steroids are superior for initial treatment of infantile spasms. The estimated effectiveness of vigabatrin is between that of ACTH/oral steroids and nonstandard therapy, although the sample was underpowered for statistical confidence. When used, vigabatrin worked best for TSC., Classification of Evidence: This study provides Class III evidence that for children with new-onset infantile spasms, ACTH or oral steroids were superior to nonstandard therapies., (© 2021 American Academy of Neurology.)
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- 2021
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50. Subclinical seizures detected on intracranial EEG: Patient characteristics and impact on surgical outcome in a single pediatric epilepsy surgery center.
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Tsuboyama M, Harini C, Liu S, Zhang B, and Bolton J
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- Boston, Child, Electrocorticography, Electroencephalography, Humans, Retrospective Studies, Treatment Outcome, Epilepsies, Partial, Epilepsy diagnosis, Epilepsy surgery
- Abstract
Objective: Subclinical seizures (SCS) are often captured during intracranial EEG monitoring of pediatric patients with refractory focal epilepsy. However, their clinical significance remains uncertain. We aimed to characterize features associated with SCS and whether their presence impacts epilepsy outcomes post-surgically., Methods: A single center retrospective chart review of patients with refractory focal epilepsy who underwent intracranial EEG monitoring at Boston Children's Hospital between 2004 and 2014 was conducted. Patient and seizure characteristics as well as post-operative outcome data were collected., Results: Of the 104 patients included in the study, SCS were recorded in 66 (63%). Fifty-eight had electroclinical seizures (ECS) and SCS (ECS + SCS), and eight patients only had SCS. There were no significant patient characteristics associated with the presence of SCS. One hundred one of the 104 patients (97%) underwent surgical resection after the intracranial EEG monitoring, 53 of which had Engel 1 outcomes (52%). Incomplete resection (OR 0.15, 95% confidence interval (CI) [0.06, 0.40], p < 0.001) or presence of temporal plus epilepsy (OR 0.23, 95% CI [0.06, 0.80], p = 0.04) was associated with poor Engel outcomes (Engel 2-4). Presence of SCS was not associated with epilepsy surgical outcomes (p = 0.99)., Significance: Nearly 2/3 of patients in our study had SCS captured on intracranial EEG monitoring, and arose in overlapping regions with the ictal onset zone of ECS. Completeness of resection remains the most important predictor of seizure outcome, regardless of the presence of SCS. In the absence of ECS during intracranial EEG monitoring, SCS onset zones may provide useful localization information to guide surgical resection plans. This is the largest cohort reported in the literature describing characteristics associated with the presence of SCS and the impact of SCS on pediatric epilepsy surgery outcomes., (Copyright © 2021 Elsevier Inc. All rights reserved.)
- Published
- 2021
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