The epitope arrangement on flavivirus particles contributes to Mab C10's extraordinary neutralization breadth across Zika and dengue viruses.

The human monoclonal antibody C10 exhibits extraordinary cross-reactivity, potently neutralizing Zika virus (ZIKV) and the four serotypes of dengue virus (DENV1-DENV4). Here we describe a comparative structure-function analysis of C10 bound to the envelope (E) protein dimers of the five viruses it neutralizes. We demonstrate that the C10 Fab has high affinity for ZIKV and DENV1 but not for DENV2, DENV3, and DENV4. We further show that the C10 interaction with the latter viruses requires an E protein conformational landscape that limits binding to only one of the three independent epitopes per virion. This limited affinity is nevertheless counterbalanced by the particle's icosahedral organization, which allows two different dimers to be reached by both Fab arms of a C10 immunoglobulin. The epitopes' geometric distribution thus confers C10 its exceptional neutralization breadth. Our results highlight the importance not only of paratope/epitope complementarity but also the topological distribution for epitope-focused vaccine design.

A comprehensive quality control and cost comparison study of branded and generic angiotensin receptor blockers.

This study was designed to assess both the quality and cost aspects of various branded and generic formulations of angiotensin receptor blockers, specifically Irbesartan, Losartan Potassium, Olmesartan Medoxomil, Telmisartan, and Valsartan. The collected samples underwent distinct quality evaluations using the methods outlined in different global Pharmacopoeias (British Pharmacopoeia/European Pharmacopoeia, Indian Pharmacopoeia and United States Pharmacopoeia). These drugs were characterized using Fourier-Transform Infrared Spectroscopy and Nuclear Magnetic Resonance techniques, while their quality and concentration were analysed using High Performance Liquid Chromatography. The release profile of the drugs was examined through dissolution testing. Additionally, a cost comparison analysis was carried out by determining the prevailing market prices of the drugs. The evaluated branded and generic angiotensin receptor blockers were found to meet the established standards for impurities, active drug content, and dissolution as set by these Pharmacopoeias, indicating their optimal quality. Notably, the generic drugs exhibited significantly lower costs compared to their branded counterparts. This study confirms that the quality of generic angiotensin receptor blockers is equivalent to that of their branded counterparts. Consequently, these findings support the practicality of utilizing generic drugs as a more economically sustainable and cost-effective approach to managing diseases, especially those of chronic nature.

Glial Cells Response in Stroke.

As the second-leading cause of death, stroke faces several challenges in terms of treatment because of the limited therapeutic interventions available. Previous studies primarily focused on metabolic and blood flow properties as a target for treating stroke, including recombinant tissue plasminogen activator and mechanical thrombectomy, which are the only USFDA approved therapies. These interventions have the limitation of a narrow therapeutic time window, the possibility of hemorrhagic complications, and the expertise required for performing these interventions. Thus, it is important to identify the contributing factors that exacerbate the ischemic outcome and to develop therapies targeting them for regulating cellular homeostasis, mainly neuronal survival and regeneration. Glial cells, primarily microglia, astrocytes, and oligodendrocytes, have been shown to have a crucial role in the prognosis of ischemic brain injury, contributing to inflammatory responses. They play a dual role in both the onset as well as resolution of the inflammatory responses. Understanding the different mechanisms driving these effects can aid in the development of therapeutic targets and further mitigate the damage caused. In this review, we summarize the functions of various glial cells and their contribution to stroke pathology. The review highlights the therapeutic options currently being explored and developed that primarily target glial cells and can be used as neuroprotective agents for the treatment of ischemic stroke.

Structural basis of potent Zika-dengue virus antibody cross-neutralization.

Zika virus is a member of the Flavivirus genus that had not been associated with severe disease in humans until the recent outbreaks, when it was linked to microcephaly in newborns in Brazil and to Guillain-Barré syndrome in adults in French Polynesia. Zika virus is related to dengue virus, and here we report that a subset of antibodies targeting a conformational epitope isolated from patients with dengue virus also potently neutralize Zika virus. The crystal structure of two of these antibodies in complex with the envelope protein of Zika virus reveals the details of a conserved epitope, which is also the site of interaction of the envelope protein dimer with the precursor membrane (prM) protein during virus maturation. Comparison of the Zika and dengue virus immunocomplexes provides a lead for rational, epitope-focused design of a universal vaccine capable of eliciting potent cross-neutralizing antibodies to protect simultaneously against both Zika and dengue virus infections.

Diversity-oriented synthesis yields novel multistage antimalarial inhibitors.

Antimalarial drugs have thus far been chiefly derived from two sources-natural products and synthetic drug-like compounds. Here we investigate whether antimalarial agents with novel mechanisms of action could be discovered using a diverse collection of synthetic compounds that have three-dimensional features reminiscent of natural products and are underrepresented in typical screening collections. We report the identification of such compounds with both previously reported and undescribed mechanisms of action, including a series of bicyclic azetidines that inhibit a new antimalarial target, phenylalanyl-tRNA synthetase. These molecules are curative in mice at a single, low dose and show activity against all parasite life stages in multiple in vivo efficacy models. Our findings identify bicyclic azetidines with the potential to both cure and prevent transmission of the disease as well as protect at-risk populations with a single oral dose, highlighting the strength of diversity-oriented synthesis in revealing promising therapeutic targets.

Lysyl-tRNA synthetase as a drug target in malaria and cryptosporidiosis.

Malaria and cryptosporidiosis, caused by apicomplexan parasites, remain major drivers of global child mortality. New drugs for the treatment of malaria and cryptosporidiosis, in particular, are of high priority; however, there are few chemically validated targets. The natural product cladosporin is active against blood- and liver-stage Plasmodium falciparum and Cryptosporidium parvum in cell-culture studies. Target deconvolution in P. falciparum has shown that cladosporin inhibits lysyl-tRNA synthetase (PfKRS1). Here, we report the identification of a series of selective inhibitors of apicomplexan KRSs. Following a biochemical screen, a small-molecule hit was identified and then optimized by using a structure-based approach, supported by structures of both PfKRS1 and C. parvum KRS (CpKRS). In vivo proof of concept was established in an SCID mouse model of malaria, after oral administration (ED90 = 1.5 mg/kg, once a day for 4 d). Furthermore, we successfully identified an opportunity for pathogen hopping based on the structural homology between PfKRS1 and CpKRS. This series of compounds inhibit CpKRS and C. parvum and Cryptosporidium hominis in culture, and our lead compound shows oral efficacy in two cryptosporidiosis mouse models. X-ray crystallography and molecular dynamics simulations have provided a model to rationalize the selectivity of our compounds for PfKRS1 and CpKRS vs. (human) HsKRS. Our work validates apicomplexan KRSs as promising targets for the development of drugs for malaria and cryptosporidiosis.

Supersaturation-Based Drug Delivery Systems: Strategy for Bioavailability Enhancement of Poorly Water-Soluble Drugs.

At present, the majority of APIs synthesized today remain challenging tasks for formulation development. Many technologies are being utilized or explored for enhancing solubility, such as chemical modification, novel drug delivery systems (microemulsions, nanoparticles, liposomes, etc.), salt formation, and many more. One promising avenue attaining attention presently is supersaturated drug delivery systems. When exposed to gastrointestinal fluids, drug concentration exceeds equilibrium solubility and a supersaturation state is maintained long enough to be absorbed, enhancing bioavailability. In this review, the latest developments in supersaturated drug delivery systems are addressed in depth.

INSTRuCT: Protocol, Infrastructure, and Governance.

Background and Purpose: Very few large scale multicentric stroke clinical trials have been done in India. The Indian Council of Medical Research funded INSTRuCT (Indian Stroke Clinical Trial Network) as a task force project with the objectives to establish a state-of-the-art stroke clinical trial network and to conduct pharmacological and nonpharmacological stroke clinical trials relevant to the nation and globally. The purpose of the article is to enumerate the structure of multicentric stroke network, with emphasis on its scope, challenges and expectations in India. Methods: Multiple expert group meetings were conducted by Indian Council of Medical Research to understand the scope of network to perform stroke clinical trials in the country. Established stroke centers with annual volume of 200 patients with stroke with prior experience of conducting clinical trials were included. Central coordinating center, standard operating procedures, data and safety monitoring board were formed. Discussion: In first phase, 2 trials were initiated namely, SPRINT (Secondary Prevention by Structured Semi-Interactive Stroke Prevention Package in India) and Ayurveda treatment in the rehabilitation of patients with ischemic stroke in India (RESTORE [Rehabilitation of Ischemic stroke Patients in India: A Randomized controlled trial]). In second phase, 4 trials have been approved. SPRINT trial was the first to be initiated. SPRINT trial randomized first patient on April 28, 2018; recruited 3048 patients with an average of 128.5 per month so far. The first follow-up was completed on May 27, 2019. RESTORE trial randomized first patient on May 22, 2019; recruited 49 patients with an average of 3.7 per month so far. The first follow-up was completed on August 30, 2019. Conclusions: In next 5 years, INSTRuCT will be able to complete high-quality large scale stroke trials which are relevant globally. REGISTRATION: URL: http://www.ctri.nic.in/; Unique Identifier: CTRI/2017/05/008507.

BOX engineering to mitigate negative differential resistance in MFIS negative capacitance FDSOI FET: an analog perspective.

Till date, the existing understanding of negative differential resistance (NDR) is obtained from metal-ferro-metal-insulator-semiconductor (MFMIS) FET, and it has been utilized for both MFMIS and metal-ferro-insulator-semiconductor (MFIS) based NCFETs. However, in MFIS architecture, the ferroelectric capacitance (CFE) is not a lumped capacitance. Therefore, for MFIS negative capacitance (NC) devices, the physical explanation which governs the NDR mechanism needs to be addressed. In this work, for the first time, we present the first principle explanation of the NDR effect in MFIS NC FDSOI. We found that the output current variation with the drain to source voltage (VDS), (i.e.gds) primarily depends upon two parameters: (a)VDSdependent inversion charge gradient (∂n/∂VDS); (b)VDSsensitive electron velocity (∂v/∂VDS), and the combined effect of these two dependencies results in NDR. Further, to mitigate the NDR effect, we proposed the BOX engineered NC FDSOI FET, in which the buried oxide (BOX) layer is subdivided into the ferroelectric (FE) layer and the SiO2layer. In doing so, the inversion charge in the channel is enhanced by the BOX engineered FE layer, which in turn mitigates the NDR and a nearly zerogdswith a minimal positive slope has been obtained. Through well-calibrated TCAD simulations, by utilizing the obtained positivegds, we also designed aVDSindependent constant current mirror which is an essential part of analog circuits. Furthermore, we discussed the impact of the FE parameter (remanent polarization and coercive field) variation on the device performances. We have also compared the acquired results with existing literature on NC-based devices, which justifies that our proposed structure exhibits complete diminution of NDR, thus enabling its use in analog circuit design.

Mucormycosis and COVID-19: An epidemic within a pandemic in India.

IMPORTANCE: Coronavirus disease (COVID-19) causes an immunosuppressed state and increases risk of secondary infections like mucormycosis. We evaluated clinical features, predisposing factors, diagnosis and outcomes for mucormycosis among patients with COVID-19 infection. METHODS: This prospective, observational, multi-centre study included 47 consecutive patients with mucormycosis, diagnosed during their course of COVID-19 illness, between January 3 and March 27, 2021. Data regarding demography, underlying medical conditions, COVID-19 illness and treatment were collected. Clinical presentations of mucormycosis, imaging and biochemical characteristics and outcome were recorded. RESULTS: Of the 2567 COVID-19 patients admitted to 3 tertiary centres, 47 (1.8%) were diagnosed with mucormycosis. Mean age was 55 ± 12.8years, and majority suffered from diabetes mellitus (n = 36, 76.6%). Most were not COVID-19 vaccinated (n = 31, 66.0%) and majority (n = 43, 91.5%) had developed moderate-to-severe pneumonia, while 20 (42.6%) required invasive ventilation. All patients had received corticosteroids and broad-spectrum antibiotics while most (n = 37, 78.7%) received at least one anti-viral medication. Mean time elapsed from COVID-19 diagnosis to mucormycosis was 12.1 ± 4.6days. Eleven (23.4%) subjects succumbed to their disease, mostly (n = 8, 72.7%) within 7 days of diagnosis. Among the patients who died, 10 (90.9%) had pre-existing diabetes mellitus, only 2 (18.2%) had received just one vaccine dose and all developed moderate-to-severe pneumonia, requiring oxygen supplementation and mechanical ventilation. CONCLUSIONS: Mucormycosis can occur among COVID-19 patients, especially with poor glycaemic control, widespread and injudicious use of corticosteroids and broad-spectrum antibiotics, and invasive ventilation. Owing to the high mortality, high index of suspicion is required to ensure timely diagnosis and appropriate treatment in high-risk populations.

Prevalence and follow-up of subclinical rheumatic heart disease among asymptomatic school children in a north-western district of India based on the World Heart Federation echocardiographic criteria.

BACKGROUND: The present study is based on the World Heart Federation (WHF) echocardiographic criteria to assess the prevalence of subclinical rheumatic heart disease (RHD) and elucidate evolution of the disease when the cases were placed on appropriate antibiotic prophylaxis and regular follow-up. The prevalence of subclinical RHD reported by previous active surveillance studies among asymptomatic school children is not comparable to our study because of major differences in screening methods. METHODS: A random inclusion strategy was adopted to recruit urban and rural school children of Bikaner district in the state of Rajasthan, India. The diagnosis of RHD was based on the echocardiographic criteria proposed by the WHF. All studies were reported on-site by a single experienced cardiologist and the digitally preserved studies were reported by a second cardiologist off-site. The final diagnosis was made by consensus. The second echocardiogram was performed for cases diagnosed with RHD after two years from start of study to document early evolution of the disease with ongoing antibiotic prophylaxis. RESULTS: A high prevalence of subclinical RHD was observed in the study population. Pathological mitral and/or aortic valve regurgitation was the commonest lesion, and a significant proportion of cases improved while on regular antibiotic prophylaxis. No case showed fixity of leaflets/ stenosis. CONCLUSION: The prevalence of subclinical RHD is high in the study population, and the disease seems to regress over time in the presence of appropriate antibiotic prophylaxis.

Towards a comprehensive safety understanding of granulocyte-colony stimulating factor biosimilars in treating chemotherapy associated febrile neutropenia: Trends from decades of data.

Filgrastim, a biopharmaceutical listed on WHO model list of essential medicines, was approved in USA in 1991 for patients with non-myeloid malignancies associated with severe neutropenia and fever. Several filgrastim biosimilars have now been approved in USA, Europe and elsewhere since 2008, based on the reference product which has lost patent exclusivity; however their immunogenicity and safety is controversial. We conducted a retrospective, post market study between 1991 and May 2018 using VigiBase®. The study included all adverse events with case reports ≥150. Overall, 11,183 adverse drugs reaction reports were identified during observation period; of which 5764; 51.5% reports concerned to Neupogen®, the originator, and rest consists of Leucostim® (N = 680), Zarzio® (N = 622), Grasin® (N = 545), Nivestim® (N = 359) and Tevagrastim® (N = 152) biosimilars. When compared with the originator, Grasin® was associated with higher reporting of pyrexia (11.5% vs 7.9%, ROR 1.52, IC025 1.12), myalgia (37% vs 2.2%, ROR 25.94, IC025 2.11) and back pain (11.3% vs 4%, ROR 3.09, IC025 2.32). Zarzio® was associated with increased reporting of arthralgia (4.5% vs 2.9%, ROR 1.59, IC025 1.25) and neutropenia (11.4% vs 4%, ROR 2.59, IC025 3.07). Bone pain was reported more often with Nivestim® (14.4% vs 8.3%, ROR 1.87, IC025 5.30). Drug ineffectiveness was reported in cases with Zarzio® (35.9%), Nivestim® (19.4%) and Tevagrastim® (42.2%). Authors observed significant differences among originator and biosimilars in particular to efficacy, adverse events reported and time to onset of occurrences. Large epidemiologic studies are needed to further confirm these finding and provide additional insights.

A multinational, multicentre study on the psychological outcomes and associated physical symptoms amongst healthcare workers during COVID-19 outbreak.

OBJECTIVE: Since the declaration of the coronavirus 2019 (COVID-19) outbreak as pandemic, there are reports on the increased prevalence of physical symptoms observed in the general population. We investigated the association between psychological outcomes and physical symptoms among healthcare workers. METHODS: Healthcare workers from 5 major hospitals, involved in the care for COVID-19 patients, in Singapore and India were invited to participate in a study by performing a self-administered questionnaire within the period of February 19 to April 17, 2020. Healthcare workers included doctors, nurses, allied healthcare workers, administrators, clerical staff and maintenance workers. This questionnaire collected information on demographics, medical history, symptom prevalence in the past month, Depression Anxiety Stress Scales (DASS-21) and the Impact of Events Scale-Revised (IES-R) instrument. The prevalence of physical symptoms displayed by healthcare workers and the associations between physical symptoms and psychological outcomes of depression, anxiety, stress, and post-traumatic stress disorder (PTSD) were evaluated. RESULTS: Out of the 906 healthcare workers who participated in the survey, 48 (5.3%) screened positive for moderate to very-severe depression, 79 (8.7%) for moderate to extremely-severe anxiety, 20 (2.2%) for moderate to extremely-severe stress, and 34 (3.8%) for moderate to severe levels of psychological distress. The commonest reported symptom was headache (32.3%), with a large number of participants (33.4%) reporting more than four symptoms. Participants who had experienced symptoms in the preceding month were more likely to be older, have pre-existing comorbidities and a positive screen for depression, anxiety, stress, and PTSD. After adjusting for age, gender and comorbidities, it was found that depression (OR 2.79, 95% CI 1.54-5.07, p = 0.001), anxiety (OR 2.18, 95% CI 1.36-3.48, p = 0.001), stress (OR 3.06, 95% CI 1.27-7.41, p = 0.13), and PTSD (OR 2.20, 95% CI 1.12-4.35, p = 0.023) remained significantly associated with the presence of physical symptoms experienced in the preceding month. Linear regression revealed that the presence of physical symptoms was associated with higher mean scores in the IES-R, DASS Anxiety, Stress and Depression subscales. CONCLUSIONS: Our study demonstrates a significant association between the prevalence of physical symptoms and psychological outcomes among healthcare workers during the COVID-19 outbreak. We postulate that this association may be bi-directional, and that timely psychological interventions for healthcare workers with physical symptoms should be considered once an infection has been excluded.

Effect of erroneous body-weight estimation on outcome of thrombolyzed stroke patients.

Intravenously administered tissue plasminogen activator (IV-tPA), dose determined by patients' body-weight, remains the only approved drug treatment for acute ischemic stroke (AIS). Since a shorter onset-to-treatment time results in better functional outcome, treatment is often initiated according to the estimated or last-known body-weight of the patient. This approach may result in underdosing or overdosing of tPA. In this multicenter retrospective study, we evaluated the extent of error in tPA dosing in our AIS cohort and its impact on functional outcome and symptomatic intracranial hemorrhage (SICH). Consecutive AIS patients, receiving IV-tPA, dose determined by the estimated body-weight, at three tertiary centers between January and December 2017 were included. Collected data included information about demographics, cardiovascular risk factors, stroke subtype and National Institute of Health Stroke Scale (NIHSS) score. Estimated and measured body-weights were recorded. Modified Rankin scale (mRS) of 2 or more defined unfavorable outcome. The study included 150 patients. Median age was 64 -years (IQR 55-75) with male preponderance (67%) and median NIHSS score of 9 points (IQR 6-17). Mean measured weight of our study population was 58 (SD 13) kg. Median difference between actual and estimated body-weight was 3 kg (IQR 1.5-6). Difference was more than 10% in 35 (23.3%) patients. Good functional outcome (mRS 0-1) was achieved by 74 (49.3%) patients and 10 (6.8%) developed SICH. NIHSS (OR 1.288; 95% CI 1.157-1.435, p < 0.001) and large artery atherosclerosis (OR 5.878; 95% CI 1.929-17.910, p = 0.002) were independent predictors of unfavorable functional outcome. Our finding of the statistically insignificant 2.5-fold increase in poor outcomes among patients where the estimated and actual weight differed by more than 10% should be interpreted with caution due to the limited sample size. Significant difference occurs between estimated and actual body-weight in a considerable proportion of thrombolysed AIS patients. However, this discrepancy does not affect functional outcome or the risk of SICH.

Continuing Burden of Rheumatic Heart Disease in India.

Rheumatic heart disease (RHD) disables millions in Asia and Africa. Epidemiological data and clinical studies in India have reported a significant decline in its prevalence in last century. Global Burden of Disease (GBD) study estimated that RHD in India led to 395/100000 disability adjusted life years (DALYs) and 9.2/100000 deaths in 1990. This declined to 270/100000 and 7.9/100000, respectively, in 2017. School-based epidemiological studies in India have reported decline in clinically diagnosed RHD. On the other hand, GBD study has reported that in terms of absolute numbers, India contributes to one-third of global RHD burden. RHD in 1990 led to 3.44 million DALYs and 80,470 deaths which has increased to 3.73 million DALYs and 108,460 deaths in 2017. India Disease Burden Initiative has reported high RHD burden in many less developed states of the country, e.g., Bihar, Odisha, Assam, Chhattisgarh, Uttar Pradesh, etc. Echocardiographic epidemiology studies have reported high burden of subclinical RHD. Significant proportions of patients in hospital-based echocardiographic clinics have RHD and it contributes to 25-45% of cardiac surgeries in government hospitals. The continuing burden of RHD needs proper public health and clinical response.

Characteristics and Outcomes of Hospitalized Young Adults with Mild Covid -19.

BACKGROUND: Stormy course has been reported among hospitalized adults with COVID-19 in high- and middle-income countries. To assess clinical outcomes in consecutively hospitalized patients with mild covid-19 in India we performed a study. METHODS: We developed a case registry of successive patients admitted with suspected covid-19 infection to our hospital (n=501). Covid-19 was diagnosed using reverse transcriptase polymerase chain reaction (RT-PCR). Demographic, clinical, investigations details and outcomes were recorded. Descriptive statistics are presented. RESULTS: Covid-19 was diagnosed in 234 (46.7%) and data compared with 267 (53.3%) negative controls. Mean age of covid-19 patients was 35.1±16.6y, 59.4% were <40y and 64% men. Symptoms were in less than 10% and comorbidities were in 4-8%. History of BCG vaccination was in 49% cases vs 10% controls. Cases compared to controls had significantly greater white cell (6.96+1.89 vs 6.12+1.69x109 cells/L) and lower lymphocyte count (1.98+0.79 vs 2.32+0.91x109 cells/L). No radiological and electrocardiographic abnormality was observed. All these were isolated or quarantined in the hospital and observed. Covid-19 patients received hydroxychloroquine and azithromycin according to prevalent guidelines. One patient needed oxygen support while hospital course was uncomplicated in the rest. All were discharged alive. Conversion to virus negative status was in 10.2±6.4 days and was significantly lower in age >40y (9.1±5.2) compared to 40-59y (11.3±6.1) and ≥60y (16.4±13.3) (p=0.001). CONCLUSIONS: This hospital-based registry shows that mildly symptomatic or asymptomatic young covid-19 patients have excellent prognosis.

"PGI Score": A Simplified Three-point Prognostic Score for Acute Aluminum Phosphide Poisoning.

INTRODUCTION: Aluminum phosphide (AlP) ingestion for self-harm is associated with a high case-fatality rate (CFR) in low- and middle-income countries. A reliable and accurate prognostic scoring tool is required for appropriate triaging, to guide clinical decision-making, and to evaluate the efficacy of therapeutic interventions for the patients with AlP toxicity. MATERIALS AND METHODS: We performed a prospective cohort study in a tertiary care hospital in north India in patients aged 15 years and over with acute AlP poisoning, investigating the parameters associated with CFR, and developing a reliable and simple prediction score. RESULTS: The CFR was 51% in this cohort of 105 patients. Three parameters-pH <7.25, score on Glasgow coma scale (GCS) <13, and systolic blood pressure (SBP) <87 mm Hg were most robust predictors of CFR (odds ratio; 12.614, 18.621, and 17.600, respectively; area under the receiver operating characteristic curve-0.808, 0.796, and 0.776, respectively). Based on these parameters (with 1 point to each), a prognostic score was developed, ranging from 0 to 3 points. A total score of 3 had a 98.2% specificity and a positive predictive value of 96.4%, whereas a score ≤1 had a 100% sensitivity and 100% negative predictive value. CONCLUSION: A scoring system based on low pH (P), low GCS score (G), and impaired or low SBP (I) ("PGI" score) may provide a simplified predictive model for mortality in AlP poisoning. HOW TO CITE THIS ARTICLE: Pannu AK, Bhalla A, Sharma A, Sharma N. "PGI Score": A Simplified Three-point Prognostic Score for Acute Aluminum Phosphide Poisoning. Indian J Crit Care Med 2020;24(9):790-793.

Can short-term video-EEG substitute long-term video-EEG monitoring in psychogenic nonepileptic seizures? A prospective observational study.

BACKGROUND: Psychogenic nonepileptic seizures (PNES), the commonest nonepileptic event, represent 20-30% of drug-resistant epilepsy. Correct identification of PNES avoids unnecessary hospitalization and exposure of antiepileptic drugs (AEDs), and helps implement appropriate psychological treatment. Long-term video-electroencephalography (LTVEEG) is the gold standard test to diagnose PNES. However, in a poor-resource country like India, hypothetically, short-term video-electroencephalography (STVEEG) may substitute it, as its usefulness is established in attack disorders. OBJECTIVE: The objective of this study was to evaluate effectiveness of STVEEG in PNES and to look into their clinical profile and outcome. DESIGN/METHODS: Consecutive cases of PNES diagnosed with STVEEG or LTVEEG during 2015-16 (two years) were enrolled. All cases were followed for 12 months or more. Detailed clinical evaluation was done including demography, semiology, coexisting anxiety/depressive disorders, and seizure frequency at time of first diagnosis and follow-up. The PNES were classified as Type I hypermotor, type II hypomotor, and type III unclassified/mixed. Favorable outcome was defined as seizure freedom or >50% reduction in seizure frequency while unfavorable outcome was defined as <50% reduction in seizure frequency on follow-up at 6 and 12 months. RESULTS: Among 57 patients with PNES [median age of onset 24 years (10-69 years), F:M ratio = 7:3)], STVEEG ± induction could record event(s) in 80.7% while the rest required LTVEEG to confirm diagnosis. Among 82 events analyzed, the mean ±â€¯2 standard deviation (SD) duration of events was 5'14″ ±â€¯13'4″. Sixty-two (75.6%) and 10 (12.1%) events were hypermotor and hypomotor respectively, while 10 (12.1%) were unclassified/mixed. Forty-five (79%) patients had pure PNES, while 12 (21%) had coexistent epilepsy. Forty-nine (86%) and 54 (94.7%) patients had statistically significant reduction of seizure frequency (favorable outcome), at 6 and 12 months of follow-up respectively, while the rest had an unfavorable outcome. CONCLUSIONS: The STVEEG has a remarkably good yield in diagnosing PNES, and it may be used when LTVEEG is not feasible. However, further studies are needed to show if it can substitute LTVEEG in PNES.

Comparison of the newer proposed diagnostic score with the World Heart Federation criteria for echocardiographic detection of rheumatic heart disease.

INTRODUCTION: Echocardiography has been found to be a much better screening tool compared to clinical examination for the detection of rheumatic heart disease (RHD) in asymptomatic school children living in the RHD endemic areas. Recently, World Heart Federation (WHF) published echocardiographic criteria for the diagnosis of RHD. The present study was done to compare the performance of the newer proposed, quantitative diagnostic score against the qualitative WHF criteria in a field survey of asymptomatic school children belonging to the district having high prevalence of RHD. METHODS: 3000 asymptomatic school children studying in rural and urban schools of Bikaner district were screened both by clinical examination and echocardiography performed in parallel. The WHF criteria and the proposed diagnostic score were applied simultaneously for the diagnosis of RHD. RESULTS: A high prevalence of subclinical RHD was found. There was complete agreement between the two sets of criteria for the diagnosis of RHD. However, there was discrepancy in grading the severity of disease. The diagnostic score proved superior to the WHF criteria in grading the disease severity accurately. CONCLUSIONS: Diagnostic score captures the disease spectrum of RHD better than WHF criteria and reduces the subjectivity in the diagnosis of RHD.