Delay in diagnosis is the most important proximate reason for mortality in hereditary angio-oedema: our experience at Chandigarh, India.

BACKGROUND: Hereditary angio-oedema (HAE) is a rare autosomal dominant disorder characterized clinically by recurrent episodes of nonpruritic subcutaneous and/or submucosal oedema. Laryngeal oedema is the commonest cause of mortality in patients with HAE. Prior to the availability of first-line treatment options for the management of HAE, mortality was as high as 30%. Mortality has significantly declined in countries where first-line treatment options are available and patients can access these therapies. There is a paucity of literature on the outcomes of patients with HAE in developing countries where availability of and access to first-line treatment options are still a challenge. OBJECTIVES: To report our experience on mortality in patients with HAE and to report factors associated with the death of these patients. METHODS: We carried out a record review of all patients diagnosed with HAE between January 1996 and August 2022. Families with HAE who had reported the death of at least one family member/relative from laryngeal oedema were studied in detail. RESULTS: Of the 65 families (170 patients) registered in the clinic, 16 families reported the death of at least one family member/relative from laryngeal oedema (total of 36 deaths). Of these 16 families, 14 reported that 1 or more family members had experienced at least 1 attack of laryngeal oedema. One patient died during follow-up when she was taking long-term prophylaxis with stanozolol and tranexamic acid, while the remaining 35 patients were not diagnosed with HAE at the time of their death. At the time of death of all 36 patients, at least 1 other family member had symptoms suggestive of HAE, but the diagnosis was not established for the family. CONCLUSIONS: To our knowledge, this is the largest single-centre cohort of patients with HAE in India reporting mortality data and factors associated with death in these families. The delay in diagnosis is the most important reason for mortality.

Epilepsy Smart Schools: Educational intervention improves knowledge, attitude, and practices regarding epilepsy among school teachers.

INTRODUCTION: Discrimination and stigma associated with epilepsy in schools impact the academic and mental aptitude of children with epilepsy. Teachers pre-sensitized to seizures exhibit a positive attitude along with better knowledge about epilepsy. The aim was to assess the impact of an interactive one-day educational workshop regarding epilepsy on the prevalent knowledge, attitude, and practices toward epilepsy among school teachers. METHODS: Conducted in December 2021 in a tertiary care teaching hospital of rural background in Northern India, this cross-sectional study included school teachers from government schools of Faridkot district of Punjab. The intervention consisted of a one-day interactive workshop on epilepsy and school health consisting of 100 minutes of lectures (4 lectures each of 25 minutes), 60 minutes of role plays, and 20 minutes of active discussion with participants (5 minutes after each session). The lectures were prepared using World Health Organization's Mental Health Gap (WHO's mhGAP) guidelines and elucidated knowledge regarding epilepsy and skills to provide first aid to seizures. School teachers were assessed on a pre and post-test structured questionnaire to assess their knowledge of, attitude, and practices regarding epilepsy before and immediately after the intervention. RESULTS: Two hundred and thirty teachers participated and the majority were from government primary schools, mean age was 43 ± 7 years and females (n = 121,53%) outnumbered males. Commonly reported sources of information regarding epilepsy by school teachers were family and friends (n = 91,40%) followed by social (n = 82, 36%) and public media (n = 81,35%), and the least common were doctors (n = 56,24%) and healthcare workers (n = 29, 13%). Fifty-six percent (n = 129) had witnessed seizures in either a stranger(n = 84,37%), family, or friend (n = 31,13%) and student of their class(n = 14,6%). Post-educational intervention, significant improvement was seen in the knowledge of and attitude regarding epilepsy including recognizing subtle features of epilepsy like blank stare (pre/post = 5/34) and transient change in behavior (pre/post = 16/32), non-contagiousness of epilepsy (pre/post = 158/187)and belief that children with epilepsy have normal intelligence (pre/post = 161/191) and a significant decrease in a number of teachers who thought that they need more time and attention in class (pre/post = 181/131). Post-educational sessions, significantly more number of teachers would allow children with epilepsy in their classroom (pre/post = 203/227), follow correct ways to provide first aid for seizures, and would allow their participation in all extracurricular activities even in high-risk outdoor games like swimming (pre/post = 4/36) and deep sea diving (pre/post = 7/18). CONCLUSION: The educational intervention had a positive impact on the knowledge, practices, and attitude regarding epilepsy but had a few, unexpected reverse effects as well. A single workshop may not be aptly adequate to provide accurate information regarding epilepsy. Sustained efforts in this direction are needed at the national and global level to develop the concept of "Epilepsy Smart Schools".

Novel SERPING1 gene mutations and clinical experience of type 1 hereditary angioedema from North India.

BACKGROUND: There is paucity of literature on long-term follow-up of patients with hereditary angioedema (HAE) from developing countries. OBJECTIVE: This study was carried out to analyze the clinical manifestations, laboratory features, and genetic profile of 32 patients (21 male and 11 female) from 23 families diagnosed with HAE between January 1996 and December 2019. METHODS: Data were retrieved from medical records of Paediatric Immunodeficiency Clinic, Postgraduate Institute of Medical Education and Research, Chandigarh, India. RESULTS: Median age at onset of symptoms was 6.25 years (range 1-25 years), and median age at diagnosis was 12 years (range 2-43 years). Serum complement C4 level was decreased in all patients. All patients had low C1-esterase inhibitor (C1-INH) quantitative level (type 1 HAE). SERPING1 gene sequencing could be carried out in 20 families. Of these, 11 were identified to have a pathogenic disease-causing variant in the SERPING1 gene. While 2 of these families had a previously reported mutation, remaining 9 families had novel pathogenic variants in SERPING1 gene. Because of non-availability of C1-INH therapy in India, all patients were given long-term prophylaxis (attenuated androgens or tranexamic acid (TA) or a combination of the 2). Life-threatening episodes of laryngeal edema were managed with fresh-frozen plasma (FPP) infusions. We recorded one disease-related mortality in our cohort. This happened in spite of long-term prophylaxis with stanozolol and TA. CONCLUSIONS: We report largest single-center cohort of patients with HAE from India. Attenuated androgens, fibrinolytic agents, and FPP may be used for management of HAE in resource-limited settings.

Association of CD4/CD8 Ratio with Viral Load, Genotype and Cirrhosis in Chronic Hepatitis C.

ABSTRACT: The interplay between Hepatitis C virus (HCV) and immune system, especially T lymphocytes play a major role in the clearance of virus and in development of liver cell injury resulting in replacement of healthy tissue with fibrous scar tissue. OBJECTIVES: To evaluate the association of CD4/CD8 ratio with viral load and genotype of HCV and to evaluate the correlation of CD4/CD8 ratio and CD4 and CD8 cell counts with liver function tests in HCV infected patients. METHODS: Forty patients of Chronic Hepatitis C infection were enrolled for study. Immunophenotyping by flowcytometry for measurement of CD4 and CD8 T cell counts was used and the percentages of cells expressing CD4 and CD8 were estimated per lymphocyte population. HCV viral load quantitative was done by Roche Taqman Method. RESULTS: The CD4/CD8 ratio was not found to have any significant correlation with HCV viral load. However, it showed a significant difference in the two HCV genotypes, the ratio being higher in genotype 3 than in genotype 1. It showed no significant correlation with liver function tests except serum albumin which had significant positive correlation with CD4/CD8 ratio. The ratio was also found to be significantly decreased in patients with cirrhosis of liver. CONCLUSION: Hepatitis C virus genotype but not viral load influences the immune response to HCV infection. The CD4/CD8 ratio significantly decreases in patients with liver cirrhosis than in normal and fatty liver.

Efficacy and Safety of Oral Tolvaptan Therapy in Hospitalized Cirrhotic Patients with Hyponatremia.

BACKGROUND: Tolvaptan is an orally administered, nonpeptide, selective arginine vasopressin V(2) receptor antagonist that increases free water clearance, thereby correcting and increasing the low serum sodium levels in patients of cirrhosis, where hyponatremai is am major encountered problem. AIMS: Evaluate the efficacy and tolerabilty of tolvaptan in cirrhotics with symptomatic hyponatremia that resist correction with fluid restriction. Intellectual improvement assessed using Short Portable Mental Status Questionnaire (SPMSQ) pre and post therapy(on conclusion). Adverse drug reactions monitored to assess safety. METHDOLOGY: Study design: Prospective, pre and post drug efficacy and safety evaluating study with permission from ethical committe. Study Population: one hundred cirrhotic patients, irrespective of etiology, with hyponatremia, who fulfill the inclusion criteria. Protocol: All enrolled patients, treated with oral Tolvaptan at doses of 15 mg once daily in addition to the concurrent treatment regimen. Tolvaptan therapy was concluded as soon as the patient reached the normal sodium levels, which were monitored daily. RESULTS: Our study population had a majority of Hepatitis C patients (49%). Mean sodium levels at baseline were 125.79 + 3.49 which had a significant (130.25+3.28), and highly significant (133+ 3.19) change post 48 and 72 hours. In clinical parameters, urine output was altered significantly (pre drug mean 1530.76+619.02 to post drug mean of 1783+563.01. Body weight and Abdominal girth changes were not significant.

A child with X-linked agammaglobulinemia and Kawasaki disease: an unusual association.

An association of X-linked agammaglobulinemia (XLA) with Kawasaki disease (KD) is very uncommon. Only two case reports are available so far in pediatric literature. Patients with XLA have recurrent infections and physical examination have absent lymph nodes and tonsils. Laboratory investigations reveal hypogammaglobulinemia and reduced or absent B cells on flow cytometry. KD is a medium vessel vasculitis. Here, we report a 12 year old boy with X-linked agammaglobulinemia on regular replacement intravenous immunoglobulin who developed KD on follow-up. This is an uncommon occurrence.

X-linked agammaglobulinemia: Twenty years of single-center experience from North West India.

BACKGROUND: X-linked agammaglobulinemia (XLA) is an X-linked genetic defect in maturation of B lymphocytes that results in the absence of B lymphocytes in the peripheral blood and profound hypogammaglobulinemia. It is caused by a mutation in the BTK gene located on the X chromosome. There are no large series describing XLA from the developing world. OBJECTIVE: To analyze the clinical features, immunologic and genetic characteristics, and outcomes of 36 patients with XLA diagnosed and managed for a period of 2 decades. METHODS: Diagnosis of XLA was made on the basis of presence of BTK gene mutation or marked reduction of B lymphocytes in peripheral blood with a family history of an affected male relative. The diagnosis was confirmed by genetic mutation studies in 28 patients with 25 unique mutations in the BTK gene. RESULTS: There was a significant delay in diagnosis in most of the patients. The mean (SD) delay in the diagnosis was 4.2 (3.5) years. Point mutations were the most common mutations detected, accounting for 68% of all mutations. Deletions and insertions were also seen in a few cases. Four of the mutations are novel mutations that have not been previously reported. Seven of the 36 patients (19%) were dead at the time of analysis in the present cohort. The mean survival was 137 months (95% confidence interval, 13-163 months). CONCLUSION: The present study is perhaps the largest series of patients with XLA from any developing country so far.

Early Complement Component Deficiency in a Single-Centre Cohort of Pediatric Onset Lupus.

OBJECTIVES: To assess complement levels C1q, C2, C3 and C4 in children with pediatric-onset lupus during the quiescent stage of disease. METHODS: Thirty-four consecutive children with pediatric-onset SLE (onset below 12 years), in the quiescent stage were enrolled for the study. Twenty-nine age and sex matched healthy children were also enrolled for the purpose of comparison. Complement C1q and C2 levels were estimated by enzyme-linked immunosorbent assay (ELISA) whereas C3 and C4 were measured by end-point nephelometry. Genetic mutation analysis and functional assessment of classical complement pathway by ELISA were carried out in children with depressed levels of these complements. The study protocol was approved by the Institute Thesis Committee and the Institute Ethics Committee. RESULTS: Mean complement C1q, C2, C3 and C4 levels were 50.32, 17.28, 1320 and 236 mg/L respectively. Levels of complements were low in 7/34 children with SLE. An early age at onset, low anti-dsDNA titres and predominant skin manifestations were noted in children with decreased levels of complement C1q. Mutation analysis of C1qA gene revealed a homozygous nonsense mutation: C1QA (NM_015991) c.622C>T, p.Q208X in one child. A homozygous acceptor splice site mutation at the -2 position of intron2 of C1QA (c.164-2A>C) was detected in another child. The age at onset of disease was early in both these children, at 2.5 and 1.5 years respectively. CONCLUSION: Children with inherited deficiency of C1q and other early complement components present with early onset lupus that has a distinct clinical and immunological profile.

IMPETUS Stroke: Assessment of hospital infrastructure and workflow for implementation of uniform stroke care pathway in India.

BACKGROUND: India accounts for 13.3% of global disability-adjusted life years (DALYs) lost due to stroke with a relatively younger age of onset compared to the Western population. In India's public healthcare system, many stroke patients seek care at tertiary-level government-funded medical colleges where an optimal level of stroke care is expected. However, there are no studies from India that have assessed the quality of stroke care, including infrastructure, imaging facilities, or the availability of stroke care units in medical colleges. AIM: This study aimed to understand the existing protocols and management of acute stroke care across 22 medical colleges in India, as part of the baseline assessment of the ongoing IMPETUS stroke study. METHODS: A semi-structured quantitative pre-tested questionnaire, developed based on review of literature and expert discussion, was mailed to 22 participating sites of the IMPETUS stroke study. The questionnaire assessed comprehensively all components of stroke care, including human resources, emergency system, in-hospital care, and secondary prevention. A descriptive analysis of their status was undertaken. RESULTS: In the emergency services, limited stroke helpline numbers, 3/22 (14%); prenotification system, 5/22 (23%); and stroke-trained physicians were available, 6/22 (27%). One-third of hospitals did not have on-call neurologists. Although non-contrast computed tomography (NCCT) was always available, 39% of hospitals were not doing computed tomography (CT) angiography and 13/22 (59%) were not doing magnetic resonance imaging (MRI) after routine working hours. Intravenous thrombolysis was being done in 20/22 (91%) hospitals, but 36% of hospitals did not provide it free of cost. Endovascular therapy was available only in 6/22 (27%) hospitals. The study highlighted the scarcity of multidisciplinary stroke teams, 8/22 (36%), and stroke units, 7/22 (32%). Lifesaving surgeries like hematoma evacuation, 11/22 (50%), and decompressive craniectomy, 9/22 (41%), were performed in limited numbers. The availability of occupational therapists, speech therapists, and cognitive rehabilitation was minimal. CONCLUSION: This study highlighted the current status of acute stroke management in publicly funded tertiary care hospitals. Lack of prenotification, limited number of stroke-trained physicians and neurosurgeons, relatively lesser provision of free thrombolytic agents, limited stroke units, and lack of rehabilitation services are areas needing urgent attention by policymakers and creation of sustainable education models for uniform stroke care by medical professionals across the country.

Assessment of Cardiovascular Parameters on Submaximal Treadmill Exercise in Obese versus Nonobese Adults.

Background: Obesity and overweight, irrespective of metabolic status, confer an increased risk of adverse consequences including cardiovascular diseases (CVDs). The mechanisms underlying altered cardiovascular responses in obese individuals during and after submaximal treadmill exercise are the subjects of great interest to public health. After graded exercise, delayed heart rate recovery (HRR), exaggerated blood pressure (BP) response, and prolongation of QT interval are the powerful predictors of cardiovascular morbidity and mortality that may facilitate timely identification of individuals at risk of CVD and help to evaluate the effectiveness of treatment interventions. Aim: To compare the cardiovascular parameters on submaximal treadmill exercise in obese and nonobese adults. Materials and Methods: This study was conducted on 80 subjects, 40 obese (cases) and 40 normal-weight individuals (controls), belonging to the age group of 18-60 years. Each participant was subjected to submaximal treadmill exercise according to the Bruce protocol. Heart rate (HR), systolic BP and diastolic BP (SBP and DBP), mean arterial pressure (MAP), QT and corrected QT (QTc) intervals, and rate pressure product (RPP) were measured preexercise, immediately after exercise, and during passive recovery at 1 min and 5 min after exercise. The Chi-square test and Mann-Whitney U-test, whichever is appropriate, were employed for the comparison of variables between the two study groups. P < 0.05 was considered statistically significant. Results: Mean HR immediately after exercise, at 1 min and 5 min postexercise was significantly higher in obese when compared to nonobese participants (P = 0.006, P = 0.001, P = 0.001) despite similar resting HR in both the groups (P = 0.874). Mean SBP, DBP, MAP, and RPP were significantly higher in obese in comparison to nonobese subjects in all stages, i.e. before exercise, immediately after exercise, at 1 min and 5 min after exercise. QT and QTc intervals were also found to be significantly greater in obese than nonobese subjects in all stages (P = 0.001 each). Conclusion: Obese subjects had higher resting BP (SBP, DBP, and MAP), QT/QTc interval, RPP, and increased response to submaximal treadmill exercise activity. Delayed HRR after exercise was also noted in obese subjects which indicates that obese populations are at risk of developing CVDs due to alteration in autonomic functions with sympathetic hyperactivity.

Assessment of factors affecting response of direct-acting antivirals in chronic hepatitis C patients.

Background: Hepatitis C virus (HCV) is a universally prevalent pathogen and a major cause of liver-related morbidity and mortality worldwide. The evolution of antiviral therapy for HCV has rapidly progressed from interferon (IFN)-based therapies to IFN-free combinations of direct-acting antivirals (DAAs). Aims: This study aims to assess the response of DAAs in chronic hepatitis C (CHC) patients and to study the various factors affecting the response of DAAs in CHC. Settings and Design: This longitudinal observational study spanning over a year was conducted in the Medicine department of a tertiary care teaching hospital. Materials and Methods: The study was conducted on 400 adult CHC patients, diagnosed by a positive anti-HCV antibody test and a detectable viral load (HCV RNA) by real time polymerase chain reaction (RT-PCR), registered for treatment with DAAs. The first 400 patients satisfying the eligibility criteria were enrolled by non-probability consecutive sampling. All the participants were treated as per the National Viral Hepatitis Control Programme (NVHCP) guidelines. Repeat HCV viral load was done at or after 12 weeks of completion of anti-viral therapy to ascertain sustained virological response (SVR). Various factors which might predict treatment response were analyzed. Statistical Analysis Used: The continuous variables were expressed as mean and standard deviation, while the categorical variables were summarized as frequencies and percentages. The Student's independent t-test was employed for the comparison of continuous variables. The Chi-square or Fisher's exact test, whichever is appropriate, was employed for the comparison of categorical variables. Multivariate Logistic Regression was used to identify the independent predictors of treatment nonresponse. A P < 0.05 was considered statistically significant. Results: The mean age of the subjects was 42.3 ± 15.23 years with a male-to-female ratio of 1.96:1. Most of the patients (80.5%) were non-cirrhotic; among 19.5% cirrhotic, 13% were compensated while 6.5% were decompensated cirrhotic. The overall SVR done at or after 12 weeks of completion of treatment was 88.75%. Age, gender distribution, occupation, socioeconomic status, educational status, body mass index, treatment regimen, duration of treatment, and baseline viral load did not alter the treatment response. Among comorbidities, only diabetes mellitus (DM) and human immunodeficiency virus (HIV) co-infection adversely affected the treatment response (P = 0.009 and P < 0.001, respectively). Intravenous (IV) drug abuse was significantly associated with treatment failure (P < 0.001). The presence of liver cirrhosis (P < 0.001), thrombocytopenia (P < 0.001), elevated transaminases (alanine transaminase: P = 0.021, aspartate transaminase: P < 0.001), and previous treatment experience (P = 0.038) were other significant predictors of treatment failure. Conclusions: DAAs are highly efficacious drugs in the treatment of CHC with a high rate of treatment response. Significant predictors of CHC treatment failure included comorbidities especially DM and HIV co-infection, IV drug abuse, presence of liver cirrhosis, thrombocytopenia, elevated transaminases, and previous treatment experience. However, independent predictors of treatment nonresponse observed in this study were thrombocytopenia, IV drug abuse, and liver cirrhosis.

Résumé Contexte: Le virus de l'hépatite C (VHC) est un agent pathogène universellement répandu et une cause majeure de morbidité et de mortalité liées au foie dans le monde. L'évolution de la thérapie antivirale pour le VHC a rapidement progressé des thérapies à base d'interféron (IFN) à des combinaisons sans IFN de médicaments à action directe antiviraux (AAD). Objectifs: Cette étude vise à évaluer la réponse des AAD chez les patients atteints d'hépatite C chronique (HCC) et à étudier les différents facteurs affectant la réponse des AAD dans les CHC. Cadres et conception : Cette étude observationnelle longitudinale s'étalant sur un an a été menée dans le département de médecine d'un hôpital universitaire de soins tertiaires. Matériels et méthodes: L'étude a été menée sur 400 patients adultes atteints d'HCC, diagnostiqués par un test d'anticorps anti-VHC positif et une charge virale détectable (ARN du VHC) par réaction en chaîne par polymérase en temps réel, inscrit pour le traitement par DAA. Les 400 premiers patients répondant aux critères d'éligibilité ont été enrôlés par échantillonnage consécutif non probabiliste. Tous les participants étaient traités conformément aux directives du programme national de contrôle de l'hépatite virale. La charge virale répétée du VHC a été effectuée à ou après 12 semaines d'achèvement traitement antiviral pour déterminer la réponse virologique soutenue (RVS). Divers facteurs susceptibles de prédire la réponse au traitement ont été analysés. Analyse statistique utilisée: les variables continues ont été exprimées sous forme de moyenne et d'écart-type, tandis que les variables catégorielles ont été résumés sous forme de fréquences et de pourcentages. Le test t indépendant de Student a été utilisé pour la comparaison des variables continues. Le chi carré ou Le test exact de Fisher, selon le cas, a été utilisé pour la comparaison des variables catégorielles. La régression logistique multivariée a été utilisée identifier les prédicteurs indépendants de la non-réponse au traitement. A P < 0.05 était considéré comme statistiquement significatif. Résultats: L'âge moyen des sujets était de 42.3 ± 15.23 ans avec un ratio hommes-femmes de 1.96:1. La plupart des patients (80.5%) étaient non cirrhotiques ; parmi 19.5% de cirrhose, 13% étaient compensés alors que 6.5% étaient cirrhotiques décompensés. La RVS globale effectuée à 12 semaines ou après la fin du traitement était 88.75%. Âge, répartition par sexe, profession, statut socio-économique, niveau d'instruction, indice de masse corporelle, schéma thérapeutique, durée du traitement, et la charge virale de base n'a pas modifié la réponse au traitement. Parmi les comorbidités, seuls le diabète sucré (DM) et l'immunodéficience humaine la co-infection par le virus (VIH) a affecté négativement la réponse au traitement (P = 0.009 et P < 0.001, respectivement). L'abus de drogues par voie intraveineuse (IV) a été significativement associée à l'échec du traitement (P < 0.001). La présence de cirrhose du foie (P < 0.001), thrombocytopénie (P < 0.001), élévation les transaminases (alanine transaminase: P = 0.021, aspartate aminotransférase: P < 0.001) et l'expérience de traitement antérieure (P = 0.038) étaient d'autres facteurs prédictifs significatifs d'échec thérapeutique. Conclusions: les AAD sont des médicaments très efficaces dans le traitement de l'HCC avec un taux de traitement élevé réponse. Les facteurs prédictifs significatifs d'échec du traitement des CHC comprenaient les comorbidités, en particulier la co-infection par le diabète et le VIH, l'abus de drogues par voie intraveineuse, la presence de cirrhose du foie, de thrombocytopénie, d'élévation des transaminases et d'antécédents de traitement. Cependant, des prédicteurs indépendants du traitement les non-réponses observées dans cette étude étaient la thrombocytopénie, l'abus de drogues intraveineuses et la cirrhose du foie. Mots-clés: Cirrhose, antiviraux à action directe, virus de l'hépatite C, toxicomanie par voie intraveineuse, réponse virologique soutenue, thrombocytopénie.

Juvenile dermatomyositis associated with autoantibodies to small ubiquitin-like modifier activating enzyme: a report of 4 cases from North India and a review of literature.

BACKGROUND: Juvenile dermatomyositis (JDM) is the commonest inflammatory myositis in children. The clinical phenotype is often characterized by the presence of myositis-specific antibodies (MSA). Antibodies to small ubiquitin-like modifier activating enzyme (SAE) are amongst the rarest MSA reported in children. MATERIALS AND METHODS: A review of medical records of all patients diagnosed to have JDM during the period January 1992-April 2022 in our institute was done. Case records of children with JDM who had significant positivity for anti-SAE antibody by myositis immunoblot were analysed in detail. RESULTS: Of the 140 children with JDM, MSA immunoblot was carried out in 53 patients-4 (7.5%) amongst these had significant positivity for anti-SAE antibodies. Median age of onset of symptoms was 5.5 years (range: 5-11 years). Clinical features at presentation included fever, photosensitivity, heliotrope rash, and Gottron papules. Clinically significant proximal muscle weakness was noted in 3/4 patients; 1 had no discernible weakness but had radiological evidence of myositis. None of the 4 patients had evidence of interstitial lung disease or calcinosis. All patients were treated with intravenous pulse methylprednisolone: subcutaneous weekly methotrexate and hydroxychloroquine. One patient received mycophenolate mofetil because of a relapse of muscle disease, while none received cyclophosphamide or biologics. Median follow-up duration was 21.5 months (range: 6-39 months). CONCLUSION: Anti-SAE antibodies were found in 4/53 (7.5%) of North Indian children with JDM. All 4 patients had predominant cutaneous manifestations followed by muscle disease. Response to treatment was brisk and sustained. None had developed calcinosis in the follow-up. KEY MESSAGES: 1. We report high prevalence of anti-SAE antibody positivity (7.5%) in North Indian cohort of JDM. 2. Cutaneous disease precedes muscle weakness in children with anti-SAE positive JDM. 3. No evidence of interstitial lung disease/calcinosis was seen in these children.

Clinico-hematological profile of pancytopenic adult patients in a tertiary care teaching hospital.

OBJECTIVE: The causes of pancytopenia vary in different populations depending on age, gender, nutrition, geographic location, standard of living, and exposure to certain infections and drugs. As the severity of pancytopenia and its underlying etiology determine the management and prognosis, identifying the correct etiology in a given case is crucial and helps in implementing timely and appropriate treatment. The objectives of this study were to study the clinical profile and hematological parameters of pancytopenic adults and to identify different etiologies of pancytopenia. This observational study was conducted in the Medicine department of a tertiary care teaching hospital. MATERIALS AND METHODS: The study was conducted on 100 adult patients aged 18-65 years presenting with pancytopenia. All the participants were subjected to detailed clinical examination and relevant investigations including bone marrow (BM) examination. Categorical variables were presented in number and percentage (%). Qualitative variables were correlated using the Chi-square test. A P =0.05 was considered statistically significant. RESULTS: A female preponderance was observed, and the majority of patients were aged between 18 and 40 years. The most common clinical features were generalized weakness, fever, and pallor. Seventy-four percent of patients were vegetarians; 58% had vitamin B12 deficiency, 25% had folic acid deficiency and 19% had a deficiency of both. The most common cause of pancytopenia was megaloblastic anemia (MA) (37%), followed by dimorphic anemia (DA) (26%), aplastic anemia (AA) (20%), and hematological malignancies (11%). CONCLUSION: MA, DA, and AA are the most prevalent etiologies of pancytopenia. BM examination is of utmost importance in the definitive diagnosis of pancytopenia and is useful in initiating timely treatment as a significant number of causes of pancytopenia are potentially curable.

Hepatitis B Prevalence and Risk Factors in Punjab, India: A Population-Based Serosurvey.

Background: The prevalence of hepatitis B virus (HBV) infection in Punjab, India, is unknown. Understanding the statewide prevalence and epidemiology can help guide public health campaigns to reduce the burden of disease and promote elimination efforts. Methods: A cross-sectional, population-based survey was conducted from October 2013 to April 2014 using a multistage stratified cluster sampling design. All members of selected households aged ≥5 years were eligible. Participants were surveyed for demographics and risk behaviors; serum samples were tested for total antibody to hepatitis B core (total anti-HBc), hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody (anti-HCV), and HCV RNA. HBsAg-positive specimens were tested for HBV genotype. Results: A total of 5543 individuals participated in the survey and provided serum samples. The prevalence of total anti-HBc was 15.2% (95% confidence interval [95% CI]: 14.1-16.5) and HBsAg was 1.4% (95% CI: 1.0-1.9). Total anti-HBc positivity was associated with male sex (adjusted odds ratio [aOR] 1.46; 95% CI: 1.21-1.75), older age (aOR 3.31; 95% CI: 2.28-4.79 for ≥60 vs. 19-29 years), and living in a rural area (aOR 2.02; 95% CI: 1.62-2.51). Receipt of therapeutic injections in the past 6 months also increased risk (4-8 injections vs. none; aOR 1.39; 95% CI: 1.05-1.84). Among those positive for total anti-HBc, 10.4% (95% CI: 8.1-13.2) were also anti-HCV positive. Conclusion: Punjab has a substantial burden of HBV infection. Hepatitis B vaccination programs and interventions to minimize the use of therapeutic injections, particularly in rural areas, should be considered.

Study Protocol: IMPETUS: Implementing a Uniform Stroke Care Pathway in Medical Colleges of India: IMPETUS Stroke.

Introduction: In India, a national program for stroke (national programme for the control of cardiovascular diseases, diabetes, cancer, and stroke) and stroke management guidelines exist. Its successful implementation would need an organized system of stroke care in practice. However, many challenges exist including lack of awareness, prehospital notification systems, stroke ready hospitals, infrastructural weaknesses, and rehabilitation. We present here a protocol to investigate the feasibility and fidelity of implementing a uniform stroke care pathway in medical colleges of India. Methods and Analysis: This is a multicentric, prospective, multiphase, mixed-method, quasi-experimental implementation study intended to examine the changes in a select set of stroke care-related indicators over time within the sites exposed to the same implementation strategy. We shall conduct process evaluation of the implementation process as well as evaluate the effect of the implementation strategy using the interrupted time series design. During implementation phase, education and training about standard stroke care pathway will be provided to all stakeholders of implementing sites. Patient-level outcomes in the form of modified Rankin Scale score will be collected for all consecutive patients throughout the study. Process evaluation outcomes will be collected and reported in the form of various stroke care indicators. We will report level and trend changes in various indicators during the three study phases. Discussion: Acute stroke requires timely detection, management, and secondary prevention. Implementation of the uniform stroke care pathway is a unique opportunity to promote the requirements of homogenous stroke care in medical colleges of India.

Correlation of Surrogate Markers of Insulin Resistance with Fasting Insulin in Type 2 Diabetes Mellitus Patients: A Study of Malwa Population in Punjab, India.

Context Insulin resistance (IR) and abnormal insulin secretion play a key role for the development of type 2 diabetes mellitus (DM). Aims We investigated the surrogate markers of IR, i.e., Homeostasis Model Assessment (HOMA), Quantitative Insulin Sensitivity Check Index (QUICKI), McAuley, and Fasting Insulin Resistance Index (FIRI) in type 2 DM patients. Also, fasting insulin (FI) levels were estimated in type 2 diabetics. Further, the correlation of FI with other surrogate markers of IR in type 2 DM was done. Settings and Design A hundred newly diagnosed patients with type 2 DM from Malwa population, Punjab, were considered for evaluation. Another 100 healthy individuals (age and sex-matched) were examined as controls. Methods and Material Fasting blood glucose, FI, and lipid profile were estimated, and IR was calculated using McAuley index (McA), HOMA, QUICKI, and FIRI. Statistical Analysis Used The statistical analysis was performed on the above-mentioned clinical interpretations. The Cohen's kappa test was used to affirm the agreement. Results FI levels in patients with type 2 diabetes were significantly higher (20.8 ± 9.05 µIU/L) than controls (7.93 ± 1.01 µIU/L). IR by surrogate markers was found significant in the study group. The 76% patients with type 2 diabetes ended up as resistant to insulin by FI measurement, almost equivalent to McA, 80%; HOMA, 88%; FIRI, 88%; and QUICKI, 90%. A notable correlation was highlighted between FI and McA manifesting IR ( p < 0.01, r = -0.85). We calculated the statistical correlation of FI with HOMA, QUICKI, and FIRI indices ( p < 0.01, r = 0.93; p < 0.01 r = -0.92; and p < 0.01, r = +0.93, respectively). The agreement visible from Cohen's kappa test also affirms the same ( k = 0.9 for McA). Conclusion We concluded that all the surrogate markers for IR were specific when compared with FI, but in terms of sensitivity McA was found to be more sensitive as it includes markers of dyslipidemia, which is the precipitating factor of metabolic derangements so as the IR in type 2 DM.

Potential role of noninvasive biomarkers during liver fibrosis.

Various types of liver disease exist, such as hepatitis and alcoholic liver disease. These liver diseases can result in scarring of liver tissue, cirrhosis, and finally liver failure. During liver fibrosis, there is an excess and disorganized accumulation of extracellular matrix (ECM) components which cause the loss of normal liver cell functions. For patients with chronic liver disease, fibrosis prediction is an essential part of the assessment and management. To diagnose liver fibrosis, several invasive and noninvasive markers have been proposed. However, the adoption of invasive markers remains limited due to their inherent characteristics and poor patient acceptance rate. In contrast, noninvasive markers can expedite the clinical decision through informed judgment about disease stage and prognosis. These noninvasive markers are classified into two types: Imaging techniques and serum biomarkers. However, the diagnostic values of biomarkers associated with liver fibrosis have also been analyzed. For example, the serum levels of ECM proteins can react to either matrix accumulation or degradation. During virus-host interactions, several regulatory steps take place to control gene expression, such as the change in cellular microRNA expression profiles. MicroRNAs are a class of non-coding RNAs (18-20 long nucleotides) that function by post-transcriptional regulation of gene expression. Although various noninvasive markers have been suggested in recent years, certain limitations have restricted their clinical applications. Understanding the potential of non-invasive biomarkers as a therapeutic option to treat liver fibrosis is still in progress.

Autoantibody Profile of Children with Juvenile Dermatomyositis.

OBJECTIVE: To study autoantibody profile in juvenile dermatomyositis (JDM) and to look for phenotypic associations of these autoantibodies, if any. METHODS: Thirty-four children with JDM with a minimum follow-up duration of 24 mo were enrolled. Clinical findings and investigations at the time of diagnosis were noted from the clinic records. At inclusion, they were clinically evaluated for residual disease, disease activity and complications. All the enrolled patients were tested for antinuclear antibodies (ANA), muscle specific antibodies (MSA) and myositis associated autoantibodies (MAA). RESULTS: ANA positivity was seen in 14/34 children. At least one MSA or MAA was present in 8/34 children. Anti-SRP, anti-MDA-5, and anti-Mi-2 antibodies were present in 4, 3, and 1 patient, respectively. Anti-SSA/Ro52 antibody was positive in 1 child. All four children with anti-SRP antibody were girls, who had polycyclic course. Two of them developed calcinosis. Prominent skin involvement with less severe muscle involvement and monocyclic course were seen in patients with anti-MDA-5 antibody. Two of them had arthritis/arthralgia at initial presentation. The only patient with anti-Mi-2 had normal muscle strength at enrollment. None of the patients had anti-synthetase antibodies (anti-Jo-1, anti-PL-7, anti-PL-12, anti-EJ), anti-Ku, anti-Scl-70, anti-NXP-2 or anti-HMG CoA. CONCLUSION: Eight patients tested positive for at least one MSA or MAA. The prevalence of autoantibodies was low. Positivity for anti-SRP, anti-MDA-5, anti-Mi-2 and anti-SSA/Ro52 antibodies was seen in 4, 3, 1 and 1 patients, respectively. Ethnic differences and testing for autoantibodies during/after therapy could be responsible for the low positivity rate for autoantibodies.

Prevalence of potentially inappropriate medication and its correlates in elderly hospitalized patients: A cross-sectional study based on Beers criteria.

BACKGROUND: The increase in the prescription of potentially inappropriate medication (PIM) in older adults with significant health consequences is a global concern. This study aimed to determine the prevalence of PIM prescription in older adults as identified by Beers criteria 2015 and 2019. MATERIALS AND METHODS: A cross-sectional study was carried out in older adults aged >65 years at a tertiary care postgraduate teaching hospital. All patients aged ≥65 years irrespective of their gender, admitted in the medical ward of the hospital with single/multiple comorbidities, and prescribed at least one daily medication, were included in the study. Data of patient history, patient case sheet, medication charts, laboratory reports, as well as radiological examinations test reports were retrieved from their files and were captured in a prevalidated data collection form. SPSS used for data analysis; multivariate logistic regression was used to determine the predictors of PIM prescribing and odds ratios (ORs) and 95% confidence intervals for ORs were computed. RESULTS: Study included 323 patients; 61.3% were male, 74% patients were 65-70 years of age, and 78% patients were illiterate. The overall prevalence of PIM uses according to the Beers criteria 2015 and 2019 was 60.1% and 61.9%, respectively. No association found between PIMs prescribes and diagnosis category. Male gender, age 76-80 years, and education 10-12th class were found to be significantly related to PIM prescription. CONCLUSION: This study reflects a critical view of noncompliance of Beers criteria for geriatric healthcare even in tertiary care hospitals in India. Creatinine clearance rate should be kept in view when prescribing medicines for elderly inpatients.