We determined the frequency and factors associated with the first clinical relapse after immunomodulator (IM) withdrawal in a cohort of children with inflammatory bowel disease on combination therapy. A total of 105 patients (89 with Crohn disease [CD]) in clinical remission were included (91 [86.7%] were on infliximab, 53 [50.5%] with methotrexate, and 52 on azathioprine). The median duration of combination therapy was 2.1 years (interquartile range [IQR] 1.3-2.8). Only 11 (10.5%) patients experienced a clinical relapse over a median duration of follow-up of 12.0 months (IQR 5.0-19.0) after IM discontinuation. The median baseline pediatric CD activity index in those with CD who relapsed after IM discontinuation was 47.5 (IQR: 35.0-55.0) versus those who did not relapse (median 35.0, IQR: 20.0-52.5; P = 0.04). In the patients who did not relapse, the median IFX trough level at IM discontinuation was 6.2 and 3.8 mu g/mL in those who relapsed.

Abstract Background Anti-tumor necrosis factor (anti-TNF) antagonists such as infliximab (IFX) are widely used for the treatment of inflammatory bowel disease (IBD). Early studies suggested that combination therapy with IFX and an immunomodulator drug (IM) such as azathioprine (AZA) or methotrexate (MTX) may help in optimising biologic pharmacokinetics, minimising immunogenicity, and improving outcomes. On the other hand, IM especially AZA, may increase infection and cancer risks with no clear evidence on long-term benefits of combination therapy. As such, stopping IM and continuation of an anti-TNF agent as a monotherapy in patients in remission seem to be a sensible strategy. However, there is no evidence to prove the efficacy of this strategy. The aim of this work was to examine frequency and factors associated with the first relapse after IM withdrawal in a cohort of children with IBD on combination therapy. Methods In a retrospective multicenter pediatric study, we determined the percentage of patients and investigated potential factors associated with the first relapse in a cohort of children and young adults with IBD on combination therapy of anti-TNF and IM after stopping IM. Cox regression analysis was used to assess factors associated with IBD relapse following IM withdrawal. Results A total of 79 patients (42, males, 62 Crohn’s disease) with 74 (93.7%) on IFX were included. In addition to the anti-TNF agent, 33 (41.8%) were on AZA and the rest were on MTX. The median duration of combination therapy was 2.0 (IQR 1.2–2.8) years. All participants were in clinical remission at the time of IM withdrawal. The median duration of follow-up after IM withdrawal was 11.0 (IQR 5.0–16.2) months. Only 8 (10.1%) patients relapsed over that period of follow-up. Age, sex, disease phenotype at diagnosis, family history of IBD, type of IM, and biochemical markers and clinical disease activity indices prior to IM stoppage did not predict a future relapse. Among those with CD on IFX who maintained remission, the median last IFX trough level before IM withdrawal was 6.25 Ug/ml (IQR: 4.04–8.70) vs. 3.8 Ug/ml (IQR: 2.40–11.6) in those who relapsed (p = 0.4). Conclusion Over short-term follow-up, the majority of children on combination therapy of IM and an anti-TNF agent remain in clinical remission after IM withdrawal.

Abstract Background Toxigenic Clostridioides difficile (C. difficile), previously known as Clostridium difficile, is an anaerobic gram-positive spore-forming opportunistic pathogen associated with profuse diarrhoea and gastroenteritis associated mortality, especially in children with inflammatory bowel disease (IBD). The aim of this work was to investigate the incidence and risk factors associated with Clostridioides difficile infection (CDI) in children with IBD in the province of Manitoba, Canada. Methods Our longitudinal population-based cohort comprised of all children and young adults <17 years diagnosed with IBD in the Canadian province of Manitoba between 2011 and 2019. The diagnosis of CDI was confirmed based on the Triage C. difficile immunoassay and polymerase chain reaction assay to detect the presence of toxigenic C. difficile. Fisher’s exact test was used to examine the relationship between categorical variables. Cox-regression model was used to estimate the risk of CDI development in IBD patients. Results Among the 261 children with IBD, 20 (7.7%) developed CDI with an incidence rate of 5.04 cases per 1000 person-years and the median age at diagnosis of 12.96 years (IQR: 9.33–15.81). The incidence rate of CDI among UC and CD patients were 4.16 cases per 1000 person-years and 5.88 cases per 1000 person-years, respectively (p = 0.46). Compared to children without CDI, those who had CDI were at increased risk of future exposure to systemic corticosteroids (hazard ratio (HR) = 4.30; 95% CI: 1.44–12.87) and anti-tumour necrosis factor (TNF) biologics (HR = 3.37; 95% CI: 1.13–10.09). Recurrence rate of CDI in our paediatric IBD population was 25%. Conclusion Our findings confirm that children with IBD are at a high risk of developing CDI, which may predict future escalation of IBD therapy.

Patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) often present with loco-regional disease; approximately 14% of patients present with metastatic disease. Despite aggressive primary therapy over 50% of newly diagnosed patients treated radically with either surgery and/or radiotherapy with/without chemotherapy will develop recurrent disease, with the majority of recurrences occurring locally. Standard therapy for these patients is a platinum-containing regime (PCCC) or PD-1 inhibitor.

ABSTRACT Objective: This prospective observational study aimed to examine the prevalence of obesity in a population‐based cohort of children and young adults newly diagnosed with inflammatory bowel disease (IBD) and assess their outcome in comparison to newly diagnosed normal/underweight patients. Methods: Our longitudinal population‐based cohort comprised all children younger than 17 years diagnosed with IBD in the province of Manitoba, Canada between 2012 and 2018. Cox regression model with adjustment for a priori covariates was used to examine the time to first relapse among patients who were obese/overweight at the time of IBD diagnosis in comparison to patients who were normal or underweight. Results: A total of 139 patients with IBD were followed up for a median duration of 1.09 (interquartile range: 0.53–2.62) years. Obesity was more common in children newly diagnosed with ulcerative colitis (UC) compared to those with Crohn disease (CD) (12.7% vs 0.0%; P = 0.005). Age at diagnosis poorly correlated with the body mass index z score ( R = 0.23; P = 0.01). The proportions of patients who were underweight at the time of IBD diagnosis among patients with UC and CD were 6.3% and 20.0%, respectively ( P = 0.01). The time to initial relapse was not found to be significantly associated with weight category at diagnosis in UC (adjusted hazard ratio = 0.77; 95% confidence interval: 0.40–1.63) or CD (adjusted hazard ratio = 0.83; 95% confidence interval: 0.20–3.51). Conclusion: Obesity was more common in children and young adults newly diagnosed with UC. The majority of the underweight children had CD.

Objective To assess the characteristics of inflammatory bowel disease and disease prognosis among children with elevated gamma glutamyltransferase (GGT) and primary sclerosing cholangitis (PSC)-ulcerative colitis (UC). Study design Our longitudinal, population-based cohort comprised all children and young adults diagnosed with UC in the Canadian province of Manitoba between 2011 and 2018. Diagnosis of PSC was confirmed based on a combination of cholestatic biochemical markers and cholangiographic features. The Fisher exact test with Bonferroni correction was used to examine the relationship between categorical variables. Results We enrolled 95 children with UC/Inflammatory bowel disease-unclassified with a median age at diagnosis of 14 years (IQR: 10.4-15.9 years) and 1399 person-years follow-up. Among them, 9 children developed PSC-UC, with an incidence rate of 6.43 new cases per 1000 person-years. In this cohort, 8 (72.7%) of 11 children with high baseline serum GGT levels developed PSC-UC in comparison with 1 (1.2%) of 84 children with normal serum GGT levels at baseline (P < .001). All children with high serum GGT levels at diagnosis had pancolitis in comparison with 63.9% of children with normal serum GGT levels (P = .01). Children with high serum GGT levels were more likely to be perinuclear neutrophil antibodies-positive than those with normal levels (90.9% vs 52.0%, P = .01). Conclusions Our findings indicated that pediatric patients with UC and with even mild elevations of serum GGT levels, especially at baseline, might be predisposed to develop PSC.

BACKGROUND:The study's objective was to investigate the incidence and risk factors associated with Clostridioides difficile (previously known as Clostridium) infection (CDI) in children with inflammatory bowel disease (IBD) in the province of Manitoba.METHODS:Our longitudinal population-based cohort was comprised of all children and young adults aged <17 years diagnosed with IBD in the Canadian province of Manitoba between 2011 and 2019. The diagnosis of CDI was confirmed based on the Triage C. difficile immunoassay and polymerase chain reaction assay to detect the presence of toxigenic C. difficile. The Fisher exact test was used to examine the relationship between categorical variables. A Cox regression model was used to estimate the risk of CDI development in IBD patients.RESULTS:Among 261 children with IBD, 20 (7.7%) developed CDI with an incidence rate of 5.04 cases per 1000 person-years, and the median age at diagnosis (interquartile range) was 12.96 (9.33-15.81) years. The incidence rates of CDI among UC and CD patients were 4.16 cases per 1000 person-years and 5.88 cases per 1000 person-years, respectively (P = 0.46). Compared with children without CDI, those who had CDI were at increased risk of future exposure to systemic corticosteroids (adjusted hazard ratio [aHR], 4.38; 95% confidence interval [CI], 1.46-13.10) and anti-tumor necrosis factor (anti-TNF) biologics (aHR, 3.31; 95% CI, 1.11-9.90). The recurrence rate of CDI in our pediatric IBD population was 25%.CONCLUSIONS:Our findings confirm that children with IBD are at high risk of developing CDI, which may predict future escalation of IBD therapy.

OBJECTIVE:Although anti-Saccharomyces cerevisiae antibodies (ASCAs) could be a useful biomarker in differentiating Crohn disease (CD) from ulcerative colitis (UC), their role as prognostic markers in children with CD has been underinvestigated. This longitudinal prospective observational study aimed to assess the prognostic value of ASCA status among children with CD managed using biologics.METHODS:The study population comprised children with inflammatory bowel disease diagnosed with CD from 2012 to 2018. Cox regression model with adjustment for a priori covariates was used to examine the response to anti-tumor necrosis factor (TNF) biological therapy among ASCA-positive patients in comparison to ASCA-negative patients.RESULTS:There were 273 measurements available from the study cohort comprising children with CD, who were followed up for a median duration of 14 months (interquartile range 5-42). ASCA-positive patients had a higher risk for moderate to severe clinical disease (odds ratio 2.88; 95% confidence interval [CI] 1.2-7.55) and extensive endoscopic distribution (odds ratio 3.30; CI 1.12-9.74) at baseline in comparison to ASCA-negative patients, respectively. In comparison to ASCA immunoglobulin G (IgG)-negative patients, ASCA IgG-positive patients who were treated with biologics had a significantly lower relapse rate (adjusted hazard ratio 0.12; CI 0.02-0.93). Ten (14%) patients had an unstable ASCA value with either ASCA immunoglobulin A or ASCA IgG status changing from positive to negative or vice versa.CONCLUSIONS:ASCA-positive children with CD present with more extensive (endoscopic) and clinically severe disease. ASCA IgG is a useful prognostic marker among children with CD who receive biologics.

Wernicke encephalopathy (WE) and Korsakoff psychosis (KP), together termed Wernicke-Korsakoff syndrome (WKS), are distinct yet overlapping neuropsychiatric disorders associated with thiamine deficiency. Thiamine pyrophosphate, the biologically active form of thiamine, is essential for multiple biochemical pathways involved in carbohydrate utilization. Both genetic susceptibilities and acquired deficiencies as a result of alcoholic and non-alcoholic factors are associated with thiamine deficiency or its impaired utilization. WKS is underdiagnosed because of the inconsistent clinical presentation and overlapping of symptoms with other neurological conditions. The identification and individualized treatment of WE based on the etiology is vital to prevent the development of the amnestic state associated with KP in genetically predisposed individuals. Through this review, we bring together the existing data from animal and human models to expound the etiopathogenesis, diagnosis, and therapeutic interventions for WE and KP.

Barth Syndrome (BTHS) is a rare X-linked genetic disease in which the specific biochemical deficit is a reduction in the mitochondrial phospholipid cardiolipin (CL) as a result of a mutation in the CL transacylase tafazzin. We compared the phosphokinome profile in Epstein-Barr-virus-transformed lymphoblasts prepared from a BTHS patient with that of an age-matched control individual. As expected, mass spectrometry analysis revealed a significant (>90%) reduction in CL in BTHS lymphoblasts compared to controls. In addition, increased oxidized phosphatidylcholine (oxPC) and phosphatidylethanolamine (PE) levels were observed in BTHS lymphoblasts compared to control. Given the broad shifts in metabolism associated with BTHS, we hypothesized that marked differences in posttranslational modifications such as phosphorylation would be present in the lymphoblast cells of a BTHS patient. Phosphokinome analysis revealed striking differences in the phosphorylation levels of phosphoproteins in BTHS lymphoblasts compared to control cells. Some phosphorylated proteins, for example, adenosine monophosphate kinase, have been previously validated as bonafide modified phosphorylation targets observed in tafazzin deficiency or under conditions of reduced cellular CL. Thus, we report multiple novel phosphokinome targets in BTHS lymphoblasts and hypothesize that alteration in the phosphokinome profile may provide insight into the pathophysiology of BTHS and potential therapeutic targets.

INTRODUCTION:The recent outbreaks of Hepatitis A in Kerala are suggestive of decrease in endemicity as most adults were not exposed during the childhood. In allopathic system of medicine, there is no established treatment for Hepatitis A and hence most people tend to rely on the alternate systems of medicine. The study was aimed at identifying the burden of Hepatitis A in the locality and to uncover the degree of dependence of the people on traditional systems of medicine. METHODS:The study spanned over 7 months and was conducted in Malappuram district of Kerala. A simple questionnaire having closed-ended questions was prepared and circulated among the physicians in the area. Demographic and other relevant details were obtained from the patients and the medicine system relied on was scrutinized. RESULTS:Of the 348 patients enrolled, majority of the patients were between the age of 10-30 years. The study revealed that females were more affected than males. Similarly people in rural areas were greater than those from urban areas. Most patients (73.28%) relied on Ayurvedic treatment after one week of onset of symptoms. DISCUSSION AND CONCLUSION:The preparations such as triphala which has great efficacy in treatment has to be further studied to establish the pathways and mechanism through which it acts. A collaborative effort between government, modern medicine and alternate medicine system can be highly effective in reducing the outbreaks of such epidemics through proper preventive and therapeutic strategies.

Coloprep is a bowel preparatory solution given before endoscopic procedures to get a unobscured internal vision. It has among its constituents’ sodium sulphate, potassium sulphate and magnesium sulphate which produce an osmotic effect in the bowel. However, the use of such agents in hyponatremic and patients predisposed to seizures can have adverse ramifications. The current case outlines manifestation of absence seizure in a 52-year-old male patient who was administered Coloprep for colonoscopy. There was absence of other predisposing factors and the symptoms were ameliorated using timely identification and rectification of the underlying derangements.

Aim: The study was aimed at assessing the cumulative incidence of hypoglycemia and precipitating risk factors among type 2 diabetes mellitus in-patients of a tertiary care hospital in South India.Methods: The prospective cross sectional study spanning 14 months was conducted in a tertiary care hospital in Kerala. All T2DM patients who were administered any form of insulin during the length of hospital stay was monitored for assessing the hypoglycemic episodes. Any patient with a GRBS value less than 70 mg/dL was defined to be hypoglycemic as per the ADA guidelines. The statistical analysis of collected data was performed using SPSS 18 for windows version.Results: Of the 1650 subjects enrolled in the study, 204 subjects developed hypoglycemia. The sample composed of 60.8% females and 39.2% males and the difference was significant with p = 0.02. A significant positive correlation was observed between HbA1c values and GRBS value, with a 2 tailed Pearson correlation coefficient of 0.027. On stratifying as per the modality of insulin dose prescribed, 72.5% of the hypoglycemic patients were found to have been administered fixed dose insulin.Conclusion: The cumulative incidence of institutional hypoglycemia among type 2 diabetic inpatients was gauged as 12.36%; among which, 26.96% had asymptomatic episodes. (C) 2016 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Abstract Background: The widespread misuse of antibiotics over the past several decades has been regarded as the contributing factor in the development of resistance toward them. Extended spectrum β-lactamases (ESBLs) are enzymes produced by certain bacteria that can make them resistant to certain antibiotics. Early detection of ESBL strains and judicious use of antibiotics and proper implementation of infection control strategies are essential to prevent the spread of this threat in the community. The study aimed at appraising the prevalence, risk factors and antimicrobial susceptibility pattern of ESBL-producing microorganisms. Methods: A prospective observational study was carried out in a tertiary care referral hospital located in Malappuram district of Kerala among inpatients with infection by ESBL-producing bacteria in order to estimate the prevalence, risk factors and their antibiotic susceptibility pattern. Results: Out of the total 1156 patients studied, 118 had confirmed diagnosis on the presence of ESBL-producing microorganisms. Overall, 9.79% of all samples growing Enterobacteriaceae yielded an ESBL producer. Out of the total isolates identified, 66.1% were urinary tract infections, 15.1% were respiratory tract infections, 14.4% were surgical site infections and the remaining constituted blood stream infections. The highest antimicrobial activity against ESBL-producing isolates was observed for meropenem. Conclusions: High prevalence of ESBL-producing organisms is evident in the study setting implicating the necessity to report the ESBL production along with the routine sensitivity reports supplemented with control measures which can assist a clinician in prescribing appropriate antibiotics.

AIM:To assess the prevalence of diabetes among inmates at old age care homes in south India and scrutinize their therapy, glycemic levels and burden of hypoglycemic episodes.MATERIALS AND METHODS:The medication record based observational study was conducted in 9 old-age care facilities across south India from February to September 2015. The cognitive and functional status were analysed and the prevalence of hypoglycemia estimated. Descriptive analysis was performed using SPSS 18.0 for windows.RESULTS:The prevalence, predisposing variables and therapeutic modalities used in 189 inmates of 9 old-age homes in Kerala. The mean age of the sample was estimated to be 71.3±3.4 years. 67.2% of the total inmates were found to be diabetic and met the inclusion criteria. Of the total patients, 72.44% had co-existence of both cognitive and functional impairment.86% patients developed hypoglycemia at least at some point during the therapy and insulin was found to be the drug used in majority of patients with the condition indicating that aggressive therapies can increase fatality due to hypoglycemia.CONCLUSIONS:Most guidelines call for an individualized therapeutic approach suing less aggressive strategies for patients vulnerable to hypoglycemia and geriatric population form such a substantial group. The current study highlights the necessity for special attention when considering therapeutic regimen among such patients.

Practice of prophylaxis against venous thromboembolism (VTE) following surgical procedures has been in the scenario for about half a century. Despite the surging evidence regarding the clinical and economic efficacy, the practice remains underutilized. The study was aimed at optimizing the prophylactic practices for prevention of VTE in the general surgical patients in a tertiary care hospital using a pharmacist assisted multi-strategy intervention. The prospective quasi-experimental study was conducted in general surgical department of a tertiary care hospital in Kerala. The initial audit phase was targeted at assessing the prevailing prophylactic practices and its adequacy in relation to American College of Chest Physicians (ACCP) guidelines. This was followed by an educational phase where physicians were provided the feedback and institutional protocol. The third phase involved intervention through patient risk stratification and prophylactic recommendation by pharmacist concomitantly with reaudit. The overall non-compliance to the therapy decreased from 52% in the control phase to 20% in the intervention phase with P = 0.0009. The partial compliance to therapy reduced from 40% in the control phase to 32% in the intervention phase with P = 0.4047. Total compliance to therapy increased from 8% in the control to 48% in the intervention stage and the difference was found to be significant with P < 0.0001. The study was effective in increasing the overall compliance to the ACCP 9th guidelines by 40% and the average duration by 1.61 days. Clinical pharmacist assisted multi-strategy interventions were effective in enhancing the appropriateness of the prophylaxis as per the ACCP recommendations. Les recommandations concernant la prévention du thrombo-embolisme veineux (VTE) postopératoire datent d'un demi-siècle. Malgré l'évidence de l'efficacité clinique et économique, les recommandations restent encore parfois peu ou mal utilisées. L'étude a visé à optimiser les pratiques de prévention du VTE chez les patients hospitalisés en chirurgie générale dans un hôpital de soin possédant des pharmaciens cliniciens. L'étude quasi expérimentale éventuelle a été conduite dans le département de chirurgie générale d'un hôpital du Kerala. La phase initiale a été un audit des pratiques prophylactiques existantes et leur adéquation avec les directives cliniques de l'American College of Chest Physicians (ACCP). Ceci a été suivi par une phase éducative où les pharmaciens cliniciens ont présenté le résultat d'audit aux médecins avec un protocole institutionnel. La troisième phase a impliqué une intervention des pharmaciens selon le profil de risque du patient avec un rappel de la recommandation prophylactique et dans la foulée un nouvel audit. Le non-respect global à la thérapie a diminué de 52 % dans la phase de contrôle à 20 % dans la phase d'intervention (p = 0,0009). La conformité partielle aux directives cliniques a été réduite de 40 % pour la phase de contrôle jusqu'à 32 % pour la phase d'intervention (p = 0,4047). La conformité totale aux directives cliniques s'est accrue significativement de 8 % pour le contrôle jusqu'à 48 % pour l'étape d'intervention (p < 0,0001). La stratégie utilisée s'est avérée efficace pour améliorer la conformité globale aux 9es directives ACCP (+ 40 %) et la durée moyenne à 1,61 jours. Les interventions du pharmacien clinicien se sont avérées efficaces pour assurer le respect des directives cliniques de l'ACCP.

Problem considered: India has the highest number of envenomation and the highest number of deaths due to snakebite in the world. However, there is wide variation in the regional prevalence of snake species involved in causation of snakebites. The objectives of the study were to determine the prevalence of causative species involved in snakebites presented to the institution and identification of risk factors that triggered the infliction.Methods: The cross-sectional study was conducted among snakebite causalties admitted to a tertiary care hospital in Malappuram district of Kerala. Data were collected from the medication charts of confirmed bite victims admitted to critical care unit of the hospital prospectively. Statistical analysis was performed using chi(2), Student's t-test and ANOVA.Results: The sample comprised of 60 (65.9%) males and 31 (34.1%) females, fashioning a gender ratio of 1.93. The causative snake species was unidentified in 48 (52.7%) instances. Russel's viper, hump nose viper (HNV), spectacled cobra and common krait were involved in 21 (23.1%), 14 (15.4%), 5 (5.5%) and 3 (3.3%) inflictions respectively. 77 (84.6%) victims were residents of rural area in opposition to 14 (15.4%) from urban area. 80 (87.9%) subjects presented with an alleged bite at lower extremities as opposed to 11 (12.1%) with infliction on upper extremities.Conclusions: Russel's viper constituted the most prevalent species among identified cases in the study setting. Male gender, working class population, outdoor occupation without adequate protective footwear, monsoon season and rural residency were identified as risk factors for contracting snakebites. (C) 2015 INDIACLEN. Published by Elsevier, a division of Reed Elsevier India, Pvt. Ltd. All rights reserved.