Psychiatric symptoms are not associated with circulating CRP concentrations after controlling for medical, social, and demographic factors.

Elevated serum concentrations (>3 mg/L) of the acute-phase protein, C-reactive protein (CRP), is used as a clinical marker of inflammation and is reported to be a strong risk factor for cardiovascular disease. In psychiatric populations, CRP concentration is reported to be higher in depressed versus healthy individuals. Positive associations between CRP and depression have been established in both clinical and community samples, but effect sizes are attenuated after controlling for confounding variables. Similarly, emerging research has begun to draw a link between inflammation, symptoms of anxiety, and substance abuse. Given the high level of comorbid anxiety and substance use disorders in many depressed populations, this study examined whether depression (Patient Health Questionnaire 9 [PHQ-9]) and substance use-related (Drug Abuse Screening Test [DAST]) symptoms were associated with CRP concentrations in the blood after adjusting for relevant medical, social, and demographic covariates in a large sample undergoing screening for several transdiagnostic psychiatric research studies. A total of 1,724 participants were analyzed for association of CRP with variables using multivariate linear regression. An unadjusted model with no covariates showed that PHQ-9 was significantly associated with CRP in All (ß = 0.125), Female (ß = 0.091), and Male (ß = 0.154) participants, but DAST was significantly associated with CRP in males only (ß = 0.120). For the adjusted model, in both males and females, mood-stabilizer treatment (ß = 0.630), opioid medication (ß = 0.360), body mass index (ß = 0.244), percent body fat (ß = 0.289), nicotine use (ß = 0.063), and self-reported sleep disturbance (ß = 0.061) were significantly associated with increased CRP concentrations. In females, oral contraceptive use (ß = 0.576), and waist-to-hip ratio (ß = 0.086), and in males, non-steroidal anti-inflammatory drug use (ß = 0.367) were also associated with increased CRP concentrations. There was no significant association between CRP and individual depressive, anxiety, or substance use-related symptoms when covariates were included in the regression models. These results suggest that associations between circulating CRP and the severity of psychiatric symptoms are dependent on the type of covariates controlled for in statistical analyses.

Do Transfusion Dependent E-Βeta Thalassemics Behave Differently from Patients with Βeta-Thalassemia Major?

OBJECTIVE: To compare the blood transfusion pattern between children with transfusion dependent Eß-thalassemia and ß-thalassemia major. METHODS: 168 children (age 3 months to 12 years) with transfusion dependent Eß thalassemia and ß thalassemia major were admitted to the hospital. 120 children who met our inclusion criteria, were selected and detailed history including various parameters indicating the blood transfusion pattern were recorded. RESULTS: In this study 72 children (60%) of the patients were transfusion dependent Eß thalassemia. They started receiving blood transfusion (BT) at a later age(p < 0.0001), they received BT less frequently(p = 0.001), the total number of blood transfusions received up to 5 years of age were less in number(p < 0.0001), the pre-transfusion Hb levels were higher (p < 0.0001) and the peak ferritin level was much lower in them (p < 0.0001). Their transfusion requirement was much less, need for splenectomy was less (p < 0.006), their spleen span and liver span were also less than the children with ß-thalassemia major. CONCLUSION: Our study clearly depicts that transfusion dependent Eß thalassemia which is more common in our region shows a wide variation from ß thalassemia major patients with respect to various parameters including their transfusion pattern.

The pitfalls of using Gaussian Process Regression for normative modeling.

Normative modeling, a group of methods used to quantify an individual's deviation from some expected trajectory relative to observed variability around that trajectory, has been used to characterize subject heterogeneity. Gaussian Processes Regression includes an estimate of variable uncertainty across the input domain, which at face value makes it an attractive method to normalize the cohort heterogeneity where the deviation between predicted value and true observation is divided by the derived uncertainty directly from Gaussian Processes Regression. However, we show that the uncertainty directly from Gaussian Processes Regression is irrelevant to the cohort heterogeneity in general.

Clinical Outcome of Guillain-Barré Syndrome in 108 Children.

OBJECTIVES: To review the clinical outcome and electrophysiologic characteristics of children with Guillain-Barré syndrome (GBS) from Eastern India. METHODS: The hospital records of the children aged less than 12 years with a final diagnosis of GBS at our hospital from November, 2015 to December, 2018 were reviewed. Disabilities were assessed at 8-weeks and 6-month follow-up using Hughes scale (0-6). RESULTS: Demyelinating variety in 57 patients (52.8%) was more common than the axonal variety (33.3%). 71.1% (32/45) of GBS patients had recovered (scale 0,1) during the follow up period of 6 months. These included 67.7% (21/31) of the axonal variety and 78.6% (11/14) of the demyelinating variety. CONCLUSIONS: Irrespective of the severity, disability is less with the demyelinating variety as compared with the axonal subtype.

Machine Learning Analysis of Electronic Nose in a Transdiagnostic Community Sample With a Streamlined Data Collection Approach: No Links Between Volatile Organic Compounds and Psychiatric Symptoms.

Non-intrusive, easy-to-use and pragmatic collection of biological processes is warranted to evaluate potential biomarkers of psychiatric symptoms. Prior work with relatively modest sample sizes suggests that under highly-controlled sampling conditions, volatile organic compounds extracted from the human breath (exhalome), often measured by an electronic nose ("e-nose"), may be related to physical and mental health. The present study utilized a streamlined data collection approach and attempted to replicate and extend prior e-nose links to mental health in a standard research setting within large transdiagnostic community dataset (N = 1207; 746 females; 18-61 years) who completed a screening visit at the Laureate Institute for Brain Research between 07/2016 and 05/2018. Factor analysis was used to obtain latent exhalome variables, and machine learning approaches were employed using these latent variables to predict three types of symptoms independent of each other (depression, anxiety, and substance use disorder) within separate training and a test sets. After adjusting for age, gender, body mass index, and smoking status, the best fitting algorithm produced by the training set accounted for nearly 0% of the test set's variance. In each case the standard error included the zero line, indicating that models were not predictive of clinical symptoms. Although some sample variance was predicted, findings did not generalize to out-of-sample data. Based on these findings, we conclude that the exhalome, as measured by the e-nose within a less-controlled environment than previously reported, is not able to provide clinically useful assessments of current depression, anxiety or substance use severity.

Correlation Between Blood Pressure Measurement by Non-invasive and Invasive Methods in Critically-ill Children.

OBJECTIVE: To determine the correlation of non-invasive blood pressure obtained by auscultatory and oscillometric methods, with invasive blood pressure in critically ill children. METHODS: We compared invasive with auscultatory and oscillometric blood pressures using paired t-test, Pearson's correlation coefficient and Bland-Altman plot in 50 children (age 1-12 y) admitted in Pediatric intensive care unit. RESULTS: Systolic, diastolic, and mean arterial pressures of invasive methods significantly correlated with auscultatory and oscillometric methods (P<0.001). Auscultatory and oscillometric measurements under-estimated systolic arterial pressures [mean (SD) difference 5.4 (12.2) mmHg and 6.3 (14.0) mmHg, respectively; P<0.001] and overestimated diastolic arterial pressures [-4.1 (5.8) mmHg and -3.6 (7.2) mmHg; P<0.001] compared to invasive blood pressure. CONCLUSIONS: Mean arterial pressure obtained by NIBP measurement is more closer than systolic or diastolic pressures, when compared with invasive blood pressure measurement.

Mediastinal Pseudocyst and Cardiac Tamponade Due to Massive Pericardial Effusion in Pediatric Chronic Calcific Pancreatitis.

A 7-year-old male patient with a history of recurrent abdominal pain over 1 year presented with cardiac tamponade due to massive pericardial effusion, which was percutaneously drained. Contrast-enhanced computed tomography revealed a large posterior mediastinal cyst and calcified, heterogeneous pancreatic parenchyma. Elevated amylase and lipase levels of the cyst fluid confirmed the diagnosis of pancreatic pseudocyst, which was treated with an octreotide infusion and Roux-en-Y cystojejunostomy. The child was discharged on pancreatic enzyme supplement and was asymptomatic on follow-up.

Clinical Features and HLA Association of 5-Aminosalicylate (5-ASA)-induced Nephrotoxicity in Inflammatory Bowel Disease.

BACKGROUND AND AIMS: Nephrotoxicity is a rare idiosyncratic reaction to 5-aminosalicylate (5-ASA) therapies. The aims of this study were to describe the clinical features of this complication and identify clinically useful genetic markers so that these drugs can be avoided or so that monitoring can be intensified in high-risk patients. METHODS: Inflammatory bowel disease patients were recruited from 89 sites around the world. Inclusion criteria included normal renal function prior to commencing 5-ASA, ≥50% rise in creatinine any time after starting 5-ASA, and physician opinion implicating 5-ASA strong enough to justify drug withdrawal. An adjudication panel identified definite and probable cases from structured case report forms. A genome-wide association study was then undertaken with these cases and 4109 disease controls. RESULTS: After adjudication, 151 cases of 5-ASA-induced nephrotoxicity were identified. Sixty-eight percent of cases were males, with nephrotoxicity occurring at a median age of 39.4 years (range 6-79 years). The median time for development of renal injury after commencing 5-ASA was 3.0 years (95% confidence interval [CI] 2.3-3.7). Only 30% of cases recovered completely after drug withdrawal, with 15 patients requiring permanent renal replacement therapy. A genome-wide association study identified a suggestive association in the HLA region (p = 1×10(-7)) with 5-ASA-induced nephrotoxicity. A sub-group analysis of patients who had a renal biopsy demonstrating interstitial nephritis (n = 55) significantly strengthened this association (p = 4×10(-9), odds ratio 3.1). CONCLUSIONS: This is the largest and most detailed study of 5-ASA-induced nephrotoxicity to date. It highlights the morbidity associated with this condition and identifies for the first time a significant genetic predisposition to drug-induced renal injury.

Mercaptopurine versus placebo to prevent recurrence of Crohn's disease after surgical resection (TOPPIC): a multicentre, double-blind, randomised controlled trial.

BACKGROUND: Up to 60% of patients with Crohn's disease need intestinal resection within the first 10 years of diagnosis, and postoperative recurrence is common. We investigated whether mercaptopurine can prevent or delay postoperative clinical recurrence of Crohn's disease. METHODS: We did a randomised, placebo-controlled, double-blind trial at 29 UK secondary and tertiary hospitals of patients (aged >16 years in Scotland or >18 years in England and Wales) who had a confirmed diagnosis of Crohn's disease and had undergone intestinal resection. Patients were randomly assigned (1:1) by a computer-generated web-based randomisation system to oral daily mercaptopurine at a dose of 1 mg/kg bodyweight rounded to the nearest 25 mg or placebo; patients with low thiopurine methyltransferase activity received half the normal dose. Patients and their carers and physicians were masked to the treatment allocation. Patients were followed up for 3 years. The primary endpoint was clinical recurrence of Crohn's disease (Crohn's Disease Activity Index >150 plus 100-point increase in score) and the need for anti-inflammatory rescue treatment or primary surgical intervention. Primary and safety analyses were by intention to treat. Subgroup analyses by smoking status, previous thiopurines, previous infliximab or methotrexate, previous surgery, duration of disease, or age at diagnosis were also done. This trial is registered with the International Standard Randomised Controlled Trial Register (ISRCTN89489788) and the European Clinical Trials Database (EudraCT number 2006-005800-15). FINDINGS: Between June 6, 2008, and April 23, 2012, 240 patients with Crohn's disease were randomly assigned: 128 to mercaptopurine and 112 to placebo. All patients received at least one dose of study drug, and no randomly assigned patients were excluded from the analysis. 16 (13%) of patients in the mercaptopurine group versus 26 (23%) patients in the placebo group had a clinical recurrence of Crohn's disease and needed anti-inflammatory rescue treatment or primary surgical intervention (adjusted hazard ratio [HR] 0·54, 95% CI 0·27-1·06; p=0·07; unadjusted HR 0·53, 95% CI 0·28-0·99; p=0·046). In a subgroup analysis, three (10%) of 29 smokers in the mercaptopurine group and 12 (46%) of 26 in the placebo group had a clinical recurrence that needed treatment (HR 0·13, 95% CI 0·04-0·46), compared with 13 (13%) of 99 non-smokers in the mercaptopurine group and 14 (16%) of 86 in the placebo group (0·90, 0·42-1·94; pinteraction=0·018). The effect of mercaptopurine did not significantly differ from placebo for any of the other planned subgroup analyses (previous thiopurines, previous infliximab or methotrexate, previous surgery, duration of disease, or age at diagnosis). The incidence and types of adverse events were similar in the mercaptopurine and placebo groups. One patient on placebo died of ischaemic heart disease. Adverse events caused discontinuation of treatment in 39 (30%) of 128 patients in the mercaptopurine group versus 41 (37%) of 112 in the placebo group. INTERPRETATION: Mercaptopurine is effective in preventing postoperative clinical recurrence of Crohn's disease, but only in patients who are smokers. Thus, in smokers, thiopurine treatment seems to be justified in the postoperative period, although smoking cessation should be strongly encouraged given that smoking increases the risk of recurrence. FUNDING: Medical Research Council.

Synthesis and biological evaluation of some novel furan derivatives.

The present work involved cyclization of Schiff bases to azetidine-2-one and thiazolidine 4-one derivatives. The schiff bases (IIIa-j) were obtained upon reaction between electrophillic carbon atom of furfuraldehyde and nucleophillic nitrogen atom of amines. Azetidine-2-one derivatives (IVa-j) were obtained by reaction between imines and monochloro acetyl chloride in the presence of triethyl amine and 1, 4 dioxan. On the other hand, preparations of thiazolidine-4-ones (Va-j) were preceded by nucleophilic attack of sulphur of thioglycolic acid on imine carbon followed by intramolecular cyclization in the presence of SnCl2. The structures of the compounds were confirmed by spectral and elemental analysis. The biological evaluation of the compounds like anti-microbial, antioxidant, analgesic, CNS depressant and anti-diabetic activity were determined. From the pharmacological investigation it was found that out of all the compounds IVa, IVb, IVe, IVf, IVh,Va, Vb, Ve, Vf, Vh had shown more potent activity.

Disseminated staphylococcal disease in healthy children-experience from two tertiary care hospitals of West Bengal.

OBJECTIVES: To assess the etiology, precipitating factors, treatment and outcome of disseminated staphylococcal disease (DSD) in healthy immunocompetent children. METHODS: This hospital based observational prospective study was conducted in two tertiary care hospitals of West Bengal, India during the period of March, 2011 through February, 2012. Inclusion criteria were 1) children between 1 and 12 y and 2) clinical features DSD characterized by i) involvement of at least two distant organs with presence of gram positive cocci in clusters and/or growth of Staphylococcus aureus from at least one normally sterile body fluid, ii) fever, persistent bacteremia despite antibiotics and focal involvement of two or more separate tissue sites (skin, bone, joint, kidney, lung, liver, heart). RESULTS: Thirty six cases fulfilled the criteria of DSD with mean age in years 6.03 ± 3.04 (range 1-12). The age group of 5-12 y was found to be more vulnerable (p < 0.001). Septic arthritis following accidental blunt closed trauma, was the significant precipitating factor for DSD in this age group (p = 0.031). Methicillin resistant Staphylococcus aureus (MRSA) was the causative agent in all the cases. Vancomycin resistant Staphylococcus aureus (VRSA) was detected in 88.9 % of cases. All cases were sensitive to linezolid. No significant side effects were observed with 28 d of linezolid therapy. CONCLUSIONS: DSD is more common in 5-12 y age group. Trauma is a significant precipitating factor for DSD in this age group. Linezolid may be considered as the first line drug in DSD with MRSA.

Evaluation of hydrogen excretion after lactulose administration as a screening test for causes of irritable bowel syndrome.

OBJECTIVE: To determine whether it is possible to separate cases of irritable bowel syndrome associated with excess total hydrogen production (as a surrogate of colonic fermentation; these patients may be offered an exclusion diet as treatment) from other causes of irritable bowel syndrome by determining the amount of hydrogen excreted on patients' breath after oral administration of lactulose. DESIGN: Comparison of 24-hour hydrogen excretion and breath hydrogen following lactulose in untreated patients fulfilling the Rome criteria for irritable bowel syndrome, normal controls and irritable bowel syndrome patients who had previously failed to improve on an exclusion diet. METHODS: Colonic fermentation was measured by indirect calorimetry over 24 h. Immediately after calorimetry, the patients who were fasting received 20 g lactulose; end-expiratory breath samples were then collected every 30 min for 3 h. Hydrogen concentrations were determined by an electro-chemical cell. RESULTS: The total 24-hour excretion of hydrogen was significantly greater in the irritable bowel syndrome group (median 333.7 ml/24 h, interquartile range 234.7-445.67) compared to the normal volunteers (median 203.1 ml/24 h, interquartile range 131.4-256; P = 0.002) or the failed-diet group (median 204.5 ml/24 h, interquartile range 111.35-289.13; P = 0.015). No difference was detected in breath excretion of hydrogen following lactulose in any group. CONCLUSION: Total hydrogen production over 24 h is increased in some patients with irritable bowel syndrome who may respond to exclusion diets. However, this sub-group of patients cannot be identified by measuring breath-hydrogen excretion after lactulose.