The Development and Initial Findings of A Study of a Prospective Adult Research Cohort with Inflammatory Bowel Disease (SPARC IBD).

BACKGROUND: Clinical and molecular subcategories of inflammatory bowel disease (IBD) are needed to discover mechanisms of disease and predictors of response and disease relapse. We aimed to develop a study of a prospective adult research cohort with IBD (SPARC IBD) including longitudinal clinical and patient-reported data and biosamples. METHODS: We established a cohort of adults with IBD from a geographically diverse sample of patients across the United States with standardized data and biosample collection methods and sample processing techniques. At enrollment and at time of lower endoscopy, patient-reported outcomes (PRO), clinical data, and endoscopy scoring indices are captured. Patient-reported outcomes are collected quarterly. The quality of clinical data entry after the first year of the study was assessed. RESULTS: Through January 2020, 3029 patients were enrolled in SPARC, of whom 66.1% have Crohn's disease (CD), 32.2% have ulcerative colitis (UC), and 1.7% have IBD-unclassified. Among patients enrolled, 990 underwent colonoscopy. Remission rates were 63.9% in the CD group and 80.6% in the UC group. In the quality study of the cohort, there was 96% agreement on year of diagnosis and 97% agreement on IBD subtype. There was 91% overall agreement describing UC extent as left-sided vs extensive or pancolitis. The overall agreement for CD behavior was 83%. CONCLUSION: The SPARC IBD is an ongoing large prospective cohort with longitudinal standardized collection of clinical data, biosamples, and PROs representing a unique resource aimed to drive discovery of clinical and molecular markers that will meet the needs of precision medicine in IBD.

Artemisinin Cocrystals for Bioavailability Enhancement. Part 2: In Vivo Bioavailability and Physiologically Based Pharmacokinetic Modeling.

We report the evaluation and prediction of the pharmacokinetic (PK) performance of artemisinin (ART) cocrystal formulations, that is, 1:1 artemisinin/orcinol (ART-ORC) and 2:1 artemisinin/resorcinol (ART2-RES), using in vivo murine animal and physiologically based pharmacokinetic (PBPK) models. The efficacy of the ART cocrystal formulations along with the parent drug ART was tested in mice infected with Plasmodium berghei. When given at the same dose, the ART cocrystal formulation showed a significant reduction in parasitaemia at day 4 after infection compared to ART alone. PK parameters including Cmax (maximum plasma concentration), Tmax (time to Cmax), and AUC (area under the curve) were obtained by determining drug concentrations in the plasma using liquid chromatography-high-resolution mass spectrometry (LC-HRMS), showing enhanced ART levels after dosage with the cocrystal formulations. The dose-response tests revealed that a significantly lower dose of the ART cocrystals in the formulation was required to achieve a similar therapeutic effect as ART alone. A PBPK model was developed using a PBPK mouse simulator to accurately predict the in vivo behavior of the cocrystal formulations by combining in vitro dissolution profiles with the properties of the parent drug ART. The study illustrated that information from classical in vitro and in vivo experimental investigations of the parent drug of ART formulations can be coupled with PBPK modeling to predict the PK parameters of an ART cocrystal formulation in an efficient manner. Therefore, the proposed modeling strategy could be used to establish in vitro and in vivo correlations for different cocrystals intended to improve dissolution properties and to support clinical candidate selection, contributing to the assessment of cocrystal developability and formulation development.

Artemisinin Cocrystals for Bioavailability Enhancement. Part 1: Formulation Design and Role of the Polymeric Excipient.

Artemisinin (ART) is a most promising antimalarial agent, which is both effective and well tolerated in patients, though it has therapeutic limitations due to its low solubility, bioavailability, and short half-life. The objective of this work was to explore the possibility of formulating ART cocrystals, i.e., artemisinin-orcinol (ART-ORC) and artemisinin-resorcinol (ART2-RES), as oral dosage forms to deliver ART molecules for bioavailability enhancement. This is the first part of the study, aiming to develop a simple and effective formulation, which can then be tested on an appropriate animal model (i.e., mouse selected for in vivo study) to evaluate their preclinical pharmacokinetics for further development. In the current work, the physicochemical properties (i.e., solubility and dissolution rate) of ART cocrystals were measured to collect information necessary for the formulation development strategy. It was found that the ART solubility can be increased significantly by its cocrystals, i.e., 26-fold by ART-ORC and 21-fold by ART2-RES, respectively. Screening a set of polymers widely used in pharmaceutical products, including poly(vinylpyrrolidone), hydroxypropyl methylcellulose, and hydroxypropyl methylcellulose acetate succinate, based on the powder dissolution performance parameter analysis, revealed that poly(vinylpyrrolidone)/vinyl acetate (PVP-VA) was the most effective crystallization inhibitor. The optimal concentration of PVP-VA at 0.05 mg/mL for the formulation was then determined by a dissolution/permeability method, which represented a simplified permeation model to simultaneously evaluate the effects of a crystallization inhibitor on the dissolution and permeation performance of ART cocrystals. Furthermore, experiments, including surface dissolution of single ART cocrystals monitored by Raman spectroscopy, scanning electron microscopy and diffusion properties of ART in solution measured by 1H and diffusion-ordered spectroscopy nuclear magnetic resonance spectroscopy, provided insights into how the excipient affects the ART cocrystal dissolution performance and bioavailability.

Inpatient Management of Inflammatory Bowel Disease-Related Complications.

Despite advances in therapeutic options, a sizeable proportion of patients with inflammatory bowel disease require hospitalization or surgery during their lifetime. While current treatment guidelines for the management of ulcerative colitis and Crohn's disease cover the spectrum of disease severity and behavior, management of acute complications of inflammatory bowel disease can present unique challenges that are not always addressed in these guidelines. In this review, the authors provide a comprehensive summary of the existing literature focused on management of patients hospitalized with complications of inflammatory bowel disease. Proposed management algorithms are provided to guide clinicians through common scenarios to determine the most appropriate interventions - escalation of medical therapies, non-surgical therapeutic interventions (drainage of intra-abdominal abscess or endoscopic balloon dilation) or surgery. Prevention of complications is proposed through a multi-disciplinary approach that involves surgeons, dieticians, radiologists, pathologists and infectious disease consultants.

Microsponges enriched gel for enhanced topical delivery of 5-fluorouracil.

This study aimed to develop microsponges based topical gel formulation of 5-Fluorouracil (5-FU) for the treatment of skin cancer with enhanced skin deposition and reduced skin irritation potential. Microsponges were prepared by Quasi-emulsion solvent diffusion method using ethyl cellulose and Eudragit RL 30 D; and was optimised through detailed in vitro characterisation. Brunauer-Emmett-Teller (BET) analysis demonstrated higher surface area (2.4393 m2/g) and pore volume of developed microsponges formulation. Optimised formulation showed better thixotropic and texture properties compared to commercial cream formulation, used as control for comparison purpose. Further, the optimised formulation demonstrated 5.5-fold increase in skin deposition documented via in-vivo local bioavailability study, with significant reduction in skin irritation compared to the commercial formulation. Hence, the developed microsponges based formulation seems to be a viable alternative with enhanced topical delivery of 5-FU as compared to the commercial formulation.

Graft-vs-Host Disease Colitis After Lung Transplant.

Graft-vs-host disease, characteristically a major complication of allogenic hematopoietic stem cell transplantation, is rare after solid organ transplantation. We report a 50-year-old man who presented with abdominal pain, vomiting, and diarrhea shortly after bilateral lung transplantation. Colonoscopy with biopsy revealed diffuse severe active colitis with ulceration and crypt apoptosis consistent with graft-vs-host disease colitis. The diagnosis was confirmed by the presence of donor lymphocytes in the peripheral blood. His symptoms were refractory to corticosteroids but responded to the addition of infliximab and extracorporeal photophoresis. He remained in remission 17 months later.

Factors That Contribute to Indeterminate Results From the QuantiFERON-TB Gold In-Tube Test in Patients With Inflammatory Bowel Disease.

BACKGROUND & AIMS: The QuantiFERON-Tuberculosis Gold In-Tube (QFT-GIT) (QIAGEN Group, Hilden, Germany) test is widely used to screen for latent Mycobacterium tuberculosis infection in patients with inflammatory bowel diseases (IBD) before treatment with a tumor necrosis factor antagonist. The test frequently produces indeterminate results, prompting additional testing. We evaluated factors associated with indeterminate results from the QFT-GIT test among patients with IBD. METHODS: We conducted a case-control study among eligible adults with QFT-GIT test results and a concomitant diagnosis of IBD receiving care at a tertiary referral center from 2011 through 2013. We compared patients with IBD with indeterminate and determinate (positive or negative) results from the QFT-GIT test. We collected data on patient demographics, clinical features, laboratory parameters, and medication use from medical charts. We calculated odds ratios (OR) and 95% CIs using multivariate logistic regression models. RESULTS: A total of 400 patients with IBD (265 Crohn's disease and 135 ulcerative colitis) were included in the final analyses. Indeterminate results were noted in 11.5% of patients. At the time of testing, a higher proportion of patients with indeterminate results from the QFT-GIT test were on systemic corticosteroid therapy (60.9% vs 30.5% of patients with conclusive test results; P < .001), had levels of C-reactive protein above 0.8 mg (62.2% vs 39.9% of patients with clear test results; P = .005), had an erythrocyte sedimentation rate above 15 mm/h (55.6% vs 35.8% of patients with clear test results; P = .01), had serum levels of albumin below 3.5 g/dL (33.3% vs 6.3% of patients with clear test results; P < .001), and had low levels of hemoglobin (52.2% vs 28.3% of patients with clear test results; P = .001). In multivariable analysis, corticosteroid use (adjusted OR, 2.92; 95% CI, 1.44-5.88; P = .003) and serum levels of albumin below 3.5 g/dL (adjusted OR, 3.62; 95% CI, 1.36-9.60; P = .009) were independently associated with increased risk of indeterminate QFT-GIT test results. We did not identify a dose-related effect with corticosteroid therapy and the odds of indeterminate QFT-GIT test results. CONCLUSIONS: In a case-control study of patients with IBD, we associated systemic corticosteroid therapy and low levels of albumin with an increased likelihood of having indeterminate QFT-GIT test result.

Perianal Crohn's Disease is Associated with Distal Colonic Disease, Stricturing Disease Behavior, IBD-Associated Serologies and Genetic Variation in the JAK-STAT Pathway.

BACKGROUND: Perianal Crohn's Disease (pCD) is a particularly severe phenotype associated with poor quality of life with a reported prevalence of 12%-40%. Previous studies investigating the etiology of pCD have been limited in the numbers of subjects and the intensity of genotyping. The aim of this study was to identify clinical, serological, and genetic factors associated with pCD. METHODS: We performed a case-control study comparing patients with (pCD+) and without perianal (pCD) involvement in CD; defined as the presence of perianal abscesses or fistulae. Data on demographics and clinical features were obtained by chart review. Inflammatory bowel disease-related serology was determined by enzyme-linked immunosorbent assay. Genetic data were generated using Illumina genotyping platforms. RESULTS: We included 1721 patients with CD of which 524 (30.4%) were pCD+ and 1197 were pPCD. pCD was associated with distal colonic disease (Odds ratio 5.54 [3.23-9.52], P < 0.001), stricturing disease behavior (1.44 [1.14-1.81], P = 0.002) and family history of inflammatory bowel disease (4.98 [3.30-7.46], P < 0.001). pCD was associated with higher anti-sacharomyces cerevisae antibodies IgA (P < 0.001) and OmpC (P = 0.008) antibody levels. pCD was associated with known inflammatory bowel disease loci, including KIF3B, CRTC3, TRAF3IP2, JAZF1, NRIP1, MST1, FUT2, and PTGER (all P < 0.05). We also identified genetic association with genes involved in autophagy (DAPK1, P = 5.11 × 10), TNF alpha pathways (NUCB2, P = 8.68 × 10; DAPK1), IFNg pathways (DAPK1; NDFIP2, P = 8.74 × 10), and extracellular matrix and scaffolding proteins (USH1C, P = 8.68 × 10; NDFIP2; TMC07, P = 8.87 × 10). Pathway analyses implicated the JAK-Stat pathway (pc = 3.72 × 10). CONCLUSION: We have identified associations between pCD, more distal colonic inflammation, Crohn's disease-associated serologies, and genetic variation in the JAK-Stat pathway.

Combined Immunosuppression Impairs Immunogenicity to Tetanus and Pertussis Vaccination Among Patients with Inflammatory Bowel Disease.

BACKGROUND: Pertussis epidemics have recently emerged across the United States, prompting broad public health recommendations for adult Tdap vaccination (tetanus, diphtheria, acellular pertussis). The impact of immunosuppressive regimens for inflammatory bowel disease (IBD) on vaccine responses to the Tdap vaccine is not known. METHODS: We performed a prospective controlled trial between April 2011 and March 2012. Adults with IBD were consecutively stratified based on therapeutic regimen into one of 5 groups: A: no IBD therapy or 5-aminosalicylates alone; B: maintenance biologic monotherapy; C: maintenance immunomodulator monotherapy; D: combined biologic and immunomodulator therapy; and E: healthy age-matched controls. Subjects received Tdap, and serum antibody levels against tetanus toxoid, pertussis toxoid, and filamentous hemagglutinin (FHA) were drawn just before and approximately 4 weeks after vaccination. The primary outcome was the booster response rate to each antigen. Secondary outcomes included the differences in pregeometric and postgeometric mean titers. RESULTS: A total of 98 subjects enrolled, and 84 completed the study. Tetanus response rates were 55%, 56%, 40%, 27%, and 63% across groups A to E, respectively. Group D rates were lower than those of group B (P = 0.02). Postvaccination pertussis toxoid responses were 59%, 72%, 47%, 45%, and 75%, while FHA responses were 86%, 72%, 80%, 64%, and 75% across groups A to E, respectively. Prevaccination and postvaccination geometric mean titer differences for FHA were lower in group D than those in group A (P = 0.05). CONCLUSIONS: Antibody responses to tetanus and pertussis vaccination may be affected by therapeutic drug regimen. Patients with IBD should optimally receive Tdap before starting immunomodulators, particularly when used in combination with anti-tumor necrosis factor alpha agents.

Pyoderma Gangrenosum among Patients with Inflammatory Bowel Disease: A Descriptive Cohort Study.

BACKGROUND: Pyoderma gangrenosum (PG) is a severe extraintestinal manifestation of inflammatory bowel disease (IBD). OBJECTIVE: To better characterize PG features and management among an IBD cohort. METHODS: Subjects with PG were identified using a large database at a tertiary center. Patient demographics and clinical characteristics were summarized using descriptive statistics. RESULTS: Eighty patients with an episode(s) of PG were identified, yielding an overall prevalence of 1.9%. Overall, 93% of patients with PG had some degree of colonic inflammation. Thirty-one (39%) patients required hospitalization for PG. Underlying bowel disease was active at the time of PG episode(s) in 52 (65%) patients. The PG location was variable, with the lower extremity being the most common. Most patients (71.3%) required multiple therapies to achieve PG healing. CONCLUSIONS: We describe one of the largest case series of PG among patients with IBD. The variety of treatment strategies used highlights the lack of clear guidelines in managing this complex group of patients.

Pyoderma Gangrenosum among Patients with Inflammatory Bowel Disease: A Descriptive Cohort Study.

BACKGROUND: Pyoderma gangrenosum (PG) is a severe extraintestinal manifestation of inflammatory bowel disease (IBD). OBJECTIVE: To better characterize PG features and management among an IBD cohort. METHODS: Subjects with PG were identified using a large database at a tertiary center. Patient demographics and clinical characteristics were summarized using descriptive statistics. RESULTS: Eighty patients with an episode(s) of PG were identified, yielding an overall prevalence of 1.9%. Overall, 93% of patients with PG had some degree of colonic inflammation. Thirty-one (39%) patients required hospitalization for PG. Underlying bowel disease was active at the time of PG episode(s) in 52 (65%) patients. The PG location was variable, with the lower extremity being the most common. Most patients (71.3%) required multiple therapies to achieve PG healing. CONCLUSIONS: We describe one of the largest case series of PG among patients with IBD. The variety of treatment strategies used highlights the lack of clear guidelines in managing this complex group of patients.

Antibiotics for Treatment of Clostridium difficile Infection in Hospitalized Patients with Inflammatory Bowel Disease.

Patients with inflammatory bowel disease (IBD), namely ulcerative colitis (UC) and Crohn's disease (CD), have worse outcomes with Clostridium difficile infection (CDI), including increased readmissions, colectomy, and death. Oral vancomycin is recommended for the treatment of severe CDI, while metronidazole is the standard of care for nonsevere infection. We aimed to assess treatment outcomes of CDI in IBD. We conducted a retrospective observational study of inpatients with CDI and IBD from January 2006 through December 2010. CDI severity was assessed using published criteria. Outcomes included readmission for CDI within 30 days and 12 weeks, length of stay, colectomy, and death. A total of 114 patients met inclusion criteria (UC, 62; CD, 52). Thirty-day readmissions were more common among UC than CD patients (24.2% versus 9.6%; P=0.04). Same-admission colectomy occurred in 27.4% of UC patients and 0% of CD patients (P<0.01). Severe CDI was more common among UC than CD patients (32.2% versus 19.4%; P=0.12) but not statistically significant. Two patients died from CDI-associated complications (UC, 1; CD, 1). Patients with UC and nonsevere CDI had fewer readmissions and shorter lengths of stay when treated with a vancomycin-containing regimen compared to those treated with metronidazole (30-day readmissions, 31.0% versus 0% [P=0.04]; length of stay, 13.62 days versus 6.38 days [P=0.02]). Patients with UC and nonsevere CDI have fewer readmissions and shorter lengths of stay when treated with a vancomycin-containing regimen relative to those treated with metronidazole alone. Patients with ulcerative colitis and CDI should be treated with vancomycin.

Clinical, serologic, and genetic factors associated with pyoderma gangrenosum and erythema nodosum in inflammatory bowel disease patients.

BACKGROUND: Pyoderma gangrenosum (PG) and erythema nodosum (EN) are the most common cutaneous manifestations of inflammatory bowel disease (IBD) but little is known regarding their etiopathogenesis. METHODS: We performed a case-control study comparing characteristics between IBD patients with a documented episode of PG (PG+) and/or EN (EN+) with those without PG (PG-) and EN (EN-). Data on clinical features were obtained by chart review. IBD-related serology was determined using enzyme-linked immunosorbent assay and genome-wide data generated using Illumina technology. Standard statistical tests for association were used. RESULTS: We identified a total of 92 cases of PG and 103 cases of EN with genetic and clinical characteristics, of which 64 PG and 55 EN cases were available for serological analyses. Fewer male subjects were identified in the PG(+) (odds ratio 0.6, P = 0.009) and EN(+) groups (odds ratio 0.31, P = 0 < 0.0001). Colonic disease, previous IBD-related surgery, and noncutaneous extra-intestinal manifestations were more common among both PG(+) and EN(+) patients compared with controls. PG(+) was associated with anti-nuclear cytoplasmic antibody seropositivity (P = 0.03) and higher anti-nuclear cytoplasmic antibody level (P = 0.02) in Crohn's disease. Genetic associations with PG included known IBD loci (IL8RA [P = 0.00003] and PRDM1 [0.03]) as well as with USP15 (4.8 × 10) and TIMP3 (5.6 ×10). Genetic associations with EN included known IBD susceptibility genes (PTGER4 [P = 8.8 × 10], ITGAL [0.03]) as well as SOCS5 (9.64 × 10), CD207 (3.14 × 10), ITGB3 (7.56 × 10), and rs6828740 (4q26) (P < 5.0 × 10). Multivariable models using clinical, serologic, and genetic parameters predicted PG (area under the curve = 0.8) and EN (area under the curve = 0.97). CONCLUSION: Cutaneous manifestations in IBD are associated with distinctive genetic characteristics and with the similar clinical characteristics, including the development of other extra-intestinal manifestations suggesting shared and distinct etiologies.

Surgical outcome of ileal pouch-anal anastomosis when used intentionally for well-defined Crohn's disease.

BACKGROUND: Crohn's disease (CD) is considered a contraindication to ileal pouch--anal anastomosis (IPAA). In this study, we compare outcomes of CD and ulcerative colitis (UC) patients undergoing IPAA. METHODS: Patients were considered to have CD before surgery based on a history of small bowel disease, perianal disease, noncrypt-associated granuloma, or pretreatment skip colonic lesions. Patients were prospectively assessed for pouchitis or CD. Postoperative CD (pouch inflammation into the afferent limb or pouch fistula) or pouch failure (need for permanent diversion) were assessed. Preoperative serum was assayed for IBD-associated antibodies using enzyme-linked immunosorbent assay (ELISA). RESULTS: Seventeen patients with preoperative CD were identified. Seven (41%) patients developed postoperative recurrent CD in the afferent limb (n = 3) or pouch fistulizing disease (n = 4). One patient (6%) required pouch excision. The incidence of postoperative CD was higher (P = 0.002) in preoperative CD patients (41%) than UC patients (11%). There was no significant difference in pouchitis or pouch failure. There was also no significant difference in any preoperative clinical feature between patients with or without postoperative CD. Afferent limb inflammation developed in three (50%) of the six patients with pANCA+/OmpC- expression compared to none of the 11 patients without this serologic profile (P = 0.03). CONCLUSIONS: Although the intentional use of IPAA in CD has a higher incidence of postoperative disease vs. UC patients, there was no significant difference in pouch failure. Demographics, clinical features, and serologic factors do not predict outcome of CD patients undergoing IPAA. IBD serology may identify the phenotype manifestation of postoperative recurrent CD.

Effect of α4ß7 blockade on intestinal lymphocyte subsets and lymphoid tissue development.

BACKGROUND: Blockade of the integrin α4ß7 has promise as a therapy for inflammatory bowel disease. α4ß7 plays diverse roles in the intestinal immune system, including lymphocyte homing and lymphoid tissue formation; however, the effects of α4ß7 blockade on these processes during inflammation and their relationship to the efficacy of α4ß7 blockade and its potential untoward effects are largely unknown. METHODS: α4ß7 function was inhibited by genetic manipulation or antibody blockade. The effects of these manipulations on lymphoid tissues and the presence of lymphocyte subpopulations in the murine small intestine and colon were evaluated in the unchallenged state, during the acute injury dextran sodium sulfate model, and during the splenocyte transfer chronic inflammation model. RESULTS: α4ß7 inhibition resulted in a decrease in the B-lymphocyte population in the diffuse lamina propria and a decrease in the number of lymphoid aggregates in the uninflamed intestine and in the acute injury model. α4ß7 blockade did not reduce the Foxp3- T-lymphocyte population but did decrease the Foxp3+ T-lymphocyte population located selectively within the lymphoid aggregates in the uninflamed intestine and in the acute injury model. In contrast, α4ß7 blockade reduced the intestinal T-lymphocyte population and decreased the production of inflammatory cytokines in the T-lymphocyte mediated chronic inflammation model. CONCLUSIONS: These findings demonstrate differential use of α4ß7 by B-lymphocytes, Foxp3- T-lymphocytes, and Foxp3+ T-lymphocytes to home to the gut, and suggest that α4ß7 blockade may serve as a targeted therapy that selectively inhibits the accumulation of pathogenic T-lymphocyte populations in the chronically inflamed intestine.

Quad shot: a short but effective schedule for palliative radiation for head and neck carcinoma.

BACKGROUND: To evaluate a 2-day course of palliative radiation in patients diagnosed to have inoperable or metastatic head and neck carcinoma. AIM: To evaluate the symptom relief and quality of life in these patients after this short course of radiation. SETTINGS AND DESIGN: A pilot study was conducted in a tertiary care institute in India. MATERIALS AND METHODS: Fifteen patients with stage IV B/C disease, KPS 50-70, were inducted after informed consent. External radiation was given in 2 days, two fractions per day, 6 h apart to a total dose of 14 Gy. Washington University quality of life questionnaire (QOL) was used for assessing QOL before and after radiation. Patients who had more than 50% regression of disease received a second course of similar radiation. All patients were followed up for a mean duration of 6 months. STATISTICAL ANALYSIS: The Wilcoxon signed rank test was used to evaluate the difference between the QOL scores before and after treatment. RESULTS AND CONCLUSIONS: Out of these 15 patients, majority (13) were males and the mean age of the patients was 62 years. After the first course, all patients had good symptom relief, improvement in the QOL, and 13 out of 15 had more than 50% objective response. The short duration of the treatment was favored by the outstation patients and their attendants. It may be concluded that this short course of radiation is an effective tool for palliative radiation and merits a larger randomized trial.

Wisconsin Card Sorting Test: Normative data and experience.

BACKGROUND: The Wisconsin Card Sorting Test (WCST) has been increasingly employed as a clinical neuropsychological instrument. However, in India the use of WCST is still in a relatively preliminary stage. AIM: To analyse the utility of WCST in the Indian population. METHODS: Fifty-three subjects in the age group of 20-50 years, comprising both men and women, were recruited for the study. The normality was established by administering the General Health Questionnaire as a screening instrument to evaluate their health status. The WCST was administered and the norms for various dimensions were established; these were compared with those of normal healthy individuals from the West as per the WCST manual. RESULTS AND CONCLUSION: The significance of differences and the experience of administration have been described. The present study found highly significant differences between the means on almost all WCST scores among the Western and the Indian sample, except for the number of correct responses.

Specific learning disabilities in children: deficits and neuropsychological profile.

The public is gradually becoming aware of specific learning disabilities (SLDs), which are very often the cause of academic difficulties. The aim of the study was to assess the SLDs in the clinic population at the Child and Adolescent Psychiatry Clinic at the Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh using the National Institute of Mental Health and Neurosciences SLD index and subsequently to assess the children's neuropsychological functions using a battery of tests. Thirty-five children in the age range of 7-14 years (both boys and girls) were recruited as the cohort, diagnosed clinically and assessed using the battery of tests for SLDs and neuropsychological tests consisting of the PGIMER memory scale for children, the Wisconsin card sorting test, the Bender visuo-motor gestalt test and Malin's intelligence scale for Indian children. The study revealed deficits in language and writing skills and impairments in specific areas of memory, executive functions and perceptuo-motor tasks. Identification of SLDs is useful in drawing up a treatment plan specific for a particular child.