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Purpose: Severe myelosuppression in patients with acute lymphoblastic leukemia (ALL) undergoing 6-MP-based maintenance therapy is attributed to TPMT gene polymorphisms, which is rare in Asian populations. This study aims to evaluate the role of selected polymorphisms in NUDT15, ITPA , and MRP4 genes in addition to TPMT in predicting 6-MP intolerance during ALL maintenance therapy., Patients and Methods: We screened for the presence of NUDT15*3 (c.415 C>T, rs116855232); MRP4 c.2269 C>T (rs3765534), ITPA c.94 C>A (rs1127354) polymorphisms in addition to TPMT *2 (rs1800462), *3A (*3B and *3C; rs1800460 and rs1142345) in ALL patients with documented severe neutropenia (cohort-1; n=42). These polymorphisms were then screened in a prospective cohort of ALL patients (cohort-2; n=133) and compared with 6-MP dose reduction, early/late myelotoxicity., Results: Nineteen (45%) patients in cohort-1 and 18 (14%) in cohort-2 had NUDT15 c.415 C>T variant while 4 (3%) patients in cohort-2 had TPMT*3C variant. Five (12%) in cohort-1 and 30 (24%) in cohort-2 had ITPA c.94 C>A variant while 9 (22%) and 15 (12%) had MRP4 c.2269 C>T variant in cohorts-1 and 2, respectively. All in cohort-1 and 36 (27%) in cohort-2 had severe myelotoxicity. Twenty-eight patients (66.6%) in cohort-1 and 40 (30%) patients in cohort-2 had significant 6-MP dose reduction. NUDT15 c.415 C>T variant explained severe myelotoxicity in 63% and 33% in cohort 1 and 2. TPMT *3C and ITPA c.94 C>A variants also explained myelotoxicity in cohort-2 (Median ANC: 376 vs 1014 mm 3 ; p=0.04 and 776 vs 1023 mm 3 ; p=0.04 respectively). NUDT15 c.415 C>T polymorphism explained significant myelotoxicity (507 vs 1298 mm 3 ; p<0.0001) in the multivariate analysis as well (β=-0.314, p<0.0001)., Conclusion: NUDT15 c.415 C>T (15*3), TPMT*3C, as well as ITPA c.94 C>A and MRP4 c.2269 C>T polymorphisms explain hematotoxicities. Preemptive genotype-based ( NUDT15*3, TPMT, ITPA c.94 C>A) 6-MP dosing could improve the outcome after maintenance therapy., Competing Interests: The authors report no conflicts of interest in this work., (© 2021 Pai et al.)

Diagnosis of scrub typhus, caused by the bacterium Orientia tsutsugamushi, is challenging because of the overlap of its non-specific symptoms with other infections coupled with the lack of sufficient data on the performance of diagnostic tests. Early diagnosis of scrub typhus is crucial to improve outcomes and this study evaluates the diagnostic performance of various tests. The present study aims at assessing the accuracy of various rapid diagnostic tests, serologic tests, and nucleic acid amplification methods on well-characterized patient samples. Adult patients with acute febrile illness and manifestations suggestive of scrub typhus confirmed by positive PCR in the blood, eschar or tissue were characterized as cases. Patients with acute febrile illness and a confirmed alternate etiology such as culture-confirmed typhoid, smear/PCR positive for malaria, PCR/NS1 antigen positive for dengue, PCR positive for influenza, PCR/MAT positive for leptospirosis, PCR positive for spotted fever were characterized as controls with other infections. The healthy controls consisted of subjects from the same geographic region. We performed the following tests on blood samples for scrub typhus and calculated the sensitivity, specificity, positive predictive value, and negative predictive value: (1) Quantitative real time PCR using 47kDa gene (qPCR); (2) Conventional PCR using 56kDa gene (cPCR); (3) Loop-mediated isothermal amplification assay (LAMP assay); (4) Immunofluorescence assay (IFA); (5) Enzyme-linked immunosorbent assay (ELISA); (6) Weil-Felix test(WF test); and (7) Immunochromatographic Rapid Diagnostic Test (RDT).Among the 316 participants, 158 had confirmed scrub typhus (cases) and 158 were controls. ELISA and RDT detecting Orientia tsutsugamushi specific IgM antibodies had excellent discriminative potential with sensitivities and specificities of 92%, 94% and 92%, 92% respectively. The sensitivity and specificity of IFA were found to be 95% and 74% respectively. IgM serology had a false positivity rate of 8% with other acute febrile illnesses such as dengue, leptospirosis and spotted fever due to the nonspecific binding of the pentavalent IgM. LAMP assay had 91.7% sensitivity and 77.2% specificity while qPCR provided excellent sensitivity (97%) and perfect specificity. In conclusion, ELISA and RDT detecting Orientia tsutsugamushi specific IgM antibodies have excellent sensitivity and specificity while the accuracy of IFA is suboptimal for the diagnosis of scrub typhus. Given its perfect specificity and superior sensitivity, qPCR is preferred for diagnostic confirmation in reference laboratories particularly for diagnosis of early disease with less than 7 days duration. This study provides a comprehensive evaluation of all currently available diagnostic tests for scrub typhus., Competing Interests: We are not affiliated with any pharmaceutical company or agency and have not been paid to write this article. The authors have declared that no competing interests exist.

Aim: To present a new protocol to optimise ultrasound (US) assessment of haemophilic arthropathy., Materials and Methods: Ultrasound of haemophilic arthropathy joints was performed using three different ultrasound protocols, namely, the Toronto-Vellore Comprehensive Ultrasound (TVC-US) protocol, the Haemophilia Early Arthropathy Detection with Ultrasound (HEAD-US), and the newly developed Universal Simplified Ultrasound (US-US) protocol. Synovial hypertrophy, haemosiderin deposition, effusion, erosion, and cartilage loss were evaluated in 20 joints. The reliability and diagnostic efficiency of these protocols was compared using magnetic resonance imaging (MRI)., Results: The correlation between the TVC-US and US-US protocols for synovial hypertrophy was excellent: kappa significance (KS) was 1, but was substantial (KS=0.65) with the HEAD-US protocol. For effusion, both the TVC-US and the HEAD-US protocols had substantial correlation with the US-US protocol (KS=0.7 and 0.6 respectively). The correlation for erosion and cartilage loss was excellent between the TVC-US and the US-US with MRI (KS=1), but poor (KS=0) with the HEAD-US protocol. The US-US protocol also had good interobserver agreement (KS=1)., Conclusion: The accuracy of the US-US protocol is comparable to the TVC-US protocol and MRI and is superior to the HEAD-US protocol in the assessment of haemophilic arthropathy., (Copyright © 2019 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Background & Objectives: Peripheral T cell lymphomas (PTCLs) are a heterogeneous group of non-Hodgkin's lymphomas (NHLs), with universally poor outcome. This study was undertaken to provide data on demographics and outcomes of patients with PTCL who underwent treatment in a single tertiary care centre in southern India., Methods: Retrospective study was done on all patients (age ≥18 yr) diagnosed with PTCL from January 2007 to December 2012. The diagnosis of PTCL was made according to the WHO Classification of Tumors of Hematopoietic and Lymphoid Tissues., Results: A total of 244 adult patients were diagnosed with PTCL (non-cutaneous). The most common subtype was PTCL-not otherwise specified (35.7%), followed by anaplastic large cell lymphoma (ALCL), ALK negative (21.3%), natural killer/T cell lymphoma, angioimmunoblastic T-cell lymphoma (AITL), ALCL, ALK positive, hepatosplenic T cell lymphoma (HSTCL) and adult T cell leukaemia/lymphoma followed in frequency with 13.1, 11.5, 8.6, 8.2 and 1.6 per cent cases, respectively. The three-year Kaplan-Meier overall survival (OS) and event-free survival (EFS) for the patients who received chemotherapy (n=122) were 33.8±5.0 and 29.3±4.7 per cent, respectively. Various prognostic indices developed for T cell lymphomas were found to be useful., Interpretation & Conclusions: Except for ALCL, ALK positive, all other PTCLs showed poor long-term outcome with CHOP-based chemotherapy. Novel therapies are needed to improve the outcome., Competing Interests: None

Patients and Methods: A longitudinal study was carried out in 255 children from 10 centres in nine developing countries over 5 years to assess the musculoskeletal outcome of children on episodic factor replacement. Outcome was documented by assessment of the annual joint bleeding rate (AJBR), WFH clinical and Pettersson radiological joint scores as well as the FISH score for activities. Of the 203 patients for whom data was available at the end of 5 years, 164 who had received only episodic treatment are included in this report., Results: The median age at the beginning of the study was 10 years (IQR 7-12). The median clotting factor concentrate (CFC) usage was 662 IU kg -1 year -1 (IQ range: 280-1437). The median AJBR was 10 (IQ range: 5-17). The median AJBR was higher in the older children with the median being 5 for the 5 year old child, while it was 9 for the 10 year old and 11 for children older than 15. Given the episodic nature of the replacement therapy, those with a higher AJBR used significantly greater annual CFC doses (P < 0.001); The median change in WFH clinical score and Pettersson radiological score over the 5 years was 0.4/year for each, while the FISH deteriorated at a rate of 0.2/year with poor correlation of these changes with CFC dose. WFH and FISH scores were significantly worse in those with an AJBR of >3 per year (P = 0.001). The change in the Pettersson score was significantly more in those with an AJBR of >5 per year (P = 0.020). Significant changes in FISH scores were only noted after 10 years of age., Conclusion: Episodic CFC replacement over a large range of doses does not alter the natural course of bleeding in haemophilia or the musculoskeletal deterioration and should not be recommended as a long term option for treatment. Prophylaxis is the only way to preserve musculoskeletal function in haemophilia., (© 2017 John Wiley & Sons Ltd.)

Objectives: This study was undertaken to determine the correlation between the radiological changes in haemophilic arthropathy [X-ray, Ultrasound (US) and MRI] and clinical assessment as determined by the Hemophilia Joint Health Score (HJHS); and to document the US and MRI changes in joints that appear normal on plain X-ray and clinical evaluation., Materials and Methods: Of 55 study joints (22 knees and 33 ankles) in 51 patients with haemophilia/von Willebrand disease, with a median age of 15 years (range: 5-17) were assessed using X-rays (Pettersson score) and clinical examination (HJHS) at two centres (Toronto, Canada; Vellore, India). MRI and ultrasonographic scoring was done through a consensus assessment by imagers at both centres using the IPSG MRI and US scores., Results: The HJHS had a good correlation with the Pettersson score (r s = 0.66). Though the HJHS had moderate correlation with the osteochondral component of the MRI and US scores (r s 0.51, 0.45 respectively), its correlation with the soft tissue component was poor (r s 0.19; 0.26 respectively). Of the 18 joints with a Pettersson score of zero, 88.9% had changes that were detected clinically by the HJHS. Osteochondral abnormalities were identified in 38.9% of these joints by the MRI, while US images of the same joints were deemed abnormal in 83.3% by the current criteria. US identified haemosiderin and other soft tissue changes in all of the joints, while the same changes were noted in 94.4% of these joints on MRI. There were four joints with a HJHS of zero, all of which had soft tissue changes on MRI (score 1-7) and US (score 2-7). Osteochondral changes were detected in three of these joints by US and in 2 by MRI. There were four joints with an MRI score of 0-1 that had significant US scores (3-5) and HJHS scores (0-6)., Conclusion: US and MRI are able to identify pathological changes in joints with normal X-ray imaging and clinical examination. However, further studies are required to be able to differentiate early abnormalities from normal. Clinical (HJHS) and radiological assessment (US/MRI) provide complimentary information and should be considered conjointly in the assessment of early joint arthropathy., (© 2016 John Wiley & Sons Ltd.)

OBJECTIVE. The purpose of this article is to assess the reliability of interpretation of ultrasound findings according to data blinding in maturing hemophilic joints and to determine the diagnostic accuracy of ultrasound compared with MRI for assessing joint components. SUBJECTS AND METHODS. Ankles (n = 34) or knees (n = 25) of boys with hemophilia or von Willebrand disease (median age, 13 years; range, 5-17 years) were imaged by ultrasound, MRI, and radiography in two centers (Toronto, Canada, and Vellore, India). Ultrasound scans were performed by two operators (one blinded and one unblinded to MRI data) and were reviewed by four reviewers who were unblinded to corresponding MRI findings according to a proposed 0- to 14-item scale that matches 14 of 17 items of the corresponding MRI scale. MRI examinations were independently reviewed by two readers. RESULTS. When data were acquired by radiologists, ultrasound was highly reliable for assessing soft-tissue changes (intraclass correlation coefficient [ICC], 0.98 for ankles and 0.97 for knees) and substantially to highly reliable for assessing osteochondral changes (ICC, 0.61 for ankles and 0.89 for knees). Ultrasound was highly sensitive (> 92%) for assessing synovial hypertrophy and hemosiderin in both ankles and knees but had borderline sensitivity for detecting small amounts of fluid in ankles (70%) in contrast to knees (93%) and variable sensitivity for evaluating osteochondral abnormalities (sensitivity range, 86-100% for ankles and 12-100% for knees). CONCLUSION. If it is performed by experienced radiologists using a standardized protocol, ultrasound is highly reliable for assessing soft-tissue abnormalities of ankles and knees and substantially to highly reliable for assessing osteochondral changes in these joints.

Background: Scrub typhus, a bacterial zoonosis caused by Orientia tsutsugamushi, may cause multiorgan dysfunction syndrome (MODS) and is associated with significant mortality. This study was undertaken to document the clinical and laboratory manifestations and complications and to study time trends and factors associated with mortality in patients with scrub typhus infection., Methods: This retrospective study, done at a university teaching hospital, included 623 patients admitted between 2005 and 2010 with scrub typhus. The diagnosis was established by a positive IgM ELISA and/or pathognomonic eschar with PCR confirmation where feasible. The clinical and laboratory profile, course in hospital, and outcome were documented. Factors associated with mortality were analyzed using multivariate logistic regression analysis., Results: The most common presenting symptoms were fever (100%), nausea/vomiting (54%), shortness of breath (49%), headache (46%), cough (38%), and altered sensorium (26%). An eschar was present in 43.5% of patients. Common laboratory findings included elevated transaminases (87%), thrombocytopenia (79%), and leukocytosis (46%). MODS was seen in 34% of patients. The overall case-fatality rate was 9.0%. Features of acute lung injury were observed in 33.7%, and 29.5% required ventilatory support. On multivariate analysis, shock requiring vasoactive agents (relative risk (RR) 10.5, 95% confidence interval (CI) 4.2-25.7, p<0.001), central nervous system (CNS) dysfunction (RR 5.1, 95% CI 2.4-10.7, p<0.001), and renal failure (RR 3.6, 95% CI 1.7-7.5, p=0.001) were independent predictors of mortality. Over 4 years, a decreasing trend was observed in the mortality rate., Conclusions: Scrub typhus can manifest with potentially life-threatening complications such as lung injury, shock, and meningoencephalitis. MODS occurred in a third of our patients. The overall case-fatality rate was 9%, with shock, renal failure, and CNS associated with a higher mortality., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: This study sought to document the clinical and laboratory manifestations, genetic variability, and outcomes of scrub typhus, an often severe infection caused by Orientia tsutsugamushi, in South India., Methods: Patients admitted to a large teaching hospital with IgM ELISA-confirmed scrub typhus were evaluated. Clinical examination with a thorough search for an eschar, laboratory testing, chest X-ray, and outcome were documented and analyzed. Additionally, a 410-bp region of the 56-kDa type-specific antigen gene of O. tsutsugamushi was sequenced and compared with isolates from other regions of Asia., Results: Most of the 154 patients evaluated presented with fever and non-specific symptoms. An eschar was found in 86 (55%) patients. Mild hepatic involvement was seen in most, with other organ involvement including respiratory, cardiovascular, and renal. Multi-organ dysfunction was noted in 59 (38.3%), and the fatality rate was 7.8%. Hypotension requiring vasoactive agents was found to be an independent predictor of mortality (p<0.001). The phylogeny of 26 samples showed 17 (65%) clustering with the Kato-like group and eight (31%) with the Karp-like group., Conclusions: The presentation of scrub typhus can be variable, often non-specific, but with potentially severe multi-organ dysfunction. Prompt recognition is key to specific treatment and good outcomes. Further study of the circulating strains is essential for the development of a successful vaccine and sensitive point-of-care testing., (Copyright © 2013 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Assessment of musculoskeletal function in individuals with haemophilia has been attempted with clinimetric instruments, which use predetermined domains for assessing the same. This study introduces the application of an instrument, the Canadian Occupational Performance Measure (COPM), which is an open-ended questionnaire that allows patients to prioritize their needs and rate their performance in different tasks of daily living as well as their satisfaction in performing them. To study the utility of COPM in evaluating the musculoskeletal functional status of patients with haemophilia and to assess its effectiveness in planning individualized management plans for them. COPM was administered to 67 individuals with haemophilia aged 10-55 years and the data were compared with functional deficits identified through FISH (Functional Independence Score for Haemophilia). A total of 31 performance difficulties in the areas of self-care (62%), productivity (21%) and leisure (17%) were identified by COPM. All eight domains of FISH were identified in COPM as problems in self-care. In addition to these, COPM identified problems in the areas of productivity and leisure. In 78% of the responses on COPM, there was concordance between the performance and satisfaction scores. However, there was discordance between the two in the remaining 22% of responses. COPM is a useful tool for assessment of musculoskeletal dysfunction in haemophilia. It provides a greater insight into the needs of each patient and helps in planning individualized intervention strategies., (© 2011 Blackwell Publishing Ltd.)

Purpose: Scrub typhus is a zoonotic illness endemic in the Asia-Pacific region. Early diagnosis and appropriate management contribute significantly to preventing adverse outcomes including mortality. Serology is widely used for diagnosing scrub typhus. Recent reports suggest that polymerase chain reaction (PCR) could be a rapid and reliable alternative. This study assessed the utility of these tests for scrub typhus diagnosis., Materials and Methods: Nested PCR to detect the 56 kDa antigen gene of O. tsutsugamushi was performed on blood clots from 87 individuals with clinically suspected scrub typhus. Weil-Felix test and scrub typhus IgM ELISA were performed on serum samples from the same patients. As a gold standard reference test was not available, latent class analysis (LCA) was used to assess the performance of the three tests., Results: The LCA analysis showed the sensitivity of Weil-Felix test, IgM ELISA and PCR to be 59%, 100% and 58% respectively. The specificity of ELISA was only 73%, whereas those of the Weil-Felix test and PCR were 94% and 100% respectively., Conclusion: Nested PCR using blood clots while specific, lacked sensitivity as compared to IgM ELISA. In resource-poor settings Weil-Felix test still remains valuable despite its moderate sensitivity.

Background: Limited data exists on the long-term treatment outcome and prognosis of childhood ALL in India., Procedure: Three hundred and seven children (1-14 years) with acute lymphoblastic leukemia (ALL) were treated with a modified BFM protocol 76/79 between 1985 and 2003. Treatment outcome and prognostic factors were evaluated., Results: The median age was 6 years; 78% had B lineage acute lymphoblastic leukemia and 22% had T lineage disease. Good prednisolone response was observed in 82% of cases. Two hundred and seventy-three children (91.6%) achieved complete remission; with 2% induction-related mortality and 6.4% having resistant disease. 52% of all evaluable patients and 56.8% of complete responders are in continuous complete remission (CCR) at a median follow up of 62 months (30-194 months). The median event free survival (EFS) was 114 months. The estimated 5 year overall survival, EFS and disease free survival was 59.8%, 56%, and 53.9%, respectively. The prognostic factors adversely affecting the EFS were poor prednisolone response, resistant disease and WBC count greater than 20 x 10(9)/L at diagnosis. The 5 year EFS in the favorable risk group (age 1-9 years, WBC count less than 20 x 10(9)/L and prednisolone good response) was 73.1 +/- 4.9%., Conclusion: This report examines a cohort of children with ALL treated with a BFM protocol in India with adequate follow up and demonstrates the need for cost effective improvements., ((c) 2008 Wiley-Liss, Inc.)

Background/objectives: Hepatitis B virus (HBV) genotypes may differ in pathogenicity. However, the interplay between different virus characteristics such as genotypes, mutants and virus loads has not been well studied . We investigated the association between HBV genotype, presence of 1896 precore mutation and HBV viral loads in patients with HBV-related liver disease., Methods: One hundred and sixteen HBV DNA-seropositive patients attending a gastroenterology outpatient clinic and 107 HBV DNA-seropositive blood donors were recruited. The subjects were stratified as those with normal (Group I, n=164) and elevated (Group II, n=59) ALT levels. The HBV genotype and the presence of the 1896 precore mutation were determined, and plasma HBV DNA levels measured., Results: Genotype C was more common in Group II than in Group I (10 (17%) vs. 4 (2.4%); p< 0.005). There was no relationship between the 1896 precore mutation and the HBV DNA levels. Subjects with genotype C (n=14) had higher HBV DNA levels than those with genotypes A (n=33) or D (n=158)., Conclusions: The infecting genotype, but not the presence of 1896 precore mutation, correlates with HBV load. The association of genotype C with higher virus loads and with elevated ALT may point to a greater pathogenicity of this genotype.

Fourteen children with a median age of 9.8 yr with SAA (10 males, four females) underwent related HLA identical allogeneic stem cell transplantation using Flu, Cy +/- ATG between 2004 and 2006. GVHD prophylaxis consisted of cyclosporine +/- mini methotrexate. Graft source included PBSCs (seven) or BM (seven). One patient expired <7 days post-transplant, while 12 (85.7%) patients engrafted with median neutrophil and platelet engraftment times of 13.8 and 14.5 days each. One patient had primary graft failure and expired on Day +27. Acute GVHD was seen in 25% of evaluable patients while limited chronic GVHD was seen in 33%. At a mean follow-up of 18 months, 12 patients (85.7%) are alive and well. Compared with a historical cohort of 12 children transplanted using Cy/ATG, there was faster engraftment (13.8 vs. 16.4 days; p = 0.002) with lower rejection rates (7.1 vs. 36.3%; p = 0.133) and improved event free (85.7 vs. 54.5%; p = 0.177) and overall survival (85.7 vs. 63.6%; p = 0.350). Flu with Cy +/- ATG reduces rejection and improves overall and event free survival in children with aplastic anemia.

Joint morbidity in haemophilia has traditionally been measured using clinical and radiological scores. There have been no reliable, validated tools for the assessment of functional independence in persons with haemophilia till recently. The Functional Independence Score in Haemophilia (FISH) has been developed as a performance based assessment tool to address this need. The FISH is designed to measure the patient's independence in performing activities of daily living (grooming and eating, bathing and dressing), transfers (chair and floor), and mobility (walking, step climbing and running). On assessment of its psychometric properties in 63 patients with haemophilia (mean age 14 years), FISH was found to have good internal consistency (Cronbach's alpha of 0.85). It had moderate correlation with the World Federation of Hemophilia clinical score (r = -0.61), and a correlation with the Pettersson score of -0.38. It had good correlation with other self-rated functional scores, such as the Stanford Health Assessment Questionnaire (r = -0.75); the Western Ontario and McMaster Universities Osteoarthritis Index (r = -0.66) and the Haemophilia Activities List (HAL) (r = -0.66). It had good reliability with a pooled intra class correlation of 0.98. On assessing responsiveness following treatment of flexion deformities of the knee in 12 patients, the FISH showed significant changes in the score with a standardized responsiveness mean of -1.93. In conclusion, the FISH was found to be a reliable and valid tool with good internal consistency and responsiveness to therapy, for the assessment of functional independence in persons with haemophilia.

Thirty-five patients (25 men and 10 women) with a median age of 20 years with severe aplastic anaemia (SAA) underwent HLA identical stem cell transplantation (HSCT) using a combination of fludarabine and cyclophosphamide +/- anti-thymocyte globulin between 2004 and 2006. Cyclosporine and mini methotrexate were used as GVHD prophylaxis. Graft source included peripheral blood stem cells (28) or G-CSF stimulated bone marrow (7). Two patients expired < 7 days post-HSCT while 32 (91.5%) patients engrafted with a median neutrophil and platelet engraftment time of 12 days each. Three patients (8.5%) developed veno-occlusive disease while acute GVHD occurred in 29% of evaluable patients, with chronic GVHD in 32%. At a mean follow-up of 22 months, 29 (82.8%) are alive and well. When compared with 26 patients previously transplanted using Cy200/antilymphocyte globulin, there was faster neutrophil engraftment (12 vs 16 days; P = 0.002) with significantly lower rejection rates (2.9 vs 30.7%; P = 0.003) and a superior event-free (82.8 vs 38.4%; P = 0.001) and overall survival (82.8 vs 46.1%; P = 0.005). A combination of fludarabine with cyclophosphamide +/- anti-thymocyte globulin reduces rejection and improves overall and event-free survival in Indian patients undergoing HSCT for severe aplastic anaemia.

Assessment of impairment and function is essential in order to monitor joint status and evaluate therapeutic interventions in patients with haemophilia. The improvements in the treatment of haemophilia have required the development of more sensitive tools to detect the more minor dysfunctions that may now be apparent. This paper outlines some of the recent developments in this field. The Haemophilia Joint Health Score (HJHS) provides a systematic and robust measure of joint impairment. The MRI Scoring System has been designed to provide a comprehensive scoring system combining both progressive and additive scales. The Functional Independence Score for Haemophilia (FISH) has been developed to assess performance of functional activities and can be used in conjunction with the Haemophilia Activities List (HAL) which provides a self report measure of function. It is recommended that both measures are evaluated as these tools measure different constructs. Further refinement and testing of the psychometric properties of all of these tools is in progress. More widespread use of these tools will enable the sharing of data across the world so promoting best practice and ultimately enhancing patient care.

Organophosphorous poisoning is a common method of deliberate self-harm in countries where the pesticides are readily available and can result in type I, II and/or III paralysis. The in-hospital morbidity and mortality of the poisoning are mostly associated with type II paralysis (intermediate syndrome). The aim of this study was to determine the role of oxidative stress in relation to the severity of poisoning and development of type II paralysis in patients suffering from acute organophosphate poisoning. This prospective study was carried out at the Christian Medical College Hospital. Thirty-two patients with acute organophosphorous poisoning, admitted in one medical unit over 17 months, were included in the study. They were clinically assessed for severity of poisoning and paralysis during the first 10 days of their hospitalisation. Temporal profiles of butyrylcholinesterase (BuChE) and oxidative stress parameters, for 4, 7 and 10 days of hospitalisation, were established in 25 of these patients. Type I and II paralysis were associated with severe poisoning. The majority of patients with type II paralysis had prior evidence of type I paralysis. The pattern of muscles that were paralysed in type I paralysis occurring alone and in type I paralysis proceeding to type II paralysis were similar. BuChE was significantly inhibited in all patients. Oxidative stress occurred in acute organophosphate poisoned patients and was greater in severe poisoning. The results suggest that type I paralysis may progress to type II paralysis in severely poisoned patients. They demonstrate early occurrence of oxidative stress in severe acute organophosphate poisoning. However, the development of type II paralysis is not associated with the level of oxidative stress. They suggest that mechanisms other than acetylcholine induced oxidative stress may be involved in the progression of type I to type II paralysis.

Objectives: To derive a clinical algorithm for diagnosis of scrub typhus among patients hospitalized with febrile illness and to determine predictors of bad prognosis., Methods: Patients hospitalized with febrile illness of 5-30 days duration were evaluated for common aetiologies. Sera were tested for antibodies (IgM and IgG) to Orientia tsutsugamushi using ELISA kit., Results: Among 207 patients, 50 had elevated levels of IgM antibodies. The data of these patients were compared with that of 16 controls having febrile illnesses in whom rickettsial infection was ruled out. Transaminase elevation (>twice normal) was present in 90% and was significantly (P=0.004) more common in those with scrub typhus. If a combination of elevated transaminases, thrombocytopenia and leukocytosis is used, the specificity and positive predictive value are about 80%. Case fatality rate was 14%. Univariate analysis showed that hyperbilirubinemia (>1.5mg%) has a RR of 9 (95% CI=1.48-58.5) and elevated creatinine level (>1.4 mg%) had a RR of 43.99 (95% CI=3.65-530.5) for death. Elevated creatinine level was found to be an independent predictor of mortality (P=0.02)., Conclusion: In developing countries with limited diagnostic facilities, it is prudent to recommend empiric therapy in patients with undifferentiated febrile illness having evidence of multiple system involvement especially if there is transaminase elevation. Elevated creatinine may predict bad outcome.

Morbidity in haemophilia has been described predominantly in terms of musculoskeletal dysfunction and assessed by the clinical and radiological joint scores. These scores document changes in a particular joint, but do not reflect the impact of these changes on the individual in terms of his overall musculoskeletal function. Several self-assessment instruments have been used to measure musculoskeletal function but none have been specifically validated for use in haemophilia. In order to objectively assess musculoskeletal function of patients with haemophilia, we developed Functional Independence Score in Hemophilia (FISH), a performance-based instrument. FISH measures the patient's independence in performing seven activities under three categories: self-care (grooming and eating, bathing and dressing), transfers (chair and floor) and mobility (walking and step climbing). Each function is graded from 1 to 4 depending on the amount of assistance needed in performing the function. We evaluated 35 patients who were over 10 years old and had had at least three major bleeds per year. All subjects were scored for clinical (World Federation of Hemophilia, WFH score) and radiological changes (Pettersson's score). Functional independence of the patient was assessed using the Stanford Health Assessment Questionnaire (HAQ) and the FISH. Correlation of the FISH score was modest with both the WFH clinical score (r = -0.68) and the radiological score (r = -0.44). While there was good correlation between FISH and HAQ (r = -0.90), FISH had better internal consistency than HAQ (Cronbach's alpha 0.83 vs. 0.66). FISH appears to be a promising disease-specific instrument for assessing overall musculoskeletal function in haemophilia. It requires evaluation in different patient populations.

Severe haemophilia (factor [F]VIII/FIX activity < 0.01 IU mL(-1)) is characterized by repeated haemarthroses resulting in severe arthropathy in adulthood. In 1958, Professor Nilsson in Sweden introduced prophylactic infusions with clotting factor concentrates at regular intervals in order to maintain clotting factor levels above 0.01 IU mL(-1) and to prevent bleeding. Since then, evidence of the long-term beneficial effects of prophylactic treatment for severe haemophilia has been increasing and it has become the recommended treatment strategy for children with severe haemophilia by both the World Health Organization and the US National Hemophilia Foundation Medical and Scientific Advisory Committee. However, the implementation of this recommendation has been hampered by issues of cost and venous access. The high costs of prophylaxis have largely prevented its use in major parts of the world. The question therefore is whether the current models of replacement of clotting factor concentrates, while certainly being effective, are also optimal. Can the data on outcome at different levels of factor replacement be used to assess their cost-effectiveness?