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Background: Leg ulcers are a frequent complication in patients with the inherited hemoglobin disorders. In thalassemia, the literature is limited, and factors associated with the development of leg ulcers in hemoglobin E (HbE) beta thalassemia, the most common form of severe beta-thalassemia worldwide, have not previously been reported. Methods: We reviewed all available medical records of patients with HbE beta thalassemia to document the onset of leg ulcers at the 2 largest treatment centers in Sri Lanka. We reviewed the literature to identify studies reporting outcomes of interventions for ulcers in severe thalassemia. Results: Of a total of 255 actively registered patients with HbE thalassemia in the 2 centers, 196 patient charts were evaluable. A leg ulcer with a documented date of onset was recorded in 45 (22%) of 196 evaluable patients, aged (mean ± SEM) 22.2 ± 1.4 years. Most had been irregularly transfused; steady-state hemoglobin was 6.4 ± 0.2 g/dL. Treatment achieving healing in 17 patients included transfusions, antibiotics, oral zinc, wound toileting, and skin grafting. Conclusion: Leg ulcers may be more common in HbE beta thalassemia than in other forms of thalassemia. A systematic approach to treatment will be needed to document the prevalence and factors placing such patients at risk for leg ulcers. Controlled trials to evaluate the optimal treatment of this common complication are indicated.

We present case histories of three patients who had β-thalassemia (β-thal) trait with 'unusual severity' managed as β-thal intermedia (β-TI) where the basis of disease severity could not be explained with routine hematological and genetic investigations. The clinical diagnosis of 'thalassemia intermedia' was justifiable as they had a β-thal mutation and disease severity that did not fit in with either β-thal trait or with β-thal major (β-TM). As mutations of α, β, and γ genes could not explain the unusual severity of the disease, further analysis with next-generation sequencing (NGS) for red cell diseases was carried out, which led to the diagnosis of coexisting membranopathies. This case series highlights the inherent difficulty in the diagnosis of β-TI with certainty in some patients where the genetic basis is not clear-cut.

In the β-thalassemias, oxidative stress, resulting from chronic hemolysis, globin chain imbalance, iron overload and depleted antioxidant defences, likely contributes to cell death, organ damage, anemia, hypoxia and inflammation. We assessed variations in these parameters in β-thalassemia syndromes in Sri Lanka. Between November 2017 and June 2018, we assessed children and adults attending two thalassemia centres in Sri Lanka: 59 patients with HbE β-thalassemia, 50 β-thalassemia major, 40 β-thalassemia intermedia and 13 HbS β-thalassemia. Median age was 26.0 years (IQR 15.3-38.8), 101 (62.3%) were female and 152 (93.8%) of Sinhalese ethnicity. Methemoglobin, plasma hemoglobin, heme and ferritin were measured as sources of oxidants; plasma total antioxidant capacity, haptoglobin, hemopexin and vitamins C and E assessed antioxidant status; plasma thiobarbituric acid reactive substances and 8-hydroxy-2'-deoxyguanosine assessed oxidative damage; hemoglobin, plasma erythropoietin and transferrin receptor assessed anemia and hypoxia and plasma interleukin-6 and C-reactive protein assessed inflammation. Fruit and vegetable intake was determined by dietary recall. Physical fitness was investigated using the 6-min walk test and measurement of handgrip strength. Oxidant sources were frequently increased and antioxidants depleted, with consequent oxidative damage, anemia, hypoxia and inflammation. Biomarkers were generally most abnormal in HbE β-thalassemia and least abnormal in β-thalassemia intermedia but also varied markedly between individuals with the same thalassemia syndrome. Oxidative stress and damage were also more severe in splenectomized patients and/or those receiving iron chelation therapy. Less than 15% of patients ate fresh fruits or raw vegetables frequently, and plasma vitamins C and E were deficient in 132/160 (82.5%) and 140/160 (87.5%) patients respectively. Overall, physical fitness was poor in all syndromes and was likely due to anemic hypoxia. Studies of antioxidant supplements to improve outcomes in patients with thalassemia should consider individual patient variation in oxidative status both between and within the thalassemia syndromes.

BACKGROUND\ud Worldwide, haemoglobin E β-thalassaemia is the most common genotype of severe β-thalassaemia. The paucity of long-term data for this form of thalassaemia makes evidence-based management challenging. We did a long-term observational study to define factors associated with survival and complications in patients with haemoglobin E thalassaemia.\ud \ud METHODS\ud In this prospective, longitudinal cohort study, we included all patients with haemoglobin E thalassaemia who attended the National Thalassaemia Centre in Kurunegala, Sri Lanka, between Jan 1, 1997, and Dec 31, 2001. Patients were assessed up to three times a year. Approaches to blood transfusions, splenectomy, and chelation therapy shifted during this period. Survival rates between groups were evaluated using Kaplan-Meier survival function estimate curves and Cox proportional hazards models were used to identify risk factors for mortality.\ud \ud FINDINGS\ud 109 patients (54 [50%] male; 55 [50%] female) were recruited and followed up for a median of 18 years (IQR 14-20). Median age at recruitment was 13 years (range 8-21). 32 (29%) patients died during follow-up. Median survival in all patients was 49 years (95% CI 45-not reached). Median survival was worse among male patients (hazard ratio [HR] 2·51, 95% CI 1·16-5·43), patients with a history of serious infections (adjusted HR 8·49, 2·90-24·84), and those with higher estimated body iron burdens as estimated by serum ferritin concentration (adjusted HR 1·03, 1·01-1·06 per 100 units). Splenectomy, while not associated with statistically significant increases in the risks of death or serious infections, ultimately did not eliminate a requirement for scheduled transfusions in 42 (58%) of 73 patients. Haemoglobin concentration less than or equal to 4·5 g/dL (vs concentration >4·5 g/dL), serum ferritin concentration more than 1300 μg/L (vs concentration ≤1300 μg/L), and liver iron concentration more than 5 mg/g dry weight of liver (vs concentration ≤5 mg/g) were associated with poorer survival.\ud \ud INTERPRETATION\ud Patients with haemoglobin E thalassaemia often had complications and shortened survival compared with that reported in high-resource countries for thalassaemia major and for thalassaemia intermedia not involving an allele for haemoglobin E. Approaches to management in this disorder remain uncertain and prospective studies should evaluate if altered transfusion regimens, with improved control of body iron, can improve survival.\ud \ud FUNDING\ud Wellcome Trust, Medical Research Council, US March of Dimes, Anthony Cerami and Ann Dunne Foundation for World Health, and Hemoglobal.

Background Though case reports and limited case series of Sickle cell disease in Sri Lanka have been reported previously, no attempt has been made hitherto to undertake a comprehensive genotypic-phenotypic analysis of this “rare” group of patients. Results All accessible Sickle cell disease patients, totaling 60, including, 51 Sickle β-thalassaemia and 9 homozygous sickle patients were enrolled from seven thalassaemia treatment centres between December 2016 - March 2019. The majority of patients were of Sinhalese ethnicity (n=52, 86.67%). Geographically, two prominent clusters were identified and the distribution of Sickle haemoglobin in the island contrasted markedly with the other haemoglobinopathies. 3/ 9 homozygous sickle patients and 3/ 51 Sickle β-thalassaemia patients were receiving regular transfusion. Joint pain was the commonest clinical presentation among all sickle cell disease patients (n=39, 65.0%). Dactylitis was significantly more common in homozygous sickle patients compared with the Sickle β-thalassaemia groups (p 0.027). Two genetic backgrounds sickle mutation were identified namely, Arab Indian and Benin. Among the regulators of Foetal hemoglobin in Sickle patients of the present study rs1427407 G>T seemed to be the most prominent modifier, with a significant association with Foetal haemoglobin levels (p 0.04). Conclusions Overall, the clinical course of the Asian version of Sickle cell disease in Sri Lanka appears to be milder than that described in India.

Summary Background BIG 3-07/TROG 07.01 is an international, multicentre, randomised, controlled, phase 3 trial evaluating tumour bed boost and hypofractionation in patients with non-low-risk ductal carcinoma in situ following breast-conserving surgery and whole breast radiotherapy. Here, we report the effects of diagnosis and treatment on health-related quality of life (HRQOL) at 2 years. Methods The BIG 3-07/TROG 07.01 trial is ongoing at 118 hospitals in 11 countries. Women aged 18 years or older with completely excised non-low-risk ductal carcinoma in situ were randomly assigned, by use of a minimisation algorithm, to tumour bed boost or no tumour bed boost, following conventional whole breast radiotherapy or hypofractionated whole breast radiotherapy using one of three randomisation categories. Category A was a 4-arm randomisation of tumour bed boost versus no boost following conventional whole breast radiotherapy (50 Gy in 25 fractions over 5 weeks) versus hypofractionated whole breast radiotherapy (42·5 Gy in 16 fractions over 3·5 weeks). Category B was a 2-arm randomisation between tumour bed boost versus no boost following conventional whole breast radiotherapy, and category C was a 2-arm randomisation between tumour bed boost versus no boost following hypofractionated whole breast radiotherapy. Stratification factors were age at diagnosis, planned endocrine therapy, and treating centre. The primary endpoint, time to local recurrence, will be reported when participants have completed 5 years of follow-up. The HRQOL statistical analysis plan prespecified eight aspects of HRQOL, assessed by four questionnaires at baseline, end of treatment, and at 6, 12, and 24 months after radiotherapy: fatigue and physical functioning (EORTC QLQ-C30); cosmetic status, breast-specific symptoms, arm and shoulder functional status (Breast Cancer Treatment Outcome Scale); body image and sexuality (Body Image Scale); and perceived risk of invasive breast cancer (Cancer Worry Scale and a study-specific question). For each of these measures, tumour bed boost was compared with no boost, and conventional whole breast radiotherapy compared with hypofractionated whole breast radiotherapy, by use of generalised estimating equation models. Analyses were by intention to treat, with Hochberg adjustment for multiple testing. This trial is registered with ClinicalTrials.gov , NCT00470236 . Findings Between June 1, 2007, and Aug 14, 2013, 1208 women were enrolled and randomly assigned to receive no tumour bed boost (n=605) or tumour bed boost (n=603). 396 of 1208 women were assigned to category A: conventional whole breast radiotherapy with tumour bed boost (n=100) or no boost (n=98), or to hypofractionated whole breast radiotherapy with tumour bed boost (n=98) or no boost (n=100). 447 were assigned to category B: conventional whole breast radiotherapy with tumour bed boost (n=223) or no boost (n=224). 365 were assigned to category C: hypofractionated whole breast radiotherapy with tumour bed boost (n=182) or no boost (n=183). All patients were followed up at 2 years for the HRQOL analysis. 1098 (91%) of 1208 patients received their allocated treatment, and most completed their scheduled HRQOL assessments (1147 [95%] of 1208 at baseline; 988 [87%] of 1141 at 2 years). Cosmetic status was worse with tumour bed boost than with no boost across all timepoints (difference 0·10 [95% CI 0·05–0·15], global p=0·00014, Hochberg-adjusted p=0·0016); at the end of treatment, the estimated difference between tumour bed boost and no boost was 0·13 (95% CI 0·06–0·20; p=0·00021), persisting at 24 months (0·13 [0·06–0·20]; p=0·00021). Arm and shoulder function was also adversely affected by tumour bed boost across all timepoints (0·08 [95% CI 0·03–0·13], global p=0·0033, Hochberg adjusted p=0·045); the difference between tumour bed boost and no boost at the end of treatment was 0·08 (0·01 to 0·15, p=0·021), and did not persist at 24 months (0·04 [–0·03 to 0·11], p=0·29). None of the other six prespecified aspects of HRQOL differed significantly after adjustment for multiple testing. Conventional whole breast radiotherapy was associated with worse body image than hypofractionated whole breast radiotherapy at the end of treatment (difference –1·10 [95% CI –1·79 to –0·42], p=0·0016). No significant differences were reported in the other PROs between conventional whole breast radiotherapy compared with hypofractionated whole breast radiotherapy. Interpretation Tumour bed boost was associated with persistent adverse effects on cosmetic status and arm and shoulder functional status, which might inform shared decision making while local recurrence analysis is pending. Funding National Health and Medical Research Council, Susan G Komen for the Cure, Breast Cancer Now, OncoSuisse, Dutch Cancer Society.

BackgroundUtilization of intracranial pressure monitors (ICPMs) has not been consistently shown to improve mortality in patients with severe traumatic brain injury (TBI). A single-center analysis concluded that venous thromboembolism (VTE) chemoprophylaxis (CP) posed no significant bleeding risk in patients following ICPM implementation; however, there is still debate about the optimal use and timing of CP in patients with ICPMs for fear of worsening intracranial hemorrhage. We hypothesized that ICPM use is associated with increased time to VTE CP and thus increased VTE in patients with severe TBI.MethodsA retrospective analysis of the Trauma Quality Improvement Program (2010-2016) was performed to compare severe TBI patients with and without ICPMs. A multivariable logistic regression analysis was completed.ResultsFrom 35,673 patients with severe TBI, 12,487 (35%) had an ICPM. Those with ICPMs had a higher rate of VTE CP (64.3% vs. 49.4%, p

Purpose Pediatric genitalia injury represents 0.6% of all pediatric trauma. It is crucial for providers to understand whether pediatric patients are at risk for violent mechanisms, such as rape, assault, or other abuse. Therefore, we sought to perform a large database analysis of pediatric and adolescent female genitalia trauma, comparing mechanisms of injury (i.e., sexual abuse) and need for operative intervention between adolescent and pediatric cohorts. Methods The National Trauma Data Bank was queried (years 2007–2015) for female patients ≤ 16 years old with external genitalia (vaginal or vulvar) trauma. Two groups were compared: pediatrics (

It is highly desirable to provide our computer science and software engineering students with hands-onexposure to currently industry techniques and technologies. One area of extreme growth and skills shortageis cloud computing which led to a curriculum redesign and a new module to teach these skills to final yearstudents. Cloud computing products are available from a number of vendors, but their academicprogrammes often leave much to be desired, with limited credits and features. In the resource-constraineduniversity sector simply buying vendor credits for students would be expensive but also wasteful as thereis no capital investment. In an attempt to provide hands-on experience with the latest technologies an inhouse “cloud in a cupboard” was designed and created at Queen’s University Belfast. This took advantageof the wide range of free open-source software systems which underpin modern cloud vendors and, for verylittle cost thanks to re-purposed equipment, was able to support a large final-year module and severalundergraduate dissertation projects successfully. Student feedback was very positive, and plans continue togrow this system further to support the current functionality and add more in the coming years.

Worsening quality indicators of health care shake public trust. Although safety and quality of care in hospitals can be improved, healthcare quality remains conceptually and operationally vague. Therefore, the aim of this analysis is to clarify the concept of healthcare quality. Walker and Avant’s method of concept analysis, the most commonly used in nursing literature, provided the framework. We searched general and medical dictionaries, public domain websites, and 5 academic literature databases. Search terms included health care and quality, as well as healthcare and quality. Peer-reviewed articles and government publications published in English from 2004 to 2016 were included. Exclusion criteria were related concepts, discussions about the need for quality care, gray literature, and conference proceedings. Similar attributes were grouped into themes during analysis. Forty-two relevant articles were analyzed after excluding duplicates and those that did not meet eligibility. Following thematic analysis, 4 defining attributes were identified: (1) effective, (2) safe, (3) culture of excellence, and (4) desired outcomes. Based on these attributes, the definition of healthcare quality is the assessment and provision of effective and safe care, reflected in a culture of excellence, resulting in the attainment of optimal or desired health. This analysis proposes a conceptualization of healthcare quality that defines its implied foundational components and has potential to improve the provision of quality care. Theoretical and practice implications presented promote a fuller, more consistent understanding of the components that are necessary to improve the provision of healthcare and steady public trust.

Introduction This patterns of practice study was conducted on behalf of the RANZCR Breast Interest Group in order to document current radiotherapy practices for breast cancer in Australia and New Zealand. The survey identifies variations and highlights potential contentious aspects of radiotherapy management of breast cancer. Methods A fifty-eight question survey was disseminated via the Survey Monkey digital platform to 388 Radiation Oncologists in Australia and New Zealand. Results In total, 156 responses were received and collated. Areas of notable consensus among respondents included hypofractionation (77.3% of respondents would ‘always’ or ‘sometimes’ consider hypofractionation in the management of ductal carcinoma in-situ and 99.3% in early invasive breast cancer); margin status in early breast cancer (73.8% believe a clear inked margin is sufficient and does not require further surgery) and use of bolus in post-mastectomy radiotherapy (PMRT) (91.1% of participants use bolus in PMRT). Areas with a wider degree of variability amongst respondents included regional nodal irradiation and components of radiotherapy planning and delivery (examples include the technique used for delivery of boost and frequency of bolus application for PMRT). Conclusion The results of these patterns of practice survey informs radiation oncologists in Australia and New Zealand of the current clinical practices being implemented by their peers. The survey identifies areas of consensus and contention, the latter of which may lead to a development of research trials and/or educational activities to address these areas of uncertainty.

Introduction: The high frequencies of carriers of severe haemoglobinopathies and of iron deficiency in Southeast Asia require reliable and affordable tests to improve on current screening procedures.Objectives: We evaluate a “one stop” approach using the THALCON dichlorophenolindophenol (DCIP) and one-tube osmotic fragility (OF) tests and measurement of Zinc Protoporphyrin (ZPP) to detect and distinguish HbE and β-thalassaemia traits from iron deficiency. We compare findings with current screening practice in Sri Lanka that relies on the identification of low mean red cell volume and/or mean red cell hemoglobin for this purpose.Methods: Between November 2017 and May 2018, we undertook a cross-sectional survey of secondary school students in Gampaha district, Sri Lanka. The THALCON–DCIP and OF tests were compared to capillary electrophoresis (CE), used as a gold standard to detect haemoglobinopathies. ZPP was measured in whole blood. Plasma ferritin and C-reactive protein (CRP) were measured in students with a raised ZPP concentration.Results: We collected venous blood samples from 1,324/1,332 (99.4%) students. The median age of the students was 17 (IQR 16–18) years, all were Sinhalese and 814/1,324 (61.5%) were female. CE identified 3 students with HbE trait and 26 students with β-thalassaemia trait. The THALCON–DCIP test was positive only in the 3 students with HbE (sensitivity 100%, 95% CI 29.2–100.0; specificity 100%, 95% CI 99.7–100.0). The THALCON–OF test identified all 26 students with β-thalassaemia trait (sensitivity = 100%, 95% CI 86.8–100.0) and 287 students with a normal CE result (specificity = 77.9%; 95% CI 75.5–80.1). It was also positive in 2/3 (66.7%) students with HbE trait. Iron deficiency (ZPP > 70 μmol/mol heme) was present in 118/1,240 (9.5%) students with a normal hemoglobin genotype, all of whom had plasma ferritin

ObjectivesOur aim was to describe the numbers and distribution of patients with different types of thalassemia and to assess the standards of care in all thalassemia treatment centers throughout Sri Lanka and the success of the ongoing prevention programme.MethodsThis cross-sectional island-wide survey was conducted by two trained medical graduates, who visited each thalassemia center to collect data from every patient, using a standardized form. Data was collected through review of patient registers and clinical records.ResultsWe collected data on 1774 patients from 23 centers. 1219 patients (68.7%) had homozygous β-thalassemia, 360 patients (20.3%) had hemoglobin E β-thalassemia, and 50 patients (2%) had sickle β-thalassemia. There were unacceptably high serum ferritin levels in almost all centers. The annual number of births of patients with β-thalassaemia varied between 45-55, with little evidence of reduction over 19 years.ConclusionsCentral coordination of the treatment and ultimately prevention of thalassemia is urgently needed in Sri Lanka. Development of expert centers with designated staff with sufficient resources will improve the quality of care and is preferred to managing patients in multiple small units.

Objectives To report the clinical and virologic epidemiology of a recent epidemic of hepatitis C in thalassaemia patients in Sri Lanka. Background Transfusion‐dependent thalassaemia patients remain at risk for hepatitis C virus (HCV). Here, we report a cluster of recent HCV infections in Sri Lankan thalassaemia patients and examine the phylogenetic relationship of viral sequences. Methods We conducted two prospective cross‐sectional surveys of 513 patients in four Sri Lankan thalassaemia centres in 2014/2015 and re‐surveyed one centre in 2016. We screened for anti‐HCV antibodies using the CTK Biotech enzyme‐linked immunosorbent assay (ELISA) kits and confirmed active infection by reverse transcription‐polymerase chain reaction (RT‐PCR) for HCV‐RNA. HCV genomes were sequenced by unbiased target enrichment. Results Anti‐HCV antibodies were found in 116/513 (22.6%) of patients initially tested. Active hepatitis C infection was found in 26 patients with no cases of active hepatitis B infection. Of 26 patients with HCV, two were infected with genotype 1(a), and the rest had 3(a). In a single centre (Ragama), 122 patients (120 new cases and two previously tested, but negative) were retested for anti‐HCV antibodies. 32/122 (26.2%) patients were seropositive. Twenty‐three (23/122; 18.8%) of these new cases were confirmed by HCV PCR (all genotype 3[a]). Conclusion There is a significant cluster of recent HCV cases in multiply transfused thalassaemia patients in several centres in Sri Lanka. Most of the viruses shared a close phylogenetic relationship. The results are consistent with recent continuing transfusion‐transmitted HCV infection. Routine surveillance for HCV of chronically transfused patients is required irrespective of screening of blood products.

More than half a million children experience non-accidental trauma (NAT) annually. Historically, NAT has been associated with an increased hospital length of stay (LOS). We hypothesized that in pediatric trauma patients, NAT is associated with longer hospital LOS, independent of injury severity, compared to accidental trauma (AT). The Pediatric Trauma Quality Improvement Program (2014–2016) was queried for patients aged 1–16 years. Patients were stratified into two groups: AT and NAT. The median LOS for the entire cohort was identified and used in a multivariable logistic regression analysis. From 93,089 pediatric trauma patients, 417 (

Previous studies have had conflicting results when comparing risk of mortality in patients with gunshot wounds (GSWs) treated at Level-I and II trauma centers. However, the populations studied were restricted geographically. We hypothesized that patients presenting after a GSW to the torso at Level-I centers would have a shorter time to surgical intervention (exploratory laparotomy or thoracotomy) and a lower risk of mortality, compared to Level-IIs in a national database. The Trauma Quality Improvement Program (2010–2016) was queried for patients presenting to Level-I or II trauma center after a GSW to the torso. A multivariable logistic regression analysis was performed. From 17,965 patients with GSWs, 13,812 (76.8%) were treated at Level-Is and 4153 (23.2%) at Level-IIs. There was no difference in the injury severity score (ISS) (p = 0.55). The Level-I cohort had a higher rate of laparotomy (38.9% vs. 36.5%, p

A 58-year-old male with no past medical history presented to the emergency department with sudden onset left lower extremity weakness and central chest pain with radiation to his back. Electrocardiogram revealed an acute inferior and posterior ST-segment elevation myocardial infarction (STEMI). Point-of-care ultrasound (POCUS) demonstrated right ventricular akinesis consistent with infarction, and an intimal defect consistent with an aortic dissection. We determined that cardiothoracic surgery was indicated rather than left-heart catheterization and anticoagulation. Using POCUS we were able to immediately diagnose a dissection of the aortic arch and considerably alter treatment in a patient presenting with STEMI.

Background Squamous cell carcinoma of the scalp is a common clinical problem in an aging population. Despite its high incidence, little has been documented regarding treatment or outcomes. Methods We retrospectively analysed 235 cases treated with curative intent at Peter MaCallum Cancer Centre between 1998 and 2010. The cohort was analysed for its characteristics, management, survival and prognostic factors. Results The patients were primarily male (88%) with a median age of 79 years (range 53–98 years). There was a high proportion of immunosuppressed patients (29%) and stage T2 (48%) tumours. Management included surgery (45%), radiotherapy (28%) and surgery and adjuvant radiotherapy (26%). Median follow up from treatment was 4.5 years. Estimated 5-year overall survival (OS), disease-specific survival and progression-free survival (PFS) were 59, 94 and 51%, respectively. The 5-year cumulative incidence of local and regional relapse was 11 and 7%, respectively. There were four patients who developed distant metastases and died of their disease. Statistically significant prognostic factors identified for poor outcomes for OS and PFS were T2 stage (hazard ratio [1.7 and 2.1) and immunosuppression (HR 3.3 and 3.4). Conclusions We conclude the presence of immunosuppression and T2 stage is prognostic for survival. Further research to establish treatment principles is warranted.

The difficulties in establishing and delivering reliable clinical hematology and laboratory services in resource-limited settings are well recognized. However, much can be achieved by better use of existing resources through a concerted quality improvement approach. The recommendations of this article are based in part upon work in the thalassemias, inherited disorders of hemoglobin that are widely prevalent in Asia, which may serve as a model that is applicable to other common, chronic disorders in resource-poor settings. Available resources are highlighted and recommendations made regarding approaches to improving services. Over the last few years, a number of low and middle-income countries, obtaining support from appropriate governmental sources, have identified and overcome difficulties and significantly improved clinical services for patients with thalassemia.

Background Visual impairment in developing countries has both social and economic impact on individuals and communities. Understanding the subjective visual functioning of populations will allow for local policymakers to identify the need for optometric or ophthalmic services in their communities. Methods The authors surveyed 644 adult patients in Mwanza, Tanzania at three clinics (Buzuruga, Mwananchi and Kisesa) using a modified Visual Functioning Questionnaire 25. Responses were categorized into General health, General vision, Ocular pain, Near activities, Distance activities, Social function, Mental health, Role difficulties, Color vision, Peripheral vision and Dependency. Results Patients at Buzuruga reported the lowest scores on most subscales. Of 100 employed patients, 37% claimed to have at least some difficulty in performing job duties due to their eyesight. At Kisesa, 146 (246/221) patients (66.1%) had never had an eye exam, compared with 134/227 (59.0%) at Buzuruga and 69/173 (39.9%) at Mwananchi (p Conclusions Due to regional differences in visual functioning in Mwanza, a national effort for vision health cannot be entirely successful without addressing the individualized needs of local communities. Reducing the cost of vision care appointments may expand vision health care utilization in Mwanza.

Background: Iron deficiency, the most common micronutrient disorder and cause of anaemia globally, impairs growth, cognition, behaviour and resistance to infection. Methods/Results: As part of a national survey of inherited haemoglobin variants in 7526 students from 72 secondary schools purposefully selected from the 25 districts of Sri Lanka, we studied 5912 students with a normal haemoglobin genotype. Median age was 16.0 (IQR 15.0–17.0) years and 3189 (53.9%) students were males. Most students were Sinhalese (65.7%), with fewer Tamils (23.1%) and Muslims (11.2%). Anaemia occurred in 470 students and was more common in females (11.1%) than males (5.6%). Haemoglobin, serum ferritin, transferrin receptor and iron were determined in 1196 students with low red cell indices and a structured sample of those with normal red cell indices (n = 513). The findings were weighted to estimate the frequencies of iron deficiency and iron deficiency anaemia classified according to WHO criteria. Iron depletion (serum ferritin 28.1 nmol/l) in 11.6% students. Iron deficiency anaemia (cellular iron deficiency with low haemoglobin) occurred in only 130/2794 (4.6%) females and 28/2789 (1.0%) males. Iron biomarkers were normal in 83/470 (14.6%) students with anaemia. In multiple regression analysis, the odds for iron depletion and cellular iron deficiency were about one-third in males compared with females, and the odds for iron deficiency anaemia were about one fifth in males compared to females. Tamil ethnicity and age Conclusions: Low iron status and anaemia remain common problems in Sri Lankan secondary school students especially females, younger students and the socioeconomically disadvantaged Tamil population. More research is needed to identify factors other than low iron status that contribute to anaemia in adolescents.

Studies of the frequency of heterozygous carriers for common inherited diseases of haemoglobin in over 7500 adolescent children in 25 districts in Sri Lanka have disclosed a highly significant variation over very short geo- graphical distances. A further analysis of these findings, including their relationship to the past frequency and distribution of malaria, climatic vari- ation, altitude, ethnic origin and consanguinity rates, have provided evi- dence regarding the evolutionary basis for the variable distribution of these conditions over short distances. It is likely that the complex interplay between malaria and the environment, together with related ethnic and social issues, exists in many countries across the tropical belt. Hence, these observations emphasise the importance of micromapping heterozygote dis- tributions in high-frequency countries in order to define their true burden and the facilities required for the prevention and management of the homozygous and compound heterozygous disorders that result from their interaction.

OBJECTIVE. We investigated occupational therapy faculty beliefs about and perceptions of interprofessional education (IPE) and to identify differences in faculty positions on IPE between programs affiliated with an on-campus academic health care center (AHC) and programs not affiliated with an on-campus AHC. METHOD. Online surveys were distributed by email to 1,466 faculty at programs accredited by the Accreditation Council for Occupational Therapy Education. The results were described using descriptive statistics and cross-tabulations. RESULTS. Faculty responses supported the need for IPE. Ethics was ranked as the most important IPE competency among both the AHC and the non-AHC groups. IPE was more commonly included in the curriculum of programs with an on-campus AHC than in the curriculum of those without an AHC. CONCLUSION. The majority of occupational therapy faculty supported the need for IPE; however, many reported limitations with faculty or time constraints as barriers to IPE.

Hemoglobin E (HbE) β-thalassemia is the most common severe thalassemia syndrome across Asia, and millions of people are carriers. Clinical heterogeneity in HbE β-thalassemia is incompletely explained by genotype, and the interaction of phenotypic variation with hepcidin is unknown. The effect of thalassemia carriage on hepcidin is also unknown, but it could be relevant for iron supplementation programs aimed at combating anemia. In 62 of 69 Sri Lankan patients with HbE β-thalassemia with moderate or severe phenotype, hepcidin was suppressed, and overall hepcidin inversely correlated with iron accumulation. On segregating by phenotype, there were no differences in hepcidin, erythropoiesis, or hemoglobin between severe or moderate disease, but multiple linear regression showed that erythropoiesis inversely correlated with hepcidin only in severe phenotypes. In moderate disease, no independent predictors of hepcidin were identifiable; nevertheless, the low hepcidin levels indicate a significant risk for iron overload. In a population survey of Sri Lankan schoolchildren, β-thalassemia (but not HbE) trait was associated with increased erythropoiesis and mildly suppressed hepcidin, suggesting an enhanced propensity to accumulate iron. In summary, the influence of erythropoiesis on hepcidin suppression associates with phenotypic disease variation and pathogenesis in HbE β-thalassemia and indicates that the epidemiology of β-thalassemia trait requires consideration when planning public health iron interventions.

Vitamin D receptor (VDR) gene polymorphisms have been implicated in susceptibility to tuberculosis (TB), but reports have been inconsistent. We genotyped the VDR single-nucleotide polymorphisms (SNPs) FokI, BsmI, ApaI, and TaqI in 1139 case patients and control subjects and 382 families from The Gambia, Guinea, and Guinea-Bissau. The transmission-disequilibrium test on family data showed a significant global association of TB with SNP combinations FokI-BsmI-ApaI-TaqI and FokI-ApaI that were driven by the increased transmission to affected offspring of the FokI F and ApaI A alleles in combination. The ApaI A allele was also transmitted to affected offspring significantly more often than expected. Case-control analysis showed no statistically significant association between TB and VDR variants. BsmI, ApaI, and TaqI showed strong linkage disequilibrium. The significance of the family-based associations found between TB and FokI-BsmI-ApaI-TaqI and the FA haplotype supports a role for VDR haplotypes, rather than individual genotypes, in susceptibility to TB.

Guillain-Barn! syndrome is a subacute inflammatory demyelinating polyradicular neuropathy of the peripheral nerves. It is characterized by varying degrees of weakness, sensory abnormalities, and autonomic dysfunction. The cause of Guillain-Barre syndrome is not completely understood, but it is believed to be a postinfectious autoimmune disorder, because approximately two thirds of all cases are preceded by an infection, such as those caused by human immunodeficiency virus, cytomegalovirus, Epstein-Barr virus, and Campylobacter jejuni. Occasionally Guillain -Barre syndrome has been reported to come after vaccinations of various types. C jejuni infection, thought to be the most common antecedent infection to Guillain-Barre syndrome and the only bacterial infection that regularly precedes it, has been implicated in 50 to 75 percent of all cases. Culture studies have proved that a high proportion of patients with Guillain-Barre syndrome have C jejuni infection in their stools at the time of the onset of neurologic symptoms as well. We describe a case of Guillain-Barre syndrome associated with gastrointestinal C jejuni infection. This case not only highlights the clinical aspects of Guillain-Barre syndrome but also illustrates the severity of this neurologic syndrome and the lack of response to both plasmapheresis and immunoglobulin therapy.

Hemoglobin E β thalassemia is the commonest form of severe thalassemia in many Asian countries. Its remarkably variable clinical phenotype presents a major challenge to determining its most appropriate management. In particular, it is not clear why some patients with this condition can develop and function well at very low hemoglobin levels. Here, we demonstrate that patients with hemoglobin Eβ thalassemia have a significant decrease in the oxygen affinity of their hemoglobin, that is an increased P50 value, in response to anemia. This may in part reflect the lower level of hemoglobin F in this condition compared with other forms of β thalassemia intermedia. The ability to right-shift the oxygen dissociation curve was retained across the spectrum of mild and severe phenotypes, despite the significantly higher levels of hemoglobin F in the former, suggesting that efforts directed at producing a modest increase in the level of hemoglobin F in symptomatic patients with this disease should be of therapeutic value.

Introduction Worldwide the greatest burden of disease related to beta thalassemia resides in Asia and is largely represented by Hemoglobin E beta thalassemia (HbE/thal) [Weatherall DJ, Ann New York Acad Sci 2005, 1054:11-17]. HbE/thal is the most common serious form of beta thalassemia in many Asian populations. In Sri Lanka, over 17 years, we have characterized over 200 affected patients and had proposed [Olivieri, NF, et al., J Pediatr Hematol Oncol, 2000, 22:593-597], as now shown in less common forms of non-transfusion dependent thalassemia [Taher AT, et al., Br J Haematol 2010, 150:486-489], that non-transfusional iron accumulation (NTIA) is a potential complication in non-transfused patients with HbE/thal. In 2009, we implemented R2-MRI [St Pierre, TG, et al., Blood 2005, 105:855-861] in Sri Lanka. Here we report the variation and severity of non-transfusional iron accumulation (NTIA), in parallel with screening tests of organ dysfunction, in a first group of patients with HbE/thal. Methods Patients aged > 7 years with clinical evidence of iron overload (generally a serum ferritin > normal range in the absence of a history of regular transfusions) were recruited from The National Thalassaemia Centre (NTC), Kurunegala, Sri Lanka. LIC was measured using R2-MRI (FerriScan¨) with facilities situated a 6 hour return bus trip from the NTC. Liver function was evaluated using serum alanine transaminase (ALT). Fasting blood glucose (FBG), thyroid stimulating hormone (TSH), serum calcium and phosphate and serum ferritin (SF) were measured in local laboratories. Cardiac function was measured using echocardiography. Correlations between parameters were assessed using non-parametric (Spearman) analysis. Receiver operating characteristic (ROC) curve analysis was used to determine the optimum cut-off values of LIC and serum ferritin for predicting ALT values above the upper limit of the laboratory reference range. Results LIC measurements were successfully acquired for 110 of 112 enrolled subjects (45 male/ 67 female) with median age [range] 22.5 [7.8 – 61.5] years over 3 years. The variation in LIC was considerably, and unexpectedly, broad: median [range] LIC was 8.8 [0.7 – 65.0] mg Fe/g dw. LIC exceeded the threshold of risk established as 7.0 mg Fe/g dw [Olivieri NF, Brittenham GM, Blood 1997, 89:739-761] in a substantial proportion (57%) of patients. In parallel, organ dysfunction was observed: in a substantial group (52%), ALT was increased above normal range, while in 11%, ejection fraction was reduced (less than 56%). FBG and TSH were elevated above normal range in a substantial proportion of patients (6% and 30% respectively). Significant correlations were observed between LIC and serum ferritin concentration (r2=0.69, p Discussion This study of Asian patients with HbE/thal using R2-MRI, an FDA-approved non-invasive method of evaluation of LIC, reveals a wide range of NTIA and, in parallel, a significant proportion of patients with evidence of liver dysfunction. Our data suggest that the liver is at direct risk from NTIA in HbE/thal at a threshold of 6.35 mg Fe/g dry liver tissue. More robust correlations with dysfunction occurring in other organs may be expected to emerge during longitudinal studies which will be critical to understanding the evolution of organ damage occurring secondary to NTIA in this disorder. These studies are urgently needed to prevent morbidity and premature death in this most common form of beta thalassemia. Disclosures: St Pierre: Resonance Health Ltd: Consultancy, Equity Ownership, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Novartis: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau. Porter:Novartis: Consultancy, Research Funding; Celgene: Consultancy; Shire: Consultancy.

Meningitis is an important cause of childhood mortality in sub-Saharan Africa. A case-control study investigating the role of the Toll-like receptor 4 gene in host susceptibility to Group A Neisseria meningitidis meningitis was conducted in 524 Gambian children. There was no association between a functional Toll-like receptor 4 gene polymorphism and meningitis, suggesting that this variant is not a major determinant of disease in this population.