Nizri Hameed

Bio: Nizri Hameed is an academic researcher. The author has contributed to research in topics: Internal medicine & Placebo. The author has an hindex of 2, co-authored 3 publications receiving 17 citations.

A nationwide survey of hospital-based thalassemia patients and standards of care and a preliminary assessment of the national prevention program in Sri Lanka.

Abstract: Objectives Our 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. Methods This 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. Results We 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. Conclusions Central 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.

A randomised double-blind placebo-controlled clinical trial of oral hydroxyurea for transfusion-dependent β-thalassaemia

Abstract: Hydroxyurea is an antimetabolite drug that induces fetal haemoglobin in sickle cell disease. However, its clinical usefulness in β-thalassaemia is unproven. We conducted a randomised, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of hydroxyurea in transfusion-dependent β-thalassaemia. Sixty patients were assigned 1:1 to oral hydroxyurea 10-20 mg/kg/day or placebo for 6 months by stratified block randomisation. Hydroxyurea treatment did not alter the blood transfusion volume overall. However, a significantly higher proportion of patients on hydroxyurea showed increases in fetal haemoglobin percentage (89% vs. 59%; p < 0.05) and reductions in erythropoietic stress as measured by soluble transferrin receptor concentration (79% vs. 40%; p < 0.05). Based on fetal haemoglobin induction (> 1.5%), 44% of patients were identified as hydroxyurea-responders. Hydroxyurea-responders, required significantly lower blood volume (77 ± SD27ml/kg) compared to hydroxyurea-non-responders (108 ± SD24ml/kg; p < 0.01) and placebo-receivers (102 ± 28ml/kg; p < 0.05). Response to hydroxyurea was significantly higher in patients with HbE β-thalassaemia genotype (50% vs. 0%; p < 0.01) and Xmn1 polymorphism of the γ-globin gene (67% vs. 27%; p < 0.05). We conclude that oral hydroxyurea increased fetal haemoglobin percentage and reduced erythropoietic stress of ineffective erythropoiesis in patients with transfusion-dependent β-thalassaemia. Hydroxyurea reduced the transfusion burden in approximately 40% of patients. Response to hydroxyurea was higher in patients with HbE β-thalassaemia genotype and Xmn1 polymorphism of the γ-globin gene.

Headache: an important symptom possibly linked to white matter lesions in thalassaemia

Abstract: Neurological manifestations are reported only occasionally in patients with thalassaemia and are given much less prominence than the complications related to anaemia and iron overload. White matter changes (WMCs) on magnetic resonance imaging (MRI) in patients with thalassaemia were first reported two decades ago but the significance of these lesions remains unclear. We studied the neurological and cognitive manifestations in 82 older patients with thalssaemia [25 Thalassaemia major (TM), 24 thalassaemia intermedia (TI) and 33 haemaglobin E β thalassaemia (EBT)] and 80 controls, and found that headaches were more common in thalassaemia patients (50/82, 61%) than in controls (18/80, 22·5%: P < 0·001). WMCs on MRI were found in 20/82 (24·3%) patients and 2/29 (6·9%) controls had (P = 0·078). WMC were more common among those with headaches (17/50: 34%) than in those without headache (3/32; 9·3%) (P = 0·023). WMCs were not associated with reduction of cognition. Nevertheless, cognition was lower in the TI and EBT groups compared with those with TM (P = 0·002). The association of headache with WMC in thalassaemia has not been reported before and warrants further study.

A "One-Stop" Screening Protocol for Haemoglobinopathy Traits and Iron Deficiency in Sri Lanka.

Abstract: 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 <15 ng/ml and CRP <5 mg/L. Conclusion: This one-stop approach offers reliable and affordable population screening for both haemoglobinopathy traits and iron deficiency in resource-limited settings where these conditions are common and ensures that iron supplements are targeted only to those who require them. Further work is warranted to refine the OF test to reduce the number of false positive results.

World distribution, population genetics, and health burden of the hemoglobinopathies

Abstract: Although information about the precise world distribution and frequency of the inherited hemoglobin disorders is still limited, there is no doubt that they are going to pose an increasing burden on global health resources in the future. Their high frequency is a reflection of natural selection combined with a high frequency of consanguineous marriages in many countries, together with an epidemiological transition; whereby, as public health measures improve in the poorer countries of the world, more babies with these disorders are surviving to present for treatment.

The parental perspective of thalassaemia in Bangladesh: lack of knowledge, regret, and barriers.

Abstract: BACKGROUND Thalassaemia, a hereditary haemoglobin disorder, is a major public health concern in some parts of the world. Although Bangladesh is in the world's thalassaemia belt, the information on this disease is scarce. Additionally, the awareness of this life threatening, but potentially preventable disease is surprisingly poor. However, mass awareness is pivotal for the development of an effective preventive strategy. In this context, the understanding of parental perspectives is essential to grasp the magnitude of the problem. Therefore, this study aimed to investigate the parental knowledge gaps and perceptions regarding thalassemia, the barriers confronted by the parents for caring for their thalassaemic children and their attitude to prenatal screening and prenatal diagnosis. METHODS This cross-sectional study was conducted between January 2018 and December 2018 at a dedicated thalassemia hospital located in Dhaka. A structured questionnaire was used for face-to-face interviews with parents of thalassaemic children. Descriptive statistics were used to analyse data. RESULTS Of 365 respondents, nearly all respondents (97%) had not heard about the term, 'thalassemia' before the disease was diagnosed in their children; all (100%) were unscreened for carrier status prior to marriage. Mean knowledge scores were significantly higher in respondents with higher income and education. Most respondents (~ 91%) had a guilty feeling for not undergoing premarital screening. Only around 36% of them had heard about prenatal diagnosis. Approximately 25% participants would consider prenatal diagnosis in a future pregnancy, while 70% of them were unsure and only ~ 5% would decline prenatal diagnosis. Only 9.3% mothers had prenatal diagnosis in a previous pregnancy. Nearly 80% of the parents faced difficulty for obtaining blood donors regularly and a similar proportion (~ 81%) of them did not receive support from any organized blood clubs. More than 40% of the parents reported they felt socially stigmatized. CONCLUSION This study suggests poor parental knowledge regarding thalassaemia including prenatal diagnosis and the challenges faced while caring for their children. These findings would be of paramount importance in planning and devising effective prevention and intervention strategies in Bangladesh as well as other countries with similar sociocultural setting.

Prevalence of Transfusion Transmitted Infections and the Quality of Life in β-thalassemia Major Patients.

Abstract: Objectives To determine the prevalence of hepatitis B, hepatitis C, and human immunodeficiency virus (HIV) in chronically transfused β-thalassemia major (TM) patients, and to assess their quality of life (QoL). Methods This cross-sectional study was conducted in three different thalassemia centers located in Peshawar, Khyber Pakhtunkhwa from January to July 2019. These centers provide screened blood and essential medical care for thalassemia patients. These centers include the Fatimid Foundation, Hamza Foundation, and Rehman Medical Institute, Peshawar, Khyber Pakhtunkhwa. A total of 431 blood transfusion-dependent β-thalassemia patients registered at these centers were selected. QoL in β-TM patients was assessed by a newly developed instrument, the TranQoL questionnaire. For the data analysis procedure, Microsoft Excel and Statistical Package for the Social Sciences; version 22 (SPSS Inc., Chicago, IL) was used. Results A total of 431 patients were included in our study. The ages ranged from five years to 23 years with a mean age of 11.54 ± 3.6 years; 58.93% were male and the rest were female with a male to female ratio of 1.43:1. A total of 129 (29.93%) patients were infected by transfusion-transmitted infections (TTIs). Hepatitis C virus (HCV) was found prevalent in 23.66%, hepatitis B virus (HBV) was found in 4.87%, and HIV was found prevalent in 1.39% cases. The results showed a high proportion of HCV in males 27.95% as compared to females 17.51% (p value = 0.31). Patients were divided into high (good) QoL score of >50 and low (poor) score of <50. In patients with hepatitis C, the QoL was poor in 90 (88.23%) patients and was good in only 12 (11.76%) patients (p value=0.01); in the hepatitis B group, it was good in only eight (38.09%) and poor in 13 (61.90%) patients (p-value 0.04), and for patients with HIV, it was poor in all six patients (p=0.001). Conclusion Our study concludes that transfusion-transmitted disease is very high and that HCV is the leading TTI followed by HBV and HIV. QoL in patients with TTIs was poor. The use of advanced technology in blood screening, voluntary donations, donor selection, and asepsis during blood transfusion is imperative to curtail the transmission.

A randomised double-blind placebo-controlled clinical trial of oral hydroxyurea for transfusion-dependent β-thalassaemia

Abstract: Hydroxyurea is an antimetabolite drug that induces fetal haemoglobin in sickle cell disease. However, its clinical usefulness in β-thalassaemia is unproven. We conducted a randomised, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of hydroxyurea in transfusion-dependent β-thalassaemia. Sixty patients were assigned 1:1 to oral hydroxyurea 10-20 mg/kg/day or placebo for 6 months by stratified block randomisation. Hydroxyurea treatment did not alter the blood transfusion volume overall. However, a significantly higher proportion of patients on hydroxyurea showed increases in fetal haemoglobin percentage (89% vs. 59%; p < 0.05) and reductions in erythropoietic stress as measured by soluble transferrin receptor concentration (79% vs. 40%; p < 0.05). Based on fetal haemoglobin induction (> 1.5%), 44% of patients were identified as hydroxyurea-responders. Hydroxyurea-responders, required significantly lower blood volume (77 ± SD27ml/kg) compared to hydroxyurea-non-responders (108 ± SD24ml/kg; p < 0.01) and placebo-receivers (102 ± 28ml/kg; p < 0.05). Response to hydroxyurea was significantly higher in patients with HbE β-thalassaemia genotype (50% vs. 0%; p < 0.01) and Xmn1 polymorphism of the γ-globin gene (67% vs. 27%; p < 0.05). We conclude that oral hydroxyurea increased fetal haemoglobin percentage and reduced erythropoietic stress of ineffective erythropoiesis in patients with transfusion-dependent β-thalassaemia. Hydroxyurea reduced the transfusion burden in approximately 40% of patients. Response to hydroxyurea was higher in patients with HbE β-thalassaemia genotype and Xmn1 polymorphism of the γ-globin gene.

Major Depression in Children with Transfusion-Dependent Thalassemia Is Strongly Associated with the Combined Effects of Blood Transfusion Rate, Iron Overload, and Increased Pro-inflammatory Cytokines.

Abstract: Beta-thalassemia major patients are treated with repeated blood transfusions, which may cause iron overload, which in turn may induce immune aberrations, and show an increased risk of depression. The aim of the present study is to examine whether repeated blood transfusions, iron overload, and immune-inflammatory responses are associated with depression in children (6–12 years) with transfusion-dependent thalassemia (TDT). The Children’s Depression Inventory (CDI), iron status (serum iron, ferritin, transferrin, TS%), and serum levels of CCL11, IL-1β, IL-10, and TNF-α were measured in TDT with (n = 54) and without (n = 57) a major depression-like episode (MDLE) and in healthy children (n = 55). The results show that MDLE due to TDT is associated with a greater number of blood transfusions and increased iron overload and IL-1β levels. Partial least squares path analysis shows that 68.8% of the variance in the CDI score is explained by the number of blood transfusions, iron overload, and increased levels of IL-1β and TNF-α. The latter two cytokines partly mediate the effects of iron overload on the CDI score, while the effects of blood transfusions on the CDI score are partly mediated by iron overload and the path from iron overload to immune activation. Iron overload is also associated with increased IL-10 and lower CCL11 levels, but these alterations are not significantly associated with depression. In conclusion, blood transfusions may be causally related to MDLE in TDT children and their effects are in part mediated by increased iron overload and the consequent immune-inflammatory response. The results suggest that effects of iron overload and its consequences including inflammation and oxidative stress toxicity may cause MDLE. Current treatment modalities with folic acid and vitamin C are insufficient to attenuate iron overload and immune-inflammatory responses and to prevent MDLE in children with TDT.