Survival and complications in patients with haemoglobin E thalassaemia in Sri Lanka: a prospective, longitudinal cohort study.

BACKGROUND: Worldwide, haemoglobin E ß-thalassaemia is the most common genotype of severe ß-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. METHODS: 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. FINDINGS: 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. INTERPRETATION: 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. FUNDING: Wellcome Trust, Medical Research Council, US March of Dimes, Anthony Cerami and Ann Dunne Foundation for World Health, and Hemoglobal.

Observational study on the current status of thalassaemia in Malaysia: a report from the Malaysian Thalassaemia Registry.

OBJECTIVE: Thalassaemia is the most common inherited blood disorder in Malaysia. This study aims to report the current status of thalassaemia in Malaysia and provide a comprehensive understanding of the disease through data obtained from the Malaysian Thalassaemia Registry. DESIGN: Data were extracted from the Malaysian Thalassaemia Registry, a web-based system accessible to enrolled users through www.mytalasemia.net.my. SETTING: The Malaysian Thalassaemia Registry data was recorded from reports obtained from 110 participating government and university hospitals in Malaysia. PARTICIPANTS: The patients were those attending the 110 participating hospitals for thalassaemia treatment. INTERVENTION: Data were collected from the Malaysian Thalassaemia Registry from 2007 until the fourth quarter of 2018. PRIMARY OUTCOME MEASURE: 7984 out of 8681 patients with thalassaemia registered in the Malaysian Thalassaemia Registry were reported alive. RESULTS: Majority of the patients were reported in the state of Sabah (22.72%); the largest age group affected was 5.0-24.9 years old (64.45%); the largest ethnic group involved was Malay (63.95%); and the major diagnosis was haemoglobin E/ß-thalassaemia (34.37%). From the 7984 patients, 56.73% were on regular blood transfusions and 61.72% were on chelation therapy. A small fraction (14.23%) has undergone splenectomy, while the percentage of patients with severe iron overload (serum ferritin ≥5000 µg/L) reduced over time. However, cardiac complications are still the main cause of death in patients with thalassaemia. CONCLUSION: Data gathered into the registry can be used to understand the progression of the disorder, to monitor iron overload management and to improve the outcomes of treatment, to enhance preventive strategies, reduce healthcare burden and improve the quality of life. Sustainability of the Malaysian Thalassaemia Registry is important for surveillance of thalassaemia management in the country and help the national health authorities to develop more effective policies.

Adherence to iron chelation therapy in patients who switched from deferasirox dispersible tablets to deferasirox film-coated tablets.

OBJECTIVE: To compare real-world adherence to and persistence with deferasirox film-coated tablets (DFX-FCT) and deferasirox dispersible tablets (DFX-DT) among patients who switched from DFX-DT to DFX-FCT, overall and by disease type (sickle cell disease [SCD], thalassemia, and myelodysplastic syndrome [MDS]). METHODS: Patients were ≥2 years old and had ≥2 DFX-FCT claims over the study period and ≥2 DFX-DT claims before the index date (first DFX-FCT claim). The DFX-DT period was defined from the first DFX-DT claim to the index date; the DFX-FCT period was defined from the index date to the end of the study period. Adherence was measured as medication possession ratio (MPR) and proportion of days covered (PDC). Persistence was defined as continuous medication use without a gap ≥30 or 60 days between refills. Comparisons were conducted using paired-sample Wilcoxon sign-rank and McNemar's tests. RESULTS: In total, 606 patients were selected (SCD: 348; thalassemia: 107; MDS: 106; other: 45). Adherence and persistence in the DFX-FCT vs DFX-DT period was significantly higher across all measures: mean MPR was 0.80 vs 0.76 (p < .001); 60.9% vs 54.3% of patients had MPR ≥ 0.8 (p = .009); mean 3-month PDC was 0.83 vs 0.71 (p < .001); 64.2% vs 45.4% of patients had 3-month PDC ≥ 0.8 (p < .001); 87.2% vs 63.4% of patients had 3-month persistence with no gap ≥30 days and 96.1% vs 79.9% with no gap ≥60 days (p < .001). Adherence and persistence improved after switching across all diseases, particularly MDS. CONCLUSIONS: Adherence and persistence improved significantly after switching from DFX-DT to DFX-FCT for all diseases, but especially MDS.

[Management of patients with major beta thalassemia in a paediatric department in the south of Tunisia: About 26 cases]. / Prise en charge thérapeutique des patients atteints de bêta-thalassémie majeure dans un service de pédiatrie du sud tunisien : à propos de 26 cas.

AIM: Our objectives were to assess the management of patients with major thalassemia and identify the various complications and monitoring means. PATIENTS AND METHODS: A retrospective study was conducted on 26 ß-thalassemic patients in the department of paediatrics, Hédi Chaker hospital, Sfax, Tunisia during a period of 25 years (from 1 January 1990 to 31 December 2014). RESULTS: The mean age of the beginning of transfusion was 11.5 months. That was with phenotyped red blood cells but not leukodepleted blood. Twenty-three patients received chelation. Before 2001, all patients received deferoxamine, poor adherence to this treatment was observed in 66% of cases. It was replaced by deferiprone since 2006 and deferasirox since 2009. A combination of 2 or 3 chelators was indicated for four patients. A total splenectomy was performed in 10 cases patients; it was due to hypersplenism. The bone marrow transplant was performed for one patient at the age of 9 year but it was rejected. Many complications were detected: endocrine complications (19 cases), immune complications (9 cases), gallbladder stones (5 cases), cardiac complications (4 cases), osteoporosis (3 cases), infectious complications (3 cases) and thromboembolic complications (2 cases). We noted some side effects related to chelation therapy in twelve cases. Four patients were dead. CONCLUSION: Improving the medical care of homozygous ß-thalassemic children requires adherence to transfusion regimen and chelation therapy. Bone marrow transplantation remains the only possible curative therapy, which must be promoted in our country.

Environmental Remediation to Address Childhood Lead Poisoning Epidemic due to Artisanal Gold Mining in Zamfara, Nigeria.

BACKGROUND: From 2010 through 2013, integrated health and environmental responses addressed an unprecedented epidemic lead poisoning in Zamfara State, northern Nigeria. Artisanal gold mining caused widespread contamination resulting in the deaths of > 400 children. Socioeconomic, logistic, and security challenges required remediation and medical protocols within the context of local resources, labor practices, and cultural traditions. OBJECTIVES: Our aim was to implement emergency environmental remediation to abate exposures to 17,000 lead poisoned villagers, to facilitate chelation treatment of children ≤ 5 years old, and to establish local technical capacity and lead health advocacy programs to prevent future disasters. METHODS: U.S. hazardous waste removal protocols were modified to accommodate local agricultural practices. Remediation was conducted over 4 years in three phases, progressing from an emergency response by international personnel to comprehensive cleanup funded and accomplished by the Nigerian government. RESULTS: More than 27,000 m3 of contaminated soils and mining waste were removed from 820 residences and ore processing areas in eight villages, largely by hand labor, and disposed in constructed landfills. Excavated areas were capped with clean soils (≤ 25 mg/kg lead), decreasing soil lead concentrations by 89%, and 2,349 children received chelation treatment. Pre-chelation geometric mean blood lead levels for children ≤ 5 years old decreased from 149 µg/dL to 15 µg/dL over the 4-year remedial program. CONCLUSIONS: The unprecedented outbreak and response demonstrate that, given sufficient political will and modest investment, the world's most challenging environmental health crises can be addressed by adapting proven response protocols to the capabilities of host countries. CITATION: Tirima S, Bartrem C, von Lindern I, von Braun M, Lind D, Anka SM, Abdullahi A. 2016. Environmental remediation to address childhood lead poisoning epidemic due to artisanal gold mining in Zamfara, Nigeria. Environ Health Perspect 124:1471-1478; http://dx.doi.org/10.1289/ehp.1510145.

Intoxicación por mercurio elemental por inyección intramuscular: presentación de caso y revisión de literatura / Poisoning with elemental mercury by intramuscular injection. Case report and review of literature

Se han reportado en la literatura pocos casos de intoxicación por mercurio por administración en tejidos blandos. No se cuenta con suficiente evidencia acerca del manejo con terapia quelante en este tipo de intoxicación. Se reporta el caso de una mujer de 34 años con antecedente psiquiátrico la cual se administró mercurio intramuscular en fosa cubital izquierda con fines autolíticos. Acudió al servicio de urgencias 24 horas posteriores a su administración, el motivo principal fue el dolor intenso en la zona y la presencia de edema, sin efectos sistémicos. La radiografía mostró depósitos metálicos en 1/3 de brazo, localizados en músculo, y que migraron a través de la fascia hacia 2/3 del antebrazo. La placa de tórax no mostró alteraciones. Fue intervenida quirúrgicamente en 3 ocasiones extrayendo mínimas cantidades de mercurio. La paciente fue manejada con antibióticos por presencia de celulitis. Un mes después presentó temblor mercurial, razón por la cual se tomaron muestras de sangre y orina para la determinación de mercurio, el cual resulto elevado en ambas muestras, por lo que se le administró terapia quelante con D-penicilamina.

There are just a few cases of mercury toxicity after administration in soft tissue, reported in the literature. There is insufficient evidence about the management with chelation therapy in this type of poisoning. We report the case of a 34 year-old woman with a psychiatric history who administered herself a mercury injection into de muscle in the left cubital fossa, referred as a suicide attempt. She came to the emergency department 24 hours after administration; the main reason was the intense pain in the area and the presence of edema, with no systemic effects. Radiography showed metallic deposits in 1/3 arm, located in muscle, which moved through the fascia to 2/3 of the forearm. Chest radiography was normal. She underwent surgery trhee times extracting trace amounts of mercury. The patient was managed with antibiotics by the presence of cellulite. One month later she had tremor mercuralis, so a blood and urine samples were sent to the laboratory in order to determinate mercury levels, which resulted high in both fluids, therefore chelation therapy with D-penicillamine was administered.

Incidence of testicular microlithiasis in patients with ß-thalassemia major.

We assessed the prevalence of testicular microlithiasis by scrotal ultrasonography in ß-thalassemia major patients older than 10 years and evaluated the association with serum ferritin levels, calcium (Ca), phosphate (Ph), and parathyroid hormone levels (PTH). In this cross-sectional study, 132 male ß-thalassemia major patients from 300 male patients older than 10 years old were randomly evaluated by scrotal ultrasonography. Parathyroid hormone, calcium, phosphate, and serum ferritin levels were also evaluated. All of the patients were urologically asymptomatic. One hundred healthy age-matched subjects were selected as control group. Testicular microlithiasis was found in 16 patients and 1 individual in control group (12.1 vs 1 %; p = 0.003). Testicular microlithiasis was associated with age and high serum ferritin levels, but there was no association between Ca, Ph, and PTH levels; blood transfusion; and oral or subcutaneous iron chelation therapy. Also, there was no significant correlation between hyperparathyroidism, history of viral hepatitis, and splenectomy with testicular microlithiasis. The frequency of testicular microlithiasis in ß-thalassemia major patients was higher than previously reported. A correlation was found between testicular microlithiasis with age and serum ferritin levels, so regular and adequate iron chelator therapy (at least 10-12 h per day for 5-6 days a week) is recommended. We suggest a close observation and treatment with iron-chelating agents of these patients. Since testicular microlithiasis is occasionally associated with germ cell tumors, clinical and sonographic follow-up is recommended.

Multicenter COMPACT study of COMplications in patients with sickle cell disease and utilization of iron chelation therapy.

BACKGROUND: Over the past few decades, lifespans of sickle cell disease (SCD) patients have increased; hence, they encounter multiple complications. Early detection, appropriate comprehensive care, and treatment may prevent or delay onset of complications. OBJECTIVE: We collected longitudinal data on sickle cell disease (SCD) complication rates and associated resource utilization relative to blood transfusion patterns and iron chelation therapy (ICT) use in patients aged ≥16 years to address a gap in the literature. RESEARCH DESIGN AND METHODS: Medical records of 254 SCD patients ≥16 years were retrospectively reviewed at three US tertiary care centers. MAIN OUTCOME MEASURES: We classified patients into cohorts based on cumulative units of blood transfused and ICT history: <15 units, no ICT (Cohort 1 [C1]), ≥15 units, no ICT (Cohort 2 [C2]), and ≥15 units with ICT (Cohort 3 [C3]). We report SCD complication rates per patient per year; cohort comparisons use rate ratios (RRs). RESULTS: Cohorts had 69 (C1), 91 (C2), and 94 (C3) patients. Pain led to most hospitalizations (76%) and emergency department (ED) (82%) visits. Among transfused patients (C2+C3), those receiving ICT were less likely to experience SCD complications than those who did not (RR [95% CI] C2 vs. C3: 1.33 [1.25-1.42]). Similar trends (RR [95% CI]) were observed in ED visits and hospitalizations associated with SCD complications (C2 vs. C3, ED: 1.94 [1.70-2.21]; hospitalizations: 1.61 [1.45-1.78]), but not in outpatient visits. CONCLUSIONS: Although the most commonly reported SCD complication among all patients was pain, patients who received ICT were less likely to experience pain and other complications than those who did not. These results highlight the need for increased patient and provider education on the importance of comprehensive disease management.

[Evaluation of transfusion hemochromatosis prevalence, SFVTT-01 study: preliminary results of the SFVTT working group]. / Évaluation de la prévalence de l'hémosidérose post-transfusionnelle, étude SFVTT-01: résultats préliminaires du groupe de travail de la SFVTT.

RATIONAL: Although notification of post-transfusion hemosiderosis is mandatory since 1994 among the French hemovigilance network, it is so far largely under reported. PATIENTS AND METHODS: We screened 42,443 patients hospitalized for blood diseases in France in 2009 and 2010 and determined which patients had received more than 20 PRC. Among them, we selected those having at least one measure of serum ferritin, and subsequently those which ferritin was greater than or equal to 1000 ng/mL. RESULTS: Three thousand eight hundred and twelve patients (9%) received more than 20 PRC, 1935 (4.5%) had a ferritin assay, which was increased in 1216 patients (2.9%). Eight hundred and eighty-one patients underwent an hemovigilance report form. Forty-nine percent had low-risk myelodysplasia or acute leukemia, 7% hemoglobinopathies. Hemosiderosis was asymptomatic for 680 patients (77%), serious 188 (88%) and life-threatening for 11 (1%). Two patients died of terminal heart failure. The most severe hemosiderosis (≥ grade 2) were low-risk myelodysplasia and idiopathic aplastic anemia. Ninety-two percent of thalassemia patients and 46% of sickle cell anemia patients received an iron chelator. For low-risk myelodysplastic syndromes and idiopathic aplastic anemia, 228 of the 317 patients whose treatment is known and who could benefit from iron chelation (72%) have not received it. CONCLUSION: These results encourage seeking optimal transmission of information (over 20 CGR) to the clinician, and prolonging hemovigilance action towards a more comprehensive statement of post-transfusion hemochromatosis.

Clinical characteristics and management of iron overload in 631 patients with chronic transfusion dependency: results from a multicentre, observational study.

BACKGROUND: Long-term red blood cell transfusion therapy results in iron overload. Consensus documents have been developed for several transfusion-dependent groups of patients to provide clinicians with guidance on the monitoring and treatment of this transfusion complication. The objective of this study was to describe the clinical characteristics and current standard of care for patients with transfusion dependency in Spain. MATERIAL AND METHODS: This observational, multicentre study was conducted from November 2008 to December 2009 in 41 Spanish hospitals and day-care centres. Patients who received their first transfusion after January 2007, and who had received at least 10 units of packed red blood cells at the time of inclusion were eligible for the study. RESULTS: We collected data from 631 patients with a mean age of 65±17 years. Haematological disease (84% of patients) was the most frequent underlying disorder. Patients had received a mean of 30±26 red blood cell units from diagnosis until inclusion in the study, and a mean of 18±18 red blood cell units in the previous year. Ferritin levels were available before and after starting the study for 116 (18%) and 412 (65%) patients, respectively. Mean ferritin level at study inclusion was 1,570 ng/mL, and 58% of patients had a ferritin level of at least 1,000 ng/mL. In spite of this, only 89 (14%) patients were receiving chelation therapy. DISCUSSION: The management of patients with transfusion dependency could be improved by using ferritin levels to diagnose iron overload and guide the timely start of chelation therapy.