Addressing Thalassaemia Management from Patients' Perspectives: An International Collaborative Assessment.

Background and Objectives: The effective management of chronic diseases, particularly hereditary and rare diseases and thalassaemia, is an important indicator of the quality of healthcare systems. We aimed to assess healthcare services in different countries for thalassaemia patients by using publicly available health indicators and by surveying thalassaemia patients and their caregivers. Materials and Methods: We reviewed official worldwide databases from the WHO, World Bank, and scientific resources, and we used a structured patient-tailored self-completed questionnaire to survey thalassaemia patients and their caregivers in 2023. Results: A total of 2082 participants were surveyed (mean age, 27 years; males, 42%). About 1 in 4 respondents did not complete high-school education, while 24% had a bachelor's degree. About a third of respondents were married and were in either full- or part-time employment. The vast majority (~80%) had initiated transfusion therapy between 1 and 4 years of age. Only 42% reported no delays in receiving blood transfusion, while 47% reported occasional delays and 8% serious delays. About half of patients reported being very satisfied (11%) or satisfied (38%) with the quality of services provided, while 1 in 3 patients reported being unsatisfied or very unsatisfied, and that their access to treatment was difficult or very difficult due to traveling expenses and the high cost of treatment. Conclusions: Important improvements in the care of thalassaemia patients have been documented during the past few decades. Nevertheless, additional focus is required through national healthcare systems to effectively address the many unmet needs revealed by our recent survey, as well as to achieve satisfactory patient outcomes.

Magnetic resonance imaging assessment of the changes of cardiac and hepatic iron load in thalassemia patients before and after hematopoietic stem cell transplantation.

To investigate the value of T2* technique on 3.0 T magnetic resonance imaging (MRI) in evaluating the changes of cardiac and hepatic iron load before and after hematopoietic stem cell transplantation (HSCT) in patients with thalassemia (TM), the 141 TM patients were divided into 6 group for subgroup analysis: 6, 12, 18, 24 and > 24 months group, according to the postoperative interval. The T2* values of heart and liver (H-T2*, L-T2*) were quantified in TM patients before and after HSCT using 3.0 T MRI T2* technology, and the corresponding serum ferritin (SF) was collected at the same time, and the changes of the three before and after HSCT were compared. The overall H-T2* (P = 0.001) and L-T2* (P = 0.041) of patients after HSCT were higher than those before HSCT (mean relative changes = 19.63%, 7.19%). The H-T2* (P < 0.001) and L-T2* (P < 0.001) > 24 months after HSCT were significantly higher than those before HSCT (mean relative changes = 69.19%, 93.73%). The SF of 6 months (P < 0.001), 12 months (P = 0.008), 18 months (P = 0.002) and > 24 months (P = 0.001) were significantly higher than those before HSCT (mean relative changes = 57.93%, 73.84%, 128.51%, 85.47%). There was no significant improvement in cardiac and liver iron content in TM patients within 24 months after HSCT, while the reduction of cardiac and liver iron content in patients is obvious when > 24 months after HSCT.

Economic burden of Thalassemia treatment: An analysis from the Vietnam Social Security perspective.

OBJECTIVES: Thalassemia is a genetic disorder that significantly impacts the health and well-being of individuals in Vietnam. This study aimed to assess the economic burden of Thalassemia treatment in Lam-Dong Province from the perspective of the Vietnam Social Security and to develop a model to forecast these costs. METHODS: This study analyzed the medical records of all 288 health-insured Thalassemia patients who received treatment in Lam-Dong Province from 2019-2021. The annual economic burden was calculated as the total direct medical cost of treatment per patient over one year. Bayesian Model Averaging (BMA) was utilized to forecast economic burdens. The best fit model was selected based on evaluation criteria including the R2 value, the Bayesian information criterion (BIC), and posterior model probabilities. RESULTS: The study found that the average annual economic burden of Thalassemia treatment was VND 9,947,000 (±6,854,000), equivalent to approximately USD 426.7 (±294.0), with blood transfusions being the main contributor to costs (63%). Using BMA, the best fit model to forecast economic burdens included variables including patient age, sex, and length of hospitalization, with age being the key factor with the greatest impact on the increase in economic burden. CONCLUSION: These findings provided important information for policymakers in Vietnam, as they highlighted the significant economic burden of Thalassemia treatment in the country. By developing a model to forecast these costs, policymakers can make informed decisions on how to allocate resources and support individuals with Thalassemia and their families.

Carrier Screening Programs for Cystic Fibrosis, Fragile X Syndrome, Hemoglobinopathies and Thalassemia, and Spinal Muscular Atrophy: A Health Technology Assessment.

Background: We conducted a health technology assessment to evaluate the safety, effectiveness, and cost-effectiveness of carrier screening programs for cystic fibrosis (CF), fragile X syndrome (FXS), hemoglobinopathies and thalassemia, and spinal muscular atrophy (SMA) in people who are considering a pregnancy or who are pregnant. We also evaluated the budget impact of publicly funding carrier screening programs, and patient preferences and values. Methods: We performed a systematic literature search of the clinical evidence. We assessed the risk of bias of each included study using the Cochrane Risk of Bias tool and the Risk of Bias Assessment tool for Non-randomized Studies (RoBANS), and the quality of the body of evidence according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria. We performed a systematic economic literature search and conducted cost-effectiveness analyses comparing preconception or prenatal carrier screening programs to no screening. We considered four carrier screening strategies: 1) universal screening with standard panels; 2) universal screening with a hypothetical expanded panel; 3) risk-based screening with standard panels; and 4) risk-based screening with a hypothetical expanded panel. We also estimated the 5-year budget impact of publicly funding preconception or prenatal carrier screening programs for the given conditions in Ontario. To contextualize the potential value of carrier screening, we spoke with 22 people who had sought out carrier screening. Results: We included 107 studies in the clinical evidence review. Carrier screening for CF, hemoglobinopathies and thalassemia, FXS, and SMA likely results in the identification of couples with an increased chance of having an affected pregnancy (GRADE: Moderate). Screening likely impacts reproductive decision-making (GRADE: Moderate) and may result in lower anxiety among pregnant people, although the evidence is uncertain (GRADE: Very low).We included 21 studies in the economic evidence review, but none of the study findings were directly applicable to the Ontario context. Our cost-effectiveness analyses showed that in the short term, preconception or prenatal carrier screening programs identified more at-risk pregnancies (i.e., couples that tested positive) and provided more reproductive choice options compared with no screening, but were associated with higher costs. While all screening strategies had similar values for health outcomes, when comparing all strategies together, universal screening with standard panels was the most cost-effective strategy for both preconception and prenatal periods. The incremental cost-effectiveness ratios (ICERs) of universal screening with standard panels compared with no screening in the preconception period were $29,106 per additional at-risk pregnancy detected and $367,731 per affected birth averted; the corresponding ICERs in the prenatal period were about $29,759 per additional at-risk pregnancy detected and $431,807 per affected birth averted.We estimated that publicly funding a universal carrier screening program in the preconception period over the next 5 years would require between $208 million and $491 million. Publicly funding a risk-based screening program in the preconception period over the next 5 years would require between $1.3 million and $2.7 million. Publicly funding a universal carrier screening program in the prenatal period over the next 5 years would require between $128 million and $305 million. Publicly funding a risk-based screening program in the prenatal period over the next 5 years would require between $0.8 million and $1.7 million. Accounting for treatment costs of the screened health conditions resulted in a decrease in the budget impact of universally provided carrier screening programs or cost savings for risk-based programs.Participants value the perceived potential positive impact of carrier screening programs such as medical benefits from early detection and treatment, information for reproductive decision-making, and the social benefit of awareness and preparation. There was a strong preference expressed for thorough, timely, unbiased information to allow for informed reproductive decision-making. Conclusions: Carrier screening for CF, FXS, hemoglobinopathies and thalassemia, and SMA is effective at identifying at-risk couples, and test results may impact preconception and reproductive decision-making.The cost-effectiveness and budget impact of carrier screening programs are uncertain for Ontario. Over the short term, carrier screening programs are associated with higher costs, and also higher chances of detecting at-risk pregnancies compared with no screening. The 5-year budget impact of publicly funding universal carrier screening programs is larger than that of risk-based programs. However, accounting for treatment costs of the screened health conditions results in a decrease in the total additional costs for universal carrier screening programs or in cost savings for risk-based programs.The people we spoke with who had sought out carrier screening valued the potential medical benefits of early detection and treatment, particularly the support and preparation for having a child with a potential genetic condition.

Differences in medical costs between TCM users and TCM nonusers in inpatients with thalassemia.

BACKGROUND: Thalassemia has brought serious health threats and economic burdens to patients worldwide. There is no sovereign remedy for thalassemia, both conventional and Traditional Medicine (TM) methods have certain effects on this disease. As typical of TM, Traditional Chinese Medicine (TCM) has been widely used in the treatment of thalassemia. Previous studies mainly focused on conventional treatments for thalassemia and patients' medical burden, but no research has examined the effects of TCM use on the economic burdens for thalassemia inpatients in mainland China. The main objective of this study is to compare the medical cost differences between TCM users and TCM nonusers, furtherly, we will discuss the role of TCM use in the treatment of thalassemia. METHODS: We employed the 2010-2016 Medicare claims database provided by the China Health Insurance Research Association (CHIRA). Chi-square and Mann-Whitney tests were used to analyze the differences between TCM users and TCM nonusers. Multiple regression analysis was performed using the ordinary least squares method to compare the TCM users' inpatient medical cost with TCM nonusers', and to further examine the correlation between TCM cost, conventional medication cost and nonpharmacy cost for TCM users. RESULTS: A total of 588 urban thalassemia inpatients were identified, including 222 TCM users and 366 TCM nonusers. The inpatient medical cost of TCM users was RMB10,048 (USD1,513), which was significantly higher than TCM nonusers (RMB1,816 (USD273)). Total inpatient cost for TCM users was 67.4% higher than those of TCM nonusers (P < 0.001). With confounding factors fixed, we found that the conventional medication cost and nonpharmacy cost were positively correlated with TCM cost. CONCLUSION: Total hospitalization expenses for TCM users were higher than TCM nonusers. Both the conventional medication cost and nonpharmacy cost of TCM users were all higher than TCM nonusers. We infer TCM plays a complementary role, rather than an alternative, in the treatment of thalassemia due to the lack of cooperative treatment guidelines. It is recommended that a cooperative diagnosis and treatment guidelines should be generated to balance the use of TCM and conventional medicine for treating thalassemia, so as to reduce the economic burdens on patients.

Race-neutral equations for assessment of lung function in children with thalassemia.

The aim of this study was to assess pulmonary dysfunction in children with transfusion-dependent thalassemia (TDT) using the Global Lung Function Initiative (GLI) 2022 race-neutral spirometric reference equations and to determine the main predicting factors. The spirometric results of 68 children with TDT were compared to the results of 68 healthy control subjects using both GLI-2012 reference equations for Caucasians and GLI-2022 global equations. Associations between the spirometric data and various anthropometric, clinical, and laboratory parameters were analyzed to detect predictors of pulmonary dysfunction in this group of patients. Children with TDT showed significantly lower values of FVC and FEV1 with a predominance of the restrictive pattern (23.53%). Thalassemic children with the restrictive pattern were significantly older, had a longer duration of regular blood transfusion, lower height, weight, and BMI z-scores, higher average serum ferritin, and higher frequency of having a serum ferritin level >2500 ng/mL. The strongest predictor for having a restrictive spirometric pattern was high serum ferritin. Our analysis shows that the transition from GLI-2012 spirometric reference equations for Caucasians to the GLI-2022 global equations has led to a reduction in the prevalence rate of restrictive pulmonary dysfunction in children with TDT, which should not affect the patient outcome in the long term. Asymptomatic children with TDT exhibited a restrictive spirometric pattern in a significant proportion. The most important predictor was high serum ferritin. We encourage the inclusion of pulmonary function testing in the routine monitoring of patients with TDT, especially in older patients and those with iron overload.

Thalassaemia in China.

Because of successful thalassaemia prevention programmes in resource-rich countries and it's huge population China now has the greatest number of new cases of thalassaemia globally as well as more people with thalassaemia than any other country. 30 million Chinese have thalassaemia-associated mutations and about 300,000 have thalassaemia major or intermedia requiring medical intervention. Over the past 2 decades there has been tremendous economic growth in China including per capita spending on health care. There is now nation-wide availability and partial or full insurance for prenatal genetic testing, RBC-transfusions, iron-chelating drugs and haematopoietic cell transplants. Prenatal screening and educational programmes have reduced the incidence of new cases. However, substantial challenges remain. For example, regional differences in access to medical care and unequal economic development require innovations to reduce the medical, financial and psychological burdens of Chinese with thalassaemia and their families. In this review we discuss success in preventing and treating thalassaemia in China highlighting remaining challenges. Our discussion has important implications for resource-poor geospaces challenged with preventing and treating thalassaemia.

Healthcare resource utilization and direct costs of transfusion-dependent thalassemia patients in Dubai, United Arab Emirates: a retrospective cost-of-illness study.

BACKGROUND: Patients with transfusion-dependent thalassemia (TDT) require lifelong blood transfusions and iron chelation therapy. Thus, patients afflicted with TDT often have to undergo blood transfusion and iron chelation therapy, which causes a major economic burden on them. However, this topic has not been reported in Dubai, United Arab Emirates (UAE). Hence, this study aimed to evaluate healthcare resource utilization and associated direct costs related to patients with TDT in Dubai, UAE. METHODS: For this study, a retrospective prevalence-based cost-of-illness analysis based on the UAE healthcare system and patient perspectives was conducted among patients with TDT treated at the Dubai Thalassemia Center in 2019. Information regarding healthcare resource utilization and direct medical costs was collected from the billing system connected to the electronic medical record system. Patients and their families were interviewed for direct non-medical cost estimations. RESULTS: A total of 255 patients with TDT were included in the study. The mean annual direct medical cost was estimated at AED 131,156 (USD 35,713) (95% CI: 124,735 - 137,578). The main driver of the medical cost for the participants as iron chelation therapy AED 78,372 (95% CI: 72,671 - 84,074) (59.8%), followed by blood transfusions, which accounted for AED 34,223 (95% CI: 32,854 - 35,593) 26.1% of the total direct medical costs. The mean annual direct non-medical costs was AED 2,223 (USD 605) (95% CI: 1,946 - 2,500). Age (p < 0.001), severe serum ferritin levels (p = 0.016), the presence of complications (p < 0.001), and the type of iron chelation therapy (p < 0.001) were significant predictors of higher direct medical costs incurred by the participants. CONCLUSION: Transfusion-dependent thalassemia poses a substantial economic burden on the healthcare system, patients, and their families. Our results show that the highest medical cost proportion was due to iron chelation therapy. In this regard, efforts must be made to improve the patients' acceptance and satisfaction with their iron chelation therapy to increase their compliance and improve the effectiveness of treatment, which could play an essential role in controlling the economic burden of this disease. Moreover, greater support is essential for families that suffer catastrophic out-of-pocket expenses.

Estimating the Cost of Thalassemia Care across the World: A Thalassemia International Federation Model.

Estimating the cost of thalassemia care is important for the optimization of care planning, resource allocation and the empowerment of patient advocacy. However, available evidence is heterogeneous, reflecting diverse healthcare systems and cost estimation methods. We sought to build a globally applicable cost model for thalassemia care. We followed a three-step approach, including (i) a targeted literature review to identify previous cost-of-illness studies on thalassemia; (ii) a generic model development based on the main determinants of cost in different countries emerged from a literature review and validated by a team of medical experts; (iii) a piloting of the model using data from two diverse countries. The literature review revealed studies focusing on the total costs of thalassemia care or the cost or cost-effectiveness of specific treatment or prevention modalities in high- and low-prevalence countries across the world. The resulting evidence was used to build a model that calculates total annual therapy cost based on entry of country-level and patient-level data, and data on healthcare modalities, indirect costs and prevention. Testing the model using published data from the UK, Iran, India and Malaysia, revealed an annual cost per patient of £81,796.00 for the UK, Iranian rial (IRR) 13,757.00 for Iran, Indian rupee (INR) 166,750.00 for India and Malyasian ringgit (or dollar) (MYR) 111,372.00 for Malaysia. A globally applicable model that calculates total annual cost of thalassemia care was built based on existing evidence. The model successfully predicted the annual cost of thalassemia care in the UK, Iran, India and Malaysia.

Risk factors for endocrine complications in transfusion-dependent thalassemia patients on chelation therapy with deferasirox: a risk assessment study from a multi-center nation-wide cohort.

Transfusion-dependent patients typically develop iron-induced cardiomyopathy, liver disease, and endocrine complications. We aimed to estimate the incidence of endocrine disorders in transfusiondependent thalassemia (TDT) patients during long-term iron-chelation therapy with deferasirox (DFX). We developed a multi-center follow-up study of 426 TDT patients treated with once-daily DFX for a median duration of 8 years, up to 18.5 years. At baseline, 118, 121, and 187 patients had 0, 1, or ≥2 endocrine diseases respectively. 104 additional endocrine diseases were developed during the follow-up. The overall risk of developing a new endocrine complication within 5 years was 9.7% (95% Confidence Interval [CI]: 6.3-13.1). Multiple Cox regression analysis identified three key predictors: age showed a positive log-linear effect (adjusted hazard ratio [HR] for 50% increase 1.2, 95% CI: 1.1-1.3, P=0.005), the serum concentration of thyrotropin showed a positive linear effect (adjusted HR for 1 mIU/L increase 1.3, 95% CI: 1.1-1.4, P<0.001) regardless the kind of disease incident, while the number of previous endocrine diseases showed a negative linear effect: the higher the number of diseases at baseline the lower the chance of developing further diseasess (adjusted HR for unit increase 0.5, 95% CI: 0.4-0.7, P<0.001). Age and thyrotropin had similar effect sizes across the categories of baseline diseases. The administration of levothyroxine as a covariate did not change the estimates. Although in DFX-treated TDT patients the risk of developing an endocrine complication is generally lower than the previously reported risk, there is considerable risk variation and the burden of these complications remains high. We developed a simple risk score chart enabling clinicians to estimate their patients' risk. Future research will look at increasing the amount of variation explained from our model and testing further clinical and laboratory predictors, including the assessment of direct endocrine magnetic resonance imaging.

Major Thalassemia, Screening or Treatment: An Economic Evaluation Study in Iran.

BACKGROUND: Beta-thalassemia minor and thalassemia major are an autosomal recessive disease with hypochromic, microcytic anemia, and morbidities, Today, therapeutic advances have significantly improved the life expectancy of thalassemia major patients, but at the cost of financial toxicity. The present study aimed to investigate the possibility of increasing the funding for thalassemia screening programs and comparing the cost-effectiveness of screening for thalassemia in the treatment of the patients. METHODS: In this study, screening for thalassemia minor was compared with the treatment of thalassemia major patients. A decision tree model was used for analysis. A hospital database, supplemented with a review of published literature, was used to derive input parameters for the model. A lifetime study horizon was used and future costs and consequences were discounted at 3%. The approach of purchases of services was used to evaluate the screening test costs for patients with thalassemia major. Also, a bottom-up method was applied to estimate other screening and treatment costs. All the costs were calculated over one year. The number of gained quality-adjusted life years (QALYs) was calculated using the EQ-5D questionnaire in the evaluated patients. RESULTS: In this study, 26.97 births of patients with thalassemia major were prevented by screening techniques. On the other hand, total screening costs for patients with thalassemia major were estimated equal to US$ 879879, while the costs of preventing the birth of each thalassaemia major patient was US$ 32 624 by screening techniques. In comparison, the cost of managing a patient with thalassemia major is about US$ 136 532 per year. The life time QALYs for this is 11.8 QALYs. Results are presented using a societal perspective. Incremental cost per QALY gained with screening as compared with managing thalassaemia major was US$ 11 571. CONCLUSION: Screening is a long-term value for money intervention that is highly cost effective and its long-term clinical and economic benefits outweigh those of managing thalassaemia major patients.

Preconception risk assessment for thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease.

BACKGROUND: Globally, about 6% of children are born with a serious birth defect of genetic or partially genetic origin. Carrier screening or testing is one way to identify couples at increased risk of having a child with an autosomal recessive condition. The most common autosomal recessive conditions are thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease, with higher carrier rates in high-risk populations of specific ancestral backgrounds. Identifying and counselling couples at genetic risk of the conditions before pregnancy enables them to make fully informed reproductive decisions, with some of these choices not being available if testing is only offered in an antenatal setting. This is an update of a previously published review. OBJECTIVES: To assess the effectiveness of systematic preconception genetic risk assessment to enable autonomous reproductive choice and to improve reproductive outcomes  in women and their partners who are both identified as carriers of thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease in healthcare settings when compared to usual care. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Registers. Date of latest search of the registers: 04 August 2021. In addition, we searched for all relevant trials from 1970 (or the date at which the database was first available if after 1970) to date using electronic databases (MEDLINE, Embase, CINAHL, PsycINFO), clinical trial databases (National Institutes of Health, Clinical Trials Search portal of the World Health Organization, metaRegister of controlled clinical trials), and hand searching of key journals and conference abstract books from 1998 to date (European Journal of Human Genetics, Genetics in Medicine, Journal of Community Genetics). We also searched the reference lists of relevant articles, reviews and guidelines and also contacted subject experts in the field to request any unpublished or other published trials. Date of latest search of all these sources: 25 June 2021.  SELECTION CRITERIA: Any randomised controlled trials (RCTs) or quasi-RCTs (published or unpublished) comparing reproductive outcomes of systematic preconception genetic risk assessment for thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease when compared to usual care. DATA COLLECTION AND ANALYSIS: We identified 37 papers, describing 22 unique trials which were potentially eligible for inclusion in the review. However, after assessment, we found no RCTs of preconception genetic risk assessment for thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease. MAIN RESULTS: No RCTs of preconception genetic risk assessment for thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease are included. A trial identified earlier has published its results and has subsequently been listed as excluded in this review. AUTHORS' CONCLUSIONS: As there are no RCTs of preconception genetic risk assessment for thalassaemia, sickle cell disease, cystic fibrosis, or Tay-Sachs disease included in either the earlier or current versions of this review, we recommend considering potential non-RCTs studies (for example prospective cohorts or before-and-after studies) for future reviews. While RCTs are desirable to inform evidence-based practice and robust recommendations, the ethical, legal and social implications associated with using this trial design to evaluate the implementation of preconception genetic risk assessment involving carrier testing and reproductive autonomy must also be considered.  In addition, rather than focusing on single gene-by-gene carrier testing for specific autosomal-recessive conditions as the intervention being evaluated, preconception expanded genetic screening should also be included in future searches as this has received much attention in recent years as a more pragmatic strategy. The research evidence for current international policy recommendations is limited to non-randomised studies.

Evaluation of role of HPLC (Merits & Pitfalls), in the diagnosis of various hemoglobinopathies & thalassemic syndromes.

BACKGROUND: : HPLC is one of the most important tools for accurate diagnosis of hemoglobinopathies and thalassemias. The advantage of the HPLC system is the excellent resolution, reproducibility &quantification of several normal and abnormal hemoglobin. RESULTS: BIO RAD Variant II analyzer was used. Sickle cell syndromes including double heterozygous states accounted for 56.13% of total cases. HbSS, HbS/ß0-th, HbS/ß+-th ß-thal trait comprises 29%, 6.5%, 5.1%& 10% of total cases respectively with mean MCV (fl) = 84, 68,71,64 respectively. The Mean HbA2 for ß-thal trait, HbE trait &HbE-ß thal showed 5.1 ± 1.1, 19 ± 9 & 24 ± 8 respectively. HbF is increased in 8.6% case (excluding SC syndromes & ß-thal disorders), of these 5.5% were infants & 12 cases of Aplastic Anemias. Peak P2 >7% (2.4% cases) was seen in uncontrolled diabetes mellitus which on quantification showed HbA1C = 8 ± 2.1 mmol/L. DISCUSSION: : HPLC in correlation with CBC parameters & family studies can aid in the diagnosis of majority of Hemoglobinopathies and thalassemic syndrome. The CBC & HPLC parameters of the present study are in good correlation with the research conducted by Tejinder Sing, RiouJ & Alla Joutovsky. Present study showed HPLC comprehensively characterizing HbS, A, A2, F, S, C, D from each other & was also applicable for the quantification of HbA1c for the monitoring of Diabetes Mellitus. CONCLUSION: : The merits of HPLC are small quantity of sample required, economical, less TAT, accurate categorization of HbS, HbA2 & F. But one has to be aware of the limitations and problems associated with this method due to variant hemoglobin within the same retention windows. The present findings show HPLC as an excellent & powerful diagnostic tool for the direct identification of hemoglobin variants with a high degree of precision in the quantification of normal and abnormal hemoglobin fractions.

An urgent need for improving thalassemia care due to the wide gap in current real-life practice and clinical practice guidelines.

Based on Thalassemia International Federation clinical practice guidelines (CPG) for non-transfusion dependent and transfusion dependent thalassemia, several measures should be routinely implemented such as monitoring and surveillance of thalassemia related complications for early detection and proper clinical management. To evaluate the prevalence and the performance of routine surveillance for thalassemia related complications during 2 periods; before and after published CPGs (2012-2014 vs 2015-2017), data from 524 adult thalassemia patients attended at Siriraj hospital were compared among different treating physician groups; thalassemia, private hematology, and internal medicine clinics. Three most common complications were osteopenia/osteoporosis (69.8%), gallstones (67.6%) and abnormal vitamin D level (67.6%). Iron overload has been widely evaluated (93.1%) followed by liver function test (82.3%). However, the rate of evaluation for other complications were significantly reduced and < 25% of patients were evaluated in several complications. Comparing among clinics, the surveillance rate has increased significantly for several endocrine complications only in patients treated at thalassemia clinic but not in others. This study was the first study that evaluated real-world practical management of thalassemia patient in terms of complication surveillance. This different clinical practice has called for an immediate policy change to improve and standardize a care for thalassemia patients in Thailand.

Phylogenetic analysis in the clinical risk management of an outbreak of hepatitis C virus infection among transfused thalassaemia patients in Italy.

BACKGROUND: Occurrence of hepatitis C virus (HCV) infection is reduced by effective risk management procedures, but patient-to-patient transmission continues to be reported in healthcare settings. AIM: To report the use of phylogenetic analysis in the clinical risk management of an HCV outbreak among 128 thalassaemia outpatients followed at a thalassaemia centre of an Italian hospital. METHODS: Epidemiological investigation and root-cause analysis were performed. All patients with acute hepatitis and known chronic infection were tested for HCV RNA, HCV genotyping, and NS3, NS5A, and NS5B HCV genomic region sequencing. To identify transmission clusters, phylogenetic trees were built for each gene employing Bayesian methods. FINDINGS: All patients with acute hepatitis were infected with HCV genotype 1b. Root-cause analysis, including a lookback procedure, excluded blood donors as the source of HCV transmission. The phylogenetic analysis, conducted on seven patients with acute infection and eight patients with chronic infection, highlighted four transmission clusters including at least one patient with chronic and one patient with acute HCV infection. All patients in the same cluster received a blood transfusion during the same day. Two patients with acute hepatitis spontaneously cleared HCV within four weeks and nine patients received ledipasvir plus sofosbuvir for six weeks, all achieving a sustained virological response. CONCLUSION: Combined use of root-cause analysis and molecular epidemiology was effective in ascertaining the origin of the HCV outbreak. Antiviral therapy avoided the chronic progression of the infection and further spread in care units and in the family environment.

Mapping PedsQL™ Generic Core Scales to EQ-5D-3L utility scores in transfusion-dependent thalassemia patients.

PURPOSE: To develop a mapping algorithm for generating EQ-5D-3L utility scores from the PedsQL Generic Core Scales (PedsQL GCS) in patients with transfusion-dependent thalassemia (TDT). METHODS: The algorithm was developed using data from 345 TDT patients. Spearman's rank correlation was used to evaluate the conceptual overlap between the instruments. Model specifications were chosen using a stepwise regression. Both direct and response mapping methods were attempted. Six mapping estimation methods ordinary least squares (OLS), a log-transformed response using OLS, generalized linear model (GLM), two-part model (TPM), Tobit and multinomial logistic regression (MLOGIT) were tested to determine the root mean squared error (RMSE) and mean absolute error (MAE). Other criterion used were accuracy of the predicted utility score, proportions of absolute differences that was less than 0.03 and intraclass correlation coefficient. An in-sample, leave-one-out cross validation was conducted to test the generalizability of each model. RESULTS: The best performing model was specified with three out of the four PedsQL GCS scales-the physical, emotional and social functioning score. The best performing estimation method for direct mapping was a GLM with a RMSE of 0.1273 and MAE of 0.1016, while the best estimation method for response mapping was the MLOGIT with a RMSE of 0.1597 and MAE of 0.0826. CONCLUSION: The mapping algorithm developed using the GLM would facilitate the calculation of utility scores to inform economic evaluations for TDT patients when EQ-5D data is not available. However, caution should be exercised when using this algorithm in patients who have poor quality of life.

Economic burden in the management of transfusion-dependent thalassaemia patients in Malaysia from a societal perspective.

BACKGROUND: Transfusion-dependent thalassaemia (TDT) is a hereditary blood disorder in which blood transfusion is the mainstay treatment to prolong survival and improve quality of life. Patients with this disease require blood transfusion at more than 100 ml/kg annually and iron-chelating therapy (ICT) to prevent iron overload (IOL) complications. There are substantial numbers of TDT patients in Malaysia, but limited data are available regarding the economic burden associated with this disease. The purpose of this study was to determine the lifetime cost of TDT from a societal perspective and identify potential factors increasing patient and family expenditures among thalassaemia populations. METHODS: The total lifetime cost per TDT patient (TC1) is the sum of lifetime healthcare cost (TC2) and lifetime patient and family healthcare expenditure (TC3). TC2 was simulated using the Markov model, taking into account all costs subsidized by the government, and TC3 was estimated through a cross-sectional health survey approach. A survey was performed using a two-stage sampling method in 13 thalassaemia centres covering all regions in Malaysia. RESULTS: A TDT patient is expected to incur TC2 of USD 561,208. ICT was the main driver of cost and accounted for 56.9% of the total cost followed by blood transfusion cost at 13.1%. TC3 was estimated to be USD 45,458. Therefore, the estimated TC1 of a TDT patient was USD 606,665. Sensitivity analyses showed that if all patients were prescribed oral ICT deferasirox for their lifetime, the total healthcare cost would increase by approximately 65%. Frequency of visits to health facilities for blood transfusion/routine monitoring and patients who were prescribed desferrioxamine were observed to be factors affecting patient and family monthly expenses. CONCLUSION: The lifetime cost per TDT patient was USD 606,665, and this result may be useful for national health allocation planning. An estimation of the economic burden will provide additional information to decision makers on implementing prevention interventions to reduce the number of new births and medical service reimbursement.

EQ-5D-3L health state utility values in transfusion-dependent thalassemia patients in Malaysia: a cross-sectional assessment.

PURPOSE: There is a gap of information describing the health state utility values (HSUVs) of transfusion-dependent thalassemia (TDT) patients in Malaysia. These values are useful in the assessment of health-related quality of life (HRQoL), economic evaluations and provide guidance to disease management decisions. The objective of this study was to estimate and derive HSUVs associated with the treatment and complications of TDT patients in Malaysia using the EQ-5D-3L instrument. METHODS: A cross-sectional survey using the EQ-5D-3L instrument was conducted between May to September 2018 across various public hospitals in Malaysia. Using a multi-stage sampling, patients diagnosed with TDT and receiving iron chelating therapy were sampled. The findings on the EQ-5D-3L survey were converted into utility values using local tariff values. A two-part model was used to examine and derive the HSUVs associated with the treatment and complications of iron overload in TDT. RESULTS: A total of 585 patients were surveyed. The unadjusted mean (SD) EQ-5D-3L utility value for TDT patients were 0.893 (0.167) while mean (SD) EQ VAS score was 81.22 (16.92). Patients who had more than two iron overload complications had a significant decline in HRQoL. Patients who were on oral monotherapy had a higher utility value of 0.9180 compared to other regimen combinations. CONCLUSION: Lower EQ-5D-3L utility values were associated with patients who developed iron overload complications and were on multiple iron chelating agents. Emphasizing compliance to iron chelating therapy to prevent the development of complications is crucial in the effort to preserve the HRQoL of TDT patients.