Pharmacogenomic landscape of the Thai population from genome sequencing of 949 individuals.

Inter-individual variability in drug responses is significantly influenced by genetic factors, underscoring the importance of population-specific pharmacogenomic studies to optimize clinical outcomes. In this study, we analyzed whole genome sequencing data from 949 unrelated Thai individuals and conducted an in-depth analysis of 3239 genes involved in drug pharmacokinetics, pharmacodynamics, or immune-mediated adverse drug reactions. We identified 43 single nucleotide polymorphisms (SNPs), 134 diplotypes, and 15 human leukocyte antigen (HLA) alleles, all with moderate to high clinical significance.

Identifying thresholds for meaningful improvements in NTDT-PRO scores to support conclusions about treatment benefit in clinical studies of patients with non-transfusion-dependent beta-thalassaemia: analysis of pooled data from a phase 2, double-blind, placebo-controlled, randomised trial.

Objectives: To estimate thresholds for defining meaningful within-patient improvement from baseline to weeks 13-24 and interpreting meaningfulness of between-group difference for the non-transfusion-dependent beta-thalassaemia patient-reported outcome (NTDT-PRO) tiredness/weakness (T/W) and shortness of breath (SoB) scores. A secondary objective was to determine the symptom severity threshold for the NTDT-PRO T/W domain to identify patients with symptomatic T/W.

Design: Pooled blinded data from the phase 2, double-blind, placebo-controlled, randomised BEYOND trial in NTDT (NCT03342404) were used.

Disease burden, management strategies, and unmet needs in α-thalassemia due to hemoglobin H disease.

Alpha-thalassemia is an inherited blood disorder caused by impaired α-globin chain production, leading to anemia and other complications. Hemoglobin H (HbH) disease is caused by a combination of mutations generally affecting the expression of three of four α-globin alleles; disease severity is highly heterogeneous, largely driven by genotype. Notably, non-deletional mutations cause a greater degree of ineffective erythropoiesis and hemolysis, higher transfusion burden, and increased complication risks versus deletional mutations.

Systematic review and evidence gap assessment of the clinical, quality of life, and economic burden of alpha-thalassemia.

A recent evidence gaps assessment of the clinical, health-related quality of life, and economic burden associated with α-thalassemia is lacking. We conducted a systematic literature review (SLR) following the methodological and reporting requirements of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and the Cochrane Handbook for Systematic Reviews, using available literature over the past decade. This SLR identified a considerable evidence gap with regard to understanding the current burden of α-thalassemia as evident from paucity of studies published in the past 10 years.

Iron chelation therapy for children with transfusion-dependent β-thalassemia: How young is too young?

In this review, we provide a summary of evidence on iron overload in young children with transfusion-dependent β-thalassemia (TDT) and explore the ideal timing for intervention. Key data from clinical trials and observational studies of the three available iron chelators deferoxamine, deferiprone, and deferasirox are also evaluated for inclusion of subsets of young children, especially those less than 6 years of age. Evidence on the efficacy and safety of iron chelation therapy for children ≥2 years of age with transfusional iron overload is widely available.