Comprehensive and long-term outcomes of enzyme replacement therapy followed by stem cell transplantation in children with Gaucher disease type 1 and 3

Background

Gaucher disease (GD) is a lysosomal storage disorder, characterized by hepatosplenomegaly, pancytopenia, bone diseases, with or without neurological symptoms. Plasma glucosylsphingosine (lyso-Gb1), a highly sensitive and specific biomarker for GD, has been used for diagnosis and monitoring the response to treatment. Enzyme replacement therapy (ERT) is an effective treatment for the non-neurologic symptoms of GD. Neuronopathic GD (type 2 and 3) accounts for 60%–70% of the Asian affected population.

Methods

We explored combination therapy of ERT followed by hematopoietic stem cell transplantation (HSCT) and its long-term outcomes in patients with GD type 3 (GD3).

Results

Four patients with GD3 and one with GD type 1 (GD1) underwent HSCT. The types of donor were one matched-related, one matched-unrelated, and three haploidentical. The age at disease onset was 6–18 months and the age at HSCT was 3.8–15 years in the patients with GD3. The latest age at follow-up was 8–22 years, with a post-HSCT duration of 3–14 years. All patients had successful HSCT. Chronic graft-versus-host disease occurred in one patient. The enzyme activities were normalized at 2 weeks post HSCT. Lyso-Gb1 concentrations became lower than the pathological value. All of the patients are still alive and physically independent. Most of them (4/5) returned to school. None of the patients with GD3 had seizures or additional neurological symptoms after HSCT, but showed varying degrees of cognitive impairment.

Conclusions

ERT followed by HSCT could be considered as an alternative treatment for patients with GD3 who have a high risk of fatal neurological progression.     

Severe Disability Among Elderly Community Dwellers in Rural Thailand: Prevalence and Associated Factors

The Thai population structure is changing, with the growing number of elderly people leading to a higher dependency ratio. Particularly, the dependency resulted from aging related disability becomes a critical problem in rural Thailand. This study was designed to determine the prevalence and factors associated with severe disability among community dwelling elderly people in rural Thailand. The findings imply that the prevalence of severe disability in the elderly was 11.9 % (95 % CI, 9.23–15.07). The factors associated with severe disability were, according to strength of association, co-morbidity (AOR 3.63; 95 % CI 1.78–7.41), fall (AOR 3.21; 95 % CI. 1.53–6.73), age (over 75 years) (AOR 2.78; 95 % CI 1.33–5.80), and dementia (AOR 2.29; 95 % CI 1.01–5.20), while participation in social activities was a protective factor for severe disability (AOR 0.13; 95 % CI 0.06–0.27). Therefore, to improve care for the community dwelling elderly people in Thailand, the government should focus on health promotion, enhancing the elderly people’s social participation in the society activities for the risk group, and providing long-term care for the elderly with severe disability.     

The provincial health office as performance manager: change in the local healthcare system after Thailand's universal coverage reforms

This paper examines the implementation of Thailand's universal coverage healthcare reforms in a rural province, using data from field studies undertaken in 2003–2005 and 2008–2011. We focus on the strand of policy that aimed to develop primary care by allocating funds to contracting units for primary care (CUPs) responsible for managing local service networks. The two studies document a striking change in the balance of power in the local healthcare system over the 8‐year period. Initially, the newly formed CUPs gained influence as ‘power followed the money’, and the provincial health offices (PHOs), which had commanded the service units, were left with a weaker co‐ordination role. However, the situation changed as a new insurance purchaser, the National Health Security Office, took financial control and established regional outposts. National Health Security Office outposts worked with PHOs to develop rationalised management tools—strategic plans, targets, KPIs and benchmarking—that installed the PHOs as performance managers of local healthcare systems. New lines of accountability and changed budgetary systems reduced the power of the CUPs to control resource allocation and patterns of services within CUP networks. Whereas some CUPs fought to retain limited autonomy, the PHO has been able to regain much of its former control. We suggest that implementation theory needs to take a long view to capture the complexity of a major reform initiative and argue for an analysis that recognises the key role of policy networks and advocacy coalitions that span national and local levels and realign over time. Copyright © 2012 John Wiley & Sons, Ltd.     

Fracture Resistance of Endodontically Treated Teeth: Three Walls versus Four Walls of Remaining Coronal Tooth Structure

Purpose: The purpose of this study was to evaluate the fracture resistance of endodontically treated teeth between those with four walls and those with three walls of remaining coronal tooth structure and the effect of the site of the missing coronal wall.
Materials and Methods: Thirty-two endodontically treated second mandibular premolars were decoronated, leaving 3 mm above the cementoenamel junction (CEJ). A 0.5-mm-wide chamfer was prepared 1 mm above the CEJ. The teeth were randomly divided into four groups. Group 1 had four walls of coronal tooth structure, whereas groups 2, 3, and 4 had only three walls, missing the buccal, lingual, and mesial wall, respectively. The cast dowel and cores and crowns (Ni–Cr alloy) were cemented with zinc phosphate cement. A compressive load was applied 45° to the long axis, 2 mm below the buccal cusp, with an Instron machine until failure at a crosshead speed of 5 mm/min. Failure load (kg) and mode of failure were recorded. Data were analyzed with one-way ANOVA and Scheffé tests ( p < 0.05).
Results: Group 1 had the highest fracture resistance (1190.3 ± 110.5 kg), significantly different from the other groups ( p < 0.05) (group 2: 578.5 ± 197.4 kg; group 3: 786.6 ± 132.8 kg; group 4: 785.4 ± 289.9 kg). There were no significant differences among the test groups. The mode of failure in group 1 was a horizontal root fracture, whereas that of the other groups was either vertical or oblique fracture.
Conclusions: Teeth with four walls of remaining coronal dentine had significantly higher fracture resistance than teeth with only three walls. The site of the missing coronal wall did not affect the fracture resistance of endodontically treated teeth.     

Family happiness among people in a Southeast Asian city: Grounded theory study

Happiness is a fundamental human aspiration. However, many families live in places where the cost of living is high, and there is a need for people to balance their lives to maintain happiness. This study explored the characteristics of happiness for families living in a city in Thailand. A grounded theory methodology was used to collect and analyze data. Thirteen participants were recruited into the study by purposive sampling based on a set of inclusion criteria, followed by theoretical sampling. The findings demonstrated that living together without financial problems was a core category of family happiness, which involved close connections, caring for one another and financial security. Families needed to balance these components when facing stress, using coping methods to restore happiness. To enhance family happiness, health professionals should focus on caring and communication within families, including coping techniques to maintain family happiness.     

Folate pathway genetic polymorphisms and susceptibility of central nervous system tumors in Thai children

Background: Folate is an important micronutrient molecule participating in DNA synthesis, methylation and repair mechanisms. Genetic polymorphisms in folate pathway related enzymes including methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, methionine synthase (MTR) A2756G, thymidylate synthase (TS) 28-bp tandem repeat, and reduced folate carrier (RFC) G80A have been shown to be associated with increased susceptibility for several cancers. The aim of the present study was to evaluate whether single nucleotide polymorphisms in the genes encoding enzymes of the folate pathway predispose to any CNS tumors in Thai children. Methods: In the present case-control study, we investigated these polymorphisms in genomic DNA from peripheral blood mononuclear cells in 73 Thai children with various types of central nervous system tumors and in 205 age and sex matched controls. Results: Thirty-one out of 73 patients were diagnosed with glial tumors (astrocytoma, oigodendroglioma and ependymoma), 28 with embryonal CNS tumors (medulloblastoma, pinealoblastoma and primitive neuroectodermal tumor), 13 with germ cell tumors and 1 with meningioma. We found that the homozygous CC allele of MTHFR A1298C conferred an increased risk of embryonal CNS tumors (OR: 3.9; 95% CI: 1.3-11.4, p = 0.02). Conclusion: Our findings thus suggest that folate metabolism may play a role in the pathogenesis of certain specific subtypes of pediatric brain tumor in Thai children, especially embryonal CNS tumors.