Intranasal hormone replacement therapy

Although the optimal route of delivery for hormone replacement therapy has not yet been determined, desirable qualities would include good efficacy, easy administration, minimal side effects, and optimal therapeutic profile. This would potentially serve to improve patient compliance and satisfaction. The intranasal route has been evaluated for the administration of menopausal hormones and seems to fulfill these requirements. The intranasal route would also seem to be a viable alternative for drugs that are poorly absorbed after ingestion by avoiding hepatic first-pass elimination. The intranasal route is, therefore, innovative for the delivery of natural sex steroids in postmenopausal women receiving hormone replacement therapy. Early studies demonstrate that it is safe, effective, and acceptable to postmenopausal women. In addition, the nasal administration of a combination of estradiol and progesterone would seem to be an attractive way to deliver hormones to nonhysterectomized postmenopausal women. Providing alternative routes of administration may also enhance compliance.     

Validation of the Modified Thai Cancer Survivor’s Unmet Needs (T-CaSUN) for Cholangiocarcinoma Patients

Background:Cancer survivors frequently experience of unmet demands that are linked to psychological illness, anxiety, and quality of life. Cholangiocarcinoma (CCA) survivors, on the other hand, still lack of validated tool to assess their particular requirements. The aims of this study were to adjust the Cancer Survivors’ Unmet Need Scale (CaSUN) to a shorter form and to examine its psychometric scale-specific features for the Thai CCA survivors. Methods:This cross-sectional study recruited 231 CCA survivors and randomly split them into 2 groups (group 1, n =115, and group 2, n =116). Firstly, we modified and translated the CaSUN to ensure Thai cultural adaptation. Secondly, we used the statistical methods to reduce some items, then an exploratory factor analysis (EFA) using group 1 to explore the factor structure of the T-CaSUN was done. Finally, a confirmatory factor analysis (CFA) using group 2 was conducted to confirm the modified structure suggested by the EFA and to test for the construct validity of the T-CaSUN. Results:Participants consisted of 231 CCA survivors. EFA and CFA organized the four components construct T-CaSUN, which included intensive care, information, relationship, and medical care. The T-CaSUN’s internal reliability was good (Cronbach’s alpha was 0.75). Furthermore, construct validity was linked to bodily consequences, anxiety and depression, support care needs, stage of cancer, and age. For assessing unmet needs among CCA survivors in Thailand, the T-CaSUN exhibited acceptable reliability and validity. Conclusion:The T-CaSUN demonstrated acceptable reliability and validity for assessing unmet needs among CCA caregivers in Thailand. This short form measurement can assist healthcare practitioners in providing successful individualized care by focusing on the particular requirements of these survivors.Key Words: CCA survivors, Thai- psychometric validation, supportive care, unmet need     

Role of amniotic membrane transplantation in treating acute ocular manifestations in Steven–Johnson syndrome and its long-term impact

Background:Steven–Johnson syndrome (SJS) is a serious disorder affecting the skin and mucous membrane, causing multiple flaccid bullae and purpuric rashes with sheet-like epithelial detachment including the ocular surface. The long-term outcomes following SJS are dismal and manifest as corneal vascularization, lid-wiper keratopathy, and severe dry eyes. The disease course can be modified if amniotic membrane graft is performed at the first week of disease, and the above-said complications can be avoided. This procedure thus not only decreases the morbidity but also improves the quality of life.Purpose:This video discusses the long-term sequelae of SJS which can be modified with timely intervention during the acute stage and thus significantly decreases morbidity.Synopsis:The video demonstrates the simple technique of amniotic membrane transplantation in the acute stage in SJS and its impact in long run.Highlights:There should be a low threshold for doing early amniotic membrane transplantation in patients with SJS with ocular surface involvement. Early intervention can change the disease course and decrease disease morbidity significantly.Video link: https://youtu.be/qgIiVcW56Oo     

Tricuspid regurgitant jet velocity and myocardial tissue Doppler parameters predict mortality in a cohort of patients with sickle cell disease spanning from pediatric to adult age groups ‐ revisiting this controversial concept after 16 years of additional evidence

Sickle cell disease (SCD) is a monogenic hemoglobinopathy associated with significant morbidity and mortality. Cardiopulmonary, vascular and sudden death are the reasons for the majority of young adult mortality in SCD. To better understand the clinical importance of multi‐level vascular dysfunction, in 2009 we assessed cardiac function including tricuspid regurgitant jet velocity (TRV), tissue velocity in systole(S′) and diastole (E′), inflammatory, rheologic and hemolytic biomarkers as predictors of mortality in patients with SCD. With up to 9 years of follow up, we determined survival in 95 children, adolescents and adults with SCD. Thirty‐eight patients (40%) were less than 21 years old at initial evaluation. Survival and Cox proportional‐hazards analysis were performed. There was 19% mortality in our cohort, with median age at death of 35 years. In the pediatric subset, there was 11% mortality during the follow up period. The causes of death included cardiovascular and pulmonary complications in addition to other end‐organ failure. On Cox proportional‐hazards analysis, our model predicts that a 0.1 m/s increase in TRV increases risk of mortality 3%, 1 cm/s increase in S′ results in a 91% increase, and 1 cm/s decrease in E′ results in a 43% increase in mortality. While excluding cardiac parameters, higher plasma free hemoglobin was significantly associated with risk of mortality (p=.049). In conclusion, elevated TRV and altered markers of cardiac systolic and diastolic function predict mortality in a cohort of adolescents and young adult patients with SCD. These predictors should be considered when counseling cardiovascular risk and therapeutic optimization at transition to adult providers.     

Comparison of hematin-targeting properties of pynacrine,an acridine analog of the benzonaphthyridine antimalarial pyronaridine

The hematin-targeting properties of pynacrine, an acridine analog of the schizontocidal antimalarial drug, pyronaridine, were evaluated to probe the role of the latter's benzonaphthyridine moiety. Pynacrine was as active as pyronaridine in inhibiting glutathione-induced hematin degradation and in enhancing hematin-mediated membrane lysis. It formed a 1:2 complex with hematin but was 50-fold less effective in inhibiting β-hematin formation. However, pynacrine was as potent as pyronaridine in inhibiting intra-erythrocytic Plasmodium falciparum growth in culture, suggesting that it has other off-target(s) effects.     

Cost-effectiveness in establishing hemophilia carrier detection and prenatal diagnosis services in a developing country with limited health resources

The cost-effectiveness of carrier detection and prenatal diagnosis for hemophilia at the International Hemophilia Training Center, Bangkok, Thailand was studied. From 1991 to 2002, 209 females from 124 families with hemophilia A and B were included. There were 180 hemophilia A carriers and 29 hemophilia B carriers which could be classified into 78 obligate and 131 possible carriers. The phenotypic analysis for possible carriers involved the determination of levels of factor VIII or IX clotting activity (FVIII:C, FIX:C) and the ratio of FVIII:C and von Willebrand factor antigen. The result revealed that 49 females (37.4%) were diagnosed as carriers, 65 females (49.6%) were normal and 17 females (13%) were undetermined. Additional genotypic analysis was provided to 46 families with 74 females with obligate, proven or undetermined carriers within the reproductive life. The polymorphisms associated with factor VIII and IX genes were used including Bcl I for the factor VIII gene and combined use of Mse I, Sal I, Nru I, Hha I and Dde I for the factor IX gene. The informative rate was 59.4% (44/74). Consequently, 12 prenatal diagnoses for fetus at risk were performed. Sex determination was initially determined and followed by the diagnosis of hemophilia through informative gene tracking and/or the measurement of fetal levels of FVIII:C or FIX:C. The result revealed that 3 male fetuses were affected. The total cost of carrier detection and prenatal diagnosis that the families had to pay in the government hospital was 238,600 Baht (US dollars 5,965). It was compared to the estimated cost of minimal replacement therapy using lyophilized cryoprecipitate for the survival time of 30 years in one patient with hemophilia of 1,012,500 Baht (US dollars 25,312.5). The cost of prevention was much less than the replacement therapy. In conclusion, it is cost-effective to establish the service for carrier detection and prenatal diagnosis for hemophilia especially in developing countries with limited health resources.