Out-of-pocket and catastrophic expenditure on treatment of haemophilia by Indian families.

In low-income countries, haemophilia treatment is not supported by national health services. Data on the burden of out-of-pocket (OOP) expenditure on households are unavailable from these countries. This study measured the OOP expenditure on treatment of haemophilia by Indian households. We used 20 weeks of follow-up data of 24 haemophilia A patients to estimate the annual bleeding rate for each patient and the actual OOP expenditure on treatment. We used this observational data to calculate the annual OOP expenditure on treatment if all bleeding episodes were to be treated with clotting factor concentrate. Using previously published methodology, we estimated if the expenditure was catastrophic to households or not. The observed monthly expenditure on treatment ranged from 1.5% to 12% of monthly income as not all bleeding episodes were treated with clotting factor concentrate. The estimated monthly expenditure if all bleeding episodes occurring over 1 year were to be treated would range from 21 to 314 times the monthly income of families. Nearly 68% of households would have experienced catastrophic expenditure. Treatment for haemophilia results in significant OOP expenditure for households, which is avoided by not providing standard treatment to patients. There is a need to mobilize prevention and care services for haemophilia in India and other low-income countries to mitigate the suffering due to lack of affordable treatment.

Combined inhibition of PDE4 and PI3Kδ modulates the inflammatory component involved in the progression of chronic obstructive pulmonary disease.

Chronic Obstructive Pulmonary Disease (COPD) represents a group of disorders with several underlying causes that hamper airflow into the lungs. Despite current intervention therapies, COPD remains a disease with a significant unmet medical need. Treatment with Phosphodiesterase (PDE) 4 inhibitors results in modest efficacy at clinically relevant doses. The objective of the current study is to evaluate the combination of a PDE4 (Roflumilast) and a Phosphoinositide-3-kinase (PI3K) δ (IC87114) inhibitor for their therapeutic potential in diminishing the inflammatory response associated with COPD. Due to their divergent and independent pathways, we hypothesize that the combination would be efficacious at low concentrations in an in vitro setting. Inhibition of TNFα, pAkt, MMP-9 in differentiated U937 macrophages upon stimulation with LPS/CSE was determined. Neutrophil functionality manifested by a modulation of elastase activity was estimated. Protective effect of drug combination on CSE induced apoptosis of lung epithelial cells was also determined. Data demonstrated that the combination of Roflumilast and IC87114 reduced TNFα, pAkt and MMP-9 at nanomolar concentrations and was several fold potent than either of the compounds alone. Inhibition of neutrophil elastase was also increased significantly with the combination along with a better protection against CSE induced apoptosis in alveolar epithelial cells, thereby providing a rationale for their evaluation in COPD patients.

Expression profiling of human donor lungs to understand primary graft dysfunction after lung transplantation.

Lung transplantation is the treatment of choice for end-stage pulmonary diseases. A limited donor supply has resulted in 4,000 patients on the waiting list. Currently, 10-20% of donor organs offered for transplantation are deemed suitable under the selection criteria, of which 15-25% fail due to primary graft dysfunction (PGD). This has spawned efforts to re-examine the current selection criteria as well as search for alternative donor lungs selection criteria. In this study, we attempt to further our understanding of PGD by observing the changes in gene expression across donor lungs that developed PGD versus those that did not. From our analysis, we have obtained differentially expressed transcripts that were involved in signaling, apoptosis and stress-activated pathways. Results also indicate that metallothionein 3 was over expressed in lungs that didn't develop PGD. This is the first such attempt to perform expression profiling of actual human lungs used for transplantation, for the identification of a molecular signature for PGD.

Acceptance of HIV-1 education & voluntary counselling/testing by & seroprevalence of HIV-1 among, pregnant women in rural south India.

BACKGROUND & OBJECTIVE: Since the first report of HIV-1 infection in Tamil Nadu, India, HIV-1 seroprevalence in India has increased steadily. Though interventions to prevent mother-to-child transmission (MTCT) are available, their implementation is a significant challenge. Therefore, among pregnant women in rural Tamil Nadu, the acceptance of education regarding HIV-1 infection and transmission and, among a systematic sample, knowledge, attitudes, and beliefs; the acceptance of HIV-1 voluntary counselling and testing (VCT); and the seroprevalence of HIV-1 infection as well as risk factors for seropositivity were assessed. METHODS: Pregnant women registered in the antenatal clinics at Namakkal District Hospital and Rasipuram Government Hospital, Tamil Nadu, India, were offered an educational session regarding HIV-1 infection and transmission. HIV-1 VCT, with informed consent, was offered. Positive results with HIV-1 rapid testing were confirmed with HIV-1 ELISA and Western blot assays. With informed consent, a systematic sample of the study population was asked to participate in pre- and posteducation assessments. Chi-square tests were used to evaluate HIV-1 risk factors. RESULTS: The educational session as well as VCT were well accepted by rural, pregnant, HIV-1- infected women. Of 3722 women registered for antenatal care at the two hospitals over a one year period, 3691 (99.2%) agreed to participate in the educational session and 3715 (99.8%) had VCT [74 had confirmed HIV-1 infection [seroprevalence: 2.0% (95% confidence interval (95%CI): 1.6%, 2.5%)]]. Of 759 eligible women, a systematic sample of 757 (99.7%) women participated in the pre- and post-education assessments. Although baseline knowledge regarding HIV-1 was limited, a highly significant improvement in such knowledge was observed (P<0.0001 for all comparisons of changes in knowledge, attitudes, and beliefs measured before and immediately after the educational session). The median per cent of correct responses increased from 26.4 per cent before the educational session to 93.8 per cent afterwards. Women whose husbands were long distance truck drivers were at increased risk of HIV-1 infection. Other factors associated with HIV-1 infection were clinical site (Namakkal District Hospital), a smaller number of persons in the household, being unmarried, and a history of previous surgeries. INTERPRETATION & CONCLUSION: The acceptability of education and of VCT among antenatal clinic attendees in this study was encouraging. However, the relatively high seroprevalence highlights the spread of HIV-1 from high risk groups to the general population and emphasizes the need for primary prevention of HIV-1 infection among adolescent girls and women of reproductive age in India.

Oral facial digital syndrome.

We report a female infant with features suggestive of Oral Facial Digital Syndrome (OFDS) Type I and associated cerebellar anomalies with Dandy-Walker malformation which suggest OFDS Type VI. The phenotypic overlap in this child OFDS type I and TypeVI raises the question as to whether they represent separate genetic entities. This pattern of abnormalities appears to be unique.