Measuring wealth-based health inequality among Indian children: the importance of equity vs efficiency

The concentration index is the most commonly used measure of socio-economic-related health inequality. However, a critical constraint has been that it is just a measure of inequality. Equity is an important goal of health policy but the average level of health also matters. In this paper, we explore evidence of both these crucial dimensions-equity (inequality) and efficiency (average health)-in child health indicators by adopting the recently developed measure of the extended concentration index on the National Family Health Survey (NFHS-3) data from India. An increasing degree of inequality aversion is used to measure health inequalities as well as achievement in the following child health indicators: under-2 child mortality, full immunization coverage, and prevalence of underweight, wasting and stunting among children. State-wise adjusted under-2 child mortality scores reveal an increasing trend with increasing values of inequality aversion, implying that under-2 child deaths have been significantly concentrated among the poor households. The level of adjusted under-2 child mortality scores increases significantly with the increasing value of aversion even in states advanced in the health transition, such as Kerala and Goa. The higher values of adjusted scores for lower values of aversion for child immunization coverage are evidence that richer households benefited most from the rise in full immunization coverage. However, the lack of radical changes in the adjusted scores for underweight among children with increasing degrees of aversion implies that household economic status was not the only determinant of poor nutritional status in India.     

Identifying Factors Associated with Maternal Deaths in Jharkhand,India: A Verbal Autopsy Study

Maternal mortality has been identified as a priority issue in health policy and research in India. The country, with an annual decrease of maternal mortality rate by 4.9% since 1990, now records 63,000 maternal deaths a year. India tops the list of countries with high maternal mortality. Based on a verbal autopsy study of 403 maternal deaths, conducted in 2008, this paper explores the missed opportunities to save maternal lives, besides probing into the socioeconomic factors contributing to maternal deaths in Jharkhand, India. This cross-sectional study was carried out in two phases, and a multistage sampling design was used in selecting deaths for verbal autopsy. Informed consent was taken into consideration before verbal autopsy. The analytical approach includes bivariate analysis using SPSS 15, besides triangulation of qualitative and quantitative findings. Most of the deceased were poor (89%), non-literates (85%), and housewives (74%). Again, 80% died in the community/at home, 28% died during pregnancy while another 26% died during delivery. Any antenatal care was received by merely 28% women, and only 20% of the deliveries were conducted by skilled birth attendants (doctors and midwives). Delays in decision-making, travel, and treatment compounded by ignorance of obstetric complications, inadequate use of maternal healthcare services, poor healthcare infrastructure, and harmful rituals are the major contributing factors of maternal deaths in India.Key words: Delays, treatment; Factors; Maternal death; Verbal autopsy; India     

The angiotensin‐converting enzyme gene insertion/deletion polymorphism in Indian patients with vitiligo: a case–control study and meta‐analysis

Background  Vitiligo is a common, acquired, idiopathic depigmenting skin disorder. Although the exact pathogenesis remains unknown, genetic susceptibility and autoimmune responses play a role in vitiligo development. Previous studies have suggested that the D allele of the insertion/deletion (I/D) polymorphism of the angiotensin‐converting enzyme (ACE) gene is associated with vitiligo in Indians and Koreans. Furthermore, significantly higher serum ACE levels have been demonstrated in patients with some autoimmune and autoinflammatory disorders. Objectives  The objectives were to investigate any association between the ACE I/D polymorphism and vitiligo susceptibility in an Indian population, and to compare serum ACE levels in patients with vitiligo and healthy subjects. Methods  The ACE I/D genotypes of 79 patients with vitiligo and 100 normal individuals were determined by polymerase chain reaction amplification. A meta‐analysis was done to compare the distribution of the ACE I/D alleles and genotypes in the current and three previous studies. Serum ACE levels were evaluated by enzyme‐linked immunosorbent assay. Results  A significant increase in the frequency of the ACE I/D D allele was evident in patients with vitiligo in both the case–control study [P = 0·005; odds ratio (OR) 1·87; 95% confidence intervals (CI) 1·22–2·85] and the meta‐analysis (P = 0·044; OR 1·44; 95% CI 1·01–2·06). Serum ACE levels were significantly increased in patients with vitiligo compared with healthy subjects (P < 0·0001). Conclusions  In agreement with earlier reports, the ACE I/D D allele is associated with vitiligo susceptibility in the Indian population. The significantly elevated serum ACE levels in our cohort of patients with vitiligo concur with those previously found in patients with some other autoimmune diseases.     

Exposure-Response (Safety) Analysis to Identify Linifanib Dose for a Phase III Study in Patients With Hepatocellular Carcinoma

Background

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related deaths and the fifth most common cancer globally. Hepatocellular carcinoma produces highly vascular tumors that overexpress vascular endothelial growth factor (VEGF), thus making VEGF a promising therapeutic target. The competitive inhibitor linifanib (ABT-869) has selectivity for VEGF and platelet-derived growth factor (PDGF) receptors and minimal activity against unrelated tyrosine and serine and threonine kinases. However, the optimal dosing regimen for linifanib in HCC patients is not yet known.

Objective

This study attempts to identify a linifanib dose or dosing regimen with an acceptable safety profile for a Phase III study in HCC patients.

Methods

The pharmacokinetic (PK) properties of linifanib were characterized from 2 Phase I and 3 Phase II clinical trials. Of the 266 patients evaluated, the median weight was 68 kg (range, 35-177 kg), 64% were male, and 87.6% of patients received an oral solution of linifanib, whereas 12.4% received a tablet formulation. Approximately 95% of patients received drug based on weight, with the remaining on a fixed-dosing regimen. A population PK analysis was conducted to characterize the linifanib exposure for each patient. Linifanib C_max and AUC derived from the population PK properties were correlated with the rates of adverse events (AEs).

Results

Linifanib PK properties are dose proportional for the 0.10-mg/kg to 0.25-mg/kg once daily dose range and are time independent after repeated oral dosing. The T_max of linifanib is approximately 3 hours, and the t_½ is approximately 1 day. The most common AEs related to linifanib PK were hypertension (P = 0.02 for C_max and P = 0.01 for AUC), diarrhea (P = 0.001 for C_max and P = 0.0012 for AUC), proteinuria (P = 0.001 for C_max and P = 0.002 for AUC), and asthenia (P = 0.03 for AUC). Weight and sex were identified as covariates for C_max, and sex was identified as a covariate for AUC. The predicted AE range for females was slightly higher compared with males; however, the AE range is tighter for the weight range for fixed dosing compared with weight-based dosing, regardless of sex.

Conclusions

The PK properties of linifanib support a one-compartment model with first-order absorption and elimination. Comparison of weight-based and fixed dosing revealed predicted AE rates to be similar, with a tighter AE range for fixed dosing. The safety profile of linifanib, therefore, supports a 17.5 mg fixed starting dose for Phase III clinical studies.     

Screening and characterization of extracelluar L-asparaginase producing Bacillus subtilis strain hswx88, isolated from Taptapani hotspring of Odisha,India

Objective

To screen and isolate an eco-friendly, a thermophilic and potent L-asparaginase producing bacterium, with novel immunological properties that may obviates hypersensitivity reactions.

Methods

In the present study bacterial strain isolated for extracellular L-asparaginase production from hotspring, identified by morphological, biochemical and physiological tests followed by 16S rDNA technology and the L-asparaginase production ability was tested by both semi quantitative and quantitative enzymatic assay.

Result

The bacterial strain was identified as Bacillus subtilis strain hswx88 (GenBank Accession Number: {"type":"entrez-nucleotide","attrs":{"text":"JQ237656.1","term_id":"374341559","term_text":"JQ237656.1"}}JQ237656.1). The extracellular enzyme yielding capacity isolate Bacillus subtilis strain hswx88 (23.8 IU/mL) was found to be 1.7 and 14.5 times higher than the reference organism Pectobacterium carotovorum MTCC 1428 (14.2 IU/mL) and Bacillus sp. BCCS 034 (1.64 IU/mL).

Conclusion

The isolate is eco-friendly and useful to produce bulk quantity of extracellular, thermophilic L-asparaginase for the treatment of various tumor cases and for preparation of acrylamide free fry food preparation.