Paying for Hemodialysis in Kerala, India: A Description of Household Financial Hardship in the Context of Medical Subsidy.

INTRODUCTION: Many low- and middle-income countries are implementing strategies to increase dialysis availability as growing numbers of people reach end-stage renal disease. Despite efforts to subsidize care, the economic sustainability of chronic dialysis in these settings remains uncertain. We evaluated the association of medical subsidy with household financial hardship related to hemodialysis in Kerala, India, a state with high penetrance of procedure-based subsidies for patients on dialysis. METHODS: Patients on maintenance hemodialysis at 15 facilities in Kerala were administered a questionnaire that ascertained demographics, dialysis details, and household finances. We estimated direct and indirect costs of hemodialysis, and described the use of medical subsidy. We evaluated whether presence of subsidy (private, charity, or government-sponsored) was associated with lower catastrophic health expenditure (defined as ≥40% of nonsubsistence expenditure spent on dialysis) or distress financing. RESULTS: Of the 835 patients surveyed, 759 (91%) reported their households experienced catastrophic health expenditure, and 644 (77%) engaged in distress financing. Median dialysis-related expenditure was 80% (25th-75th percentile: 60%-90%) of household nonsubsistence expenditure. Government subsidies were used by 238 (29%) of households, 139 (58%) of which were in the lowest income category. Catastrophic health expenditure was present in 215 (90%) of households receiving government subsidy and 332 (93%) without subsidy. CONCLUSIONS: Provision of medical subsidy in Kerala, India was not associated with lower rates of household financial hardship related to long-term hemodialysis therapy. Transparent counseling on impending costs and innovative strategies to mitigate household financial distress are necessary for persons with end-stage renal disease in resource-limited settings

Fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin with gemtuzumab ozogamicin improves event-free survival in younger patients with newly diagnosed aml and overall survival in patients with npm1 and flt3 mutations

Purpose To determine the optimal induction chemotherapy regimen for younger adults with newly diagnosed AML without known adverse risk cytogenetics. Patients and Methods One thousand thirty-three patients were randomly assigned to intensified (fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin [FLAG-Ida]) or standard (daunorubicin and Ara-C [DA]) induction chemotherapy, with one or two doses of gemtuzumab ozogamicin (GO). The primary end point was overall survival (OS). Results There was no difference in remission rate after two courses between FLAG-Ida + GO and DA + GO (complete remission [CR] + CR with incomplete hematologic recovery 93% v 91%) or in day 60 mortality (4.3% v 4.6%). There was no difference in OS (66% v 63%; P = .41); however, the risk of relapse was lower with FLAG-Ida + GO (24% v 41%; P < .001) and 3-year event-free survival was higher (57% v 45%; P < .001). In patients with an NPM1 mutation (30%), 3-year OS was significantly higher with FLAG-Ida + GO (82% v 64%; P = .005). NPM1 measurable residual disease (MRD) clearance was also greater, with 88% versus 77% becoming MRD-negative in peripheral blood after cycle 2 (P = .02). Three-year OS was also higher in patients with a FLT3 mutation (64% v 54%; P = .047). Fewer transplants were performed in patients receiving FLAG-Ida + GO (238 v 278; P = .02). There was no difference in outcome according to the number of GO doses, although NPM1 MRD clearance was higher with two doses in the DA arm. Patients with core binding factor AML treated with DA and one dose of GO had a 3-year OS of 96% with no survival benefit from FLAG-Ida + GO. Conclusion Overall, FLAG-Ida + GO significantly reduced relapse without improving OS. However, exploratory analyses show that patients with NPM1 and FLT3 mutations had substantial improvements in OS. By contrast, in patients with core binding factor AML, outcomes were excellent with DA + GO with no FLAG-Ida benefit

Remodeling Indirect Procurement in a Global Organization

In the case organization, a need to improve the process efficiency was felt by the leadership of the organization. During the current state analysis, it was discovered that indirect procurement functions of the case organization were decentralized globally and caused process inefficiency. The objective of this thesis was to generate proposals for remodeling the indirect procurement in the case organization to improve process efficiency. This thesis utilized qualitative research methods to collect all the relevant data. The thesis started with evaluating the current state of indirect procurement in the case organization. The theoretical framework focused on the topics related to indirect procurement, which was followed by developing a proposal for remodeling the current indirect procurement practices. To arrive at the proposal, data collection and data analysis was done by adopting inductive approach. Indirect procurement experts at the case organization were interviewed to gain insight of the current situation with indirect procurement. Thematic analysis of the data pointed to the development options for tackling indirect procurement challenges in the case organization. The outcome of this thesis is the proposal for remodeling the indirect procurement, which the case organization can adopt. This thesis proposed three options for remodeling the indirect procurement for the case organization, which is a global organization. The organization accepted one of the presented proposals, which is the hybrid mode of operation, formed by combining selectively the outsourcing and shared services center models. The interviews with the leadership also confirmed their willingness to consider adopting other proposals for remodeling the indirect procurement possibly in the future

Spectrum of biopsy-proven renal diseases: A single center experience

Kidney biopsy is one of the most important tools in the assessment of kidney disease as histopathological diagnosis promotes evidence-based practice in Nephrology. This study included 271 consecutive percutaneous kidney biopsies (145 males and 126 females) performed at EMS Memorial Cooperative Hospital, Perinthalmanna, Kerala, India, from September 2009 to March 2016. Among the biopsy-proven renal diseases (BPRD), primary glomerular diseases (PGD) were the most common (77.78%) followed by secondary glomerular diseases (SGD) (12.22%) and tubulointerstitial diseases (10%). The IgA nephropathy (IgAN) was the most common PGD and majority had mesangial hypercellularity (M1) (93.54%), tubular atrophy (T1 or T2 68.25%), and the most common pattern was M1, E0, S0, and T1, suggesting that patients of Indian subcontinent have aggressive disease type, unlike western literature. The focal segmental glomerulosclerosis (FSGS) was the second most common PGD and the majority were of not otherwise specified type. FSGS, membranous nephropathy and minimal change disease were the three most common causes for PGD causing nephrotic syndrome. Diabetic nephropathy and lupus nephritis were the two most common biopsy-proven SGDs. Among the patients of diabetes mellitus who underwent renal biopsy with suspicion of nondiabetic renal disease (NDRD), 58.33% had NDRD, 16.67% had DN+ NDRD, and 26.67% had DN alone. This study shows the changing pattern BPRD in comparison to earlier studies. This study also confirms the aggressive nature of IgAN in Indian patients and underlines the importance of renal biopsy in patients of DM

Case Report: Application of whole exome sequencing for accurate diagnosis of rare syndromes of mineralocorticoid excess [version 2; referees: 2 approved]

Syndromes of mineralocorticoid excess (SME) are closely related clinical manifestations occurring within a specific set of diseases. Overlapping clinical manifestations of such syndromes often create a dilemma in accurate diagnosis, which is crucial for disease surveillance and management especially in rare genetic disorders. Here we demonstrate the use of whole exome sequencing (WES) for accurate diagnosis of rare SME and report that p.R337C variation in the HSD11B2 gene causes progressive apparent mineralocorticoid excess (AME) syndrome in a South Indian family of Mappila origin

Leveraging big data using a novel clinical database and analytic platform based on 323,145 individuals with and without of Diabetes

Large volumes of biomedical data are being produced every day. Leveraging such voluminous amount of patient data using data science approaches help to uncover hidden patterns, unknown correlations, and other insights of the disease. Integration of diverse genomic data with comprehensive electronic health records (EHRs) exhibit challenges, but essentially, they provide a feasible opportunity to better understand the underlying diseases, treatment patterns and develop an efficient and effective approach to identify biomarkers for diagnosis and improve therapy. Here, we describe a big data solution for diabetes, providing an efficient and responsive scientific discovery platform for researchers. Clinical phenotype data was collected from EHR of a tertiary care diabetes centre across 20 locations in India. It encompasses &gt;20 million data points on 323,145 patients registered over 25 years. The biomedical data includes diverse collection of information such as well characterized clinical phenotypes, biochemical investigations, drug prescriptions, genotype mapping, micro- macrovascular complications of diabetes, pedigree charts. Additionally, more than 3 million genomic variants from high-throughput next generation sequencing (NGS) were analyzed, annotated and integrated into the respective patient phenotype data. Statistical methods such as t-test, ANOVA were used to describe the significance of clinical variables between subject groups. Time based visualization methods for showing temporal patterns in key clinical variables such fasting glucose, HbA1c, Albuminuria, etc. are provided. It provides a novel clinical database of information on 323,145 patients with type 2 diabetes (n=294,371), type 1 diabetes (n=1,945), gestational diabetes (n=645), prediabetes (n=7,363), patients with miscellaneous forms of diabetes including monogenic forms of diabetes (n=4,601) and normal glucose tolerance (n=12,579). It has about 144,926 diabetes patients (44.8% of total) with microvascular complications and 15,008 (4.6%) patients with macrovascular complications. It offers analytical tools to compute descriptive statistics of clinical variables for cohorts as well as visualizations to understand the disease progression of diabetes, uncover key event patterns such as episodes of high glucose levels, or drug treatments and their association with progression of disease over time. Thus, the database portal promotes practice of precision medicine and therefore useful to researchers, clinicians and pharmaceutical industry

Decreased Expression of the DNA Mismatch Repair Gene Mlh1 under Hypoxic Stress in Mammalian Cells

The hypoxic tumor microenvironment has been shown to contribute to genetic instability. As one possible mechanism for this effect, we report that expression of the DNA mismatch repair (MMR) gene Mlh1 is specifically reduced in mammalian cells under hypoxia, whereas expression of other MMR genes, including Msh2, Msh6, and Pms2, is not altered at the mRNA level. However, levels of the PMS2 protein are reduced, consistent with destabilization of PMS2 in the absence of its heterodimer partner, MLH1. The hypoxia-induced reduction in Mlh1 mRNA was prevented by the histone deacetylase inhibitor trichostatin A, suggesting that hypoxia causes decreased Mlh1 transcription via histone deacetylation. In addition, treatment of cells with the iron chelator desferrioxamine also reduced MLH1 and PMS2 levels, in keeping with low oxygen tension being the stress signal that provokes the altered MMR gene expression. Functional MMR deficiency under hypoxia was detected as induced instability of a (CA)(29) dinucleotide repeat and by increased mutagenesis in a chromosomal reporter gene. These results identify a potential new pathway of genetic instability in cancer: hypoxia-induced reduction in the expression of key MMR proteins. In addition, this stress-induced genetic instability may represent a conceptual parallel to the pathway of stationary-phase mutagenesis seen in bacteria