The Impact of Alternate Methodological and Structural Assumptions on Results of Cost-effectiveness Analysis: Empirical Evidence using Three Indian Economic Evaluations.

BACKGROUND: Despite advancement in methods and application of economic evaluations (EEs), there are several uncertainties. OBJECTIVES: To assess the impact of alternate methodological and structural assumptions for four key principles of EE, on the results of cost-effectiveness analysis. MATERIALS AND METHODS: Three previously published model-based EEs were used: (1) Integrated Management of Neonatal and Childhood Illnesses (IMNCIs) intervention; (2) intervention for multiple myeloma, and (3) safety-engineered syringes (SES) intervention. A series of empirical analyses was undertaken to assess the impact of alternate assumptions for discount-rate, time-horizon, study perspective, and health outcome measure, on incremental cost-effectiveness ratio (ICER), and interpretation of cost-effectiveness. RESULTS: Increasing discount rate resulted in an increase in ICERs, for all three case-studies; however, there was no change in the conclusions. Using shorter time-horizons resulted in a significant increase in ICERs, the multiple myeloma intervention remained cost-ineffective, SES intervention became cost-ineffective, whereas IMNCI intervention remained cost-effective, despite a three-fold increase in ICER. On using disability adjusted life years instead of quality adjusted life years, ICERs increased to 0.04, 2 and 4 times for SES, IMNCI and multiple myeloma interventions, respectively. On analyzing results from a societal perspective, a decline in ICERs was observed. The decline was significant for IMNCI where the intervention turned dominant/cost-saving. In the other two case-studies decline in ICERs was modest, 32% for multiple myeloma, and 4% for SES. CONCLUSION: We observed a significant impact of using alternate assumptions on ICERs which can potentially impact resource-allocation decisions. Our findings provide strong argument in favor of standardization of processes and development of country-specific guidelines for conduct of EE.

Adherence to country-specific guidelines among economic evaluations undertaken in three high-income and middle-income countries: a systematic review.

OBJECTIVE: To assess the adherence of economic evaluations to the recommendations on principles of economic evaluation as stated in the country-specific guidelines for three countries across different income groups, namely, Canada, South Africa, and Egypt. METHODS: Searches were undertaken in three databases to identify economic evaluations meeting predefined inclusion criteria. Methodological and reporting standards listed in the country-specific guidelines were converted into discrete binary variables to calculate mean adherence scores. Quality appraisal was done using Drummond's checklist. Stratified analysis was undertaken to identify independent variables affecting adherence. RESULTS: We identified forty-four, seventy-nine, and sixteen economic evaluations for Canada, South Africa, and Egypt, respectively. The mean adherence score was the highest for Canada (71%), followed by South Africa (65%) and Egypt (60%). Adherence to guidelines was positively correlated with quality of studies, r = .72. Furthermore, the mean adherence score was significantly (p < .05) higher for studies using a cost-utility analysis design (72%), having local/national funding aid (72%), undertaken by a health economist (71%) and for pharmacoeconomic evaluations (70%). CONCLUSION: The quality of economic evaluations improves with adherence to country-specific guidelines. Locally funded and health-economist led health technology assessments (HTAs) should be encouraged for greater adherence to the guidelines. The HTA researchers and the HTA bodies should lay emphasis on adherence to the country-specific guidelines for improving the quality of HTA evidence.

Criteria Used for Priority-Setting for Public Health Resource Allocation in Low- and Middle-Income Countries: A Systematic Review.

OBJECTIVES: This systematic review aimed to identify criteria being used for priority setting for resource allocation decisions in low- and middle-income countries (LMICs). Furthermore, the included studies were analyzed from a policy perspective to understand priority setting processes in these countries. METHODS: Searches were carried out in PubMed, Embase, Econlit, and Cochrane databases, supplemented with pre-identified Web sites and bibliographic searches of relevant papers. Quality appraisal of included studies was undertaken. The review protocol is registered in International Prospective Register of Systematic Reviews PROSPERO CRD42017068371. RESULTS: Of 16,412 records screened by title and abstract, 112 papers were identified for full text screening and 44 studies were included in the final analysis. At an overall level, cost-effectiveness 52 percent (n = 22) and health benefits 45 percent (n = 19) were the most cited criteria used for priority setting for public health resource allocation. Inter-region (LMICs) and between various approaches (like health technology assessment, multi-criteria decision analysis (MCDA), accountability for reasonableness (AFR) variations among criteria were also noted. Our review found that MCDA approach was more frequently used in upper middle-income countries and AFR in lower-income countries for priority setting in health. Policy makers were the most frequently consulted stakeholders in all regions. CONCLUSIONS AND RECOMMENDATIONS: Priority-setting criteria for health resource allocation decisions in LMICs largely comprised of cost-effectiveness and health benefits criteria at overall level. Other criteria like legal and regulatory framework conducive for implementation, fairness/ethics, and political considerations were infrequently reported and should be considered.

Out-of-pocket expenditure for hospitalization in Haryana State of India: Extent, determinants & financial risk protection.

BACKGROUND & OBJECTIVES: India aspires to achieve universal health coverage, which requires ensuring financial risk protection (FRP). This study was done to assess the extent of out-of-pocket (OOP) expenditure and FRP for hospitalization in Haryana State, India. Further, the determinants for FRP were also evaluated. METHODS: Data collected as a part of a household level survey conducted in Haryana 'Concurrent Evaluation of National Rural Health Mission: Haryana Health Survey' were analyzed. Descriptive analysis was undertaken to assess socio-demographic characteristics, hospitalization rate, extent and determinants of OOP expenditure and FRP. Prevalence of catastrophic health expenditure (CHE) (more than 40% of non-food expenditure) and impoverishment (Int$ 1.25) were estimated. Multivariate logistic regression was used to assess determinants of FRP. RESULTS: Hospitalization rate was found to be 3106 persons or 3307 episodes per 100,000 population. Median OOP expenditure on hospitalization was ₹ 8000 (USD 133), which was predominantly attributed to medicines (37%). Prevalence of CHE was 25.2 per cent with higher prevalence amongst males [odds ratio (OR)=1.30], those belonging to scheduled caste and scheduled tribes (OR=1.35), poorest 20 per cent households (OR=3.05), having injuries (OR=4.03) and non-communicable diseases (OR=3.13) admitted in a private hospital (OR=2.69) and those who were insured (OR=1.74). There was a 12 per cent relative increase in poverty head count due to OOP payments on healthcare. INTERPRETATION & CONCLUSIONS: Our findings showed that hospitalization resulted in significant OOP expenditure, leading to CHEs and impoverishment of households. Impact of OOP expenditures was inequitably more on the vulnerable groups. OOP expenditure may be curtailed through provision of free medicines and diagnostics and removal of any form of user charges.

Healthcare cost accounting in the Indian hospital sector.

Setting reimbursement rates in national insurance schemes requires robust cost data. Collecting provider generated cost accounting information is a potential mechanism for improving the cost evidence. To inform strategies for obtaining cost data to set reimbursement rates, this analysis aims to describe the role of cost accounting in public and private health sectors in India and describe the importance, perceived barriers, and facilitators to improving cost accounting systems. In-depth interviews (IDI) were conducted with 11 key informants. The interview tool guide was informed by a review of published and grey literature and government websites. The interviews were recorded for both audio and video and transcribed. A thematic coding framework was developed for the analysis. Multiple discussions were held to add, delete, classify, or merge the themes. The themes identified were: the status of cost accounting in the Indian hospital sector, legal and regulatory requirements for cost reporting, challenges to implementing cost accounting, and recommendations for improving cost reporting by healthcare providers. The findings indicate that the sector lacks maturity in cost accounting due to a lack of understanding of its benefits, limited capacity, and weak enforcement of cost reporting regulations. Providers recognize the value of cost analysis for investment decisions but have mixed opinions on the willingness to gather and report cost information, citing resource constraints and a lack of trust in payers. Additionally, heterogeneity among providers will require tailored approaches in developing cost accounting reporting frameworks and regulations. Healthcare cost accounting systems in India are rudimentary with a few exceptions, raising questions about how to source these data sustainably. Strengthening cost accounting systems will be contingent upon developing standardized formats that generate sufficient information for policymaking, are acceptable to private providers, and can be integrated with the existing data management systems.

Understanding the extent of economic evidence usage for informing policy decisions in the context of India's national health insurance scheme: Ayushman Bharat Pradhan Mantri Jan Aarogya Yojana (PM-JAY).

INTRODUCTION: Ayushman Bharat Pradhan Mantri Jan Aarogya Yojana (PM-JAY) is one of the world's largest tax-funded insurance schemes. The present study was conducted to understand the decision-making process around the evolution (and revision) of health benefit packages (HBPs) and reimbursement rates within PM-JAY, with a specific focus on assessing the extent of use of economic evidence and role of various stakeholders in shaping these policy decisions. METHODS: A mixed-methods study was adopted involving in-depth interviews with seven key stakeholders involved in HBP design and reimbursement rates decisions, and a survey of 80 government staff and other relevant stakeholders engaged in the implementation of PM-JAY. The data gathered were thematically analysed, and a coding framework was developed to explore specific themes. Additionally, publicly available documents were reviewed to ensure a comprehensive understanding of the decision-making processes. RESULTS: Findings reveal a progressive transition towards evidence-based practices for policy decisions within PM-JAY. The initial version of HBP relied heavily on key criteria like disease burden, utilisation rates, and out-of-pocket expenditures, along with clinical opinion in shaping decisions around the inclusion of services in the HBP and setting reimbursement rates. Revised HBPs were informed based on evidence from a national-level costing study and broader stakeholder consultations. The use of health economic evidence increased with each additional revision with consideration of health technology assessment (HTA) evidence for some packages and reimbursement rates based on empirical cost evidence in the most recent update. The establishment of the Health Financing and Technology Assessment unit further signifies the use of evidence-based policymaking within PM-JAY. However, challenges persist, notably with regard to staff capacity and understanding of HTA principles, necessitating ongoing education and training initiatives. CONCLUSION: While substantial progress has been made in transitioning towards evidence-based practices within PM-JAY, sustained efforts and political commitment are required for the ongoing systematisation of processes.

Development of the Indian Reference Case for undertaking economic evaluation for health technology assessment.

Background: Health technology assessment (HTA) is globally recognised as an important tool to guide evidence-based decision-making. However, heterogeneity in methods limits the use of any such evidence. The current research was undertaken to develop a set of standards for conduct of economic evaluations for HTA in India, referred to as the Indian Reference Case. Methods: Development of the reference case comprised of a four-step process: (i) review of existing international HTA guidelines; (ii) systematic review of economic evaluations for three countries to assess adherence with pre-existing country-specific HTA guidelines; (iii) empirical analysis to assess the impact of alternate assumptions for key principles of economic evaluation on the results of cost-effectiveness analysis; (iv) stakeholder consultations to assess appropriateness of the recommendations. Based on the inferences drawn from the first three processes, a preliminary draft of the reference case was developed, which was finalised based on stakeholder consultations. Findings: The Indian Reference Case provides twelve recommendations on eleven key principles of economic evaluation: decision problem, comparator, perspective, source of effectiveness evidence, measure of costs, health outcomes, time-horizon, discounting, heterogeneity, uncertainty analysis and equity analysis, and for presentation of results. The recommendations are user-friendly and have scope to allow for context-specific flexibility. Interpretation: The Indian Reference Case is expected to provide guidance in planning, conducting, and reporting of economic evaluations. It is anticipated that adherence to the Reference Case would increase the quality and policy utilisation of future evaluations. However, with advancement in the field of health economics efforts aimed at refining the Indian Reference Case would be needed. Funding: This research received no specific grant from any funding agency, commercial, or not-for-profit sectors. The research was undertaken as part of doctoral thesis of Sharma D, who received scholarship from the Indian Council of Medical Research (ICMR), New Delhi, India.

Validating the rigour of adaptive methods of economic evaluation.

BACKGROUND: There has been a lot of debate on how to 'generalise' or 'translate' findings of economic evaluation (EE) or health technology assessment (HTA) to other country contexts. Researchers have used various adaptive HTA (aHTA) methods like model-adaptation, price-benchmarking, scorecard-approach, etc., for transferring evidence from one country to other. This study was undertaken to assess the degree of accuracy in results generated from aHTA approaches specifically for EE. METHODS: By applying selected aHTA approaches, we adapted findings of globally published EE to Indian context. The first-step required identifying two interventions for which Indian EE (referred to as the 'Indian reference study') has been conducted. The next-step involved identification of globally published EE. The third-step required undertaking quality and transferability check. In the fourth step, outcomes of EE meeting transferability standards, were adapted using selected aHTA approaches. Lastly, adapted results were compared with findings of the Indian reference study. RESULTS: The adapted cost estimates varied considerably, while adapted quality-adjusted life-years did not differ much, when matched with the Indian reference study. For intervention I (trastuzumab), adapted absolute costs were 11 and 6 times higher than the costs reported in the Indian reference study for control and intervention arms, respectively. Likewise, adapted incremental cost and incremental cost-effectiveness ratio (ICER) were around 3.5-8 times higher than the values reported in the Indian reference study. For intervention II (intensity-modulated radiation therapy), adapted absolute cost was 35% and 12% lower for the comparator and intervention arms, respectively, than the values reported in the Indian reference study. The mean incremental cost and ICER were 2.5 times and 1.5 times higher, respectively, than the Indian reference study values. CONCLUSION: We conclude that findings from aHTA methods should be interpreted with caution. There is a need to develop more robust aHTA approaches for cost adjustment. aHTA may be used for 'topic prioritisation' within the overall HTA process, whereby interventions which are highly cost-ineffective, can be directly ruled out, thus saving time and resources for conducting full HTA for interventions that are not well studied or where evidence is inconclusive.

Health-Related Quality of Life Among Liver Disorder Patients in Northern India.

Objective: The present study aims to determine the health-related quality of life (HRQoL) among liver disorder patients being treated in tertiary care hospital in north India and exploration of factors affecting HRQoL. Methodology: The HRQoL was assessed among 230 patients visiting either the outpatient department (OPD) or those admitted in high dependency unit (HDU) or liver intensive care unit (ICU) using direct measuring tools such as Euro QoL five-dimension questionnaire (EQ-5D) and EQ visual analog scale. Multivariate regression was used to explore the factors influencing HRQoL. Results: Mean EQ-5D scores among chronic hepatitis and compensated cirrhosis patients were 0.639 ± 0.062 and 0.562 ± 0.048, respectively. Among those who were admitted in the ICU or HDU, mean EQ-5D score was 0.295 ± 0.031. At discharge, this score improved significantly to 0.445 ± 0.055 (P < 0.001). The multivariate results implied that HRQoL was significantly better among patients with lower literacy level (P = 0.018) and those treated in OPD settings (P < 0.001). Conclusion: HRQoL is impaired among patients suffering from liver disorders specifically those admitted in ICU. Further, there is a need to generate more evidence to explore the impact of determinants and treatment-associated costs on the HRQoL.

Identification of quantitative trait loci (QTLs) and candidate genes for seed shape and 100-seed weight in soybean [Glycine max (L.) Merr.].

Seed size and shape are important traits determining yield and quality in soybean. Seed size and shape are also desirable for specialty soy foods like tofu, natto, miso, and edamame. In order to find stable quantitative trait loci (QTLs) and candidate genes for seed shape and 100-seed weight, the current study used vegetable type and seed soybean-derived F2 and F2:3 mapping populations. A total of 42 QTLs were mapped, which were dispersed across 13 chromosomes. Of these, seven were determined to be stable QTLs and five of them were major QTLs, namely qSL-10-1, qSW-4-1, qSV-4-1, qSLW-10-1, and qSLH-10-1. Thirteen of the 42 QTLs detected in the current study were found at known loci, while the remaining 29 were discovered for the first time. Out of these 29 novel QTLs, 17 were major QTLs. Based on Protein Analysis Through Evolutionary Relationships (PANTHER), gene annotation information, and literature search, 66 genes within seven stable QTLs were predicted to be possible candidate genes that might regulate seed shape and seed weight in soybean. The current study identified the key candidate genes and quantitative trait loci (QTLs) controlling soybean seed shape and weight, and these results will be very helpful in marker-assisted breeding for developing soybean varieties with improved seed weight and desired seed shape.

National Healthcare Economic Evaluation Guidelines: A Cross-Country Comparison.

BACKGROUND AND OBJECTIVES: Globally, a number of countries have developed guidelines that describe the design and conduct of economic evaluations as part of health technology assessment (HTA) or pharmacoeconomic analysis for decision making. The current scoping review was undertaken with an objective to summarize the recommendations made on methods of economic evaluation by the national healthcare economic evaluation (HEE) guidelines. METHODOLOGY: A comprehensive search was undertaken in the website repositories of the International Society for Pharmacoeconomic and Outcomes Research (ISPOR) and Guide to Economic Analysis and Research (GEAR), and websites of national HTA agencies and ministries of health of individual countries. All guidelines in the English language were included in this review. Data were extracted with respect to general and methodological characteristics, and a descriptive analysis of recommendations made across the countries was undertaken. RESULTS: Overall, our review included 31 national HEE guidelines, published between 1997 and August 2020. Nearly half (45%) of the guidelines targeted the evaluation of pharmaceuticals. The nature of the guidelines was either mandatory (31%), recommendatory (42%), or voluntary (16%). There was a substantial consensus among the guidelines on several key principles, including type of economic evaluation (cost-utility analysis), time horizon of the analysis (long enough), health outcome measure (quality-adjusted life-years) and use of sensitivity analyses. The recommendations on study perspective, comparator, discount rate and type of costs to be included (particularly the inclusion of indirect costs) varied widely. CONCLUSION: Despite similarity in the overall processes, variation in several recommendations given by various national HEE guidelines was observed. This is perhaps unsurprising given the differences in the health systems and financing mechanisms, capacity of local researchers, and data availability. This review offers important lessons and a starting point for countries that are planning to develop their own HEE guidelines.

DO-BOD modeling of River Yamuna for national capital territory, India using STREAM II, a 2D water quality model.

The study illustrates the utility of STREAM II as a modeling package to determine the pollution load due to organic matter in the River Yamuna during its course through the National Capital Territory that is Delhi, India. The study was done for a period from 1995-2005. Model simulates the dissolved oxygen and biochemical oxygen demand parameters in a two-dimensional fashion by performing the numerical solution to a set of differential equations representing aquatic life with the help of Crank-Nicholson finite difference method. The model was simulated and calibrated through the field water-quality primary data and the secondary data which were taken from Central Pollution Control Board. The main reasons for the high river pollution is increasing population of Delhi and other states, leading to generation of huge amounts of domestic sewage into the river Yamuna. The model gave a good agreement between calibrated and observed data, thus, actualizing the validity of the model. However, discrepancies noticed during model calibrations were attributed to the assumptions adopted in the model formulation and to lack of field data.

Out-of-pocket expenditure and catastrophic health expenditure for hospitalization due to injuries in public sector hospitals in North India.

BACKGROUND: Injuries are a major public health problem, resulting in high health care demand and economic burden. They result in loss of disability adjusted life years (DALYs) and high out-of-pocket expenditure. However, there is little evidence on the economic burden of injuries in India. We undertook this study to report out-of-pocket expenditure and the prevalence of catastrophic health expenditure for injuries related hospitalizations in public sector hospitals in North India. Further, we also evaluate the determinants of catastrophic health expenditure. METHODS AND ANALYSIS: A prospective observational study was conducted. Participants were recruited from three hospitals for all injury cases. Data were collected via face-to-face baseline interviews and follow-up interviews over the phone at 1, 2, 4 and 12 months post-injury. Prevalence of catastrophic health expenditure (more than 30% of consumption expenditure) and impoverishment (International dollar 1.90) were estimated. RESULTS: Road traffic injuries (57%) were the leading cause of injury. Direct out-of-pocket expenditure for hospitalizations was INR 16,768 (USD 263) while indirect productivity loss was INR 8,164 (USD 128). The prevalence of catastrophic expenditure was 22.2% with 12.2% slipping below poverty line. Prevalence of catastrophic health expenditure and impoverishment was higher and significantly associated with poorest quintile, tertiary care hospital and increased duration of hospitalization (p< 0.001). CONCLUSION: The economic impact of injuries is notably high both in terms of out-of-pocket expenditure and productivity loss. A high proportion of households experienced catastrophic expenditure and impoverishment following an injury, highlighting need for programs to prevent injuries.

ß-N-oxalyl-L-α,ß-diaminopropionic acid induces wound healing by stabilizing HIF-1α and modulating associated protein expression.

BACKGROUND: ß-N-oxalyl-L-α,ß-diaminopropionic acid (L-ODAP) is a non-protein amino acid with haemostatic property present in Lathyrus sativus. It is considered to be the causative agent of neurolathyrism that occurs upon prolonged overconsumption of Lathyrus sativus seeds. L-ODAP is used as a haemostatic drug in surgical dressings. We previously reported that it can stabilize hypoxia inducible factor (HIF)-1α in normoxic conditions. HYPOTHESIS: We hypothesised that L-ODAP might affect wound healing by modulating cellular proliferation, migration and angiogenesis via HIF-1α stabilization. STUDY DESIGN: We performed in vitro assays to evaluate wound healing activity of L-ODAP. Further, we prepared pharmaceutical gel containing L-ODAP and checked its effect on healing of full thickness excision wounds using Wistar albino rats. METHODS: Effect of L-ODAP on HT1080 cell line proliferation, migration and invasion was investigated. Further, gel containing L-ODAP was applied on full thickness excision wounds of Wistar rats. Western blot and zymography were performed with wound tissue extracts obtained 2 days post-wounding and histological and immunohistochemical analysis with regenerated tissue obtained 10 days post-wounding. Evaluation was made based on wound contraction percentage, histological analysis and protein expression levels. RESULTS: L-ODAP significantly (P < 0.05) affected wound healing both in vitro and in vivo. At non-toxic concentrations, it induced cell proliferation, migration, invasion and MMP-2 & -9 expressions. L-ODAP treated wounds healed faster than vehicle treated ones. Significantly higher expression level of HIF-1α, VEGF-A, PDGF-A and matrix metalloproteases were observed in L-ODAP treated wounds. CONCLUSION: The present investigation explores potential of L-ODAP as a wound healing agent. L-ODAP positively affected wound healing both in vitro and in vivo and thus could be considered a natural wound healing agent.

ß-N-oxalyl-L-α, ß- diaminopropionic acid induces HRE expression by inhibiting HIF-prolyl hydroxylase-2 in normoxic conditions.

Hypoxia inducible factor (HIF)-1α, a subunit of HIF transcription factor, regulates cellular response to hypoxia. In normoxic conditions, it is hydroxylated by prolyl hydroxylase (PHD)-2 and targeted for proteosomal degradation. Drugs which inhibit PHD-2 have implications in conditions arising from insufficient blood supply. ß-ODAP (ß-N- oxalyl-L-α, ß- diaminopropionic acid), a non-protein excitatory amino acid present in Lathyrus sativus, is an α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor agonist known to activate conventional protein kinase C and stabilize HIF-1α under normoxic conditions. However, the mechanism of HIF-1α stabilization by this compound is unknown. In silico approach was used to understand the mechanism of stabilization of HIF-1α which revealed ß-ODAP interacts with key amino acid residues and Fe2+ at the catalytic site of PHD-2. These results were further corroborated with luciferase HRE (hypoxia response element) reporter system in HeLa cells. Different chemical modulators of PHD-2 activity and HIF-1α levels were included in the study for comparison. Results obtained indicate that ß-ODAP inhibits PHD-2 and facilitates HIF dependent HRE expression and hence, might be helpful in conditions arising from hypoxia.

S137 phosphorylation of profilin 1 is an important signaling event in breast cancer progression.

BACKGROUND: Profilins are actin-modulating proteins regulating many intracellular functions based on their multiple and diverse ligand interactions. They have been implicated to play a role in many pathological conditions such as allergies, cardiovascular diseases, muscular atrophy, diabetes, dementia and cancer. Post-translational modifications of profilin 1 can alter its properties and subsequently its function in a cell. In the present study, we identify the importance of phosphorylation of profilin 1 at serine 137 (S137) residue in breast cancer progression. METHODS/PRINCIPAL FINDINGS: We found elevated profilin 1 (PFN) in human breast cancer tissues when compared to adjacent normal tissues. Overexpression of wild-type profilin 1 (PFN-WT) in breast cancer MCF7 cells made them more migratory, invasive and adherent independent in comparison to empty vector transfected cells. Mutation in serine phosphorylation site (S137) of profilin 1 (PFN-S137A) significantly abrogated these properties. Mutation affecting actin-binding ability (PFN-R74E) of profilin 1 enhanced its tumorigenic function whereas mutation affecting its poly-L-proline binding function (PFN-H133S) alleviated these mechanisms in breast cancer cells. PFN-WT was found to activate matrix metalloproteinases by zymography, MMP2 and MMP9 in presence of PDBu (phorbol 12, 13 dibutyrate, PI3K agonist) to enhance migration and invasion in MCF7 cells while PFN-S137A did not. Phosphorylation increased migration and invasion in other mutants of profilin 1. Nuclear profilin levels also increased in the presence of PDBu. CONCLUSIONS: Previous studies show that profilin could be executing a dual role in cancer by either suppressing or promoting tumorigenesis in a context dependent manner. In this study we demonstrate for the first time that phosphorylation of profilin 1 at serine 137 enhances oncogenic properties in breast cancer cells. Inhibitors targeting profilin 1 phosphorylation directly or indirectly through inhibition of kinases that phosphorylate profilin could be valuable therapeutic agents that can alter its activity and thereby control the progression of cancer.

A study of platelet volume indices in a patients of ischaemic cerebrovascular disease.

Background: The objective of the study is to estimate platelet volume indices in patients of cerebral ischemic vascular disease. Methods: The present study was conducted on 170 subjects in Department of Medicine, NIMS Medical College and Hospital, Jaipur, Rajasthan over eighteen months. The study was conducted on 60 patients admitted in the wards and ICU under the Department of Medicine and 110 controls who were the normal and healthy during the study period. In this study the values of platelet indices – MPV, PDW and platelet count were observed in patients of cerebral ischemia. It was found that large platelets contribute to the prethrombotic state in ischemic syndromes and they may play a specific role in infarction. Because larger platelets are haemostatically more active and hence, their presence is probably a risk factor for developing thrombosis. Statistical analysis was done using Chi – square test, unpaired ‘t’ test and ANOVA test. A p value <0.05 was considered statistically significant. Results: In this study it was found that in cerebrovascular disease patients, MPV was 10.30±0.83 fL, PDW was 14.50±0.55 fL, platelet count was 260×109 ± 29×109 /L while in control, MPV was 8.14± 0.72 fL, PDW was 10.71±0.48 fL, platelet count was 285×109 ± 50 ×109 /L. MPV and PDW were higher and platelet count lower in cerebrovascular disease group and a highly significant difference (p<0.001) was found on comparing with controls. Conclusion: In this study, it was found that MPV and PDW were raised in cerebrovascular disease suggestive of statistically highly significant when compared to normal control group.