Protocol for a randomised phase 3 trial evaluating the role of Finasteride in active surveillance for men with low and intermediate-risk prostate cancer: the FINESSE study

Background Prostate cancer (PCa) is the most common male malignancy in the western world. Many men (40%) are diagnosed with localised low or intermediate-risk PCa, which is suitable for active surveillance (AS). AS affords careful monitoring to identify changes in otherwise non-life-threatening cancers. While AS reduces overtreatment (and quality of life impact), long-term compliance can be poor, with many men undergoing radical treatment after starting AS. Methods and analysis Finasteride in Active Surveillance for men with low and intermediate-risk prostate cancer (FINESSE) is a prospective, open-label, two-arm, phase 3 trial, in which men with low or intermediate PCa are randomised (1:1) to receive AS with or without finasteride (5 mg once a day for 2 years). Randomisation is stratified by age and PCa risk. AS includes regular prostate-specific antigen testing, MRI scans and the offer of repeat biopsy (at 3 years, or if imaging suggests progression). Additional MRI scans and/or biopsies will be performed for biochemical or clinical indications. We aim to recruit 550 men (aged 50 to 75 years) from up to eight sites. Active outpatient follow-up will be for 3–5 years (depending on date recruited), followed by passive registry-based follow-up for up to 10 years. Primary outcome is adherence to AS. Secondary outcomes include rates and type of disease progression, treatments received (for PCa and benign prostatic enlargement), overall and PCa-specific mortality, an understanding of patients/professionals views of this approach and health-related quality of life. An external panel of experts blinded to allocation will review all AS cessation and progression events. Trial pathologist’s and radiologist’s, blinded to allocation, will review representative cases. Analysis is Intention to Treat. Ethics and dissemination The study received Health Research Authority and South-Central Oxford Research Ethics Committee (14/12/2021: 21/SC/0349) and CTA/MHRA (29/12/2021: 21304/0274/001–0001) approvals. Results will be made available to providers and researchers via publicly accessible scientific journals. Trial registration number ISRCTN1686795

The importance of providing counselling and financial support to patients receiving treatment for multi-drug resistant TB: Mixed method qualitative and pilot intervention studies

Background: People with multi-drug resistant tuberculosis (MDR-TB) in low-income countries face many problems during treatment, and cure rates are low. The purpose of the study was (a) to identify and document the problems experienced by people receiving care for MDR-TB, and how they cope when support is not provided, to inform development of strategies; (b) to estimate the effectiveness of two resultant strategies, counselling alone, and joint counselling and financial support, of increasing DOTS-plus treatment success under routine programme conditions. Methods. A mixed-method study comprising a formative qualitative study, pilot intervention study and explanatory qualitative study to better understand barriers to completion of treatment for MDR-TB. Participants were all people starting MDR-TB treatment in seven DOTS-plus centres in the Kathmandu Valley, Nepal during January to December 2008. The primary outcome measure was cure, as internationally defined. Results: MDR-TB treatment caused extreme social, financial and employment hardship. Most patients had to move house and leave their job, and reported major stigmatisation. They were concerned about the long-term effects of their disease, and feared infecting others. In the resultant pilot intervention study, the two strategies appeared to improve treatment outcomes: cure rates for those receiving counselling, combined support and no support were 85%, 76% and 67% respectively. Compared with no support, the (adjusted) risk ratios of cure for those receiving counselling and receiving combined support were 1.2 (95% CI 1.0 to 1.6) and 1.2 (95% CI 0.9 to 1.6) respectively. The explanatory study demonstrated that patients valued both forms of support. Conclusions: MDR-TB patients are extremely vulnerable to stigma and extreme financial hardship. Provision of counselling and financial support may not only reduce their vulnerability, but also increase cure rates. National Tuberculosis Programmes should consider incorporating financial support and counselling into MDR-TB care: costs are low, and benefits high, especially since costs to society of incomplete treatment and potential for incurable TB are extremely high

Living knowledge of the healing plants: Ethno-phytotherapy in the Chepang communities from the Mid-Hills of Nepal

Contribution of indigenous knowledge in developing more effective drugs with minimum or no side effects helped to realise importance of study of indigenous remedies and the conservation of biological resources. This study analysed indigenous knowledge regarding medicinal plants use among the Chepang communities from ward number 3 and 4 of Shaktikhor Village Development Committee located in the central mid hills of Nepal. Data were collected in a one-year period and included interviews with traditional healers and elders. Chepangs are rich in knowledge regarding use of different plants and were using a total 219 plant parts from 115 species including one mushroom (belonging 55 families) for medicinal uses. Out of these, 75 species had 118 different new medicinal uses and 18 of them were not reported in any previous documents from Nepal as medicinal plants. Spiritual belief, economy and limitation of alternative health facilities were cause of continuity of people's dependency on traditional healers. Change in socio-economic activities not only threatened traditional knowledge but also resource base of the area. Enforcement of local institution in management of forest resources and legitimating traditional knowledge and practices could help to preserve indigenous knowledge

An empirical study of software design balance dynamics

The Design Metrics Research Team in the Computer Science Department at Ball State University has been engaged in developing and validating quality design metrics since 1987. Since then a number of design metrics have been developed and validated. One of the design metrics developed by the research team is design balance (DB). This thesis is an attempt to validate the metric DB. In this thesis, results of the analysis of five systems are presented. The main objective of this research is to examine if DB can be used to evaluate the complexity of a software design and hence the quality of the resulting software. Two of the five systems analyzed were student projects and the remaining three were from industry. The five systems analyzed were written in different languages, had different sizes and exhibited different error rates.Department of Computer ScienceThesis (M.S.

An empirical study of software design balance dynamics

The Design Metrics Research Team in the Computer Science Department at Ball State University has been engaged in developing and validating quality design metrics since 1987. Since then a number of design metrics have been developed and validated. One of the design metrics developed by the research team is design balance (DB). This thesis is an attempt to validate the metric DB. In this thesis, results of the analysis of five systems are presented. The main objective of this research is to examine if DB can be used to evaluate the complexity of a software design and hence the quality of the resulting software. Two of the five systems analyzed were student projects and the remaining three were from industry. The five systems analyzed were written in different languages, had different sizes and exhibited different error rates.Thesis (M.S.)Department of Computer Scienc

Abstract 5189: The transcriptional regulation of the long non-coding RNA HOTAIR in ovarian cancer.

Abstract The Polycomb Group (PcG) Repressive Complexes 1 and 2 (PRC1 and PRC2) maintain gene expression patterns by epigenetically modifying chromatin. PRC2 suppresses transcription by catalyzing the trimethylation of histone H3 at lysine 27 (H3K27me3), a hallmark of repressed chromatin. Although overexpression of PRC2 components has been implicated in cancer initiation, progression and metastasis how PRC2 is recruited to its target genes remains poorly understood. Recent work suggests the interaction of PRC2 with the long-non coding (lnc) RNA HOX transcript antisense intergenic RNA (HOTAIR) could serve as a potential guide to silence target genes, but the mechanism has yet to be defined. In this study, we performed whole transcriptome RNA-seq analysis of isogenic cisplatin- sensitive and -resistant A2780 ovarian cancer (OC) cell lines. Of the lncRNA examined, HOTAIR was markedly induced in the cisplatin resistant cells (5-fold upregulation compared to the cisplatin-sensitve A2780 parental line). shRNA depletion of HOTAIR resensitized the drug-resistant cells to cisplatin. Based on analysis of the HOTAIR promoter using luciferase assays, we identified two putative NF-κB binding sites and three E-box binding sites. To further investigate whether these sites contributed to HOTAIR expression, platinum-sensitive cells were treated with different growth factors and cytokines (0 to 48hrs) and analyzed for changes in HOTAIR expression. Treatment with TNF-α, a well-known inflammatory cytokine and established activator of NF-κB, resulted in 16 fold-induction of HOTAIR. In accord with these results, we observed significant enrichment of both NF-κB and cMYC on the HOTAIR promoter using ChIP assay. Pharmacological inhibition of cMYC and NF-κB reduced HOTAIR expression by 2-fold, and siRNA depletion of the NF-κB p65 subunit or cMYC similarly reduced (P&amp;lt;0.01) HOTAIR expression. Based on these results, we hypothesize a positive feedback loop for HOTAIR transcriptional regulation: HOTAIR inhibits Iκ-Bα (an inhibitor of NF-κB) allowing the lncRNA to enter the nucleus and activate not only its own expression but also cMYC expression to further drive HOTAIR expression as well as cMYC-inducible genes. We are currently testing this hypothesis. We believe this novel pathway, whose components have been implicated in numerous other cancers, may be involved in cisplatin-resistant OC. Citation Format: Ali R. Ozes, Dave Miller, Cong Guo, Anurag Bhattrai, Yunlong Liu, Kenneth P. Nephew. The transcriptional regulation of the long non-coding RNA HOTAIR in ovarian cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5189. doi:10.1158/1538-7445.AM2013-5189</jats:p

Addressing the Needs of Nepalese Migrant Workers in Nepal and in Delhi, India

International labor migration is an increasingly important livelihood strategy in Nepal. There is little documentation of the movements of migrant workers or of their remittances. It is estimated that Nepalese migrants send remittances equivalent to about one quarter of Nepal's gross national product. Migrants and their families lack information about safe migration procedures, host countries, their rights as migrants, and awareness about HIV/AIDS. The present article examines two projects that address these migrants’ needs in their home country and in one destination. The first project is a Nepal-wide radio program based in Kathmandu that provides information on migration issues. The second is a community outreach project based in Delhi, India, focusing on education of migrants

Contemporary childbirth practices in Nepal: improving outcomes

Nepal has one of the highest infant and maternal mortality rates in the world, second only to parts of Africa. Using in-depth interviews, fifteen postpartum mothers and eight mothers-in- law were interviewed to examine current cultural, social and contextual birthing process in Nepal. Analysis of this qualitative data through a grounded theory approach identified the dichotomy between 'traditional birthing' and modern medical obstetric care. This dichotomy limits technical, social and cultural collaborative birthing practices between the many traditional birthing attendants and medical staff. The emerging themes suggest other approaches for childbirth care; bringing harmony to traditional as well as modern clinical approaches. The outcomes of this study hope to enfranchise women with safer and more acceptable birthing experiences and outcomes not only in Nepal but also in other developing countries