Identifying polymorphic cis-regulatory variants as risk markers for lung carcinogenesis and chemotherapy responses in tobacco smokers from eastern India.

Aberrant expression of xenobiotic metabolism and DNA repair genes is critical to lung cancer pathogenesis. This study aims to identify the cis-regulatory variants of the genes modulating lung cancer risk among tobacco smokers and altering their chemotherapy responses. From a list of 2984 SNVs, prioritization and functional annotation revealed 22 cis-eQTLs of 14 genes within the gene expression-correlated DNase I hypersensitive sites using lung tissue-specific ENCODE, GTEx, Roadmap Epigenomics, and TCGA datasets. The 22 cis-regulatory variants predictably alter the binding of 44 transcription factors (TFs) expressed in lung tissue. Interestingly, 6 reported lung cancer-associated variants were found in linkage disequilibrium (LD) with 5 prioritized cis-eQTLs from our study. A case-control study with 3 promoter cis-eQTLs (p < 0.01) on 101 lung cancer patients and 401 healthy controls from eastern India with confirmed smoking history revealed an association of rs3764821 (ALDH3B1) (OR = 2.53, 95% CI = 1.57-4.07, p = 0.00014) and rs3748523 (RAD52) (OR = 1.69, 95% CI = 1.17-2.47, p = 0.006) with lung cancer risk. The effect of different chemotherapy regimens on the overall survival of lung cancer patients to the associated variants showed that the risk alleles of both variants significantly decreased (p < 0.05) patient survival.

No association of the common Asian mitochondrial DNA haplogroups with lung cancer in East Indian population.

OBJECTIVES: Mitochondrial dysfunction has long been associated with the pathogenesis of lung cancer (LC). Mitochondrial DNA (mtDNA) haplogroups have been reported to modify the risk of LC in a few different populations; however, no study has been done among the Indians. Here, we explore the relationship between mtDNA haplogroups and LC in a representative eastern Indian sample set. METHODS: Different combinations of six mtDNA SNPs, which define the major Asian mtDNA haplogroups M and N, and their sub-haplogroups D, G, M7, R, and F were genotyped via polymerase chain reaction (PCR) - restriction fragment length polymorphism (RFLP) - sequencing approach in 94 smoker LC patients and 100 healthy smoker controls from an eastern Indian cohort. RESULTS: The distribution of 7 mtDNA haplogroups did not show any significant differences between patients and controls (p<0.05). We did not find sub-haplogroup M7 in our study population. CONCLUSIONS: Our study is the first to indicate that the major Asian mtDNA haplogroups have no significant (p<0.05) association with LC in East Indian population.

Feasibility of a Palliative Care Intervention Utilizing Community Health Workers to Facilitate Delivery of Home-based Palliative Care in India.

Objectives: The purpose of this study was to evaluate the feasibility of a home-based palliative care program delivered by community health workers (CHW) in rural areas outside of Kolkata, India. The specific aims were to assess CHWs' ability to implement the intervention protocol and maintain records of care, to characterize patient problems and CHW activities to assist patients, and to assess change in patient pain scores over the course of the intervention. Materials and Methods: Four CHWs were hired to facilitate delivery of home-based palliative care services. CHWs were trained using the Worldwide Hospice and Palliative Care Alliance's Palliative Care Toolkit. CHWs provided care for patients for 3-months, making regular home visits to monitor health, making and implementing care plans, and referring patients back to the cancer center team for serious problems. Results: Eleven patients enrolled in the intervention, with ten of these patients participating in the intervention and one patient passing away before starting the intervention. All ten participants reported physical pain, for which CHWs commonly recommended additional or higher dose medication and/or instructed patients how to take medication properly. For two patients, pain levels decreased between baseline and end of study, while pain scores did not decrease for the remaining patients. Other symptoms for which CHWs provided care included gastro-intestinal, bleeding, and respiratory problems. Conclusion: The study findings suggest that utilization of CHWs to provide palliative care in low-resource settings may be a feasible approach for expanding access to palliative care. CHWs were able to carry out the study visit protocol and assess and document patient problems and their activities to assist. They were also able to alleviate many common problems patients experienced with simple suggestions or referrals. However, most patients did not see a decrease in pain levels and more emphasis was needed on the emotional aspects of palliative care, and so CHWs may require additional training on provision of pain management and emotional support services.

A comprehensive meta-analysis and a case-control study give insights into genetic susceptibility of lung cancer and subgroups.

Reports of genetic association of polymorphisms with lung cancer in the Indian subcontinent are often conflicting. To summarise and replicate published evidence for association with lung cancer and its subgroups. We performed a meta-analysis of candidate associations on lung cancer, its histological subtypes and smoking status in the Indian subcontinent following PRISMA guidelines. Multiple testing corrections were done by the Benjamini-Hochberg method through assessment of significance at a false discovery rate of 10%. We genotyped and investigated rs1048943/CYP1A1 in a case-control sample from eastern India, followed by its global meta-analysis using a similar protocol. Meta-analysis of 18 variants of 11 genes reported in 39 studies (7630 cases and 8169 controls) showed significant association of rs1048943/CYP1A1 [2.07(1.49-2.87)] and rs4646903/CYP1A1 [1.48(1.93-1.95)] with overall lung cancer risk at 10% FDR, while nominal association (p < 0.05) was observed for del1/GSTT1, del2/GSTM1, rs1695/GSTP1 and rs17037102/ DKK2. Subtype analysis showed a significant association of del1/GSTT1 with adenocarcinoma, rs4646903/CYP1A1 with squamous carcinoma, and rs1048943/CYP1A1 with both. Association of rs4646903/CYP1A1 in smokers and effect modification by meta-regression analysis was observed. Genotyping of rs1048943/CYP1A1 that presented significant heterogeneity (p < 0.1) revealed an association with adenocarcinoma among eastern Indian smokers, while a global meta-analysis in 10458 cases and 10871 controls showed association with lung cancer and its subgroups. This study identified the susceptibility loci for lung cancer and its covariate-subgroups.

Barriers, Facilitators and Recommended Strategies for Implementing a Home-Based Palliative Care Intervention in Kolkata, India.

BACKGROUND: 40 million people in the world are in need of palliative care, but only one-seventh of that population receive services. Underuse of palliative care in low resource countries exacerbates suffering in patients with life limiting illnesses such as cancer. OBJECTIVES: The current study was conducted to identify barriers, facilitators and recommended strategies for informing development of a home-based palliative care intervention for poor and medically underserved rural patients in Kolkata, India. METHODS: Semi-structured interviews were conducted with 20 clinical and patient stakeholders in Kolkata, India. Questions queried current practices for delivering palliative care, along with barriers, facilitators and optimal strategies for implementing homebased palliative care. RESULTS: We identified some key barriers to palliative care delivery in rural areas: lack of access to palliative care till late stages; patients unaware of their cancer stage; lack of affordability of medication and treatment costs; transportation challenges to access care; strict morphine distribution regulations making it challenging for patients to obtain morphine; cultural factors discouraging patients from seeking palliative care; resistance from medical community to use "rural medical practitioners (RMPs)" to deliver care. We also identified important facilitators, including availability of existing palliative care infrastructure at the cancer center, network of RMPs to serve as CHWs to facilitate palliative care delivery, low morphine cost and family support system for patients. CONCLUSION: Our findings provide evidence that a palliative care intervention which leverages an existing CHW infrastructure may be a feasible model for expanding the reach of palliative care to rural underserved patients.

An Observational Study to Assess the Socioeconomic Status and Demographic Profile of Advanced Cancer Patients Receiving Palliative Care in a Tertiary-Level Cancer Hospital of Eastern India.

INTRODUCTION: Socioeconomic status (SES) comprises of not just gross income but also educational qualification, financial security and individual perceptions of social status and class. It has been observed that people with low SES have less access and utilization of palliative care services. With this background, this observational study was carried out at SGCCRI to assess and evaluate the SES of patients attending the palliative care department and analyse the major social concerns of patients in the last days of life. OBJECTIVES: Assessment of socio- economic status and demographic profile of patients with advanced cancer receiving palliative care. MATERIALS AND METHODS: From May 2017 to October 2017 we assessed the demographic features and socio-economic status of 80 advanced cancer patients receiving palliative care by interviewing them face to face with the help of a self designed social assessment sheet. RESULTS: A total of 80 patients consented to be interviewed with regards to assessment of their socio-economic conditions. Majority were male patients (64%) with the highest percentage in the age group of 60-70years (33%). 38% of the patients interviewed were from rural surroundings. Only 38% of the patients had completed their basic education. Approximately 30% of the patients interviewed had income less than 1lakh/month while majority (>60%) had income in the bracket of 1lakh- 2lakh. In 30% of cases, the patient was the sole earner in the family. CONCLUSION: It was observed that majority of patients and their family were constrained with regards to financial resources and large percentage of patients had social insecurity with respect to future of family members.

A Systematic Review of Palliative Care Intervention Outcomes and Outcome Measures in Low-Resource Countries.

CONTEXT: To meet the growing need for palliative care in low-resource countries, palliative care programs should be evidence based and contextually appropriate. This study was conducted to synthesize the current evidence to guide future programmatic and research efforts. OBJECTIVES: This systematic review evaluated palliative care outcome measures, outcomes, and interventions in low-resource countries. METHODS: After title searches, abstracts and full-text articles were screened for inclusion. Data were extracted to report on intervention models, outcome measures used, and intervention outcomes. RESULTS: Eighteen papers were reviewed, reporting on interventions conducted across nine low-resource countries. These interventions evaluated home-based palliative care models; a community-managed model; palliative care integrated with hospitals, hospices, or HIV clinics; and models focused on patients' self-management. Three studies were randomized controlled trials. Other studies used nonrandomized trials, cohort studies, mixed methods, pre-post test evaluation, cost-accounting evaluation, and cross-sectional surveys. Thirteen studies measured physical outcomes, 10 using multidimensional instruments. Nine studies measured psychological outcomes, eight using multidimensional instruments. Nine studies measured social outcomes, seven using multidimensional instruments. Nine studies measured outcomes across multiple domains. Across outcomes evaluated, results were reported in the direction of benefit associated with palliative care interventions. CONCLUSION: Many palliative care intervention models exist to serve patients in low-resource countries. Yet, limited high-quality evidence from low-resource countries is available to document intervention outcomes. Rigorous experimental studies and greater measurement of multidimensional aspects of palliative care are needed to advance the science of palliative care in low-resource settings.

Cocoon production, morphology, hatching pattern and fecundity in seven tropical earthworm species - a laboratory-based investigation.

Data on the reproductive biology of seven Indian species of earthworms, viz. Perionyx excavatus Perrier, Lampito mauritii Kinberg, Polypheretima elongata (Perrier), Pontoscolex corethrurus (Muller), Eutyphoeus gammiei (Beddard), Dichogaster modiglianii (Rosa) and Drawida nepalensis Michaelsen are presented. The peregrine earthworms such as Perionyx excavatus, Pontoscolex corethrurus, Dichogaster modiglianii, and Polypheretima elongata are considered to be continuous breeders with high fecundity. Native Lampito mauritii and Drawida nepalensis are semi-continuous and Eutyphoeus gammiei discrete breeders. There is a dramatic increase in cocoon production by most earthworm species of Tripura in the summer and monsoon with a corresponding peak during April and July. Cocoon production decreased or ceased during winter. Temperature affected the incubation period of cocoons. With increase in temperature, incubation period increased in the endogeic worms, Pontoscolex corethrurus, Polypheretima elongata and Drawida nepalensis and decreased in the epigeic worms, Perionyx excavatus and Dichogaster modiglianii, within a temperature range between 28-32 degrees C under laboratory conditions. There was a significant (P < 0.05) positive correlation between number of hatchlings per cocoon and incubation period in Lampito mauritii. High rate of cocoon production, short development time with high hatching success, as well as continuous breeding strategies in the epigeic species Perionyx excavatus and Dichogaster modiglianii and the top soil endogeic species, Pontoscolex corethrurus, Drawida nepalensis and Lampito mauritii, indicate their possible usefulness in vermiculture. The giant anecic worm, Eutyphoeus gammiei, which has a very long cocoon development time, discrete breeding strategy and very low rate of cocoon production, is not a suitable species for vermiculture.

Capacity of various experimental diets to support biomass and reproduction of Perionyx excavatus.

Biomass production and reproduction of a group of four adult Perionyx excaratus were studied in limited supplies of four experimental diets; cowdung alone and its mixtures with straw, bamboo leaf litter or kitchen waste, in order to select a suitable diet medium for vermiculture. P. excavatus showed maximum rate of biomass increase and reproduction in the mixtures with straw and bamboo leaf litter. In spite of achieving the highest final biomass value. P. excavatus showed the lowest rate of biomass increase and reproduction in the mixture with kitchen waste. Cowdung, a natural food of P. excavatus, was marginally better than the mixture with kitchen waste with regard to the rate of biomass increase and reproduction.