Factors influencing end-of-life morbidity: an epidemiological evaluation of population aging theories

Population aging theories were proposed to explain the effect of an increasing life expectancy on the duration of the morbid period at the end of life. Despite several decades of research, the epidemiological basis of these theories has not been investigated adequately. This dissertation uses data from the Cardiovascular Health Study, a community based cohort of older adults, to explore the epidemiologic basis of the basic tenets of these theories. Hospital stay at the end of life is an economically important measure of terminal morbidity. We examined the effect of lifestyle factors measured late in life on the duration of hospital days in the last 5 years of life. We found that alcohol consumption, smoking, obesity and social networks were independently associated with hospital stay, indicating that a late-life lifestyle could impact end-of-life morbidity after accounting for the accumulated disease burden. Cardiovascular mortality rates have been falling but it is not clear whether the morbidity associated with these events have reduced. We compared the risks for disability and death associated with cardiovascular events and found that angina, MI, CHD and CHF had stronger associations with death than disability. Cardiovascular events, therefore, do not seem to increase the disability burden in the population. The relationship between age at death and the duration of terminal morbidity has not been elucidated in community based populations with average life expectancy. We examined the association between age at death and the length of terminal self-rated poor health and found that survival is associated with the duration of end-of-life morbidity in a curvilinear fashion; morbid period is shorter for those who die in their seventies and nineties. Identifying factors that promote survival to the nineties would help delineate factors associated with a compressed period of morbidity. What are the public health implications of these findings? First, some preventive health behaviors can be harnessed to reduce the public health burden of terminal morbidity. Second, chronic diseases with low mortality risk need to be targeted to reduce the disability burden in populations. Third, survival to the nineties might hold the key to compressing morbidity in the older population

Results from a meta-analysis of immune checkpoint inhibitors in first-line renal cancer patients: does PD-L1 matter?

Background: The aim of this study was to perform a literature-based meta-analysis to assess the efficacy of the novel immune checkpoint inhibitors (ICIs) in first-line metastatic renal cell carcinoma (RCC), focusing on the predictive role of PD-L1 expression. Methods: The primary outcome was overall survival, and secondary outcomes were progression-free survival (PFS) and objective response. We planned a subgroup analysis for overall survival according to PD-L1 status. Results: Five studies were included in the analysis for a total of 4063 cases. Overall survival was greater in PD-L1 positive tumours (HR = 0.49, 95% CI: 0.36\u20130.67; p < 0.001). The pooled analysis of the unselected cases showed a statistically significative improvement in PFS with the use of ICIs (HR = 0.85, 95% CI: 0.72\u20130.99; p = 0.04) and we found a greater PFS benefit (HR = 0.65, 95% CI: 0.57\u20130.74; p < 0.001) in patients with PD-L1 positive tumours. Conclusions: This study supports the efficacy of ICIs and, although a significant clinical benefit has been reported in PD-L1 negative patients, a greater efficacy of ICIs was observed in PD-L1 positive patients. More prospective randomized studies are needed to clarify the role of PDL-1 status in metastatic RCC treated with ICIs

Family centred approach for HIV services: Pilot study in South Africa

In 2003, UNICEF estimated that nearly 250,000 children were infected with HIV in South Africa. While scale-up of prevention of mother-to-child transmission (PMTCT) programs has improved testing and care for perinatally infected infants, uptake of these services remains low in much of sub-Saharan Africa and few HIV infected children are diagnosed and receive services through PMTCT programs. With support from USAID/PEPFAR, the Horizons Program adapted a family-centered model for children and families in need of broader-reaching HIV diagnostic services in South Africa. The Family Centered Approach (FCA) pilot intervention was designed to expand access to HIV testing for family members with children ages 0–14 years in their care. This approach gives health-care providers a method for encouraging HIV-positive individuals to refer family members for HIV testing, with the aim of identifying HIV-positive children ages 0–14 years who may have been missed through PMTCT early infant diagnosis programs. This research summary describes the FCA pilot intervention

Immune checkpoint inhibitors in pre-treated gastric cancer patients: Results from a literature-based meta-analysis

Immunotherapy has recently changed the treatment of several cancers. We performed a literature-based meta-analysis of randomised controlled trials to assess the efficacy of the novel immune checkpoint inhibitors (ICIs) in metastatic gastric cancer. The main outcome was overall survival. Based on age (cut-off agreed at 65 years), tumour location (gastric vs. gastro-oesophageal junction), programmed death-ligand 1 (PD-L1) status, sex and Eastern Cooperative Oncology Group (ECOG) status (1 vs. 0), we scheduled a subgroup analysis for the overall survival. Three studies were included in the analysis for a total of 1456 cases (811 cases were in the experimental group and 645 cases in the control group). The pooled analysis showed improved overall survival in the experimental arm in the absence of statistical significance (hazard ratio (HR) = 0.87, 95% CI: 0.64\u20131.18; p = 0.37). The subgroup of patients with PD-L1-positive tumours (HR = 0.82 vs. 1.04) and gastro-oesophageal junction cancer (HR = 0.82 vs. 1.04) showed a statistically significant advantage of overall survival. This study supports the efficacy of immune checkpoint inhibitors in the subgroup of patients with metastatic gastric cancer with PD-L1-positive and gastro-oesophageal junction tumour location. Future studies are needed with the aim of identifying reliable predictive biomarkers of ICI efficacy

പൗരാവകാശ രേഖ ഐ.സി.എ.ആർ. - സി.എം.എഫ്.ആർ.ഐ 2016-2017

Citizens’ Charter ICAR-Central Marine Fisheries Research Institute 2016-201

Citizens’ Charter ICAR-Central Marine Fisheries Research Institute 2016-2017

Citizens’ Charter ICAR-Central Marine Fisheries Research Institute 2016-201

Application of protein lysate microarrays to molecular marker verification and quantification

This study presents the development and application of protein lysate microarray (LMA) technology for verification of presence and quantification of human tissue samples for protein biomarkers. Sub-picogram range sensitivity has been achieved on LMA using a non-enzymatic protein detection methodology. Results from a set of quality control experiments are presented and demonstrate the high sensitivity and reproducibility of the LMA methodology. The optimized LMA methodology has been applied for verification of the presence and quantification of disease markers for atherosclerosis. LMA were used to measure lipoprotein [a] and apolipoprotein B100 in 52 carotid endarterectomy samples. The data generated by LMA were validated by ELISA using the same protein lysates. The correlations of protein amounts estimated by LMA and ELISA were highly significant, with r(2 )≥ 0.98 (p ≤ 0.001) for lipoprotein [a] and with r(2 )≥ 0.94 (p ≤ 0.001) for apolipoprotein B100. This is the first report to compare data generated using proteins microarrays with ELISA, a standard technology for the verification of the presence of protein biomarkers. The sensitivity, reproducibility, and high-throughput quality of LMA technology make it a potentially powerful technology for profiling disease specific protein markers in clinical samples

Systematics, fishery and biology of the white sardine Escualosa thoracata (Valenciennes, 1847) exploited off Kerala, south-west coast of India

Landings of the white sardine Escualosa thoracata (Valenciennes, 1847) indicated a shift in their abundance from north-east to south-west coast of India and a sharp decline in the resource landings during the last decade along the entire range of its distribution. High local demand coupled with competitive price for the species might have led to overexploitation of this otherwise seasonal resources along the major areas of its abundance along the Indian coast. Detailed study on the systematics, fishery and biology of the species landed along Kerala coast was undertaken during 2015 and 2016. Stock assessment studies indicated near optimum fishing pressure on the resource along the Kerala coast

Pharmacokinetic study of gemcitabine, given as prolonged infusion at fixed dose rate, in combination with cisplatin in patients with advanced non-small-cell lung cancer.

International audienc

New insights learned from the pulmonary to systemic blood flow ratio to predict the outcome in patients with hypoplastic left heart syndrome in the pre-Glenn stage: a single-center study

BackgroundTo the best of our knowledge, no study has been made until now to determine whether the ratio between pulmonary and systemic blood flow (Qp/Qs) in the pre-stage II (PS2) or pre-Glenn stage can predict the outcome in patients with hypoplastic left heart syndrome (HLHS) who underwent Norwood (NW) palliation.Patients and methodsFrom January 2016 to August 2022, 80 cardiac catheterizations in 69 patients with HLHS in NW palliation stage with modified Blalock–Taussig shunt (MBTS) were retrospectively recruited. The Qp/Qs was measured under stable conditions using the Fick formula. None of the patients were intubated. Patients were divided into two groups: Group 1 included patients who underwent planned cardiac catheterization (n = 56), and Group 2 had unplanned examination (n = 13), in which the indication for cardiac catheterization was desaturation in 11 patients and pulmonary over-circulation in two. The composite primary outcome was defined as accomplishing the planned operations (Glenn and Fontan) with freedom from death and reoperation, referring to palliative therapy or heart transplantation. The secondary outcome was freedom from transcatheter intervention in MBTS or pulmonary arteries.ResultsThe median follow-up was 48 months (range 6–72 months). The median value of Qp/Qs in Group 1 was 1.75 (range 1.5–2.2). In Group 2, the 11 patients with desaturation, the median value of Qp/Qs was 1.25 (range 0.9–1.45). The two patients with suspected pulmonary overcalculation showed Qp/Qs of 2.3 and 2.5, respectively; a reduction of the shunt size was required. Approximately 96.4% of patients in Group 1 achieved the primary outcome compared with only 30.7% in Group 2. The need for reintervention was 1.8% in Group 1 compared with 61.3% in Group 2. There is a significant relationship between Qp/Qs and the impaired outcome (death, palliative therapy, or heart transplantation) with a p-value of 0.001, a relative risk factor of 3.1, and a 95% confidence interval of 1.4–7.1. No significant relationship between the Qp/Qs and the size of MBTS (p-value of 0.073) was noted.ConclusionThe Qp/Qs in PS2 can predict outcomes in patients with HLHS in Norwood stage with MBTS. The Qp/Qs between 1.5 and 2.2 with a median of 1.75 seems to be optimal in the patients in PS2. Qp/Qs of &lt;1.5 is associated with pulmonary stenosis, shunt stenosis, and pulmonary hypertension