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

The role of body size in the foraging strategies and management of avian herbivores : a comparison of dusky Canada geese (Branta canadensis occidentalis) and cackling geese (B. hutchinsii minima) wintering in the Willamette Valley of Oregon

Body size explains much of the interspecific variation in the physiology, behavior, and morphology of birds, such as metabolic rate, diet selection, intake rate, gut size, and bill size. Based on mass-specific metabolic requirements and relative energetic costs of activities, being a certain body size has both advantages and disadvantages. In particular, avian herbivores such as geese possess a relatively simple digestive system, consume foods with low digestibility and poor nutrient content, and have increased energetic demands compared to other bird taxa; therefore, any effects of body size on foraging strategies should be readily apparent in this foraging guild. The influence of body size on the behavior and management of Canada Geese (Branta canadensis) and Cackling Geese (B. hutchinsii) as avian herbivores has not been well studied. My dissertation explores the role of body size in comparative foraging behavior, habitat selection, and winter conservation planning for two congeneric geese, the Dusky Canada Goose (B. c. occidentalis; hereafter Duskys) and the Cackling Goose (B. h. minima; hereafter Cacklers). These two taxa share the same over-winter foraging environment (grass seed fields) in the same restricted geographic area (the Willamette Valley) during winter. Duskys and Cacklers differ by more than a factor of two in body size and have different relative bill sizes and social organization. Because of smaller body size, Cacklers have greater relative energy demands and less fasting endurance compared to Duskys; however, Cacklers have comparatively low energetic costs for flight and transport. Duskys, however, have higher total energy requirements than Cacklers. Additionally, Cacklers form large, high-density flocks and have a total over-wintering population size in the study area of about 200,000. Duskys occur in relatively small family groups and have a total over-wintering population size of about 13,000. My study demonstrated that interspecific differences in body size between Cacklers and Duskys was associated with differences in foraging behavior, movements, and habitat selection. Cacklers foraged a greater percentage of time (30%) in all habitats and across the entire winter compared to Duskys. Cacklers had higher peck rates (up to 100 pecks min⁻¹ greater) than Duskys in all foraging habitats expect pasture. The pecking rate of Cacklers was greatest in fields of young grass (200 pecks min⁻¹), which may indicate that Cacklers had relatively high intake rates in this foraging habitat. Based on differences in foraging behavior among habitats, Cacklers may have the foraging strategy of energy intake maximizers, whereas the foraging strategy of Duskys is more towards time-energy expenditure minimizers, at least for part of the winter. Cacklers moved across the landscape very differently from Duskys, exhibiting less site fidelity and greater commuting distances to foraging areas. Cacklers showed a preference for young grass during all periods of the winter, reaffirming that Cacklers are specialized grazers on short green forage, whereas Duskys preferred young grass and pasture. Fields of young grass were the preferred foraging habitat of Cacklers, had less standing crop biomass, and may have enabled higher foraging efficiencies, which may have led to higher intake rates. The ability of the landscape to support wintering geese changed across the winter because total available plant biomass fluctuated with the rate of grass regrowth. The estimated carrying capacity of the landscape for geese decline by almost one-half during mid-winter (mid-December to mid-February) compared to early winter or late winter periods. Although Cacklers have lower individual energy requirements compared to Duskys, due to a much larger target population size, Cacklers required 89% more foraging habitat than Duskys. Forage requirements encountered a bottleneck during mid-winter, when grass regrowth rates were low and day length was short. Commensurate with this pattern of forage availability, goose body condition declined during the mid-winter period. To support Pacific Flyway target populations for geese, approximately 18,000 ha of total grazing habitat in young and mature grass is needed in the Willamette Valley to support a total over-wintering population composed of 340,000 geese belonging to four subspecies. The role of body size in influencing the foraging behavior and decisions of over-wintering geese has important implications for conservation planning of goose populations. Small-bodied Cacklers are selective in field choice, yet more likely to redistribute across the landscape. Disturbances (e.g., hunting, hazing, or predation) will have a disproportionate effect on the movements of smaller-bodied geese compared to larger geese. These characteristics of Cacklers will make conservation planning to retain geese on public land more difficult. Coordinated management with private landowners and farming practices that maximize preferred goose foraging habitat on public lands may attract geese to utilize protected areas and minimize conflicts with agriculture in the Willamette Valley. Availability of resources during critical periods in winter is an important factor affecting the distribution of geese, but may affect small and large bodied geese differently. Management could be targeted during these critical time periods. By considering the role of body size in the context of life history characteristics, foraging behavior and habitat selection, appropriate management strategies can be developed and implemented to reduce the effects of agricultural depredation by geese, while promoting the future conservation of wintering geese in the Willamette Valley

Role of novel hormonal therapies in the management of non-metastatic castration-resistant prostate cancer:a literature-based meta-analysis of randomized trials

BACKGROUND: Novel hormonal therapies have been recently investigated in non-metastatic castration-resistant prostate cancer (CRPC). We performed a meta-analysis to assess the efficacy and safety of novel hormonal therapies in non-metastatic CRPC.MATERIALS AND METHODS: The primary outcome was metastasis-free survival (MFS). The secondary endpoints were overall survival (OS), time to PSA progression and safety. We planned a subgroup analysis according to the PSA doubling time (&gt; 6 vs &lt; 6 months), Eastern Cooperative Oncology Group (ECOG) performance status (1 vs 0) and concomitant use of bone-targeting agent (yes vs no).RESULTS: Pooled analysis of novel hormonal therapies revealed significantly increased MFS compared with placebo (hazard ratio (HR): HR = 0.32, 95% CI 0.25-0.41; p &lt; 0.00001). The subgroup analysis showed a statistically significant MFS advantage in favour of men with the lower ECOG performance status. Other secondary endpoints favoured the novel hormonal therapies. The relative risk (RR) of grade ≥ 3 adverse events and ≥ 3 hypertension was 1.31 and 1.39, respectively.CONCLUSIONS: This study confirmed the efficacy and safety of the novel hormonal therapies in non-metastatic CRPC.</p

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

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

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

Nanoparticle albumin-bound paclitaxel: a big nano for the treatment of gastric cancer

Gastric cancer (GC) is the third cause of cancer-related death worldwide. Patients with unresectable GC can be treated with chemotherapy such as paclitaxel, which is a microtubule stabilizer. The use of nanoparticle albumin-bound paclitaxel (nab-ptx) avoids hypersensitivity reactions due to the absence of solvent needed to dissolve paclitaxel and it can be administered at higher doses. The ABSOLUTE randomized phase-3 clinical trial showed the non-inferiority of the nab-ptx used every week compared to the solvent-based paclitaxel used every week. This review describes the current advancements of the use of nab-ptx in GC in preclinical and clinical study investigations. The possibility of combining nab-ptx with other medications to improve response of patients to their specific molecular needs will also be debated