Utilization of acute and long-term care in the last year of life: comparison with survivors in a population-based study

Background. It is well-known that the use of care services is most intensive in the last phase of life. However, so far only a few determinants of end-of-life care utilization are known. The aims of this study were to describe the utilization of acute and long-term care among older adults in their last year of life as compared to those not in their last year of life, and to examine which of a broad range of determinants can account for observed differences in care utilization. Methods. Data were used from the Longitudinal Aging Study Amsterdam (LASA). In a random, age and sex stratified population-based cohort of 3107 persons aged 55 ? 85 years at baseline and representative of the Netherlands, follow-up cycles took place at 3, 6 and 9 years. Those who died within one year directly after a cycle were defined as the "end-of-life group" (n = 262), and those who survived at least three years after a cycle were defined as the "survivors". Utilization of acute and long-term care services, including professional and informal care, were recorded at each cycle, as well as a broad range of health-related and psychosocial variables. Results. The end-of-life group used more care than the survivors. In the younger-old this difference was most pronounced for acute care, and in the older-old, for long-term care. Use of both acute and long-term home care in the last year of life was fully accounted for by health problems. Use of institutional care at the end of life was partly accounted for by health problems, but was not fully explained by the determinants included. Conclusion. This study shows that severity of health problems are decisive in the explanation of the increase in use of care services towards the end-of-life. This information is essential for an appropriate allocation of professional health care to the benefit of older persons themselves and their informal caregivers. © 2009 Pot et al; licensee BioMed Central Ltd

Biomarkers in anal cancer: from biological understanding to stratified treatment

Squamous cell carcinomas of the anus and anal canal represent a model of a cancer and perhaps the first where level 1 evidence supported primary chemoradiotherapy (CRT) in treating locoregional disease with curative intent. The majority of tumours are associated with infection with oncogenic subtypes of human papilloma virus and this plays a significant role in their sensitivity to treatment. However, not all tumours are cured with CRT and there remain opportunities to improve outcomes in terms of oncological control and also reducing late toxicities. Understanding the biology of ASCC promises to allow a more personalised approach to treatment, with the development and validation of a range of biomarkers and associated techniques that are the focus of this review

A dualistic model of primary anal canal adenocarcinoma with distinct cellular origins, etiologies, inflammatory microenvironments and mutational signatures: implications for personalised medicine.

Primary adenocarcinoma of the anal canal is a rare and aggressive gastrointestinal disease with unclear pathogenesis. Because of its rarity, no clear clinical practice guideline has been defined and a targeted therapeutic armamentarium has yet to be developed. The present article aimed at addressing this information gap by in-depth characterising the anal glandular neoplasms at the histologic, immunologic, genomic and epidemiologic levels. In this multi-institutional study, we first examined the histological features displayed by each collected tumour (n = 74) and analysed their etiological relationship with human papillomavirus (HPV) infection. The intratumoural immune cell subsets (CD4, CD8, Foxp3), the expression of immune checkpoints (PD-1, PD-L1), the defect in mismatch repair proteins and the mutation analysis of multiple clinically relevant genes in the gastrointestinal cancer setting were also determined. Finally, the prognostic significance of each clinicopathological variable was assessed. Phenotypic analysis revealed two region-specific subtypes of anal canal adenocarcinoma. The significant differences in the HPV status, density of tumour-infiltrating lymphocytes, expression of immune checkpoints and mutational profile of several targetable genes further supported the separation of these latter neoplasms into two distinct entities. Importantly, anal gland/transitional-type cancers, which poorly respond to standard treatments, displayed less mutations in downstream effectors of the EGFR signalling pathway (i.e., KRAS and NRAS) and demonstrated a significantly higher expression of the immune inhibitory ligand-receptor pair PD-1/PD-L1 compared to their counterparts arising from the colorectal mucosa. Taken together, the findings reported in the present article reveal, for the first time, that glandular neoplasms of the anal canal arise by HPV-dependent or independent pathways. These etiological differences leads to both individual immune profiles and mutational landscapes that can be targeted for therapeutic benefits

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

Burden of allergic respiratory disease:a systematic review

Additional file 1: Table S1. Database search strategies; Figure S1. RQLQ domain scores by allergy phenotype. Studies are listed from the top as SAR, Mixed, and PAR; Figure S2 SF-36 domain scores by allergy phenotype. Studies are listed from the top as SAR, Mixed, and PAR