Intensity of care in cancer patients in the last year of life: a retrospective data linkage study

Background Delivering high-quality palliative and end-of-life care for cancer patients poses major challenges for health services. We examine the intensity of cancer care in England in the last year of life.Methods We included cancer decedents aged 65+ who died between January 1, 2010 and December 31, 2017. We analysed healthcare utilisation and costs in the last 12 months of life including hospital-based activities and primary care.Results Healthcare utilisation and costs increased sharply in the last month of life. Hospital costs were the largest cost elements and decreased with age (0.78, 95% CI: 0.73–0.72, p < 0.005 for age group 90+ compared to age 65–69 and increased substantially with comorbidity burden (2.2, 95% CI: 2.09–2.26, p < 0.005 for those with 7+ comorbidities compared to those with 1–3 comorbidities). The costs were highest for haematological cancers (1.45, 95% CI: 1.38–1.52, p < 0.005) and those living in the London region (1.10, 95% CI: 1.02–1.19, p < 0.005).Conclusions Healthcare in the last year of life for advanced cancer patients is costly and offers unclear value to patients and the healthcare system. Further research is needed to understand distinct cancer populations’ pathways and experiences before recommendations can be made about the most appropriate models of care.Subject terms: Cancer, Cancer     

Chronic venous leg ulcers benefit from surgery: long-term results from 173 legs

OBJECTIVE: The purpose of this retrospective study was to present 7 years of data from operations of currently active, chronic venous leg ulcers (CEAP: C6), focusing on the short- and long-term effects of healing and recurrence and considering concomitant risk factors. METHODS: Between January 1997 and March 2004, 173 patients (239 legs) with a currently active, chronic venous leg ulcer were surgically treated. The surgical procedures included two main steps: (1) the surgical interruption of reflux in the superficial and perforating veins to reduce venous hypertension in the entire leg and/or the affected area and (2) the surgical procedure involving the ulcer. A total of 123 patients (173 legs) who came to the follow-up were examined. The follow-up period ranged from 3 months to 7 years. The data collection integrated a preoperative examination that included medical history and clinical diagnoses and incorporated measurements such as body mass index, ankle-brachial pressure index, and the neutral position method at the follow-up. The function of the veins was measured with duplex ultrasonography. Finally, the data were analyzed by using various statistical methods, including Kaplan-Meier analysis, Cox regression analysis, and paired t tests. RESULTS: Initially, ulcer healing occurred in 87% of the cases (151 legs). A total of 13% (22 legs) of the venous ulcers never healed, and recurrent venous ulcers occurred in 5% (9 legs). The Kaplan-Meier analyses of ulcer healing showed a healing rate of 85% in 6 months for all legs. The mean time of healing was 1.5 months. Furthermore, the Kaplan-Meier analyses of ulcer recurrence showed a 1.7% rate of recurrence in 6 months for all legs. The 5-year ulcer recurrence rate was 4.6%. The mean time of recurrence was 70.4 months. CONCLUSIONS: On the basis of the results from the 7 years of data from functional surgery of venous leg ulcers and as a result of the outcomes of our study, we recommend surgical treatment of venous leg ulcers at any stage. We therefore conclude that surgery is indicated before an ulcer is intractable to treatment. In general, our findings are based on the understanding and identification of the causes and symptoms of venous ulceration and illustrate that standard surgical methods can be applied for the therapy of venous leg ulcers at any stage.     

The role of nitric oxide radicals in removal of hyper-radiosensitivity by priming irradiation

In this study, a mechanism in which low-dose hyper-radiosensitivity (HRS) is permanently removed, induced by low-dose-rate (LDR) (0.2–0.3 Gy/h for 1 h) but not by high-dose-rate priming (0.3 Gy at 40 Gy/h) was investigated. One HRS-negative cell line (NHIK 3025) and two HRS-positive cell lines (T-47D, T98G) were used. The effects of different pretreatments on HRS were investigated using the colony assay. Cell-based ELISA was used to measure nitric oxide synthase (NOS) levels, and microarray analysis to compare gene expression in primed and unprimed cells. The data show how permanent removal of HRS, previously found to be induced by LDR priming irradiation, can also be induced by addition of nitric oxide (NO)-donor DEANO combined with either high-dose-rate priming or exposure to prolonged cycling hypoxia followed by reoxygenation, a treatment not involving radiation. The removal of HRS appears not to involve DNA damage induced during priming irradiation as it was also induced by LDR irradiation of cell-conditioned medium without cells present. The permanent removal of HRS in LDR-primed cells was reversed by treatment with inducible nitric oxide synthase (iNOS) inhibitor 1400W. Furthermore, 1400W could also induce HRS in an HRS-negative cell line. The data suggest that LDR irradiation for 1 h, but not 15 min, activates iNOS, and also that sustained iNOS activation is necessary for the permanent removal of HRS by LDR priming. The data indicate that nitric oxide production is involved in the regulatory processes determining cellular responses to low-dose-rate irradiation.     

Pro Re Nata Drug Use in Nursing Home Residents: A Systematic Review

Objectives

In addition to routinely administered long-term medication, complex drug regimens of nursing home residents often include as needed or pro re nata (PRN) medication. However, there has been no systematic evaluation of the frequency and concomitants of PRN medication in nursing homes. The main objective of this systematic review was to provide a current assessment of PRN drug use in nursing homes.

Effects of the chemokine MIP-1alpha on anemia and inflammation in rheumatoid arthritis

Macrophage inflammatory protein-1alpha (MIP-1alpha) is an interesting chemokine because in addition to its variety proinflammatory activities including chemotaxis and immunomodulation, it is a potent inhibitor of hematopoetic stem cell proliferation. Inhibition of erythroid progenitor cells due to MIP-1alpha or other cytokines can play a role in the pathogenesis of anemia which is one of the most common extra-articular features of active rheumatoid arthritis (RA). In 84 patients with RA, serological and immunological parameters were assessed to detect inflammatory mechanisms and anemia in relation to the serum concentrations of MIP-1alpha. All patients fulfilled the ACR criteria for the diagnosis of a definite or classic RA. We used a quantitative enzyme immuno assay for the detection of MIP-1alpha as well as for the measurement of the acute phase protein serum amyloid A (SAA), the erythropoiesis inducer erythropoietin (EPO) and the transferrin receptor (TfR). The immune activation marker neopterin was measured radioimmunologically. Half of the patients with RA were anemic with hemoglobin values below 12 g/dl. MIP-1alpha was found to be elevated significantly in serum of patients with active rheumatoid arthritis and in patients with anemia. Most of the anemic patients with markedly elevated acute phase reactions had an anemia with chronic diseases and not a functional iron deficiency alone. TfR correlated with EPO. The results show that enhanced expression of MIP-1alpha is indicative of systemic inflammation in RA. Moreover, besides the regulation of inflammatory processes, this chemokine may influence the pathogenesis of anemia in RA patients.     

Sorafenib, but not sunitinib, affects function of dendritic cells and induction of primary immune responses

The tyrosine kinase inhibitors sorafenib and sunitinib are approved for the treatment of patients with malignant diseases. To analyze the possible use of these compounds in combination with immunotherapeutic approaches, we analyzed the effects of both inhibitors on the immunostimulatory capacity of human dendritic cells (DCs) and the induction of primary immune responses in vivo. Sorafenib, but not sunitinib, inhibits function of DCs, characterized by reduced secretion of cytokines and expression of CD1a, major histocompatibility complex, and costimulatory molecules in response to TLR ligands as well as by their impaired ability to migrate and stimulate T-cell responses. These inhibitory effects are mediated by inhibition of PI3 and MAP kinases and NFB signaling. In contrast, sorafenib had no influence on the phenotype and proliferation of T cells. To analyze the effects of both TKIs on cytotoxic T-cell induction in vivo, C57BL/6 mice were pretreated with sorafenib or sunitinib and immunized with OVA_257-264 peptide. Sorafenib, but not sunitinib, application significantly reduced the induction of antigen-specific T cells. Numbers of regulatory T cells were reduced in peripheral blood mononuclear cells from mice treated with sunitinib. These results indicate that sunitinib, but not sorafenib, is suitable for combination with immunotherapeutic approaches for treatment of cancer patients.