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Erythropoiesis‐stimulating agents (ESAs) reduce anemia in cancer patients and may improve quality of life, but there are concerns that ESAs might increase mortality.
Our objectives were to examine the effect of ESAs and identify factors that modify the effects of ESAs on overall survival, progression free survival, thromboembolic and cardiovascular events as well as need for transfusions and other important safety and efficacy outcomes in cancer patients.
We searched the Cochrane Library, Medline, Embase and conference proceedings for eligible trials. Manufacturers of ESAs were contacted to identify additional trials.
We included randomized controlled trials comparing epoetin or darbepoetin plus red blood cell transfusions (as necessary) versus red blood cell transfusions (as necessary) alone, to prevent or treat anemia in adult or pediatric cancer patients with or without concurrent antineoplastic therapy.
Data collection and analysis
We performed a meta‐analysis of randomized controlled trials comparing epoetin alpha, epoetin beta or darbepoetin alpha plus red blood cell transfusions versus transfusion alone, for prophylaxis or therapy of anemia while or after receiving anti‐cancer treatment. Patient‐level data were obtained and analyzed by independent statisticians at two academic departments, using fixed‐effects and random‐effects meta‐analysis. Analyses were according to the intention‐to‐treat principle. Primary endpoints were on study mortality and overall survival during the longest available follow‐up, regardless of anticancer treatment, and in patients receiving chemotherapy. Tests for interactions were used to identify differences in effects of ESAs on mortality across pre‐specified subgroups. The present review reports only the results for the primary endpoint.
A total of 13933 cancer patients from 53 trials were analyzed, 1530 patients died on‐study and 4993 overall. ESAs increased on study mortality (combined hazard ratio [cHR] 1.17; 95% CI 1.06‐1.30) and worsened overall survival (cHR 1.06; 95% CI 1.00‐1.12), with little heterogeneity between trials (I2 0%, p=0.87 and I2 7.1%, p=0.33, respectively). Thirty‐eight trials enrolled 10441 patients receiving chemotherapy. The cHR for on study mortality was 1.10 (95% CI 0.98‐1.24) and 1.04; 95% CI 0.97‐1.11) for overall survival. There was little evidence for a difference between trials of patients receiving different cancer treatments (P for interaction=0.42).
ESA treatment in cancer patients increased on study mortality and worsened overall survival. For patients undergoing chemotherapy the increase was less pronounced, but an adverse effect could not be excluded.
Erythropoietin or Darbepoetin for patients with cancer ‐ meta‐analysis based on individual patient data
Monitoring Editor: Julia Bohlius,corresponding author Kurt Schmidlin, Corinne Brillant, Guido Schwarzer, Sven Trelle, Jerome Seidenfeld, Marcel Zwahlen, Mike J Clarke, Olaf Weingart, Sabine Kluge, Margaret Piper, Maryann Napoli, Dirk Rades, David Steensma, Benjamin Djulbegovic, Martin F Fey, Isabelle Ray‐Coquard, Volker Moebus, Gillian Thomas, Michael Untch, Martin Schumacher, Matthias Egger, Andreas Engert, and Cochrane Haematological Malignancies Group
Each year new exotic species are transported across the world through global commerce, causing considerable economic and ecological damage. An important component of managing invasion pathways is to identify source populations. Some of the most widespread exotic species are haplodiploid ambrosia beetles. The ability to mate with siblings (inbreed) and their transportable food source (symbiotic fungus) have enabled them to colonize most of the world and become pests of plant nurseries, lumber, and forests. One of the fastest spreading ambrosia beetles is Xylosandrus crassiusculus. In order to discover the source populations of this globally invasive species, track its movement around the world, and test biogeographical scenarios, we combined restriction site‐associated DNA sequencing (RADseq) with comprehensive sampling across the species native and introduced range. From 1,365 genotyped SNP loci across 198 individuals, we determined that in its native range, X. crassiusculus is comprised of a population in Southeast Asia that includes mainland China, Thailand, and Taiwan, and a second island population in Japan. North America and Central America were colonized from the island populations, while Africa and Oceania were colonized from the mainland Asia, and Hawaii was colonized by both populations. Populations of X. crassiusculus in North America were genetically diverse and highly structured, suggesting (1) numerous, repeated introductions; (2) introduction of a large founding population; or (3) both scenarios with higher than expected outcrossing. X. crassiusculus, other wood‐boring insects, and indeed many other pests with unusual genetic structure continue to spread around the world. We show that contemporary genetic methods offer a powerful tool for understanding and preventing pathways of future biosecurity threats.
ambrosia beetle, ddRADseq, inbreeding, invasive species, population structure, single‐nucleotide polymorphisms
Cryptic genetic variation in an inbreeding and cosmopolitan pest, Xylosandrus crassiusculus, revealed using ddRADseq
Caroline Storer,corresponding author 1 Adam Payton, 2 Stuart McDaniel, 2 Bjarte Jordal, 3 and Jiri Hulcr 1 , 4
According to a conceptual model described in this analysis, place of death is determined by an interplay of factors associated with the illness, the individual, and the environment.
Our objective was to evaluate the determinants of place of death for adult patients who have been diagnosed with an advanced, life-limiting condition and are not expected to stabilize or improve.
A literature search was performed using Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid Embase, EBSCO Cumulative Index to Nursing & Allied Health Literature (CINAHL), and EBM Reviews, for studies published from January 1, 2004, to September 24, 2013.
Different places of death are considered in this analysis—home, nursing home, inpatient hospice, and inpatient palliative care unit, compared with hospital. We selected factors to evaluate from a list of possible predictors—i.e., determinants—of death. We extracted the adjusted odds ratios and 95% confidence intervals of each determinant, performed a meta-analysis if appropriate, and conducted a stratified analysis if substantial heterogeneity was observed.
From a literature search yielding 5,899 citations, we included 2 systematic reviews and 29 observational studies. Factors that increased the likelihood of home death included multidisciplinary home palliative care, patient preference, having an informal caregiver, and the caregiver’s ability to cope. Factors increasing the likelihood of a nursing home death included the availability of palliative care in the nursing home and the existence of advance directives. A cancer diagnosis and the involvement of home care services increased the likelihood of dying in an inpatient palliative care unit. A cancer diagnosis and a longer time between referral to palliative care and death increased the likelihood of inpatient hospice death. The quality of the evidence was considered low.
Our results are based on those of retrospective observational studies.
The results obtained were consistent with previously published systematic reviews. The analysis identified several factors that are associated with place of death.
The Determinants of Place of Death: An Evidence-Based Analysis