Bmc Med
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These are exciting times for cancer immunotherapy. After many years of disappointing results, the tide has finally changed and immunotherapy has become a clinically validated treatment for many cancers. ⋯ The recent success of several immunotherapeutic regimes, such as monoclonal antibody blocking of cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD1), has boosted the development of this treatment modality, with the consequence that new therapeutic targets and schemes which combine various immunological agents are now being described at a breathtaking pace. In this review, we outline some of the main strategies in cancer immunotherapy (cancer vaccines, adoptive cellular immunotherapy, immune checkpoint blockade, and oncolytic viruses) and discuss the progress in the synergistic design of immune-targeting combination therapies.
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Evidence-based practice in eating disorders incorporates three essential components: research evidence, clinical expertise, and patient values, preferences, and characteristics. Conceptualized as a 'three-legged stool' by Sackett et al. in 1996 (BMJ), all of these components of evidence-based practice are considered essential for providing optimal care in the treatment of eating disorders. However, the extent to which these individual aspects of evidence-based practice are valued among clinicians and researchers is variable, with each of these stool 'legs' being neglected at times. As a result, empirical support and patient preferences for treatment are not consistently considered in the selection and implementation of eating disorder treatment. In addition, clinicians may not have access to training to provide treatments supported by research and preferred by patients. Despite these challenges, integrating these three components of evidence-based practice is critical for the effective treatment of eating disorders. ⋯ Current research supports the use of several types of psychotherapies, including cognitive-behavioral, interpersonal, and family-based therapies, as well as certain types of medications for the treatment of eating disorders. However, limitations in current research, including sample heterogeneity, inconsistent efficacy, a paucity of data, the need for tailored approaches, and the use of staging models highlight the need for clinical expertise. Although preliminary data also support the importance of patient preferences, values, and perspectives for optimizing treatment, enhancing treatment outcome, and minimizing attrition among patients with eating disorders, the extent to which patient preference is consistently predictive of outcome is less clear and requires further investigation. All three components of evidence-based practice are integral for the optimal treatment of eating disorders. Integrating clinical expertise and patient perspective may also facilitate the dissemination of empirically-supported and emerging treatments as well as prevention programs. Further research is imperative to identify ways in which this three-legged approach to eating disorder treatment could be most effectively implemented.
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New treatment options are needed to maintain and improve therapy for tuberculosis, which caused the death of 1.5 million people in 2013 despite potential for an 86 % treatment success rate. A greater understanding of Mycobacterium tuberculosis (M.tb) bacilli that persist through drug therapy will aid drug development programs. Predictive biomarkers for treatment efficacy are also a research priority. ⋯ This study defines the transcriptional signature of M.tb bacilli that have been expectorated in sputum after two weeks of drug therapy, characterizing the phenotypic state of bacilli that persist through treatment. We demonstrate that variability in clinical manifestations of disease are detectable in bacterial sputa signatures, and that the changing M.tb mRNA profiles 0-2 weeks into chemotherapy predict the efficacy of treatment 6 weeks later. These observations advocate assaying dynamic bacterial phenotypes through drug therapy as biomarkers for treatment success.
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Smoking is the most important individual risk factor for many cancer sites but its association with breast and prostate cancer is not entirely clear. Rate advancement periods (RAPs) may enhance communication of smoking related risk to the general population. Thus, we estimated RAPs for the association of smoking exposure (smoking status, time since smoking cessation, smoking intensity, and duration) with total and site-specific (lung, breast, colorectal, prostate, gastric, head and neck, and pancreatic) cancer incidence and mortality. ⋯ This investigation shows that smoking, even among older adults, considerably advances, and cessation delays, the risk of developing and dying from cancer. These findings may be helpful in more effectively communicating the harmful effects of smoking and the beneficial effect of smoking cessation.
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Epidemiological studies have observed a positive association between an earlier age at sexual development and prostate cancer, but markers of sexual maturation in boys are imprecise and observational estimates are likely to suffer from a degree of uncontrolled confounding. To obtain causal estimates, we examined the role of pubertal development in prostate cancer using genetic polymorphisms associated with Tanner stage in adolescent boys in a Mendelian randomization (MR) approach. ⋯ Older age at sexual maturation is causally linked to a reduced risk of later prostate cancer, especially aggressive disease.