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Biomarkers are indispensable to the development of new tuberculosis therapeutics and vaccines. The most robust biomarkers measure factors that are essential to the underlying pathological process of the disease being treated, and thus can capture the full effects of many types of interventions on clinical outcomes in multiple prospective, randomised clinical trials. Many Mycobacterium tuberculosis and human biomarkers have been studied over the past decade. Present research focuses on three areas: biomarkers predicting treatment efficacy and cure of active tuberculosis, the reactivation of latent tuberculosis infection, and the induction of protective immune responses by vaccination. Many older, non-specific markers of inflammation, when considered in isolation, do not have sufficient predictive values for clinical use in tuberculosis. Although no new accurate, tuberculosis-specific biomarkers have yet been discovered, substantial progress has been made in some areas. However, the qualification of biomarkers as a surrogate for a clinical endpoint in tuberculosis is very challenging, and, for biomarkers that are non-culture-based, impossible to pursue without the availability of well characterised biobanks containing biospecimens from patients who have had adequate follow-up to establish long-term treatment outcome. We review progress in tuberculosis biomarker development and efforts being made to harness resources to meet future challenges.

Background Despite the high global disease burden of tuberculosis (TB), the disease caused by Mycobacterium tuberculosis  ( Mtb ) infection, novel treatments remain an urgent medical need. Development efforts continue to be hampered by the reliance on culture-based methods, which often take weeks to obtain due to the slow growth rate of Mtb . The availability of a “real-time” measure of treatment efficacy could accelerate TB drug development. Sputum lipoarabinomannan (LAM; an Mtb cell wall glycolipid) has promise as a pharmacodynamic biomarker of mycobacterial sputum load. Methods The present analysis evaluates LAM as a surrogate for Mtb burden in the sputum samples from 4 cohorts of a total of 776 participants. These include those from 2 cohorts of 558 non-TB and TB participants prior to the initiation of treatment (558 sputum samples), 1 cohort of 178 TB patients under a 14-day bactericidal activity trial with various mono- or multi-TB drug therapies, and 1 cohort of 40 TB patients with data from the first 56-day treatment of a standard 4-drug regimen. Results Regression analysis demonstrated that LAM was a predictor of colony-forming unit (CFU)/mL values obtained from the 14-day treatment cohort, with well-estimated model parameters (relative standard error ≤ 22.2%). Moreover, no changes in the relationship between LAM and CFU/mL were observed across the different treatments, suggesting that sputum LAM can be used to reasonably estimate the CFU/mL in the presence of treatment. The integrated analysis showed that sputum LAM also appears to be as good a predictor of time to Mycobacteria Growth Incubator Tube (MGIT) positivity as CFU/mL. As a binary readout, sputum LAM positivity is a strong predictor of solid media or MGIT culture positivity with an area-under-the-curve value of 0.979 and 0.976, respectively, from receiver-operator curve analysis. Conclusions Our results indicate that sputum LAM performs as a pharmacodynamic biomarker for rapid measurement of Mtb burden in sputum, and thereby may enable more efficient early phase clinical trial designs (e.g., adaptive designs) to compare candidate anti-TB regimens and streamline dose selection for use in pivotal trials. Trial registration NexGen EBA study (NCT02371681)

A guided-debate strategy was developed for a graduate-level core course in current issues based on the Jesuit method of discernment (group decision making). The strategy encourages students to use up-to-date Internet sources to determine the range of opinions on current controversies in the discipline. In addition to providing a structured process to engage in persuasive discussion of difficult issues, the strategy facilitates critical thinking about the quality of the debate itself. Thus, students learn to avoid the pitfalls associated with consensus, such as failing to express reservations or negative opinions that might be important, while learning how to express concerns that might not be easily received by others in a group. [A guided-debate strategy was developed for a graduate-level core course in current issues based on the Jesuit method of discernment (group decision making). The strategy encourages students to use up-to-date Internet sources to determine the range of opinions on current controversies in the discipline. In addition to providing a structured process to engage in persuasive discussion of difficult issues, the strategy facilitates critical thinking about the quality of the debate itself. Thus, students learn to avoid the pitfalls associated with consensus, such as failing to express reservations or negative opinions that might be important, while learning how to express concerns that might not be easily received by others in a group. [ J Nurs Educ. 2014;53(6):352–355.]

Moral distress, a complex human experience, has lacked a clear, complete definition. Intuitively, clinicians know that moral distress might be occurring for patients with increasing frequency due to technological advances that alter the natural order of life and death. Yet clinicians have not been able to evaluate the presence or extent of moral distress. To date, moral distress has been investigated mainly as an occupational issue using Jameton's (1984) definition, which has been problematic for several reasons. Without an adequate definition, moral distress can be unrecognized, yet have a silent, clinically significant impact on health. The literature is discussed from several perspectives to show the current state of the science in this topical area, and its potential future.

The author proposes the development of different levels of certification in the knowledge of nursing theory that would be based on the level of formal education attained. At present, nurses are being required to obtain higher levels of formal education in order to serve patients safely in a technologically complex health care system. Although evidence-based practice is strongly desired in contemporary health care, less consideration has been given to the value of theory-based nursing practice or the relationship between theory and research. The author explains multiple background issues and then highlights several questions that are important for disciplinary discussion at this point in time.

The concept of moral distress has been studied mainly as an occupational issue and has not been developed for use in clinical practice. This study was designed to bridge prior studies of occupational moral distress with future clinical investigations of moral distress. Study aims were to discover the essence, properties, and full content domain of the concept of moral distress in order to develop a universal definition of the concept. A modified phenomenological study of nurses' experience of a particular moral issue was conducted. A maximum variation sampling strategy was used to recruit a final sample of registered nurses (N = 10). Interior aversion is the essential act of moral distress. Five properties of the lived experience of moral distress were identified: perception, pain, valuing, altered participation, and perspective. Three types of moral distress identified in this study were: shocked, muted, and suppressed (persistent). Type of moral distress was related to situational conditions, recognition of moral ends, quality of coping processes, and temporal breadth. Negative outcomes of moral distress, which probably exist, were undetectable with this study design. The definition has been composed in universal terms, but remains tentative, since the full content domain of moral distress was largely but not definitively identified.

Repositioning a pazient every 2 hours remains the gold standard of nursing care to prevent pressure ulcers. Findings from this study showed silent factors are clinical realities that can increase nurses' work to reposition patients. Silent factors also can affect how nurses prioritize their work.