Early Exacerbation Relapse is Increased in Patients with Asthma and Bronchiectasis (a Post hoc Analysis).

PURPOSE: Asthma is a common comorbidity in patients with bronchiectasis and has been shown to increase the risk of bronchiectasis exacerbations. This paper explores the impact of comorbid asthma on patients receiving intravenous antibiotic treatment for bronchiectasis exacerbations. METHODS: This was a post hoc analysis of the Meropenem randomised controlled trial of 90 patients that had intravenous antibiotic treatment for bronchiectasis exacerbations. The participants were split into two groups: group 1 (asthma and bronchiectasis) and group 2 (bronchiectasis). The authors assessed response to treatment and time to next exacerbation. RESULTS: There were 38 participants in group 1 and 34 participants in group 2. The groups were found to be comparable in terms of age, sex, and bronchiectasis severity (median (95% CI) group 1 and then group 2 data): age 64.0(59.3, 68.6) and 63.6(57.9, 69.4) years old, p = 0.8; 57.9% and 64.7% female, p = 0.6; Bronchiectasis Severity Index 11.1(9.8, 12.4) and 10.1(8.2, 12.0), p = 0.3. There was a similar response to treatment between the groups, but group 1 were found to relapse early by day 14, 31.6% in group 1 and 11.8% in group 2, p = 0.03. In the Cox proportional hazards model, asthma was the only independent risk factor for early relapse by day 14 (odds ratio (95% CI) 3.16 (1.02-9.79), p = 0.047). CONCLUSION: The clinical response to treatment was similar but patients with coexisting asthma were at increased risk of early relapse within 14 days of stopping intravenous antibiotic therapy. CLINICAL TRIAL REGISTRATION: NCT02047773.

Best Current Practice and Research Priorities in Active Surveillance for Prostate Cancer-A Report of a Movember International Consensus Meeting.

BACKGROUND: Active surveillance (AS) is recommended for low-risk and some intermediate-risk prostate cancer. Uptake and practice of AS vary significantly across different settings, as does the experience of surveillance-from which tests are offered, and to the levels of psychological support. OBJECTIVE: To explore the current best practice and determine the most important research priorities in AS for prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: A formal consensus process was followed, with an international expert panel of purposively sampled participants across a range of health care professionals and researchers, and those with lived experience of prostate cancer. Statements regarding the practice of AS and potential research priorities spanning the patient journey from surveillance to initiating treatment were developed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Panel members scored each statement on a Likert scale. The group median score and measure of consensus were presented to participants prior to discussion and rescoring at panel meetings. Current best practice and future research priorities were identified, agreed upon, and finally ranked by panel members. RESULTS AND LIMITATIONS: There was consensus agreement that best practice includes the use of high-quality magnetic resonance imaging (MRI), which allows digital rectal examination (DRE) to be omitted, that repeat standard biopsy can be omitted when MRI and prostate-specific antigen (PSA) kinetics are stable, and that changes in PSA or DRE should prompt MRI ± biopsy rather than immediate active treatment. The highest ranked research priority was a dynamic, risk-adjusted AS approach, reducing testing for those at the least risk of progression. Improving the tests used in surveillance, ensuring equity of access and experience across different patients and settings, and improving information and communication between and within clinicians and patients were also high priorities. Limitations include the use of a limited number of panel members for practical reasons. CONCLUSIONS: The current best practice in AS includes the use of high-quality MRI to avoid DRE and as the first assessment for changes in PSA, with omission of repeat standard biopsy when PSA and MRI are stable. Development of a robust, dynamic, risk-adapted approach to surveillance is the highest research priority in AS for prostate cancer. PATIENT SUMMARY: A diverse group of experts in active surveillance, including a broad range of health care professionals and researchers and those with lived experience of prostate cancer, agreed that best practice includes the use of high-quality magnetic resonance imaging, which can allow digital rectal examination and some biopsies to be omitted. The highest research priority in active surveillance research was identified as the development of a dynamic, risk-adjusted approach.

Feasibility of shortening intravenous antibiotic therapy for bronchiectasis based on bacterial load: a proof-of-concept randomised controlled trial.

BACKGROUND: There is a lack of evidence to guide the duration of intravenous antibiotics for bronchiectasis exacerbations. AIMS: The aim of this study was to assess whether it is feasible, based on bacterial load, to shorten intravenous antibiotics during exacerbations and whether 14 days of treatment is superior. METHODS: We recruited participants requiring intravenous antibiotics for exacerbations. Participants were randomised into two groups: to receive antibiotics for 14 days (14-day group) or to have a shorter duration of treatment based on bacterial load (bacterial load-guided group (BLGG)). Bacterial load was checked on days 0, 7, 10, 14 and 21. If the bacterial load was <106 CFU·mL-1 on day 7 or day 10 in the BLGG, antibiotics were stopped the following day. RESULTS: A total of 47 participants were in the 14-day group and 43 were in the BLGG. 88% of participants in the BLGG were able to stop antibiotics by day 8 and potentially 81% of participants in the 14-day group could have stopped antibiotics at day 8. There was a nonsignificant trend for increased clinical improvement by day 21 in the 14-day group compared to the BLGG. However, overall group data showed the median (interquartile range) time to next exacerbation was 27.5 days (12.5-60 days) in the 14-day group and 60 days (18-110 days) in the in BLGG (p=0.0034). In a Cox proportional hazard model, participants in the 14-day group were more likely to experience exacerbations (HR 1.80, 95% CI 1.16-2.80, p=0.009) than those in the BLGG, and those with mild bronchiectasis were less likely to experience exacerbations than patients with more severe bronchiectasis (HR 0.359, 95% CI 0.13-0.99, p=0.048). CONCLUSIONS: Bacterial load-guided therapy is feasible in most exacerbations requiring intravenous antibiotics. There was a nonsignificant trend for increased clinical improvement by day 21 with 14 days of antibiotics compared with bacterial load-guided therapy but paradoxically there was a prolonged time to next exacerbation in the BLGG.

Managing patients receiving new and unfamiliar cancer treatments: A qualitative study of general practitioners' experience.

BACKGROUND AND OBJECTIVES: As systemic cancer treatments increase in complexity, general practitioners (GPs) need access to reliable information to support patients on new and often unfamiliar treatments. The authors explored the experience of GPs in supporting patients receiving anticancer therapy, and the barriers and facilitators to the implementation of a new resource designed to support GPs in this role. METHOD: Semi-structured qualitative interviews were conducted with 15 GPs and oncology clinicians. Thematic analysis of interviews used inductive coding. RESULTS: Themes identified were GPs not feeling part of the team when looking after patients on cancer treatment, the role a new set of eviQ information resources could play in supporting GPs and barriers and facilitators to the implementation of these resources. DISCUSSION: GPs value reliable, published cancer treatment information, but it does not remove the need for individualised patient correspondence or the inclusion of the GP in the treating team.

Human Mucosal-Associated Invariant T Cells in Older Individuals Display Expanded TCRαß Clonotypes with Potent Antimicrobial Responses.

Mucosal-associated invariant T (MAIT) cells are important for immune responses against microbial infections. Although known to undergo marked numerical changes with age in humans, our understanding of how MAIT cells are altered during different phases across the human life span is largely unknown. Although also abundant in the tissues, our study focuses on MAIT cell analyses in blood. Across the human life span, we show that naive-like MAIT cells in umbilical cord blood switch to a central/effector memory-like profile that is sustained into older age. Whereas low-grade levels of plasma cytokine/chemokine were apparent in older donors (>65 y old), surprisingly, they did not correlate with the ex vivo MAIT hyperinflammatory cytokine profile observed in older adults. Removal of MAIT cells from older individuals and an aged environment resulted in the reversal of the baseline effector molecule profile comparable with MAIT cells from younger adults. An upregulated basal inflammatory profile accounted for reduced Escherichia coli-specific responses in aged MAIT cells compared with their young adult counterparts when fold change in expression levels of GzmB, CD107a, IFN-γ, and TNF was examined. However, the magnitude of antimicrobial MR1-dependent activation remained as potent and polyfunctional as with younger adults. Paired TCRαß analyses of MAIT cells revealed large clonal expansions in older adults and tissues that rivalled, remarkably, the TCRαß repertoire diversity of virus-specific CD8+ T cells. These data suggest that MAIT cells in older individuals, although associated with large clonal TCRαß expansions and increased baseline inflammatory potential, demonstrate plasticity and provide potent antimicrobial immunity.

The impact of multidisciplinary team meetings on patient assessment, management and outcomes in oncology settings: A systematic review of the literature.

BACKGROUND: Conducting regular multidisciplinary team (MDT) meetings requires significant investment of time and finances. It is thus important to assess the empirical benefits of such practice. A systematic review was conducted to evaluate the literature regarding the impact of MDT meetings on patient assessment, management and outcomes in oncology settings. METHODS: Relevant studies were identified by searching OVID MEDLINE, PsycINFO, and EMBASE databases from 1995 to April 2015, using the keywords: multidisciplinary team meeting* OR multidisciplinary discussion* OR multidisciplinary conference* OR case review meeting* OR multidisciplinary care forum* OR multidisciplinary tumour board* OR case conference* OR case discussion* AND oncology OR cancer. Studies were included if they assessed measurable outcomes, and used a comparison group and/or a pre- and post-test design. RESULTS: Twenty-seven articles met inclusion criteria. There was limited evidence for improved survival outcomes of patients discussed at MDT meetings. Between 4% and 45% of patients discussed at MDT meetings experienced changes in diagnostic reports following the meeting. Patients discussed at MDT meetings were more likely to receive more accurate and complete pre-operative staging, and neo-adjuvant/adjuvant treatment. Quality of studies was affected by selection bias and the use of historical cohorts impacted study quality. CONCLUSIONS: MDT meetings impact upon patient assessment and management practices. However, there was little evidence indicating that MDT meetings resulted in improvements in clinical outcomes. Future research should assess the impact of MDT meetings on patient satisfaction and quality of life, as well as, rates of cross-referral between disciplines.

Prostate cancer testing: a snapshot of the attitudes and practice of Australian general practitioners.

The role of the General Practitioner (GP) in testing for and managing men with prostate cancer (PCa) is significant. Very few studies have explored the attitudes and practices of Australian GPs in the context of the role of PCa testing. In this study, a 46-item web-based questionnaire was used to assess self-reported PCa testing attitudes and practices of GPs. This questionnaire was circulated to divisions of general practice and Medicare locals for further distribution to their GP members across Australia. GPs from all states and territories participated, and a total of 136 GPs completed the survey. Of the responding GPs, 57% always or usually offered PCa testing to asymptomatic men ≤ 70 years of age and 60% of GPs always or usually included a digital rectal examination (DRE). Many (80%) of the GPs stated that the current PCa testing guidelines were not clear. PCa testing was offered opportunistically by 56% while 39% offered testing at the patient's request. The results captured in this study represent a snapshot of GP attitudes and practices from across Australia. The results presented indicate a wide variation in the approaches to PCa testing in general practice across Australia, which in most part appear to be related to the lack of clarity of the current prostate cancer testing guidelines.

The Melbourne Consensus Statement on the early detection of prostate cancer.

Various conflicting guidelines and recommendations about prostate cancer screening and early detection have left both clinicians and their patients quite confused. At the Prostate Cancer World Congress held in Melbourne in August 2013, a multidisciplinary group of the world's leading experts in this area gathered together and generated this set of consensus statements to bring some clarity to this confusion. The five consensus statements provide clear guidance for clinicians counselling their patients about the early detection of prostate cancer.

Mechanisms for an effect of acetylcysteine on renal function after exposure to radio-graphic contrast material: study protocol.

BACKGROUND: Contrast-induced nephropathy is a common complication of contrast administration in patients with chronic kidney disease and diabetes. Its pathophysiology is not well understood; similarly the role of intravenous or oral acetylcysteine is unclear. Randomized controlled trials to date have been conducted without detailed knowledge of the effect of acetylcysteine on renal function. We are conducting a detailed mechanistic study of acetylcysteine on normal and impaired kidneys, both with and without contrast. This information would guide the choice of dose, route, and appropriate outcome measure for future clinical trials in patients with chronic kidney disease. METHODS/DESIGN: We designed a 4-part study. We have set up randomised controlled cross-over studies to assess the effect of intravenous (50 mg/kg/hr for 2 hrs before contrast exposure, then 20 mg/kg/hr for 5 hrs) or oral acetylcysteine (1200 mg twice daily for 2 days, starting the day before contrast exposure) on renal function in normal and diseased kidneys, and normal kidneys exposed to contrast. We have also set up a parallel-group randomized controlled trial to assess the effect of intravenous or oral acetylcysteine on patients with chronic kidney disease stage III undergoing elective coronary angiography. The primary outcome is change in renal blood flow; secondary outcomes include change in glomerular filtration rate, tubular function, urinary proteins, and oxidative balance. DISCUSSION: Contrast-induced nephropathy represents a significant source of hospital morbidity and mortality. Over the last ten years, acetylcysteine has been administered prior to contrast to reduce the risk of contrast-induced nephropathy. Randomized controlled trials, however, have not reliably demonstrated renoprotection; a recent large randomized controlled trial assessing a dose of oral acetylcysteine selected without mechanistic insight did not reduce the incidence of contrast-induced nephropathy. Our study should reveal the mechanism of effect of acetylcysteine on renal function and identify an appropriate route for future dose response studies and in time randomized controlled trials. TRIAL REGISTRATION: Clinical Trials.gov: NCT00558142; EudraCT: 2006-003509-18.