Head-to-head trials of antibiotics for bronchiectasis

Background The diagnosis of bronchiectasis is defined by abnormal dilation of the airways related to a pathological mechanism of progressive airway destruction that is due to a 'vicious cycle' of recurrent bacterial infection, inflammatory mediator release, airway damage, and subsequent further infection. Antibiotics are the main treatment option for reducing bacterial burden in people with exacerbations of bronchiectasis and for longer‐term eradication, but their use is tempered against potential adverse effects and concerns regarding antibiotic resistance. The comparative effectiveness, cost‐effectiveness, and safety of different antibiotics have been highlighted as important issues, but currently little evidence is available to help resolve uncertainty on these questions. Objectives To evaluate the comparative effects of different antibiotics in the treatment of adults and children with bronchiectasis. Search methods We identified randomised controlled trials (RCTs) through searches of the Cochrane Airways Group Register of trials and online trials registries, run 30 April 2018. We augmented these with searches of the reference lists of published studies. Selection criteria We included RCTs reported as full‐text articles, those published as abstracts only, and unpublished data. We included adults and children (younger than 18 years) with a diagnosis of bronchiectasis by bronchography or high‐resolution computed tomography who reported daily signs and symptoms, such as cough, sputum production, or haemoptysis, and those with recurrent episodes of chest infection; we included studies that compared one antibiotic versus another when they were administered by the same delivery method. Data collection and analysis Two review authors independently assessed trial selection, data extraction, and risk of bias. We assessed overall quality of the evidence using GRADE criteria. We made efforts to collect missing data from trial authors. We have presented results with their 95% confidence intervals (CIs) as mean differences (MDs) or odds ratios (ORs). Main results Four randomised trials were eligible for inclusion in this systematic review ‐ two studies with 83 adults comparing fluoroquinolones with β‐lactams and two studies with 55 adults comparing aminoglycosides with polymyxins. None of the included studies reported information on exacerbations ‐ one of our primary outcomes. Included studies reported no serious adverse events ‐ another of our primary outcomes ‐ and no deaths. We graded this evidence as low or very low quality. Included studies did not report quality of life. Comparison between fluoroquinolones and β‐lactams (amoxicillin) showed fewer treatment failures in the fluoroquinolone group than in the amoxicillin group (OR 0.07, 95% CI 0.01 to 0.32; low‐quality evidence) after 7 to 10 days of therapy. Researchers reported that Pseudomonas aeruginosa infection was eradicated in more participants treated with fluoroquinolones (Peto OR 20.09, 95% CI 2.83 to 142.59; low‐quality evidence) but provided no evidence of differences in the numbers of participants showing improvement in sputum purulence (OR 2.35, 95% CI 0.96 to 5.72; very low‐quality evidence). Study authors presented no evidence of benefit in relation to forced expiratory volume in one second (FEV₁). The two studies that compared polymyxins versus aminoglycosides described no clear differences between groups in the proportion of participants with P aeruginosa eradication (OR 1.40. 95% CI 0.36 to 5.35; very low‐quality evidence) or improvement in sputum purulence (OR 0.16, 95% CI 0.01 to 3.85; very low‐quality evidence). The evidence for changes in FEV₁ was inconclusive. Two of three trials reported adverse events but did not report the proportion of participants experiencing one or more adverse events, so we were unable to interpret the information. Authors' conclusions Limited low‐quality evidence favours short‐term oral fluoroquinolones over beta‐lactam antibiotics for patients hospitalised with exacerbations. Very low‐quality evidence suggests no benefit from inhaled aminoglycosides verus polymyxins. RCTs have presented no evidence comparing other modes of delivery for each of these comparisons, and no RCTs have included children. Overall, current evidence from a limited number of head‐to‐head trials in adults or children with bronchiectasis is insufficient to guide the selection of antibiotics for short‐term or long‐term therapy. More research on this topic is needed

Using formative research with older adults to inform a community physical activity programme: Get Healthy, Get Active

Aim: The purpose of this formative study was to explore current knowledge and attitudes towards physical activity, as well as perceived barriers, facilitators and opportunities for physical activity participation among older adults living in the community. The findings have subsequently informed the design, delivery and recruitment strategies of a local community physical activity intervention programme which forms part of Sport England’s national Get Healthy, Get Active initiative. Background: There is a growing public health concern regarding the amount of time spent in sedentary and physical activity behaviours within the older adult population. Methods: Between March and June 2016, 34 participants took part in one of six focus groups as part of a descriptive formative study. A homogenous purposive sample of 28 community dwelling white, British older adults (six male), aged 65-90 years (M=78, SD=7 years) participated in one of five focus group sessions. An additional convenience pragmatic sub-sample of six participants (three male), aged 65-90 years (M=75, SD=4 years), recruited from an assisted living retirement home participated in a sixth focus group. Questions for focus groups were structured around the PRECEDE stage of the PRECEDE-PROCEDE model of health programme design, implementation, and evaluation. Questions addressed knowledge, attitudes and beliefs towards physical activity, as well as views on barriers and opportunities for physical activity participation. All data were transcribed verbatim. Thematic analysis was then conducted with outcomes represented as pen profiles. Findings: Consistent views regarding both the potential physical and psychosocial benefits of physical activity were noted regardless of living status. The themes of, opportunities and awareness for physical activity participation, cost, transport, location and season/weather varied between participants living in an assisted living retirement home and community dwelling older adults. Further comparative research on the physical activity requirements of older adults living in assisted living versus community settings are warranted

The implementation of a Technician Enhanced Administration of Medications [TEAM] model: An evaluative study of impact on working practices in a children's hospital

Background: Children are frequently prescribed unlicensed and off-label medicines meaning dosing and administration of medicines to children is often based on poor quality guidance. In UK hospitals, nursing staff are often responsible for administering medications. Medication Errors [MEs] are problematic for health services, though are poorly reported and therefore difficult to quantify with confidence. In the UK, children's medicines require administration by at least two members of ward staff, known as a ‘second check’ system, thought to reduce Medication Administration Errors [MAEs]. Objectives: To assess the impact on working practices of the introduction of a new way of working, using Technician Enhanced Administration of Medications [TEAM] on two specialist wards within a children's’ hospital. To evidence any potential impact of a TEAM ward-based pharmacy technician [PhT] on the reporting of MEs. Methods: A TEAM PhT was employed on two wards within the children's hospital and trained in medicines administration. Firstly, an observational pre-and-post cohort design was used to identify the effect of TEAM on MEs. We analysed the hospital's official reporting system for incidents and ‘near misses’, as well as the personal incident log of the TEAM PhT. Secondly, after implementation, we interviewed staff about their perceptions of TEAM and its impact on working practices. Results: We affirm MEs are considerably under-reported in hospital settings, but TEAM PhTs can readily identify them. Further, placing TEAM PhTs on wards may create opportunities for inter-professional knowledge exchange and increase nurses’ awareness of potential MAEs, although this requires facilitation. Conclusions: TEAM PhT roles may be beneficial for pharmacy technicians’ motivation, job satisfaction, and career development. Hospitals will need to consider the balance between resources invested in TEAM PhTs and the level of impact on reporting MEs. Health economic analyses could provide evidence to fully endorse integration of TEAM PhTs for all hospital settings

Evaluation of wrist and hip sedentary behaviour and moderate-to-vigorous physical activity raw acceleration cutpoints in older adults

Wrist-based accelerometers are now common in assessing physical activity (PA) and sedentary behaviour (SB) in population-based studies, but there is a scarcity of raw acceleration cutpoints in older adults. The study aimed to determine and evaluate wrist-based GENEActiv (GA) and hip-based ActiGraph GT3X+ (AG) raw acceleration cutpoints for SB and moderate-to-vigorous PA (MVPA) in older adults ≥60 years of age. A laboratory-based calibration analyses of 34 healthy older adults involved receiver operator characteristic (ROC) curves to determine raw acceleration cutpoints for SB and MVPA. ROC analysis revealed an area under the curve (AUC) of 0.88 for GA SB and MVPA, and 0.90 for AG SB and 0.94 for AG MVPA. Sensitivity optimised SB and specificity optimised MVPA GA cutpoints of 57 mg and 104 mg, and AG cutpoints of 15 mg and 69 mg were also generated, respectively. Cross-validation analysis revealed moderate agreement for GA and AG SB cutpoints, and fair to substantial agreement for GA and AG MVPA cutpoints, respectively. The resultant cutpoints can classify older adults as engaging in SB or not engaging in MVPA but the sensitivity optimised SB cutpoints should be interpreted with a degree of caution due to their modest cross-validation results

From Creating Spaces for Civic Discourse to Creating Resources for Action

In this paper, we investigate the role of technology to address the concerns of a civil society group carrying out community-level consultation on the allocation of £1 million of community funds. We explore issues of devolved decision-making through the evaluation of a sociodigital system designed to foster deliberative virtues. We describe the ways in which this group used our system in their consultation practices. Our findings highlight how they adopted our technology to privilege specific forms of expression, ascertain issues in their community, make use of and make sense of community data, and create resources for action within their existing practices. Based on related fieldwork we discuss the impacts of structuring and configuring tools for ‘talk-based’ consultation in order to turn attention to the potential pitfalls and prospects for designing civic technologies that create resources for action for civil society

Y-box protein-1/p18 fragment identifies malignancies in patients with chronic liver disease

<p>Abstract</p> <p>Background</p> <p>Immunohistochemical detection of cold shock proteins is predictive for deleterious outcome in various malignant diseases. We recently described active secretion of a family member, denoted Y-box (YB) protein-1. We tested the clinical and diagnostic value of YB-1 protein fragment p18 (YB-1/p18) detection in blood for malignant diseases.</p> <p>Methods</p> <p>We used a novel monoclonal anti-YB-1 antibody to detect YB-1/p18 by immunoblotting in plasma samples of healthy volunteers (n = 33), patients with non-cancerous, mostly inflammatory diseases (n = 60), hepatocellular carcinoma (HCC; n = 25) and advanced solid tumors (n = 20). YB-1/p18 was then tested in 111 patients with chronic liver diseases, alongside established tumor markers and various diagnostic measures, during evaluation for potential liver transplantation.</p> <p>Results</p> <p>We developed a novel immunoblot to detect the 18 kD fragment of secreted YB-1 in human plasma (YB-1/p18) that contains the cold-shock domains (CSD) 1-3 of the full-length protein. YB-1/p18 was detected in 11/25 HCC and 16/20 advanced carcinomas compared to 0/33 healthy volunteers and 10/60 patients with non-cancerous diseases. In 111 patients with chronic liver disease, YB-1/p18 was detected in 20 samples. Its occurrence was not associated with advanced Child stages of liver cirrhosis or liver function. In this cohort, YB-1/p18 was not a good marker for HCC, but proved most powerful in detecting malignancies other than HCC (60% positive) with a lower rate of false-positive results compared to established tumor markers. Alpha-fetoprotein (AFP) was most sensitive in detecting HCC, but simultaneous assessment of AFP, CA19-9 and YB-1/p18 improved overall identification of HCC patients.</p> <p>Conclusions</p> <p>Plasma YB-1/p18 can identify patients with malignancies, independent of acute inflammation, renal impairment or liver dysfunction. The detection of YB-1/p18 in human plasma may have potential as a tumor marker for screening of high-risk populations, e.g. before organ transplantation, and should therefore be evaluated in larger prospective studies.</p