Living With Ambiguity: A Metasynthesis of Qualitative Research on Mild Cognitive Impairment

Purpose of the study: Mild Cognitive Impairment (MCI) is a diagnosis proposed to describe an intermediate state between normal cognitive aging and dementia. MCI has been criticised for its conceptual fuzziness, its ambiguous relationship to dementia, and the tension it creates between medical and sociological understandings of “normal aging”. Design and Methods: We examined the published qualitative literature on experiences of being diagnosed and living with MCI using metasynthesis as the methodological framework. Results: Two overarching conceptual themes were developed. The first, MCI and myself-in-time, showed that a diagnosis of MCI could profoundly affect a person’s understanding of their place in the world. This impact appears to be mediated by multiple factors including a person’s social support networks, which daily activities are affected, and subjective interpretations of the meaning of MCI. The second theme, Living with Ambiguity, describes the difficulties people experienced in making sense of their diagnosis. Uncertainty arose, in part, from lack of clarity and consistency in the information received by people with MCI, including whether they are even told MCI is the diagnosis. Implications: We conclude by suggesting an ethical tension is always at play when a MCI diagnosis is made. Specifically, earlier support and services afforded by a diagnosis may come at the expense of a person’s anxiety about the future, with continued uncertainty about how his or her concerns and needs can be addressed

Degarelix for Treating Advanced Hormone-Dependent Prostate Cancer: An Evidence Review Group Perspective of a NICE Single Technology Appraisal

As part of its Single Technology Appraisal Process, the National Institute for Health and Care Excellence (NICE) invited the manufacturer of degarelix (Ferring Pharmaceuticals) to submit evidence for the clinical and cost effectiveness of degarelix for the treatment of advanced hormone-dependent prostate cancer. The School of Health and Related Research Technology Appraisal Group at the University of Sheffield was commissioned to act as the independent Evidence Review Group (ERG). The ERG produced a critical review of the evidence contained within the company’s submission to NICE. The evidence, which included a randomised controlled trial (RCT) of degarelix versus leuprorelin, found that degarelix was non-inferior to leuprorelin for reduction of testosterone levels and that degarelix achieved a more rapid suppression of prostate-specific antigen levels and subsequently decreased incidences of testosterone flare associated with luteinising hormone releasing-hormone (LHRH) agonists. However, protection against testosterone flare for the comparators in the clinical trials was not employed in line with UK clinical practice. Further claims surrounding overall survival, cardiovascular adverse events and clinical equivalence of the comparator drugs from six RCTs of degarelix should be regarded with caution because of flaws and inconsistencies in the pooling of trial data to draw conclusions. The cost-effectiveness evidence included a de novo economic model. Based on the ERG’s preferred base case, the deterministic incremental cost-effectiveness analysis (ICER) for degarelix versus 3-monthly triptorelin was £14,798 per quality-adjusted life-year (QALY) gained. Additional scenario analyses undertaken by the ERG resulted in ICERs for degarelix versus 3-monthly triptorelin ranging from £17,067 to £35,589 per QALY gained. Subgroup analyses undertaken using the Appraisal Committee’s preferred assumptions suggested that degarelix was not cost effective for the subgroup with metastatic disease but could be cost effective for the subgroup with spinal metastases. The company submitted further evidence to NICE following an initial negative Appraisal Committee decision. Further analyses from the Decision Support Unit found that that, whilst some evidence indicated that degarelix could be cost effective for a small subgroup of people with spinal cord compression (SCC), data on the potential size of this subgroup and the rate of SCC were insufficient to estimate an ICER based on the evidence submitted by the company and a separately commissioned systematic review. NICE recommended degarelix as an option for treating advanced hormone-dependent prostate cancer in people with spinal metastases, only if the commissioner can achieve at least the same discounted drug cost as that available to the UK NHS in June 2016

Surgical Helmets and SARS Infection

Performance testing of two brands of surgical helmets indicated that their efficiency at in vivo filtration of sub–micrometer-sized particles is inadequate for their use as respirators. These helmets are not marketed for respiratory protection and should not be used alone for protection against severe acute respiratory syndrome when performing aerosol-generating procedures

Infographic. All health professionals should talk about physical activity with patients

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Australia and Other Nations are Failing to Meet Sedentary Behaviour Guidelines for Children: Implications and a Way Forward

BACKGROUND: Australia has joined a growing number of nations which have evaluated the physical activity and sedentary behaviour status of their children. Australia received a 'D minus' in the first Active Healthy Kids Australia Physical Activity Report Card. METHODS: An expert subgroup of the Australian Report Card Research Working Group iteratively reviewed available evidence to answer three questions: 1) What are the main sedentary behaviours of children?, 2) What are the potential mechanisms for sedentary behaviour to impact on child health and development? and, 3) What are the effects of different types of sedentary behaviours on child health and development? RESULTS: Neither sedentary time nor screen time are homogeneous activities likely to result in homogenous effects. There are several mechanisms by which various sedentary behaviours may positively or negatively affect cardiometabolic, neuro-musculoskeletal, and psycho-social health, though the strength of evidence varies. National surveillance systems, and mechanistic, longitudinal and experimental studies are needed for Australia and other nations to improve their grade. CONCLUSIONS: Despite limitations, available evidence is sufficiently convincing that the total exposure and pattern of exposure to sedentary behaviours are critical to the healthy growth, development and wellbeing of children. Nations therefore need strategies to address these common behaviours

Investigating the Impact of Crohn's Disease on the Bioaccessibility of a Lipid-Based Formulation with an in Vitro Dynamic Gastrointestinal Model

The aim of the study was to investigate the impact of Crohn's disease (CD) on the performance of a lipid-based formulation of ciprofloxacin in a complex gastrointestinal simulator (TIM-1, TNO) and to compare the luminal environment in terms of bile salt and lipid composition in CD and healthy conditions. CD conditions were simulated in the TIM-1 system with a reduced concentration of porcine pancreatin and porcine bile. The bioaccessibility of ciprofloxacin was similar in simulated CD and healthy conditions considering its extent as well as its time course in the jejunum and ileum filtrate. Differences were observed in terms of the luminal concentration of triglycerides, monoglycerides, and fatty acids in the different TIM-1 compartments, indicating a reduction and delay in the lipolysis of formulation excipients in CD. The quantitative analysis of bile salts revealed higher concentrations for healthy conditions (standard TIM-1 fasted-state protocol) in the duodenum and jejunum TIM-1 compartments compared to published data in human intestinal fluids of healthy subjects. The reduced concentrations of bile salts in simulated CD conditions correspond to the levels observed in human intestinal fluids of healthy subjects in the fasted state.A lipidomics approach with ultra performance liquid chromatography (UPLC)/mass spectrometry (MS) has proven to be a time-efficient method to semiquantitatively analyze differences in fatty acid and bile salt levels between healthy and CD conditions. The dynamic luminal environment in CD and healthy conditions after administration of a lipid-based formulation can be simulated using the TIM-1 system. For ciprofloxacin, an altered luminal lipid composition had no impact on its performance indicating a low risk of altered performance in CD patients. </p

Peer support for the maintenance of physical activity and health in cancer survivors: the PEER trial - a study protocol of a randomised controlled trial

BACKGROUND: Despite an overwhelming body of evidence showing the benefits of physical activity (PA) and exercise for cancer survivors, few survivors meet the exercise oncology guidelines. Moreover, initiating, let alone maintaining exercise programs with cancer survivors continues to have limited success. The aim of this trial is to evaluate the influence of peer support on moderate-to-vigorous PA (MVPA) and various markers of health 12 months following a brief supervised exercise intervention in cancer survivors. METHODS: Men and women previously diagnosed with histologically-confirmed breast, colorectal or prostate cancer (n = 226), who are \u3e1-month post-treatment, will be invited to participate in this trial. Once enrolled, participants will complete 4 weeks (12 sessions) of supervised high intensity interval training (HIIT). On completion of the supervised phase, both groups will be provided with written recommendations and verbally encouraged to achieve three HIIT sessions per week, or equivalent exercise that meets the exercise oncology guidelines. Participants will be randomly assigned to receive 12 months of peer support, or no peer support (control). Primary and secondary outcomes will be assessed at baseline, after the 4-week supervised HIIT phase and at 3-, 6- and 12-months. Primary outcomes will include accelerometry-derived MVPA and prescribed HIIT session adherence; whilst secondary outcomes will include cardiorespiratory fitness ([Formula: see text]), body composition, quality of life and select cytokines, myokines and inflammatory markers. Random effects mixed modelling will be used to compare mean changes in outcomes between groups at each time point. A group x time interaction will be used to formally test for differences between groups (alpha =0.05); utilising intention-to-treat analyses. DISCUSSION: If successful, peer support may be proposed, adopted and implemented as a strategy to encourage cancer survivors to maintain exercise beyond the duration of a short-term, supervised intervention. A peer support-exercise model has the long-term potential to reduce comorbidities, improve physical and mental wellbeing, and significantly reduce the burden of disease in cancer survivors. ETHICS: Human Research Ethics Committee of Bellberry Ltd. (#2015-12-840). TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registry 12618001855213 . Retrospectively registered 14 November 2018. Trial registration includes all components of the WHO Trial Registration Data Set, as recommended by the ICMJE

A hard day’s night: time use in shift workers

Background Differences in how shift workers accumulate physical activity (PA) while at work and in leisure time, on days when they are working at night, during the day, or on non-work days, are largely unexplored. The aim of this study was to improve understanding of physical activity patterns in two groups of shift workers, and to measure variations according to their shift schedules. Methods This pragmatic pilot study was conducted in two workplaces. Employees in Workplace 1 (n = 10) were required to drive for most of their shift. Workplace 2 was a manufacturing company where most of the employees’ (n = 30) occupational tasks were completed while standing. Use of time was assessed using the adult version of the Multimedia Activity Recall for Children and Adults (MARCA) administered by telephone interview. Three MARCA interviews were conducted with each participant, in order to capture a typical profile of a day-shift day, a night-shift day and a non-work day, using a two-day recall for each interview. Participants were asked to wear the activPAL3™ activity monitor, for 7 consecutive days. Paired and independent t-tests were used to compute significant differences between day-shift, night-shift and non-work days within and between workplaces. Results The total number of days quantified for the MARCA data was 192 days (64 day-shift, 60 night-shift and 68 non-work days). Workplace 2 participants reported more physical activity and less sedentary behaviour on day-shift and night shift days than on non-work days. Time spent in sedentary behaviour was similar on day-shift, night-shift and non-work days in Workplace 1. Workplace 1 participants were more sedentary (p = 0.003) and engaged in more light intensity PA (p = 0.031) on day-shift and night-shift workdays, than those from Workplace 2. Sleep times were lowest on day-shift days. Conclusion As the occupational tasks for participants in Workplace 2 involved physical activities, the findings do not support the conventional view that shift workers are more sedentary than those who only work during the day. Rather occupational tasks appear to be a more important determinant of physical activity patterns both on work and non-work days than varying shift patterns

Fractional exhaled nitric oxide for the management of asthma in adults: Systematic review

The aim of this review was to evaluate the clinical effectiveness of fractional exhaled nitric oxide (FeNO) measured in a clinical setting for the management of asthma in adults. 13 electronic databases were searched and studies were selected against predefined inclusion criteria. Quality assessment was conducted using QUADAS-2. Class effect meta-analyses were performed. Six studies were included. Despite high levels of heterogeneity in multiple study characteristics, exploratory class effect meta-analyses were conducted. Four studies reported a wider definition of exacerbation rates (major or severe exacerbation) with a pooled rate ratio of 0.80 (95% CI 0.63–1.02). Two studies reported rates of severe exacerbations (requiring oral corticosteroid use) with a pooled rate ratio of 0.89 (95% CI 0.43–1.72). Inhaled corticosteroid use was reported by four studies, with a pooled standardised mean difference of −0.24 (95% CI −0.56–0.07). No statistically significant differences for health-related quality of life or asthma control were found. FeNO guided management showed no statistically significant benefit in terms of severe exacerbations or ICS use, but showed a statistically significant reduction in exacerbations of any severity. However, further research is warranted to clearly define which management protocols (including cut-off points) offer best efficacy and which patient groups would benefit the most