Effectiveness of adult community-based physical activity interventions with objective physical activity measurements and long-term follow-up: a systematic review and meta-analysis.

OBJECTIVE: To identify randomised controlled trials (RCTs) of physical activity (PA) interventions with objective PA outcomes in adults and to evaluate whether intervention effects were sustained beyond 12 months. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Seven databases (Medline, Embase, PsycINFO, Web of Science, Cochrane library, CINAHL (Cumulative Index of Nursing and Allied Health Literature) and ASSIA (Applied Social Sciences Index and Abstracts)) were searched from January 2000 until December 2019. ELIGIBILITY CRITERIA: RCTs reporting objective PA outcomes beyond 12 months with community-based participants aged ≥18 years were included; those where controls received active interventions, including advice to increase PA levels, were excluded. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers completed extraction of aggregate data and assessed risk of bias. Meta-analyses used random-effects models at different follow-up points. Primary outcomes were daily steps and weekly minutes of moderate-to-vigorous PA (MVPA). RESULTS: Of 33 282 records identified, nine studies (at generally low risk of bias) were included, five in meta-analyses with 12 months to 4 year follow-up. We observed 12 month increases for intervention vs control participants in steps/day (mean difference (MD)=554 (95% CIs: 384 to 724) p<0.0001, I2=0%; 2446 participants; four studies) and weekly MVPA minutes (MD=35 (95% CI: 27 to 43) p<0.0001, I2=0%; 2647 participants; four studies). Effects were sustained up to 4 years for steps/day (MD=494 (95% CI: 251 to 738) p<0.0001, I2=0%; 1944 participants; four studies) and weekly MVPA minutes (MD=25 (95% CI: 13 to 37) p<0.0001, I2=0%; 1458 participants; three studies). CONCLUSIONS: There are few PA interventions with objective follow-up beyond 12 months, more studies are needed. However, this review provided evidence of PA intervention effects beyond 12 months and sustained up to 4 years for both steps/day and MVPA. These findings have important implications for potential long-term health benefits. PROSPERO REGISTRATION NUMBER: CRD42017075753

Phosphodiesterase-4 inhibitors for chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with cough, sputum production or dyspnoea, and a reduction in lung function, quality of life, and life expectancy. Apart from smoking cessation, no other treatments that slow lung function decline are available. Roflumilast and cilomilast are oral phosphodiesterase-4 (PDE₄) inhibitors proposed to reduce the airway inflammation and bronchoconstriction seen in COPD. This Cochrane Review was first published in 2011, and was updated in 2017 and 2020. OBJECTIVES: To evaluate the efficacy and safety of oral PDE₄ inhibitors for management of stable COPD. SEARCH METHODS: We identified randomised controlled trials (RCTs) from the Cochrane Airways Trials Register (date of last search 9 March 2020). We found other trials at web-based clinical trials registers. SELECTION CRITERIA: We included RCTs if they compared oral PDE₄ inhibitors with placebo in people with COPD. We allowed co-administration of standard COPD therapy. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Two independent review authors selected trials for inclusion, extracted data, and assessed risk of bias. We resolved discrepancies by involving a third review author. We assessed our confidence in the evidence by using GRADE recommendations. Primary outcomes were change in lung function (minimally important difference (MID) = 100 mL) and quality of life (scale 0 to 100; higher score indicates more limitations). MAIN RESULTS: We found 42 RCTs that met the inclusion criteria and were included in the analyses for roflumilast (28 trials with 18,046 participants) or cilomilast (14 trials with 6457 participants) or tetomilast (1 trial with 84 participants), with a duration between six weeks and one year or longer. These trials included people across international study centres with moderate to very severe COPD (Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades II to IV), with mean age of 64 years. We judged risks of selection bias, performance bias, and attrition bias as low overall amongst the 39 published and unpublished trials. Lung function Treatment with a PDE₄ inhibitor was associated with a small, clinically insignificant improvement in forced expiratory volume in one second (FEV₁) over a mean of 40 weeks compared with placebo (mean difference (MD) 49.33 mL, 95% confidence interval (CI) 44.17 to 54.49; participants = 20,815; studies = 29; moderate-certainty evidence). Forced vital capacity (FVC) and peak expiratory flow (PEF) were also improved over 40 weeks (FVC: MD 86.98 mL, 95% CI 74.65 to 99.31; participants = 22,108; studies = 17; high-certainty evidence; PEF: MD 6.54 L/min, 95% CI 3.95 to 9.13; participants = 4245; studies = 6; low-certainty evidence). Quality of life Trials reported improvements in quality of life over a mean of 33 weeks (St George's Respiratory Questionnaire (SGRQ) MD -1.06 units, 95% CI -1.68 to -0.43; participants = 7645 ; moderate-certainty evidence). Incidence of exacerbations Treatment with a PDE₄ inhibitor was associated with a reduced likelihood of COPD exacerbation over a mean of 40 weeks (odds ratio (OR) 0.78, 95% CI 0.73 to 0.84; participants = 20,382; studies = 27; high-certainty evidence), that is, for every 100 people treated with PDE₄ inhibitors, five more remained exacerbation-free during the study period compared with those given placebo (number needed to treat for an additional beneficial outcome (NNTB) 20, 95% CI 16 to 27). No change in COPD-related symptoms nor in exercise tolerance was found. Adverse events More participants in the treatment groups experienced an adverse effect compared with control participants over a mean of 39 weeks (OR 1.30, 95% CI 1.22 to 1.38; participants = 21,310; studies = 30; low-certainty evidence). Participants experienced a range of gastrointestinal symptoms such as diarrhoea, nausea, vomiting, or dyspepsia. Diarrhoea was more commonly reported with PDE₄ inhibitor treatment (OR 3.20, 95% CI 2.74 to 3.50; participants = 20,623; studies = 29; high-certainty evidence), that is, for every 100 people treated with PDE₄ inhibitors, seven more suffered from diarrhoea during the study period compared with those given placebo (number needed to treat for an additional harmful outcome (NNTH) 15, 95% CI 13 to 17). The likelihood of psychiatric adverse events was higher with roflumilast 500 µg than with placebo (OR 2.13, 95% CI 1.79 to 2.54; participants = 11,168; studies = 15 (COPD pool data); moderate-certainty evidence). Roflumilast in particular was associated with weight loss during the trial period and with an increase in insomnia and depressive mood symptoms. Participants treated with PDE₄ inhibitors were more likely to withdraw from trial participation; on average, 14% in the treatment groups withdrew compared with 8% in the control groups. Mortality No effect on mortality was found (OR 0.98, 95% CI 0.77 to 1.24; participants = 19,786; studies = 27; moderate-certainty evidence), although mortality was a rare event during these trials. AUTHORS' CONCLUSIONS: For this current update, five new studies from the 2020 search contributed to existing findings but made little impact on outcomes described in earlier versions of this review. PDE₄ inhibitors offered a small benefit over placebo in improving lung function and reducing the likelihood of exacerbations in people with COPD; however, they had little impact on quality of life or on symptoms. Gastrointestinal adverse effects and weight loss were common, and the likelihood of psychiatric symptoms was higher, with roflumilast 500 µg. The findings of this review provide cautious support for the use of PDE₄ inhibitors in COPD. In accordance with GOLD 2020 guidelines, they may have a place as add-on therapy for a subgroup of people with persistent symptoms or exacerbations despite optimal COPD management (e.g. people whose condition is not controlled by fixed-dose long-acting beta₂-agonist (LABA) and inhaled corticosteroid (ICS) combinations). More longer-term trials are needed to determine whether or not PDE₄ inhibitors modify FEV₁ decline, hospitalisation, or mortality in COPD

Orbital dynamics of "smart dust" devices with solar radiation pressure and drag

This paper investigates how perturbations due to asymmetric solar radiation pressure, in the presence of Earth shadow, and atmospheric drag can be balanced to obtain long-lived Earth centred orbits for swarms of micro-scale 'smart dust' devices, without the use of active control. The secular variation of Keplerian elements is expressed analytically through an averaging technique. Families of solutions are then identified where Sun-synchronous apse-line precession is achieved passively to maintain asymmetric solar radiation pressure. The long-term orbit evolution is characterized by librational motion, progressively decaying due to the non-conservative effect of atmospheric drag. Long-lived orbits can then be designed through the interaction of energy gain from asymmetric solar radiation pressure and energy dissipation due to drag. In this way, the usual short drag lifetime of such high area-to-mass spacecraft can be greatly extended (and indeed selected). In addition, the effect of atmospheric drag can be exploited to ensure the rapid end-of-life decay of such devices, thus preventing long-lived orbit debris

Quantum Eavesdropping without Interception: An Attack Exploiting the Dead Time of Single Photon Detectors

The security of quantum key distribution (QKD) can easily be obscured if the eavesdropper can utilize technical imperfections of the actual implementation. Here we describe and experimentally demonstrate a very simple but highly effective attack which even does not need to intercept the quantum channel at all. Only by exploiting the dead time effect of single photon detectors the eavesdropper is able to gain (asymptotically) full information about the generated keys without being detected by state-of-the-art QKD protocols. In our experiment, the eavesdropper inferred up to 98.8% of the key correctly, without increasing the bit error rate between Alice and Bob significantly. Yet, we find an evenly simple and effective countermeasure to inhibit this and similar attacks

Prevalence and clinical implications of respiratory viruses in stable chronic obstructive pulmonary disease (COPD) and exacerbations: a systematic review and meta-analysis protocol.

INTRODUCTION: Both stable chronic obstructive pulmonary disease (COPD) and acute exacerbations represent leading causes of death, disability and healthcare expenditure. They are complex, heterogeneous and their mechanisms are poorly understood. The role of respiratory viruses has been studied extensively but is still not adequately addressed clinically. Through a rigorous evidence update, we aim to define the prevalence and clinical burden of the different respiratory viruses in stable COPD and exacerbations, and to investigate whether viral load of usual respiratory viruses could be used for diagnosis of exacerbations triggered by viruses, which are currently not diagnosed or treated aetiologically. METHODS AND ANALYSIS: Based on a prospectively registered protocol, we will systematically review the literature using standard methods recommended by the Cochrane Collaboration and the Grading of Recommendations Assessment, Development and Evaluation working group. We will search Medline/PubMed, Excerpta Medica dataBASE (EMBASE), the Cochrane Library, the WHO's Clinical Trials Registry and the proceedings of relevant international conferences on 2 March 2020. We will evaluate: (A) the prevalence of respiratory viruses in stable COPD and exacerbations, (B) differences in the viral loads of respiratory viruses in stable COPD vs exacerbations, to explore whether the viral load of prevalent respiratory viruses could be used as a diagnostic biomarker for exacerbations triggered by viruses and (C) the association between the presence of respiratory viruses and clinical outcomes in stable COPD and in exacerbations. ETHICS AND DISSEMINATION: Ethics approval is not required since no primary data will be collected. Our findings will be presented in national and international scientific conferences and will be published in peer reviewed journals. Respiratory viruses currently represent a lost opportunity to improve the outcomes of both stable COPD and exacerbations. Our work aspires to 'demystify' the prevalence and clinical burden of viruses in stable COPD and exacerbations and to promote clinical and translational research. PROSPERO REGISTRATION NUMBER: CRD42019147658

Writing in the Disciplines: How Math Fits Into the Equation [post-print]

© 2018 International Literacy Association Writing is an important mode of thinking and learning for elementary students. Consistent efforts have been made to encourage discipline-specific writing, yet defining qualities of elementary mathematical writing have historically been underdeveloped. This article offers educators a new framework that conceptualizes mathematical writing as writing to reason and to communicate mathematically. Specifically, the framework defines four types of elementary mathematical writing: exploratory, informative/explanatory, argumentative, and mathematically creative. The authors explain and explore these types and their associated purposes through classroom vignettes. Informed by existing practices in mathematics and writing, strategies are offered to support teachers in the implementation of mathematical writing

A comparative analysis of predictive models of morbidity in intensive care unit after cardiac surgery – Part II: an illustrative example

<p>Abstract</p> <p>Background</p> <p>Popular predictive models for estimating morbidity probability after heart surgery are compared critically in a unitary framework. The study is divided into two parts. In the first part modelling techniques and intrinsic strengths and weaknesses of different approaches were discussed from a theoretical point of view. In this second part the performances of the same models are evaluated in an illustrative example.</p> <p>Methods</p> <p>Eight models were developed: Bayes linear and quadratic models, <it>k</it>-nearest neighbour model, logistic regression model, Higgins and direct scoring systems and two feed-forward artificial neural networks with one and two layers. Cardiovascular, respiratory, neurological, renal, infectious and hemorrhagic complications were defined as morbidity. Training and testing sets each of 545 cases were used. The optimal set of predictors was chosen among a collection of 78 preoperative, intraoperative and postoperative variables by a stepwise procedure. Discrimination and calibration were evaluated by the area under the receiver operating characteristic curve and Hosmer-Lemeshow goodness-of-fit test, respectively.</p> <p>Results</p> <p>Scoring systems and the logistic regression model required the largest set of predictors, while Bayesian and <it>k</it>-nearest neighbour models were much more parsimonious. In testing data, all models showed acceptable discrimination capacities, however the Bayes quadratic model, using only three predictors, provided the best performance. All models showed satisfactory generalization ability: again the Bayes quadratic model exhibited the best generalization, while artificial neural networks and scoring systems gave the worst results. Finally, poor calibration was obtained when using scoring systems, <it>k</it>-nearest neighbour model and artificial neural networks, while Bayes (after recalibration) and logistic regression models gave adequate results.</p> <p>Conclusion</p> <p>Although all the predictive models showed acceptable discrimination performance in the example considered, the Bayes and logistic regression models seemed better than the others, because they also had good generalization and calibration. The Bayes quadratic model seemed to be a convincing alternative to the much more usual Bayes linear and logistic regression models. It showed its capacity to identify a minimum core of predictors generally recognized as essential to pragmatically evaluate the risk of developing morbidity after heart surgery.</p

The Difference in Pharmacists’ Interventions across the Diverse Settings in a Children’s Hospital

Aims: This study aimed to document and compare the nature of clinical pharmacists’ interventions made in different practice settings within a children’s hospital. Methods: The primary investigator observed and documented all clinical interventions performed by clinical pharmacists for between 35–37 days on each of the five study wards from the three practice settings, namely general medical, general surgical and hematology-oncology. The rates, types and significance of the pharmacists’ interventions in the different settings were compared.Results: A total of 982 interventions were documented, related to the 16,700 medication orders reviewed on the five wards in the three practice settings over the duration of the study. Taking medication histories and/or patient counselling were the most common pharmacists’ interventions in the general settings; constituting more than half of all interventions. On the Hematology-Oncology Ward the pattern was different with drug therapy changes being the most common interventions (n = 73/195, 37.4% of all interventions). Active interventions (pharmacists’ activities leading to a change in drug therapy) constituted less than a quarter of all interventions on the general medical and surgical wards compared to nearly half on thespecialty Hematology-Oncology Ward. The majority (n = 37/42, 88.1%) of a random sample of the active interventions reviewed were rated as clinically significant. Dose adjustment was the most frequent active interventions in the general settings, whilst drug addition constituted the most common active interventions on the Hematology-Oncology Ward. The degree of acceptance of pharmacists’ active interventions by prescribers was high (n = 223/244, 91.4%).Conclusions: The rate of pharmacists’ active interventions differed across different practice settings, being most frequent in the specialty hematology-oncology setting. The nature and type of the interventions documented in the hematologyoncology were also different compared to those in the general medical and surgical settings

Using a computerized provider order entry system to meet the unique prescribing needs of children: description of an advanced dosing model

<p>Abstract</p> <p>Background</p> <p>It is well known that the information requirements necessary to safely treat children with therapeutic medications cannot be met with the same approaches used in adults. Over a 1-year period, Duke University Hospital engaged in the challenging task of enhancing an established computerized provider order entry (CPOE) system to address the unique medication dosing needs of pediatric patients.</p> <p>Methods</p> <p>An advanced dosing model (ADM) was designed to interact with our existing CPOE application to provide decision support enabling complex pediatric dose calculations based on chronological age, gestational age, weight, care area in the hospital, indication, and level of renal impairment. Given that weight is a critical component of medication dosing that may change over time, alerting logic was added to guard against erroneous entry or outdated weight information.</p> <p>Results</p> <p>Pediatric CPOE was deployed in a staggered fashion across 6 care areas over a 14-month period. Safeguards to prevent miskeyed values became important in allowing providers the flexibility to override the ADM logic if desired. Methods to guard against over- and under-dosing were added. The modular nature of our model allows us to easily add new dosing scenarios for specialized populations as the pediatric population and formulary change over time.</p> <p>Conclusions</p> <p>The medical needs of pediatric patients vary greatly from those of adults, and the information systems that support those needs require tailored approaches to design and implementation. When a single CPOE system is used for both adults and pediatrics, safeguards such as redirection and suppression must be used to protect children from inappropriate adult medication dosing content. Unlike other pediatric dosing systems, our model provides active dosing assistance and dosing process management, not just static dosing advice.</p