Summary
Objective
Family‐based interventions represent a potentially valuable route to increasing child physical activity (PA) in children. A dual meta‐analysis and realist synthesis approach ...examined existing interventions to assist those developing programmes to encourage uptake and maintenance of PA in children.
Design
Studies were screened for inclusion based on including participants aged 5–12 years, having a substantive aim of increasing PA by engaging the family and reporting on PA outcome. Duplicate data extraction and quality assessment were conducted. Meta‐analysis was conducted in STATA. Realist synthesis included theory development and evidence mapping.
Results
Forty‐seven studies were included, of which three received a ‘strong’ quality rating, 21 ‘moderate’ and 23 ‘weak’. The meta‐analysis (19 studies) demonstrated a significant small effect in favour of the experimental group (standardized mean difference: 0.41; 95%CI 0.15–0.67). Sensitivity analysis, removing one outlier, reduced this to 0.29 (95%CI 0.14–0.45). Realist synthesis (28 studies) provided insight into intervention context (particularly, family constraints, ethnicity and parental motivation), and strategies to change PA (notably, goal‐setting and reinforcement combined).
Conclusion
This review provides key recommendations to inform policy makers and other practitioners in developing evidence‐based interventions aimed at engaging the family to increase PA in children, and identifies avenues for future research.
We report the discovery of ASASSN-15lh (SN 2015L), which we interpret as the most luminous supernova yet found. At redshift z = 0.2326, ASASSN-15lh reached an absolute magnitude of Mu,AB = −23.5 ± ...0.1 and bolometric luminosity Lbol = (2.2 ± 0.2) × 10⁴⁵ ergs s⁻¹, which is more than twice as luminous as any previously known supernova. It has several major features characteristic of the hydrogen-poor super-luminous supernovae (SLSNe-l), whose energy sources and progenitors are currently poorly understood. In contrast to most previously known SLSNe-l that reside in star-forming dwarf galaxies, ASASSN-15lh appears to be hosted by a luminous galaxy (MK ≈ −25.5) with little star formation. In the 4 months since first detection, ASASSN-15lh radiated (1.1 ± 0.2) × 10⁵² ergs, challenging the magnetar model for its engine.
Liraglutide and Renal Outcomes in Type 2 Diabetes Mann, Johannes F E; Ørsted, David D; Brown-Frandsen, Kirstine ...
New England journal of medicine/The New England journal of medicine,
08/2017, Letnik:
377, Številka:
9
Journal Article
Recenzirano
Odprti dostop
In a randomized, controlled trial that compared liraglutide, a glucagon-like peptide 1 analogue, with placebo in patients with type 2 diabetes and high cardiovascular risk who were receiving usual ...care, we found that liraglutide resulted in lower risks of the primary end point (nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes) and death. However, the long-term effects of liraglutide on renal outcomes in patients with type 2 diabetes are unknown.
We report the prespecified secondary renal outcomes of that randomized, controlled trial in which patients were assigned to receive liraglutide or placebo. The secondary renal outcome was a composite of new-onset persistent macroalbuminuria, persistent doubling of the serum creatinine level, end-stage renal disease, or death due to renal disease. The risk of renal outcomes was determined with the use of time-to-event analyses with an intention-to-treat approach. Changes in the estimated glomerular filtration rate and albuminuria were also analyzed.
A total of 9340 patients underwent randomization, and the median follow-up of the patients was 3.84 years. The renal outcome occurred in fewer participants in the liraglutide group than in the placebo group (268 of 4668 patients vs. 337 of 4672; hazard ratio, 0.78; 95% confidence interval CI, 0.67 to 0.92; P=0.003). This result was driven primarily by the new onset of persistent macroalbuminuria, which occurred in fewer participants in the liraglutide group than in the placebo group (161 vs. 215 patients; hazard ratio, 0.74; 95% CI, 0.60 to 0.91; P=0.004). The rates of renal adverse events were similar in the liraglutide group and the placebo group (15.1 events and 16.5 events per 1000 patient-years), including the rate of acute kidney injury (7.1 and 6.2 events per 1000 patient-years, respectively).
This prespecified secondary analysis shows that, when added to usual care, liraglutide resulted in lower rates of the development and progression of diabetic kidney disease than placebo. (Funded by Novo Nordisk and the National Institutes of Health; LEADER ClinicalTrials.gov number, NCT01179048 .).
The performance of tracheotomy is a common procedural request by critical care departments to the surgical services of general surgery, thoracic surgery and otolaryngology - head & neck surgery. A ...Canadian Society of Otolaryngology - Head & Neck Surgery (CSO-HNS) task force was convened with multi-specialty involvement from otolaryngology-head & neck surgery, general surgery, critical care and anesthesiology to develop a set of recommendations for the performance of tracheotomies during the COVID-19 pandemic.
The tracheotomy procedure is highly aerosol generating and directly exposes the entire surgical team to the viral aerosol plume and secretions, thereby increasing the risk of transmission to healthcare providers. As such, we believe extended endotracheal intubation should be the standard of care for the entire duration of ventilation in the vast majority of patients. Pre-operative COVID-19 testing is highly recommended for any non-emergent procedure.
The set of recommendations in this document highlight the importance of avoiding tracheotomy procedures in patients who are COVID-19 positive if at all possible. Recommendations for appropriate PPE and environment are made for COVID-19 positive, negative and unknown patients requiring consideration of tracheotomy. The safety of healthcare professionals who care for ill patients and who keep critical infrastructure operating is paramount.
The next-generation cystic fibrosis transmembrane conductance regulator (CFTR) corrector VX-659, in triple combination with tezacaftor and ivacaftor (VX-659-tezacaftor-ivacaftor), was developed to ...restore the function of Phe508del CFTR protein in patients with cystic fibrosis.
We evaluated the effects of VX-659-tezacaftor-ivacaftor on the processing, trafficking, and function of Phe508del CFTR protein using human bronchial epithelial cells. A range of oral VX-659-tezacaftor-ivacaftor doses in triple combination were then evaluated in randomized, controlled, double-blind, multicenter trials involving patients with cystic fibrosis who were heterozygous for the Phe508del CFTR mutation and a minimal-function CFTR mutation (Phe508del-MF genotypes) or homozygous for the Phe508del CFTR mutation (Phe508del-Phe508del genotype). The primary end points were safety and the absolute change from baseline in the percentage of predicted forced expiratory volume in 1 second (FEV
).
VX-659-tezacaftor-ivacaftor significantly improved the processing and trafficking of Phe508del CFTR protein as well as chloride transport in vitro. In patients, VX-659-tezacaftor-ivacaftor had an acceptable safety and side-effect profile. Most adverse events were mild or moderate. VX-659-tezacaftor-ivacaftor resulted in significant mean increases in the percentage of predicted FEV
through day 29 (P<0.001) of up to 13.3 points in patients with Phe508del-MF genotypes; in patients with the Phe508del-Phe508del genotype already receiving tezacaftor-ivacaftor, adding VX-659 resulted in a further 9.7-point increase in the percentage of predicted FEV
. The sweat chloride concentrations and scores on the respiratory domain of the Cystic Fibrosis Questionnaire-Revised improved in both patient populations.
Robust in vitro activity of VX-659-tezacaftor-ivacaftor targeting Phe508del CFTR protein translated into improvements for patients with Phe508del-MF or Phe508del-Phe508del genotypes. VX-659 triple-combination regimens have the potential to treat the underlying cause of disease in approximately 90% of patients with cystic fibrosis. (Funded by Vertex Pharmaceuticals; VX16-659-101 and VX16-659-001 ClinicalTrials.gov numbers, NCT03224351 and NCT03029455 .).
Gambiense human African trypanosomiasis (gHAT) is a virulent disease declining in burden but still endemic in West and Central Africa. Although it is targeted for elimination of transmission by 2030, ...there remain numerous questions about the drivers of infection and how these vary geographically. In this study we focus on the Democratic Republic of Congo (DRC), which accounted for 84% of the global case burden in 2016, to explore changes in transmission across the country and elucidate factors which may have contributed to the persistence of disease or success of interventions in different regions. We present a Bayesian fitting methodology, applied to 168 endemic health zones (∼100,000 population size), which allows for calibration of a mechanistic gHAT model to case data (from the World Health Organization HAT Atlas) in an adaptive and automated framework. It was found that the model needed to capture improvements in passive detection to match observed trends in the data within former Bandundu and Bas Congo provinces indicating these regions have substantially reduced time to detection. Health zones in these provinces generally had longer burn-in periods during fitting due to additional model parameters. Posterior probability distributions were found for a range of fitted parameters in each health zone; these included the basic reproduction number estimates for pre-1998 (R0) which was inferred to be between 1 and 1.14, in line with previous gHAT estimates, with higher median values typically in health zones with more case reporting in the 2000s. Previously, it was not clear whether a fall in active case finding in the period contributed to the declining case numbers. The modelling here accounts for variable screening and suggests that underlying transmission has also reduced greatly-on average 96% in former Equateur, 93% in former Bas Congo and 89% in former Bandundu-Equateur and Bandundu having had the highest case burdens in 2000. This analysis also sets out a framework to enable future predictions for the country.
Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes Marso, Steven P; Daniels, Gilbert H; Brown-Frandsen, Kirstine ...
New England journal of medicine/The New England journal of medicine,
07/2016, Letnik:
375, Številka:
4
Journal Article
Recenzirano
Odprti dostop
The cardiovascular effect of liraglutide, a glucagon-like peptide 1 analogue, when added to standard care in patients with type 2 diabetes, remains unknown.
In this double-blind trial, we randomly ...assigned patients with type 2 diabetes and high cardiovascular risk to receive liraglutide or placebo. The primary composite outcome in the time-to-event analysis was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The primary hypothesis was that liraglutide would be noninferior to placebo with regard to the primary outcome, with a margin of 1.30 for the upper boundary of the 95% confidence interval of the hazard ratio. No adjustments for multiplicity were performed for the prespecified exploratory outcomes.
A total of 9340 patients underwent randomization. The median follow-up was 3.8 years. The primary outcome occurred in significantly fewer patients in the liraglutide group (608 of 4668 patients 13.0%) than in the placebo group (694 of 4672 14.9%) (hazard ratio, 0.87; 95% confidence interval CI, 0.78 to 0.97; P<0.001 for noninferiority; P=0.01 for superiority). Fewer patients died from cardiovascular causes in the liraglutide group (219 patients 4.7%) than in the placebo group (278 6.0%) (hazard ratio, 0.78; 95% CI, 0.66 to 0.93; P=0.007). The rate of death from any cause was lower in the liraglutide group (381 patients 8.2%) than in the placebo group (447 9.6%) (hazard ratio, 0.85; 95% CI, 0.74 to 0.97; P=0.02). The rates of nonfatal myocardial infarction, nonfatal stroke, and hospitalization for heart failure were nonsignificantly lower in the liraglutide group than in the placebo group. The most common adverse events leading to the discontinuation of liraglutide were gastrointestinal events. The incidence of pancreatitis was nonsignificantly lower in the liraglutide group than in the placebo group.
In the time-to-event analysis, the rate of the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke among patients with type 2 diabetes mellitus was lower with liraglutide than with placebo. (Funded by Novo Nordisk and the National Institutes of Health; LEADER ClinicalTrials.gov number, NCT01179048.).
Gambiense human African trypanosomiasis (sleeping sickness, gHAT) is a disease targeted for elimination of transmission by 2030. While annual new cases are at a historical minimum, the likelihood of ...achieving the target is unknown. We utilised modelling to study the impacts of four strategies using currently available interventions, including active and passive screening and vector control, on disease burden and transmission across 168 endemic health zones in the Democratic Republic of the Congo. Median projected years of elimination of transmission show only 98 health zones are on track despite significant reduction in disease burden under medical-only strategies (64 health zones if > 90% certainty required). Blanket coverage with vector control is impractical, but is predicted to reach the target in all heath zones. Utilising projected disease burden under the uniform medical-only strategy, we provide a priority list of health zones for consideration for supplementary vector control alongside medical interventions.
The Ultraviolet/Optical Telescope (UVOT) is one of three instruments onboard the Swift observatory. The photometric calibration has been published, and this paper follows up with details on other ...aspects of the calibration including a measurement of the point spread function with an assessment of the orbital variation and the effect on photometry. A correction for large-scale variations in sensitivity over the field of view is described, as well as a model of the coincidence loss which is used to assess the coincidence correction in extended regions. We have provided a correction for the detector distortion and measured the resulting internal astrometric accuracy of the UVOT, also giving the absolute accuracy with respect to the International Celestial Reference System. We have compiled statistics on the background count rates, and discuss the sources of the background, including instrumental scattered light. In each case, we describe any impact on UVOT measurements, whether any correction is applied in the standard pipeline data processing or whether further steps are recommended.
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