Whether a healthy lifestyle impacts longevity in the presence of multimorbidity is unclear. We investigated the associations between healthy lifestyle and life expectancy in people with and without ...multimorbidity.
A total of 480,940 middle-aged adults (median age of 58 years range 38-73, 46% male, 95% white) were analysed in the UK Biobank; this longitudinal study collected data between 2006 and 2010, and participants were followed up until 2016. We extracted 36 chronic conditions and defined multimorbidity as 2 or more conditions. Four lifestyle factors, based on national guidelines, were used: leisure-time physical activity, smoking, diet, and alcohol consumption. A combined weighted score was developed and grouped participants into 4 categories: very unhealthy, unhealthy, healthy, and very healthy. Survival models were applied to predict life expectancy, adjusting for ethnicity, working status, deprivation, body mass index, and sedentary time. A total of 93,746 (19.5%) participants had multimorbidity. During a mean follow-up of 7 (range 2-9) years, 11,006 deaths occurred. At 45 years, in men with multimorbidity an unhealthy score was associated with a gain of 1.5 (95% confidence interval CI -0.3 to 3.3; P = 0.102) additional life years compared to very unhealthy score, though the association was not significant, whilst a healthy score was significantly associated with a gain of 4.5 (3.3 to 5.7; P < 0.001) life years and a very healthy score with 6.3 (5.0 to 7.7; P < 0.001) years. Corresponding estimates in women were 3.5 (95% CI 0.7 to 6.3; P = 0.016), 6.4 (4.8 to 7.9; P < 0.001), and 7.6 (6.0 to 9.2; P < 0.001) years. Results were consistent in those without multimorbidity and in several sensitivity analyses. For individual lifestyle factors, no current smoking was associated with the largest survival benefit. The main limitations were that we could not explore the consistency of our results using a more restrictive definition of multimorbidity including only cardiometabolic conditions, and participants were not representative of the UK as a whole.
In this analysis of data from the UK Biobank, we found that regardless of the presence of multimorbidity, engaging in a healthier lifestyle was associated with up to 6.3 years longer life for men and 7.6 years for women; however, not all lifestyle risk factors equally correlated with life expectancy, with smoking being significantly worse than others.
Microneedle-based microdevices promise to expand the scope for delivery of vaccines and therapeutic agents through the skin and withdrawing biofluids for point-of-care diagnostics – so-called ...theranostics. Unskilled and painless applications of microneedle patches for blood collection or drug delivery are two of the advantages of microneedle arrays over hypodermic needles. Developing the necessary microneedle fabrication processes has the potential to dramatically impact the health care delivery system by changing the landscape of fluid sampling and subcutaneous drug delivery. Microneedle designs which range from sub-micron to millimetre feature sizes are fabricated using the tools of the microelectronics industry from metals, silicon, and polymers. Various types of subtractive and additive manufacturing processes have been used to manufacture microneedles, but the development of microneedle-based systems using conventional subtractive methods has been constrained by the limitations and high cost of microfabrication technology. Additive manufacturing processes such as 3D printing and two-photon polymerization fabrication are promising transformative technologies developed in recent years. The present article provides an overview of microneedle systems applications, designs, material selection, and manufacturing methods.
The American Diabetes Association and the European Association for the Study of Diabetes convened a panel to update the previous consensus statements on the management of hyperglycemia in type 2 ...diabetes in adults, published since 2006 and last updated in 2019. The target audience is the full spectrum of the professional health care team providing diabetes care in the U.S. and Europe. A systematic examination of publications since 2018 informed new recommendations. These include additional focus on social determinants of health, the health care system, and physical activity behaviors, including sleep. There is a greater emphasis on weight management as part of the holistic approach to diabetes management. The results of cardiovascular and kidney outcomes trials involving sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists, including assessment of subgroups, inform broader recommendations for cardiorenal protection in people with diabetes at high risk of cardiorenal disease. After a summary listing of consensus recommendations, practical tips for implementation are provided.
Abstract
We introduce ProFound, a source finding and image analysis package. ProFound provides methods to detect sources in noisy images, generate segmentation maps identifying the pixels belonging ...to each source, and measure statistics like flux, size, and ellipticity. These inputs are key requirements of ProFit, our recently released galaxy profiling package, where the design aim is that these two software packages will be used in unison to semi-automatically profile large samples of galaxies. The key novel feature introduced in ProFound is that all photometry is executed on dilated segmentation maps that fully contain the identifiable flux, rather than using more traditional circular or ellipse-based photometry. Also, to be less sensitive to pathological segmentation issues, the de-blending is made across saddle points in flux. We apply ProFound in a number of simulated and real-world cases, and demonstrate that it behaves reasonably given its stated design goals. In particular, it offers good initial parameter estimation for ProFit, and also segmentation maps that follow the sometimes complex geometry of resolved sources, whilst capturing nearly all of the flux. A number of bulge–disc decomposition projects are already making use of the ProFound and ProFit pipeline, and adoption is being encouraged by publicly releasing the software for the open source r data analysis platform under an LGPL-3 license on GitHub (github.com/asgr/ProFound).
Vitamin D is a particularly important sterol hormone, with evidence emerging of its beneficial effects well beyond bone. In consequence of this and increased global recognition of vitamin D ...deficiency in the general population, there has been a resurgence in treatment with vitamin D preparations. However, the increasing use of vitamin D treatments has also seen a substantial increase in the number of reports of vitamin D intoxication, with the majority (75%) of reports published since 2010. Many of these cases are a consequence of inappropriate prescribing, and the use of high‐dose over‐the‐counter preparations or unlicensed preparations. This review highlights that the majority of cases were preventable and discusses the inappropriate use of poorly formulated, and unlicensed vitamin D preparations.
Aims
To compare efficacy and safety of glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) in people with type 2 diabetes.
Materials and methods
We electronically searched, up to June 3, 2016, ...published randomized clinical trials lasting between 24 and 32 weeks that compared a GLP‐1RA (albiglutide, dulaglutide, twice‐daily exenatide and once‐weekly exenatide, liraglutide, lixisenatide, semaglutide and taspoglutide) with placebo or another GLP‐1RA. Data on cardiometabolic and safety outcomes were analysed using a mixed‐treatment comparison meta‐analysis.
Results
A total of 34 trials (14 464 participants) met the inclusion criteria; no published data for semaglutide were available. Compared with placebo, all GLP‐1RAs reduced glycated haemoglobin (HbA1c) and fasting plasma glucose (FPG) levels (reductions ranged from −0.55% and −0.73 mmol/L, respectively, for lixisenatide to −1.21% and −1.97 mmol/L, respectively, for dulaglutide). There were no differences within short‐acting (twice‐daily exenatide and lixisenatide) or long‐acting (albiglutide, dulaglutide, once‐weekly exenatide, liraglutide and taspoglutide) groups. Compared with twice‐daily exenatide, dulaglutide treatment was associated with the greatest HbA1c and FPG reduction (0.51% and 1.04 mmol/L, respectively), followed by liraglutide (0.45% and 0.93 mmol/L, respectively) and once‐weekly exenatide (0.38% and 0.85 mmol/L, respectively); similar reductions were found when these 3 agents were compared with lixisenatide. Compared with placebo, all GLP‐1RAs except albiglutide reduced weight and increased the risk of hypoglycaemia and gastrointestinal side effects, and all agents except dulaglutide and taspoglutide reduced systolic blood pressure. When all GLP‐1RAs were compared with each other, no clinically meaningful differences were observed in weight loss, blood pressure reduction or hypoglycaemia risk. Albiglutide had the lowest risk of nausea and diarrhoea and once‐weekly exenatide the lowest risk of vomiting.
Conclusions
The RCTs in the present analysis show that all GLP‐1RAs improve glycaemic control, reduce body weight and increase the risk of adverse gastrointestinal symptoms compared with placebo. Although there were no differences when short‐acting agents were compared with each other or when long‐acting agents were compared with each other, dulaglutide, liraglutide and once‐weekly exenatide were superior to twice‐daily exenatide and lixisenatide at lowering HbA1c and FPG levels. There were no differences in hypoglycaemia between these 3 agents, whilst once‐weekly exenatide had the lowest risk of vomiting. These results, along with patient's preferences and individualized targets, should be considered when selecting a GLP‐1RA.
Transition zone slab deformation influences Earth's thermal, chemical, and tectonic evolution. However, the mechanisms responsible for the wide range of imaged slab morphologies remain debated. Here ...we use 2‐D thermo‐mechanical models with a mobile trench, an overriding plate, a temperature and stress‐dependent rheology, and a 10, 30, or 100‐fold increase in lower mantle viscosity, to investigate the effect of initial subducting and overriding‐plate ages on slab‐transition zone interaction. Four subduction styles emerge: (i) a “vertical folding” mode, with a quasi‐stationary trench, near‐vertical subduction, and buckling/folding at depth (VF); (ii) slabs that induce mild trench retreat, which are flattened/“horizontally deflected” and stagnate at the upper‐lower mantle interface (HD); (iii) inclined slabs, which result from rapid sinking and strong trench retreat (ISR); (iv) a two‐stage mode, displaying backward‐bent and subsequently inclined slabs, with late trench retreat (BIR). Transitions from regime (i) to (iii) occur with increasing subducting plate age (i.e., buoyancy and strength). Regime (iv) develops for old (strong) subducting and overriding plates. We find that the interplay between trench motion and slab deformation at depth dictates the subduction style, both being controlled by slab strength, which is consistent with predictions from previous compositional subduction models. However, due to feedbacks between deformation, sinking rate, temperature, and slab strength, the subducting plate buoyancy, overriding plate strength, and upper‐lower mantle viscosity jump are also important controls in thermo‐mechanical subduction. For intermediate upper‐lower mantle viscosity jumps (×30), our regimes reproduce the diverse range of seismically imaged slab morphologies.
Key Points
Varying initial plate ages (20–100 Myr) gives four distinct subduction modes
Evolving slab strength exerts key control on trench motion and slab deformation
For a ×30 viscosity jump slab morphologies encompass the imaged range
Diabetic peripheral neuropathy (DPN) is a common complication of both type 1 and 2 diabetes. It is a leading cause of lower-limb amputation and disabling neuropathic pain. Amputations in patients ...with diabetes have a devastating effect on quality of life and are associated with an alarmingly low life expectancy (on average only 2 years from the amputation). Amputation also places a substantial financial burden on health-care systems and society in general. With the introduction of national diabetes eye screening programmes, the prevalence of blindness in working-age adults is falling. This is not the case, however, with diabetes related amputations. In this Review, we appraise innovative point-of-care devices that enable the early diagnosis of DPN and assess the evidence for early risk factor-based management strategies to reduce the incidence and slow the progression of DPN. We also propose a framework for screening and early multifactorial interventions as the best prospect for preventing or halting DPN and its devastating sequelae.
To determine the effects of glucagon-like peptide-1 receptor agonists compared with placebo and other anti-diabetic agents on weight loss in overweight or obese patients with type 2 diabetes ...mellitus.
Electronic searches were conducted for randomised controlled trials that compared a glucagon-like peptide-1 receptor agonist therapy at a clinically relevant dose with a comparator treatment (other type 2 diabetes treatment or placebo) in adults with type 2 diabetes and a mean body mass index ≥ 25 kg/m2. Pair-wise meta-analyses and mixed treatment comparisons were conducted to examine the difference in weight change at six months between the glucagon-like peptide-1 receptor agonists and each comparator.
In the mixed treatment comparison (27 trials), the glucagon-like peptide-1 receptor agonists were the most successful in terms of weight loss; exenatide 2 mg/week: -1.62 kg (95% CrI: -2.95 kg, -0.30 kg), exenatide 20 μg: -1.37 kg (95% CI: -222 kg, -0.52 kg), liraglutide 1.2 mg: -1.01 kg (95%CrI: -2.41 kg, 0.38 kg) and liraglutide 1.8 mg: -1.51 kg (95% CI: -2.67 kg, -0.37 kg) compared with placebo. There were no differences between the GLP-1 receptor agonists in terms of weight loss.
This review provides evidence that glucagon-like peptide-1 receptor agonist therapies are associated with weight loss in overweight or obese patients with type 2 diabetes with no difference in weight loss seen between the different types of GLP-1 receptor agonists assessed.
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