Objective
To assess the efficacy of metformin in megestrol acetate (MA)‐based fertility‐sparing treatment for patients with atypical endometrial hyperplasia (AEH) and endometrioid endometrial cancer ...(EEC).
Design
A randomised, single‐centre, open‐label, controlled trial conducted between October 2013 and December 2017.
Setting
Shanghai OBGYN Hospital of Fudan University, China.
Population
A total of 150 patients (18–45 years old) with primary AEH or well‐differentiated EEC were randomised into an MA group (n = 74) and an MA plus metformin group (n = 76).
Methods
Patients with AEH or EEC were firstly stratified, then randomised to receive MA (160 mg orally, daily) or MA (160 mg orally, daily) plus metformin (500 mg orally, three times a day).
Main outcomes and measures
The primary efficacy parameter was the cumulate complete response (CR) rate within 16 weeks of treatment (16w‐CR rate); the secondary efficacy parameters were 30w‐CR rate and adverse events.
Results
The 16w‐CR rate was higher in the metformin plus MA group than in the MA‐only group (34.3 versus 20.7%, odds ratio OR 2.0, 95% confidence interval CI 0.89–4.51, P = 0.09) but the difference was more significant in 102 AEH patients (39.6 versus 20.4%, OR 2.56, 95% CI 1.06–6.21, P = 0.04). This effect of metformin was also significant in non‐obese (51.4 versus 24.3%, OR 3.28, 95% CI 1.22–8.84, P = 0.02) and insulin‐sensitive (54.8 versus 28.6%, OR 3.04, 95% CI 1.03–8.97, P = 0.04) subgroups of AEH women. No significant result was found in secondary endpoints.
Conclusion
As a fertility‐sparing treatment, metformin plus MA was associated with a higher early CR rate compared with MA alone in AEH patients.
Tweetable
For AEH patients, metformin plus MA might be a better fertility‐sparing treatment to achieve a higher early CR rate compared with MA alone.
Tweetable
For AEH patients, metformin plus MA might be a better fertility‐sparing treatment to achieve higher early CR rate compared with MA alone.
Boarding in the emergency department (ED) is a critical indicator of quality of care for hospitals. It is defined as the time between the admission decision and departure from the ED. As a result of ...boarding, patients stay in the ED until inpatient beds are available; moreover, boarding is associated with various adverse events.
The objective of our systematic review was to determine whether ED boarding (EDB) time is associated with in-hospital mortality (IHM).
A systematic search was conducted in academic databases to identify relevant studies. Medline, PubMed, Scopus, Embase, Cochrane, Web of Science, Cochrane, CINAHL and PsychInfo were searched. We included all peer-reviewed published studies from all previous years until November 2018. Studies performed in the ED and focused on the association between EDB and IHM as the primary objective were included. Extracted data included study characteristics, prognostic factors, outcomes, and IHM. A search update in PubMed was performed in May 2019 to ensure the inclusion of recent studies before publishing.
From the initial 4,321 references found through the systematic search, the manual screening of reference lists and the updated search in PubMed, a total of 12 studies were identified as eligible for a descriptive analysis. Overall, six studies found an association between EDB and IHM, while five studies showed no association. The last remaining study included both ICU and non-ICU subgroups and showed conflicting results, with a positive association for non-ICU patients but no association for ICU patients. Overall, a tendency toward an association between EDB and IHM using the pool random effect was observed.
Our systematic review did not find a strong evidence for the association between ED boarding and IHM but there is a tendency toward this association. Further well-controlled, international multicenter studies are needed to demonstrate whether this association exists and whether there is a specific EDB time cut-off that results in increased IHM.
In this paper, the existing multi-user detector technology (MUD) is analyzed and discussed, and the principle of the new technology is studied in detail. Based on the affine projection algorithm ...(APA), combining Rake receiver and blind multi-user detector, a blind multi-user detector that can be used in multi-path fading channel is designed. The simulation shows that APA fits well in convergence speed and computational burden. Moreover, the designed receiver has faster convergence speed and better tracking properties than LMS-based detector and lower computational cost than LS-based detector.
It has been reported that the miR-106b∼25 cluster, a paralog of the miR-17∼92 cluster, possesses oncogenic activities. However, the precise role of each microRNA (miRNA) in the miR-106b∼25 cluster is ...not yet known. In this study, we examined the function of miR-93, one of the microRNAs within the miR-106b∼25 cluster, in angiogenesis and tumor formation. We found that miR-93 enhanced cell survival, promoted sphere formation and augmented tumor growth. Most strikingly, when miR-93-overexpressing U87 cells were co-cultured with endothelial cells, they supported endothelial cell spreading, growth, migration and tube formation. In vivo studies revealed that miR-93-expressing cells induced blood vessel formation, allowing blood vessels to extend to tumor tissues in high densities. Angiogenesis promoted by miR-93 in return facilitated cell survival, resulting in enhanced tumor growth. We further showed that integrin-β8 is a target of miR-93. Higher levels of integrin-β8 are associated with cell death in tumor mass and in human glioblastoma. Silencing of integrin-β8 expression using small interfering RNA promoted cell proliferation, whereas ectopic expression of integrin-β8 decreased cell growth. These findings showed that miR-93 promotes tumor growth and angiogenesis by suppressing, at least in part, integrin-β8 expression. Our results suggest that inhibition of miR-93 function may be a feasible approach to suppress angiogenesis and tumor growth.
The fundamental processes that govern plasticity and determine strength in crystalline materials at small length scales have been studied for over fifty years. Recent studies of single-crystal ...metallic pillars with diameters of a few tens of micrometres or less have clearly demonstrated that the strengths of these pillars increase as their diameters decrease, leading to attempts to augment existing ideas about pronounced size effects with new models and simulations. Through in situ nanocompression experiments inside a transmission electron microscope we can directly observe the deformation of these pillar structures and correlate the measured stress values with discrete plastic events. Our experiments show that submicrometre nickel crystals microfabricated into pillar structures contain a high density of initial defects after processing but can be made dislocation free by applying purely mechanical stress. This phenomenon, termed 'mechanical annealing', leads to clear evidence of source-limited deformation where atypical hardening occurs through the progressive activation and exhaustion of dislocation sources.
Coronavirus disease 2019 (COVID‐19) continues to impact older adults disproportionately with respect to serious consequences ranging from severe illness and hospitalization to increased mortality ...risk. Concurrently, concerns about potential shortages of healthcare professionals and health supplies to address these issues have focused attention on how these resources are ultimately allocated and used. Some strategies, for example, misguidedly use age as an arbitrary criterion that disfavors older adults in resource allocation decisions. This is a companion article to the American Geriatrics Society (AGS) position statement, “Resource Allocation Strategies and Age‐Related Considerations in the COVID‐19 Era and Beyond.” It is intended to inform stakeholders including hospitals, health systems, and policymakers about ethical considerations that should be considered when developing strategies for allocation of scarce resources during an emergency involving older adults. This review presents the legal and ethical background for the position statement and discusses these issues that informed the development of the AGS positions: (1) age as a determining factor, (2) age as a tiebreaker, (3) criteria with a differential impact on older adults, (4) individual choices and advance directives, (5) racial/ethnic disparities and resource allocation, and (6) scoring systems and their impact on older adults. It also considers the role of advance directives as expressions of individual preferences in pandemics. J Am Geriatr Soc 68:1143–1149, 2020.
See related paper by Farrell et al.
We have investigated the rate sensitivity of flow stress and the extent of strengthening in polycrystalline copper containing different volume fractions of nano-sized twins, but having the same ...average grain size. The specimens were produced by pulsed electrodeposition, wherein the concentration of twins was varied systematically by varying the processing parameters. Depth-sensing instrumented indentation experiments performed at loading rates spanning three orders of magnitude on specimens with the higher density of twins (twin lamellae width ∼20
nm) revealed an up to sevenfold increase in rate-sensitivity of hardness compared to an essentially twin-free pure Cu of the same grain size. A reduction in twin density for the same grain size (with twin lamellae width ∼90
nm) also resulted in a noticeable reduction in rate-sensitivity and hardness. The presence of a high density of nano-scale twins is also seen to impart significant hardness, which is comparable to that achieved in nano-grained Cu. Post-indentation analyses of indented Cu with nano-scale twins in the transmission electron microscope reveal deformation-induced displacement of coherent twin boundaries (CTBs), formation of steps and jogs along CTBs, and blockage of dislocations at CTBs. These processes appear to significantly influence the evolution of thermal activation volume for plastic flow which is some three orders of magnitude smaller than that known for microcrystalline Cu. Transmission electron microscopy also reveals CTBs with a high density of dislocation debris and points to the possibility that displaced CTBs may serve as barriers to dislocation motion and that they may also provide sources for dislocation nucleation, especially near stress concentrations, very much like grain boundaries. Possible consequences of these trends for deformation are explored.
Coronavirus disease 2019 (COVID‐19) continues to impact older adults disproportionately, from severe illness and hospitalization to increased mortality risk. Concurrently, concerns about potential ...shortages of healthcare professionals and health supplies to address these needs have focused attention on how resources are ultimately allocated and used. Some strategies misguidedly use age as an arbitrary criterion, inappropriately disfavoring older adults. This statement represents the official policy position of the American Geriatrics Society (AGS). It is intended to inform stakeholders including hospitals, health systems, and policymakers about ethical considerations to consider when developing strategies for allocating scarce resources during an emergency involving older adults. Members of the AGS Ethics Committee collaborated with interprofessional experts in ethics, law, nursing, and medicine (including geriatrics, palliative care, emergency medicine, and pulmonology/critical care) to conduct a structured literature review and examine relevant reports. The resulting recommendations defend a particular view of distributive justice that maximizes relevant clinical factors and deemphasizes or eliminates factors placing arbitrary, disproportionate weight on advanced age. The AGS positions include (1) avoiding age per se as a means for excluding anyone from care; (2) assessing comorbidities and considering the disparate impact of social determinants of health; (3) encouraging decision makers to focus primarily on potential short‐term (not long‐term) outcomes; (4) avoiding ancillary criteria such as “life‐years saved” and “long‐term predicted life expectancy” that might disadvantage older people; (5) forming and staffing triage committees tasked with allocating scarce resources; (6) developing institutional resource allocation strategies that are transparent and applied uniformly; and (7) facilitating appropriate advance care planning. The statement includes recommendations that should be immediately implemented to address resource allocation strategies during COVID‐19, aligning with AGS positions. The statement also includes recommendations for post‐pandemic review. Such review would support revised strategies to ensure that governments and institutions have equitable emergency resource allocation strategies, avoid future discriminatory language and practice, and have appropriate guidance to develop national frameworks for emergent resource allocation decisions. J Am Geriatr Soc 68:1136–1142, 2020.
See related paper by Farrell et al.
PDF
