Acute deep venous thrombosis (DVT) causes leg pain. Elastic compression stockings (ECS) have potential to relieve DVT-related leg pain by diminishing the diameter of distended veins and increasing ...venous blood flow. It was our objective to determine whether ECS reduce leg pain in patients with acute DVT. We performed a secondary analysis of the SOX Trial, a multicentre randomised placebo controlled trial of active ECS versus placebo ECS to prevent the post-thrombotic syndrome.The study was performed in 24 hospital centres in Canada and the U.S. and included 803 patients with a first episode of acute proximal DVT. Patients were randomised to receive active ECS (knee length, 30-40 mm Hg graduated pressure) or placebo ECS (manufactured to look identical to active ECS, but lacking therapeutic compression). Study outcome was leg pain severity assessed on an 11-point numerical pain rating scale (0, no pain; 10, worst possible pain) at baseline, 14, 30 and 60 days after randomisation. Mean age was 55 years and 60% were male. In active ECS patients (n=409), mean (SD) pain severity at baseline and at 60 days were 5.18 (3.29) and 1.39 (2.19), respectively, and in placebo ECS patients (n=394) were 5.38 (3.29) and 1.13 (1.86), respectively. There were no significant differences in pain scores between groups at any assessment point, and no evidence for subgroup interaction by age, sex or anatomical extent of DVT. Results were similar in an analysis restricted to patients who reported wearing stockings every day. In conclusion, ECS do not reduce leg pain in patients with acute proximal DVT.
Accurate measurements of arterial P CO 2 ( P a,CO 2 ) currently require blood sampling because the end-tidal P CO 2 ( P ET,CO 2 ) of the expired gas often does not accurately reflect the mean ...alveolar P CO 2 and P a,CO 2 . Differences between P ET,CO 2 and P a,CO 2 result from regional inhomogeneities in perfusion and gas exchange. We hypothesized that breathing via a sequential gas delivery
circuit would reduce these inhomogeneities sufficiently to allow accurate prediction of P a,CO 2 from P ET,CO 2 . We tested this hypothesis in five healthy middle-aged men by comparing their P ET,CO 2 values with P a,CO 2 values at various combinations of P ET,CO 2 (between 35 and 50 mmHg), P O 2 (between 70 and 300 mmHg), and breathing frequencies ( f ; between 6 and 24 breaths min â1 ). Once each individual was in a steady state, P a,CO 2 was collected in duplicate by consecutive blood samples to assess its repeatability. The difference between P ET,CO 2 and average P a,CO 2 was 0.5 ± 1.7 mmHg ( P = 0.53; 95% CI â2.8, 3.8 mmHg) whereas the mean difference between the two measurements of P a,CO 2 was â0.1 ± 1.6 mmHg (95% CI â3.7, 2.6 mmHg). Repeated measures ANOVAs revealed no significant differences between P ET,CO 2 and P a,CO 2 over the ranges of P O 2 , f and target P ET,CO 2 . We conclude that when breathing via a sequential gas delivery circuit, P ET,CO 2 provides as accurate a measurement of P a,CO 2 as the actual analysis of arterial blood.
Older patients with cancer and their caregivers worry about the effects of cancer treatment on aging-related domains (eg, function and cognition). Quality conversations with oncologists about ...aging-related concerns could improve patient-centered outcomes. A geriatric assessment (GA) can capture evidence-based aging-related conditions associated with poor clinical outcomes (eg, toxic effects) for older patients with cancer.
To determine whether providing a GA summary and GA-guided recommendations to oncologists can improve communication about aging-related concerns.
This cluster-randomized clinical trial enrolled 541 participants from 31 community oncology practices within the University of Rochester National Cancer Institute Community Oncology Research Program from October 29, 2014, to April 28, 2017. Patients were aged 70 years or older with an advanced solid malignant tumor or lymphoma who had at least 1 impaired GA domain; patients chose 1 caregiver to participate. The primary outcome was assessed on an intent-to-treat basis.
Oncology practices were randomized to receive either a tailored GA summary with recommendations for each enrolled patient (intervention) or alerts only for patients meeting criteria for depression or cognitive impairment (usual care).
The predetermined primary outcome was patient satisfaction with communication about aging-related concerns (modified Health Care Climate Questionnaire score range, 0-28; higher scores indicate greater satisfaction), measured after the first oncology visit after the GA. Secondary outcomes included the number of aging-related concerns discussed during the visit (from content analysis of audiorecordings), quality of life (measured with the Functional Assessment of Cancer Therapy scale for patients and the 12-Item Short Form Health Survey for caregivers), and caregiver satisfaction with communication about aging-related patient concerns.
A total of 541 eligible patients (264 women, 276 men, and 1 patient did not provide data; mean SD age, 76.6 5.2 years) and 414 caregivers (310 women, 101 men, and 3 caregivers did not provide data; mean age, 66.5 12.5 years) were enrolled. Patients in the intervention group were more satisfied after the visit with communication about aging-related concerns (difference in mean score, 1.09 points; 95% CI, 0.05-2.13 points; P = .04); satisfaction with communication about aging-related concerns remained higher in the intervention group over 6 months (difference in mean score, 1.10; 95% CI, 0.04-2.16; P = .04). There were more aging-related conversations in the intervention group's visits (difference, 3.59; 95% CI, 2.22-4.95; P < .001). Caregivers in the intervention group were more satisfied with communication after the visit (difference, 1.05; 95% CI, 0.12-1.98; P = .03). Quality of life outcomes did not differ between groups.
Including GA in oncology clinical visits for older adults with advanced cancer improves patient-centered and caregiver-centered communication about aging-related concerns.
ClinicalTrials.gov identifier: NCT02107443.
The RNA exosome is a ubiquitously expressed complex of nine core proteins (EXOSC1-9) and associated nucleases responsible for RNA processing and degradation. Mutations in
,
,
, and the exosome ...cofactor
cause pontocerebellar hypoplasia and motor neuronopathy. We investigated the consequences of exosome mutations on RNA metabolism and cellular survival in zebrafish and human cell models. We observed that levels of mRNAs encoding p53 and ribosome biogenesis factors are increased in zebrafish lines with homozygous mutations of
or
, respectively. Consistent with higher p53 levels, mutant zebrafish have a reduced head size, smaller brain, and cerebellum caused by an increased number of apoptotic cells during development. Down-regulation of
and
in human cells leads to p53 protein stabilisation and G2/M cell cycle arrest. Increased p53 transcript levels were also observed in muscle samples from patients with
mutations. Our work provides explanation for the pathogenesis of exosome-related disorders and highlights the link between exosome function, ribosome biogenesis, and p53-dependent signalling. We suggest that exosome-related disorders could be classified as ribosomopathies.
We wanted to probe the opinions and current practices on preimplantation genetic screening (PGS), and more specifically on PGS in its newest form: PGS 2.0?
Consensus is lacking on which patient ...groups, if any at all, can benefit from PGS 2.0 and, a fortiori, whether all IVF patients should be offered PGS.
It is clear from all experts that PGS 2.0 can be defined as biopsy at the blastocyst stage followed by comprehensive chromosome screening and possibly combined with vitrification. Most agree that mosaicism is less of an issue at the blastocyst stage than at the cleavage stage but whether mosaicism is no issue at all at the blastocyst stage is currently called into question.
A questionnaire was developed on the three major aspects of PGS 2.0: the Why, with general questions such as PGS 2.0 indications; the How, specifically on genetic analysis methods; the When, on the ideal method and timing of embryo biopsy. Thirty-five colleagues have been selected to address these questions on the basis of their experience with PGS, and demonstrated by peer-reviewed publications, presentations at meetings and participation in the discussion. The first group of experts who were asked about 'The Why' comprised fertility experts, the second group of molecular biologists were asked about 'The How' and the third group of embryologists were asked about 'The When'. Furthermore, the geographical distribution of the experts has been taken into account. Thirty have filled in the questionnaire as well as actively participated in the redaction of the current paper.
The 30 participants were from Europe (Belgium, Germany, Greece, Italy, Netherlands, Spain, UK) and the USA. Array comparative genome hybridization is the most widely used method amongst the participants, but it is slowly being replaced by massive parallel sequencing. Most participants offering PGS 2.0 to their patients prefer blastocyst biopsy. The high efficiency of vitrification of blastocysts has added a layer of complexity to the discussion, and it is not clear whether PGS in combination with vitrification, PGS alone, or vitrification alone, followed by serial thawing and eSET will be the favoured approach. The opinions range from in favour of the introduction of PGS 2.0 for all IVF patients, over the proposal to use PGS as a tool to rank embryos according to their implantation potential, to scepticism towards PGS pending a positive outcome of robust, reliable and large-scale RCTs in distinct patient groups.
Care was taken to obtain a wide spectrum of views from carefully chosen experts. However, not all invited experts agreed to participate, which explains a lack of geographical coverage in some areas, for example China. This paper is a collation of current practices and opinions, and it was outside the scope of this study to bring a scientific, once-and-for-all solution to the ongoing debate.
This paper is unique in that it brings together opinions on PGS 2.0 from all different perspectives and gives an overview of currently applied technologies as well as potential future developments. It will be a useful reference for fertility specialists with an expertise outside reproductive genetics.
none.
No specific funding was obtained to conduct this questionnaire.
The cloning of animals by somatic cell nuclear transfer (SCNT) has the potential to allow rapid dissemination of desirable traits from elite animals. However, concern has been expressed that aberrant ...epigenetic marks in SCNT-derived animals may be passed onto the next generation, even though the offspring of clones appear to be mainly normal. Here, we compared the DNA methylation patterns at 10 genomic regions in sperm from SCNT bulls with that from normal, naturally conceived bulls and with the nuclear donor somatic cells. Eight of the 10 genomic regions were differentially methylated in sperm compared with the donor cell DNA. All three satellite sequences examined here were less methylated in sperm than in the donor cells, contradicting the belief that the sperm genome is always highly methylated. The DNA methylation patterns at all 10 regions were almost identical between SCNT and control sperm, with only one out of the 175 CpG sites/groups of sites examined showing significant difference. These results provide the first molecular evidence that the donor cell genome is correctly reprogrammed upon passage through the germ line in males, and that any epigenetic aberrations harbored by SCNT bulls are unlikely to be passed onto their offspring.
Physical activity may be a way to increase and maintain fat-free mass (FFM) in later life, similar to the prevention of fractures by increasing peak bone mass.
A study is presented of the association ...between FFM and physical activity in relation to age.
In a cross-sectional study, FFM was analyzed in relation to physical activity in a large participant group as compiled in the International Atomic Energy Agency Doubly Labeled Water database. The database included 2000 participants, age 3–96 y, with measurements of total energy expenditure (TEE) and resting energy expenditure (REE) to allow calculation of physical activity level (PAL = TEE/REE), and calculation of FFM from isotope dilution.
PAL was a main determinant of body composition at all ages. Models with age, fat mass (FM), and PAL explained 76% and 85% of the variation in FFM in females and males < 18 y old, and 32% and 47% of the variation in FFM in females and males ≥ 18 y old, respectively. In participants < 18 y old, mean FM-adjusted FFM was 1.7 kg (95% CI: 0.1, 3.2 kg) and 3.4 kg (95% CI: 1.0, 5.6 kg) higher in a very active participant with PAL = 2.0 than in a sedentary participant with PAL = 1.5, for females and males, respectively. At age 18 y, height and FM–adjusted FFM was 3.6 kg (95% CI: 2.8, 4.4 kg) and 4.4 kg (95% CI: 3.2, 5.7 kg) higher, and at age 80 y 0.7 kg (95% CI: −0.2, 1.7 kg) and 1.0 kg (95% CI: −0.1, 2.1 kg) higher, in a participant with PAL = 2.0 than in a participant with PAL = 1.5, for females and males, respectively.
If these associations are causal, they suggest physical activity is a major determinant of body composition as reflected in peak FFM, and that a physically active lifestyle can only partly protect against loss of FFM in aging adults.
Abstract Background The American College of Chest Physicians (ACCP) guidelines recommends thromboprophylaxis for total hip replacement (THR) and total knee replacement (TKR) patients. We examined ...alignment with ACCP thromboprophylaxis guidelines among THR/TKR patients, and compared symptomatic venous thromboembolism (VTE), bleeding event rates and risk factors for VTE between patients receiving ACCP-recommended thromboprophylaxis (‘ACCP’) and those who did not (‘non-ACCP’). Methods This retrospective observational study used a large US health plan claims database that was linked to an inpatient database containing detailed inpatient medication use and a database containing date-of-death information. Patients who had THR/TKR surgery between April 01, 2004 and December 31, 2006 were included. Comparisons of VTE and bleeding events between ACCP and non-ACCP patients were analyzed using chi-squared tests and multivariate logistic regression. Results Of 3,497 linked patients, 1,395 (40%) received ACCP recommended thromboprophylaxis. Of the patients who received non-ACCP recommended prophylaxis the majority (81%) received shorter than the recommended minimum 10 day prophylaxis and 118 (5.6%) of patients received no prophylaxis. Overall, non-ACCP patients were almost twice as likely to experience an incident DVT (3.76% versus 2.01%, p = 0.003) and more than eight times as likely to experience an incident PE (1.19% versus 0.14%, p = 0.001) relative to ACCP patients; there were no statistically significant difference in bleeding rates. Multivariate logistic regression indicated that the odds of a VTE event were significantly lower for ACCP patients (DVT: OR = 0.54; p = 0.006; PE: OR = 0.12; p = 0.004). Conclusions This study offers a unique perspective on ‘real-world’ thromboprophylaxis patterns and associated outcomes in THR and TKR patients in the US. It suggests that only 40% of THR/TKR patients receive ACCP-recommended thromboprophylaxis and that not receiving ACCP thromboprophylaxis is an independent risk factor for both DVT and PE.
The purpose was to synthesize evidence on the association between nature-based Early Childhood Education (ECE) and children's physical activity (PA) and motor competence (MC).
A literature search of ...9 databases was concluded in August 2020. Studies were eligible if (1) children were aged 2-7 years old and attending ECE, (2) ECE settings integrated nature, and (3) assessed physical outcomes. Two reviewers independently screened full-text articles and assessed study quality. Synthesis was conducted using effect direction (quantitative), thematic analysis (qualitative), and combined using a results-based convergent synthesis.
1370 full-text articles were screened and 39 (31 quantitative and 8 qualitative) studies were eligible; 20 quantitative studies assessed PA and 6 assessed MC. Findings indicated inconsistent associations between nature-based ECE and increased moderate to vigorous PA, and improved speed/agility and object control skills. There were positive associations between nature-based ECE and reduced sedentary time and improved balance. From the qualitative analysis, nature-based ECE affords higher intensity PA and risky play, which could improve some MC domains. The quality of 28/31 studies was weak.
More controlled experimental designs that describe the dose and quality of nature are needed to better inform the effectiveness of nature-based ECE on PA and MC.
The ongoing Russian aggression against Ukraine has forced over eight million people to migrate out of Ukraine. Understanding the dynamics of forced migration is essential for policy-making and for ...delivering humanitarian assistance. Existing work is hindered by a reliance on observational data which is only available well after the fact. In this work, we study the efficacy of a data-driven agent-based framework motivated by social and behavioral theory in predicting outflow of migrants as a result of conflict events during the initial phase of the Ukraine war. We discuss policy use cases for the proposed framework by demonstrating how it can leverage refugee demographic details to answer pressing policy questions. We also show how to incorporate conflict forecast scenarios to predict future conflict-induced migration flows. Detailed future migration estimates across various conflict scenarios can both help to reduce policymaker uncertainty and improve allocation and staging of limited humanitarian resources in crisis settings.
PDF
