Delirium is a common and serious complication in elderly patients undergoing major abdominal surgery, with significant adverse outcomes. Successful strategies or therapies to reduce the incidence of ...delirium are scarce. The objective of this study was to assess the role of prehabilitation in reducing the incidence of delirium in elderly patients.
A single-center uncontrolled before-and-after study was conducted, including patients aged 70 years or older who underwent elective abdominal surgery for colorectal carcinoma or an abdominal aortic aneurysm between January 2013 and October 2015 (control group) and between November 2015 and June 2018 (prehabilitation group). The prehabilitation group received interventions to improve patients' physical health, nutritional status, factors of frailty and preoperative anaemia prior to surgery. The primary outcome was incidence of delirium, diagnosed with the DSM-V criteria or the confusion assessment method. Secondary outcomes were additional complications, length of stay, unplanned ICU admission, length of ICU stay, readmission rate, institutionalization, and in-hospital or 30-day mortality.
A total of 360 control patients and 267 prehabilitation patients were included in the final analysis. The mean number of prehabilitation days was 39 days. The prehabilitation group had a higher burden of comorbidities and was more physically and visually impaired at baseline. At adjusted logistic regression analysis, delirium incidence was reduced significantly from 11.7 to 8.2% (OR 0.56; 95% CI 0.32-0.98; P = 0.043). No statistically significant effects were seen on secondary outcomes.
Current prehabilitation program is feasible and safe, and can reduce delirium incidence in elderly patients undergoing elective major abdominal surgery. This program merits further evaluation.
Dutch Trial Registration, NTR5932.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
MicroRNAs (miRNAs) control the expression of protein-coding genes in normal hematopoietic cells and, consequently, aberrant expression may contribute to leukemogenesis. To identify miRNAs relevant to ...pediatric acute lymphoblastic leukemia (ALL), we cloned 105 known and 8 new miRNA genes expressed in patients' leukemia cells. Instead of known miRNA genes, new miRNA genes were not evolutionarily conserved. Quantification of 19 selected miRNA genes revealed an aberrant expression in ALL as compared with normal CD34+ cells (P <or= 0.02); both upregulated (14/19) and downregulated (5/19) expressions were observed. Eight miRNAs were differentially expressed between MLL and non-MLL precursor B-ALL cases (P<0.05). Most remarkably, miR-708 was 250- up to 6500-fold higher expressed in 57 TEL-AML1, BCR-ABL, E2A-PBX1, hyperdiploid and B-other cases than in 20 MLL-rearranged and 15 T-ALL cases (0.0001<P<0.01), whereas the expression of miR-196b was 500-fold higher in MLL-rearranged and 800-fold higher in 5 of 15 T-ALL cases as compared with the expression level in the remaining precursor B-ALL cases (P<0.001). The expression did not correlate with the maturation status of leukemia cells based on immunoglobulin and T-cell receptor rearrangements, immunophenotype or MLL-fusion partner. In conclusion, we identified new miRNA genes and showed that miRNA expression profiles are ALL subtype-specific rather than linked to the differentiation stadium associated with these subtypes.
The 2017 Dutch Physical Activity Guidelines Weggemans, Rianne M; Backx, Frank J G; Borghouts, Lars ...
The international journal of behavioral nutrition and physical activity,
06/2018, Letnik:
15, Številka:
1
Journal Article
Recenzirano
Odprti dostop
The objective of this study was to derive evidence-based physical activity guidelines for the general Dutch population.
Two systematic reviews were conducted of English language meta-analyses in ...PubMed summarizing separately randomized controlled trials and prospective cohort studies on the relation between physical activity and sedentary behaviour on the one hand and the risk of all-cause mortality and incidence of 15 major chronic diseases and conditions on the other hand. Other outcome measures were risk factors for cardiovascular disease and type 2 diabetes, physical functioning, and fitness. On the basis of these reviews, an expert committee derived physical activity guidelines. In deriving the guidelines, the committee first selected only experimental and observational prospective findings with a strong level of evidence and then integrated both lines of evidence.
The evidence found for beneficial effects on a large number of the outcome measures was sufficiently strong to draw up guidelines to increase physical activity and reduce sedentary behaviour, respectively. At the same time, the current evidence did not provide a sufficient basis for quantifying how much physical activity is minimally needed to achieve beneficial health effects, or at what amount sedentary behaviour becomes detrimental. A general tenet was that at every level of current activity, further increases in physical activity provide additional health benefits, with relatively larger effects among those who are currently not active or active only at light intensity. Three specific guidelines on (1) moderate- and vigorous-intensity physical activity, (2) bone- and muscle-strengthening activities, and (3) sedentary behaviour were formulated separately for adults and children.
There is an unabated need for evidence-based physical activity guidelines that can guide public health policies. Research in which physical activity is measured both objectively (quantity) and subjectively (type and quality) is needed to provide better estimates of the type and actual amount of physical activity required for health.
We assess evidence relevant to Earth's equilibrium climate sensitivity per doubling of atmospheric CO2, characterized by an effective sensitivity S . This evidence includes feedback process ...understanding, the historical climate record, and the paleoclimate record. An S value lower than 2 K is difficult to reconcile with any of the three lines of evidence. The amount of cooling during the Last Glacial Maximum provides strong evidence against values of S greater than 4.5 K. Other lines of evidence in combination also show that this is relatively unlikely. We use a Bayesian approach to produce a probability density (PDF) for S given all the evidence, including tests of robustness to difficult‐to‐quantify uncertainties and different priors. The 66% range is 2.6‐3.9 K for our Baseline calculation, and remains within 2.3‐4.5 K under the robustness tests; corresponding 5‐95% ranges are 2.3‐4.7 K, bounded by 2.0‐5.7 K (although such high‐confidence ranges should be regarded more cautiously). This indicates a stronger constraint on S than reported in past assessments, by lifting the low end of the range. This narrowing occurs because the three lines of evidence agree and are judged to be largely independent, and because of greater confidence in understanding feedback processes and in combining evidence. We identify promising avenues for further narrowing the range in S , in particular using comprehensive models and process understanding to address limitations in the traditional forcing‐feedback paradigm for interpreting past changes.
As little information is available on children with non-classic presentations of Pompe disease, we wished to gain knowledge of specific clinical characteristics and genotypes. We included all ...patients younger than 18 years, who had been evaluated at the Pompe Center in Rotterdam, the Netherlands, between 1975 and 2012, excluding those with the classic-infantile form. None were treated with enzyme replacement therapy at the time of evaluation. We collected information on first symptoms, diagnosis, use of a wheelchair and/or respirator, and enzyme and mutation analysis and assessed muscle strength, pulmonary function, and cardiac parameters.
Thirty-one patients participated. Median age at symptom onset was 2.6 years (range 0.5-13y) and at diagnosis 4.0 years. Most first problems were delayed motor development and problems related to limb-girdle weakness. Fatigue, persistent diarrhea and problems in raising the head in supine position were other first complaints. Ten patients were asymptomatic at time of diagnosis. Five of them developed symptoms before inclusion in this study. Over 50 % of all patients had low or absent reflexes, a myopathic face, and scoliosis; 29 % were underweight. Muscle strength of the neck flexors, hip extensors, hip flexors, and shoulder abductors were most frequently reduced. Pulmonary function was decreased in over 48 % of the patients; 2 patients had cardiac hypertrophy. Patients with mutations other than the c.-32-13T > G were overall more severely affected, while 18 out of the 21 patients (86 %) with the c.-32-13T > G/'null' genotype were male.
Our study shows that Pompe disease can present with severe mobility and respiratory problems during childhood. Pompe disease should be considered in the differential diagnosis of children with less familiar signs such as disproportional weakness of the neck flexors, unexplained fatigue, persistent diarrhea and unexplained high CK/ASAT/ALAT. Disease presentation appears to be different from adult patients. The majority of affected children with GAA genotype c.-32-13T > G/'null' appeared to be male.
Chemical functionalization is a powerful approach to tailor the physical and chemical properties of two-dimensional (2D) materials, increase their processability and stability, tune their ...functionalities and, even, create new 2D materials. This is typically achieved through post-synthetic functionalization by anchoring molecules on the surface of an exfoliated 2D crystal, but it inevitably alters the long-range structural order of the material. Here we present a pre-synthetic approach that allows the isolation of crystalline, robust and magnetic functionalized monolayers of coordination polymers. A series of five isostructural layered magnetic coordination polymers based on Fe(II) centres and different benzimidazole derivatives (bearing a Cl, H, CH
, Br or NH
side group) were first prepared. On mechanical exfoliation, 2D materials are obtained that retain their long-range structural order and exhibit good mechanical and magnetic properties. This combination, together with the possibility to functionalize their surface at will, makes them good candidates to explore magnetism in the 2D limit and to fabricate mechanical resonators for selective gas sensing.
Eye tracking research has been conducted for decades to gain understanding of visual diagnosis such as in radiology. For educational purposes, it is important to identify visual search patterns that ...are related to high perceptual performance and to identify effective teaching strategies. This review of eye-tracking literature in the radiology domain aims to identify visual search patterns associated with high perceptual performance. Databases PubMed, EMBASE, ERIC, PsycINFO, Scopus and Web of Science were searched using ‘visual perception’ OR ‘eye tracking’ AND ‘radiology’ and synonyms. Two authors independently screened search results and included eye tracking studies concerning visual skills in radiology published between January 1, 1994 and July 31, 2015. Two authors independently assessed study quality with the Medical Education Research Study Quality Instrument, and extracted study data with respect to design, participant and task characteristics, and variables. A thematic analysis was conducted to extract and arrange study results, and a textual narrative synthesis was applied for data integration and interpretation. The search resulted in 22 relevant full-text articles. Thematic analysis resulted in six themes that informed the relation between visual search and level of expertise: (1) time on task, (2) eye movement characteristics of experts, (3) differences in visual attention, (4) visual search patterns, (5) search patterns in cross sectional stack imaging, and (6) teaching visual search strategies. Expert search was found to be characterized by a global-focal search pattern, which represents an initial global impression, followed by a detailed, focal search-to-find mode. Specific task-related search patterns, like drilling through CT scans and systematic search in chest X-rays, were found to be related to high expert levels. One study investigated teaching of visual search strategies, and did not find a significant effect on perceptual performance. Eye tracking literature in radiology indicates several search patterns are related to high levels of expertise, but teaching novices to search as an expert may not be effective. Experimental research is needed to find out which search strategies can improve image perception in learners.
Chimeric antigen receptor (CAR) therapy targeting CD19 is an effective treatment for refractory B cell malignancies, especially acute lymphoblastic leukemia (ALL)
. Although a majority of patients ...will achieve a complete response following a single infusion of CD19-targeted CAR-modified T cells (CD19 CAR T cells)
, the broad applicability of this treatment is hampered by severe cytokine release syndrome (CRS), which is characterized by fever, hypotension and respiratory insufficiency associated with elevated serum cytokines, including interleukin-6 (IL-6)
. CRS usually occurs within days of T cell infusion at the peak of CAR T cell expansion. In ALL, it is most frequent and more severe in patients with high tumor burden
. CRS may respond to IL-6 receptor blockade but can require further treatment with high dose corticosteroids to curb potentially lethal severity
. Improved therapeutic and preventive treatments require a better understanding of CRS physiopathology, which has so far remained elusive. Here we report a murine model of CRS that develops within 2-3 d of CAR T cell infusion and that is potentially lethal and responsive to IL-6 receptor blockade. We show that its severity is mediated not by CAR T cell-derived cytokines, but by IL-6, IL-1 and nitric oxide (NO) produced by recipient macrophages, which enables new therapeutic interventions.
IMPORTANCE: Results of studies on use of prophylactic haloperidol in critically ill adults are inconclusive, especially in patients at high risk of delirium. OBJECTIVE: To determine whether ...prophylactic use of haloperidol improves survival among critically ill adults at high risk of delirium, which was defined as an anticipated intensive care unit (ICU) stay of at least 2 days. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, placebo-controlled investigator-driven study involving 1789 critically ill adults treated at 21 ICUs, at which nonpharmacological interventions for delirium prevention are routinely used in the Netherlands. Patients without delirium whose expected ICU stay was at least a day were included. Recruitment was from July 2013 to December 2016 and follow-up was conducted at 90 days with the final follow-up on March 1, 2017. INTERVENTIONS: Patients received prophylactic treatment 3 times daily intravenously either 1 mg (n = 350) or 2 mg (n = 732) of haloperidol or placebo (n = 707), consisting of 0.9% sodium chloride. MAIN OUTCOME AND MEASURES: The primary outcome was the number of days that patients survived in 28 days. There were 15 secondary outcomes, including delirium incidence, 28-day delirium-free and coma-free days, duration of mechanical ventilation, and ICU and hospital length of stay. RESULTS: All 1789 randomized patients (mean, age 66.6 years SD, 12.6; 1099 men 61.4%) completed the study. The 1-mg haloperidol group was prematurely stopped because of futility. There was no difference in the median days patients survived in 28 days, 28 days in the 2-mg haloperidol group vs 28 days in the placebo group, for a difference of 0 days (95% CI, 0-0; P = .93) and a hazard ratio of 1.003 (95% CI, 0.78-1.30, P=.82). All of the 15 secondary outcomes were not statistically different. These included delirium incidence (mean difference, 1.5%, 95% CI, −3.6% to 6.7%), delirium-free and coma-free days (mean difference, 0 days, 95% CI, 0-0 days), and duration of mechanical ventilation, ICU, and hospital length of stay (mean difference, 0 days, 95% CI, 0-0 days for all 3 measures). The number of reported adverse effects did not differ between groups (2 0.3% for the 2-mg haloperidol group vs 1 0.1% for the placebo group). CONCLUSIONS AND RELEVANCE: Among critically ill adults at high risk of delirium, the use of prophylactic haloperidol compared with placebo did not improve survival at 28 days. These findings do not support the use of prophylactic haloperidol for reducing mortality in critically ill adults. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01785290
ABSTRACT
We analyse the physical properties of a large, homogeneously selected sample of ALMA-located sub-millimetre galaxies (SMGs). This survey, AS2UDS, identified 707 SMGs across the ∼1 deg2 ...field, including ∼17 per cent, which are undetected at K ≳ 25.7 mag. We interpret their ultraviolet-to-radio data using magphys and determine a median redshift of z = 2.61 ± 0.08 (1σ range of z = 1.8–3.4) with just ∼6 per cent at z > 4. Our survey provides a sample of massive dusty galaxies at z ≳ 1, with median dust and stellar masses of Md = (6.8 ± 0.3) × 108 M⊙ (thus, gas masses of ∼1011 M⊙) and M* = (1.26 ± 0.05) × 1011 M⊙. We find no evolution in dust temperature at a constant far-infrared luminosity across z ∼ 1.5–4. The gas mass function of our sample increases to z ∼ 2–3 and then declines at z > 3. The space density and masses of SMGs suggest that almost all galaxies with M* ≳ 3 × 1011 M⊙ have passed through an SMG-like phase. The redshift distribution is well fit by a model combining evolution of the gas fraction in haloes with the growth of halo mass past a critical threshold of Mh ∼ 6 × 1012 M⊙, thus SMGs may represent the highly efficient collapse of gas-rich massive haloes. We show that SMGs are broadly consistent with simple homologous systems in the far-infrared, consistent with a centrally illuminated starburst. Our study provides strong support for an evolutionary link between the active, gas-rich SMG population at z > 1 and the formation of massive, bulge-dominated galaxies across the history of the Universe.
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