There is concern about excessive bleeding when low-molecular-weight heparins (LMWHs) are used for venous thromboembolism (VTE) prophylaxis in renal dysfunction. Our objective was to evaluate whether ...LMWH VTE prophylaxis was safe and effective in critically ill patients with renal dysfunction by conducting a subgroup analysis of PROTECT, a randomized blinded trial.
We studied intensive care unit (ICU) patients with pre-ICU dialysis-dependent end-stage renal disease (ESRD; pre-specified subgroup; n = 118), or severe renal dysfunction at ICU admission (defined as ESRD or non-dialysis dependent with creatinine clearance CrCl <30 ml/min; post hoc subgroup; n = 590). We compared dalteparin, 5000 IU daily, with unfractionated heparin (UFH), 5000 IU twice daily, and considered outcomes of proximal leg deep vein thrombosis (DVT); pulmonary embolism (PE); any VTE; and major bleeding. Adjusted hazard ratios HR were calculated using Cox regression.
In patients with ESRD, there was no significant difference in DVT (8.3% vs. 5.2%, p = 0.76), any VTE (10.0% vs. 6.9%; p = 0.39) or major bleeding (5.0% vs. 8.6%; p = 0.32) between UFH and dalteparin. In patients with severe renal dysfunction, there was no significant difference in any VTE (10.0% vs. 6.4%; p = 0.07) or major bleeding (8.9% vs. 11.0%; p = 0.66) but an increase in DVT with dalteparin (7.6% vs. 3.7%; p = 0.04). Interaction p-values for comparisons of HRs (ESRD versus not) were non-significant.
In critically ill patients with ESRD, or severe renal dysfunction, there was no significant difference in any VTE or major bleeding between UFH and dalteparin. Patients with severe renal dysfunction who received dalteparin had more proximal DVTs than those on UFH; this finding did not hold in patients with ESRD alone.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Mitral valve transcatheter edge-to-edge repair (M-TEER) is an effective option for treatment of mitral regurgitation (MR). We previously reported favorable 2-year outcomes for the PASCAL ...transcatheter valve repair system.
We report 3-year outcomes from the multinational, prospective, single-arm CLASP study with analysis by functional MR (FMR) and degenerative MR (DMR).
Patients with core-lab determined MR ≥ 3+ were deemed candidates for M-TEER by the local heart team. Major adverse events were assessed by an independent clinical events committee to 1 year and by sites thereafter. Echocardiographic outcomes were evaluated by the core laboratory to 3 years.
The study enrolled 124 patients, 69% FMR; 31% DMR (60% NYHA class III-IVa, 100% MR ≥ 3+). The 3-year Kaplan-Meier estimate for survival was 75% (66% FMR; 92% DMR) and freedom from heart failure hospitalization (HFH) was 73% (64% FMR; 91% DMR), with 85% reduction in annualized HFH rate (81% FMR; 96% DMR) (p < 0.001). MR ≤ 2+ was achieved and maintained in 93% of patients (93% FMR; 94% DMR) and MR ≤ 1+ in 70% of patients (71% FMR; 67% DMR) (p < 0.001). The mean left ventricular end-diastolic volume (181 mL at baseline) decreased progressively by 28 mL p < 0.001. NYHA class I/II was achieved in 89% of patients (p < 0.001).
The 3-year results from the CLASP study demonstrated favorable and durable outcomes with the PASCAL transcatheter valve repair system in patients with clinically significant MR. These results add to the growing body of evidence establishing the PASCAL system as a valuable therapy for patients with significant symptomatic MR.
Three contemporary leadership challenges face local governments today. The first encourages department heads to more actively work the intersection between political and administrative arenas. The ...second promotes cottaborative work, synchronizing city and county boundaries with problems that have no jurisdicnonal homes. The third argues that citizen engagement is no longer optional—it is imperative—and that connecting engagement initiatives to traditional political values and governing processes is an important mark of successful community building. These three leadership challenges stemfom a widening gap between the arenas of politics and administration—that is, between what is politically acceptable in public policy making and what is administratively sustainable. The gap is fueled by conflicting trends experienced locally and common internationally. Failure to bndge this gap between political acceptability and administrative sustainability results in decreasing legitimacy for governing institutions and increasing challenges.
Abstract Objective The aim of this systematic review was to determine the validity and inter- and intra-observer reliability of the assessment of knee joint effusion in osteoarthritis (OA) of the ...knee. Methods MEDLINE, Web of Knowledge, CINAHL, EMBASE, and AMED were searched from their inception to February 2015. Articles were included according to a priori defined criteria: samples containing participants with knee OA; prospective evaluation of clinical tests and assessments of knee effusion that included reliability, sensitivity, and specificity of these tests. Results A total of 10 publications were reviewed. Eight of these considered reliability and four on validity of clinical assessments against ultrasound effusion. It was not possible to undertake a meta-analysis of reliability or validity because of differences in study designs and the clinical tests. Intra-observer kappa agreement for visible swelling ranged from 0.37 (suprapatellar) to 1.0 (prepatellar); for bulge sign 0.47 and balloon sign 0.37. Inter-observer kappa agreement for visible swelling ranged from −0.02 (prepatellar) to 0.65 (infrapatellar), the balloon sign −0.11 to 0.82, patellar tap −0.02 to 0.75 and bulge sign kappa −0.04 to 0.14 or reliability coefficient 0.97. Reliability and diagnostic accuracy tended to be better in experienced observers. Very few data looked at performance of individual clinical tests with sensitivity ranging 18.2–85.7% and specificity 35.3–93.3%, both higher with larger effusions. Conclusion The majority of unstandardized clinical tests to assess joint effusion in knee OA had relatively low intra- and inter-observer reliability. There is some evidence experience improved reliability and diagnostic accuracy of tests. Currently there is insufficient evidence to recommend any particular test in clinical practice.
Expanded glutamine repeats of the ataxin-2 (ATXN2) protein cause spinocerebellar ataxia type 2 (SCA2), a rare neurodegenerative disorder. More recent studies have suggested that expanded ATXN2 ...repeats are a genetic risk factor for amyotrophic lateral sclerosis (ALS) via an RNA-dependent interaction with TDP-43. Given the phenotypic diversity observed in SCA2 patients, we set out to determine the polymorphic nature of the ATXN2 repeat length across a spectrum of neurodegenerative disorders. In this study, we genotyped the ATXN2 repeat in 3919 neurodegenerative disease patients and 4877 healthy controls and performed logistic regression analysis to determine the association of repeat length with the risk of disease. We confirmed the presence of a significantly higher number of expanded ATXN2 repeat carriers in ALS patients compared with healthy controls (OR = 5.57; P= 0.001; repeat length >30 units). Furthermore, we observed significant association of expanded ATXN2 repeats with the development of progressive supranuclear palsy (OR = 5.83; P= 0.004; repeat length >30 units). Although expanded repeat carriers were also identified in frontotemporal lobar degeneration, Alzheimer's and Parkinson's disease patients, these were not significantly more frequent than in controls. Of note, our study identified a number of healthy control individuals who harbor expanded repeat alleles (31-33 units), which suggests caution should be taken when attributing specific disease phenotypes to these repeat lengths. In conclusion, our findings confirm the role of ATXN2 as an important risk factor for ALS and support the hypothesis that expanded ATXN2 repeats may predispose to other neurodegenerative diseases, including progressive supranuclear palsy.
Although there is evidence that vitamin D inadequacy may be linked to adverse cognitive outcomes, results from studies on this topic have been inconsistent. The aim of this trial was to examine the ...association between 25-hydroxyvitamin D (25(OH)D) levels and cognitive performance in middle-aged and older European men.
This population-based cross-sectional study included 3,369 men aged 40-79 years from eight centres enrolled in the European Male Ageing Study. Cognitive function was assessed using the Rey-Osterrieth Complex Figure (ROCF) test, the Camden Topographical Recognition Memory (CTRM) test and the Digit Symbol Substitution Test (DSST). Serum 25(OH)D levels were measured by radioimmunoassay. Additional assessments included measurement of physical activity, functional performance and mood/depression. Associations between cognitive function and 25(OH)D levels were explored using locally weighted and linear regression models.
In total, 3,133 men (mean (+/-SD) age 60+/-11 years) were included in the analysis. The mean (+/-SD) 25(OH)D concentration was 63+/-31 nmol/l. In age-adjusted linear regressions, high levels of 25(OH)D were associated with high scores on the copy component of the ROCF test (beta per 10 nmol/l = 0.096; 95% CI 0.049 to 0.144), the CTRM test (beta per 10 nmol/l = 0.075; 95% CI 0.026 to 0.124) and the DSST (beta per 10 nmol/l = 0.318; 95% CI 0.235 to 0.401). After adjusting for additional confounders, 25(OH)D levels were associated with only score on the DSST (beta per 10 nmol/l = 0.152; 95% CI 0.051 to 0.253). Locally weighted and spline regressions suggested the relationship between 25(OH)D concentration and cognitive function was most pronounced at 25(OH)D concentrations below 35 nmol/l.
In this study, lower 25(OH)D levels were associated with poorer performance on the DSST. Further research is warranted to determine whether vitamin D sufficiency might have a role in preserving cognitive function in older adults.
Repair of midsize (4–6 cm) ventral hernias is challenging given lack of guidelines. Within this context, we sought to characterize surgical approach among patients undergoing repair of midsize ...ventral hernias within the only population-level, clinically-nuanced hernia registry in the US.
Retrospective cohort study of patients undergoing ventral hernia repair in the Michigan Surgical Quality Collaborative Core Optimization Hernia Registry (MSQCCOHR). MSQCCOHR is the only US population-level registry that captures clinically-nuanced data pertaining to patient hernia characteristics. We included patients who underwent repair of a 4–6 cm hernia from January 1, 2020-June 30, 2022. We stratified repair type as open or minimally invasive and used a multivariable logistic regression model to identify factors associated with MIS approach. Secondary outcomes included complications rate.
Among 771 patients, mean hernia width (SD) was 4.7 cm (0.8) and 339 (44 %) underwent MIS approach. Patients with MIS approach had lower BMI (33.5 vs 34.8, p = 0.02) and less often were ASA class III (47.5% vs 54.6 %, p = 0.02) or ASA class IV (2.4% vs 4.2 %, p = 0.02). MIS approach was associated with smaller mean hernia width (4.71 cm vs 4.84 cm, p = 0.02) and was used more often in the elective setting (94.4% vs 84.0 %, p < 0.01). In the multivariable logistic regression model, higher BMI (aOR 0.97, 95 % CI 0.94–0.99) and urgent/emergent surgery (aOR 0.43, 95 % CI 0.24–0.79) were associated with lower odds of MIS. We found no significant association between MIS and risk of complications (aOR 0.62, 95 % CI 0.37–1.04). Among patients undergoing MIS, more than half (n = 236, 69.6 %) had a robotic approach but there were few patient factors associated with this.
Among patients with midsize hernias, few patient-level factors are associated with approach. This may indicate that surgeon preference factors largely into this decision.
Liver tumors account for approximately 2% of all pediatric malignancies. Children with advanced stages of hepatoblastoma (HB) are cured only 50–70% of the time while children with advanced ...hepatocellular carcinoma (HCC) have a <20% 5-year overall survival. This scoping review was performed to highlight the paucity of rigorous, reliable data guiding the management of relapsed pediatric HB or HCC. When these patients are enrolled on prospective trials, the trials are often histology-agnostic, exclude patients less than a year of age, lack a liquid formulary of the drug under study, exclude recipients of a solid organ transplant, and enroll only 1–2 patients limiting the ability to deduce efficacious regimens for current use or future study. We highlight the creation of a global pediatric consortium intended to source retrospective relapse data from over 100 institutions spanning 4 continents. The data collected from this effort will inform future relapse trials.
•Large Atlantic bluefin tuna tagged off the coast of Ireland utilize the warm North Atlantic Current to access foraging areas in the North Atlantic Ocean.•Five hotspots of Atlantic bluefin tuna occur ...in the central and eastern North Atlantic Ocean. Each are in regions with long-lived, quasi-stationary anticyclonic features (i.e., eddies or recirculation).•Daily maximum depth and time at mesopelagic depths (i.e., greater than 200 m) are positively correlated with absolute dynamic topography in the open ocean.•In the Winter, a majority of Atlantic bluefin tuna tagged in Irish waters travel to the Newfoundland Basin, a region with intense mesoscale eddy activity and high mesopelagic fish biomass.•Some Atlantic bluefin tuna migrated in the Spring to the Mediterranean Sea, an important spawning ground for this species.
Electronic tagging of Atlantic bluefin tuna (ABT; Thunnus thynnus) has shaped our understanding of their movements and migrations throughout the Atlantic basin. In this study, we used pop-up satellite archival tagging data to examine the movements of 51 large (CFL µ ± σ: 215 ± 15 cm) ABT tagged off the coast of Ireland. When combined with satellite oceanographic data, we found that ABT take advantage of the warm North Atlantic Current to access foraging areas in the North Atlantic Ocean. We identified four potential foraging regions: (1) off the coast of Ireland, (2) the Bay of Biscay, (3) the Newfoundland Basin, and (4) the West European Basin. In addition, 14 ABT migrated to their spawning grounds in the Mediterranean Sea, entering by May 16 and exiting by July 7, on average. In all five regions, anticyclonic ocean features (i.e., eddies or recirculation) were present. In the open ocean, these features often co-occurred with areas where the daily maximum depth of tuna exceeded 400 m and tuna spent extended time at mesopelagic depths (i.e., greater than 200 m). We hypothesize that ABT exploit anticyclonic structures to forage on the abundant mesopelagic fish communities. Additionally, our results suggest that ABT are travelling across the North Atlantic Ocean in a directed migration to the Newfoundland Basin to reach what may be one of the best mesopelagic feeding grounds in the world.