Split-thickness skin grafts can provide effective autologous wound closure in patients with dysvascular comorbidities. Meshing the graft allows for reduced donor site morbidity and expanded coverage. ...This study directly compares outcomes across varying meshing ratios used to treat chronic lower extremity wounds. Patients who received split-thickness skin grafts to their lower extremity for chronic ulcers from December 2014 to December 2019 at a single center were retrospectively reviewed. Patients were stratified by meshing ratios: nonmeshed (including pie crusting), 1.5:1, and 3:1. The primary outcome was clinical "healing" as determined by surgeon discretion at 30 days, 60 days, and the latest follow-up. Secondary outcomes included postoperative complications, graft loss, ulcer recurrence, progression to amputation, and mortality. A total of 321 patients were identified. Wound sizes and location differed significantly, with 3:1 meshing applied to the largest wounds (187.8 ± 157.6 cm
; 1.5:1 meshed, 110.4 ± 103.9 cm
; nonmeshed 38.7 ± 55.5 cm
; p < .0001) mostly of the lower leg (n = 18, 75%; 1.5:1 meshed, n = 23, 43.4%; nonmeshed n = 62, 25.7%; p < .0001). Meshed grafts displayed a significantly higher proportion of healing at 30 and 60 days, but no differences persisted by the final follow-up (16.5 ± 20.5 months). Longitudinally, nonmeshed STSG was associated with most graft loss (46, 19.1%; p = .011) and ulcer recurrence (44, 18.3%; p = .011). Of the 3 meshing ratios, 3:1 exhibited the lowest rates of complications. Our results suggest that 3:1 meshing is a safe option for coverage of large lower extremity wounds to minimize donor site morbidity.
Highlights • Zinc is a contaminant in common electrophysiological buffers and labware. • Contaminating zinc levels enhance glycine receptor function. • Different vial types do not affect zinc ...mediated glycine receptor enhancement. • Washing vials did not affect zinc mediated glycine receptor enhancement. • Use of polystyrene serological pipets can lead to zinc contamination of solutions.
Objective
Atrial fibrillation (AF) carries substantial morbidity and mortality. Evidence‐based guidelines have been synthesized into emergency department (ED) AF care pathways, but the effectiveness ...and scalability of such approaches are not well established. We thus evaluated the impacts of an algorithmic care pathway for ED management of non‐valvular AF (EDAFMP) on hospital use and care process measures.
Methods
We deployed a voluntary‐use EDAFMP in 4 EDs (1 tertiary hospital, 1 cardiac hospital, 2 community hospitals) of an integrated delivery organization using a multifaceted implementation approach. We compared outcomes between patients with AF treated using the EDAFMP and historical and contemporaneous “usual care” controls, using a propensity‐score adjusted generalized estimating equation. Patients with an index ED encounter for a primary visit reason of non‐valvular AF (and no excluding concurrent diagnoses) were eligible for inclusion.
Results
Preimplementation (January 1, 2016–December 31, 2016), 628 AF patients were eligible; postimplementation (September 1, 2017–June 30, 2019), 1296, including 271 (20.9%) treated with the EDAFMP, were eligible. EDAFMP patients were less likely to be admitted than both historical (adjusted odds ratio aOR, 95% confidence interval CI: 0.45, 0.29–0.71) and contemporaneous controls (aOR, 95%CI: 0.63, 0.46–0.86). ED visits and hospital readmissions over 90 days subsequent to index ED encounters were similar between postimplementation EDAFMP and usual care groups. EDAFMP patients were more likely to be prescribed anticoagulation (38% v. 5%, P < 0.001) and be referred to a cardiologist (93% vs 29%, P < 0.001) versus the comparator group.
Conclusion
EDAFMP use is associated with decreased hospital admission during an index ED encounter for non‐valvular AF, and improved delivery of AF care processes.
The objective was to test if low-risk emergency department patients with vitamin K antagonist (venous thromboembolism VTE; including venous thrombosis and pulmonary embolism PE) can be safely and ...effectively treated at home with direct acting oral (monotherapy) anticoagulation in a large-scale, real-world pragmatic effectiveness trial.
This was a single-arm trial, conducted from 2016 to 2019 in accordance with the Standards for Reporting Implementation Studies guideline in 33 emergency departments in the United States. Participants had newly diagnosed VTE with low risk of death based upon either the modified Hestia criteria, or physician judgment plus the simplified PE severity index score of zero, together with nonhigh bleeding risk were eligible. Patients had to be discharged within 24 hours of triage and treated with either apixaban or rivaroxaban. Effectiveness was defined by the primary efficacy and safety outcomes, image-proven recurrent VTE and bleeding requiring hospitalization >24 hours, respectively, with an upper limit of the 95% CI for the 30-day frequency of VTE recurrence below 2.0% for both outcomes.
We enrolled 1421 patients with complete outcomes data, including 903 with venous thrombosis and 518 with PE. The recurrent VTE requiring hospitalization occurred in 14/1421 (1.0% 95% CI, 0.5%-1.7%), and bleeding requiring hospitalization occurred in 12/1421 (0.8% 0.4%-1.5%). The rate of severe bleeding using International Society for Thrombosis and Haemostasis criteria was 2/1421 (0.1% 0%-0.5%). No patient died, and serious adverse events occurred in 2.5% of venous thrombosis patients and 2.3% of patients with PE. Medication nonadherence was reported by patients in 8.0% (6.6%-9.5%) and was associated with a risk ratio of 6.0 (2.3-15.2) for VTE recurrence. Among all patients diagnosed with VTE in the emergency department during the period of study, 18% of venous thrombosis patients and 10% of patients with PE were enrolled.
Monotherapy treatment of low-risk patients with venous thrombosis or PE in the emergency department setting produced a low rate of bleeding and VTE recurrence, but may be underused. Patients with venous thrombosis and PE should undergo risk-stratification before home treatment. Improved patient adherence may reduce rate of recurrent VTE. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03404635.
Heterotrimeric G-proteins are ubiquitously expressed in several cancers, and they transduce signals from activated G-protein coupled receptors. These proteins have numerous biological functions, and ...they are becoming interesting target molecules in cancer therapy. Previously, we have shown that heterotrimeric G-protein subunit alphai2 (Gαi2) has an essential role in the migration and invasion of prostate cancer cells. Using a structure-based approach, we have synthesized optimized small molecule inhibitors that are able to prevent specifically the activation of the Gαi2 subunit, keeping the protein in its inactive GDP-bound state. We observed that two of the compounds (13 and 14) at 10 μΜ significantly inhibited the migratory behavior of the PC3 and DU145 prostate cancer cell lines. Additionally, compound 14 at 10 μΜ blocked the activation of Gαi2 in oxytocin-stimulated prostate cancer PC3 cells, and inhibited the migratory capability of DU145 cells overexpressing the constitutively active form of Gαi2, under basal and EGF-stimulated conditions. We also observed that the knockdown or inhibition of Gαi2 negatively regulated migration of renal and ovarian cancer cell lines. Our results suggest that small molecule inhibitors of Gαi2 have potential as leads for discovering novel anti-metastatic agents for attenuating the capability of cancer cells to spread and invade to distant sites.
Unintended overdoses of opiate medications are potentially lethal events. Monitoring patients for oversedation is fundamental to ensuring safe use of opiates, and the timing of this evaluation is ...guided by the onset of action, time to max effect and duration of action of the opiate. The study's aim was to describe the timing of oversedation in relation to the predicted duration of action of the administered opiate.
This study was conducted as a retrospective review of all opiate-related oversedation events during a 2-year period involving patients admitted to an urban teaching hospital.
Of the 53 opiate-related oversedation events evaluated, 47% occurred after the predicted maximal duration of action of the administered opiate.
Opiate-induced oversedation routinely occurs after predicted based upon duration of action. The study findings have profound implications upon nursing practice regarding duration of time required to monitor for opiate-induced oversedation.
Inhaled nitric oxide has been reported to benefit patients with acute pulmonary embolism (PE). To date, all published literature has derived from case reports or case series conducted without a ...structured protocol. Here we report the results of a phase I trial with a predefined clinical protocol to treat patients with CT-demonstrated, submassive PE and moderate to severe dyspnoea.
Patients were recruited from the emergency department of an academic teaching hospital. Informed consent and the entire treatment protocol was administered by a study physician. Nitric oxide was administered using a commercial device (Inovent) and a custom-made non-rebreathing face mask. The NO concentration was increased at 1 ppm/min (parts per million) until a maximum of 25 ppm and continued for 120 min and then weaned at 1 ppm/min. Dyspnoea was assessed with the Borg score, oxygenation by pulse oximetry, and haemodynamic status by shock index (HR/SBP).
Eight patients were enrolled. All patients tolerated the entire protocol without adverse events, and all had decreased numerical Borg score by >50%. The changes from baseline to 155 min were as follows: Borg score 7.5±2.5 to 2.3±1.9 (p=0.06, Signed rank test), SaO2% 93±5 to 97±3 and shock index 1.0±0.11 to 0.86±0.09. No patient experienced worsening during weaning.
Inhaled NO reduced dyspnoea without adverse events in eight patients with severe submassive PE. This protocol can serve as the basis for a phase II trial or for a compassionate use protocol.
The rise of food security up international political, societal and academic agendas has led to increasing interest in novel means of improving primary food production and reducing waste. There are ...however, also many ‘post-farm gate’ activities that are critical to food security, including processing, packaging, distributing, retailing, cooking and consuming. These activities all affect a range of important food security elements, notably availability, affordability and other aspects of access, nutrition and safety. Addressing the challenge of universal food security, in the context of a number of other policy goals (e.g. social, economic and environmental sustainability), is of keen interest to a range of UK stakeholders but requires an up-to-date evidence base and continuous innovation. An exercise was therefore conducted, under the auspices of the UK Global Food Security Programme, to identify priority research questions with a focus on the UK food system (though the outcomes may be broadly applicable to other developed nations). Emphasis was placed on incorporating a wide range of perspectives (‘world views’) from different stakeholder groups: policy, private sector, non-governmental organisations, advocacy groups and academia. A total of 456 individuals submitted 820 questions from which 100 were selected by a process of online voting and a three-stage workshop voting exercise. These 100 final questions were sorted into 10 themes and the ‘top’ question for each theme identified by a further voting exercise. This step also allowed four different stakeholder groups to select the top 7–8 questions from their perspectives. Results of these voting exercises are presented. It is clear from the wide range of questions prioritised in this exercise that the different stakeholder groups identified specific research needs on a range of post-farm gate activities and food security outcomes. Evidence needs related to food affordability, nutrition and food safety (all key elements of food security) featured highly in the exercise. While there were some questions relating to climate impacts on production, other important topics for food security (e.g. trade, transport, preference and cultural needs) were not viewed as strongly by the participants.
Signal transducer and activator of transcription 3 (Stat3) is a cytosolic transcription factor that relates signals from the cell membrane directly to the nucleus where it, in complex with other ...proteins, initiates the transcription of antiapoptotic and cell cycling genes, e.g., Bcl-xL and cyclin D1. In normal cells Stat3 transduces signals from cytokines such as IL-6 and growth factors such as the epidermal growth factor. Stat3 is constitutively activated in a number of human tumors. Antisense and dominant negative gene delivery result in apoptosis and reduced cell growth, thus this protein is an attractive target for anticancer drug design. As part of our research on the design of Src homology 2 (SH2) directed peptidomimetic inhibitors of Stat3, in this paper we describe structure−activity relationship studies that provide information on the nature of peptide−protein interactions of a high-affinity phosphopeptide inhibitor of Stat3 dimerization and DNA binding, Ac-Tyr(PO3H2)-Leu-Pro-Gln-Thr-Val-NH2, peptide 1. There is a hydrophobic surface on the SH2 domain that can accommodate lipophilic groups on the N-terminus. Of the amino acids tested, leucine provided the highest affinity at pY+1 and its main chain NH is involved with a hydrogen bond with Stat3, presumably Ser636. cis-3,4-Methanoproline is optimal as a backbone constraint at pY+2. The side chain amide protons of Gln are required for high-affinity interactions. The C-terminal dipeptide, Thr-Val, can be replaced with groups ranging in size from methyl to benzyl. We synthesized a phosphopeptide incorporating groups that provided increases in affinity at each position. Thus, hydrocinnamoyl-Tyr(PO3H2)-Leu-cis-3,4-methanoPro-Gln-NHBn, 50, was the highest affinity peptide, exhibiting an IC50 of 125 nM versus 290 nM for peptide 1 in a fluorescence polarization assay.
A brief motivational intervention with 117 homeless adolescents was evaluated using a randomized design and 3-month follow-up. The intervention was designed to raise youths' concerns about their ...substance use, support harm reduction, and encourage greater service utilization at a collaborating agency. The study was designed to strengthen initial promising results of an earlier study (
P. L. Peterson, J. S. Baer, E. A. Wells, J. A. Ginzler, & S. B. Garrett, 2006
). Several modifications in the clinical protocol were included to enhance engagement with the intervention. Analyses revealed no significant benefits for intervention participants when homeless youths' substance use rates were compared with those of control participants. Service utilization during the intervention period increased for those receiving the intervention but returned to baseline levels at follow-up. Participants reported overall reductions in substance use over time. Differences between sampling methods for the current and previous study are discussed, as are the limitations of brief interventions with this population. Future research needs to elucidate mechanisms of change and service engagement for highly vulnerable youth.
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