Dissolvable hydrogel-based wound dressings for in vivo applications

Controlled hydrogel dissolution allows for: 1) atraumatic material removal after it served its function, 2) site-specific delivery of encapsulated therapeutics (e.g., proteins, small molecules), and 3) a tailored administration of an agent with high efficiency. Dissolution of covalently crosslinked hydrogels has been accomplished by incorporating cleavable moieties that undergo ester hydrolysis or enzymatic degradation. Recently, thiol-disulfide exchange, retro Michal-type reactions, retro Diels-Alder reactions, and thiol-thioester exchange chemistries have gained attention, as they provide a responsive synthetic handle for engineering hydrogel dissolution rates. We synthesized, characterized and tested in vivo two on-demand dissolvable dendritic thioester hydrogel dressings for second-degree burn care and hemorrhage control. The hydrogels are composed of lysine-based dendrons and PEG-based crosslinkers, which were prepared in high yields. In context of hemorrhage, there is an unmet clinical need for an on-demand dissolvable sealant for non-compressible hemorrhage or areas of body not amenable to treatment with a torniquet. In a model of in vivo hemorrhage control of intra-abdominal wounds, our hydrogel reduced blood loss by 33% in severe hepatic hemorrhage and by 22% in aortic injury, as compared to untreated controls. There is an unmet clinical need for a second-degree burn dressing that can be removed atraumatically and serve as a barrier to bacterial infection. When our hydrogel was used as a dressing, local and systemic bacterial proliferation after wound contamination was significantly lower than in the untreated group. The total bacterial burden of the burn wound in the positive controls was significantly higher than in the hydrogel group and the negative controls (1.39x10E8 ± 8.30x10E7 CFU/g v. 4.04x10E3 ± 3.99x10E3 CFU/g v. 6.88x10E2 ± 6.38x10E2 respectively; P = 0.009). Also, the total systemic bacterial burden in the positive controls was significantly higher than the hydrogel group and the negative controls (9x10E2 ± 7.76x10E7 CFU/g v. 5x10E1 ± 0 CFU/g v. 5x10E1 ± 0 CFU/g, respectively; P = 0.031). A unique feature of both hydrogel systems is their capability to be dissolved on-demand via thiol-thioester exchange reaction with a biocompatible solution following its initial application – thus the wound area can be re-exposed to allow for definitive surgical care

Meta-analysis and systematic review of skin graft donor-site dressings with future guidelines.

Background: Many types of split-thickness skin graft (STSG) donor-site dressings are available with little consensus from the literature on the optimal dressing type. The purpose of this systematic review was to analyze the most recent outcomes regarding moist and nonmoist dressings for STSG donor sites. Methods: A comprehensive systematic review was conducted across PubMed/MEDLINE, EMBASE, and Cochrane Library databases to search for comparative studies evaluating different STSG donor-site dressings in adult subjects published between 2008 and 2017. The quality of randomized controlled trials was assessed using the Jadad scale. Data were collected on donor-site pain, rate of epithelialization, infection rate, cosmetic appearance, and cost. Meta-analysis was performed for reported pain scores. Results: A total of 41 articles were included comparing 44 dressings. Selected studies included analysis of donor-site pain (36 of 41 articles), rate of epithelialization (38 of 41), infection rate (25 of 41), cosmetic appearance (20 of 41), and cost (10 of 41). Meta-analysis revealed moist dressings result in lower pain (pooled effect size = 1.44). A majority of articles (73%) reported better reepithelialization rates with moist dressings. Conclusion: The literature on STSG donor-site dressings has not yet identified an ideal dressing. Although moist dressings provide superior outcomes with regard to pain control and wound healing, there continues to be a lack of standardization. The increasing commercial availability and marketing of novel dressings necessitates the development of standardized research protocols to design better comparison studies and assess true efficacy.R01 EB021308 - NIBIB NIH HHSPublished versio

Pendekatan Ekologis Dan Tektonika Bahan Pada Perancangan Galeri Seni Ketukangan

Arsitektur di nusantara saat ini lebih mengedepankan ‘tren\u27 modern dan kurang mempertimbangkan seni ketukangan dengan aspek lokal dalam berkarya sehingga identitas arsitektur nusantara semakin terkikis dan budaya/kearifan lokal bukan lagi menjadi pertimbangan utama para penggiat arsitektur dalam merancang. Perancangan objek ini berusaha untuk meningkatkan kemampuan para tukang agar terus berinovasi dalam mencipta serta mengenalkan potensi ketukangan lokal kepada masyarakat umum. Dengan mengeksplorasi potensi alam dan ketukangan menggunakan pendekatan arsitektur ekologis kedalam objek rancang Galeri Seni Ketukangan diharapkan dapat melestarikan identitas kelokalan arsitektur nusantara serta para tukang di masa depan dapat terus berinovasi dalam berkarya dan dapat menarik antusias masyarakat terutama para penggiat arsitektur untuk kembali menerapkan aspek budaya lokal nusantara dalam mencipta karya. Objek rancang mewadahi kegiatan eksplorasi ketukangan untuk melestarikan identitas serta potensi material arsitektur di nusantara. Metoda desain yang akan digunakan adalah metoda desain William M. Pena & Steven A. Pharsall dengan pendekatan ekologis guna meminimalisir dampak objek rancang terhadap lahan dan lingkungan

Oxidation as an Additional Mechanism Underlying Reduced Clot Permeability and Impaired Fibrinolysis in Type 2 Diabetes

Aims. We sought to investigate whether enhanced oxidation contributes to unfavorable fibrin clot properties in patients with diabetes. Methods. We assessed plasma fibrin clot permeation ( , a measure of the pore size in fibrin networks) and clot lysis time induced by recombinant tissue plasminogen activator (CLT) in 163 consecutive type 2 diabetic patients (92 men and 71 women) aged 65 ± 8.8 years with a mean glycated hemoglobin (HbA1c) of 6.8%. We also measured oxidative stress markers, including nitrotyrosine, the soluble form of receptor for advanced glycation end products (sRAGE), 8-iso-prostaglandin F 2 (8-iso-PGF 2 ), oxidized low-density lipoprotein (oxLDL), and advanced glycation end products (AGE). Results. There were inverse correlations between and nitrotyrosine, sRAGE, 8-iso-PGF 2 , and oxLDL. CLT showed a positive correlation with oxLDL and nitrotyrosine but not with other oxidation markers. All these associations remained significant for after adjustment for fibrinogen, disease duration, and HbA1c (all < 0.05), while oxLDL was the only independent predictor of CLT. Conclusions. Our study shows that enhanced oxidative stress adversely affects plasma fibrin clot properties in type 2 diabetic patients, regardless of disease duration and glycemia control

Day hospital versus admission for acute psychiatric disorders

Backgroun

Day hospital versus out-patient care for psychiatric disorders

Obstacle, adventure and endurance competitions in challenging or remote settings are increasing in popularity. A literature search indicates a dearth of evidence-based research on the organisation of medical care for wilderness competitions. The organisation of medical care for each event is best tailored to specific race components, participant characteristics, geography, risk assessments, legal requirements, and the availability of both local and outside resources. Considering the health risks and logistical complexities inherent in these events, there is a compelling need for guiding principles that bridge the fields of wilderness medicine and sports medicine in providing a framework for the organisation of medical care delivery during wilderness and remote obstacle, adventure and endurance competitions. This narrative review, authored by experts in wilderness and operational medicine, provides such a framework. The primary goal is to assist organisers and medical providers in planning for sporting events in which participants are in situations or locations that exceed the capacity of local emergency medical services resources

Hypofibrinolysis in diabetes: a therapeutic target for the reduction of cardiovascular risk

An enhanced thrombotic environment and premature atherosclerosis are key factors for the increased cardiovascular risk in diabetes. The occlusive vascular thrombus, formed secondary to interactions between platelets and coagulation proteins, is composed of a skeleton of fibrin fibres with cellular elements embedded in this network. Diabetes is characterised by quantitative and qualitative changes in coagulation proteins, which collectively increase resistance to fibrinolysis, consequently augmenting thrombosis risk. Current long-term therapies to prevent arterial occlusion in diabetes are focussed on anti-platelet agents, a strategy that fails to address the contribution of coagulation proteins to the enhanced thrombotic milieu. Moreover, antiplatelet treatment is associated with bleeding complications, particularly with newer agents and more aggressive combination therapies, questioning the safety of this approach. Therefore, to safely control thrombosis risk in diabetes, an alternative approach is required with the fibrin network representing a credible therapeutic target. In the current review, we address diabetes-specific mechanistic pathways responsible for hypofibrinolysis including the role of clot structure, defects in the fibrinolytic system and increased incorporation of anti-fibrinolytic proteins into the clot. Future anti-thrombotic therapeutic options are discussed with special emphasis on the potential advantages of modulating incorporation of the anti-fibrinolytic proteins into fibrin networks. This latter approach carries theoretical advantages, including specificity for diabetes, ability to target a particular protein with a possible favourable risk of bleeding. The development of alternative treatment strategies to better control residual thrombosis risk in diabetes will help to reduce vascular events, which remain the main cause of mortality in this condition

Day hospital versus admission for acute psychiatric disorders

BACKGROUND: Inpatient treatment is an expensive way of caring for people with acute psychiatric disorders. It has been proposed that many of those currently treated as inpatients could be cared for in acute psychiatric day hospitals. OBJECTIVES: To assess the effects of day hospital versus inpatient care for people with acute psychiatric disorders. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register (Cochrane Library, issue 4, 2000), MEDLINE (January 1966 to December 2000), EMBASE (1980 to December 2000), CINAHL (1982 to December 2000), PsycLIT (1966 to December 2000), and the reference lists of articles. We approached trialists to identify unpublished studies. SELECTION CRITERIA: Randomised controlled trials of day hospital versus inpatient care, for people with acute psychiatric disorders. Studies were ineligible if a majority of participants were under 18 or over 65, or had a primary diagnosis of substance abuse or organic brain disorder. DATA COLLECTION AND ANALYSIS: Data were extracted independently by two reviewers and cross-checked. Relative risks and 95% confidence intervals (CI) were calculated for dichotomous data. Weighted or standardised means were calculated for continuous data. Day hospital trials tend to present similar outcomes in slightly different formats, making it difficult to synthesise data. Individual patient data were therefore sought so that outcomes could be reanalysed in a common format. MAIN RESULTS: Nine trials (involving 1568 people) met the inclusion criteria. Individual patient data were obtained for four trials (involving 594 people). Combined data suggested that, at the most pessimistic estimate, day hospital treatment was feasible for 23% (n=2268, CI 21 to 25) of those currently admitted to inpatient care. Individual patient data from three trials showed no difference in number of days in hospital between day hospital patients and controls (n=465, 3 RCTs, WMD -0.38 days/month CI -1.32 to 0.55). However, compared to controls, people randomised to day hospital care spent significantly more days in day hospital care (n=265, 3 RCTs, WMD 2.34 days/month CI 1.97 to 2.70) and significantly fewer days in inpatient care (n=265, 3 RCTs, WMD -2.75 days/month CI -3.63 to -1.87). There was no significant difference in readmission rates between day hospital patients and controls (n=667, 5 RCTs, RR 0.91 CI 0.72 to 1.15). For patients judged suitable for day hospital care, individual patient data from three trials showed a significant time-treatment interaction, indicating a more rapid improvement in mental state (n=407, Chi-squared 9.66, p=0.002), but not social functioning (n=295, Chi-squared 0.006, p=0.941) amongst patients treated in the day hospital. Four of five trials found that day hospital care was cheaper than inpatient care (with cost reductions ranging from 20.9 to 36.9%). REVIEWER'S CONCLUSIONS: Caring for people in acute day hospitals can achieve substantial reductions in the numbers of people needing inpatient care, whilst improving patient outcome

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation