Myocard Infarct en Cerebrovasculair Accident keten (MICK) studie

For patients with acute coronary syndrome (ACS) and stroke prompt diagnosis and treatment is essential. Before a patient reaches the hospital he may have had contact with a general practitioner (GP), a GP cooperative (GPC), ambulance service, or Emergency Department. Optimal use and efficient functioning of the acute health care chain is imperative. The aim of the MICK study is to obtain insight into circumstances in which symptoms of patients occur, medical contacts throughout the acute care chain, delays, door-to-balloon and door-to-needle time. This is a prospective observational study including 202 patients suspected of having ACS and 239 suspected of ischemic stroke. Patients filled out a questionnaire and additional data was obtained using registries.\ud Over 40% of all patients suspected of ACS waited more than 6 hours before contacting a health care provider and over 30% of all patients suspected of having a stroke waited more than 4 hours. Patients reached the hospital through many different health care chains. Once a care provider was contacted, 45% of all patients with ACS were hospitalized within 90 minutes at the CCU and 65% of patients with stroke within 4 hours at the stroke unit.\ud Most patients first contacted the GP or GPC. For patients who immediately called 112 time to hospitalization was the shortest.\ud Overall are noticeable the long patient delays in seeking care, the various chains through which patients reach the CCU or stroke unit and the different throughput times

Dutch Prospective Observational Study on Prehospital Treatment of Severe Traumatic Brain Injury: The BRAIN-PROTECT Study Protocol

Background: Severe traumatic brain injury (TBI) is associated with a high mortality rate and those that survive commonly have permanent disability. While there is a broad consensus that appropriate prehospital treatment is crucial for a favorable neurological outcome, evidence to support currently applied treatment strategies is scarce. In particular, the relationship between prehospital treatments and patient outcomes is unclear. The BRAIN-PROTECT study therefore aims to identify prehospital treatment strategies associated with beneficial or detrimental outcomes. Here, we present the study protocol. Study Protocol: BRAIN-PROTECT is the acronym for BRAin INjury: Prehospital Registry of Outcome, Treatments and Epidemiology of Cerebral Trauma. It is a prospective observational study on the prehospital treatment of patients with suspected severe TBI in the Netherlands. Prehospital epidemiology, interventions, medication strategies, and nonmedical factors that may affect outcome are studied. Multivariable regression based modeling will be used to identify confounder-adjusted relationships between these factors and patient outcomes, including mortality at 30 days (primary outcome) or mortality and functional neurological outcome at 1 year (secondary outcomes). Patients in whom severe TBI is suspected during prehospital treatment (Glasgow Coma Scale score 8 in combination with a trauma mechanism or clinical findings suggestive of head injury) are identified by all four helicopter emergency medical services (HEMS) in the Netherlands. Patients are prospectively followed up in 9 participating trauma centers for up to one year. The manuscript reports in detail the objectives, setting, study design, patient inclusion, and data collection process. Ethical and juridical aspects, statistical considerations, as well as limitations of the study design are discussed. Discussion: Current prehospital treatment of patients with suspected severe TBI is based on marginal evidence, and optimal treatment is basically unknown. The BRAINPROTECT study provides an opportunity to evaluate and compare different treatment strategies with respect to patient outcomes. To our knowledge, this study project is the first large-scale prospective prehospital registry of patients with severe TBI that also collects long-term follow-up data and ma

Gelatin Nanoparticles for Complexation and Enhanced Cellular Delivery of mRNA

Messenger RNA (mRNA) is increasingly gaining interest as a modality in vaccination and protein replacement therapy. In regenerative medicine, the mRNA-mediated expression of growth factors has shown promising results. In contrast to protein delivery, successful mRNA delivery requires a vector to induce cellular uptake and subsequent endosomal escape to reach its end destination, the ribosome. Current non-viral vectors such as lipid- or polymer-based nanoparticles have been successfully used to express mRNA-encoded proteins. However, to advance the use of mRNA in regenerative medicine, it is required to assess the compatibility of mRNA with biomaterials that are typically applied in this field. Herein, we investigated the complexation, cellular uptake and maintenance of the integrity of mRNA complexed with gelatin nanoparticles (GNPs). To this end, GNPs with positive, neutral or negative surface charge were synthesized to assess their ability to bind and transport mRNA into cells. Positively charged GNPs exhibited the highest binding affinity and transported substantial amounts of mRNA into pre-osteoblastic cells, as assessed by confocal microscopy using fluorescently labeled mRNA. Furthermore, the GNP-bound mRNA remained stable. However, no expression of mRNA-encoded protein was detected, which is likely related to insufficient endosomal escape and/or mRNA release from the GNPs. Our results indicate that gelatin-based nanomaterials interact with mRNA in a charge-dependent manner and also mediate cellular uptake. These results create the basis for the incorporation of further functionality to yield endosomal release

Protein Expression Correlates Linearly with mRNA Dose over Up to Five Orders of Magnitude In Vitro and In Vivo

Contains fulltext : 233735.pdf (Publisher’s version ) (Open Access

Prehospital paths and hospital arrival time of patients with acute coronary syndrome or stroke, a prospective observational study

Background: Patients with a presumed diagnosis of acute coronary syndrome (ACS) or stroke may have had contact with several healthcare providers prior to hospital arrival. The aim of this study was to describe the various prehospital paths and the effect on time delays of patients with ACS or stroke. Methods: This prospective observational study included patients with presumed ACS or stroke who may choose to contact four different types of health care providers. Questionnaires were completed by patients, general practitioners (GP), GP cooperatives, ambulance services and emergency departments (ED). Additional data were retrieved from hospital registries. Results: Two hundred two ACS patients arrived at the hospital by 15 different paths and 243 stroke patients by ten different paths. Often several healthcare providers were involved (60.8 % ACS, 95.1 % stroke). Almost half of all patients first contacted their GP (47.5 % ACS, 49.4 % stroke). Some prehospital paths were more frequently used, e.g. GP (cooperative) and ambulance in ACS, and GP or ambulance and ED in stroke. In 65 % of all events an ambulance was involved. Median time between start of symptoms and hospital arrival for ACS patients was over 6 h and for stroke patients 4 h. Of ACS patients 47.7 % waited more than 4 h before seeking medical advice compared to 31.6 % of stroke patients. Median time between seeking medical advice to arrival at hospital was shortest in paths involving the ambulance only (60 min ACS, 54 min stroke) or in combination with another healthcare provider (80 to 100 min ACS, 99 to 106 min stroke). Conclusions: Prehospital paths through which patients arrived in hospital are numerous and often complex, and various time delays occurred. Delays depend on the entry point of the health care system, and dialing the emergency number seems to be the best choice. Since reducing patient delay is difficult and noticeable differences exist between various prehospital paths, further research into reasons for these different entry choices may yield possibilities to optimize paths and reduce overall time delay