Beginning in 2000 and accelerating in 2004, the Berlin Heart EXCOR (Berlin Heart Inc Woodlands, TX) became the first pediatric-specific ventricular assist device (VAD) applied throughout North ...America for children of all sizes. This retrospective study analyzed the initial Berlin Heart EXCOR pediatric experience as a bridge to transplantation.
Between June 2000 and May 2007, 97 EXCOR VADs were implanted in North America at 29 different institutions. The analysis is limited to 73 patients (75%) from 17 institutions, for which retrospective data were available.
Median age and weight at VAD implant were 2.1 years (range, 12 days-17.8 years) and 11 kg (range, 3-87.6 kg), respectively. The primary diagnoses were dilated cardiomyopathy in 42 (58%), congenital heart disease in 19 (26%), myocarditis in 7 (10%), and other cardiomyopathies in 5 (7%). Pre-implant clinical condition was critical cardiogenic shock in 38 (52%), progressive decline in 33 (45%), or other in 2 (3%). Extracorporeal membrane oxygenation was used as a bridge to EXCOR in 22 patients (30%). Device selection was left VAD (LVAD) in 42 (57%) and biventricular assist devices (BiVAD) in 31 (43%). The EXCOR bridged 51 patients (70%) to transplant and 5 (7%) to recovery. Mortality on the EXCOR was 23% (n = 17) overall, including 35% (11 of 31) in BiVAD vs 14% (6 of 42) in LVAD patients (p = 0.003). Multivariate analysis showed younger age and BiVAD support were significant risk factors for death while on the EXCOR.
This limited but large preliminary North American experience with the Berlin Heart EXCOR VAD as a bridge to cardiac transplantation for children of all ages and sizes points to the feasibility of this approach. The prospective investigational device evaluation trial presently underway will further characterize the safety and efficacy of the EXCOR as a bridge to pediatric cardiac transplantation.
The ventricular assist device (VAD) Berlin Heart EXCOR Pediatrics was utilized at our institution since 2004 for bridging pediatric patients to cardiac transplantation or myocardial recovery. The ...present study reviewed our results following VAD implantation. We retrospectively reviewed patients that underwent implantation of a VAD between October 2004 and October 2008. Data collected included age at implantation, gender, weight, underlying disease, pre‐ and postdevice clinical status, complications, and outcome. Fifteen patients were identified (9 female and 6 male, average age: 8.8 years, range 0.3–14.8; average weight 31.1 kg, range 5.2–86.4). Indications for VAD support were dilated cardiomyopathy in 14 patients and progressing heart failure with a single ventricle physiology (bidirectional Glenn shunt) in one patient. Three patients (20%) were bridged from extracorporeal membrane oxygenation to VAD. Average support was 29 (1–108) days. Fourteen patients were on a bi‐VAD, one patient (single ventricle) had single VAD support. Three patients developed mediastinal/pericardial fluid collections, requiring surgical exploration in two, and drain insertion in one. Three patients presented with neurological symptoms. In two patients, a total of three blood pumps were exchanged due to thrombus formation. No patient was weaned off the VAD; two patients (13%) died on the VAD. All surviving patients are neurologically intact at follow‐up. In our experience, VAD support provides an effective means of bridging children with advanced dilated cardiomyopathy or heart failure to transplantation with a relatively small number of complications and deaths given the complexity of the patient population.
Caring for pediatric patients with a ventricular assist device (VAD) requires a collaborative approach from an interprofessional team to ensure maximum patient safety and optimal outcomes. Initiating ...a VAD program is challenging, due to the complex medical and technical nature of this device and associated learning needs. At our institution, the development of the interprofessional VAD support team was established in four phases. Initial Education, Core Team Formation, Expansion, and Evaluation. A “core VAD team” was created after the initial education at an established VAD center. In a third step, all efforts were directed toward increasing the number of health care professionals caring for the VAD patients in the Cardiac Critical Care setting and on the Cardiac ward. The last phase consists of ongoing evaluation. Several key areas imperative to the care of a patient on a VAD were identified and further elaborated. The complex care of a patient on a VAD needs a specialized team approach to cover all patient care needs. Ongoing interprofessional education continues to improve competency of care. Continuity of care was assured on all levels of service to ensure the best possible outcomes.
G protein–coupled receptors (GPCRs) are critical regulators of cellular function acting via heterotrimeric G proteins as their primary transducers with individual GPCRs capable of pleiotropic ...coupling to multiple G proteins. Structural features governing G protein selectivity and promiscuity are currently unclear. Here, we used cryo-electron microscopy (cryo-EM) to determine structures of the cholecystokinin (CCK) type 1 receptor (CCK1R) bound to the CCK peptide agonist, CCK-8 and 2 distinct transducer proteins, its primary transducer Gq, and the more weakly coupled Gs. As seen with other Gq/11–GPCR complexes, the Gq–α5 helix (αH5) bound to a relatively narrow pocket in the CCK1R core. Surprisingly, the backbone of the CCK1R and volume of the G protein binding pocket were essentially equivalent when Gs was bound, with the Gs αH5 displaying a conformation that arises from “unwinding” of the far carboxyl-terminal residues, compared to canonically Gs coupled receptors. Thus, integrated changes in the conformations of both the receptor and G protein are likely to play critical roles in the promiscuous coupling of individual GPCRs.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
The class B secretin GPCR (SecR) has broad physiological effects, with target potential for treatment of metabolic and cardiovascular disease. Molecular understanding of SecR binding and ...activation is important for its therapeutic exploitation. We combined cryo-electron microscopy, molecular dynamics, and biochemical cross-linking to determine a 2.3 Å structure, and interrogate dynamics, of secretin bound to the SecR:Gs complex. SecR exhibited a unique organization of its extracellular domain (ECD) relative to its 7-transmembrane (TM) core, forming more extended interactions than other family members. Numerous polar interactions formed between secretin and the receptor extracellular loops (ECLs) and TM helices. Cysteine-cross-linking, cryo-electron microscopy multivariate analysis and molecular dynamics simulations revealed that interactions between peptide and receptor were dynamic, and suggested a model for initial peptide engagement where early interactions between the far N-terminus of the peptide and SecR ECL2 likely occur following initial binding of the peptide C-terminus to the ECD.
Measuring joint range of motion is an important skill for many allied health professionals. While the Universal Goniometer is the most commonly utilised clinical tool for measuring joint range of ...motion, the evolution of smartphone technology and applications (apps) provides the clinician with more measurement options. However, the reliability and validity of these smartphones and apps is still somewhat uncertain. The aim of this study was to systematically review the literature regarding the intra- and inter-rater reliability and validity of smartphones and apps to measure joint range of motion. Eligible studies were published in English peer-reviewed journals with full text available, involving the assessment of reliability and/or validity of a non-videographic smartphone app to measure joint range of motion in participants >18 years old. An electronic search using PubMed, Medline via Ovid, EMBASE, CINAHL, and SPORTSDiscus was performed. The risk of bias was assessed using a standardised appraisal tool. Twenty-three of the eligible 25 studies exceeded the minimum 60% score to be classified as a low risk of bias, although 3 of the 13 criteria were not achieved in >50% of the studies. Most of the studies demonstrated adequate intra-rater or inter-rater reliability and/or validity for >50% of the range of motion tests across all joints assessed. However, this level of evidence appeared weaker for absolute (e.g. mean difference ± limit of agreement, minimal detectable change) than relative (e.g. intraclass correlation, correlation) measures; and for spinal rotation than spinal extension, flexion and lateral flexion. Our results provide clinicians with sufficient evidence to support the use of smartphones and apps in place of goniometers to measure joint motion. Future research should address some methodological limitations of the literature, especially including the inclusion of absolute and not just relative reliability and validity statistics.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Xerostomia (the feeling of dry mouth) is a common symptom especially in older adults. Causes of dry mouth include medications, autoimmune disease (Sjögren's Syndrome), radiotherapy or ...chemotherapy for cancer, hormone disorders and infections.
Objectives
To determine which topical treatments for dry mouth are effective in reducing this symptom.
Search methods
We searched the following electronic databases: the Cochrane Oral Health Group Trials Register (28 October 2011), The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 4 2011), MEDLINE via OVID (1950 to 28 October 2011), EMBASE via OVID (1980 to 28 October 2011), CINAHL via EBSCO (1980 to 28 October 2011), AMED via OVID (1985 to 28 October 2011), CANCERLIT via PubMed (1950 to 28 October 2011).
Selection criteria
We included randomised controlled trials of topical interventions such as lozenges, sprays, mouthrinses, gels, oils, chewing gum or toothpastes for the treatment of dry mouth symptom. We classified interventions into two broad categories, saliva stimulants and saliva substitutes, and these were compared with either placebo or another intervention. We included both parallel group and crossover trials.
Data collection and analysis
Two or more review authors independently carried out data extraction and assessed risk of bias. Trial authors were contacted for additional information as required.
Main results
Thirty‐six randomised controlled trials involving 1597 participants met the inclusion criteria. Two trials compared saliva stimulants to placebo, nine trials compared saliva substitutes to placebo, five trials compared saliva stimulants directly with saliva substitutes, 18 trials directly compared two or more saliva substitutes, and two trials directly compared two or more saliva stimulants. Only one trial was at low risk of bias and 17 were at high risk of bias. Due to the range of interventions, comparisons and outcome measures in the trials, meta‐analysis was possible for only a few comparisons. Oxygenated glycerol triester (OGT) saliva substitute spray shows evidence of effectiveness compared to an electrolyte spray (standardised mean difference (SMD) 0.77, 95% confidence interval (CI) 0.38 to 1.15) which corresponds to approximately a mean difference of 2 points on a 10‐point visual analogue scale (VAS) for mouth dryness. Both integrated mouthcare systems (toothpaste + gel + mouthwash) and oral reservoir devices show promising results but there is insufficient evidence at present to recommend their use. Although chewing gum is associated with increased saliva production in the majority of those with residual capacity, there is no evidence that gum is more or less effective than saliva substitutes.
Authors' conclusions
There is no strong evidence from this review that any topical therapy is effective for relieving the symptom of dry mouth. OGT spray is more effective than an aqueous electrolyte spray (SMD 0.77, 95% CI 0.38 to 1.15) which is approximately equivalent to a mean difference of 2 points on a 10‐point VAS scale for mouth dryness. Chewing gums appear to increase saliva production in those with residual secretory capacity and may be preferred by patients, but there is no evidence that gum is better or worse than saliva substitutes. Integrated mouthcare systems and oral reservoir devices may be helpful but further research is required to confirm this. Well designed, adequately powered randomised controlled trials of topical interventions for dry mouth, which are designed and reported according to CONSORT guidelines, are required to provide evidence to guide clinical care. For many people the symptom of dry mouth is a chronic problem and trials should evaluate whether treatments are palatable, effective in reducing xerostomia, as well as the long‐term effects of treatments on quality of life of those with chronic dry mouth symptoms.
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