176 research outputs found

    Improving Effective Surgical Delivery in Humanitarian Disasters: Lessons from Haiti

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    Kathryn Chu and colleagues describe the experiences of Médecins sans Frontières after the 2010 Haiti earthquake, and discuss how to improve delivery of surgery in humanitarian disasters

    Early outcome of facial reconstructive surgery abroad: a comparative study

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    Every year, many medical missions are undertaken in the developing world but there is almost a universal lack of outcome data on the quality of these missions. The present study compares early clinical outcome and complication rate in two consecutive missions (facial reconstruction) undertaken to Ethiopia in 2007 and 2008. The object was to establish if measures adopted following feedback from the first mission led to improvement of the results. A significant improvement was observed in early clinical outcome and there were less severe complications in the 2008 compared to the 2007 mission. On both occasions, significantly more complications were experienced after complex compared to simple procedures. Despite improved outcome in 2008, 50% of the complex cases had an unfavourable clinical result. The data suggest that early outcome studies are a useful method of critically evaluating the quality of surgical mission. The unsatisfactory outcome of complex procedures underlines the need for feedback on the quality of these missions

    Quality of Care in Humanitarian Surgery

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    Humanitarian surgical programs are set up de novo, within days or hours in emergency or disaster settings. In such circumstances, insuring quality of care is extremely challenging. Basic structural inputs such as a safe structure, electricity, clean water, a blood bank, sterilization equipment, a post-anesthesia recovery unit, appropriate medications should be established. Currently, no specific credentials are needed for surgeons to operate in a humanitarian setting; the training of more humanitarian surgeons is desperately needed. Standard perioperative protocols for the humanitarian setting after common procedures such as Cesarean section, burn care, open fractures, and amputations and antibiotic prophylaxis, and post-operative pain management must be developed. Outcome data, especially long-term outcomes, are difficult to collect as patients often do not return for follow-up and may be difficult to trace; standard databases for post-operative infections and mortality rates should be established. Checklists have recently received significant attention as an instrument to support the improvement of surgical quality; knowing which items are most applicable to humanitarian settings remains unknown. In conclusion, the quality of surgical services in humanitarian settings must be regulated. Many other core medical activities of humanitarian organizations such as therapeutic feeding, mass vaccination, and the treatment of infectious diseases, such as tuberculosis and human immunodeficiency virus, are subject to rigorous reporting of quality indicators. There is no reason why surgery should be exempted from quality oversight. The surgical humanitarian community should pull together before the next disaster strikes

    Genome-wide linkage analysis of 972 bipolar pedigrees using single-nucleotide polymorphisms.

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    Because of the high costs associated with ascertainment of families, most linkage studies of Bipolar I disorder (BPI) have used relatively small samples. Moreover, the genetic information content reported in most studies has been less than 0.6. Although microsatellite markers spaced every 10 cM typically extract most of the genetic information content for larger multiplex families, they can be less informative for smaller pedigrees especially for affected sib pair kindreds. For these reasons we collaborated to pool family resources and carried out higher density genotyping. Approximately 1100 pedigrees of European ancestry were initially selected for study and were genotyped by the Center for Inherited Disease Research using the Illumina Linkage Panel 12 set of 6090 single-nucleotide polymorphisms. Of the ~1100 families, 972 were informative for further analyses, and mean information content was 0.86 after pruning for linkage disequilibrium. The 972 kindreds include 2284 cases of BPI disorder, 498 individuals with bipolar II disorder (BPII) and 702 subjects with recurrent major depression. Three affection status models (ASMs) were considered: ASM1 (BPI and schizoaffective disorder, BP cases (SABP) only), ASM2 (ASM1 cases plus BPII) and ASM3 (ASM2 cases plus recurrent major depression). Both parametric and non-parametric linkage methods were carried out. The strongest findings occurred at 6q21 (non-parametric pairs LOD 3.4 for rs1046943 at 119 cM) and 9q21 (non-parametric pairs logarithm of odds (LOD) 3.4 for rs722642 at 78 cM) using only BPI and schizoaffective (SA), BP cases. Both results met genome-wide significant criteria, although neither was significant after correction for multiple analyses. We also inspected parametric scores for the larger multiplex families to identify possible rare susceptibility loci. In this analysis, we observed 59 parametric LODs of 2 or greater, many of which are likely to be close to maximum possible scores. Although some linkage findings may be false positives, the results could help prioritize the search for rare variants using whole exome or genome sequencing

    Intensive medical student involvement in short-term surgical trips provides safe and effective patient care: a case review

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    <p>Abstract</p> <p>Background</p> <p>The hierarchical nature of medical education has been thought necessary for the safe care of patients. In this setting, medical students in particular have limited opportunities for experiential learning. We report on a student-faculty collaboration that has successfully operated an annual, short-term surgical intervention in Haiti for the last three years. Medical students were responsible for logistics and were overseen by faculty members for patient care. Substantial planning with local partners ensured that trip activities supplemented existing surgical services. A case review was performed hypothesizing that such trips could provide effective surgical care while also providing a suitable educational experience.</p> <p>Findings</p> <p>Over three week-long trips, 64 cases were performed without any reported complications, and no immediate perioperative morbidity or mortality. A plurality of cases were complex urological procedures that required surgical skills that were locally unavailable (43%). Surgical productivity was twice that of comparable peer institutions in the region. Student roles in patient care were greatly expanded in comparison to those at U.S. academic medical centers and appropriate supervision was maintained.</p> <p>Discussion</p> <p>This demonstration project suggests that a properly designed surgical trip model can effectively balance the surgical needs of the community with an opportunity to expose young trainees to a clinical and cross-cultural experience rarely provided at this early stage of medical education. Few formalized programs currently exist although the experience above suggests the rewarding potential for broad-based adoption.</p

    An organizational framework and strategic implementation for system-level change to enhance research-based practice: QUERI Series

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    <p>Abstract</p> <p>Background</p> <p>The continuing gap between available evidence and current practice in health care reinforces the need for more effective solutions, in particular related to organizational context. Considerable advances have been made within the U.S. Veterans Health Administration (VA) in systematically implementing evidence into practice. These advances have been achieved through a system-level program focused on collaboration and partnerships among policy makers, clinicians, and researchers.</p> <p>The Quality Enhancement Research Initiative (QUERI) was created to generate research-driven initiatives that directly enhance health care quality within the VA and, simultaneously, contribute to the field of implementation science. This paradigm-shifting effort provided a natural laboratory for exploring organizational change processes. This article describes the underlying change framework and implementation strategy used to operationalize QUERI.</p> <p>Strategic approach to organizational change</p> <p>QUERI used an evidence-based organizational framework focused on three contextual elements: 1) cultural norms and values, in this case related to the role of health services researchers in evidence-based quality improvement; 2) capacity, in this case among researchers and key partners to engage in implementation research; 3) and supportive infrastructures to reinforce expectations for change and to sustain new behaviors as part of the norm. As part of a QUERI Series in <it>Implementation Science</it>, this article describes the framework's application in an innovative integration of health services research, policy, and clinical care delivery.</p> <p>Conclusion</p> <p>QUERI's experience and success provide a case study in organizational change. It demonstrates that progress requires a strategic, systems-based effort. QUERI's evidence-based initiative involved a deliberate cultural shift, requiring ongoing commitment in multiple forms and at multiple levels. VA's commitment to QUERI came in the form of visionary leadership, targeted allocation of resources, infrastructure refinements, innovative peer review and study methods, and direct involvement of key stakeholders. Stakeholders included both those providing and managing clinical care, as well as those producing relevant evidence within the health care system. The organizational framework and related implementation interventions used to achieve contextual change resulted in engaged investigators and enhanced uptake of research knowledge. QUERI's approach and progress provide working hypotheses for others pursuing similar system-wide efforts to routinely achieve evidence-based care.</p

    Calcitonin receptor N-glycosylation enhances peptide hormone affinity by controlling receptor dynamics

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    The class B G protein-coupled receptor (GPCR) calcitonin receptor (CTR) is a drug target for osteoporosis and diabetes. N-glycosylation of asparagine 130 in its extracellular domain (ECD) enhances calcitonin hormone affinity with the proximal GlcNAc residue mediating this effect through an unknown mechanism. Here, we present two crystal structures of salmon calcitonin-bound, GlcNAc-bearing CTR ECD at 1.78 and 2.85 Å resolutions and analyze the mechanism of the glycan effect. The N130 GlcNAc does not contact the hormone. Surprisingly, the structures are nearly identical to a structure of hormone-bound, N-glycan-free ECD, which suggested that the GlcNAc might affect CTR dynamics not observed in the static crystallographic snapshots. Hydrogen-deuterium exchange mass spectrometry and molecular dynamics simulations revealed that glycosylation stabilized a β-sheet adjacent to the N130 GlcNAc and the N-terminal α-helix near the peptide-binding site, while increasing flexibility of the peptide-binding site turret loop. These changes due to N-glycosylation increased the ligand on-rate and decreased its off rate. The glycan effect extended to RAMP-CTR amylin receptor complexes and was also conserved in the related CGRP receptor. These results reveal that N-glycosylation can modulate GPCR function by altering receptor dynamics

    Pro-inflammatory mechanisms of muscarinic receptor stimulation in airway smooth muscle

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    Background: Acetylcholine, the primary parasympathetic neurotransmitter in the airways, plays an important role in bronchoconstriction and mucus production. Recently, it has been shown that acetylcholine, by acting on muscarinic receptors, is also involved in airway inflammation and remodelling. The mechanism(s) by which muscarinic receptors regulate inflammatory responses are, however, still unknown. Methods: The present study was aimed at characterizing the effect of muscarinic receptor stimulation on cytokine secretion by human airway smooth muscle cells (hASMc) and to dissect the intracellular signalling mechanisms involved. hASMc expressing functional muscarinic M(2) and M(3) receptors were stimulated with the muscarinic receptor agonist methacholine, alone, and in combination with cigarette smoke extract (CSE), TNF-alpha, PDGF-AB or IL-1 beta. Results: Muscarinic receptor stimulation induced modest IL-8 secretion by itself, yet augmented IL-8 secretion in combination with CSE, TNF-alpha or PDGF-AB, but not with IL-1 beta. Pretreatment with GF109203X, a protein kinase C (PKC) inhibitor, completely normalized the effect of methacholine on CSE-induced IL-8 secretion, whereas PMA, a PKC activator, mimicked the effects of methacholine, inducing IL-8 secretion and augmenting the effects of CSE. Similar inhibition was observed using inhibitors of I kappa B-kinase-2 (SC514) and MEK1/2 (U0126), both downstream effectors of PKC. Accordingly, western blot analysis revealed that methacholine augmented the degradation of I kappa B alpha and the phosphorylation of ERK1/2 in combination with CSE, but not with IL-1b in hASMc. Conclusions: We conclude that muscarinic receptors facilitate CSE-induced IL-8 secretion by hASMc via PKC dependent activation of I kappa B alpha and ERK1/2. This mechanism could be of importance for COPD patients usin

    Overview of the VA Quality Enhancement Research Initiative (QUERI) and QUERI theme articles: QUERI Series

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    <p>Abstract</p> <p>Background</p> <p>Continuing challenges to timely adoption of evidence-based clinical practices in healthcare have generated intense interest in the development and application of new implementation methods and frameworks. These challenges led the United States (U.S.) Department of Veterans Affairs (VA) to create the Quality Enhancement Research Initiative (QUERI) in the late 1990s. QUERI's purpose was to harness VA's health services research expertise and resources in an ongoing system-wide effort to improve the performance of the VA healthcare system and, thus, quality of care for veterans. QUERI in turn created a systematic means of involving VA researchers both in enhancing VA healthcare quality, by implementing evidence-based practices, and in contributing to the continuing development of implementation science.</p> <p>The efforts of VA researchers to improve healthcare delivery practices through QUERI and related initiatives are documented in a growing body of literature. The scientific frameworks and methodological approaches developed and employed by QUERI are less well described. A QUERI Series of articles in <it>Implementation Science </it>will illustrate many of these QUERI tools. This <it>Overview </it>article introduces both QUERI and the Series.</p> <p>Methods</p> <p>The <it>Overview </it>briefly explains the purpose and context of the QUERI Program. It then describes the following: the key operational structure of QUERI Centers, guiding frameworks designed to enhance implementation and related research, QUERI's progress and promise to date, and the Series' general content. QUERI's frameworks include a core set of steps for diagnosing and closing quality gaps and, simultaneously, advancing implementation science. Throughout the paper, the envisioned involvement and activities of VA researchers within QUERI Centers also are highlighted. The Series is then described, illustrating the use of QUERI frameworks and other tools designed to respond to implementation challenges.</p> <p>Conclusion</p> <p>QUERI's simultaneous pursuit of improvement and research goals within a large healthcare system may be unique. However, descriptions of this still-evolving effort, including its conceptual frameworks, methodological approaches, and enabling processes, should have applicability to implementation researchers in a range of health care settings. Thus, the <it>Series </it>is offered as a resource for other implementation research programs and researchers pursuing common goals in improving care and developing the field of implementation science.</p
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