Posterior lumbar interbody fusion using non resorbable poly-ether-ether-ketone versus resorbable poly-l-lactide-co-d,l-lactide fusion devices. Clinical outcome at a minimum of 2-year follow-up

Previous papers on resorbable poly-l-lactide-co-d,l-lactide (PLDLLA) cages in spinal fusion have failed to report adequately on patient-centred clinical outcome measures. Also comparison of PLDLLA cage with a traditionally applicable counterpart has not been previously reported. This is the first randomized prospective study that assesses clinical outcome of PLDLLA cage compared with a poly-ether-ether-ketone (PEEK) implant. Twenty-six patients were randomly assigned to undergo instrumented posterior lumbar interbody fusion (PLIF) whereby either a PEEK cage or a PLDLLA cage was implanted. Clinical outcome based on visual analogue scale scores for leg pain and back pain, as well as Oswestry Disability Index (ODI) and SF-36 questionnaires were documented and analysed. When compared with preoperative values, all clinical parameters have significantly improved in the PEEK group at 2 years after surgery with the exception of SF-36 general health, SF-36 mental health and SF-36 role emotional scores. No clinical parameter showed significant improvement at 2 years after surgery compared with preoperative values in the PLDLLA patient group. Only six patients (50%) in the PLDLLA group showed improvement in the VAS scores for leg and back pain as well as the ODI, as opposed to 10 patients (71%) in the PEEK group. One-third of the patients in the PLDLLA group actually reported worsening of their pain scores and ODI. Three cases of mild to moderate osteolysis were seen in the PLDLLA group. Following up on our preliminary report, these 2-year results confirm the superiority of the PEEK implant to the resorbable PLDLLA implant in aiding spinal fusion and alleviating symptoms following PLIF in patients with degenerative spondylolisthesis associated with either canal stenosis or foramen stenosis or both and emanating from a single lumbar segment

Sedation in palliative care – a critical analysis of 7 years experience

BACKGROUND: The administration of sedatives in terminally ill patients becomes an increasingly feasible medical option in end-of-life care. However, sedation for intractable distress has raised considerable medical and ethical concerns. In our study we provide a critical analysis of seven years experience with the application of sedation in the final phase of life in our palliative care unit. METHODS: Medical records of 548 patients, who died in the Palliative Care Unit of GK Havelhoehe between 1995–2002, were retrospectively analysed with regard to sedation in the last 48 hrs of life. The parameters of investigation included indication, choice and kind of sedation, prevalence of intolerable symptoms, patients' requests for sedation, state of consciousness and communication abilities during sedation. Critical evaluation included a comparison of the period between 1995–1999 and 2000–2002. RESULTS: 14.6% (n = 80) of the patients in palliative care had sedation given by the intravenous route in the last 48 hrs of their life according to internal guidelines. The annual frequency to apply sedation increased continuously from 7% in 1995 to 19% in 2002. Main indications shifted from refractory control of physical symptoms (dyspnoea, gastrointestinal, pain, bleeding and agitated delirium) to more psychological distress (panic-stricken fear, severe depression, refractory insomnia and other forms of affective decompensation). Patients' and relatives' requests for sedation in the final phase were significantly more frequent during the period 2000–2002. CONCLUSION: Sedation in the terminal or final phase of life plays an increasing role in the management of intractable physical and psychological distress. Ethical concerns are raised by patients' requests and needs on the one hand, and the physicians' self-understanding on the other hand. Hence, ethically acceptable criteria and guidelines for the decision making are needed with special regard to the nature of refractory and intolerable symptoms, patients' informed consent and personal needs, the goals and aims of medical sedation in end-of-life care

What we talk about when we talk about "global mindset": managerial cognition in multinational corporations

Recent developments in the global economy and in multinational corporations have placed significant emphasis on the cognitive orientations of managers, giving rise to a number of concepts such as “global mindset” that are presumed to be associated with the effective management of multinational corporations (MNCs). This paper reviews the literature on global mindset and clarifies some of the conceptual confusion surrounding the construct. We identify common themes across writers, suggesting that the majority of studies fall into one of three research perspectives: cultural, strategic, and multidimensional. We also identify two constructs from the social sciences that underlie the perspectives found in the literature: cosmopolitanism and cognitive complexity and use these two constructs to develop an integrative theoretical framework of global mindset. We then provide a critical assessment of the field of global mindset and suggest directions for future theoretical and empirical research

Overcoming the barriers of teaching physical examination at the bedside: More than just curriculum design

Background: Physicians in training must achieve a high degree of proficiency in performing physical examinations and must strive to become experts in the field. Concerns are emerging about physicians' abilities to perform these basic skills, essential for clinical decision making. Learning at the bedside has the potential to support skill acquisition through deliberate practice. Previous skills improvement programs, targeted at teaching physical examinations, have been successful at increasing the frequency of performing and teaching physical examinations. It remains unclear what barriers might persist after such program implementation. This study explores residents' and physicians' perceptions of physical examinations teaching at the bedside following the implementation of a new structured bedside curriculum: What are the potentially persisting barriers and proposed solutions for improvement? Methods: The study used a constructivist approach using a qualitative inductive thematic analysis that was oriented to construct an understanding of the barriers and facilitators of physical examination teaching in the context of a new bedside curriculum. Participants took part in individual interviews and subsequently focus groups. Transcripts were coded and themes were identified. Results: Data analyses yielded three main themes: (1) the culture of teaching physical examination at the bedside is shaped and threatened by the lack of hospital support, physicians' motivation and expertise, residents' attitudes and dependence on technology, (2) the hospital environment makes bedside teaching difficult because of its chaotic nature, time constraints and conflicting responsibilities, and finally (3) structured physical examination curricula create missed opportunities in being restrictive and pose difficulties in identifying patients with findings. Conclusions: Despite the implementation of a structured bedside curriculum for physical examination teaching, our study suggests that cultural, environmental and curriculum-related barriers remain important issues to be addressed. Institutions wishing to develop and implement similar bedside curricula should prioritize recruitment of expert clinical teachers, recognizing their time and efforts. Teaching should be delivered in a protected environment, away from clinical duties, and with patients with real findings. Physicians must value teaching and learning of physical examination skills, with multiple hands-on opportunities for direct role modeling, coaching, observation and deliberate practice. Ideally, clinical teachers should master the art of combining both patient care and educational activities

Modelling study of dimerization in mammalian defensins

BACKGROUND: Defensins are antimicrobial peptides of innate immunity functioning by non-specific binding to anionic phospholipids in bacterial membranes. Their cationicity, amphipathicity and ability to oligomerize are considered key factors for their action. Based on structural information on human β-defensin 2, we examine homologous defensins from various mammalian species for conserved functional physico-chemical characteristics. RESULTS: Based on homology greater than 40%, structural models of 8 homologs of HBD-2 were constructed. A conserved pattern of electrostatics and dynamics was observed across 6 of the examined defensins; models backed by energetics suggest that the defensins in these 6 organisms are characterized by dimerization-linked enhanced functional potentials. In contrast, dimerization is not energetically favoured in the sheep, goat and mouse defensins, suggesting that they function efficiently as monomers. CONCLUSION: β-defensin 2 from some mammals may work as monomers while those in others, including humans, work as oligomers. This could potentially be used to design human defensins that may be effective at lower concentrations and hence have therapeutic benefits

Calcium Handling in Human Induced Pluripotent Stem Cell Derived Cardiomyocytes

BACKGROUND: The ability to establish human induced pluripotent stem cells (hiPSCs) by reprogramming of adult fibroblasts and to coax their differentiation into cardiomyocytes opens unique opportunities for cardiovascular regenerative and personalized medicine. In the current study, we investigated the Ca(2+)-handling properties of hiPSCs derived-cardiomyocytes (hiPSC-CMs). METHODOLOGY/PRINCIPAL FINDINGS: RT-PCR and immunocytochemistry experiments identified the expression of key Ca(2+)-handling proteins. Detailed laser confocal Ca(2+) imaging demonstrated spontaneous whole-cell [Ca(2+)](i) transients. These transients required Ca(2+) influx via L-type Ca(2+) channels, as demonstrated by their elimination in the absence of extracellular Ca(2+) or by administration of the L-type Ca(2+) channel blocker nifedipine. The presence of a functional ryanodine receptor (RyR)-mediated sarcoplasmic reticulum (SR) Ca(2+) store, contributing to [Ca(2+)](i) transients, was established by application of caffeine (triggering a rapid increase in cytosolic Ca(2+)) and ryanodine (decreasing [Ca(2+)](i)). Similarly, the importance of Ca(2+) reuptake into the SR via the SR Ca(2+) ATPase (SERCA) pump was demonstrated by the inhibiting effect of its blocker (thapsigargin), which led to [Ca(2+)](i) transients elimination. Finally, the presence of an IP3-releasable Ca(2+) pool in hiPSC-CMs and its contribution to whole-cell [Ca(2+)](i) transients was demonstrated by the inhibitory effects induced by the IP3-receptor blocker 2-Aminoethoxydiphenyl borate (2-APB) and the phospholipase C inhibitor U73122. CONCLUSIONS/SIGNIFICANCE: Our study establishes the presence of a functional, SERCA-sequestering, RyR-mediated SR Ca(2+) store in hiPSC-CMs. Furthermore, it demonstrates the dependency of whole-cell [Ca(2+)](i) transients in hiPSC-CMs on both sarcolemmal Ca(2+) entry via L-type Ca(2+) channels and intracellular store Ca(2+) release

Effectiveness of electronic guideline-based implementation systems in ambulatory care settings - a systematic review

<p>Abstract</p> <p>Background</p> <p>Electronic guideline-based decision support systems have been suggested to successfully deliver the knowledge embedded in clinical practice guidelines. A number of studies have already shown positive findings for decision support systems such as drug-dosing systems and computer-generated reminder systems for preventive care services.</p> <p>Methods</p> <p>A systematic literature search (1990 to December 2008) of the English literature indexed in the Medline database, Embase, the Cochrane Central Register of Controlled Trials, and CRD (DARE, HTA and NHS EED databases) was conducted to identify evaluation studies of electronic multi-step guideline implementation systems in ambulatory care settings. Important inclusion criterions were the multidimensionality of the guideline (the guideline needed to consist of several aspects or steps) and real-time interaction with the system during consultation. Clinical decision support systems such as one-time reminders for preventive care for which positive findings were shown in earlier reviews were excluded. Two comparisons were considered: electronic multidimensional guidelines versus usual care (comparison one) and electronic multidimensional guidelines versus other guideline implementation methods (comparison two).</p> <p>Results</p> <p>Twenty-seven publications were selected for analysis in this systematic review. Most designs were cluster randomized controlled trials investigating process outcomes more than patient outcomes. With success defined as at least 50% of the outcome variables being significant, none of the studies were successful in improving patient outcomes. Only seven of seventeen studies that investigated process outcomes showed improvements in process of care variables compared with the usual care group (comparison one). No incremental effect of the electronic implementation over the distribution of paper versions of the guideline was found, neither for the patient outcomes nor for the process outcomes (comparison two).</p> <p>Conclusions</p> <p>There is little evidence at the moment for the effectiveness of an increasingly used and commercialised instrument such as electronic multidimensional guidelines. After more than a decade of development of numerous electronic systems, research on the most effective implementation strategy for this kind of guideline-based decision support systems is still lacking. This conclusion implies a considerable risk towards inappropriate investments in ineffective implementation interventions and in suboptimal care.</p