Posterior transdural discectomy: a new approach for the removal of a central thoracic disc herniation

BACKGROUND: The optimal surgical approach for thoracic disc herniation remains a matter of debate, especially for central disc herniation. In this paper, we present a new technique to remove central thoracic disc herniation, the posterior transdural approach, and report a series of 13 cases operated on in this way at our institute. METHODS: Between September 2004 and October 2010, 13 patients with symptomatic central thoracic disc herniation were operated on, utilising this posterior transdural approach. All patients underwent magnetic resonance imaging (MRI) of the thoracic spine before surgery. All patients were followed at our outpatient department for at least 3 months. In addition, all patients were interviewed in April 2009 and February 2011 to evaluate the final results. A seven-point Likert scale was applied and the Frankel score was determined preoperatively and postoperatively. Additionally, a postoperative MRI was obtained for all but two patients. RESULTS: The most frequently involved levels were T10-11 and T12-L1. Median operative time was 210 min (range 140-360). Three patients experienced reversible complications. No patient required spinal fixation. The median duration of hospitalisation was 6 days (range 4-20 days). With a median follow-up of 18 months, symptoms improved in 12 patients (92%), including the three patients with complications. One patient was unchanged (8%), while none of the patients experienced worsening of symptoms. CONCLUSIONS: The posterior transdural approach is well tolerated by the patient and has a relatively high success rate. It is a relatively simple and safe procedure, suitable for the operative treatment of almost all types of thoracic disc herniation, but especially the centrally located disc herniation

Molecular differences between ductal carcinoma in situ and adjacent invasive breast carcinoma: a multiplex ligation-dependent probe amplification study

Ductal carcinoma in situ (DCIS) accounts for approximately 20% of mammographically detected breast cancers. Although DCIS is generally highly curable, some women with DCIS will develop life-threatening invasive breast cancer, but the determinants of progression to infiltrating ductal cancer (IDC) are largely unknown. In the current study, we used multiplex ligation-dependent probe amplification (MLPA), a multiplex PCR-based test, to compare copy numbers of 21 breast cancer related genes between laser-microdissected DCIS and adjacent IDC lesions in 39 patients. Genes included in this study were ESR1, EGFR, FGFR1, ADAM9, IKBKB, PRDM14, MTDH, MYC, CCND1, EMSY, CDH1, TRAF4, CPD, MED1, HER2, CDC6, TOP2A, MAPT, BIRC5, CCNE1 and AURKA

Dopamine transporter (DAT1) and dopamine receptor D4 (DRD4) genotypes differentially impact on electrophysiological correlates of error processing

Peer reviewedPublisher PD

Fostering implementation of health services research findings into practice: a consolidated framework for advancing implementation science

Abstract Background Many interventions found to be effective in health services research studies fail to translate into meaningful patient care outcomes across multiple contexts. Health services researchers recognize the need to evaluate not only summative outcomes but also formative outcomes to assess the extent to which implementation is effective in a specific setting, prolongs sustainability, and promotes dissemination into other settings. Many implementation theories have been published to help promote effective implementation. However, they overlap considerably in the constructs included in individual theories, and a comparison of theories reveals that each is missing important constructs included in other theories. In addition, terminology and definitions are not consistent across theories. We describe the Consolidated Framework For Implementation Research (CFIR) that offers an overarching typology to promote implementation theory development and verification about what works where and why across multiple contexts. Methods We used a snowball sampling approach to identify published theories that were evaluated to identify constructs based on strength of conceptual or empirical support for influence on implementation, consistency in definitions, alignment with our own findings, and potential for measurement. We combined constructs across published theories that had different labels but were redundant or overlapping in definition, and we parsed apart constructs that conflated underlying concepts. Results The CFIR is composed of five major domains: intervention characteristics, outer setting, inner setting, characteristics of the individuals involved, and the process of implementation. Eight constructs were identified related to the intervention (e.g., evidence strength and quality), four constructs were identified related to outer setting (e.g., patient needs and resources), 12 constructs were identified related to inner setting (e.g., culture, leadership engagement), five constructs were identified related to individual characteristics, and eight constructs were identified related to process (e.g., plan, evaluate, and reflect). We present explicit definitions for each construct. Conclusion The CFIR provides a pragmatic structure for approaching complex, interacting, multi-level, and transient states of constructs in the real world by embracing, consolidating, and unifying key constructs from published implementation theories. It can be used to guide formative evaluations and build the implementation knowledge base across multiple studies and settings.http://deepblue.lib.umich.edu/bitstream/2027.42/78272/1/1748-5908-4-50.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78272/2/1748-5908-4-50-S1.PDFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78272/3/1748-5908-4-50-S3.PDFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78272/4/1748-5908-4-50-S4.PDFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78272/5/1748-5908-4-50.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/78272/6/1748-5908-4-50-S2.PDFPeer Reviewe

Onset dynamics of type A botulinum neurotoxin-induced paralysis

Experimental studies have demonstrated that botulinum neurotoxin serotype A (BoNT/A) causes flaccid paralysis by a multi-step mechanism. Following its binding to specific receptors at peripheral cholinergic nerve endings, BoNT/A is internalized by receptor-mediated endocytosis. Subsequently its zinc-dependent catalytic domain translocates into the neuroplasm where it cleaves a vesicle-docking protein, SNAP-25, to block neurally evoked cholinergic neurotransmission. We tested the hypothesis that mathematical models having a minimal number of reactions and reactants can simulate published data concerning the onset of paralysis of skeletal muscles induced by BoNT/A at the isolated rat neuromuscular junction (NMJ) and in other systems. Experimental data from several laboratories were simulated with two different models that were represented by sets of coupled, first-order differential equations. In this study, the 3-step sequential model developed by Simpson (J Pharmacol Exp Ther 212:16–21,1980) was used to estimate upper limits of the times during which anti-toxins and other impermeable inhibitors of BoNT/A can exert an effect. The experimentally determined binding reaction rate was verified to be consistent with published estimates for the rate constants for BoNT/A binding to and dissociating from its receptors. Because this 3-step model was not designed to reproduce temporal changes in paralysis with different toxin concentrations, a new BoNT/A species and rate (kS) were added at the beginning of the reaction sequence to create a 4-step scheme. This unbound initial species is transformed at a rate determined by kS to a free species that is capable of binding. By systematically adjusting the values of kS, the 4-step model simulated the rapid decline in NMJ function (kS ≥0.01), the less rapid onset of paralysis in mice following i.m. injections (kS = 0.001), and the slow onset of the therapeutic effects of BoNT/A (kS < 0.001) in man. This minimal modeling approach was not only verified by simulating experimental results, it helped to quantitatively define the time available for an inhibitor to have some effect (tinhib) and the relation between this time and the rate of paralysis onset. The 4-step model predicted that as the rate of paralysis becomes slower, the estimated upper limits of (tinhib) for impermeable inhibitors become longer. More generally, this modeling approach may be useful in studying the kinetics of other toxins or viruses that invade host cells by similar mechanisms, e.g., receptor-mediated endocytosis

Developing and testing a measure of consultation-based reassurance for people with low back pain in primary care:a cross-sectional study

BACKGROUND: Reassurance from physicians is commonly recommended in guidelines for the management of low back pain (LBP), but the process of reassurance and its impact on patients is poorly researched. We aimed to develop a valid and reliable measure of the process of reassurance during LBP consultations. METHODS: Items representing the data-gathering stage of the consultation and affective and cognitive reassurance were generated from literature on physician-patient communication and piloted with expert researchers and physicians, a Patient and Public Involvement group, and LBP patients to form a questionnaire. Patients presenting for LBP at 43 General Practice surgeries were sent the questionnaire. The questionnaire was analysed with Rasch modelling, using two samples from the same population of recent LBP consultations: the first (n = 157, follow-up n = 84) for exploratory analysis and the second (n = 162, follow-up n = 74) for confirmatory testing. Responses to the questionnaire were compared with responses to satisfaction and enablement scales to assess the external validity of the items, and participants completed the questionnaire again one-week later to assess test-retest reliability. RESULTS: The questionnaire was separated into four subscales: data-gathering, relationship-building, generic reassurance, and cognitive reassurance, each containing three items. All subscales showed good validity within the Rasch models, and good reliability based on person- and item-separations and test-retest reliability. All four subscales were significantly positively correlated with satisfaction and enablement for both samples. The final version of the questionnaire is presented here. CONCLUSIONS: Overall, the measure has demonstrated a good level of validity and generally acceptable reliability. This is the first measure to focus specifically on reassurance for LBP in primary care settings, and will enable researchers to further understanding of what is reassuring within the context of low back pain consultations, and how outcomes are affected by different types of reassurance. Additionally, the measure may provide a useful training and audit tool for physicians. The new measure requires testing in prospective cohorts, and would benefit from further validation against ethnographic observation of consultations in real time

EQUIP: Implementing chronic care principles and applying formative evaluation methods to improve care for schizophrenia: QUERI Series

<p>Abstract</p> <p>Background</p> <p>This paper presents a case study that demonstrates the evolution of a project entitled "Enhancing QUality-of-care In Psychosis" (EQUIP) that began approximately when the U.S. Department of Veterans Affairs' Quality Enhancement Research Initiative (QUERI), and implementation science were emerging. EQUIP developed methods and tools to implement chronic illness care principles in the treatment of schizophrenia, and evaluated this implementation using a small-scale controlled trial. The next iteration of the project, EQUIP-2, was further informed by implementation science and the use of QUERI tools.</p> <p>Methods</p> <p>This paper reports the background, development, results and implications of EQUIP, and also describes ongoing work in the second phase of the project (EQUIP-2). The EQUIP intervention uses implementation strategies and tools to increase the adoption and implementation of chronic illness care principles. In EQUIP-2, these strategies and tools are conceptually grounded in a stages-of-change model, and include clinical and delivery system interventions and adoption/implementation tools. Formative evaluation occurs in conjunction with the intervention, and includes developmental, progress-focused, implementation-focused, and interpretive evaluation.</p> <p>Results</p> <p>Evaluation of EQUIP provided an understanding of quality gaps <it>and </it>how to address related problems in schizophrenia. EQUIP showed that solutions to quality problems in schizophrenia differ by treatment domain and are exacerbated by a lack of awareness of evidence-based practices. EQUIP also showed that improving care requires creating resources for physicians to help them easily implement practice changes, plus intensive education as well as product champions who help physicians use these resources. Organizational changes, such as the addition of care managers and informatics systems, were shown to help physicians with identifying problems, making referrals, and monitoring follow-up. In EQUIP-2, which is currently in progress, these initial findings were used to develop a more comprehensive approach to implementing and evaluating the chronic illness care model.</p> <p>Discussion</p> <p>In QUERI, small-scale projects contribute to the development and enhancement of hands-on, action-oriented service-directed projects that are grounded in current implementation science. This project supports the concept that QUERI tools can be useful in implementing complex care models oriented toward evidence-based improvement of clinical care.</p