Miljanich G.,Airmid Incorporated |
Rauck R.,Center for Clinical Research |
Saulino M.,Thomas Jefferson University
Pain Practice | Year: 2013
Chronic pain-especially that which is refractory to conventional treatment-presents particular challenges to physicians and patients. Examination of the molecular and cellular mechanisms involved in this pathophysiology suggests that spinal instillation of therapeutic agents may offer an effective treatment option through the modification of the processing and sensation of chronic pain. Intrathecal therapy, used alone or in combination with other analgesic agents, may reduce chronic pain by attenuating both pre- and postsynaptic activities. This article reviews chronic pain pathophysiology and the mechanisms whereby spinally administered analgesics may modify chronic pain. Available treatment options are also considered, including recommendations from the 2007 Polyanalgesic Consensus Conference (PACC) guidelines on the use of intrathecal agents for nociceptive, neuropathic, and mixed pain. © 2012 World Institute of Pain.
Atay C.,Center for Clinical Research
Journal of Head Trauma Rehabilitation | Year: 2015
OBJECTIVE:: (1) To investigate outcomes in language competence and self-reported satisfaction with social relationships in long-term survivors of childhood traumatic brain injury (TBI); and (2) to establish whether language competence contributes to self-reported satisfaction with social relationships decades after sustaining childhood TBI. PARTICIPANTS:: Twelve females and 8 males aged 30 to 55 (mean = 39.80, standard deviation = 7.54) years who sustained a TBI during childhood and were on average 31 years postinjury (standard deviation = 9.69). An additional 20 participants matched for age, sex, handedness, years of education, and socioeconomic status constituted a control group. MAIN MEASURES:: Test of Language Competence—Expanded Edition and the Quality of Life in Brain Injury questionnaire. RESULTS:: Individuals with a history of childhood TBI performed significantly poorer than their non-injured peers on 2 (Ambiguous Sentences and Oral Expression: Recreating Sentences) out of the 4 Test of Language Competence—Expanded Edition subtests used and on the Quality of Life in Brain Injury subscale assessing satisfaction with social relationships. In the TBI group, scores obtained on the Ambiguous Sentences subtest were found to be a significant predictor of satisfaction with social relationships, explaining 25% of the variance observed. CONCLUSIONS:: The implication of high-level language skills to self-reported satisfaction with social relationships many decades post-childhood TBI suggests that ongoing monitoring of emerging language skills and support throughout the school years and into adulthood may be warranted if adult survivors of childhood TBI are to experience satisfying social relationships. © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Stengel D.,Center for Clinical Research
Journal of Bone and Joint Surgery - Series A | Year: 2012
Controversy exists about whether or not similar standards apply to the clinical evaluation of orthopaedic implants and pharmaceuticals. The long-lasting dispute is likely to be abandoned shortly, given that certain regulatory bodies in Europe now mandate proof of effectiveness by randomized controlled trials (RCTs) prior to market approval of innovative devices. This is a timely signal - it will help to strengthen both the credibility of orthopaedic researchers among all health-care disciplines and the role of manufacturers as creative minds and scientific partners. Yet, it must be accompanied by substantial changes in the current trial landscape. Given the level of perfection of available orthopaedic technology, superiority of a new product over an established standard will become a rare finding. Noninferiority or equivalence must be accepted as important trial results by investigators, sponsors, clinicians, and health authorities to enhance the spectrum of therapeutic options and help to individualize patient care. Specific problems are slow recruitment rates and long intervals from the protocol stage to publication of results. This may counteract the innovative potential of a novel product. Pragmatic trial designs, lean but complete documentation, limited but precise end points, the avoidance of competing trials, and the fostering of international collaboration are possible ways to streamline clinical trials of orthopaedic devices. Finally, RCTs should be conducted, conditional to the presumed level of innovation of a new implant, and supplemented by data from registries to fully determine the utility, value, and safety of the intervention. Copyright © 2012 by The Journal of Bone and Joint Surgery, Incorporated.
Sanders D.R.,Center for Clinical Research |
Sanders M.L.,Center for Clinical Research
Journal of Refractive Surgery | Year: 2010
PURPOSE: To assess the efficacy of the Tetraflex (Lenstec Inc) intraocular lens (IOL) to provide enhanced near reading ability and spectacle independence relative to a monofocal control IOL in bilaterally implanted eyes tested binocularly. METHODS: A prospective, age-matched, non-randomized US Food and Drug Administration clinical trial of 255 Tetraflex and 101 monofocal IOL control patients was performed. To date, 239 Tetraflex and 96 control patients were examined at 12 months postoperatively. RESULTS: At 12 months postoperative, the Tetraflex patients read better than the controls at print sizes of 20/80 (P=.04), 20/63 (P=.01), 20/50 (P<.001), 20/40 (P=.001), 20/32 (P<.001), and 20/25 (P=.001). The proportion of patients reading at a speed of ≥80 words per minute was significantly higher with the Tetraflex IOL (P=.003). Ninety-six percent of Tetraflex patients reported never wearing glasses for distance compared with 80% of control patients (P<.001). Seventy-five percent of the Tetraflex patients reported near spectacle wear either never or only occasionally for small print and/or dim light (21% never) compared with 46% of control patients (P<.001) (9% never). Near add power requirement for corrected near visual acuity was less in the Tetraflex group (P<.001); 28% of Tetraflex patients required ≤1.25 diopters of near add, compared to only 7% of control patients. Spectacle independence, as measured by the proportion of patients with uncorrected distance visual acuity of 20/25 or better and various degrees of uncorrected near visual acuity, was also significantly better (P<.001) as was distance-corrected near visual acuity (P<.001). CONCLUSIONS: The results support the efficacy of the Tetraflex IOL to provide enhanced near reading ability and spectacle independence relative to a monofocal IOL control. Copyright © SLACK Incorporated.
Stengel D.,Center for Clinical Research
The Cochrane database of systematic reviews | Year: 2013
Ultrasonography is regarded as the tool of choice for early diagnostic investigations in patients with suspected blunt abdominal trauma. Although its sensitivity is too low for definite exclusion of abdominal organ injury, proponents of ultrasound argue that ultrasound-based clinical pathways enhance the speed of primary trauma assessment, reduce the number of computed tomography scans and cut costs. To assess the effects of trauma algorithms that include ultrasound examinations in patients with suspected blunt abdominal trauma. We searched the Cochrane Injuries Group's Specialised Register, CENTRAL (The Cochrane Library), MEDLINE (OvidSP), EMBASE (OvidSP), CINAHL (EBSCO), publishers' databases, controlled trials registers and the Internet. Bibliographies of identified articles and conference abstracts were searched for further elligible studies. Trial authors were contacted for further information and individual patient data. The searches were updated in February 2013. Studies: randomised controlled trials (RCTs) and quasi-randomised trials (qRCTs). Participants: patients with blunt torso, abdominal or multiple trauma undergoing diagnostic investigations for abdominal organ injury. Interventions: diagnostic algorithms comprising emergency ultrasonography (US). Controls: diagnostic algorithms without ultrasound examinations (for example, primary computed tomography [CT] or diagnostic peritoneal lavage [DPL]). Outcome measures: mortality, use of CT and DPL, cost-effectiveness, laparotomy and negative laparotomy rates, delayed diagnoses, and quality of life. Two authors independently selected trials for inclusion, assessed methodological quality and extracted data. Where possible, data were pooled and relative risks (RRs), risk differences (RDs) and weighted mean differences, each with 95% confidence intervals (CIs), were calculated by fixed- or random-effects modelling, as appropriate. We identified four studies meeting our inclusion criteria. Overall, trials were of moderate methodological quality. Few trial authors responded to our written inquiries seeking to resolve controversial issues and to obtain individual patient data. We pooled mortality data from three trials involving 1254 patients; relative risk in favour of the US arm was 1.00 (95% CI 0.50 to 2.00). US-based pathways significantly reduced the number of CT scans (random-effects RD -0.52, 95% CI -0.83 to -0.21), but the meaning of this result is unclear. Given the low sensitivity of ultrasound, the reduction in CT scans may either translate to a number needed to treat or number needed to harm of two. There is currently insufficient evidence from RCTs to justify promotion of ultrasound-based clinical pathways in diagnosing patients with suspected blunt abdominal trauma.
Faulkner G.,Dalhousie University |
Garduno R.A.,Center for Clinical Research
Methods in Molecular Biology | Year: 2013
Those investigators who study the morphology of Legionella and Legionella-infected cells have greatly benefited from the superior resolution afforded by electron microscopy (EM). It can also be said with confidence that EM will continue to reveal as yet to be discovered features of this fascinating intracellular pathogen. In this chapter we detail our practical experience in the application of three transmission electron microscopy (TEM) techniques to the study of Legionella: conventional ultrastructural analysis, immuno-gold labeling, and negative staining. Each of these techniques has particular, well-defined applications, which are discussed in the context of our in-house developed methods. We invite researchers to try the methods given here in the study of Legionella, and adopt TEM as part of their research tools arsenal. © 2013 Springer Science+Business Media New York.
Andre M.,Center for Clinical Research |
Vernby A.,Karolinska Institutet |
Berg J.,Karolinska Institutet |
Lundborg C.S.,Karolinska Institutet
Journal of Antimicrobial Chemotherapy | Year: 2010
Objectives: To examine the level of knowledge about antibiotic treatment and awareness of antibiotic resistance among the general public in Sweden. Methods: A quantitative, cross-sectional interview study based on a structured questionnaire used during telephone interviews. The sample comprised 1000 randomly selected individuals aged 21-80 years throughout Sweden. Demographic data as well as level of agreement with various statements concerning antibiotics and antibiotic use were provided by the respondents. Results: The response rate was 74.7%. Of the respondents, 19.1% agreed that antibiotics cure common colds more quickly; this belief was higher in those who had not previously received antibiotics. A high proportion, 80.7%, agreed that bacteria could become resistant to antibiotics. Trust in doctors was high, and significantly more respondents reported trusting the doctor not prescribing an antibiotic, 87.0%, than the doctor prescribing an antibiotic, 81.0%. The respondents showed some confusion surrounding the terms 'bacteria' and 'viruses', and the meaning of these in relation to the prescribing decision. Conclusions: The high level of trust in restrictive prescribing as well as the awareness of antibiotic resistance expressed by the Swedish public should be recognized by health professionals and utilized in future campaigns. © The Author 2010. Published by Oxford University Press.
Hawkes C.H.,Institute of Cell and Molecular Science |
Del Tredici K.,Center for Clinical Research |
Braak H.,Center for Clinical Research
Parkinsonism and Related Disorders | Year: 2010
It is reasonably well established that prior to the motor phase of classical Parkinson's disease (PD) there is a prodromal period of several years duration. Once typical motor features appear, the disease continues up to 20 years depending on multiple variables. The clinical features of the prodromal and motor phases may be correlated with pathological changes in the central and autonomic nervous systems to allow a sequential plan of disease progression. We present a 'best guess' for a typical individual presenting with PD in their sixties and speculate that the disease will last approximately 40 years from the earliest non-motor features to death. Appreciation of this concept may allow better strategies for slowing or halting disease progression. © 2009 Elsevier Ltd.
Hellberg D.A.N.,Center for Clinical Research |
Hellberg D.A.N.,Uppsala University |
Tibor T.O.T.,Falun Hospital
Anticancer Research | Year: 2014
Background/Aim: Histopathological and clinical scores to predict prognosis in cervical cancer have been of limited value. In the present study a tumor marker expression score was evaluated for prognostication in early-stage cervical cancer. Materials and Methods: The entire study population included 128 women with invasive squamous cell cervical cancer followed-up for at least 10 years. Results: Expression of 12 tumor markers (epidermal growth factor receptor (EGFR), Ki-67, c-MYC, p53, p27, E-cadherin, CD44, vascular endothelial growth factor receptor (VEGF), cyclooxygenase-2 (COX2), CD4, and leucine-rich immunoglobulin-like repeats-1 (LRIG1) and LRIG2, considered relevant for cervical cancer prognostication was evaluated by immunohistochemistry. Expression of five markers, LRIG1, LRIG2, p53, COX2 and c-MYC were useful to make a prognostication score, ranging from 0 to 5. Score 0-1 correlated to less than 5% 10-year mortality, while the mortality rate of those with score 4-5 approached 70%; those with score 2 formed an intermediate group. Using different models, a high sensitivity, specificity, positive predictive value and negative predictive value was attained. Conclusion: Tumor marker scoring could be an adjunct to histopathological and clinical parameters in prognostication of early-stage cervical cancer. © 2014, International Institute of Anticancer Research. All rights reserved.
Stengel D.,Center for Clinical Research
Scandinavian journal of trauma, resuscitation and emergency medicine | Year: 2014
Single-pass, contrast-enhanced whole body multidetector computed tomography (MDCT) emerged as the diagnostic standard for evaluating patients with major trauma. Modern iterative image algorithms showed high image quality at a much lower radiation dose in the non-trauma setting. This study aims at investigating whether the radiation dose can safely be reduced in trauma patients without compromising the diagnostic accuracy and image quality. Prospective observational study with two consecutive cohorts of patients. A high-volume, academic, supra-regional trauma centre in Germany. Consecutive male and female patients who 1. had been exposed to a high-velocity trauma mechanism, 2. present with clinical evidence or high suspicion of multiple trauma (predicted Injury Severity Score [ISS] ≥16) and 3. are scheduled for primary MDCT based on the decision of the trauma leader on call.Imaging protocols: In a before/after design, a consecutive series of 500 patients will undergo single-pass, whole-body 128-row multi-detector computed tomography (MDCT) with a standard, as low as possible radiation dose. This will be followed by a consecutive series of 500 patients undergoing an approved ultra-low dose MDCT protocol using an image processing algorithm. Routine administrative data and electronic patient records, as well as digital images stored in a picture archiving and communications system will serve as the primary data source. The protocol was approved by the institutional review board. (1) incidence of delayed diagnoses, (2) diagnostic accuracy, as correlated to the reference standard of a synopsis of all subsequent clinical, imaging, surgical and autopsy findings, (3) patients' safety, (4) radiation exposure (e.g. effective dose), (5) subjective image quality (assessed independently radiologists and trauma surgeons on a 100-mm visual analogue scale), (6) objective image quality (e.g., contrast-to-noise ratio). Multivariate regression will be employed to adjust and correct the findings for time and cohort effects. An exploratory interim analysis halfway after introduction of low-dose MDCT will be conducted to assess whether this protocol is clearly inferior or superior to the current standard. Although non-experimental, this study will generate first large-scale data on the utility of imaging-enhancing algorithms in whole-body MDCT for major blunt trauma. Current Controlled Trials ISRCTN74557102.