Validity and reliability of a new ankle dorsiflexion measurement device.

PubMed

Gatt, Alfred; Chockalingam, Nachiappan

2013-08-01

The assessment of the maximum ankle dorsiflexion angle is an important clinical examination procedure. Evidence shows that the traditional goniometer is highly unreliable, and various designs of goniometers to measure the maximum ankle dorsiflexion angle rely on the application of a known force to obtain reliable results. Hence, an innovative ankle dorsiflexion measurement device was designed to make this measurement more reliable by holding the foot in a selected posture without the application of a known moment. To report on the comprehensive validity and reliability testing carried out on the new device. Following validity testing, four different trials to test reliability of the ankle dorsiflexion measurement device were performed. These trials included inter-rater and intra-rater testings with a controlled moment, intra-rater reliability testing with knees flexed and extended without a controlled moment, intra-rater testing with a patient population, and inter-rater reliability testing between four raters of varying experience without controlling moment. All raters were blinded. A series of trials to test intra-rater and inter-rater reliabilities. Intra-rater reliability intraclass correlation coefficient was 0.98 and inter-rater reliability intraclass correlation coefficient (2,1) was 0.953 with a controlled moment. With uncontrolled moment, very high reliability for intra-tester was also achieved (intraclass correlation coefficient = 0.94 with knees extended and intraclass correlation coefficient = 0.95 with knees flexed). For the trial investigating test-retest reliability with actual patients, intraclass correlation coefficient of 0.99 was obtained. In the trial investigating four different raters with uncontrolled moment, intraclass correlation coefficient of 0.91 was achieved. The new ankle dorsiflexion measurement device is a valid and reliable device for measuring ankle dorsiflexion in both healthy subjects and patients, with both controlled and uncontrolled moments, even by multiple raters of varying experience when the foot is dorsiflexed to its end of range of motion. An ankle dorsiflexion measuring device has been designed to increase the reliability of ankle dorsiflexion measurement and replace the traditional goniometer. While the majority of similar devices rely on application of a known moment to perform this measurement, it has been shown that this is not required with the new ankle dorsiflexion measurement device and, rather, foot posture should be taken into consideration as this affects the maximum ankle dorsiflexion angle.

Assessment of Safety and Effectiveness of the Extracorporeal Continuous-Flow Ventricular Assist Device (BR16010) Use as a Bridge-to-Decision Therapy for Severe Heart Failure or Refractory Cardiogenic Shock: Study Protocol for Single-Arm Non-randomized, Uncontrolled, and Investigator-Initiated Clinical Trial.

PubMed

Fukushima, Norihide; Tatsumi, Eisuke; Seguchi, Osamu; Takewa, Yoshiaki; Hamasaki, Toshimitsu; Onda, Kaori; Yamamoto, Haruko; Hayashi, Teruyuki; Fujita, Tomoyuki; Kobayashi, Junjiro

2018-06-08

The management of heart failure patients presenting in a moribund state remains challenging, despite significant advances in the field of ventricular assist systems. Bridge to decision involves using temporary devices to stabilize the hemodynamic state of such patients while further assessment is performed and a decision can be made regarding patient management. The purpose of this study (NCVC-BTD_01, National Cerebral and Cardiovascular Center-Bridge to Dicision_01) is to assess the safety and effectiveness of the newly developed extracorporeal continuous-flow ventricular assist system employing a disposable centrifugal pump with a hydrodynamically levitated bearing (BR16010) use as a bridge-to-decision therapy for patients with severe heart failure or refractory cardiogenic shock. NCVC-BTD_01 is a single-center, single-arm, open-label, exploratory, medical device, investigator-initiated clinical study. It is conducted at the National Cerebral and Cardiovascular Center in Japan. A total of nine patients will be enrolled in the study. The study was planned using Simon's minimax two-stage phase design. The primary endpoint is a composite of survival free of device-related serious adverse events and complications during device support. For left ventricular assistance, withdrawal of a trial device due to cardiac function recovery or exchange to other ventricular assist devices (VADs) for the purpose of bridge to transplantation (BTT) during 30 days after implantation will be considered study successes. For right ventricular assistance, withdrawal of tal device due to right ventricular function recovery within 30 days after implantation will be considered a study success. Secondary objectives include changes in brain natriuretic peptide levels (7 days after implantation of a trial device and the day of withdrawal of a trial device), period of mechanical ventricular support, changes in left ventricular ejection fraction (7 days after implantation of a trial device and the day of withdrawal of a trial device), and changes in left ventricular diastolic dimension (7 days after implantation of a trial device and the day of withdrawal of a trial device). We will disseminate the findings through regional, national, and international conferences and through peer-reviewed journals. UMIN Clinical Trials Registry (UMIN-CTR; R000033243) registered on 8 September 2017.

Evaluation of a Low-Cost Bubble CPAP System Designed for Resource-Limited Settings.

PubMed

Bennett, Desmond J; Carroll, Ryan W; Kacmarek, Robert M

2018-04-01

Respiratory compromise is a leading contributor to global neonatal death. CPAP is a method of treatment that helps maintain lung volume during expiration, promotes comfortable breathing, and improves oxygenation. Bubble CPAP is an effective alternative to standard CPAP. We sought to determine the reliability and functionality of a low-cost bubble CPAP device designed for low-resource settings. The low-cost bubble CPAP device was compared to a commercially available bubble CPAP system. The devices were connected to a lung simulator that simulated neonates of 4 different weights with compromised respiratory mechanics (∼1, ∼3, ∼5, and ∼10 kg). The devices' abilities to establish and maintain pressure and flow under normal conditions as well as under conditions of leak were compared. Multiple combinations of pressure levels (5, 8, and 10 cm H 2 O) and flow levels (3, 6, and 10 L/min) were tested. The endurance of both devices was also tested by running the systems continuously for 8 h and measuring the changes in pressure and flow. Both devices performed equivalently during the no-leak and leak trials. While our testing revealed individual differences that were statistically significant and clinically important (>10% difference) within specific CPAP and flow-level settings, no overall comparisons of CPAP or flow were both statistically significant and clinically important. Each device delivered pressures similar to the desired pressures, although the flows delivered by both machines were lower than the set flows in most trials. During the endurance trials, the low-cost device was marginally better at maintaining pressure, while the commercially available device was better at maintaining flow. The low-cost bubble CPAP device evaluated in this study is comparable to a bubble CPAP system used in developed settings. Extensive clinical trials, however, are necessary to confirm its effectiveness. Copyright © 2018 by Daedalus Enterprises.

The ANKLE TRIAL (ANKLE treatment after injuries of the ankle ligaments): what is the benefit of external support devices in the functional treatment of acute ankle sprain? : a randomised controlled trial

PubMed Central

2012-01-01

Background Acute lateral ankle ligament injuries are very common problems in present health care. Still there is no hard evidence about which treatment strategy is superior. Current evidence supports the view that a functional treatment strategy is preferable, but insufficient data are present to prove the benefit of external support devices in these types of treatment. The hypothesis of our study is that external ankle support devices will not result in better outcome in the treatment of acute ankle sprains, compared to a purely functional treatment strategy. Overall objective is to compare the results of three different strategies of functional treatment for acute ankle sprain, especially to determine the advantages of external support devices in addition to functional treatment strategy, based on balance and coordination exercises. Methods/design This study is designed as a randomised controlled multi-centre trial with one-year follow-up. Adult and healthy patients (N = 180) with acute, single sided and first inversion trauma of the lateral ankle ligaments will be included. They will all follow the same schedule of balancing exercises and will be divided into 3 treatment groups, 1. pressure bandage and tape, 2. pressure bandage and brace and 3. no external support. Primary outcome measure is the Karlsson scoring scale; secondary outcomes are FAOS (subscales), number of recurrent ankle injuries, Visual Analogue Scales of pain and satisfaction and adverse events. They will be measured after one week, 6 weeks, 6 months and 1 year. Discussion The ANKLE TRIAL is a randomized controlled trial in which a purely functional treated control group, without any external support is investigated. Results of this study could lead to other opinions about usefulness of external support devices in the treatment of acute ankle sprain. Trial registration Netherlands Trial Register (NTR): NTR2151 PMID:22340371

Stroke treatment academic industry roundtable: research priorities in the assessment of neurothrombectomy devices.

PubMed

Saver, Jeffrey L; Jovin, Tudor G; Smith, Wade S; Albers, Gregory W; Baron, Jean-Claude; Boltze, Johannes; Broderick, Joseph P; Davis, Lisa A; Demchuk, Andrew M; DeSena, Salvatore; Fiehler, Jens; Gorelick, Philip B; Hacke, Werner; Holt, Bill; Jahan, Reza; Jing, Hui; Khatri, Pooja; Kidwell, Chelsea S; Lees, Kennedy R; Lev, Michael H; Liebeskind, David S; Luby, Marie; Lyden, Patrick; Megerian, J Thomas; Mocco, J; Muir, Keith W; Rowley, Howard A; Ruedy, Richard M; Savitz, Sean I; Sipelis, Vitas J; Shimp, Samuel K; Wechsler, Lawrence R; Wintermark, Max; Wu, Ona; Yavagal, Dileep R; Yoo, Albert J

2013-12-01

The goal of the Stroke Treatment Academic Industry Roundtable (STAIR) meetings is to advance the development of stroke therapies. At STAIR VIII, consensus recommendations were developed for clinical trial strategies to demonstrate the benefit of endovascular reperfusion therapies for acute ischemic stroke. Prospects for success with forthcoming endovascular trials are robust, because new neurothrombectomy devices have superior reperfusion efficacy compared with earlier-generation interventions. Specific recommendations are provided for trial designs in 3 populations: (1) patients undergoing intravenous fibrinolysis, (2) early patients ineligible for or having failed intravenous fibrinolysis, and (3) wake-up and other late-presenting patients. Among intravenous fibrinolysis-eligible patients, key principles are that CT or MRI confirmation of target arterial occlusions should precede randomization; endovascular intervention should be pursued with the greatest rapidity possible; and combined intravenous and neurothrombectomy therapy is more promising than neurothrombectomy alone. Among patients ineligible for or having failed intravenous fibrinolysis, scientific equipoise was affirmed and the need to randomize all eligible patients emphasized. Vessel imaging to confirm occlusion is mandatory, and infarct core and penumbral imaging is desirable in later time windows. Additional STAIR VIII recommendations include approaches to test multiple devices in a single trial, utility weighting of disability end points, and adaptive designs to delineate time and tissue injury thresholds at which benefits from intervention no longer accrue. Endovascular research priorities in acute ischemic stroke are to perform trials testing new, highly effective neuro thrombectomy devices rapidly deployed in patients confirmed to have target vessel occlusions.

Imposed Power of Breathing Associated With Use of an Impedance Threshold Device

DTIC Science & Technology

2007-02-01

threshold device and a sham impedance threshold device. DESIGN: Prospective randomized blinded protocol. SETTING: University medical center. PATIENTS...for males). METHODS: The volunteers completed 2 trials of breathing through a face mask fitted with an active impedance threshold device set to open...at -7cmH 2 O pressure, or with a sham impedance threshold device, which was identical to the active device except that it did not contain an

Reading aids for adults with low vision

PubMed Central

Virgili, Gianni; Acosta, Ruthy; Grover, Lori L; Bentley, Sharon A; Giacomelli, Giovanni

2014-01-01

Background The purpose of low-vision rehabilitation is to allow people to resume or to continue to perform daily living tasks, with reading being one of the most important. This is achieved by providing appropriate optical devices and special training in the use of residual-vision and low-vision aids, which range from simple optical magnifiers to high-magnification video magnifiers. Objectives To assess the effects of reading aids for adults with low vision. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2013, Issue 1), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE, (January 1950 to January 2013), EMBASE (January 1980 to January 2013), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to January 2013), OpenGrey (System for Information on Grey Literature in Europe) (www.opengrey.eu/), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov/) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 31 January 2013. We searched the reference lists of relevant articles and used the Science Citation Index to find articles that cited the included studies and contacted investigators and manufacturers of low-vision aids. We handsearched the British Journal of Visual Impairment from 1983 to 1999 and the Journal of Visual Impairment and Blindness from 1976 to 1991. Selection criteria This review includes randomised and quasi-randomised trials in which any device or aid used for reading had been compared to another device or aid in people aged 16 or over with low vision as defined by the study investigators. Data collection and analysis At least two authors independently assessed trial quality and extracted data. Main results We included nine small studies with a cross-over-like design (181 people overall) and one study with three parallel arms (243 participants) in the review. All studies reported the primary outcome, results for reading speed. Two studies including 92 participants found moderate- or low-quality evidence suggesting that reading speed is higher with stand-mounted electronic devices or electronic devices with the camera mounted in a ‘mouse’ than with optical magnifiers, which in these trials were generally stand-mounted or, less frequently, hand-held magnifiers or microscopic lenses. In another study of 20 participants there was moderate-quality evidence that optical devices are better than head-mounted electronic devices (four types). There was low-quality evidence from three studies (93 participants) that reading using head-mounted electronic devices is slower than with stand-based electronic devices. The technology of electronic devices may have changed and improved since these studies were conducted. One study suggested no difference between a diffractive spectacle-mounted magnifier and either refractive (15 participants) or aplanatic (15 participants) magnifiers. One study of 10 people suggested that several overlay coloured filters were no better and possibly worse than a clear filter. A parallel-arm study including 243 participants with age-related macular degeneration found that custom or standard prism spectacles were no different from conventional reading spectacles, although the data did not allow precise estimates of performance to be made. Authors' conclusions There is insufficient evidence on the effect of different types of low-vision aids on reading performance. It would be necessary to investigate which patient characteristics predict performance with different devices, including costly electronic devices. Better-quality research should also focus on assessing sustained long-term use of each device. Authors of studies testing several devices on the same person should consider design and reporting issues related to their sequential presentation and to the cross-over-like study design. PMID:24154864

Field-testing UV disinfection of drinking water

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gadgil, A.; Drescher, A.; Greene, D.

A recently invented device, ``UV Waterworks,`` uses ultraviolet (UV) light to disinfect drinking water. Its novel features are: low cost, robust design, rapid disinfection, low electricity use, low maintenance, high flow rate and ability to work with unpressurized water sources. The device could service a community of 1,000 persons, at an annual total cost of less than 10 US cents per person. UV Waterworks has been successfully tested in the laboratory. Limited field trials of an early version of the device were conducted in India in 1994--95. Insights from these trials led to the present design. Extended field trials ofmore » UV Waterworks, initiated in South Africa in February 1997, will be coordinated by the South African Center for Essential Community Services (SACECS), with technical and organizational support from Lawrence Berkeley National Laboratory(LBNL) and the Natural Resources Defense Council (both US). The first of the eight planned sites of the year long trial is an AIDS hospice near Durban. Durban metro Water and LBNL lab-tested a UV Waterworks unit prior to installing it at the hospice in August, 1997. The authors describe the field test plans and preliminary results from Durban.« less

Design and rationale of the AngioSeal versus the Radial approach In acute coronary SyndromE (ARISE) trial: a randomized comparison of a vascular closure device versus the radial approach to prevent vascular access site complications in non-ST-segment elevation acute coronary syndrome patients.

PubMed

de Andrade, Pedro Beraldo; E Mattos, Luiz Alberto Piva; Tebet, Marden André; Rinaldi, Fábio Salerno; Esteves, Vinícius Cardozo; Nogueira, Ederlon Ferreira; França, João Ítalo Dias; de Andrade, Mônica Vieira Athanazio; Barbosa, Robson Alves; Labrunie, André; Abizaid, Alexandre Antônio Cunha; Sousa, Amanda Guerra de Moraes Rego

2013-12-18

Arterial access is a major site of bleeding complications after invasive coronary procedures. Among strategies to decrease vascular complications, the radial approach is an established one. Vascular closure devices provide more comfort to patients and decrease hemostasis and need for bed rest. However, the inconsistency of data proving their safety limits their routine adoption as a strategy to prevent vascular complications, requiring evidence through adequately designed randomized trials. The aim of this study is to compare the radial versus femoral approach using a vascular closure device for the incidence of arterial puncture site vascular complications among non-ST-segment elevation acute coronary syndrome patients submitted to an early invasive strategy. ARISE is a national, multicenter, non-inferiority randomized clinical trial. Two hundred patients with non-ST-segment elevation acute coronary syndrome will be randomized to either radial or femoral access using a vascular closure device. The primary outcome is the occurrence of vascular complications at an arterial puncture site 30 days after the procedure, including major bleeding, retroperitoneal hematoma, compartment syndrome, hematoma ≥ 5 cm, pseudoaneurysm, arterio-venous fistula, infection, limb ischemia, arterial occlusion, adjacent nerve injury or the need for vascular surgical repair. Enrollment was initiated in September 2012, and until October 2013 91 patients were included. The inclusion phase is expected to last until the second half of 2014. The ARISE trial will help define the role of a vascular closure device as a bleeding avoidance strategy in patients with NSTEACS. ClinicalTrials.gov identifier: NCT01653587.

Analysis software can put surgical precision into medical device design.

PubMed

Jain, S

2005-11-01

Use of finite element analysis software can give design engineers greater freedom to experiment with new designs and materials and allow companies to get products through clinical trials and onto the market faster. This article suggests how.

Clinical trial design and rationale of the Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy With HeartMate 3 (MOMENTUM 3) investigational device exemption clinical study protocol.

PubMed

Heatley, Gerald; Sood, Poornima; Goldstein, Daniel; Uriel, Nir; Cleveland, Joseph; Middlebrook, Don; Mehra, Mandeep R

2016-04-01

The HeartMate 3 left ventricular assist system (LVAS; St. Jude Medical, Inc., formerly Thoratec Corporation, Pleasanton, CA) was recently introduced into clinical trials for durable circulatory support in patients with medically refractory advanced-stage heart failure. This centrifugal, fully magnetically levitated, continuous-flow pump is engineered with the intent to enhance hemocompatibility and reduce shear stress on blood elements, while also possessing intrinsic pulsatility. Although bridge-to-transplant (BTT) and destination therapy (DT) are established dichotomous indications for durable left ventricular assist device (LVAD) support, clinical practice has challenged the appropriateness of these designations. The introduction of novel LVAD technology allows for the development of clinical trial designs to keep pace with current practices. The prospective, randomized Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy With HeartMate 3 (MOMENTUM 3) clinical trial aims to evaluate the safety and effectiveness of the HeartMate 3 LVAS by demonstrating non-inferiority to the HeartMate II LVAS (also St. Jude Medical, Inc.). The innovative trial design includes patients enrolled under a single inclusion and exclusion criteria , regardless of the intended use of the device, with outcomes ascertained in the short term (ST, at 6 months) and long term (LT, at 2 years). This adaptive trial design includes a pre-specified safety phase (n = 30) analysis. The ST cohort includes the first 294 patients and the LT cohort includes the first 366 patients for evaluation of the composite primary end-point of survival to transplant, recovery or LVAD support free of debilitating stroke (modified Rankin score >3), or re-operation to replace the pump. As part of the adaptive design, an analysis by an independent statistician will determine whether sample size adjustment is required at pre-specified times during the study. A further 662 patients will be enrolled to reach a total of 1,028 patients for evaluation of the secondary end-point of pump replacement at 2 years. Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Risk assessment and comparative effectiveness of left ventricular assist device and medical management in ambulatory heart failure patients: design and rationale of the ROADMAP clinical trial.

PubMed

Rogers, Joseph G; Boyle, Andrew J; O'Connell, John B; Horstmanshof, Douglas A; Haas, Donald C; Slaughter, Mark S; Park, Soon J; Farrar, David J; Starling, Randall C

2015-02-01

Mechanical circulatory support is now a proven therapy for the treatment of patients with advanced heart failure and cardiogenic shock. The role for this therapy in patients with less severe heart failure is unknown. The objective of this study is to examine the impact of mechanically assisted circulation using the HeartMate II left ventricular assist device in patients who meet current US Food and Drug Administration-defined criteria for treatment but are not yet receiving intravenous inotropic therapy. This is a prospective, nonrandomized clinical trial of 200 patients treated with either optimal medical management or a mechanical circulatory support device. This trial will be the first prospective clinical evaluation comparing outcomes of patients with advanced ambulatory heart failure treated with either ongoing medical therapy or a left ventricular assist device. It is anticipated to provide novel insights regarding relative outcomes with each treatment and an understanding of patient and provider acceptance of the ventricular assist device therapy. This trial will also provide information regarding the risk of events in "stable" patients with advanced heart failure and guidance for the optimal timing of left ventricular assist device therapy. Copyright © 2014 Elsevier Inc. All rights reserved.

Evaluating the importance of sham controlled trials in the investigation of medical devices in interventional cardiology.

PubMed

Byrne, Robert A; Capodanno, Davide; Mahfoud, Felix; Fajadet, Jean; Windecker, Stephan; Jüni, Peter; Baumbach, Andreas; Wijns, William; Haude, Michael

2018-05-22

Cardiovascular medicine is one of the specialties that has relied most heavily on evidence from randomized clinical trials in determining best practice for the management of common disease conditions. When comparing treatment approaches, trials incorporating random allocation are the most appropriate method for protecting against treatment allocation bias. In order to protect against performance and ascertainment bias, trial designs including placebo control are preferable where feasible. In contrast to testing of medicines, treatments based on procedures or use of medical devices are more challenging to assess, as sham procedures are necessary to facilitate blinding of participants. However, in many cases, ethical concerns exist, as individual patients allocated to sham procedure are exposed only to risk without potential for benefit. Accordingly, the potential benefits to the general patient population must be carefully weighed against the risks of the exposed individuals. For this reason, trial design and study conduct are critically important to ensure that the investigation has the best chance of answering the study question at hand. In the current manuscript, we aim to review issues relating to the conduct of sham-controlled trials and discuss a number of recent examples in the field of interventional cardiology.

Assessment of the Incorporation of Patient-Centric Outcomes in Studies of Minimally Invasive Glaucoma Surgical Devices

PubMed Central

Le, Jimmy T.; Viswanathan, Shilpa; Tarver, Michelle E.; Eydelman, Malvina; Li, Tianjing

2017-01-01

IMPORTANCE Minimally invasive glaucoma surgical (MIGS) devices are one option for lowering intraocular pressure in patients with glaucoma. OBJECTIVE To examine how often existing clinical studies of MIGS devices registered on ClinicalTrials.gov measure patient-centric outcomes that patients value directly. DESIGN, SETTING, AND PARTICIPANTS We searched ClinicalTrials.gov, a registry of publicly and privately supported clinical studies, on February 20, 2015, for records of MIGS device studies involving patients with glaucoma. Two investigators independently abstracted study design and outcome details from eligible records. We classified outcomes as patient-centric or not patient-centric using a prespecified definition. MAIN OUTCOMES AND MEASURES Proportion of patient-centric and nonpatient-centric outcomes registered on ClinicalTrials.gov. RESULTS We identified 51 eligible studies specifying 127 outcomes. Reduction in intraocular pressure was the most frequent outcome specified (78/127; 61%) and a primary outcome in 41 studies. Patient-centric outcomes—such as adverse events (n = 19; 15%), topical medication use (n = 16; 13%), visual acuity (n = 4; 3%), and health-related quality of life (n = 1; 1%)—were less frequently specified (n = 40; 32%) and a primary outcome in only 12 studies. CONCLUSION AND RELEVANCE Patient-centric outcomes that provide insight into the relative desirability and acceptability of the benefits and risks of MIGS devices are not well represented in current clinical studies. PMID:27389667

47 CFR 5.602 - Market trials.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL EXPERIMENTAL RADIO SERVICE Product Development and..., experimental radio licenses granted for the purpose of market trials pursuant to § 5.3(k) are subject to the... authorized under this rule section, including those devices that are designed to operate under parts 15, 18...

47 CFR 5.602 - Market trials.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL EXPERIMENTAL RADIO SERVICE Product Development and..., experimental radio licenses granted for the purpose of market trials pursuant to § 5.3(k) are subject to the... authorized under this rule section, including those devices that are designed to operate under parts 15, 18...

The futility study—progress over the last decade

PubMed Central

Levin, Bruce

2015-01-01

We review the futility clinical trial design (also known as the non-superiority design) with respect to its emergence and methodologic developments over the last decade, especially in regard to its application to clinical trials for neurological disorders. We discuss the design’s strengths as a programmatic screening device to weed out unpromising new treatments, its limitations and pitfalls, and a recent critique of the logic of the method. PMID:26123873

Remote biomonitoring of temperatures in mothers and newborns: design, development and testing of a wearable sensor device in a tertiary-care hospital in southern India.

PubMed

Mony, Prem K; Thankachan, Prashanth; Bhat, Swarnarekha; Rao, Suman; Washington, Maryann; Antony, Sumi; Thomas, Annamma; Nagarajarao, Sheela C; Rao, Hiteshwar; Amrutur, Bharadwaj

2018-04-01

Newer technologies such as wearables, sensors, mobile telephony and computing offer opportunities to monitor vital physiological parameters and tackle healthcare problems, thereby improving access and quality of care. We describe the design, development and testing of a wearable sensor device for remote biomonitoring of body temperatures in mothers and newborns in southern India. Based on client needs and technological requirements, a wearable sensor device was designed and developed using principles of 'social innovation' design. The device underwent multiple iterations in product design and engineering based on user feedback, and then following preclinical testing, a techno-feasibility study and clinical trial were undertaken in a tertiary-care teaching hospital in Bangalore, India. Clinical trial phases I and IIa for evaluation of safety and efficacy were undertaken in the following sequence: 7 healthy adult volunteers; 18 healthy mothers; 3 healthy babies; 10 stable babies in the neonatal care intensive unit and 1 baby with morbidities. Time-stamped skin temperature readings obtained at 5 min intervals over a 1-hour period from the device secured on upper arms of mothers and abdomen of neonates were compared against readings from thermometers used routinely in clinical practice. Devices were comfortably secured on to adults and neonates, and data were efficiently transmitted via the gateway device for secure storage and retrieval for analysis. The mean skin temperatures in mothers were lower than the axillary temperatures by 2°C; and in newborns, there was a precision of -0.5°C relative to axillary measurements. While occasional minimal adverse events were noted in healthy volunteers, no adverse events were noted in mothers or neonates. This proof-of-concept study shows that this device is promising in terms of feasibility, safety and accuracy (with appropriate calibration) with potential for further refinements in device accuracy and pursuit of further phases of clinical research for improved maternal and neonatal health.

Smartphone app design for the wireless control of a neuromuscular electrical stimulator device with integrated randomization allocation process for RCT applications.

PubMed

Sweeney, Dean; Quinlan, Leo R; OLaighin, Gearoid

2015-08-01

The use of NMES has evolved over the last five decades. Technological advancements have transformed these once complex systems into user-friendly devices with enhanced control functions, leading to new applications of NMES being investigated. The use of Randomized Control Trial (RCT) methodology in evaluating the effectiveness of new and existing applications of NMES is a demanding process adding time and cost to a translation into clinical practice. Poor quality trials may result in poor evidence of NMES effectiveness. In this paper some of the key challenges encountered in NMES clinical trials are identified with the aim of purposing a solution to address these challenges through the adoption of Smartphone technology. The design and evaluation of a smartphone application to provide automatic blind randomization control and facilitating the wireless temporal control of a portable Bluetooth enabled NMES is presented.

Rationale and design of a randomised clinical trial comparing vascular closure device and manual compression to achieve haemostasis after diagnostic coronary angiography: the Instrumental Sealing of ARterial puncture site - CLOSURE device versus manual compression (ISAR-CLOSURE) trial.

PubMed

Xhepa, Erion; Byrne, Robert A; Schulz, Stefanie; Helde, Sandra; Gewalt, Senta; Cassese, Salvatore; Linhardt, Maryam; Ibrahim, Tareq; Mehilli, Julinda; Hoppe, Katharina; Grupp, Katharina; Kufner, Sebastian; Böttiger, Corinna; Hoppmann, Petra; Burgdorf, Christof; Fusaro, Massimiliano; Ott, Ilka; Schneider, Simon; Hengstenberg, Christian; Schunkert, Heribert; Laugwitz, Karl-Ludwig; Kastrati, Adnan

2014-06-01

Vascular closure devices (VCD) have been introduced into clinical practice with the aim of increasing the procedural efficiency and clinical safety of coronary angiography. However, clinical studies comparing VCD and manual compression have yielded mixed results, and large randomised clinical trials comparing the two strategies are missing. Moreover, comparative efficacy studies between different VCD in routine clinical use are lacking. The Instrumental Sealing of ARterial puncture site - CLOSURE device versus manual compression (ISAR-CLOSURE) trial is a prospective, randomised clinical trial designed to compare the outcomes associated with the use of VCD or manual compression to achieve femoral haemostasis. The test hypothesis is that femoral haemostasis after coronary angiography achieved using VCD is not inferior to manual compression in terms of access-site-related vascular complications. Patients undergoing coronary angiography via the common femoral artery will be randomised in a 1:1:1 fashion to receive FemoSeal VCD, EXOSEAL VCD or manual compression. The primary endpoint is the incidence of the composite of arterial access-related complications (haematoma ≥5 cm, pseudoaneurysm, arteriovenous fistula, access-site-related bleeding, acute ipsilateral leg ischaemia, the need for vascular surgical/interventional treatment or documented local infection) at 30 days after randomisation. According to power calculations based on non-inferiority hypothesis testing, enrolment of 4,500 patients is planned. The trial is registered at www.clinicaltrials.gov (study identifier: NCT01389375). The safety of VCD as compared to manual compression in patients undergoing transfemoral coronary angiography remains an issue of clinical equipoise. The aim of the ISAR-CLOSURE trial is to assess whether femoral haemostasis achieved through the use of VCD is non-inferior to manual compression in terms of access-site-related vascular complications.

Development of high impedance measurement system for water leakage detection in implantable neuroprosthetic devices.

PubMed

Yousif, Aziz; Kelly, Shawn K

2016-08-01

There has been a push for a greater number of channels in implantable neuroprosthetic devices; but, that number has largely been limited by current hermetic packaging technology. Microfabricated packaging is becoming reality, but a standard testing system is needed to prepare these devices for clinical trials. Impedance measurements of electrodes built into the packaging layers may give an early warning of device failure and predict device lifetime. Because the impedance magnitudes of such devices can be on the order of gigaohms, a versatile system was designed to accommodate ultra-high impedances and allow future integrated circuit implementation in current neural prosthetic technologies. Here we present the circuitry, control software, and preliminary testing results of our designed system.

Multicenter Clinical Trial of Keratin Biomaterial for Peripheral Nerve Regeneration

DTIC Science & Technology

2012-10-01

Drug Evaluation Research (CDER), the Center for Biologics E valuation Research (CBER), and the Center for Devices and Radiological Health ( CDRH ) on May...Research (CBER) , and the Center for Devices and Radiological Health ( CDRH ) to clar ify the designation of the keratin hydrogel. During this m eeting

A Novel Nasal Expiratory Positive Airway Pressure (EPAP) Device for the Treatment of Obstructive Sleep Apnea: A Randomized Controlled Trial

PubMed Central

Berry, Richard B.; Kryger, Meir H.; Massie, Clifford A.

2011-01-01

Study Objectives: Investigate the efficacy of a novel nasal expiratory positive airway pressure (EPAP) device as a treatment for obstructive sleep apnea (OSA). Design: A prospective, multicenter, sham-controlled, parallel-group, randomized, double-blind clinical trial. Setting: 19 sites including both academic and private sleep disorder centers Patients: Obstructive sleep apnea with a pre-study AHI ≥ 10/hour Interventions: Treatment with a nasal EPAP device (N = 127) or similar appearing sham device (N = 123) for 3 months. Polysomnography (PSG) was performed on 2 non-consecutive nights (random order: device-on, device-off) at week 1 and after 3 months of treatment. Analysis of an intention to treat group (ITT) (patients completing week 1 PSGs) (EPAP N = 119, sham N = 110) was performed. Measurements and Results: At week 1, the median AHI value (device-on versus device-off) was significantly lower with EPAP (5.0 versus 13.8 events/h, P < 0.0001) but not sham (11.6 versus 11.1 events/h, P = NS); the decrease in the AHI (median) was greater (−52.7% vs. −7.3%, P < 0.0001) for the ITT group. At month 3, the percentage decrease in the AHI was 42.7% (EPAP) and 10.1% (sham), P < 0.0001. Over 3 months of EPAP treatment the Epworth Sleepiness Scale decreased (9.9 ± 4.7 to 7.2 ± 4.2, P < 0.0001), and the median percentage of reported nights used (entire night) was 88.2%. Conclusions: The nasal EPAP device significantly reduced the AHI and improved subjective daytime sleepiness compared to the sham treatment in patients with mild to severe OSA with excellent adherence. Clinical Trial Information: Registrations: ClinicalTrials.gov. Trial name: Randomized Study of Provent Versus Sham Device to Treat Obstructive Sleep Apnea (AERO). URL: http://www.clinicaltrials.gov/ct2/show/NCT00772044?term=Ventus&rank=1. Registration Number: NCT00772044. Citation: Berry RB; Kryger MH; Massie CA. A novel nasal expiratory positive airway pressure (EPAP) device for the treatment of obstructive sleep apnea: a randomized controlled trial. SLEEP 2011;34(4):479-485. PMID:21461326

Pre-market version of a commercially available hearing instrument with a tinnitus sound generator: feasibility of evaluation in a clinical trial.

PubMed

Sereda, Magdalena; Davies, Jeff; Hall, Deborah A

2017-04-01

This report considers feasibility of conducting a UK trial of combination devices for tinnitus, using data from the study which evaluated different listener programmes available within the pre-market version of Oticon Alta with Tinnitus Sound Generator. Open and closed questions addressed the following feasibility issues: (1) Participant recruitment; (2) Device acceptability; (3) Programme preferences in different self-nominated listening situations; (4) Usability; (5) Compliance; (6) Adverse events. Eight current combination hearing aid users (all males) aged between 62-72 years (mean age 67.25 years, SD = 3.8). All eight participants reported the physical aspects and noise options on the experimental device to be acceptable. Programmes with amplification and masking features were equally preferred over the basic amplification-only programme. Individual preferences for the different programme options varied widely, both across participants and across listening situations. A set of recommendations for future trials were formulated which calls for more "real world" trial design rather than tightly controlling the fitting procedure.

Innovations in design and technology. The story of hip arthroplasty.

PubMed

Amstutz, H C

2000-09-01

The current study reviews the early history of surgeon-initiated trial and error development in hip joint arthroplasty and the subsequent methodological evolution to proper criteria for hypothesis testing using bioengineers and other research scientists. The interplay and relationships to industry, universities, scientific organizations, and the Food and Drug Administration with respect to device development in hip arthroplasty are reviewed. The ethics of and responsibilities to involved parties are outlined, citing the history of many contemporary developments. Examples are provided from the evolution and introduction of unsuccessful innovations, and the problems inherent in the current methodology of the approval process from the Food and Drug Administration using the 5-10K, Investigative Device Exemption, and the Pre-Market Approval protocols. The pros and cons of randomized trials for devices are outlined with the conclusion that they are not appropriate for device introduction. The proper, rational methodology for introduction of new devices is a phased-in clinical trial process after pertinent bench testing. Finally, the ethical dilemmas created by managed care are addressed. Industry involvements of the surgeon-spokesmen are cited.

Dynamics of device innovation: implications for assessing value.

PubMed

Gelijns, Annetine C; Russo, Mark J; Hong, Kimberly N; Brown, Lawrence D; Ascheim, Deborah D; Moskowitz, Alan J

2013-10-01

In recent years, there has been growing interest in evaluating the health and economic impact of medical devices. Payers increasingly rely on cost-effectiveness analyses in making their coverage decisions, and are adopting value-based purchasing initiatives. These analytic approaches, however, have been shaped heavily by their use in the pharmaceutical realm, and are ill-adapted to the medical device context. This study focuses on the development and evaluation of left ventricular assist devices (LVADs) to highlight the unique challenges involved in the design and conduct of device trials compared with pharmaceuticals. Devices are moving targets characterized by a much higher degree of post-introduction innovation and "learning by using" than pharmaceuticals. The cost effectiveness ratio of left ventricular assist devices for destination therapy, for example, decreased from around $600,000 per life year saved based on results from the pivotal trial to around $100,000 within a relatively short time period. These dynamics pose fundamental challenges to the evaluation enterprise as well as the policy-making world, which this paper addresses.

Evaluation of a novel vital sign device to reduce maternal mortality and morbidity in low-resource settings: a mixed method feasibility study for the CRADLE-3 trial.

PubMed

Vousden, Nicola; Lawley, Elodie; Nathan, Hannah L; Seed, Paul T; Brown, Adrian; Muchengwa, Tafadzwa; Charantimath, Umesh; Bellad, Mrutyunjaya; Gidiri, Muchabayiwa Francis; Goudar, Shivaprasad; Chappell, Lucy C; Sandall, Jane; Shennan, Andrew H

2018-04-27

The CRADLE-3 trial is a stepped-wedge randomised controlled trial aiming to reduce maternal mortality and morbidity by implementing a novel vital sign device (CRADLE Vital Sign Alert) and training package into routine maternity care in 10 low-income sites. The MRC Guidance on complex interventions proposes that interventions and implementation strategies be shaped by early phase piloting and development work. We present the findings of a three-month mixed-methodology feasibility study for this trial, describe how this was informed by the MRC guidance and the study design was refined. The fidelity, dose, feasibility and acceptability of implementation and training materials were assessed in three representative non-trial sites (Zimbabwe, Ethiopia, India) using multiple-choice questionnaires, evaluation of clinical management (action log), healthcare provider (HCP) semi-structured interviews and focus groups 4-10 weeks after implementation. Simultaneously, the 10 sites included in the main trial (eight countries) collected primary outcome data to inform the power calculation and randomisation allocation and assess the feasibility of data collection. The package was implemented with high fidelity (85% of HCP trained, n = 204). The questionnaires indicated a good understanding of device use with 75% of participants scoring > 75% (n = 97; 90% of those distributed). Action logs were inconsistently completed but indicated that the majority of HCP responded appropriately to abnormal results. From 18 HCP interviews and two focus groups it was widely reported that the intervention improved capacity to make clinical decisions, escalate care and make appropriate referrals. Nine of the ten main trial sites achieved ethical approval for pilot data collection. Intensive care was an inconsistent marker of morbidity and stroke an infrequent outcome and therefore they were removed from the main trial composite outcome. Tools and methods of data collection were optimized and event rates used to inform randomisation. This feasibility study demonstrates that the components of the intervention were acceptable, methods of implementing were successful and the main trial design would be feasible. Qualitative work identified key moderators that informed the main trial process evaluation. Changes to the training package, implementation strategy, study design and processes were identified to refine the implementation in the main trial. ISRCTN41244132 ; Registered 24/11/2015.

Role of preliminary registry data in development of a clinical trial for an innovative device: a small but integral piece of a health policy initiative

PubMed Central

Ricci, Donald R.; de Vries, Joost; Blanc, Raphael

2017-01-01

ABSTRACT Establishing a national health policy at a macro level involves the integration of a series of health initiatives across a spectrum of activities, including clinical care. Evaluation of the safety and efficacy of a new medical device ultimately evolves to testing in humans. The pathway to a formal prospective clinical trial includes a stepwise appreciation of pre-clinical data and detailed analysis of data obtained from preliminary registries, where information about appropriate patient selection and use of the device is obtained. Evaluation of procedural and follow-up efficacy and safety data in a preliminary series of cases, chosen to simulate published data, allows the design and conduct of clinical trials that are required to verify preliminary observations, closing the loop on one aspect of modifying health policy decisions. PMID:28321285

Evaluating Varied Label Designs for Use with Medical Devices: Optimized Labels Outperform Existing Labels in the Correct Selection of Devices and Time to Select.

PubMed

Bix, Laura; Seo, Do Chan; Ladoni, Moslem; Brunk, Eric; Becker, Mark W

2016-01-01

Effective standardization of medical device labels requires objective study of varied designs. Insufficient empirical evidence exists regarding how practitioners utilize and view labeling. Measure the effect of graphic elements (boxing information, grouping information, symbol use and color-coding) to optimize a label for comparison with those typical of commercial medical devices. Participants viewed 54 trials on a computer screen. Trials were comprised of two labels that were identical with regard to graphics, but differed in one aspect of information (e.g., one had latex, the other did not). Participants were instructed to select the label along a given criteria (e.g., latex containing) as quickly as possible. Dependent variables were binary (correct selection) and continuous (time to correct selection). Eighty-nine healthcare professionals were recruited at Association of Surgical Technologists (AST) conferences, and using a targeted e-mail of AST members. Symbol presence, color coding and grouping critical pieces of information all significantly improved selection rates and sped time to correct selection (α = 0.05). Conversely, when critical information was graphically boxed, probability of correct selection and time to selection were impaired (α = 0.05). Subsequently, responses from trials containing optimal treatments (color coded, critical information grouped with symbols) were compared to two labels created based on a review of those commercially available. Optimal labels yielded a significant positive benefit regarding the probability of correct choice ((P<0.0001) LSM; UCL, LCL: 97.3%; 98.4%, 95.5%)), as compared to the two labels we created based on commercial designs (92.0%; 94.7%, 87.9% and 89.8%; 93.0%, 85.3%) and time to selection. Our study provides data regarding design factors, namely: color coding, symbol use and grouping of critical information that can be used to significantly enhance the performance of medical device labels.

2017 Cardiovascular and Stroke Endpoint Definitions for Clinical Trials.

PubMed

Hicks, Karen A; Mahaffey, Kenneth W; Mehran, Roxana; Nissen, Steven E; Wiviott, Stephen D; Dunn, Billy; Solomon, Scott D; Marler, John R; Teerlink, John R; Farb, Andrew; Morrow, David A; Targum, Shari L; Sila, Cathy A; Hai, Mary T Thanh; Jaff, Michael R; Joffe, Hylton V; Cutlip, Donald E; Desai, Akshay S; Lewis, Eldrin F; Gibson, C Michael; Landray, Martin J; Lincoff, A Michael; White, Christopher J; Brooks, Steven S; Rosenfield, Kenneth; Domanski, Michael J; Lansky, Alexandra J; McMurray, John J V; Tcheng, James E; Steinhubl, Steven R; Burton, Paul; Mauri, Laura; O'Connor, Christopher M; Pfeffer, Marc A; Hung, H M James; Stockbridge, Norman L; Chaitman, Bernard R; Temple, Robert J

2018-02-27

This publication describes uniform definitions for cardiovascular and stroke outcomes developed by the Standardized Data Collection for Cardiovascular Trials Initiative and the US Food and Drug Administration (FDA). The FDA established the Standardized Data Collection for Cardiovascular Trials Initiative in 2009 to simplify the design and conduct of clinical trials intended to support marketing applications. The writing committee recognizes that these definitions may be used in other types of clinical trials and clinical care processes where appropriate. Use of these definitions at the FDA has enhanced the ability to aggregate data within and across medical product development programs, conduct meta-analyses to evaluate cardiovascular safety, integrate data from multiple trials, and compare effectiveness of drugs and devices. Further study is needed to determine whether prospective data collection using these common definitions improves the design, conduct, and interpretability of the results of clinical trials. © 2018 American Heart Association, Inc.

AplusB: A Web Application for Investigating A + B Designs for Phase I Cancer Clinical Trials.

PubMed

Wheeler, Graham M; Sweeting, Michael J; Mander, Adrian P

2016-01-01

In phase I cancer clinical trials, the maximum tolerated dose of a new drug is often found by a dose-escalation method known as the A + B design. We have developed an interactive web application, AplusB, which computes and returns exact operating characteristics of A + B trial designs. The application has a graphical user interface (GUI), requires no programming knowledge and is free to access and use on any device that can open an internet browser. A customised report is available for download for each design that contains tabulated operating characteristics and informative plots, which can then be compared with other dose-escalation methods. We present a step-by-step guide on how to use this application and provide several illustrative examples of its capabilities.

Incorporation of stochastic engineering models as prior information in Bayesian medical device trials.

PubMed

Haddad, Tarek; Himes, Adam; Thompson, Laura; Irony, Telba; Nair, Rajesh

2017-01-01

Evaluation of medical devices via clinical trial is often a necessary step in the process of bringing a new product to market. In recent years, device manufacturers are increasingly using stochastic engineering models during the product development process. These models have the capability to simulate virtual patient outcomes. This article presents a novel method based on the power prior for augmenting a clinical trial using virtual patient data. To properly inform clinical evaluation, the virtual patient model must simulate the clinical outcome of interest, incorporating patient variability, as well as the uncertainty in the engineering model and in its input parameters. The number of virtual patients is controlled by a discount function which uses the similarity between modeled and observed data. This method is illustrated by a case study of cardiac lead fracture. Different discount functions are used to cover a wide range of scenarios in which the type I error rates and power vary for the same number of enrolled patients. Incorporation of engineering models as prior knowledge in a Bayesian clinical trial design can provide benefits of decreased sample size and trial length while still controlling type I error rate and power.

Remote biomonitoring of temperatures in mothers and newborns: design, development and testing of a wearable sensor device in a tertiary-care hospital in southern India

PubMed Central

Mony, Prem K; Thankachan, Prashanth; Bhat, Swarnarekha; Rao, Suman; Washington, Maryann; Antony, Sumi; Thomas, Annamma; Nagarajarao, Sheela C; Rao, Hiteshwar; Amrutur, Bharadwaj

2018-01-01

Objective Newer technologies such as wearables, sensors, mobile telephony and computing offer opportunities to monitor vital physiological parameters and tackle healthcare problems, thereby improving access and quality of care. We describe the design, development and testing of a wearable sensor device for remote biomonitoring of body temperatures in mothers and newborns in southern India. Methods Based on client needs and technological requirements, a wearable sensor device was designed and developed using principles of ‘social innovation’ design. The device underwent multiple iterations in product design and engineering based on user feedback, and then following preclinical testing, a techno-feasibility study and clinical trial were undertaken in a tertiary-care teaching hospital in Bangalore, India. Clinical trial phases I and IIa for evaluation of safety and efficacy were undertaken in the following sequence: 7 healthy adult volunteers; 18 healthy mothers; 3 healthy babies; 10 stable babies in the neonatal care intensive unit and 1 baby with morbidities. Time-stamped skin temperature readings obtained at 5 min intervals over a 1-hour period from the device secured on upper arms of mothers and abdomen of neonates were compared against readings from thermometers used routinely in clinical practice. Results Devices were comfortably secured on to adults and neonates, and data were efficiently transmitted via the gateway device for secure storage and retrieval for analysis. The mean skin temperatures in mothers were lower than the axillary temperatures by 2°C; and in newborns, there was a precision of –0.5°C relative to axillary measurements. While occasional minimal adverse events were noted in healthy volunteers, no adverse events were noted in mothers or neonates. Conclusions This proof-of-concept study shows that this device is promising in terms of feasibility, safety and accuracy (with appropriate calibration) with potential for further refinements in device accuracy and pursuit of further phases of clinical research for improved maternal and neonatal health. PMID:29670758

Grave fraudulence in medical device research: a narrative review of the PIN seeding study for the Pinnacle hip system.

PubMed

Steffen, Joan E; Fassler, Ella A; Reardon, Kevin J; Egilman, David S

2018-01-01

In 2001, DePuy, a wholly-owned subsidiary of Johnson & Johnson (J&J/DePuy), initiated a seeding study called the "Multi-center, Prospective, Clinical Evaluation of Pinnacle Acetabular Implants in Total Hip Arthroplasty" (PIN Study). J&J/DePuy designed this study to develop new business opportunities during the launch of their Pinnacle Hip System (PHS) and generate survivorship data for marketing. This article, the first review of a seeding trial for a medical device, examines internal company documents relating to the PIN Study; the analysis herein focuses on the integrity of J&J/DePuy's research practices in conception, implementation, and analysis. J&J/DePuy violated the study protocol and manipulated data; consented participants in violation of standards protecting human subjects; and did not secure Institutional Review Board approval for all study sites. J&J/DePuy used PIN Study results as the "fundamental selling point" for the PHS. Medical device seeding trials are distinct from previously-documented pharmaceutical seeding trials because companies can profit directly from device sales and because these studies may be the first clinical evaluation of the device (as was the case for the PIN Study). Seeding trials are malleable marketing projects, not rigorous scientific studies. Regulatory bodies, physicians, and others should be vigilant for persuasive marketing accounts disguised as science.

Transcatheter Interatrial Shunt Device for the Treatment of Heart Failure: Rationale and Design of the Randomized Trial to REDUCE Elevated Left Atrial Pressure in Heart Failure (REDUCE LAP-HF I).

PubMed

Feldman, Ted; Komtebedde, Jan; Burkhoff, Daniel; Massaro, Joseph; Maurer, Mathew S; Leon, Martin B; Kaye, David; Silvestry, Frank E; Cleland, John G F; Kitzman, Dalane; Kubo, Spencer H; Van Veldhuisen, Dirk J; Kleber, Franz; Trochu, Jean-Noël; Auricchio, Angelo; Gustafsson, Finn; Hasenfuβ, Gerd; Ponikowski, Piotr; Filippatos, Gerasimos; Mauri, Laura; Shah, Sanjiv J

2016-07-01

Heart failure with preserved ejection fraction (HFpEF), a major public health problem with high morbidity and mortality rates, remains difficult to manage because of a lack of effective treatment options. Although HFpEF is a heterogeneous clinical syndrome, elevated left atrial pressure-either at rest or with exertion-is a common factor among all forms of HFpEF and one of the primary reasons for dyspnea and exercise intolerance in these patients. On the basis of clinical experience with congenital interatrial shunts in mitral stenosis, it has been hypothesized that the creation of a left-to-right interatrial shunt to decompress the left atrium (without compromising left ventricular filling or forward cardiac output) is a rational, nonpharmacological strategy for alleviating symptoms in patients with HFpEF. A novel transcatheter interatrial shunt device has been developed and evaluated in patients with HFpEF in single-arm, nonblinded clinical trials. These studies have demonstrated the safety and potential efficacy of the device. However, a randomized, placebo-controlled evaluation of the device is required to further evaluate its safety and efficacy in patients with HFpEF. In this article, we give the rationale for a therapeutic transcatheter interatrial shunt device in HFpEF, and we describe the design of REDUCE Elevated Left Atrial Pressure in Heart Failure (REDUCE LAP-HF I), the first randomized controlled trial of a device-based therapy to reduce left atrial pressure in HFpEF. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02600234. © 2016 American Heart Association, Inc.

Industry Collaboration and Primary Guest Authorship of High-Impact Randomized Clinical Trials: A Cross-Sectional Study.

PubMed

Roper, Nitin; Korenstein, Deborah

2015-10-01

Journals have increased disclosure requirements in recent years, in part to deter guest authorship. The prevalence of guest authorship among primary authors (first and last) in the current era of increased disclosure requirements is unknown. Our aim was to examine the self-reported prevalence of guest authorship among primary authors from a sample of randomized clinical trials with and without industry funding and industry collaboration in the design, analysis or reporting of trials. Cross-sectional analysis of randomized, drug/device clinical trials with published details on the "Role of the Funding Source/Sponsor" published in high-impact biomedical journals between 1 December 2011 and 31 November 2012. Phase 1 or 2 trials, secondary trial analyses, and trials that were not listed on ClinicalTrials.gov were excluded. Primary guest authorship was defined, based on International Committee of Medical Journal Editors (ICMJE) criteria, when neither the first nor last author contributed to either of the following: 1) the design of the trial or the analysis/interpretation of data; or 2) drafting part or all of the manuscript. One hundred and sixty-eight randomized clinical trials that met inclusion criteria were included. We measured differences in the prevalence of guest authorship between trials with neither industry funding nor collaboration and 1) trials with industry funding without collaboration, and 2) trials with industry funding with collaboration. The overall prevalence of primary guest authorship was 6 % (10/168). Primary guest authorship was significantly more common in trials with industry funding with collaboration than in those with neither industry funding nor collaboration [13.2 % (10/76) vs. 0 % (0/39); p < 0.02]. Primary guest authorship did not differ between trials with industry funding without collaboration and trials with neither industry funding nor collaboration. Among a sample of randomized, drug/device clinical trials in high-impact biomedical journals, primary guest authorship was overall uncommon and occurred exclusively among trials with industry funding with collaboration.

ERic Acute StrokE Recanalization: A study using predictive analytics to assess a new device for mechanical thrombectomy.

PubMed

Siemonsen, Susanne; Forkert, Nils D; Bernhardt, Martina; Thomalla, Götz; Bendszus, Martin; Fiehler, Jens

2017-08-01

Aim and hypothesis Using a new study design, we investigate whether next-generation mechanical thrombectomy devices improve clinical outcomes in ischemic stroke patients. We hypothesize that this new methodology is superior to intravenous tissue plasminogen activator therapy alone. Methods and design ERic Acute StrokE Recanalization is an investigator-initiated prospective single-arm, multicenter, controlled, open label study to compare the safety and effectiveness of a new recanalization device and distal access catheter in acute ischemic stroke patients with symptoms attributable to acute ischemic stroke and vessel occlusion of the internal cerebral artery or middle cerebral artery. Study outcome The primary effectiveness endpoint is the volume of saved tissue. Volume of saved tissue is defined as difference of the actual infarct volume and the brain volume that is predicted to develop infarction by using an optimized high-level machine learning model that is trained on data from a historical cohort treated with IV tissue plasminogen activator. Sample size estimates Based on own preliminary data, 45 patients fulfilling all inclusion criteria need to complete the study to show an efficacy >38% with a power of 80% and a one-sided alpha error risk of 0.05 (based on a one sample t-test). Discussion ERic Acute StrokE Recanalization is the first prospective study in interventional stroke therapy to use predictive analytics as primary and secondary endpoint. Such trial design cannot replace randomized controlled trials with clinical endpoints. However, ERic Acute StrokE Recanalization could serve as an exemplary trial design for evaluating nonpivotal neurovascular interventions.

The development of neural stimulators: a review of preclinical safety and efficacy studies.

PubMed

Shepherd, Robert K; Villalobos, Joel; Burns, Owen; Nayagam, David

2018-05-14

Given the rapid expansion of the field of neural stimulation and the rigorous regulatory approval requirements required before these devices can be applied clinically, it is important that there is clarity around conducting preclinical safety and efficacy studies required for the development of this technology. The present review examines basic design principles associated with the development of a safe neural stimulator and describes the suite of preclinical safety studies that need to be considered when taking a device to clinical trial. Neural stimulators are active implantable devices that provide therapeutic intervention, sensory feedback or improved motor control via electrical stimulation of neural or neuro-muscular tissue in response to trauma or disease. Because of their complexity, regulatory bodies classify these devices in the highest risk category (Class III), and they are therefore required to go through a rigorous regulatory approval process before progressing to market. The successful development of these devices is achieved through close collaboration across disciplines including engineers, scientists and a surgical/clinical team, and the adherence to clear design principles. Preclinical studies form one of several key components in the development pathway from concept to product release of neural stimulators. Importantly, these studies provide iterative feedback in order to optimise the final design of the device. Key components of any preclinical evaluation include: in vitro studies that are focussed on device reliability and include accelerated testing under highly controlled environments; in vivo studies using animal models of the disease or injury in order to assess safety and, given an appropriate animal model, the efficacy of the technology under both passive and electrically active conditions; and human cadaver and ex vivo studies designed to ensure the device's form factor conforms to human anatomy, to optimise the surgical approach and to develop any specialist surgical tooling required. The pipeline from concept to commercialisation of these devices is long and expensive; careful attention to both device design and its preclinical evaluation will have significant impact on the duration and cost associated with taking a device through to commercialisation. Carefully controlled in vitro and in vivo studies together with ex vivo and human cadaver trials are key components of a thorough preclinical evaluation of any new neural stimulator. © 2018 IOP Publishing Ltd.

Use of Mobile Devices and the Internet for Multimedia Informed Consent Delivery and Data Entry in a Pediatric Asthma Trial: Study Design and Rationale

PubMed Central

Blake, Kathryn; Holbrook, Janet T.; Antal, Holly; Shade, David; Bunnell, H. Timothy; McCahan, Suzanne M.; Wise, Robert A.; Pennington, Chris; Garfinkel, Paul; Wysocki, Tim

2015-01-01

Introduction Phase III / IV clinical trials are expensive and time consuming and often suffer from poor enrollment and retention rates. Pediatric trials are particularly difficult because scheduling around the parent, participant and potentially other sibling schedules can be burdensome. We are evaluating using the internet and mobile devices to conduct the consent process and study visits in a streamlined pediatric asthma trial. Our hypothesis is that these study processes will be noninferior and will be less expensive compared to a traditional pediatric asthma trial. Materials/Methods Parents and participants, aged 12 through 17 years, complete the informed consent process by viewing a multi-media website containing a consent video and study material in the streamlined trial. Participants are provided an iPad with WiFi and EasyOne spirometer for use during FaceTime visits and online twice daily symptom reporting during an 8-week run-in followed by 12-week study period. Outcomes are compared with participants completing a similarly designed traditional trial comparing the same treatments within the same pediatric health-system. After 8 weeks of open-label Advair 250/50 twice daily, participants in both trial types are randomized to Advair 250/50, Flovent 250, or Advair 100/50 given 1 inhalation twice daily. Study staff track time spent to determine study costs. Results Participants have been enrolled in the streamlined and traditional trials and recuitment is ongoing. Conclusions This project will provide important information on both clinical and economic outcomes for a novel method of conducting clinical trials. The results will be broadly applicable to trials of other diseases. PMID:25847579

Use of mobile devices and the internet for multimedia informed consent delivery and data entry in a pediatric asthma trial: Study design and rationale.

PubMed

Blake, Kathryn; Holbrook, Janet T; Antal, Holly; Shade, David; Bunnell, H Timothy; McCahan, Suzanne M; Wise, Robert A; Pennington, Chris; Garfinkel, Paul; Wysocki, Tim

2015-05-01

Phase III/IV clinical trials are expensive and time consuming and often suffer from poor enrollment and retention rates. Pediatric trials are particularly difficult because scheduling around the parent, participant and potentially other sibling schedules can be burdensome. We are evaluating using the internet and mobile devices to conduct the consent process and study visits in a streamlined pediatric asthma trial. Our hypothesis is that these study processes will be non-inferior and will be less expensive compared to a traditional pediatric asthma trial. Parents and participants, aged 12 through 17 years, complete the informed consent process by viewing a multi-media website containing a consent video and study material in the streamlined trial. Participants are provided an iPad with WiFi and EasyOne spirometer for use during FaceTime visits and online twice daily symptom reporting during an 8-week run-in followed by a 12-week study period. Outcomes are compared with participants completing a similarly designed traditional trial comparing the same treatments within the same pediatric health-system. After 8 weeks of open-label Advair 250/50 twice daily, participants in both trial types are randomized to Advair 250/50, Flovent 250, or Advair 100/50 given 1 inhalation twice daily. Study staff track time spent to determine study costs. Participants have been enrolled in the streamlined and traditional trials and recruitment is ongoing. This project will provide important information on both clinical and economic outcomes for a novel method of conducting clinical trials. The results will be broadly applicable to trials of other diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

Statistical innovations in the medical device world sparked by the FDA.

PubMed

Campbell, Gregory; Yue, Lilly Q

2016-01-01

The world of medical devices while highly diverse is extremely innovative, and this facilitates the adoption of innovative statistical techniques. Statisticians in the Center for Devices and Radiological Health (CDRH) at the Food and Drug Administration (FDA) have provided leadership in implementing statistical innovations. The innovations discussed include: the incorporation of Bayesian methods in clinical trials, adaptive designs, the use and development of propensity score methodology in the design and analysis of non-randomized observational studies, the use of tipping-point analysis for missing data, techniques for diagnostic test evaluation, bridging studies for companion diagnostic tests, quantitative benefit-risk decisions, and patient preference studies.

[Mechanical thrombectomy in acute ischemic stroke. What is the position after the latest study results?].

PubMed

Hacke, W; Diener, H-C

2015-06-01

Mechanical devices for the recanalization of vessel occlusions in severe acute ischemic stroke have been developed for more than a decade. Several devices have been approved for clinical use on the basis of uncontrolled case series. Many neurologists have asked for randomized clinical trials comparing the new devices with standard treatment, e.g. thrombolytic therapy within a 4.5 h time window. The first 3 investigator initiated randomized trials published in 2013 failed to show superiority of mechanical thrombectomy over standard treatment. In the aftermath of these negative results several new trials with changes in design (e.g. shorter time window and only proximal vessel occlusions) and the use of modern devices with proven higher recanalization rates, so called stent retrievers, have been launched. In October 2014 the first of these new trials was presented and showed a clear superiority of thrombectomy. Based on this result interim analyses of five other studies were performed and most were prematurely terminated because of overwhelming efficacy. Only one trial testing another type of recanalization device failed to reach a statistically significant result. Currently five studies have already been published and two more studies have been presented at scientific conferences. This article provides an overview of the study protocols and the results of the individual studies, their common features and the characteristics of patients who benefit from this treatment. Finally, the consequences that these results may have for the treatment of patients with severe stroke caused by proximal vessel occlusion are discussed.

Patients' ability to treat anaphylaxis using adrenaline autoinjectors: a randomized controlled trial.

PubMed

Umasunthar, T; Procktor, A; Hodes, M; Smith, J G; Gore, C; Cox, H E; Marrs, T; Hanna, H; Phillips, K; Pinto, C; Turner, P J; Warner, J O; Boyle, R J

2015-07-01

Previous work has shown patients commonly misuse adrenaline autoinjectors (AAI). It is unclear whether this is due to inadequate training, or poor device design. We undertook a prospective randomized controlled trial to evaluate ability to administer adrenaline using different AAI devices. We allocated mothers of food-allergic children prescribed an AAI for the first time to Anapen or EpiPen using a computer-generated randomization list, with optimal training according to manufacturer's instructions. After one year, participants were randomly allocated a new device (EpiPen, Anapen, new EpiPen, JEXT or Auvi-Q), without device-specific training. We assessed ability to deliver adrenaline using their AAI in a simulated anaphylaxis scenario six weeks and one year after initial training, and following device switch. Primary outcome was successful adrenaline administration at six weeks, assessed by an independent expert. Secondary outcomes were success at one year, success after switching device, and adverse events. We randomized 158 participants. At six weeks, 30 of 71 (42%) participants allocated to Anapen and 31 of 73 (43%) participants allocated to EpiPen were successful - RR 1.00 (95% CI 0.68-1.46). Success rates at one year were also similar, but digital injection was more common at one year with EpiPen (8/59, 14%) than Anapen (0/51, 0%, P = 0.007). When switched to a new device without specific training, success rates were higher with Auvi-Q (26/28, 93%) than other devices (39/80, 49%; P < 0.001). AAI device design is a major determinant of successful adrenaline administration. Success rates were low with several devices, but were high using the audio-prompt device Auvi-Q. © 2015 The Authors Allergy Published by John Wiley & Sons Ltd.

21 CFR 886.1415 - Ophthalmic trial lens frame.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Ophthalmic trial lens frame. 886.1415 Section 886...) MEDICAL DEVICES OPHTHALMIC DEVICES Diagnostic Devices § 886.1415 Ophthalmic trial lens frame. (a) Identification. An opthalmic trial lens frame is a mechanical device intended to hold trial lenses for vision...

Neurosecurity: security and privacy for neural devices.

PubMed

Denning, Tamara; Matsuoka, Yoky; Kohno, Tadayoshi

2009-07-01

An increasing number of neural implantable devices will become available in the near future due to advances in neural engineering. This discipline holds the potential to improve many patients' lives dramatically by offering improved-and in some cases entirely new-forms of rehabilitation for conditions ranging from missing limbs to degenerative cognitive diseases. The use of standard engineering practices, medical trials, and neuroethical evaluations during the design process can create systems that are safe and that follow ethical guidelines; unfortunately, none of these disciplines currently ensure that neural devices are robust against adversarial entities trying to exploit these devices to alter, block, or eavesdrop on neural signals. The authors define "neurosecurity"-a version of computer science security principles and methods applied to neural engineering-and discuss why neurosecurity should be a critical consideration in the design of future neural devices.

Overview of the 2016 U.S. Food and Drug Administration Circulatory System Devices Advisory Panel Meeting on the Absorb Bioresorbable Vascular Scaffold System.

PubMed

Steinvil, Arie; Rogers, Toby; Torguson, Rebecca; Waksman, Ron

2016-09-12

This study aims to describe the discussions and recommendations made during the U.S. Food and Drug Administration (FDA) Circulatory System Device Panel pre-market approval application for the Absorb Bioresorbable Vascular Scaffold (BVS) System. The Absorb BVS System is a first-of-its-kind fully bioresorbable percutaneous coronary intervention technology. The absorb BVS was studied in the ABSORB III (A Clinical Evaluation of Absorb BVS, the Everolimus Eluting Bioresorbable Vascular Scaffold in the Treatment of Subjects with de Novo Native Coronary Artery Lesions) trial, the pivotal U.S. investigational device exemption trial. Observational report of the FDA Circulatory System Device Panel pre-market approval application meeting held on March 15, 2016. The U.S. FDA Circulatory System Device Panel members reviewed the ABSROB III trial outcomes and additional post hoc analyses presented by the sponsor and the FDA. The ABSORB III trial met the primary endpoint of noninferiority of Absorb BVS compared with the control, XIENCE drug-eluting stent, for target lesion failure at 1 year. Although a higher numerical trend for adverse outcomes was reported for the Absorb BVS, there were no statistical differences between Absorb BVS and XIENCE for any safety or effectiveness components for target lesion failure or for the secondary pre-specified outcomes. Panel members raised concerns with regard to the ABSORB III results and post hoc analyses focusing mainly on the noninferiority design of the trial, the apparent safety issues of the Absorb BVS in small vessels, the mismatch of visually versus intravascular imaging assessed vessel size found in ABSORB III and its implications on the adequate device labeling, the safety of Absorb BVS in specific patient and lesion subsets, and the post-approval commitments of the sponsor. Following panel discussions and the evidence presented, the panel voted for approval of the device. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Clinical Trial Design Principles and Endpoint Definitions for Transcatheter Mitral Valve Repair and Replacement: Part 1: Clinical Trial Design Principles: A Consensus Document From the Mitral Valve Academic Research Consortium.

PubMed

Stone, Gregg W; Vahanian, Alec S; Adams, David H; Abraham, William T; Borer, Jeffrey S; Bax, Jeroen J; Schofer, Joachim; Cutlip, Donald E; Krucoff, Mitchell W; Blackstone, Eugene H; Généreux, Philippe; Mack, Michael J; Siegel, Robert J; Grayburn, Paul A; Enriquez-Sarano, Maurice; Lancellotti, Patrizio; Filippatos, Gerasimos; Kappetein, Arie Pieter

2015-07-21

Mitral regurgitation (MR) is one of the most prevalent valve disorders and has numerous etiologies, including primary (organic) MR, due to underlying degenerative/structural mitral valve (MV) pathology, and secondary (functional) MR, which is principally caused by global or regional left ventricular remodeling and/or severe left atrial dilation. Diagnosis and optimal management of MR requires integration of valve disease and heart failure specialists, MV cardiac surgeons, interventional cardiologists with expertise in structural heart disease, and imaging experts. The introduction of transcatheter MV therapies has highlighted the need for a consensus approach to pragmatic clinical trial design and uniform endpoint definitions to evaluate outcomes in patients with MR. The Mitral Valve Academic Research Consortium is a collaboration between leading academic research organizations and physician-scientists specializing in MV disease from the United States and Europe. Three in-person meetings were held in Virginia and New York during which 44 heart failure, valve, and imaging experts, MV surgeons and interventional cardiologists, clinical trial specialists and statisticians, and representatives from the U.S. Food and Drug Administration considered all aspects of MV pathophysiology, prognosis, and therapies, culminating in a 2-part document describing consensus recommendations for clinical trial design (Part 1) and endpoint definitions (Part 2) to guide evaluation of transcatheter and surgical therapies for MR. The adoption of these recommendations will afford robustness and consistency in the comparative effectiveness evaluation of new devices and approaches to treat MR. These principles may be useful for regulatory assessment of new transcatheter MV devices, as well as for monitoring local and regional outcomes to guide quality improvement initiatives. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

2017 Cardiovascular and Stroke Endpoint Definitions for Clinical Trials.

PubMed

Hicks, Karen A; Mahaffey, Kenneth W; Mehran, Roxana; Nissen, Steven E; Wiviott, Stephen D; Dunn, Billy; Solomon, Scott D; Marler, John R; Teerlink, John R; Farb, Andrew; Morrow, David A; Targum, Shari L; Sila, Cathy A; Thanh Hai, Mary T; Jaff, Michael R; Joffe, Hylton V; Cutlip, Donald E; Desai, Akshay S; Lewis, Eldrin F; Gibson, C Michael; Landray, Martin J; Lincoff, A Michael; White, Christopher J; Brooks, Steven S; Rosenfield, Kenneth; Domanski, Michael J; Lansky, Alexandra J; McMurray, John J V; Tcheng, James E; Steinhubl, Steven R; Burton, Paul; Mauri, Laura; O'Connor, Christopher M; Pfeffer, Marc A; Hung, H M James; Stockbridge, Norman L; Chaitman, Bernard R; Temple, Robert J

2018-03-06

This publication describes uniform definitions for cardiovascular and stroke outcomes developed by the Standardized Data Collection for Cardiovascular Trials Initiative and the U.S. Food and Drug Administration (FDA). The FDA established the Standardized Data Collection for Cardiovascular Trials Initiative in 2009 to simplify the design and conduct of clinical trials intended to support marketing applications. The writing committee recognizes that these definitions may be used in other types of clinical trials and clinical care processes where appropriate. Use of these definitions at the FDA has enhanced the ability to aggregate data within and across medical product development programs, conduct meta-analyses to evaluate cardiovascular safety, integrate data from multiple trials, and compare effectiveness of drugs and devices. Further study is needed to determine whether prospective data collection using these common definitions improves the design, conduct, and interpretability of the results of clinical trials. Copyright © 2018 American College of Cardiology Foundation and American Heart Association, Inc. Published by Elsevier Inc. All rights reserved.

The LIBERTY study: Design of a prospective, observational, multicenter trial to evaluate the acute and long-term clinical and economic outcomes of real-world endovascular device interventions in treating peripheral artery disease.

PubMed

Adams, George L; Mustapha, Jihad; Gray, William; Hargus, Nick J; Martinsen, Brad J; Ansel, Gary; Jaff, Michael R

2016-04-01

Most peripheral artery disease (PAD) clinical device trials are supported by commercial manufacturers and designed for regulatory device approval, with extensive inclusion/exclusion criteria to support homogeneous patient populations. High-risk patients with advanced disease, including critical limb ischemia (CLI), are often excluded leading to difficulty in translating trial results into real-world clinical practice. As a result, physicians have no direct guidance regarding the use of endovascular devices. There is a need for objectively assessed studies to evaluate clinical, functional, and economic outcomes in PAD patient populations. LIBERTY is a prospective, observational, multicenter study sponsored by Cardiovascular Systems Inc (St Paul, MN) to evaluate procedural and long-term clinical and economic outcomes of endovascular device interventions in patients with symptomatic lower extremity PAD. Approximately 1,200 patients will be enrolled and followed up to 5 years: 500 patients in the "Claudicant Rutherford 2-3" arm, 600 in the "CLI Rutherford 4-5" arm, and 100 in the "CLI Rutherford 6" arm. The study will use 4 core laboratories for independent analysis and will evaluate the following: procedural and lesion success, rates of major adverse events, duplex ultrasound interpretations, wound status, quality of life, 6-minute walk test, and economic analysis. The LIBERTY Patient Risk Score(s) will be developed as a clinical predictor of outcomes to provide guidance for interventions in this patient population. LIBERTY will investigate real-world PAD patients treated with endovascular revascularization with rigorous study guidelines and independent oversight of outcomes. This study will provide observational, all-comer patient clinical data to guide future endovascular therapy. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

A P300-based Brain-Computer Interface with Stimuli on Moving Objects: Four-Session Single-Trial and Triple-Trial Tests with a Game-Like Task Design

PubMed Central

Ganin, Ilya P.; Shishkin, Sergei L.; Kaplan, Alexander Y.

2013-01-01

Brain-computer interfaces (BCIs) are tools for controlling computers and other devices without using muscular activity, employing user-controlled variations in signals recorded from the user’s brain. One of the most efficient noninvasive BCIs is based on the P300 wave of the brain’s response to stimuli and is therefore referred to as the P300 BCI. Many modifications of this BCI have been proposed to further improve the BCI’s characteristics or to better adapt the BCI to various applications. However, in the original P300 BCI and in all of its modifications, the spatial positions of stimuli were fixed relative to each other, which can impose constraints on designing applications controlled by this BCI. We designed and tested a P300 BCI with stimuli presented on objects that were freely moving on a screen at a speed of 5.4°/s. Healthy participants practiced a game-like task with this BCI in either single-trial or triple-trial mode within four sessions. At each step, the participants were required to select one of nine moving objects. The mean online accuracy of BCI-based selection was 81% in the triple-trial mode and 65% in the single-trial mode. A relatively high P300 amplitude was observed in response to targets in most participants. Self-rated interest in the task was high and stable over the four sessions (the medians in the 1st/4th sessions were 79/84% and 76/71% in the groups practicing in the single-trial and triple-trial modes, respectively). We conclude that the movement of stimulus positions relative to each other may not prevent the efficient use of the P300 BCI by people controlling their gaze, e.g., in robotic devices and in video games. PMID:24302977

REmote SUpervision to Decrease HospitaLization RaTe. Unified and integrated platform for data collected from devices manufactured by different companies: Design and rationale of the RESULT study.

PubMed

Tajstra, Mateusz; Sokal, Adam; Gwóźdź, Arkadiusz; Wilczek, Marcin; Gacek, Adam; Wojciechowski, Konrad; Gadula-Gacek, Elżbieta; Adamowicz-Czoch, Elżbieta; Chłosta-Niepiekło, Katarzyna; Milewski, Krzysztof; Rozentryt, Piotr; Kalarus, Zbigniew; Gąsior, Mariusz; Poloński, Lech

2017-07-01

The number of patients with heart failure implantable cardiac electronic devices (CIEDs) is growing. Hospitalization rate in this group is very high and generates enormous costs. To avoid the need for hospital treatment, optimized monitoring and follow-up is crucial. Remote monitoring (RM) has been widely put into practice in the management of CIEDs but it may be difficult due to the presence of differences in systems provided by device manufacturers and loss of gathered data in case of device reimplantation. Additionally, conclusions derived from studies about usefulness of RM in clinical practice apply to devices coming only from a single company. An integrated monitoring platform allows for more comprehensive data analysis and interpretation. Therefore, the primary objective of Remote Supervision to Decrease Hospitalization Rate (RESULT) study is to evaluate the impact of RM on the clinical status of patients with ICDs or CRT-Ds using an integrated platform. Six hundred consecutive patients with ICDs or CRT-Ds implanted will be prospectively randomized to either a traditional or RM-based follow-up model. The primary clinical endpoint will be a composite of all-cause mortality or hospitalization for cardiovascular reasons within 12 months after randomization. The primary technical endpoint will be to construct and evaluate a unified and integrated platform for the data collected from RM devices manufactured by different companies. This manuscript describes the design and methodology of the prospective, randomized trial designed to determine whether remote monitoring using an integrated platform for different companies is safe, feasible, and efficacious (ClinicalTrials.gov Identifier: NCT02409225). © 2016 Wiley Periodicals, Inc.

21 CFR 886.1410 - Ophthalmic trial lens clip.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Ophthalmic trial lens clip. 886.1410 Section 886...) MEDICAL DEVICES OPHTHALMIC DEVICES Diagnostic Devices § 886.1410 Ophthalmic trial lens clip. (a) Identification. An ophthalmic trial lens clip is a device intended to hold prisms, spheres, cylinders, or...

Moisture vapor transport channels for the improved attachment of a medical device to the human body.

PubMed

Cunningham, David D; Lowery, Michael G

2004-06-01

Attachment of a small, medical device to the human body for an extended period of time in an ambulatory setting requires the careful consideration of the physical form of the device and the physiological constraints limiting the time a device will stay on the skin. Factors such as the size of the device, the area of the device available for attachment to the skin, and the occlusive nature of the materials in the device are likely to affect adhesion. Here, plastic acrylic disks, 25 mm in diameter, containing a crisscross pattern of air-filled channels were tested on the forearm and abdomen using a moderately aggressive, unsupported, pressure-sensitive transfer adhesive in a pilot human clinical study. After vigorous exercise, droplets of moisture were observed in the channels followed by evaporation of the droplets over time. Disks without channels remained attached to the skin for about a day and a half, while disks containing 450 microm deep channels remained on the skin about three times longer. Little difference was found when the channel-to-channel spacing was increased from 1.3 to 1.6 mm, however 230 microm deep channels were less effective than 450 microm deep channels. Overall, the moisture vapor transport channels appear capable of reducing the moisture content of the outermost stratum corneum layer of the skin, increasing the strength of the stratum corneum, and increasing the time a device remains attached to the skin. The median trial-to-trial relative standard deviation of 45% observed in the pilot study can be used to design appropriately powered studies for the comparison of different device designs.

Head-to-head randomized trials are mostly industry sponsored and almost always favor the industry sponsor.

PubMed

Flacco, Maria Elena; Manzoli, Lamberto; Boccia, Stefania; Capasso, Lorenzo; Aleksovska, Katina; Rosso, Annalisa; Scaioli, Giacomo; De Vito, Corrado; Siliquini, Roberta; Villari, Paolo; Ioannidis, John P A

2015-07-01

To map the current status of head-to-head comparative randomized evidence and to assess whether funding may impact on trial design and results. From a 50% random sample of the randomized controlled trials (RCTs) published in journals indexed in PubMed during 2011, we selected the trials with ≥ 100 participants, evaluating the efficacy and safety of drugs, biologics, and medical devices through a head-to-head comparison. We analyzed 319 trials. Overall, 238,386 of the 289,718 randomized subjects (82.3%) were included in the 182 trials funded by companies. Of the 182 industry-sponsored trials, only 23 had two industry sponsors and only three involved truly antagonistic comparisons. Industry-sponsored trials were larger, more commonly registered, used more frequently noninferiority/equivalence designs, had higher citation impact, and were more likely to have "favorable" results (superiority or noninferiority/equivalence for the experimental treatment) than nonindustry-sponsored trials. Industry funding [odds ratio (OR) 2.8; 95% confidence interval (CI): 1.6, 4.7] and noninferiority/equivalence designs (OR 3.2; 95% CI: 1.5, 6.6), but not sample size, were strongly associated with "favorable" findings. Fifty-five of the 57 (96.5%) industry-funded noninferiority/equivalence trials got desirable "favorable" results. The literature of head-to-head RCTs is dominated by the industry. Industry-sponsored comparative assessments systematically yield favorable results for the sponsors, even more so when noninferiority designs are involved. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

OARSI Clinical Trials Recommendations: Design and conduct of clinical trials of rehabilitation interventions for osteoarthritis.

PubMed

Fitzgerald, G K; Hinman, R S; Zeni, J; Risberg, M A; Snyder-Mackler, L; Bennell, K L

2015-05-01

A Task Force of the Osteoarthritis Research Society International (OARSI) has previously published a set of guidelines for the conduct of clinical trials in osteoarthritis (OA) of the hip and knee. Limited material available on clinical trials of rehabilitation in people with OA has prompted OARSI to establish a separate Task Force to elaborate guidelines encompassing special issues relating to rehabilitation of OA. The Task Force identified three main categories of rehabilitation clinical trials. The categories included non-operative rehabilitation trials, post-operative rehabilitation trials, and trials examining the effectiveness of devices (e.g., assistive devices, bracing, physical agents, electrical stimulation, etc.) that are used in rehabilitation of people with OA. In addition, the Task Force identified two main categories of outcomes in rehabilitation clinical trials, which include outcomes related to symptoms and function, and outcomes related to disease modification. The guidelines for rehabilitation clinical trials provided in this report encompass these main categories. The report provides guidelines for conducting and reporting on randomized clinical trials. The topics include considerations for entering patients into trials, issues related to conducting trials, considerations for selecting outcome measures, and recommendations for statistical analyses and reporting of results. The focus of the report is on rehabilitation trials for hip, knee and hand OA, however, we believe the content is broad enough that it could be applied to rehabilitation trials for other regions as well. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

An investigation into the feasibility of locating portable medical devices using radio frequency identification devices and technology.

PubMed

Britton, J

2007-01-01

Portable medical devices represent an important resource for assisting healthcare delivery. The movement of portable devices often results in them being unavailable when needed. Tracking equipment using radiofrequency identification technology/devices (RFID) may provide a promising solution to the problems encountered in locating portable equipment. An RFID technology trial was undertaken at Royal Alexandra Hospital, Paisley. This involved the temporary installation of three active readers and attaching actively transmitting radio frequency tags to different portable medical devices. The active readers and computer system were linked using a bespoke data network. Tags and readers from two separate manufacturers were tested. Reliability difficulties were encountered when testing the technology from the first manufacturer, probably due to the casing of the medical device interfering with the signal from the tag. Improved results were obtained when using equipment from the second manufacturer with an overall error rate of 12.3%. Tags from this manufacturer were specifically designed to overcome problems observed with the first system tested. Findings from this proof of concept trial suggest that RFID technology could be used to track the location of equipment in a hospital.

An innovative approach to near-infrared spectroscopy using a standard mobile device and its clinical application in the real-time visualization of peripheral veins.

PubMed

Juric, Simon; Zalik, Borut

2014-11-25

Excessive venipunctures are a significant problem both in emergency rooms and during hospital stays. Near-infrared (NIR) illumination devices improve venipuncture success rate but their usage is limited by their availability and economic cost. The objectives of this study were to develop a low-cost NIR spectroscopy prototype from a standard mobile device, to evaluate its efficacy and acceptance as an educational tool, and in a clinical setting. Through a user-centric design process a prototype device was developed. Its educational efficacy was evaluated through a non-invasive, observational study (20 student clinicians, 25 subjects) and its acceptance was assessed using quantitative and qualitative analysis. A smaller clinical trial was performed by a group of 4 medical professionals over a period of 6 weeks that involved 64 patients. The prototype enables real-time visualization of peripheral veins on a variety of Android-based devices. The prototype was 35.2% more successful in visualizing and locating veins (n = 500 attempts) than the nursing students. The acceptance assessment revealed high perception of usefulness, satisfaction, and ease of use. In the clinical trial, 1.6 (SD 1.3) additional veins per patient were identified compared with the traditional visualization methods. To the best of our knowledge this is the first study that describes the design, feasibility and application of an NIR spectroscopy prototype developed on a standard mobile device.

21 CFR 886.1405 - Ophthalmic trial lens set.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Ophthalmic trial lens set. 886.1405 Section 886...) MEDICAL DEVICES OPHTHALMIC DEVICES Diagnostic Devices § 886.1405 Ophthalmic trial lens set. (a) Identification. An ophthalmic trial lens set is a device that is a set of lenses of various dioptric powers...

Awareness Enhancing and Monitoring Device plus Habit Reversal in the Treatment of Trichotillomania: An Open Feasibility Trial.

PubMed

Himle, Joseph A; Bybee, Deborah; O'Donnell, Lisa A; Weaver, Addie; Vlnka, Sarah; DeSena, Daniel T; Rimer, Jessica M

2018-01-01

Habit Reversal Therapy (HRT) is helpful for many persons suffering from trichotillomania. However successful habit reversal therapy requires awareness of hair pulling behaviors. Available methods to monitor hair pulling behaviors are less than ideal, particularly when sufferers are unaware of their pulling-related behaviors. This open feasibility trial included 20 persons with trichotillomania who were treated with nine weeks of HRT with experienced clinicians following a well-established HRT protocol. HRT was augmented with an electronic Awareness Enhancing and Monitoring Device (AEMD) designed to alert users of hand to head contact and to monitor the frequency of pulling-related behaviors. The AEMD included a neck unit and two wrist units, each equipped with vibrating alert functions. The results of the open trial revealed significant improvements in trichotillomania symptoms as measured by clinician and self-report rating scales. Most participants met study criteria for HRT completion and treatment effects were large. Participants reported that the AEMD, when operational, was effective in alerting participants to TTM-related behaviors. The monitoring function of the AEMD did not operate as designed. Subjective feedback focused on the AEMD concept was positive but AEMD reliability problems and complaints about the wearability the units were common. Recommendations for AEMD design modifications were included.

Ready-Made Versus Custom-Made Mandibular Repositioning Devices in Sleep Apnea: A Randomized Clinical Trial.

PubMed

Johal, Ama; Haria, Priya; Manek, Seema; Joury, Easter; Riha, Renata

2017-02-15

To compare the effectiveness of a custom-made (MRDc) versus ready-made (MRDr) mandibular repositioning devices (MRD) in the management of obstructive sleep apnea (OSA). A randomized crossover trial design was adopted in which patients with a confirmed diagnosis of OSA were randomly allocated to receive either a 3-month period of ready-made or custom-made MRD, with an intervening washout period of 2 weeks, prior to crossover. Treatment outcomes included both objective sleep monitoring and patient-centered measures (daytime sleepiness, partner snoring and quality of life). Twenty-five patients, with a mild degree of OSA (apnea-hypopnea index of 13.3 [10.9-25] events/h) and daytime sleepiness (Epworth Sleepiness Scale of 11 [6-16]), completed both arms of the trial. The MRDc achieved a complete treatment response in 64% of participants, compared with 24% with the MRDr (p < 0.001). A significant difference was observed in treatment failures, when comparing the MRDr (36%) with the MRDc (4%). Excessive daytime sleepiness (Epworth Sleepiness Scale ≥ 10) persisted in 33% (MRDc) and 66% (MRDr) of OSA subjects, following treatment. A statistically significant improvement was observed in quality of life scales following MRDc therapy only. Significant differences were observed in relation to both the number of nights per week (p = 0.004) and hours per night (p = 0.006) between the two different designs of device. The study demonstrates the significant clinical effectiveness of a custom-made mandibular repositioning device, particularly in terms of patient compliance and tolerance, in the treatment of OSA. © 2017 American Academy of Sleep Medicine

Stokes polarimetry probe for skin lesion evaluation: preliminary results

NASA Astrophysics Data System (ADS)

Louie, Daniel C.; Tchvialeva, Lioudmilla; Kalia, Sunil; Lui, Harvey; Lee, Tim K.

2018-02-01

This paper reports on the design of a prototype in-vivo Stokes polarimetry probe for skin lesion evaluation, and preliminary results from skin phantom and clinical trials of this device. The probe releases a single millisecond-long pulse from a laser diode with either linear or circular polarization. It then captures the resulting backscattered far-field polarization speckle and calculates the Stokes parameters. This probe was designed with three novel innovations in mind. First, the Stokes vector is captured quickly, using low-cost components without the use of moving parts. Second, a compact collimated laser diode was used as the light source. Third, the device and detector geometry were designed to produce and capture a uniform speckle field. In the first clinical trial of this device, measurements were taken from a variety of skin lesions, both cancerous and benign. The Stokes vector was measured and used to calculate the degree of polarization (DOP), the azimuth angle, and the ellipticity angle of the polarization ellipse for two input light polarizations. Among other findings, the DOP for circular polarized input light was consistently lower than the DOP for linear polarized input light. These findings indicate the potential for a fast and low-cost in-vivo skin cancer screening tool, and encourages the continuing development of this probe's techniques.

Prospective randomized evaluation of the watchman left atrial appendage closure device in patients with atrial fibrillation versus long-term warfarin therapy: The PREVAIL trial.

PubMed

Belgaid, Djouhar Roufeida; Khan, Zara; Zaidi, Mariam; Hobbs, Adrian

2016-09-15

Assessing the safety and effectiveness of left atrial appendage (LAA) (pouch found in the upper chambers of the heart) occlusion, using the Watchman device compared to long term warfarin therapy (drug that reduces clot formation), in preventing the risk of stroke in patients with atrial fibrillation (most common type of irregular heart beat). 90% of strokes in atrial fibrillation arise from clots forming in this pouch. By mechanically blocking it using the device less clots are suggested to be formed. This is an alternative to taking warfarin especially in patients who cannot take it. 50 sites in the United States enrolled 407 participants. After being randomly allocated, the device group had 269 participants and warfarin group (comparator)had 138 participants. Patients with atrial fibrillation and at high risk of stroke were randomly allocated a group after they were deemed eligible. Patients in the device group had to take warfarin and aspirin for 45days till the complete closure of the LAA. The oral anticoagulant was followed by dual antiplatelet therapy until 6months and then ASA. Patients in the warfarin group have to take it for life and were continually monitored. The study ran for 26months. The trial assessed the rate of adverse events using three endpoints: The PREVAIL trial was not designed to show superiority, but non-inferiority. It met the safety endpoint and one efficacy endpoint for the watchman device compared to long term warfarin for overall efficacy of the device. The results established that LAA occlusion is not worse than warfarin intake for the prevention of stroke more than 1week after randomization. Compared to previous trials, the safety of the device has also improved. LAA occlusion is a reasonable alternative to chronic warfarin therapy in stroke prevention for patients with atrial fibrillation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Design of the evolution of management strategies of heart failure patients with implantable defibrillators (EVOLVO) study to assess the ability of remote monitoring to treat and triage patients more effectively

PubMed Central

Marzegalli, Maurizio; Landolina, Maurizio; Lunati, Maurizio; Perego, Giovanni B; Pappone, Alessia; Guenzati, Giuseppe; Campana, Carlo; Frigerio, Maria; Parati, Gianfranco; Curnis, Antonio; Colangelo, Irene; Valsecchi, Sergio

2009-01-01

Background Heart failure patients with implantable defibrillators (ICD) frequently visit the clinic for routine device monitoring. Moreover, in the case of clinical events, such as ICD shocks or alert notifications for changes in cardiac status or safety issues, they often visit the emergency department or the clinic for an unscheduled visit. These planned and unplanned visits place a great burden on healthcare providers. Internet-based remote device interrogation systems, which give physicians remote access to patients' data, are being proposed in order to reduce routine and interim visits and to detect and notify alert conditions earlier. Methods The EVOLVO study is a prospective, randomized, parallel, unblinded, multicenter clinical trial designed to compare remote ICD management with the current standard of care, in order to assess its ability to treat and triage patients more effectively. Two-hundred patients implanted with wireless-transmission-enabled ICD will be enrolled and randomized to receive either the Medtronic CareLink® monitor for remote transmission or the conventional method of in-person evaluations. The purpose of this manuscript is to describe the design of the trial. The results, which are to be presented separately, will characterize healthcare utilizations as a result of ICD follow-up by means of remote monitoring instead of conventional in-person evaluations. Trial registration ClinicalTrials.gov: NCT00873899 PMID:19538734

Development and marketing of a prosthetic urinary control valve system

NASA Technical Reports Server (NTRS)

Tenney, J. B., Jr.; Rabinowitz, R.; Rogers, D. W.; Harrison, H. N.

1983-01-01

An implantable prosthetic for the control of urinary incontinence was developed and marketed. Three phases are presented: bench development studies, animal trials, and human clinical trials. This work was performed under the direction of a Research Team at Rochester General Hospital (RGH). Bench trials were completed on prototype hardware and provided early verification of the device's ability to withstand repeated cyclic testing. Configurational variants were evaluated and a preferred design concept was established. Silicone rubber (medical grade) was selected as the preferred material for the prosthesis.

Mobile Traffic Alert and Tourist Route Guidance System Design Using Geospatial Data

NASA Astrophysics Data System (ADS)

Bhattacharya, D.; Painho, M.; Mishra, S.; Gupta, A.

2017-09-01

The present study describes an integrated system for traffic data collection and alert warning. Geographical information based decision making related to traffic destinations and routes is proposed through the design. The system includes a geospatial database having profile relating to a user of a mobile device. The processing and understanding of scanned maps, other digital data input leads to route guidance. The system includes a server configured to receive traffic information relating to a route and location information relating to the mobile device. Server is configured to send a traffic alert to the mobile device when the traffic information and the location information indicate that the mobile device is traveling toward traffic congestion. Proposed system has geospatial and mobile data sets pertaining to Bangalore city in India. It is envisaged to be helpful for touristic purposes as a route guidance and alert relaying information system to tourists for proximity to sites worth seeing in a city they have entered into. The system is modular in architecture and the novelty lies in integration of different modules carrying different technologies for a complete traffic information system. Generic information processing and delivery system has been tested to be functional and speedy under test geospatial domains. In a restricted prototype model with geo-referenced route data required information has been delivered correctly over sustained trials to designated cell numbers, with average time frame of 27.5 seconds, maximum 50 and minimum 5 seconds. Traffic geo-data set trials testing is underway.

Impact of Alternative Medical Device Approval Processes on Costs and Health

PubMed Central

George, Benjamin P.; Venkataraman, Vinayak; Dorsey, E. Ray

2014-01-01

Background Medical devices are often introduced prior to randomized‐trial evidence of efficacy and this slows completion of trials. Alternative regulatory approaches include restricting device use outside of trials prior to trial evidence of efficacy (like the drug approval process) or restricting out‐of‐trial use but permitting coverage within trials such as Medicare's Coverage with Study Participation (CSP). Methods We compared the financial impact to manufacturers and insurers of three regulatory alternatives: (1) limited regulation (current approach), (2) CSP, and (3) restrictive regulation (like the current drug approval process). Using data for patent foramen ovale closure devices, we modeled key parameters including recruitment time, probability of device efficacy, market adoption, and device cost/price to calculate profits to manufacturers, costs to insurers, and overall societal impact on health. Results For manufacturers, profits were greatest under CSP—driven by faster market adoption of effective devices—followed by restrictive regulation. Societal health benefit in total quality‐adjusted life years was greatest under CSP. Insurers’ expenditures for ineffective devices were greatest with limited regulation. Findings were robust over a reasonable range of probabilities of trial success. Conclusions Regulation restricting out‐of‐trial device use and extending limited insurance coverage to clinical trial participants may balance manufacturer and societal interests. PMID:25185975

Testing the effectiveness of an aquatic hazing device on waterbirds in the San Francisco Bay estuary of California

USGS Publications Warehouse

Whisson, Desley A.; Takekawa, John Y.

2000-01-01

Aquatic hazing devices recently have been developed as a possible means of deterring waterbirds from oil spills, thereby reducing casualties. However, the effectiveness of these devices has not been examined with rigorous statistical tests. We conducted a study in the San Francisco Bay estuary to develop a design for testing the effectiveness of an aquatic hazing device on waterbirds in open water. Transects marked with poles at 100-m inter- vals up to 800 m from the hazing device were established at two sites separated by three km in the north bay. Alter- nating two-day test and control periods were conducted at each site. Observers in over-water blinds counted the number, species and behavior (swimming, diving, or preening) of birds on transects each day. Aerial surveys of birds within four km of the device were conducted at the beginning of each test. For both aerial and ground surveys, a three-way mixed model analysis of variance test was used to examine trial, distance from the device, and treatment (device on or off) fixed effects, and site as a random effect on numbers of Greater and Lesser scaup (Aythya affinis and A. marila), Surf Scoter (Melanitta perspicillata), and all other waterbirds. We could not detect a significant deter- rent effect of the hazing device in either aerial surveys of all ducks or scaup (all ducks, F,283 = 1.1; Scaup, F28,230 = 0.9, all n.s.; 3-factor ANOVA), or ground surveys for all ducks or scaup (all ducks, F28,23 = 1.0; scaup, F2s,230 = 0.9, all n.s.; 3-factor ANOVA). There was a significant trial-by-treatment interaction for Surf Scoters (F4,9 = 5.4, P = 0.02; 3-factor ANOVA), but Surf Scoter numbers fluctuated greatly among trials so the effect of the device on this species was not clear. Birds did not alter their behavior when the device was active. In general, although aquatic hazing devices have potential to reduce waterbird mortality in oil spills, the tested device was not effective as a deterrent for waterfowl in experimental trials on the estuary. Received 27 September 1999, accepted 3January 2000.

Evaluation of pharmacokinetics, user handling, and tolerability of peginterferon alfa-2a (40 kDa) delivered via a disposable autoinjector device

PubMed Central

Varunok, Peter; Lawitz, Eric; Beavers, Kimberly L; Matusow, Gary; Leong, Ruby; Lambert, Nathalie; Bernaards, Coen; Solsky, Jonathan; Brennan, Barbara J; Wat, Cynthia; Bertasso, Anne

2011-01-01

Background Peginterferon alfa-2a (40 kDa) is currently administered using a prefilled syringe. The peginterferon alfa-2a disposable autoinjector is a new safety-engineered device designed to facilitate injection and reduce the risk of needlestick injuries. The analysis of two open-label Phase I trials evaluated the pharmacokinetics, successful administration, and tolerability of peginterferon alfa-2a when using the autoinjector. The studies were performed to support the filing and registration of the autoinjector device. Methods In trial 1, 50 healthy adult subjects received one 180 μg dose of peginterferon alfa-2a via the autoinjector. Serial blood samples were collected predose, up to 336 hours following drug administration, and at follow-up (28 ± 3 days post-dosing) for noncompartmental pharmacokinetic analysis. Trial 2 randomized 60 adult patients with chronic hepatitis C to 180 μg peginterferon alfa-2a once weekly by the autoinjector or prefilled syringe for 3 weeks followed by the alternative device (prefilled syringe or autoinjector, respectively) for 3 weeks. Patients also received ribavirin. Administration by the devices was evaluated under direct observation by a study staff member and by patient subjective assessment. Results In trial 1, following a single dose of peginterferon alfa-2a, the maximum plasma concentration was 16.1 ± 5.3 ng/mL (mean ± standard deviation), and area under the concentration time curve (0–168 hours) was 1996 ± 613 ng · hour/mL, similar to that reported using a vial/syringe or prefilled syringe. In trial 2, few patients showed handling difficulties with either device. Generally, patients were observed to be more satisfied and confident, followed instructions better, and successfully initiated injection with the autoinjector versus the prefilled syringe. Patients reported the autoinjector to be more convenient and easier to use. No pain or discomfort was experienced using the autoinjector. The autoinjector safety profile was consistent with that known for peginterferon alfa-2a/ribavirin. Conclusion These results indicate that peginterferon alfa-2a can be successfully and safely delivered via the autoinjector and that the device is easy to handle. PMID:22163158

What makes a good home-based nocturnal seizure detector? A value sensitive design.

PubMed

van Andel, Judith; Leijten, Frans; van Delden, Hans; van Thiel, Ghislaine

2015-01-01

A device for the in-home detection of nocturnal seizures is currently being developed in the Netherlands, to improve care for patients with severe epilepsy. It is recognized that the design of medical technology is not value neutral: perspectives of users and developers are influential in design, and design choices influence these perspectives. However, during development processes, these influences are generally ignored and value-related choices remain implicit and poorly argued for. In the development process of the seizure detector we aimed to take values of all stakeholders into consideration. Therefore, we performed a parallel ethics study, using "value sensitive design." Analysis of stakeholder communication (in meetings and e-mail messages) identified five important values, namely, health, trust, autonomy, accessibility, and reliability. Stakeholders were then asked to give feedback on the choice of these values and how they should be interpreted. In a next step, the values were related to design choices relevant for the device, and then the consequences (risks and benefits) of these choices were investigated. Currently the process of design and testing of the device is still ongoing. The device will be validated in a trial in which the identified consequences of design choices are measured as secondary endpoints. Value sensitive design methodology is feasible for the development of new medical technology and can help designers substantiate the choices in their design.

New mainstream double-end carbon dioxide capnograph for human respiration

NASA Astrophysics Data System (ADS)

Yang, Jiachen; An, Kun; Wang, Bin; Wang, Lei

2010-11-01

Most of the current respiratory devices for monitoring CO2 concentration use the side-stream structure. In this work, we engage to design a new double-end mainstream device for monitoring CO2 concentration of gas breathed out of the human body. The device can accurately monitor the cardiopulmonary status during anesthesia and mechanical ventilation in real time. Meanwhile, to decrease the negative influence of device noise and the low sample precision caused by temperature drift, wavelet packet denoising and temperature drift compensation are used. The new capnograph is proven by clinical trials to be helpful in improving the accuracy of capnography.

Precision Medicine for Hypertension Management in Chronic Kidney Disease: Relevance of SPRINT for Therapeutic Targets in Nondiabetic Renal Disease.

PubMed

Ruzicka, Marcel; Burns, Kevin D; Hiremath, Swapnil

2017-05-01

In this review we evaluate the literature to determine if lower blood pressure (BP) targets are beneficial for patients with nondiabetic chronic kidney disease (CKD). Modification of Diet in Renal Disease (MDRD), African American Study of Kidney Disease and Hypertension (AASK), and Ramipril Efficacy in Nephropathy-2 (REIN-2), designed to assess the benefit of lower BP on progression of nondiabetic CKD, generally came to the same negative conclusion. They were not designed and powered to assess an effect of lower BP on cardiovascular outcomes. The Systolic Blood Pressure Intervention Trial (SPRINT) was the first trial designed and powered to address this issue, and showed a clear benefit of a lower targeted and achieved BP. SPRINT did not show any renal benefits from lower BP, and it was not designed to assess this outcome, and it enrolled patients with less "renal risk" per se. A distinguishing feature of SPRINT compared with other large trials is that it highlighted the importance of precise BP measurement methods in defining targets in hypertension treatment. Accordingly, we propose that SPRINT is truly a "game-changing" clinical trial that sets the bar for management of hypertension in select patients with nondiabetic CKD. In these patients, systolic BP target depends critically on the BP measurement method: < 140 mm Hg when derived from 3 readings using a mercury sphygmomanometer after 5 minutes of rest, < 130 mm Hg when calculated from at a minimum of 3 readings using an automated oscillometric device, and < 120 mm Hg when taken using an automated oscillometric device after 5 minutes of unattended rest. Copyright © 2017 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Low-level light therapy for androgenetic alopecia: a 24-week, randomized, double-blind, sham device-controlled multicenter trial.

PubMed

Kim, Hyojin; Choi, Jee Woong; Kim, Jun Young; Shin, Jung Won; Lee, Seok-Jong; Huh, Chang-Hun

2013-08-01

Androgenetic alopecia (AGA) is a common disorder affecting men and women. Finasteride and minoxidil are well-known, effective treatment methods, but patients who exhibit a poor response to these methods have no additional adequate treatment modalities. To evaluate the efficacy and safety of a low-level light therapy (LLLT) device for the treatment of AGA. This study was designed as a 24-week, randomized, double-blind, sham device-controlled trial. Forty subjects with AGA were enrolled and scheduled to receive treatment with a helmet-type, home-use LLLT device emitting wavelengths of 630, 650, and 660 nm or a sham device for 18 minutes daily. Investigator and subject performed phototrichogram assessment (hair density and thickness) and global assessment of hair regrowth for evaluation. After 24 weeks of treatment, the LLLT group showed significantly greater hair density than the sham device group. Mean hair diameter improved statistically significantly more in the LLLT group than in the sham device group. Investigator global assessment showed a significant difference between the two groups, but that of the subject did not. No serious adverse reactions were detected. LLLT could be an effective treatment for AGA. © 2013 by the American Society for Dermatologic Surgery, Inc. Published by Wiley Periodicals, Inc.

The nightmare of FDA clearance/approval to market: perception or reality?

PubMed

Tylenda, C A

1996-09-01

Over the last few years the Center for Device Evaluation and Research (CDRH) at the Food and Drug Administration (FDA) has received annually over 16 thousand submissions related to medical devices. Over 10,000 of these are major submissions which include applications to conduct clinical trials and applications to market medical devices for a specified indication for use. Each application is carefully considered. FDA personnel work closely with applicants to ensure that clinical trial design minimizes risk to the patients and maximizes benefit with respect to addressing the safety and effectiveness of the device being tested. Applicants are given every opportunity to provide additional information when necessary to assure that applications to market medical devices are complete. Applicants have the opportunity to meet with FDA staff prior to submitting applications in cases where the application is other than a straight forward, uncomplicated submission. In addition, FDA assists applicants through the development of guidance documents, which discuss the type of information that would be beneficial to include in a submission. The Division of Small Manufacturers Assistance at FDA is dedicated to helping interested persons understand the clearance/approval process. This paper will discuss the role of FDA in the regulation of medical devices, with an emphasis on the pathway to obtaining permission to market medical devices in the United States.

New Japanese Regulatory Frameworks for Clinical Research and Marketing Authorization of Gene Therapy and Cellular Therapy Products.

PubMed

Nagai, Sumimasa; Ozawa, Keiya

2017-01-01

In Japan, the Pharmaceuticals and Medical Devices Law was passed in 2014. In this new law, regenerative medical products were defined, and a conditional and term-limited approval system only for regenerative medical products was instituted. Therefore, regenerative medical products can be approved based on phase I and/or II trials. Gene therapy and adoptive cellular therapy are categorized as regenerative medical products. This law is intended for registration trials for marketing authorization. The Act on the Safety of Regenerative Medicine was also implemented in 2014. This act is intended for clinical research and medical practice involving processed cells other than registration trials. Under this act, a review of plans on medical treatments or clinical studies by a certified committee and submission of the plans to the Ministry of Health, Labour and Welfare (MHLW) are mandatory. The MHLW instituted the SAKIGAKE (meaning a pioneer or forerunner in Japanese) designation system in 2015. This designation is similar to the breakthrough therapy designation in the US and PRIME in the EU. In addition, the MHLW started the "Project for Enhanced Practical Application of Innovative Drugs, Medical Devices and Regenerative Medical Products" to promote personnel exchange and cooperation in writing of guidelines on the evaluation of innovative medical products between the Pharmaceuticals and Medical Devices Agency and academia. Some new guidelines regarding gene and cellular therapy were published. In this review, we comprehensively described these complicated regulations and problems to be solved in order to facilitate global readers' understanding of Japanese regulatory frameworks. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Advances in Retinal Prosthetic Research: A Systematic Review of Engineering and Clinical Characteristics of Current Prosthetic Initiatives.

PubMed

Cheng, Derrick L; Greenberg, Paul B; Borton, David A

2017-03-01

To date, reviews of retinal prostheses have focused primarily on devices undergoing human trials in the Western Hemisphere and fail to capture significant advances in materials and engineering research in countries such as Japan and Korea, as well as projects in early stages of development. To address these gaps, this systematic review examines worldwide advances in retinal prosthetic research, evaluates engineering characteristics and clinical progress of contemporary device initiatives, and identifies potential directions for future research in the field of retinal prosthetics. A literature search using PubMed, Google Scholar, and IEEExplore was conducted following the PRISMA Guidelines for Systematic Review. Inclusion criteria were peer-reviewed papers demonstrating progress in human or animal trials and papers discussing the prosthetic engineering design. For each initiative, a description of the device, its engineering considerations, and recent clinical results were provided. Ten prosthetic initiatives met our inclusion criteria and were organized by stimulation location. Of these initiatives, four have recently completed human trials, three are undergoing multi- or single-center human trials, and three are undergoing preclinical animal testing. Only the Argus II (FDA 2013, CE 2011) has obtained FDA approval for use in the United States; the Alpha-IMS (CE 2013) has achieved the highest visual acuity using a Landolt-C test to date and is the only device presently undergoing a multicenter clinical trial. Several distinct approaches to retinal stimulation have been successful in eliciting visual precepts in animals and/or humans. However, many clinical needs are still not met and engineering challenges must be addressed before a retinal prosthesis with the capability to fully and safely restore functional vision can be realized.

Soft robotic devices for hand rehabilitation and assistance: a narrative review.

PubMed

Chu, Chia-Ye; Patterson, Rita M

2018-02-17

The debilitating effects on hand function from a number of a neurologic disorders has given rise to the development of rehabilitative robotic devices aimed at restoring hand function in these patients. To combat the shortcomings of previous traditional robotics, soft robotics are rapidly emerging as an alternative due to their inherent safety, less complex designs, and increased potential for portability and efficacy. While several groups have begun designing devices, there are few devices that have progressed enough to provide clinical evidence of their design's therapeutic abilities. Therefore, a global review of devices that have been previously attempted could facilitate the development of new and improved devices in the next step towards obtaining clinical proof of the rehabilitative effects of soft robotics in hand dysfunction. A literature search was performed in SportDiscus, Pubmed, Scopus, and Web of Science for articles related to the design of soft robotic devices for hand rehabilitation. A framework of the key design elements of the devices was developed to ease the comparison of the various approaches to building them. This framework includes an analysis of the trends in portability, safety features, user intent detection methods, actuation systems, total DOF, number of independent actuators, device weight, evaluation metrics, and modes of rehabilitation. In this study, a total of 62 articles representing 44 unique devices were identified and summarized according to the framework we developed to compare different design aspects. By far, the most common type of device was that which used a pneumatic actuator to guide finger flexion/extension. However, the remainder of our framework elements yielded more heterogeneous results. Consequently, those results are summarized and the advantages and disadvantages of many design choices as well as their rationales were highlighted. The past 3 years has seen a rapid increase in the development of soft robotic devices for hand rehabilitative applications. These mostly preclinical research prototypes display a wide range of technical solutions which have been highlighted in the framework developed in this analysis. More work needs to be done in actuator design, safety, and implementation in order for these devices to progress to clinical trials. It is our goal that this review will guide future developers through the various design considerations in order to develop better devices for patients with hand impairments.

Enhancing public involvement in assistive technology design research.

PubMed

Williamson, Tracey; Kenney, Laurence; Barker, Anthony T; Cooper, Glen; Good, Tim; Healey, Jamie; Heller, Ben; Howard, David; Matthews, Martin; Prenton, Sarah; Ryan, Julia; Smith, Christine

2015-05-01

To appraise the application of accepted good practice guidance on public involvement in assistive technology research and to identify its impact on the research team, the public, device and trial design. Critical reflection and within-project evaluation were undertaken in a case study of the development of a functional electrical stimulation device. Individual and group interviews were undertaken with lay members of a 10 strong study user advisory group and also research team members. Public involvement was seen positively by research team members, who reported a positive impact on device and study designs. The public identified positive impact on confidence, skills, self-esteem, enjoyment, contribution to improving the care of others and opportunities for further involvement in research. A negative impact concerned the challenge of engaging the public in dissemination after the study end. The public were able to impact significantly on the design of an assistive technology device which was made more fit for purpose. Research team attitudes to public involvement were more positive after having witnessed its potential first hand. Within-project evaluation underpins this case study which presents a much needed detailed account of public involvement in assistive technology design research to add to the existing weak evidence base. The evidence base for impact of public involvement in rehabilitation technology design is in need of development. Public involvement in co-design of rehabilitation devices can lead to technologies that are fit for purpose. Rehabilitation researchers need to consider the merits of active public involvement in research.

Clinical trial design principles and endpoint definitions for transcatheter mitral valve repair and replacement: part 1: clinical trial design principles: A consensus document from the mitral valve academic research consortium.

PubMed

Stone, Gregg W; Vahanian, Alec S; Adams, David H; Abraham, William T; Borer, Jeffrey S; Bax, Jeroen J; Schofer, Joachim; Cutlip, Donald E; Krucoff, Mitchell W; Blackstone, Eugene H; Généreux, Philippe; Mack, Michael J; Siegel, Robert J; Grayburn, Paul A; Enriquez-Sarano, Maurice; Lancellotti, Patrizio; Filippatos, Gerasimos; Kappetein, Arie Pieter

2015-08-01

Mitral regurgitation (MR) is one of the most prevalent valve disorders and has numerous aetiologies, including primary (organic) MR, due to underlying degenerative/structural mitral valve (MV) pathology, and secondary (functional) MR, which is principally caused by global or regional left ventricular remodelling and/or severe left atrial dilation. Diagnosis and optimal management of MR requires integration of valve disease and heart failure specialists, MV cardiac surgeons, interventional cardiologists with expertise in structural heart disease, and imaging experts. The introduction of transcatheter MV therapies has highlighted the need for a consensus approach to pragmatic clinical trial design and uniform endpoint definitions to evaluate outcomes in patients with MR. The Mitral Valve Academic Research Consortium is a collaboration between leading academic research organizations and physician-scientists specializing in MV disease from the United States and Europe. Three in-person meetings were held in Virginia and New York during which 44 heart failure, valve, and imaging experts, MV surgeons and interventional cardiologists, clinical trial specialists and statisticians, and representatives from the U.S. Food and Drug Administration considered all aspects of MV pathophysiology, prognosis, and therapies, culminating in a 2-part document describing consensus recommendations for clinical trial design (Part 1) and endpoint definitions (Part 2) to guide evaluation of transcatheter and surgical therapies for MR. The adoption of these recommendations will afford robustness and consistency in the comparative effectiveness evaluation of new devices and approaches to treat MR. These principles may be useful for regulatory assessment of new transcatheter MV devices, as well as for monitoring local and regional outcomes to guide quality improvement initiatives. Published on behalf of the European Society of Cardiology. All rights reserved. © American College of Cardiology 2015. For permissions please email: journals.permissions@oup.com. This article is being published concurrently in Journal of the American College of Cardiology [1]. The articles are identical except for minor stylistic and spelling differences in keeping with each journal's style. Either citation can be used when citing this article. [1] Stone GW, Vahanian AS, Adams DH, Abraham WT, Borer JS et al. Clinical trial design principles and endpoint definitions for transcatheter mitral valve repair and replacement: Part 1: Clinical Trial Design Principles. J Am Coll Cardiol 2015;66:278–307. doi: 10.1016/j.jacc.2015.05.046.

A Bayesian approach to the statistical analysis of device preference studies.

PubMed

Fu, Haoda; Qu, Yongming; Zhu, Baojin; Huster, William

2012-01-01

Drug delivery devices are required to have excellent technical specifications to deliver drugs accurately, and in addition, the devices should provide a satisfactory experience to patients because this can have a direct effect on drug compliance. To compare patients' experience with two devices, cross-over studies with patient-reported outcomes (PRO) as response variables are often used. Because of the strength of cross-over designs, each subject can directly compare the two devices by using the PRO variables, and variables indicating preference (preferring A, preferring B, or no preference) can be easily derived. Traditionally, methods based on frequentist statistics can be used to analyze such preference data, but there are some limitations for the frequentist methods. Recently, Bayesian methods are considered an acceptable method by the US Food and Drug Administration to design and analyze device studies. In this paper, we propose a Bayesian statistical method to analyze the data from preference trials. We demonstrate that the new Bayesian estimator enjoys some optimal properties versus the frequentist estimator. Copyright © 2012 John Wiley & Sons, Ltd.

Standardized End Point Definitions for Coronary Intervention Trials: The Academic Research Consortium-2 Consensus Document.

PubMed

Garcia-Garcia, Hector M; McFadden, Eugène P; Farb, Andrew; Mehran, Roxana; Stone, Gregg W; Spertus, John; Onuma, Yoshinobu; Morel, Marie-Angèle; van Es, Gerrit-Anne; Zuckerman, Bram; Fearon, William F; Taggart, David; Kappetein, Arie-Pieter; Krucoff, Mitchell W; Vranckx, Pascal; Windecker, Stephan; Cutlip, Donald; Serruys, Patrick W

2018-06-14

The Academic Research Consortium (ARC)-2 initiative revisited the clinical and angiographic end point definitions in coronary device trials, proposed in 2007, to make them more suitable for use in clinical trials that include increasingly complex lesion and patient populations and incorporate novel devices such as bioresorbable vascular scaffolds. In addition, recommendations for the incorporation of patient-related outcomes in clinical trials are proposed. Academic Research Consortium-2 is a collaborative effort between academic research organizations in the United States and Europe, device manufacturers, and European, US, and Asian regulatory bodies. Several in-person meetings were held to discuss the changes that have occurred in the device landscape and in clinical trials and regulatory pathways in the last decade. The consensus-based end point definitions in this document are endorsed by the stakeholders of this document and strongly advocated for clinical trial purposes. This Academic Research Consortium-2 document provides further standardization of end point definitions for coronary device trials, incorporating advances in technology and knowledge. Their use will aid interpretation of trial outcomes and comparison among studies, thus facilitating the evaluation of the safety and effectiveness of these devices.

Comparison Between THOR Anthropomorphic Test Device and THOR Finite Element Model

NASA Technical Reports Server (NTRS)

Moore, Erik

2014-01-01

Extended time spent in reduced gravity can cause physiologic deconditioning of astronauts, reducing their ability to sustain excessive forces during dynamic phases of spaceflight such as landing. To make certain that the crew is safe during these phases, NASA must take caution when determining what types of landings are acceptable based on the accelerations applied to the astronaut. In order to test acceptable landings, various trials have been run accelerating humans, cadavers, and Anthropomorphic Test Devices (ATDs), or crash test dummies, at different acceleration and velocity rates on a sled testing platform. Using these tests, risks of injury will be created and metrics will be developed for the likelihood of injuries due to the acceleration. A finite element model (FEM) of the Test Device for Human Occupant Restraint (THOR) ATD has been developed that can simulate these test trials and others (Putnam, 2014), reducing the need for human and ATD testing. Additionally, this will give researchers a more effective way to test the accelerations and orientations encountered during spaceflight landings during design of new space vehicles for crewed missions. However, the FEM has not been proven and must be validated by comparing the forces, accelerations, and other measurements of all parts of the body between the physical tests already completed and computer simulated trials. The purpose of my research was to validate the FEM for the ATD using previously run trials with the physical THOR ATD.

Delivery of inhaled drugs for infants and small children: a commentary on present and future needs.

PubMed

Fink, James B

2012-11-01

Although the manufacture of inhaled medications is a multibillion dollar industry, virtually no pharmaceutical drug/device combination has been approved for inhalation across the range of pediatric patient ages and sizes. The clinician who treats neonates, infants, or toddlers is often faced with the dilemma of prescribing inhaled medications that may be disease appropriate but have not been approved for use in patients in these age categories. Their use is thus technically "off label," with limited empirical data to guide both dose and device selection. This dilemma requires the prescribing physician to go beyond the limitations of the product label, often without benefit of appropriately designed clinical trials, in an attempt to select safe and effective doses for use with these smallest of patients. The vast majority of drugs approved for inhalation were studied by using aerosol devices designed for older children and adults using a mouthpiece interface, which may not be practical for use in infants and patients aged <4 years. The selection of the most age-appropriate device and interface is critical for the effective administration of the prescribed therapy. In the absence of industry-sponsored clinical trials in neonates, infants, and toddlers, in vitro and in vivo strategies may help guide age-appropriate dosing, device, and interface selection to better inform clinical practice. In this commentary, the challenges in developing and prescribing effective formulations for aerosol delivery across the range of pediatric ages and sizes are explored, with guidance for device and interface selection. Recommendations for future collaborative sharing of in vitro models and age-specific breathing patterns between academic and industry researchers could help regulators and clinicians better understand the impact age and size have on pulmonary drug delivery. Copyright © 2012 Elsevier HS Journals, Inc. All rights reserved.

An Electronic Pillbox for Continuous Monitoring of Medication Adherence

PubMed Central

Hayes, Tamara. L.; Hunt, John M.; Adami, Andre; Kaye, Jeffrey A.

2010-01-01

We have developed an instrumented pillbox, called a MedTracker, which allows monitoring of medication adherence on a continuous basis. This device improves on existing systems by providing mobility, frequent and automatic data collection, more detailed information about nonadherence and medication errors, and the familiar interface of a 7-day drug store pillbox. We report on the design of the MedTracker, and on the results of a field trial in 39 homes to evaluate the device. PMID:17946369

Radiological Medical Device Innovation: Approvals via the Premarket Approval Pathway From 2000 to 2015.

PubMed

Ghobadi, Comeron W; Hayman, Emily L; Finkle, Joshua H; Walter, Jessica R; Xu, Shuai

2017-01-01

The aim of this study was to critically assess the clinical evidence leading to radiologic medical device approvals via the premarket approval pathway from 2000 to 2015. This study used the publically available FDA premarket database for radiologic device approvals over the past 15 years (September 1, 2000, to August 31, 2015). Approval characteristics were collected for each device, and statistical analysis was performed on the data for each pivotal trial. Additionally, methodological quality of the pivotal trial was determined using the Quality Assessment of Diagnostic Accuracy Studies tool. Twenty-three class III radiologic device approvals were identified, with breast imaging accounting for 16 (70%) and computer-aided detection software accounting for 9 (39%) approvals. The median premarket approval time was 475 days (range, 180-1,116). Twenty-one devices were approved on the basis of multireader, multicenter studies, one on the basis of a randomized controlled trial, and one on the basis of a preclinical technical equivalence trial. The median number of patients per pivotal trial was 201 (range, 25-3,946). Twenty-six of the 34 pivotal trials (76%) had at least one methodologic bias. Breast imaging devices had a greater number of patients per pivotal trial (P = .009) and more prospective studies. With regard to all modalities, increased time to device approval correlated with weaker trial quality (r = 0.600, P < .001). Radiologic devices are largely approved by multireader, multicenter studies, the recommended standard for assessing diagnostic technologies. Given that radiologic devices play a key role in modern medicine, further efforts should be made to increase transparency of clinical data leading to approval. Copyright © 2016 American College of Radiology. Published by Elsevier Inc. All rights reserved.

Artificial vision: needs, functioning, and testing of a retinal electronic prosthesis.

PubMed

Chader, Gerald J; Weiland, James; Humayun, Mark S

2009-01-01

Hundreds of thousands around the world have poor vision or no vision at all due to inherited retinal degenerations (RDs) like retinitis pigmentosa (RP). Similarly, millions suffer from vision loss due to age-related macular degeneration (AMD). In both of these allied diseases, the primary target for pathology is the retinal photoreceptor cells that dysfunction and die. Secondary neurons though are relatively spared. To replace photoreceptor cell function, an electronic prosthetic device can be used such that retinal secondary neurons receive a signal that simulates an external visual image. The composite device has a miniature video camera mounted on the patient's eyeglasses, which captures images and passes them to a microprocessor that converts the data to an electronic signal. This signal, in turn, is transmitted to an array of electrodes placed on the retinal surface, which transmits the patterned signal to the remaining viable secondary neurons. These neurons (ganglion, bipolar cells, etc.) begin processing the signal and pass it down the optic nerve to the brain for final integration into a visual image. Many groups in different countries have different versions of the device, including brain implants and retinal implants, the latter having epiretinal or subretinal placement. The device furthest along in development is an epiretinal implant sponsored by Second Sight Medical Products (SSMP). Their first-generation device had 16 electrodes with human testing in a Phase 1 clinical trial beginning in 2002. The second-generation device has 60+ electrodes and is currently in Phase 2/3 clinical trial. Increased numbers of electrodes are planned for future versions of the device. Testing of the device's efficacy is a challenge since patients admitted into the trial have little or no vision. Thus, methods must be developed that accurately and reproducibly record small improvements in visual function after implantation. Standard tests such as visual acuity, visual field, electroretinography, or even contrast sensitivity may not adequately capture some aspects of improvement that relate to a better quality of life (QOL). Because of this, some tests are now relying more on "real-world functional capacity" that better assesses possible improvement in aspects of everyday living. Thus, a new battery of tests have been suggested that include (1) standard psychophysical testing, (2) performance in tasks that are used in real-life situations such as object discrimination, mobility, etc., and (3) well-crafted questionnaires that assess the patient's own feelings as to the usefulness of the device. In the Phase 1 trial of the SSMP 16-electrode device, six subjects with severe RP were implanted with ongoing, continuing testing since then. First, it was evident that even limited sight restoration is a slow, learning process that takes months for improvement to become evident. However, light perception was restored in all six patients. Moreover, all subjects ultimately saw discrete phosphenes and could perform simple visual spatial and motion tasks. As mentioned above, a Phase 2/3 trial is now ongoing with a 60+ device. A 250+ device is on the drawing board, and one with over 1000 electrodes is being planned. Each has the possibility of significantly improving a patient's vision and QOL, being smaller and safer in design and lasting for the lifetime of the patient. From theoretical modeling, it is estimated that a device with approximately 1000 electrodes could give good functional vision, i.e., face recognition and reading ability. This could be a reality within 5-10 years from now. In summary, no treatments are currently available for severely affected patients with RP and dry AMD. An electrical prosthetic device appears to offer hope in replacing the function of degenerating or dead photoreceptor neurons. Devices with new, sophisticated designs and increasing numbers of electrodes could allow for long-term restoration of functional sight in patients with improvement in object recognition, mobility, independent living, and general QOL.

Characterization and outcomes of reinterventions in Food and Drug Administration-approved versus trial endovascular aneurysm repair devices.

PubMed

Fairman, Alexander S; Wang, Grace J; Jackson, Benjamin M; Foley, Paul J; Damrauer, Scott M; Kalapatapu, Venkat; Golden, Michael A; Fairman, Ronald M

2018-04-01

Published rates of reintervention after endovascular aneurysm repair (EVAR) range from 10% to 30%. We evaluated a single university center's experience with reinterventions in the context of Food and Drug Administration (FDA)-approved and trial devices. Retrospective data collection was performed for patients who underwent infrarenal EVAR and required reintervention from 2000 to 2016. Trial devices included those used in FDA feasibility and pivotal trials. Time-to-event analysis was performed using Cox regression. Predictors of mortality and explantation were evaluated using logistic regression; survival analysis was performed using Kaplan-Meier methods. From 2000 to 2016, there were 1835 EVARs performed, and 137 patients (116 men; mean age, 72.2 ± 10.0 years) underwent reintervention with a mean aneurysm size of 5.9 ± 1.2 cm. The median follow-up was 5 years with an overall survival of 70.1%. The overall reintervention rate was 7.5%. FDA-approved devices had a reintervention rate of 6.4%, whereas trial devices had a rate of 14.4% (P < .001). For all devices, the most common cause of reintervention was type II endoleak (52.5%), followed by type I endoleak (18.2%), type III endoleak (9.5%), limb kink (7.3%), iliac occlusive disease (5.8%), endotension (1.5%), and other. The overall mean time to first reintervention was 2.3 ± 2.5 years, and univariate Cox regression identified male gender (hazard ratio, 1.91; 95% confidence interval [CI], 1.17-3.10; P = .010) and age at the time of EVAR (hazard ratio, 1.03; 95% CI, 1.01-1.05; P = .006) as risk factors for time to first reintervention. Among patients requiring reintervention, the mean number of reinterventions for trial devices was significantly greater than that for FDA-approved devices (2.18 vs 1.65; P = .01). Trial devices requiring reintervention had a nearly threefold higher odds for the need for more than two reinterventions (odds ratio, 2.88; 95% CI, 1.12-7.37; P = .034). Trial device, cause of reintervention, and type of reintervention were not predictive of the need for explantation or mortality, but the number of reinterventions was significantly associated with the need for explantation (odds ratio, 1.86; 95% CI, 1.17-2.96; P = .012). EVAR device and the need for explantation did not have an impact on mortality. Despite the rigorous nature of patient enrollment in clinical trials and the development of newer iterations of investigational devices, patients undergoing EVAR with trial devices are more likely to undergo a greater number of reinterventions than with FDA-approved devices. Although mortality and the need for explantation were not significantly associated with trial devices, the finding of a greater number of reinterventions highlights the need to properly inform patients willing to partake in investigational device trials. Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Regional Changes in Word-Production Laterality after a Naming Treatment Designed to Produce a Rightward Shift in Frontal Activity

ERIC Educational Resources Information Center

Crosson, Bruce; Moore, Anna Bacon; McGregor, Keith M.; Chang, Yu-Ling; Benjamin, Michelle; Gopinath, Kaundinya; Sherod, Megan E.; Wierenga, Christina E.; Peck, Kyung K.; Briggs, Richard W.; Rothi, Leslie J. Gonzalez; White, Keith D.

2009-01-01

Five nonfluent aphasia patients participated in a picture-naming treatment that used an intention manipulation (opening a box and pressing a button on a device in the box with the left hand) to initiate naming trials and was designed to re-lateralize word production mechanisms from the left to the right frontal lobe. To test the underlying…

SOLITAIRE™ with the intention for thrombectomy (SWIFT) trial: design of a randomized, controlled, multicenter study comparing the SOLITAIRE™ Flow Restoration device and the MERCI Retriever in acute ischaemic stroke.

PubMed

Saver, J L; Jahan, R; Levy, E I; Jovin, T G; Baxter, B; Nogueira, R; Clark, W; Budzik, R; Zaidat, O O

2014-07-01

Self-expanding stent retrievers are a promising new device class designed for rapid flow restoration in acute cerebral ischaemia. The SOLITAIRE™ Flow Restoration device (SOLITAIRE) has shown high rates of recanalization in preclinical models and in uncontrolled clinical series. (1) To demonstrate non-inferiority of SOLITAIRE compared with a legally marketed device, the MERCI Retrieval System®; (2) To demonstrate safety, feasibility, and efficacy of SOLITAIRE in subjects requiring mechanical thrombectomy diagnosed with acute ischaemic stroke. DESIGN : Multicenter, randomized, prospective, controlled trial with blinded primary end-point ascertainment. Key entry criteria include: age 22-85; National Institute of Health Stroke Scale (NIHSS) ≥8 and <30; clinical and imaging findings consistent with acute ischaemic stroke; patient ineligible or failed intravenous tissue plasminogen activator; accessible occlusion in M1 or M2 middle cerebral artery, internal carotid artery, basilar artery, or vertebral artery; and patient able to be treated within 8 h of onset. Sites first participate in a roll-in phase, treating two patients with the SOLITAIRE device, before proceeding to the randomized phase. In patients unresponsive to the initially assigned therapy, after the angiographic component of the primary end-point is ascertained (reperfusion with the initial assigned device), rescue therapy with other reperfusion techniques is permitted. The primary efficacy end-point is successful recanalization with the assigned study device (no use of rescue therapy) and with no symptomatic intracranial haemorrhage. Successful recanalization is defined as achieving Thrombolysis In Myocardial Ischemia 2 or 3 flow in all treatable vessels. The primary safety end-point is the incidence of device-related and procedure-related serious adverse events. A major secondary efficacy end-point is time to achieve initial recanalization. Additional secondary end-points include clinical outcomes at 90 days and radiologic haemorrhagic transformation. © 2012 The Authors. International Journal of Stroke © 2012 World Stroke Organization.

Single event upset sensitivity of low power Schottky devices

NASA Technical Reports Server (NTRS)

Price, W. E.; Nichols, D. K.; Measel, P. R.; Wahlin, K. L.

1982-01-01

Data taken from tests involving heavy ions in the Berkeley 88 in. cyclotron being directed at low power Schottky barrier devices are reported. The tests also included trials in the Harvard cyclotron with 130 MeV protons, and at the U.C. Davis cyclotron using 56 MeV protons. The experiments were performed to study the single event upsets in MSI logic devices containing flip-flops. Results are presented of single-event upsets (SEU) causing functional degradation observed in post-exposure tests of six different devices. The effectiveness of the particles in producing SEUs in logic device functioning was found to be directly proportional to the proton energy. Shielding was determined to offer negligible protection from the particle bombardment. The results are considered significant for the design and fabrication of LS devices for space applications.

Development of a Real-Time Repeated-Measures Assessment Protocol to Capture Change over the Course of a Drinking Episode

PubMed Central

Luczak, Susan E.; Rosen, I. Gary; Wall, Tamara L.

2015-01-01

Aims: We report on the development of a real-time assessment protocol that allows researchers to assess change in BrAC, alcohol responses, behaviors, and contexts over the course of a drinking event. Method: We designed a web application that uses timed text messages (adjusted based on consumption pattern) containing links to our website to obtain real-time participant reports; camera and location features were also incorporated into the protocol. We used a transdermal alcohol sensor device along with software we designed to convert transdermal data into estimated BrAC. Thirty-two college students completed a laboratory session followed by a 2-week field trial. Results: Results for the web application indicated we were able to create an effective tool for obtaining repeated measures real-time drinking data. Participants were willing to monitor their drinking behavior with the web application, and this did not appear to strongly affect drinking behavior during, or 6 weeks following, the field trial. Results for the transdermal device highlighted the willingness of participants to wear the device despite some discomfort, but technical difficulties resulted in limited valid data. Conclusion: The development of this protocol makes it possible to capture detailed assessment of change over the course of naturalistic drinking episodes. PMID:25568142

Clinical Trial Design Principles and Endpoint Definitions for Transcatheter Mitral Valve Repair and Replacement: Part 2: Endpoint Definitions: A Consensus Document From the Mitral Valve Academic Research Consortium.

PubMed

Stone, Gregg W; Adams, David H; Abraham, William T; Kappetein, Arie Pieter; Généreux, Philippe; Vranckx, Pascal; Mehran, Roxana; Kuck, Karl-Heinz; Leon, Martin B; Piazza, Nicolo; Head, Stuart J; Filippatos, Gerasimos; Vahanian, Alec S

2015-07-21

Mitral regurgitation (MR) is one of the most prevalent valve disorders and has numerous etiologies, including primary (organic) MR, due to underlying degenerative/structural mitral valve (MV) pathology, and secondary (functional) MR, which is principally caused by global or regional left ventricular remodeling and/or severe left atrial dilation. Diagnosis and optimal management of MR requires integration of valve disease and heart failure specialists, MV cardiac surgeons, interventional cardiologists with expertise in structural heart disease, and imaging experts. The introduction of transcatheter MV therapies has highlighted the need for a consensus approach to pragmatic clinical trial design and uniform endpoint definitions to evaluate outcomes in patients with MR. The Mitral Valve Academic Research Consortium is a collaboration between leading academic research organizations and physician-scientists specializing in MV disease from the United States and Europe. Three in-person meetings were held in Virginia and New York during which 44 heart failure, valve, and imaging experts, MV surgeons and interventional cardiologists, clinical trial specialists and statisticians, and representatives from the U.S. Food and Drug Administration considered all aspects of MV pathophysiology, prognosis, and therapies, culminating in a 2-part document describing consensus recommendations for clinical trial design (Part 1) and endpoint definitions (Part 2) to guide evaluation of transcatheter and surgical therapies for MR. The adoption of these recommendations will afford robustness and consistency in the comparative effectiveness evaluation of new devices and approaches to treat MR. These principles may be useful for regulatory assessment of new transcatheter MV devices, as well as for monitoring local and regional outcomes to guide quality improvement initiatives. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Use of a modified bubble continuous positive airway pressure (bCPAP) device for children in respiratory distress in low- and middle-income countries: a safety study.

PubMed

Bjorklund, Ashley R; Odongkara Mpora, Beatrice; Steiner, Marie E; Fischer, Gwenyth; Davey, Cynthia S; Slusher, Tina M

2018-06-18

While bubble continuous positive airway pressure (bCPAP) is commonly used in low- and middle-income countries (LMIC) to support neonates with respiratory distress, there are limited non-invasive support options for non-neonatal children. To demonstrate safety of a new device designed to support children during respiratory distress in LMIC. A paediatric bCPAP device was designed called SEAL-bCPAP (Simplified Ear-plug Adapted-bCPAP). SEAL-bCPAP is constructed from inexpensive, easily obtainable materials. The nasal prong interface was modified from previously described neonatal bCPAP set-ups using commercial ear-plug material to improve nasal seal. A prospective interventional study was conducted to evaluate safety in children with respiratory distress treated with SEAL-bCPAP. Patients aged 30 days to 5 years presenting to a hospital in northern Uganda from July 2015 to June 2016 were screened. Those with moderate-severe respiratory distress and/or hypoxia despite nasal cannula oxygen were eligible for study. Enrolled patients were supported with SEAL-bCPAP until respiratory improvement or death. Complications attributable to SEAL-bCPAP were recorded. Clinical outcomes were compared with historical control pre-trial data. Eighty-three of 87 enrolled patients were included in the final analysis. No patients had significant SEAL-bCPAP complications. Five patients had mild complications which resolved (four with nasal irritation and one with abdominal distention). Trial patients had significant (p < 0.0001) improvement in their TAL score, respiratory rate and O 2 sat after 2 h of SEAL-bCPAP. Fifty-two of 64 patients (62.7%) with severe illness at Time1 did not have severe illness at Time2 (after 2 h of SEAL-bCPAP) (p < 0.0001). Unadjusted mortality rates were 12.2% (6/49) and 9.6% (8/83), respectively, for pre-trial (historical control) and trial patients (p = 0.64); the study was not powered to show efficacy. The SEAL-bCPAP device is safe for treatment of respiratory distress in non-neonatal children in LMIC. There is a trend toward decreased mortality that should be evaluated with adequately powered clinical trials.

A single center analysis of factors influencing study start-up timeline in clinical trials.

PubMed

Krafcik, Brianna M; Doros, Gheorghe; Malikova, Marina A

2017-11-01

Efficient start-up phase in clinical trials is crucial to execution. The goal was to determine factors contributing to delays. The start-up milestones were assessed for 38 studies and analyzed. Total start-up time was shorter for following studies: device trials, no outsourcing, fewer ancillary services used and in interventional versus observational designs. The use of a centralized Institutional Review Board (IRB) versus a local IRB reduced time to approval. Studies that never enrolled took longer on average to finalize their budget/contract, and obtain IRB than ones that did enroll. Different features of clinical trials can affect timeline of start-up process. An understanding of the impact of each feature allows for optimization.

A comparison of Percutaneous femoral access in Endovascular Repair versus Open femoral access (PiERO): study protocol for a randomized controlled trial.

PubMed

Vierhout, Bastiaan P; Saleem, Ben R; Ott, Alewijn; van Dijl, Jan Maarten; de Kempenaer, Ties D van Andringa; Pierie, Maurice E N; Bottema, Jan T; Zeebregts, Clark J

2015-09-14

Access for endovascular repair of abdominal aortic aneurysms (EVAR) is obtained through surgical cutdown or percutaneously. The only devices suitable for percutaneous closure of the 20 French arteriotomies of the common femoral artery (CFA) are the Prostar(™) and Proglide(™) devices (Abbott Vascular). Positive effects of these devices seem to consist of a lower infection rate, and shorter operation time and hospital stay. This conclusion was published in previous reports comparing techniques in patients in two different groups (cohort or randomized). Access techniques were never compared in one and the same patient; this research simplifies comparison because patient characteristics will be similar in both groups. Percutaneous access of the CFA is compared to surgical cutdown in a single patient; in EVAR surgery, access is necessary in both groins in each patient. Randomization is performed on the introduction site of the larger main device of the endoprosthesis. The contralateral device of the endoprosthesis is smaller. When we use this type of randomization, both groups will contain a similar number of main and contralateral devices. Preoperative nose cultures and perineal cultures are obtained, to compare colonization with postoperative wound cultures (in case of a surgical site infection). Furthermore, patient comfort will be considered, using VAS-scores (Visual analog scale). Punch biopsies of the groin will be harvested to retrospectively compare skin of patients who suffered a surgical site infection (SSI) to patients who did not have an SSI. The PiERO trial is a multicenter randomized controlled clinical trial designed to show the consequences of using percutaneous access in EVAR surgery and focuses on the occurrence of surgical site infections. NTR4257 10 November 2013, NL44578.042.13.

Evaluation of a training program for device operators in the Australian Government's Point of Care Testing in General Practice Trial: issues and implications for rural and remote practices.

PubMed

Shephard, Mark D; Mazzachi, Beryl C; Watkinson, Les; Shephard, Anne K; Laurence, Caroline; Gialamas, Angela; Bubner, Tanya

2009-01-01

From September 2005 to February 2007 the Australian Government funded the Point of Care Testing (PoCT) in General Practice Trial, a multi-centre, cluster randomised controlled trial to determine the safety, clinical effectiveness, cost-effectiveness and satisfaction of PoCT in General Practice. In total, 53 practices (23 control and 30 intervention) based in urban, rural or remote locations across three states (South Australia [SA], New South Wales [NSW] and Victoria [VIC]) participated in the Trial. Control practices had pathology testing performed by their local laboratory, while intervention practices conducted pathology testing by PoCT. In total, 4968 patients (1958 control and 3010 intervention) participated in the Trial. The point-of-care (PoC) tests performed by intervention practices were: haemoglobin A1c (HbA1c) and urine albumin:creatinine ratio (ACR) on patients with diabetes, total cholesterol, triglyceride and high density lipoprotein (HDL) cholesterol on patients with hyperlipidaemia, and international normalised ratio (INR) on patients on anticoagulant therapy. Three PoCT devices measured these tests: the Siemens DCA 2000 (Siemens HealthCare Diagnostics, Melbourne, VIC, Australia) for HbA1c and urine ACR; Point of Care Diagnostics Cholestech LDX analyser (Point of Care Diagnostics; Sydney, NSW, Australia) for lipids; and the Roche CoaguChek S (Roche Diagnostics; Sydney, NSW, Australia) for INR. Point-of-care testing in the General Practice Trial was underpinned by a quality management framework which included an on-going training and competency program for PoCT device operators. This article describes the design, implementation and results of the training and competency program. An education and training resource package was developed for the Trial consisting of a training manual, a set of A3 laminated posters and a CD ROM. Five initial training workshops were held for intervention practices from each geographic region between August and October 2005 at three centres - Adelaide (SA), Bendigo (VIC) and Dubbo (NSW). These workshops combined theoretical training in the principles and practice of PoCT with 'hands on' practical training delivered in interactive small group sessions. At the completion of training, practice staff undertook a written and practical competency assessment and received a certificate of competency as a qualified device operator. Following each initial training workshop, practice staff completed a short satisfaction survey. Five refresher training workshops covering all geographic regions were delivered during late August 2006, coinciding with the 12 month point of the live phase of the Trial. At the completion of the Trial in February 2007, device operators completed a further questionnaire. Sixty device operators from 31 practices completed training and competency assessment as part of the Initial Training Workshop series. A further 20 device operators from 12 of the practices were trained in the 12 month period after the initial workshops; 19 of these staff were from rural or remote practices. In total 80 device operators comprising 74 practice staff and six GPs from 31 practices were trained and received competency certificates as part of Trial. In all, 19 device operators left the Trial either through personal resignation from an existing practice or because their practice withdrew from the Trial; the majority (84%) were from rural and remote practices. A total of 42 device operators from 25 practices attended refresher training in the second half of 2006. Results from the satisfaction questionnaire completed by device operators following the initial training workshops showed there was unanimous agreement that the posters were useful for the conduct of daily PoCT and practical training in small groups was satisfactory as a training method. The quality and appropriateness of the PoCT training resources and the workshop overall was rated as either good or excellent by all respondents (100% and 78%, respectively). The responses by device operators to the post-Trial satisfaction questionnaire found a high level of satisfaction with PoCT across all geographic regions. Device operators from remote practices had the highest satisfaction levels for quality of training, usefulness of the training manual, ease of use of devices, confidence in the accuracy of PoCT results and preference for PoCT over laboratory testing. The usefulness of the posters for conducting PoCT achieved the highest satisfaction rating among operators from all three geographic regions. However the highest staff turnover rates and the highest number of requests for training of additional staff were from rural and remote practices. The methods established for the implementation and delivery of training and competency assessment for the PoCT in General Practice Trial were appropriate and effective. Results of the evaluation showed rural and remote practices have a greater need for training and support compared to their urban counterparts and may require more flexible training options to cater for much higher rates of staff turnover.

Thermic sealing in femoral catheterisation: First experience with the Secure Device.

PubMed

Sacherer, Michael; Kolesnik, Ewald; von Lewinski, Friederike; Verheyen, Nicolas; Brandner, Karin; Wallner, Markus; Eaton, Deborah M; Luha, Olev; Zweiker, Robert; von Lewinski, Dirk

2018-04-03

Devices currently used to achieve hemostasis of the femoral artery following percutaneous cardiac catheterization are associated with vascular complications and remnants of artificial materials are retained at the puncture site. The SECURE arterial closure device induces hemostasis by utilizing thermal energy, which causes collagen shrinking and swelling. In comparison to established devices, it has the advantage of leaving no foreign material in the body following closing. This study was designed to evaluate the efficacy and safety of the SECURE device to close the puncture site following percutaneous cardiac catheterization. The SECURE device was evaluated in a prospective non-randomized single-centre trial with patients undergoing 6 F invasive cardiac procedures. A total of 67 patients were enrolled and the device was utilized in 63 patients. 50 diagnostic and 13 interventional cases were evaluated. Femoral artery puncture closure was performed immediately after completion of the procedure. Time to hemostasis (TTH), time to ambulation (TTA) and data regarding short-term and 30-day clinical follow-up were recorded. Mean TTH was 4:30 ± 2:15 min in the overall observational group. A subpopulation of patients receiving anticoagulants had a TTH of 4:53 ± 1:43 min. There were two access site complications (hematoma > 5 cm). No major adverse events were identified during hospitalization or at the 30 day follow-up. The new SECURE device demonstrates that it is feasible in diagnostic and interventional cardiac catheterization. With respect to safety, the SECURE device was non-inferior to other closure devices as tested in the ISAR closure trial.

Animal trials of a Magnetically Levitated Left-Ventricular Assist Device

NASA Technical Reports Server (NTRS)

Paden, Brad; Antaki, James; Groom, Nelson

2000-01-01

The University of Pittsburgh/Magnetic Moments mag-lev left-ventricular assist devices (LVADs), the Streamliner HG3b and HG3c, have successfully been implanted in calves. The first was implanted for 4 hours on July 10, 1998 and the second for 34 days on August 24, 1999 respectively. The tests confirmed the feasibility of low power levitation (1.5 watts coil power) and very low blood damage in a mag-lev ventricular assist device. In this paper, we describe the unique geometry of this pump and its design. Key features of this LVAD concept are the passive radial suspension and active voice-coil thrust bearing.

Practice of Regulatory Science (Development of Medical Devices).

PubMed

Niimi, Shingo

2017-01-01

Prototypes of medical devices are made in accordance with the needs of clinical practice, and for systems required during the initial process of medical device development for new surgical practices. Verification of whether these prototypes produce the intended performance specifications is conducted using basic tests such as mechanical and animal tests. The prototypes are then improved and modified until satisfactory results are obtained. After a prototype passes through a clinical trial process similar to that for new drugs, application for approval is made. In the approval application process, medical devices are divided into new, improved, and generic types. Reviewers judge the validity of intended use, indications, operation procedures, and precautions, and in addition evaluate the balance between risk and benefit in terms of efficacy and safety. Other characteristics of medical devices are the need for the user to attain proficiency in usage techniques to ensure efficacy and safety, and the existence of a variety of medical devices for which assessment strategies differ, including differences in impact on the body in cases in which a physical burden to the body or failure of a medical device develops. Regulatory science of medical devices involves prediction, judgment, and evaluation of efficacy, safety, and quality, from which data result which can become indices in the development stages from design to application for approval. A reduction in the number of animals used for testing, improvement in efficiency, reduction of the necessity for clinical trials, etc. are expected through rational setting of evaluation items.

Standardized End Point Definitions for Coronary Intervention Trials: The Academic Research Consortium-2 Consensus Document.

PubMed

Garcia-Garcia, Hector M; McFadden, Eugène P; Farb, Andrew; Mehran, Roxana; Stone, Gregg W; Spertus, John; Onuma, Yoshinobu; Morel, Marie-Angèle; van Es, Gerrit-Anne; Zuckerman, Bram; Fearon, William F; Taggart, David; Kappetein, Arie-Pieter; Krucoff, Mitchell W; Vranckx, Pascal; Windecker, Stephan; Cutlip, Donald; Serruys, Patrick W

2018-06-12

The Academic Research Consortium (ARC)-2 initiative revisited the clinical and angiographic end point definitions in coronary device trials, proposed in 2007, to make them more suitable for use in clinical trials that include increasingly complex lesion and patient populations and incorporate novel devices such as bioresorbable vascular scaffolds. In addition, recommendations for the incorporation of patient-related outcomes in clinical trials are proposed. Academic Research Consortium-2 is a collaborative effort between academic research organizations in the United States and Europe, device manufacturers, and European, US, and Asian regulatory bodies. Several in-person meetings were held to discuss the changes that have occurred in the device landscape and in clinical trials and regulatory pathways in the last decade. The consensus-based end point definitions in this document are endorsed by the stakeholders of this document and strongly advocated for clinical trial purposes. This Academic Research Consortium-2 document provides further standardization of end point definitions for coronary device trials, incorporating advances in technology and knowledge. Their use will aid interpretation of trial outcomes and comparison among studies, thus facilitating the evaluation of the safety and effectiveness of these devices. © 2018 American Heart Association, Inc., and European Society of Cardiology.

Understanding United States Investigational Device Exemption Studies-Clinical Relevance and Importance for Healthcare Economics.

PubMed

Ament, Jared D; Mollan, Scott; Greenan, Krista; Binyamin, Tamar; Kim, Kee D

2017-06-01

The US Food and Drug Administration allows a previously unapproved device to be used clinically to collect safety and effectiveness data under their Investigational Device Exemption (IDE) category. The process usually falls under 3 different trial categories: noninferiority, equivalency, and superiority. To confidently inform our patients, understanding the basic concepts of these trials is paramount. The purpose of this manuscript was to provide a comprehensive review of these topics using recently published IDE trials and economic analyses of cervical total disc replacement as illustrative examples. In 2006, an IDE was initiated to study the safety and effectiveness of total disc replacement controlled against the standard of care, anterior cervical discectomy, and fusion. Under the IDE, randomized controlled trials comparing both 1 and 2 level cervical disease were completed. The sponsor designed the initial trial as noninferiority; however, using adaptive methodology, superiority could be claimed in the 2-level investigation. Healthcare economics are critical in medical decision making and reimbursement practices. Once both cost- and quality-adjusted life-year (QALY) are known for each patient, the incremental cost-effectiveness ratio is calculated. Willingness-to-pay is controversial, but a commonly cited guideline considers interventions costing below 20 000 $/QALY strongly cost effective and more than 100 000 $/QALY as not cost effective. While large Food and Drug Administration IDE studies are often besieged by complex statistical considerations and calculations, it is fundamentally important that clinicians understand at least the terminology and basic concepts on a practical level. Copyright © 2017 by the Congress of Neurological Surgeons

Transcatheter Mitral Valve Replacement for Native and Failed Bioprosthetic Mitral Valves

PubMed Central

Sarkar, Kunal; Reardon, Michael J.; Little, Stephen H.; Barker, Colin M.; Kleiman, Neal S.

2017-01-01

Transcatheter mitral valve replacement (TMVR) is a novel approach for treatment of severe mitral regurgitation. A number of TMVR devices are currently undergoing feasibility trials using both transseptal and transapical routes for device delivery. Overall experience worldwide is limited to fewer than 200 cases. At present, the 30-day mortality exceeds 30% and is attributable to both patient- and device-related factors. TMVR has been successfully used to treat patients with degenerative mitral stenosis (DMS) as well as failed mitral bioprosthesis and mitral repair using transcatheter mitral valve-in-valve (TMViV)/valve-in-ring (ViR) repair. These patients are currently treated with devices designed for transcatheter aortic valve replacement. Multicenter registries have been initiated to collect outcomes data on patients currently undergoing TMViV/ViR and TMVR for DMS and have confirmed the feasibility of TMVR in these patients. However, the high periprocedural and 30-day event rates underscore the need for further improvements in device design and multicenter randomized studies to delineate the role of these technologies in patients with mitral valve disease. PMID:29743999

Development of a Portable Knee Rehabilitation Device That Uses Mechanical Loading.

PubMed

Fitzwater, Daric; Dodge, Todd; Chien, Stanley; Yokota, Hiroki; Anwar, Sohel

2013-12-01

Joint loading is a recently developed mechanical modality, which potentially provides a therapeutic regimen to activate bone formation and prevent degradation of joint tissues. To our knowledge, however, few joint loading devices are available for clinical or point-of-care applications. Using a voice-coil actuator, we developed an electromechanical loading system appropriate for human studies and preclinical trials that should prove both safe and effective. Two specific tasks for this loading system were development of loading conditions (magnitude and frequency) suitable for humans, and provision of a convenient and portable joint loading apparatus. Desktop devices have been previously designed to evaluate the effects of various loading conditions using small and large animals. However, a portable knee loading device is more desirable from a usability point of view. In this paper, we present such a device that is designed to be portable, providing a compact, user-friendly loader. The portable device was employed to evaluate its capabilities using a human knee model. The portable device was characterized for force-pulse width modulation duty cycle and loading frequency properties. The results demonstrate that the device is capable of producing the necessary magnitude of forces at appropriate frequencies to promote the stimulation of bone growth and which can be used in clinical studies for further evaluations.

Magnetic resonance imaging in patients with cardiac pacemakers: era of "MR Conditional" designs.

PubMed

Shinbane, Jerold S; Colletti, Patrick M; Shellock, Frank G

2011-10-27

Advances in cardiac device technology have led to the first generation of magnetic resonance imaging (MRI) conditional devices, providing more diagnostic imaging options for patients with these devices, but also new controversies. Prior studies of pacemakers in patients undergoing MRI procedures have provided groundwork for design improvements. Factors related to magnetic field interactions and transfer of electromagnetic energy led to specific design changes. Ferromagnetic content was minimized. Reed switches were modified. Leads were redesigned to reduce induced currents/heating. Circuitry filters and shielding were implemented to impede or limit the transfer of certain unwanted electromagnetic effects. Prospective multicenter clinical trials to assess the safety and efficacy of the first generation of MR conditional cardiac pacemakers demonstrated no significant alterations in pacing parameters compared to controls. There were no reported complications through the one month visit including no arrhythmias, electrical reset, inhibition of generator output, or adverse sensations. The safe implementation of these new technologies requires an understanding of the well-defined patient and MR system conditions. Although scanning a patient with an MR conditional device following the strictly defined patient and MR system conditions appears straightforward, issues related to patients with pre-existing devices remain complex. Until MR conditional devices are the routine platform for all of these devices, there will still be challenging decisions regarding imaging patients with pre-existing devices where MRI is required to diagnose and manage a potentially life threatening or serious scenario. A range of other devices including ICDs, biventricular devices, and implantable physiologic monitors as well as guidance of medical procedures using MRI technology will require further biomedical device design changes and testing. The development and implementation of cardiac MR conditional devices will continue to require the expertise and collaboration of multiple disciplines and will need to prove safety, effectiveness, and cost effectiveness in patient care.

Magnetic resonance imaging in patients with cardiac pacemakers: era of "MR Conditional" designs

PubMed Central

2011-01-01

Advances in cardiac device technology have led to the first generation of magnetic resonance imaging (MRI) conditional devices, providing more diagnostic imaging options for patients with these devices, but also new controversies. Prior studies of pacemakers in patients undergoing MRI procedures have provided groundwork for design improvements. Factors related to magnetic field interactions and transfer of electromagnetic energy led to specific design changes. Ferromagnetic content was minimized. Reed switches were modified. Leads were redesigned to reduce induced currents/heating. Circuitry filters and shielding were implemented to impede or limit the transfer of certain unwanted electromagnetic effects. Prospective multicenter clinical trials to assess the safety and efficacy of the first generation of MR conditional cardiac pacemakers demonstrated no significant alterations in pacing parameters compared to controls. There were no reported complications through the one month visit including no arrhythmias, electrical reset, inhibition of generator output, or adverse sensations. The safe implementation of these new technologies requires an understanding of the well-defined patient and MR system conditions. Although scanning a patient with an MR conditional device following the strictly defined patient and MR system conditions appears straightforward, issues related to patients with pre-existing devices remain complex. Until MR conditional devices are the routine platform for all of these devices, there will still be challenging decisions regarding imaging patients with pre-existing devices where MRI is required to diagnose and manage a potentially life threatening or serious scenario. A range of other devices including ICDs, biventricular devices, and implantable physiologic monitors as well as guidance of medical procedures using MRI technology will require further biomedical device design changes and testing. The development and implementation of cardiac MR conditional devices will continue to require the expertise and collaboration of multiple disciplines and will need to prove safety, effectiveness, and cost effectiveness in patient care. PMID:22032338

Multicenter Clinical Trial of Keratin Biomaterial for Peripheral Nerve Regeneration

DTIC Science & Technology

2015-12-01

Radiological Health ( CDRH ) to clarify the designation of the hydrogel. As a result of this meeting, steps required for an IND for the keratin...the Center for Biologics Evaluation Research (CBER), and the Center for Devices and Radiological Health 8 ( CDRH ) to clarify the designation of the...application to the CDRH for a new product. This new product is the material that is produced in the validated manufacturing facility at KeraNetics. This

Sample Size Calculations for Micro-randomized Trials in mHealth

PubMed Central

Liao, Peng; Klasnja, Predrag; Tewari, Ambuj; Murphy, Susan A.

2015-01-01

The use and development of mobile interventions are experiencing rapid growth. In “just-in-time” mobile interventions, treatments are provided via a mobile device and they are intended to help an individual make healthy decisions “in the moment,” and thus have a proximal, near future impact. Currently the development of mobile interventions is proceeding at a much faster pace than that of associated data science methods. A first step toward developing data-based methods is to provide an experimental design for testing the proximal effects of these just-in-time treatments. In this paper, we propose a “micro-randomized” trial design for this purpose. In a micro-randomized trial, treatments are sequentially randomized throughout the conduct of the study, with the result that each participant may be randomized at the 100s or 1000s of occasions at which a treatment might be provided. Further, we develop a test statistic for assessing the proximal effect of a treatment as well as an associated sample size calculator. We conduct simulation evaluations of the sample size calculator in various settings. Rules of thumb that might be used in designing a micro-randomized trial are discussed. This work is motivated by our collaboration on the HeartSteps mobile application designed to increase physical activity. PMID:26707831

Current Status and Perspectives of Hyperthermia in Cancer Therapy

NASA Astrophysics Data System (ADS)

Hiraoka, Masahiro; Nagata, Yasushi; Mitsumori, Michihide; Sakamoto, Masashi; Masunaga, Shin-ichiro

2004-08-01

Clinical trials of hyperthermia in combination with radiation therapy or chemotherapy undertaken over the past decades in Japan have been reviewed. Originally developed heating devices were mostly used for these trials, which include RF (radiofrequency) capacitive heating devices, a microwave heating device with a lens applicator, an RF intracavitary heating device, an RF current interstitial heating device, and ferromagnetic implant heating device. Non-randomized trials for various cancers, demonstrated higher response rate in thermoradiotherapy than in radiotherapy alone. Randomized trials undertaken for esophageal cancers also demonstrated improved local response with the combined use of hyperthermia. Furthermore, the complications associated with treatment were not generally serious. These clinical results indicate the benefit of combined treatment of hyperthermia and radiotherapy for various malignancies. On the other hand, the presently available heating devices are not satisfactory from the clinical viewpoints. With the advancement of heating and thermometry technologies, hyperthermia will be more widely and safely used in the treatment of cancers.

Reporting discrepancies between the ClinicalTrials.gov results database and peer-reviewed publications.

PubMed

Hartung, Daniel M; Zarin, Deborah A; Guise, Jeanne-Marie; McDonagh, Marian; Paynter, Robin; Helfand, Mark

2014-04-01

ClinicalTrials.gov requires reporting of result summaries for many drug and device trials. To evaluate the consistency of reporting of trials that are registered in the ClinicalTrials.gov results database and published in the literature. ClinicalTrials.gov results database and matched publications identified through ClinicalTrials.gov and a manual search of 2 electronic databases. 10% random sample of phase 3 or 4 trials with results in the ClinicalTrials.gov results database, completed before 1 January 2009, with 2 or more groups. One reviewer extracted data about trial design and results from the results database and matching publications. A subsample was independently verified. Of 110 trials with results, most were industry-sponsored, parallel-design drug studies. The most common inconsistency was the number of secondary outcome measures reported (80%). Sixteen trials (15%) reported the primary outcome description inconsistently, and 22 (20%) reported the primary outcome value inconsistently. Thirty-eight trials inconsistently reported the number of individuals with a serious adverse event (SAE); of these, 33 (87%) reported more SAEs in ClinicalTrials.gov. Among the 84 trials that reported SAEs in ClinicalTrials.gov, 11 publications did not mention SAEs, 5 reported them as zero or not occurring, and 21 reported a different number of SAEs. Among 29 trials that reported deaths in ClinicalTrials.gov, 28% differed from the matched publication. Small sample that included earliest results posted to the database. Reporting discrepancies between the ClinicalTrials.gov results database and matching publications are common. Which source contains the more accurate account of results is unclear, although ClinicalTrials.gov may provide a more comprehensive description of adverse events than the publication. Agency for Healthcare Research and Quality.

Propellant injection systems and processes

NASA Technical Reports Server (NTRS)

Ito, Jackson I.

1995-01-01

The previous 'Art of Injector Design' is maturing and merging with the more systematic 'Science of Combustion Device Analysis.' This technology can be based upon observation, correlation, experimentation and ultimately analytical modeling based upon basic engineering principles. This methodology is more systematic and far superior to the historical injector design process of 'Trial and Error' or blindly 'Copying Past Successes.' The benefit of such an approach is to be able to rank candidate design concepts for relative probability of success or technical risk in all the important combustion device design requirements and combustion process development risk categories before committing to an engine development program. Even if a single analytical design concept cannot be developed to predict satisfying all requirements simultaneously, a series of risk mitigation key enabling technologies can be identified for early resolution. Lower cost subscale or laboratory experimentation to demonstrate proof of principle, critical instrumentation requirements, and design discriminating test plans can be developed based on the physical insight provided by these analyses.

A voice-input voice-output communication aid for people with severe speech impairment.

PubMed

Hawley, Mark S; Cunningham, Stuart P; Green, Phil D; Enderby, Pam; Palmer, Rebecca; Sehgal, Siddharth; O'Neill, Peter

2013-01-01

A new form of augmentative and alternative communication (AAC) device for people with severe speech impairment-the voice-input voice-output communication aid (VIVOCA)-is described. The VIVOCA recognizes the disordered speech of the user and builds messages, which are converted into synthetic speech. System development was carried out employing user-centered design and development methods, which identified and refined key requirements for the device. A novel methodology for building small vocabulary, speaker-dependent automatic speech recognizers with reduced amounts of training data, was applied. Experiments showed that this method is successful in generating good recognition performance (mean accuracy 96%) on highly disordered speech, even when recognition perplexity is increased. The selected message-building technique traded off various factors including speed of message construction and range of available message outputs. The VIVOCA was evaluated in a field trial by individuals with moderate to severe dysarthria and confirmed that they can make use of the device to produce intelligible speech output from disordered speech input. The trial highlighted some issues which limit the performance and usability of the device when applied in real usage situations, with mean recognition accuracy of 67% in these circumstances. These limitations will be addressed in future work.

Mobile-Based Video Learning Outcomes in Clinical Nursing Skill Education: A Randomized Controlled Trial.

PubMed

Lee, Nam-Ju; Chae, Sun-Mi; Kim, Haejin; Lee, Ji-Hye; Min, Hyojin Jennifer; Park, Da-Eun

2016-01-01

Mobile devices are a regular part of daily life among the younger generations. Thus, now is the time to apply mobile device use to nursing education. The purpose of this study was to identify the effects of a mobile-based video clip on learning motivation, competence, and class satisfaction in nursing students using a randomized controlled trial with a pretest and posttest design. A total of 71 nursing students participated in this study: 36 in the intervention group and 35 in the control group. A video clip of how to perform a urinary catheterization was developed, and the intervention group was able to download it to their own mobile devices for unlimited viewing throughout 1 week. All of the students participated in a practice laboratory to learn urinary catheterization and were blindly tested for their performance skills after participation in the laboratory. The intervention group showed significantly higher levels of learning motivation and class satisfaction than did the control. Of the fundamental nursing competencies, the intervention group was more confident in practicing catheterization than their counterparts. Our findings suggest that video clips using mobile devices are useful tools that educate student nurses on relevant clinical skills and improve learning outcomes.

SPEAR Trial: Smartphone Pediatric ElectrocARdiogram Trial

PubMed Central

Nguyen, Hoang H.; Van Hare, George F.; Rudokas, Michael; Bowman, Tammy; Silva, Jennifer N. A.

2015-01-01

Objectives Smartphone-enabled ECG devices have the potential to improve patient care by enabling remote ECG assessment of patients with potential and diagnosed arrhythmias. This prospective study aimed to assess the usefulness of pediatric ECG tracings generated by the AliveCor device (Oklahoma City, OK) and to assess user satisfaction. Study Design Enrolled pediatric patients with documented paroxysmal arrhythmia used the AliveCor device over a yearlong study period. Pediatric electrophysiologists reviewed all transmitted ECG tracings. Patient completed surveys were analyzed to assess user satisfaction. Results 35 patients were enrolled with the following diagnoses: supraventricular tachycardia (SVT, 57%), atrial fibrillation (AF, 11%), ectopic atrial tachycardia (EAT, 6%), atrial tachycardia (AT, 3%), and ventricular tachycardia (VT, 23%). A total of 238 tracings were received from 20 patients, 96% of which were of diagnostic quality for sinus rhythm, sinus tachycardia, SVT, and AF. 126 patient satisfaction surveys (64% from parents) were completed. 98% of the survey responses indicated that it was easy to obtain tracings, 93% found it easy to transmit the tracings, 98% showed added comfort in managing arrhythmia by having the device, and 93% showed interest in continued use of the device after the study period ended. Conclusions Smartphone-enabled ECG devices can generate tracings of diagnostic quality in children. User satisfaction was extremely positive. Use of the device to manage certain patients with AF and SVT showcases the future role of remote ECGs in the successful outpatient management of arrhythmias in children by potentially reducing Emergency Department visits and healthcare costs. PMID:26295569

Clinical evaluation of an inspiratory impedance threshold device during standard cardiopulmonary resuscitation in patients with out-of-hospital cardiac arrest.

PubMed

Aufderheide, Tom P; Pirrallo, Ronald G; Provo, Terry A; Lurie, Keith G

2005-04-01

To determine whether an impedance threshold device, designed to enhance circulation, would increase acute resuscitation rates for patients in cardiac arrest receiving conventional manual cardiopulmonary resuscitation. Prospective, randomized, double-blind, intention-to-treat. Out-of-hospital trial conducted in the Milwaukee, WI, emergency medical services system. Adults in cardiac arrest of presumed cardiac etiology. On arrival of advanced life support, patients were treated with standard cardiopulmonary resuscitation combined with either an active or a sham impedance threshold device. We measured safety and efficacy of the impedance threshold device; the primary end point was intensive care unit admission. Statistical analyses performed included the chi-square test and multivariate regression analysis. One hundred sixteen patients were treated with a sham impedance threshold device, and 114 patients were treated with an active impedance threshold device. Overall intensive care unit admission rates were 17% with the sham device vs. 25% in the active impedance threshold device (p = .13; odds ratio, 1.64; 95% confidence interval, 0.87, 3.10). Patients in the subgroup presenting with pulseless electrical activity had intensive care unit admission and 24-hr survival rates of 20% and 12% in sham (n = 25) vs. 52% and 30% in active impedance threshold device groups (n = 27) (p = .018, odds ratio, 4.31; 95% confidence interval, 1.28, 14.5, and p = .12, odds ratio, 3.09; 95% confidence interval, 0.74, 13.0, respectively). A post hoc analysis of patients with pulseless electrical activity at any time during the cardiac arrest revealed that intensive care unit and 24-hr survival rates were 20% and 11% in the sham (n = 56) vs. 41% and 27% in the active impedance threshold device groups (n = 49) (p = .018, odds ratio, 2.82; 95% confidence interval, 1.19, 6.67, and p = .037, odds ratio, 3.01; 95% confidence interval, 1.07, 8.96, respectively). There were no statistically significant differences in outcomes for patients presenting in ventricular fibrillation and asystole. Adverse event and complication rates were also similar. During this first clinical trial of the impedance threshold device during standard cardiopulmonary resuscitation, use of the new device more than doubled short-term survival rates in patients presenting with pulseless electrical activity. A larger clinical trial is underway to determine the potential longer term benefits of the impedance threshold device in cardiac arrest.

Left ventricular assist devices as destination therapy: a new look at survival.

PubMed

Park, Soon J; Tector, Alfred; Piccioni, William; Raines, Edward; Gelijns, Annetine; Moskowitz, Alan; Rose, Eric; Holman, William; Furukawa, Satoshi; Frazier, O Howard; Dembitsky, Walter

2005-01-01

The REMATCH trial compared the use of left ventricular assist devices with optimal medical management for patients with end-stage heart failure. When the trial met its primary end point criteria in July 2001, left ventricular assist device therapy was shown to significantly improve survival and quality of life. With extended follow-up, 2 critical questions emerge: (1) Did these benefits persist, and (2) did outcomes improve over the course of the trial, given the evolving nature of the technology? We analyzed survival in this randomized trial by using the product-limit method of Kaplan and Meier. Changes in the benefits of therapy were analyzed by examining the effect of the enrollment period. The survival rates for patients receiving left ventricular assist devices (n = 68) versus patients receiving optimal medical management (n = 61) were 52% versus 28% at 1 year and 29% versus 13% at 2 years ( P = .008, log-rank test). As of July 2003, 11 patients were alive on left ventricular assist device support out of a total 16 survivors (including 3 patients receiving optimal medical management who crossed over to left ventricular assist device therapy). There was a significant improvement in survival for left ventricular assist device-supported patients who enrolled during the second half of the trial compared with the first half ( P = .03). The Minnesota Living with Heart Failure scores improved significantly over the course of the trial. The extended follow-up confirms the initial observation that left ventricular assist device therapy renders significant survival and quality-of-life benefits compared with optimal medical management for patients with end-stage heart failure. Furthermore, we observed an improvement in the survival of patients receiving left ventricular assist devices over the course of the trial, suggesting the effect of greater clinical experience.

Stem Cell Trials for Cardiovascular Medicine: Ethical Rationale

PubMed Central

Teraa, Martin; Hesam, Husna; van Delden, Johannes J.M.; Verhaar, Marianne C.; Bredenoord, Annelien L.

2014-01-01

Stem cell-based interventions provide new treatment prospects for many disease conditions, including cardiovascular disorders. Clinical trials are necessary to collect adequate evidence on (long-term) safety and efficacy of novel interventions such as stem cells, but the design and launch of clinical trials, from first-in-human studies to larger randomized controlled trials (RCTs), is scientifically and ethically challenging. Stem cells are different from traditional pharmaceuticals, surgical procedures, and medical devices in the following ways: the novelty and complexity of stem cells, the invasiveness of the procedures, and the novel aim of regeneration. These specifics, combined with the characteristics of the study population, will have an impact on the design and ethics of RCTs. The recently closed JUVENTAS trial will serve as an example to identify the (interwoven) scientific and ethical challenges in the design and launch of stem cell RCTs. The JUVENTAS trial has investigated the efficacy of autologous bone marrow cells in end-stage vascular patients, in a double-blind sham-controlled design. We first describe the choices, considerations, and experiences of the JUVENTAS team. Subsequently, we identify the main ethical and scientific challenges and discuss what is important to consider in the design of future stem cell RCTs: assessment of risks and benefits, the choice for outcome measures, the choice for the comparator, the appropriate selection of participants, and adequate informed consent. Additionally, the stem cell field is highly in the spotlight due to the (commercial) interests and expectations. This warrants a cautious pace of translation and scrupulous set up of clinical trials, as failures could put the field in a negative light. At the same time, knowledge from clinical trials is necessary for the field to progress. We conclude that in the scientifically and ethically challenging field of stem cell RCTs, researchers and clinicians have to maneuver between the Skylla of hyper accelerated translation without rigorously conducted RCTs and the Charybdis of the missed opportunity of valuable knowledge. PMID:24164351

Design of a terminal solution for integration of in-home health care devices and services towards the Internet-of-Things

NASA Astrophysics Data System (ADS)

Pang, Zhibo; Zheng, Lirong; Tian, Junzhe; Kao-Walter, Sharon; Dubrova, Elena; Chen, Qiang

2015-01-01

In-home health care services based on the Internet-of-Things are promising to resolve the challenges caused by the ageing of population. But the existing research is rather scattered and shows lack of interoperability. In this article, a business-technology co-design methodology is proposed for cross-boundary integration of in-home health care devices and services. In this framework, three key elements of a solution (business model, device and service integration architecture and information system integration architecture) are organically integrated and aligned. In particular, a cooperative Health-IoT ecosystem is formulated, and information systems of all stakeholders are integrated in a cooperative health cloud as well as extended to patients' home through the in-home health care station (IHHS). Design principles of the IHHS includes the reuse of 3C platform, certification of the Health Extension, interoperability and extendibility, convenient and trusted software distribution, standardised and secured electrical health care record handling, effective service composition and efficient data fusion. These principles are applied to the design of an IHHS solution called iMedBox. Detailed device and service integration architecture and hardware and software architecture are presented and verified by an implemented prototype. The quantitative performance analysis and field trials have confirmed the feasibility of the proposed design methodology and solution.

FDA's perspectives on cardiovascular devices.

PubMed

Chen, Eric A; Patel-Raman, Sonna M; O'Callaghan, Kathryn; Hillebrenner, Matthew G

2009-06-01

The Food and Drug Administration (FDA) decision process for approving or clearing medical devices is often determined by a review of robust clinical data and extensive preclinical testing of the device. The mission statement for the Center for Devices and Radiological Health (CDRH) is to review the information provided by manufacturers so that it can promote and protect the health of the public by ensuring the safety and effectiveness of medical devices deemed appropriate for human use (Food, Drug & Cosmetic Act, Section 903(b)(1, 2(C)), December 31, 2004; accessed December 17, 2008 http://www.fda.gov/opacom/laws/fdcact/fdctoc.htm). For high-risk devices, such as ventricular assist devices (VADs), mechanical heart valves, stents, cardiac resynchronization therapy (CRT) devices, pacemakers, and defibrillators, the determination is based on FDA's review of extensive preclinical bench and animal testing followed by use of the device in a clinical trial in humans. These clinical trials allow the manufacturer to evaluate a device in the intended use population. FDA reviews the data from the clinical trial to determine if the device performed as predicted and the clinical benefits outweigh the risks. This article reviews the regulatory framework for different marketing applications related to cardiovascular devices and describes the process of obtaining approval to study a cardiovascular device in a U.S. clinical trial.

The Post-Myocardial Infarction Pacing Remodeling Prevention Therapy (PRomPT) Trial: Design and Rationale.

PubMed

Chung, Eugene S; Fischer, Trent M; Kueffer, Fred; Anand, Inder S; Bax, Jeroen J; Gold, Michael R; Gorman, Robert C; Theres, Heinz; Udelson, James E; Stancak, Branislav; Svendsen, Jesper H; Stone, Gregg W; Leon, Angel

2015-07-01

Despite considerable improvements in the medical management of patients with myocardial infarction (MI), patients with large MI still have substantial risk of developing heart failure. In the early post-MI setting, implantable cardioverter defibrillators have reduced arrhythmic deaths but have no impact on overall mortality. Therefore, additional interventions are required to further reduce the overall morbidity and mortality of patients with large MI. The Pacing Remodeling Prevention Therapy (PRomPT) trial is designed to study the effects of peri-infarct pacing in preventing adverse post-MI remodeling. Up to 120 subjects with peak creatine phosphokinase >3,000 U/L (or troponin T >10 μg/L) at time of MI will be randomized to either dual-site or single-site biventricular pacing with the left ventricular lead implanted in a peri-infarct region or to a nonimplanted control group. Those randomized to a device will be blinded to the pacing mode, but randomization to a device or control cannot be blinded. Subjects randomized to pacing will have the device implanted within 10 days of MI. The primary objective is to assess the change in left ventricular end-diastolic volume from baseline to 18 months. Secondary objectives are to assess changes in clinical and mechanistic parameters between the groups, including rates of hospitalization for heart failure and cardiovascular events, the incidence of sudden cardiac death and all-cause mortality, New York Heart Association functional class, 6-minute walking distance, and quality of life. The PRomPT trial will provide important evidence regarding the potential of peri-infarct pacing to interrupt adverse remodeling in patients with large MI. Copyright © 2015 Elsevier Inc. All rights reserved.

Evolution of endovascular stroke therapies and devices.

PubMed

Wallace, Adam N; Kansagra, Akash P; McEachern, James; Moran, Christopher J; Cross, Dewitte T; Derdeyn, Colin P

2016-01-01

Acute ischemic stroke is caused by occlusion of a cerebral artery, resulting in loss of brain tissue and neurologic deficits. However, a portion of the ischemic brain can be salvaged if blood flow is restored within an appropriate time frame. The past year has seen the publication of five positive randomized controlled trials demonstrating substantial benefit of mechanical thrombectomy in select patients with large vessel cerebrovascular occlusion. This progress is related to several factors, but most importantly, dramatic improvements in speed and rates of recanalization with the latest generation devices. In this article, we review the evolution of endovascular acute ischemic stroke therapies and key design features of the most widely used devices.

Clinical trials in peripheral vascular disease: pipeline and trial designs: an evaluation of the ClinicalTrials.gov database.

PubMed

Subherwal, Sumeet; Patel, Manesh R; Chiswell, Karen; Tidemann-Miller, Beth A; Jones, W Schuyler; Conte, Michael S; White, Christopher J; Bhatt, Deepak L; Laird, John R; Hiatt, William R; Tasneem, Asba; Califf, Robert M

2014-11-11

Tremendous advances have occurred in therapies for peripheral vascular disease (PVD); until recently, however, it has not been possible to examine the entire clinical trial portfolio of studies for the treatment of PVD (both arterial and venous disease). We examined interventional trials registered in ClinicalTrials.gov from October 2007 through September 2010 (n=40,970) and identified 676 (1.7%) PVD trials (n=493 arterial only, n=170 venous only, n=13 both arterial and venous). Most arterial studies investigated lower-extremity peripheral artery disease and acute stroke (35% and 24%, respectively), whereas most venous studies examined deep vein thrombosis/pulmonary embolus prevention (42%) or venous ulceration (25%). A placebo-controlled trial design was used in 27% of the PVD trials, and 4% of the PVD trials excluded patients >65 years of age. Enrollment in at least 1 US site decreased from 51% of trials in 2007 to 41% in 2010. Compared with noncardiology disciplines, PVD trials were more likely to be double-blinded, to investigate the use of devices and procedures, and to have industry sponsorship and assumed funding source, and they were less likely to investigate drug and behavioral therapies. Geographic access to PVD clinical trials within the United States is limited to primarily large metropolitan areas. PVD studies represent a small group of trials registered in ClinicalTrials.gov, despite the high prevalence of vascular disease in the general population. This low number, compounded by the decreasing number of PVD trials in the United States, is concerning and may limit the ability to inform current clinical practice of patients with PVD. © 2014 American Heart Association, Inc.

It’s Only a Little Ice

PubMed Central

2012-01-01

First, parallels are drawn between the conduct of clinical trials and a few events in history that share a management style known as “top-down” management or a hierarchal decision-making process. The author suggests that this process isolates investigative sites from sponsors and contributes to the failure of clinical trials. Trial design, patient recruitment, site selection, the use of electronic data devices, and enrollment timelines are examined in greater detail. Suggestions for a more open or shared process are offered, with the belief that fewer trials might fail and fewer questions might remain in the case of those that do. Next, in the companion commentary, some of the problems arising in drug development and clinical trials are mentioned along with a partial listing of solution providers. An outline of circumstances involved in the decision-making process in drug development are presented along with some factors leading to decreased signal detection. PMID:22468240

Successive and discrete spaced conditioning in active avoidance learning in young and aged zebrafish.

PubMed

Yang, Peng; Kajiwara, Riki; Tonoki, Ayako; Itoh, Motoyuki

2018-05-01

We designed an automated device to study active avoidance learning abilities of zebrafish. Open source tools were used for the device control, statistical computing, and graphic outputs of data. Using the system, we developed active avoidance tests to examine the effects of trial spacing and aging on learning. Seven-month-old fish showed stronger avoidance behavior as measured by color preference index with discrete spaced training as compared to successive spaced training. Fifteen-month-old fish showed a similar trend, but with reduced cognitive abilities compared with 7-month-old fish. Further, in 7-month-old fish, an increase in learning ability during trials was observed with discrete, but not successive, spaced training. In contrast, 15-month-old fish did not show increase in learning ability during trials. Therefore, these data suggest that discrete spacing is more effective for learning than successive spacing, with the zebrafish active avoidance paradigm, and that the time course analysis of active avoidance using discrete spaced training is useful to detect age-related learning impairment. Copyright © 2017 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

Design and Implementation of User-Created Information Systems with Mobile RFID

NASA Astrophysics Data System (ADS)

Lee, Jae Kwoen; Chin, Sungho; Kim, Hee Cheon; Chung, Kwang Sik

RFID (Radio Frequency Identification) has been usually applied at physical distribution field. The Mobile RFID can be the only technology that we can lead the market. In our country, ETRI standardizes MOBION (MOBile Identification ON), and the mobile-telecommunication companies provide the trial-mobile RFID service from 2006. In the trial-mobile RFID services, the Broker model is used to decode the mobile RFID code. However, the Broker model has some problems, such as communication overhead caused by the frequent ODS query, service performance, and various services for users. In this paper, we developed device application that is capable for filtering unrelated code from RFID service to improve the decoding performance. We also improve the performance through simplifying connection process between device application and the broker. Finally, we propose and develop the user-created information system to widely distribute the Mobile RFID service.

Traceable working standards with SI units of radiance for characterizing the measurement performance of investigational clinical NIRF imaging devices

NASA Astrophysics Data System (ADS)

Zhu, Banghe; Rasmussen, John C.; Litorja, Maritoni; Sevick-Muraca, Eva M.

2017-03-01

All medical devices for Food and Drug market approval require specifications of performance based upon International System of Units (SI) or units derived from SI for reasons of traceability. Recently, near-infrared fluorescence (NIRF) imaging devices of a variety of designs have emerged on the market and in investigational clinical studies. Yet the design of devices used in the clinical studies vary widely, suggesting variable device performance. Device performance depends upon optimal excitation of NIRF imaging agents, rejection of backscattered excitation and ambient light, and selective collection of fluorescence emanating from the fluorophore. There remains no traceable working standards with SI units of radiance to enable prediction that a given molecular imaging agent can be detected in humans by a given NIRF imaging device. Furthermore, as technologies evolve and as NIRF imaging device components change, there remains no standardized means to track device improvements over time and establish clinical performance without involving clinical trials, often costly. In this study, we deployed a methodology to calibrate luminescent radiance of a stable, solid phantom in SI units of mW/cm2/sr for characterizing the measurement performance of ICCD and IsCMOS camera based NIRF imaging devices, such as signal-to-noise ratio (SNR) and contrast. The methodology allowed determination of superior SNR of the ICCD over the IsCMOS system; comparable contrast of ICCD and IsCMOS depending upon binning strategies.

Incentivizing Orphan Product Development: United States Food and Drug Administration Orphan Incentive Programs.

PubMed

Le, Tran T

2017-01-01

Over 30 years ago, the United States (US) Congress passed the Orphan Drug Act (ODA) to encourage the development of products for rare diseases or conditions ("orphan products"). The Act provided incentives to sponsors for developing products with orphan designation and established a grant program to fund studies of orphan products. Since its enactment in 1983, the ODA has been credited for bringing more than 590 orphan drugs to the market, inspiring the implementation of orphan legislation globally, and enabling the creation of other programs that extend existing knowledge of the natural history of rare diseases and stimulate the development of medical devices for children and patients with rare diseases. This chapter provides a brief overview of the main features and successes of 5 of the orphan incentive programs administered by the US Food and Drug Administration (FDA): the Orphan Drug Designation Program, the Humanitarian Use Device (HUD) Designation Program, the Orphan Products Clinical Trials Grants Program, the Pediatric Device Consortia (PDC) Grant Program, and the Orphan Products Natural History Grants Program.

Pictures and text in instructions for medical devices: effects on recall and actual performance.

PubMed

Kools, Marieke; van de Wiel, Margaretha W J; Ruiter, Robert A C; Kok, Gerjo

2006-12-01

The present study aimed to contribute to the design of effective health education information. Based on cognitive-psychological theory, pictures were expected to improve understanding of two existing textual instructions for using asthma devices (inhaler chamber and peak flow meter). From an analysis of the affordances and constraints of both devices this effect was expected to be stronger with the inhaler chamber than with the peak flow meter. To test this, both instructions were systematically illustrated with seven line-drawings visualizing the actions. In two separate randomized controlled trials with in total 99 participants from the general public, the original text-only versions were compared to the text-picture versions of the same instruction. Dependent variables were participants' recall of the instructions and the quality of their performance with the instruction observed from video-recordings. Conform expectations, the results showed significant positive effects of pictures on recall and performance in both instructions, especially with the inhaler chamber. Thus, pictures may contribute to a better comprehension and use of medical devices that are inherently less clear. Health educators may optimize instruction design by careful analysis of the device with instruction and observational testing with potential users.

The FDA role in contact lens development and safety.

PubMed

Lippman, R E

1990-01-01

The Food and Drug Administration (FDA) exercises a multifaceted role in fulfilling its mission of enforcing the Federal Food, Drug and Cosmetic Act (Act), functioning not only as industry regulator and consumer protector, but also as scientific advisor and consumer educator regarding medical devices, drugs, foods, cosmetics, and veterinary medicine. Medical devices are regulated within the Center for Devices and Radiological Health. Contact lenses are regulated under the authority of the medical device amendments. The Center is responsible for promulgating regulations, publishing guidelines, and developing written guidance in enforcing the Act, and also for guiding manufacturers of medical devices in safe and effective product development. Other components deal with the compliance of manufacturers with the marketing of medical devices within the meaning of the Act, and through labeling requirements of the Act and consumer education and informational activities. As for contact lenses, the process of updating product development regulations and guidelines is an ongoing activity. The most recent version of the Contact Lens Guideline Document, issued in April 1988, contains two major revisions involving preclinical and clinical testing. The first redefines plastics into one materials category, thus reducing testing requirements with respect to animal toxicology studies and other preclinical areas. The second revision restricts clinical testing requirements to allow confirmatory trials in applications for new daily wear lenses. The intention was to maintain the ability of studies to detect major material or design flaws in lenses, thus boosting confidence in their performance while eliminating unnecessary trials.(ABSTRACT TRUNCATED AT 250 WORDS)

Custom-made titanium devices as membranes for bone augmentation in implant treatment: Clinical application and the comparison with conventional titanium mesh.

PubMed

Sumida, Tomoki; Otawa, Naruto; Kamata, Y U; Kamakura, Satoshi; Mtsushita, Tomiharu; Kitagaki, Hisashi; Mori, Shigeo; Sasaki, Kiyoyuki; Fujibayashi, Shunsuke; Takemoto, Mitsuru; Yamaguchi, Atsushi; Sohmura, Taiji; Nakamura, Takashi; Mori, Yoshihide

2015-12-01

Development of new custom-made devices to reconstruct alveolar bone for implantation, and comparison with conventional methods were the goals of this study. Using a computer-aided design technique, three-dimensional images were constructed. From these data, custom-made devices were produced by a selective laser melting method with pure titanium. Clinical trials also have been conducted with 26 participants who needed bone reconstruction before implantation; they were divided into 2 groups with 13 patients each. The first group uses custom-made devices; the other uses commercial titanium meshes that need to bend during operation. Some clinical aspects are evaluated after the trial. The custom-made devices can be produced closely by following the data precisely. Devices are fit for bone defect site. Moreover, the operation time of the custom-made group (75.4 ± 11.6 min) was significantly shorter than that of the conventional group (111.9 ± 17.8 min) (p < 0.01). Mucosal rupture occurs, without significant difference (p = 0.27), in a patient in the custom-made without severe infection (7.7%), and 3 in conventional (23.1%), respectively. The retaining screw is significantly fewer in the custom-made group than commercial mesh group (p < 0.01). These results indicate that our novel protocol could be simple and safe for providing powerful support for guided bone regeneration. Copyright © 2015 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Challenges of recording human fetal auditory-evoked response using magnetoencephalography.

PubMed

Eswaran, H; Lowery, C L; Robinson, S E; Wilson, J D; Cheyne, D; McKenzie, D

2000-01-01

Our goals were to successfully perform fetal auditory-evoked responses using the magnetoencephalography technique, understand its problems and limitations, and propose instrument design modifications to improve the signal quality and success rate. Fetal auditory-evoked responses were recorded from four fetuses with gestational ages ranging from 33-40+ weeks. The signals were recorded using a gantry-based superconducting quantum interference device. Auditory stimulus was 1 kHz tone burst. The evoked signals were digitized and averaged over an 800 ms window. After several trials of positioning and repositioning the subjects, we were able to record auditory-evoked responses in three out of the four fetuses. Since the superconducting quantum interference device array design was not shaped to fit over the mother's abdomen, we experienced difficulty in positioning the sensors over the fetal head. Based on this pilot study, we propose instrument design that may improve signal quality and success rate of the fetal magnetic auditory-evoked response.

The Methodology of Clinical Studies Used by the FDA for Approval of High-Risk Orthopaedic Devices.

PubMed

Barker, Jordan P; Simon, Stephen D; Dubin, Jonathan

2017-05-03

The purpose of this investigation was to examine the methodology of clinical trials used by the U.S. Food and Drug Administration (FDA) to determine the safety and effectiveness of high-risk orthopaedic devices approved between 2001 and 2015. Utilizing the FDA's online public database, this systematic review audited study design and methodological variables intended to minimize bias and confounding. An additional analysis of blinding as well as the Checklist to Evaluate a Report of a Nonpharmacological Trial (CLEAR NPT) was applied to the randomized controlled trials (RCTs). Of the 49 studies, 46 (94%) were prospective and 37 (76%) were randomized. Forty-seven (96%) of the studies were controlled in some form. Of 35 studies that reported it, blinding was utilized in 21 (60%), of which 8 (38%) were reported as single-blinded and 13 (62%) were reported as double-blinded. Of the 37 RCTs, outcome assessors were clearly blinded in 6 (16%), whereas 15 (41%) were deemed impossible to blind as implants could be readily discerned on imaging. When the CLEAR NPT was applied to the 37 RCTs, >70% of studies were deemed "unclear" in describing generation of allocation sequences, treatment allocation concealment, and adequate blinding of participants and outcome assessors. This study manifests the highly variable reporting and strength of clinical research methodology accepted by the FDA to approve high-risk orthopaedic devices.

Advanced Sensor Arrays and Packaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ryter, John Wesley; Romero, Christopher J.; Ramaiyan, Kannan

2016-08-11

Novel sensor packaging elements were designed, fabricated, and tested in order to facilitate the transition of electrochemical mixed-potential sensors toward commercialization. Of the two designs completed, the first is currently undergoing field trials, taking direct measurements within vehicle exhaust streams, while the second is undergoing preliminary laboratory testing. The sensors’ optimal operating conditions, sensitivity to hydrogen, and long-­term baseline stability were also investigated. The sensing capabilities of lanthanum chromite (La 0.8Sr 0.2CrO 3) and indium-­doped tin oxide (ITO) working electrodes were compared, and the ITO devices were selected for pre-­commercial field trials testing at a hydrogen fuel cell vehicle fuelingmore » station in California. Previous data from that fueling station were also analyzed, and the causes of anomalous baseline drift were identified.« less

Comparing performance of mothers using simplified mid-upper arm circumference (MUAC) classification devices with an improved MUAC insertion tape in Isiolo County, Kenya.

PubMed

Grant, Angeline; Njiru, James; Okoth, Edgar; Awino, Imelda; Briend, André; Murage, Samuel; Abdirahman, Saida; Myatt, Mark

2018-01-01

A novel approach for improving community case-detection of acute malnutrition involves mothers/caregivers screening their children for acute malnutrition using a mid-upper arm circumference (MUAC) insertion tape. The objective of this study was to test three simple MUAC classification devices to determine whether they improved the sensitivity of mothers/caregivers at detecting acute malnutrition. Prospective, non-randomised, partially-blinded, clinical diagnostic trial describing and comparing the performance of three "Click-MUAC" devices and a MUAC insertion tape. The study took place in twenty-one health facilities providing integrated management of acute malnutrition (IMAM) services in Isiolo County, Kenya. Mothers/caregivers classified their child ( n =1040), aged 6-59 months, using the "Click-MUAC" devices and a MUAC insertion tape. These classifications were compared to a "gold standard" classification (the mean of three measurements taken by a research assistant using the MUAC insertion tape). The sensitivity of mother/caregiver classifications was high for all devices (>93% for severe acute malnutrition (SAM), defined by MUAC < 115 mm, and > 90% for global acute malnutrition (GAM), defined by MUAC < 125 mm). Mother/caregiver sensitivity for SAM and GAM classification was higher using the MUAC insertion tape (100% sensitivity for SAM and 99% sensitivity for GAM) than using "Click-MUAC" devices. Younden's J for SAM classification, and sensitivity for GAM classification, were significantly higher for the MUAC insertion tape (99% and 99% respectively). Specificity was high for all devices (>96%) with no significant difference between the "Click-MUAC" devices and the MUAC insertion tape. The results of this study indicate that, although the "Click-MUAC" devices performed well, the MUAC insertion tape performed best. The results for sensitivity are higher than found in previous studies. The high sensitivity for both SAM and GAM classification by mothers/caregivers with the MUAC insertion tape could be due to the use of an improved MUAC tape design which has a number of new design features. The one-on-one demonstration provided to mothers/caregivers on the use of the devices may also have helped improve sensitivity. The results of this study provide evidence that mothers/caregivers can perform sensitive and specific classifications of their child's nutritional status using MUAC. Clinical trials registration number: NCT02833740.

Trialing a Tablet PC Based Language Test

ERIC Educational Resources Information Center

Litzler, Mary Frances; Garcia Laborda, Jesus

2015-01-01

Designing tests is a sophisticated task due to issues such as rubrics, validation and impact. Delivery has become another key issue in recent years. Recent research projects in Spain (García Laborda et al.s, 2010, García Laborda, 2012; García Laborda et al., 2014; Bueno Alastuey et al., 2014) have been working mainly with technological devices as…

Characterizing the Utility and Limitations of Repurposing an Open-Field Optical Imaging Device for Fluorescence-Guided Surgery in Head and Neck Cancer Patients.

PubMed

Moore, Lindsay S; Rosenthal, Eben L; Chung, Thomas K; de Boer, Esther; Patel, Neel; Prince, Andrew C; Korb, Melissa L; Walsh, Erika M; Young, E Scott; Stevens, Todd M; Withrow, Kirk P; Morlandt, Anthony B; Richman, Joshua S; Carroll, William R; Zinn, Kurt R; Warram, Jason M

2017-02-01

The purpose of this study was to assess the potential of U.S. Food and Drug Administration-cleared devices designed for indocyanine green-based perfusion imaging to identify cancer-specific bioconjugates with overlapping excitation and emission wavelengths. Recent clinical trials have demonstrated potential for fluorescence-guided surgery, but the time and cost of the approval process may impede clinical translation. To expedite this translation, we explored the feasibility of repurposing existing optical imaging devices for fluorescence-guided surgery. Consenting patients (n = 15) scheduled for curative resection were enrolled in a clinical trial evaluating the safety and specificity of cetuximab-IRDye800 (NCT01987375). Open-field fluorescence imaging was performed preoperatively and during the surgical resection. Fluorescence intensity was quantified using integrated instrument software, and the tumor-to-background ratio characterized fluorescence contrast. In the preoperative clinic, the open-field device demonstrated potential to guide preoperative mapping of tumor borders, optimize the day of surgery, and identify occult lesions. Intraoperatively, the device demonstrated robust potential to guide surgical resections, as all peak tumor-to-background ratios were greater than 2 (range, 2.2-14.1). Postresection wound bed fluorescence was significantly less than preresection tumor fluorescence (P < 0.001). The repurposed device also successfully identified positive margins. The open-field imaging device was successfully repurposed to distinguish cancer from normal tissue in the preoperative clinic and throughout surgical resection. This study illuminated the potential for existing open-field optical imaging devices with overlapping excitation and emission spectra to be used for fluorescence-guided surgery. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

A glucose meter evaluation co-designed with both health professional and consumer input.

PubMed

Thompson, Harmony; Chan, Huan; Logan, Florence J; Heenan, Helen F; Taylor, Lynne; Murray, Chris; Florkowski, Christopher M; Frampton, Christopher M A; Lunt, Helen

2013-11-22

Health consumer's input into assessment of medical device safety is traditionally given either as part of study outcome (trial participants) or during post marketing surveillance. Direct consumer input into the methodological design of device assessment is less common. We discuss the difference in requirements for assessment of a measuring device from the consumer and clinician perspectives, using the example of hand held glucose meters. Around 80,000 New Zealanders with diabetes recently changed their glucose meter system, to enable ongoing access to PHARMAC subsidised meters and strips. Consumers were most interested in a direct comparison of their 'old' meter system (Accu-Chek Performa) with their 'new' meter system (CareSens brand, including the CareSens N POP), rather than comparisons against a laboratory standard. This direct comparison of meter/strip systems showed that the CareSens N POP meter read around 0.6 mmol/L higher than the Performa system. Whilst this difference is unlikely to result in major errors in clinical decision making such as major insulin dosing errors, this information is nevertheless of interest to consumers who switched meters so that they could maintain access to PHARMAC subsidised meters and strips. We recommend that when practical, the consumer perspective be incorporated into study design related to medical device assessment.

Design of a single-arm clinical trial of regenerative therapy by periurethral injection of adipose-derived regenerative cells for male stress urinary incontinence in Japan: the ADRESU study protocol.

PubMed

Shimizu, Shinobu; Yamamoto, Tokunori; Nakayama, Shinobu; Hirakawa, Akihiro; Kuwatsuka, Yachiyo; Funahashi, Yasuhito; Matsukawa, Yoshihisa; Takanari, Keisuke; Toriyama, Kazuhiro; Kamei, Yuzuru; Narimoto, Kazutaka; Yamanishi, Tomonori; Ishizuka, Osamu; Mizuno, Masaaki; Gotoh, Momokazu

2017-09-25

Male stress urinary incontinence is a prevalent condition after radical prostatectomy. While the standard recommendation for the management of urine leakage is pelvic floor muscle training, its efficacy is still unsatisfactory. Therefore, we have focused on regenerative therapy, which consists of administering a periurethral injection of autologous regenerative cells from adipose tissue, separated using the Celution® system. Based on an interim data analysis of our exploratory study, we confirmed the efficacy and acceptable safety profile of this treatment. Accordingly, we began discussions with Japanese regulatory authorities regarding the development of this therapy in Japan. The Ministry of Health, Labour and Welfare suggested that we implement a clinical trial of a new medical device based on the Pharmaceutical Affaires Act in Japan. Next, we discussed the design of this investigator-initiated clinical trial (the ADRESU study) aimed at evaluating the efficacy and safety of this therapy, in a consultation meeting with the Pharmaceuticals and Medical Device Agency. The ADRESU study is an open-label, multi-center, single-arm study involving a total of 45 male stress urinary incontinence patients with mild-to-moderate urine leakage persisting more than 1 year after prostatectomy, in spite of behavioral and pharmacological therapies. The primary endpoint is the rate of patients at 52 weeks with improvement of urine leakage volume defined as a reduction from baseline greater than 50% by 24-h pad test. Our specific hypothesis is that the primary endpoint result will be higher than a pre-specified threshold of 10%. The ADRESU study is the first clinical trial of regenerative treatment for stress urinary incontinence by adipose-derived regenerative cells using the Celution® system based on the Japanese Pharmaceutical Affaires Act. We will evaluate the efficacy and safety in this trial to provide an adequate basis for marketing approval with the final objective of making this novel therapy widely available for Japanese patients. This trial was registered at the University Hospital Medical information Network Clinical Trial Registry (UMIN-CTR Unique ID: UMIN000017901 ; Registered July 1, 2015) and at ClinicalTrials.gov (ClinicalTrials.gov Identifier: NCT02529865 ; Registered August 18, 2015).

Statistical inference on censored data for targeted clinical trials under enrichment design.

PubMed

Chen, Chen-Fang; Lin, Jr-Rung; Liu, Jen-Pei

2013-01-01

For the traditional clinical trials, inclusion and exclusion criteria are usually based on some clinical endpoints; the genetic or genomic variability of the trial participants are not totally utilized in the criteria. After completion of the human genome project, the disease targets at the molecular level can be identified and can be utilized for the treatment of diseases. However, the accuracy of diagnostic devices for identification of such molecular targets is usually not perfect. Some of the patients enrolled in targeted clinical trials with a positive result for the molecular target might not have the specific molecular targets. As a result, the treatment effect may be underestimated in the patient population truly with the molecular target. To resolve this issue, under the exponential distribution, we develop inferential procedures for the treatment effects of the targeted drug based on the censored endpoints in the patients truly with the molecular targets. Under an enrichment design, we propose using the expectation-maximization algorithm in conjunction with the bootstrap technique to incorporate the inaccuracy of the diagnostic device for detection of the molecular targets on the inference of the treatment effects. A simulation study was conducted to empirically investigate the performance of the proposed methods. Simulation results demonstrate that under the exponential distribution, the proposed estimator is nearly unbiased with adequate precision, and the confidence interval can provide adequate coverage probability. In addition, the proposed testing procedure can adequately control the size with sufficient power. On the other hand, when the proportional hazard assumption is violated, additional simulation studies show that the type I error rate is not controlled at the nominal level and is an increasing function of the positive predictive value. A numerical example illustrates the proposed procedures. Copyright © 2013 John Wiley & Sons, Ltd.

Three-dimensional printed upper-limb prostheses lack randomised controlled trials: A systematic review

PubMed Central

Diment, Laura E; Thompson, Mark S; Bergmann, Jeroen HM

2017-01-01

Background: Three-dimensional printing provides an exciting opportunity to customise upper-limb prostheses. Objective: This review summarises the research that assesses the efficacy and effectiveness of three-dimensional printed upper-limb prostheses. Study design: Systematic review. Methods: PubMed, Web of Science and OVID were systematically searched for studies that reported human trials of three-dimensional printed upper-limb prostheses. The studies matching the language, peer-review and relevance criteria were ranked by level of evidence and critically appraised using the Downs and Black Quality Index. Results: After removing duplicates, 321 records were identified. Eight papers met the inclusion criteria. No studies used controls; five were case studies and three were small case-series studies. All studies showed promising results, but none demonstrated external validity, avoidance of bias or statistically significant improvements over conventional prostheses. The studies demonstrated proof-of-concept rather than assessing efficacy, and the devices were designed to prioritise reduction of manufacturing costs, not customisability for comfort and function. Conclusion: The potential of three-dimensional printing for individual customisation has yet to be fully realised, and the efficacy and effectiveness to be rigorously assessed. Until randomised controlled trials with follow-up are performed, the comfort, functionality, durability and long-term effects on quality of life remain unknown. Clinical relevance Initial studies suggest that three-dimensional printing shows promise for customising low-cost upper-limb prosthetics. However, the efficacy and effectiveness of these devices have yet to be rigorously assessed. Until randomised controlled trials with follow-up are performed, the comfort, functionality, durability and long-term effects on patient quality of life remain unknown. PMID:28649911

Sea trials of a ducted tip propeller designed for improved cavitation performance

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hordnes, I.; Bidaud, A.; Green, S.I.

1994-12-31

Studies have shown that ``ring-wing`` or ``ducted`` tip devices reduce substantially the inception index of trailing vortices generated by a hydrofoil (Green et al. 1988). It has also been shown that these devices improve the lift/drag ratio of an airfoil at high angle of incidence (Duan et al. 1992). These finding indicate that there may be a marine application for the ducted tip. Experimental equipment has been designed and manufactured in preparation for upcoming tests of a propeller with ducted tips. The tips are tubes aligned with the propeller blade tips that will replace a radial fraction of the originalmore » blade tips equal to the diameter of the tubes. The tube dimensions have been chosen according to the span/tip diameter and chord/tip length ratios used by Duan et al. (1992), and the tubes will be given a curvature equal to the propeller tip radius. Field trials will be given a curvature equal to the propeller tip radius. Field trials will be conducted on a 36 inch diameter propeller that is used to propel a 45 ft. fishing (seine) boat operating in the coastal waters outside Vancouver. The performance of the propeller will be measured in terms of the propeller efficiency as a function of advance ratio. A special force transducer has been designed that is capable of recording both torque and thrust on the propeller shaft even though these are expected to produce shaft strains of different orders of magnitude. As a supplementary means of monitoring the propeller performance, a hydrophone will be located near the propeller wake in order to measure the tip vortex cavitation noise.« less

Effects of standard training in the use of closed-circuit televisions in visually impaired adults: design of a training protocol and a randomized controlled trial

PubMed Central

2010-01-01

Background Reading problems are frequently reported by visually impaired persons. A closed-circuit television (CCTV) can be helpful to maintain reading ability, however, it is difficult to learn how to use this device. In the Netherlands, an evidence-based rehabilitation program in the use of CCTVs was lacking. Therefore, a standard training protocol needed to be developed and tested in a randomized controlled trial (RCT) to provide an evidence-based training program in the use of this device. Methods/Design To develop a standard training program, information was collected by studying literature, observing training in the use of CCTVs, discussing the content of the training program with professionals and organizing focus and discussion groups. The effectiveness of the program was evaluated in an RCT, to obtain an evidence-based training program. Dutch patients (n = 122) were randomized into a treatment group: normal instructions from the supplier combined with training in the use of CCTVs, or into a control group: instructions from the supplier only. The effect of the training program was evaluated in terms of: change in reading ability (reading speed and reading comprehension), patients' skills to operate the CCTV, perceived (vision-related) quality of life and tasks performed in daily living. Discussion The development of the CCTV training protocol and the design of the RCT in the present study may serve as an example to obtain an evidence-based training program. The training program was adjusted to the needs and learning abilities of individual patients, however, for scientific reasons it might have been preferable to standardize the protocol further, in order to gain more comparable results. Trial registration http://www.trialregister.nl, identifier: NTR1031 PMID:20219120

Safety and effectiveness of the INVATEC MO.MA proximal cerebral protection device during carotid artery stenting: results from the ARMOUR pivotal trial.

PubMed

Ansel, Gary M; Hopkins, L Nelson; Jaff, Michael R; Rubino, Paolo; Bacharach, J Michael; Scheinert, Dierk; Myla, Subbarao; Das, Tony; Cremonesi, Alberto

2010-07-01

The multicenter ARMOUR (ProximAl PRotection with the MO.MA Device DUring CaRotid Stenting) trial evaluated the 30-day safety and effectiveness of the MO.MA Proximal Cerebral Protection Device (Invatec, Roncadelle, Italy) utilized to treat high surgical risk patients undergoing carotid artery stenting (CAS). Distal embolic protection devices (EPD) have been traditionally utilized during CAS. The MO.MA device acts as a balloon occlusion "endovascular clamping" system to achieve cerebral protection prior to crossing the carotid stenosis. This prospective registry enrolled 262 subjects, 37 roll-in and 225 pivotal subjects evaluated with intention to treat (ITT) from September 2007 to February 2009. Subjects underwent CAS using the MO.MA device. The primary endpoint, myocardial infarction, stroke, or death through 30 days (30-day major adverse cardiac and cerebrovascular events [MACCE]) was compared to a performance goal of 13% derived from trials utilizing distal EPD. For the ITT population, the mean age was 74.7 years with 66.7% of the cohort being male. Symptomatic patients comprised 15.1% and 28.9% were octogenarians. Device success was 98.2% and procedural success was 93.2%. The 30-day MACCE rate was 2.7% [95% CI (1.0-5.8%)] with a 30-day major stroke rate of 0.9%. No symptomatic patient suffered a stroke during this trial. The ARMOUR trial demonstrated that the MO.MA(R) Proximal Cerebral Protection Device is safe and effective for high surgical risk patients undergoing CAS. The absence of stroke in symptomatic patients is the lowest rate reported in any independently adjudicated prospective multicenter registry trial to date. (c) 2010 Wiley-Liss, Inc.

Barriers to investigator-initiated deep brain stimulation and device research

PubMed Central

Malone, Donald; Okun, Michael S.; Booth, Joan; Machado, Andre G.

2014-01-01

The success of device-based research in the clinical neurosciences has overshadowed a critical and emerging problem in the biomedical research environment in the United States. Neuroprosthetic devices, such as deep brain stimulation (DBS), have been shown in humans to be promising technologies for scientific exploration of neural pathways and as powerful treatments. Large device companies have, over the past several decades, funded and developed major research programs. However, both the structure of clinical trial funding and the current regulation of device research threaten investigator-initiated efforts in neurologic disorders. The current atmosphere dissuades clinical investigators from pursuing formal and prospective research with novel devices or novel indications. We review our experience in conducting a federally funded, investigator-initiated, device-based clinical trial that utilized DBS for thalamic pain syndrome. We also explore barriers that clinical investigators face in conducting device-based clinical trials, particularly in early-stage studies or small disease populations. We discuss 5 specific areas for potential reform and integration: (1) alternative pathways for device approval; (2) eliminating right of reference requirements; (3) combining federal grant awards with regulatory approval; (4) consolidation of oversight for human subjects research; and (5) private insurance coverage for clinical trials. Careful reformulation of regulatory policy and funding mechanisms is critical for expanding investigator-initiated device research, which has great potential to benefit science, industry, and, most importantly, patients. PMID:24670888

Development of a real-time repeated-measures assessment protocol to capture change over the course of a drinking episode.

PubMed

Luczak, Susan E; Rosen, I Gary; Wall, Tamara L

2015-03-01

We report on the development of a real-time assessment protocol that allows researchers to assess change in BrAC, alcohol responses, behaviors, and contexts over the course of a drinking event. We designed a web application that uses timed text messages (adjusted based on consumption pattern) containing links to our website to obtain real-time participant reports; camera and location features were also incorporated into the protocol. We used a transdermal alcohol sensor device along with software we designed to convert transdermal data into estimated BrAC. Thirty-two college students completed a laboratory session followed by a 2-week field trial. Results for the web application indicated we were able to create an effective tool for obtaining repeated measures real-time drinking data. Participants were willing to monitor their drinking behavior with the web application, and this did not appear to strongly affect drinking behavior during, or 6 weeks following, the field trial. Results for the transdermal device highlighted the willingness of participants to wear the device despite some discomfort, but technical difficulties resulted in limited valid data. The development of this protocol makes it possible to capture detailed assessment of change over the course of naturalistic drinking episodes. Published by Oxford University Press on behalf of Medical Council on Alcohol 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Accurate measurement of chest compression depth using impulse-radio ultra-wideband sensor on a mattress

PubMed Central

Kim, Yeomyung

2017-01-01

Objective We developed a new chest compression depth (CCD) measuring technology using radar and impulse-radio ultra-wideband (IR-UWB) sensor. This study was performed to determine its accuracy on a soft surface. Methods Four trials, trial 1: chest compressions on the floor using an accelerometer device; trial 2: chest compressions on the floor using an IR-UWB sensor; trial 3: chest compressions on a foam mattress using an accelerometer device; trial 4: chest compressions on a foam mattress using an IR-UWB sensor, were performed in a random order. In all the trials, a cardiopulmonary resuscitation provider delivered 50 uninterrupted chest compressions to a manikin. Results The CCD measured by the manikin and the device were as follows: 57.42 ± 2.23 and 53.92 ± 2.92 mm, respectively in trial 1 (p < 0.001); 56.29 ± 1.96 and 54.16 ± 3.90 mm, respectively in trial 2 (p < 0.001); 55.61 ± 1.57 and 103.48 ± 10.48 mm, respectively in trial 3 (p < 0.001); 57.14 ± 3.99 and 55.51 ± 3.39 mm, respectively in trial 4 (p = 0.012). The gaps between the CCD measured by the manikin and the devices (accelerometer device vs. IR-UWB sensor) on the floor were not different (3.50 ± 2.08 mm vs. 3.15 ± 2.27 mm, respectively, p = 0.136). However, the gaps were significantly different on the foam mattress (48.53 ± 5.65 mm vs. 4.10 ± 2.47 mm, p < 0.001). Conclusion The IR-UWB sensor could measure the CCD accurately both on the floor and on the foam mattress. PMID:28854262

Accurate measurement of chest compression depth using impulse-radio ultra-wideband sensor on a mattress.

PubMed

Yu, Byung Gyu; Oh, Je Hyeok; Kim, Yeomyung; Kim, Tae Wook

2017-01-01

We developed a new chest compression depth (CCD) measuring technology using radar and impulse-radio ultra-wideband (IR-UWB) sensor. This study was performed to determine its accuracy on a soft surface. Four trials, trial 1: chest compressions on the floor using an accelerometer device; trial 2: chest compressions on the floor using an IR-UWB sensor; trial 3: chest compressions on a foam mattress using an accelerometer device; trial 4: chest compressions on a foam mattress using an IR-UWB sensor, were performed in a random order. In all the trials, a cardiopulmonary resuscitation provider delivered 50 uninterrupted chest compressions to a manikin. The CCD measured by the manikin and the device were as follows: 57.42 ± 2.23 and 53.92 ± 2.92 mm, respectively in trial 1 (p < 0.001); 56.29 ± 1.96 and 54.16 ± 3.90 mm, respectively in trial 2 (p < 0.001); 55.61 ± 1.57 and 103.48 ± 10.48 mm, respectively in trial 3 (p < 0.001); 57.14 ± 3.99 and 55.51 ± 3.39 mm, respectively in trial 4 (p = 0.012). The gaps between the CCD measured by the manikin and the devices (accelerometer device vs. IR-UWB sensor) on the floor were not different (3.50 ± 2.08 mm vs. 3.15 ± 2.27 mm, respectively, p = 0.136). However, the gaps were significantly different on the foam mattress (48.53 ± 5.65 mm vs. 4.10 ± 2.47 mm, p < 0.001). The IR-UWB sensor could measure the CCD accurately both on the floor and on the foam mattress.

Lifestyle intervention using Internet of Things (IoT) for the elderly: A study protocol for a randomized control trial (the BEST-LIFE study).

PubMed

Kato, Sawako; Ando, Masahiko; Kondo, Takaaki; Yoshida, Yasuko; Honda, Hiroyuki; Maruyama, Shoichi

2018-05-01

Modification of lifestyle habits, including diet and physical activity, is essential for the prevention and control of type 2 diabetes mellitus (T2DM) in elderly patients. However, individualized treatment is more critical for the elderly than for general patients. This study aimed to determine lifestyle interventions that resulted in lowering hemoglobin A 1c (HbA 1c ) in Japanese pre- and early diabetic elderly subjects. The BEST-LIFE trial is an ongoing, open-label, 6-month, randomized (1:1) parallel group trial. Subjects with HbA 1c of ≥5.6%-randomly assigned to the intervention or control group -use wearable monitoring devices loaded with Internet of things (IoT) systems that aids them with self-management and obtaining monthly remote health guidance from a public health nurse. The primary outcome is changes in HbA 1c after a 6-month intervention relative to the baseline values. The secondary outcome is the change of behavior modification stages. The background, rationale, and study design of this trial are also presented. One hundred forty-five subjects have already been enrolled in this lifestyle intervention program, which will end in 2019. The BEST-LIFE trial will provide new evidence regarding the effectiveness and safety of our program on lowering HbA 1c in elderly subjects with T2DM. It will also investigate whether information communication technology tools and monitoring devices loaded with IoT can support health care in elderly subjects. The trial registration number is UMIN-CTR: UMIN 000023356.

Underwater Sound Levels at a Wave Energy Device Testing Facility in Falmouth Bay, UK.

PubMed

Garrett, Joanne K; Witt, Matthew J; Johanning, Lars

2016-01-01

Passive acoustic monitoring devices were deployed at FaBTest in Falmouth Bay, UK, a marine renewable energy device testing facility during trials of a wave energy device. The area supports considerable commercial shipping and recreational boating along with diverse marine fauna. Noise monitoring occurred during (1) a baseline period, (2) installation activity, (3) the device in situ with inactive power status, and (4) the device in situ with active power status. This paper discusses the preliminary findings of the sound recording at FabTest during these different activity periods of a wave energy device trial.

Linking quantitative microbial risk assessment and epidemiological data: informing safe drinking water trials in developing countries.

PubMed

Enger, Kyle S; Nelson, Kara L; Clasen, Thomas; Rose, Joan B; Eisenberg, Joseph N S

2012-05-01

Intervention trials are used extensively to assess household water treatment (HWT) device efficacy against diarrheal disease in developing countries. Using these data for policy, however, requires addressing issues of generalizability (relevance of one trial in other contexts) and systematic bias associated with design and conduct of a study. To illustrate how quantitative microbial risk assessment (QMRA) can address water safety and health issues, we analyzed a published randomized controlled trial (RCT) of the LifeStraw Family Filter in the Congo. The model accounted for bias due to (1) incomplete compliance with filtration, (2) unexpected antimicrobial activity by the placebo device, and (3) incomplete recall of diarrheal disease. Effectiveness was measured using the longitudinal prevalence ratio (LPR) of reported diarrhea. The Congo RCT observed an LPR of 0.84 (95% CI: 0.61, 1.14). Our model predicted LPRs, assuming a perfect placebo, ranging from 0.50 (2.5-97.5 percentile: 0.33, 0.77) to 0.86 (2.5-97.5 percentile: 0.68, 1.09) for high (but not perfect) and low (but not zero) compliance, respectively. The calibration step provided estimates of the concentrations of three pathogen types (modeled as diarrheagenic E. coli, Giardia, and rotavirus) in drinking water, consistent with the longitudinal prevalence of reported diarrhea measured in the trial, and constrained by epidemiological data from the trial. Use of a QMRA model demonstrated the importance of compliance in HWT efficacy, the need for pathogen data from source waters, the effect of quantifying biases associated with epidemiological data, and the usefulness of generalizing the effectiveness of HWT trials to other contexts. © 2012 American Chemical Society

The feasibility of determining the effectiveness and cost-effectiveness of medication organisation devices compared with usual care for older people in a community setting: systematic review, stakeholder focus groups and feasibility randomised controlled trial.

PubMed

Bhattacharya, Debi; Aldus, Clare F; Barton, Garry; Bond, Christine M; Boonyaprapa, Sathon; Charles, Ian S; Fleetcroft, Robert; Holland, Richard; Jerosch-Herold, Christina; Salter, Charlotte; Shepstone, Lee; Walton, Christine; Watson, Steve; Wright, David J

2016-07-01

Medication organisation devices (MODs) provide compartments for a patient's medication to be organised into the days of the week and the recommended times the medication should be taken. To define the optimal trial design for testing the clinical effectiveness and cost-effectiveness of MODs. The feasibility study comprised a systematic review and focus groups to inform a randomised controlled trial (RCT) design. The resulting features were tested on a small scale, using a 2 × 2 factorial design to compare MODs with usual packaging and to compare weekly with monthly supply. The study design was then evaluated. Potential participants were identified by medical practices. Aged over 75 years, prescribed at least three solid oral dosage form medications, unintentionally non-adherent and self-medicating. Participants were excluded if deemed by their health-care team to be unsuitable. One of three MODs widely used in routine clinical practice supplied either weekly or monthly. To identify the most effective method of participant recruitment, to estimate the prevalence of intentional and unintentional non-adherence in an older population, to provide a point estimate of the effect size of MODs relative to usual care and to determine the feasibility and acceptability of trial participation. The systematic review included MOD studies of any design reporting medication adherence, health and social outcomes, resource utilisation or dispensing or administration errors. Focus groups with patients, carers and health-care professionals supplemented the systematic review to inform the RCT design. The resulting design was implemented and then evaluated through questionnaires and group discussions with participants and health-care professionals involved in trial delivery. Studies on MODs are largely of poor quality. The relationship between adherence and health outcomes is unclear. Of the limited studies reporting health outcomes, some reported a positive relationship while some reported increased hospitalisations associated with MODs. The pre-trial focus groups endorsed the planned study design, but suggested a minimum recruitment age of 50-60 years. A total of 35.4% of patients completing the baseline questionnaire were excluded because they already used a MOD. Active recruitment yielded a higher consent rate, but passive recruitment was more cost-effective. The prevalence of intentional non-adherence was 24.7% [n = 71, 95% confidence interval (CI) 19.7% to 29.6%] of participants. Of the remaining 76 participants, 46.1% (95% CI 34.8% to 57.3%) were unintentionally non-adherent. There was no indication of a difference in adherence between the study arms. Participants reported a high level of satisfaction with the design. Five adverse/serious adverse events were identified in the MOD study arms and none was identified in the control arms. There was no discernible difference in health economic outcomes between the four study arms; the mean intervention cost was £20 per month greater for MOD monthly relative to usual supply monthly. MOD provision to unintentionally non-adherent older people may cause medication-related adverse events. The primary outcome for a definitive MOD trial should be health outcomes. Such a trial should recruit patients by postal invitation and recruit younger patients. A study examining the association between MOD initiation and adverse effects is necessary and a strategy to safely introduce MODs should be explored. A definitive study testing the clinical effectiveness and cost-effectiveness of MODs is also required. Current Controlled Trials ISRCTN 30626972 and UKCRN 12739. This project was funded by National Institute for Health Research (NIHR) Health Technology Assessment Programme and will be published in full in Health Technology Assessment; Vol. 20, No. 50. See the NIHR Journals Library website for further project information.

Current transcatheter devices to treat functional tricuspid regurgitation with discussion of issues relevant to clinical trial design

PubMed Central

2017-01-01

Functional or secondary tricuspid regurgitation (TR) has seen increased attention in recent times as relationships with clinically-relevant outcomes have come to light. Despite the association of increased mortality with significant TR, the disease remains under-recognized and thus relatively untreated. In addition, the disease itself has not been extensively studied and the interactions between annular dilatation, right heart disease and pulmonary hypertension are poorly understood. However, the high mortality and recurrence rate with current surgical replacement or repair techniques is well recognised, opening the door to transcatheter therapies for functional TR. The current perspective reviews the rationale for transcatheter solutions, describes some of the current approaches and discusses the ongoing questions of a poorly-studied condition which may limit the design of clinical trials for this disease. PMID:28706866

Cost-effectiveness analysis alongside clinical trials II-An ISPOR Good Research Practices Task Force report.

PubMed

Ramsey, Scott D; Willke, Richard J; Glick, Henry; Reed, Shelby D; Augustovski, Federico; Jonsson, Bengt; Briggs, Andrew; Sullivan, Sean D

2015-03-01

Clinical trials evaluating medicines, medical devices, and procedures now commonly assess the economic value of these interventions. The growing number of prospective clinical/economic trials reflects both widespread interest in economic information for new technologies and the regulatory and reimbursement requirements of many countries that now consider evidence of economic value along with clinical efficacy. As decision makers increasingly demand evidence of economic value for health care interventions, conducting high-quality economic analyses alongside clinical studies is desirable because they broaden the scope of information available on a particular intervention, and can efficiently provide timely information with high internal and, when designed and analyzed properly, reasonable external validity. In 2005, ISPOR published the Good Research Practices for Cost-Effectiveness Analysis Alongside Clinical Trials: The ISPOR RCT-CEA Task Force report. ISPOR initiated an update of the report in 2014 to include the methodological developments over the last 9 years. This report provides updated recommendations reflecting advances in several areas related to trial design, selecting data elements, database design and management, analysis, and reporting of results. Task force members note that trials should be designed to evaluate effectiveness (rather than efficacy) when possible, should include clinical outcome measures, and should obtain health resource use and health state utilities directly from study subjects. Collection of economic data should be fully integrated into the study. An incremental analysis should be conducted with an intention-to-treat approach, complemented by relevant subgroup analyses. Uncertainty should be characterized. Articles should adhere to established standards for reporting results of cost-effectiveness analyses. Economic studies alongside trials are complementary to other evaluations (e.g., modeling studies) as information for decision makers who consider evidence of economic value along with clinical efficacy when making resource allocation decisions. Copyright © 2015 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Understanding the C-pulse device and its potential to treat heart failure.

PubMed

Sales, Virna L; McCarthy, Patrick M

2010-03-01

The Sunshine Heart C-Pulse (C-Pulse; Sunshine Heart Inc., Tustin, CA) device is an extra-aortic implantable counterpulsation pump designed as a non-blood contacting ambulatory heart assist device, which may provide relief from symptoms for class II-III congestive heart failure patients. It has a comparable hemodynamic augmentation to intra-aortic balloon counterpulsation devices. The C-Pulse cuff is implanted through a median sternotomy, secured around the ascending aorta, and pneumatically driven by an external system controller. Pre-clinical studies in the acute pig model, and initial temporary clinical studies in patients undergoing off-pump coronary bypass surgery have shown substantial increase in diastolic perfusion of the coronary vessels, which translated to a favorable improvement in ventricular function. A U.S. prospective multi-center trial to evaluate the safety and efficacy of the C-Pulse in class III patients with moderate heart failure is now in progress.

Estimating BrAC from transdermal alcohol concentration data using the BrAC estimator software program.

PubMed

Luczak, Susan E; Rosen, I Gary

2014-08-01

Transdermal alcohol sensor (TAS) devices have the potential to allow researchers and clinicians to unobtrusively collect naturalistic drinking data for weeks at a time, but the transdermal alcohol concentration (TAC) data these devices produce do not consistently correspond with breath alcohol concentration (BrAC) data. We present and test the BrAC Estimator software, a program designed to produce individualized estimates of BrAC from TAC data by fitting mathematical models to a specific person wearing a specific TAS device. Two TAS devices were worn simultaneously by 1 participant for 18 days. The trial began with a laboratory alcohol session to calibrate the model and was followed by a field trial with 10 drinking episodes. Model parameter estimates and fit indices were compared across drinking episodes to examine the calibration phase of the software. Software-generated estimates of peak BrAC, time of peak BrAC, and area under the BrAC curve were compared with breath analyzer data to examine the estimation phase of the software. In this single-subject design with breath analyzer peak BrAC scores ranging from 0.013 to 0.057, the software created consistent models for the 2 TAS devices, despite differences in raw TAC data, and was able to compensate for the attenuation of peak BrAC and latency of the time of peak BrAC that are typically observed in TAC data. This software program represents an important initial step for making it possible for non mathematician researchers and clinicians to obtain estimates of BrAC from TAC data in naturalistic drinking environments. Future research with more participants and greater variation in alcohol consumption levels and patterns, as well as examination of gain scheduling calibration procedures and nonlinear models of diffusion, will help to determine how precise these software models can become. Copyright © 2014 by the Research Society on Alcoholism.

Real-world geographic variations in the use of cardiac implantable electronic devices - The PANORAMA 2 observational cohort study.

PubMed

Bastian, Dirk; Ebrahim, Iftikhar O; Chen, Ju-Yi; Chen, Mien-Cheng; Huang, Dejia; Huang, Jin-Long; Kuznetsov, Vadim A; Maus, Bärbel; Naik, Ajay M; Verhees, Koen J P; Fagih, Ahmed R Al

2018-06-13

Currently, several geographies around the world remain underrepresented in medical device trials. The PANORAMA 2 study was designed to assess contemporary region-specific differences in clinical practice patterns of patients with cardiac implantable electronic devices (CIEDs). In this prospective, multicenter, observational, multi-national study, baseline and implant data of 4,706 patients receiving Medtronic CIEDs (either de novo device implants, replacements, or upgrades) were analyzed, consisting of: 54% implantable pulse generators (IPGs), 20.3% implantable cardiac defibrillators (ICDs), 15% cardiac resynchronization therapy defibrillators (CRT-Ds), 5.1% cardiac resynchronization therapy pacemakers (CRT-Ps), from 117 hospitals in 23 countries across 4 geographical regions between 2012 and 2016. For all device types, in all regions, there were less females than males enrolled, and women were less likely to have ischemic cardiomyopathy. Implant procedure duration differed significantly across the geographies for all device types. Subjects from emerging countries, women and older patients were less likely to receive a magnetic resonance imaging (MRI)-compatible device. Defibrillation testing differed significantly between the regions. European patients had the highest rates of atrial fibrillation (AF), and the lowest number of implanted single-chamber IPGs. Evaluation of stroke history suggested that the general embolic risk is more strongly associated with stroke than AF. We provide comprehensive descriptive data on patients receiving Medtronic CIEDs from several geographies, some of which are understudied in randomized controlled trials (RCTs). We found significant variations in patient characteristics. Several medical decisions appear to be affected by socioeconomic factors. Long-term follow-up data will help evaluate if these variations require adjustments to outcome expectations. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Effectiveness of robot-assisted therapy on ankle rehabilitation--a systematic review.

PubMed

Zhang, Mingming; Davies, T Claire; Xie, Shane

2013-03-21

The aim of this study was to provide a systematic review of studies that investigated the effectiveness of robot-assisted therapy on ankle motor and function recovery from musculoskeletal or neurologic ankle injuries. Thirteen electronic databases of articles published from January, 1980 to June, 2012 were searched using keywords 'ankle*', 'robot*', 'rehabilitat*' or 'treat*' and a free search in Google Scholar based on effects of ankle rehabilitation robots was also conducted. References listed in relevant publications were further screened. Eventually, twenty-nine articles were selected for review and they focused on effects of robot-assisted ankle rehabilitation. Twenty-nine studies met the inclusion criteria and a total of 164 patients and 24 healthy subjects participated in these trials. Ankle performance and gait function were the main outcome measures used to assess the therapeutic effects of robot-assisted ankle rehabilitation. The protocols and therapy treatments were varied, which made comparison among different studies difficult or impossible. Few comparative trials were conducted among different devices or control strategies. Moreover, the majority of study designs met levels of evidence that were no higher than American Academy for Cerebral Palsy (CP) and Developmental Medicine (AACPDM) level IV. Only one study used a Randomized Control Trial (RCT) approach with the evidence level being II. All the selected studies showed improvements in terms of ankle performance or gait function after a period of robot-assisted ankle rehabilitation training. The most effective robot-assisted intervention cannot be determined due to the lack of universal evaluation criteria for various devices and control strategies. Future research into the effects of robot-assisted ankle rehabilitation should be carried out based on universal evaluation criteria, which could determine the most effective method of intervention. It is also essential to conduct trials to analyse the differences among different devices or control strategies.

A comparative analysis of speed profile models for wrist pointing movements.

PubMed

Vaisman, Lev; Dipietro, Laura; Krebs, Hermano Igo

2013-09-01

Following two decades of design and clinical research on robot-mediated therapy for the shoulder and elbow, therapeutic robotic devices for other joints are being proposed: several research groups including ours have designed robots for the wrist, either to be used as stand-alone devices or in conjunction with shoulder and elbow devices. However, in contrast with robots for the shoulder and elbow which were able to take advantage of descriptive kinematic models developed in neuroscience for the past 30 years, design of wrist robots controllers cannot rely on similar prior art: wrist movement kinematics has been largely unexplored. This study aimed at examining speed profiles of fast, visually evoked, visually guided, target-directed human wrist pointing movements. One thousand three-hundred ninety-eight (1398) trials were recorded from seven unimpaired subjects who performed center-out flexion/extension and abduction/adduction wrist movements and fitted with 19 models previously proposed for describing reaching speed profiles. A nonlinear, least squares optimization procedure extracted parameters' sets that minimized error between experimental and reconstructed data. Models' performances were compared based on their ability to reconstruct experimental data. Results suggest that the support-bounded lognormal is the best model for speed profiles of fast, wrist pointing movements. Applications include design of control algorithms for therapeutic wrist robots and quantitative metrics of motor recovery.

Graphic representation of data resulting from measurement comparison trials in cataract and refractive surgery.

PubMed

Krummenauer, Frank; Storkebaum, Kristin; Dick, H Burkhard

2003-01-01

The evaluation of new diagnostic measurement devices allows intraindividual comparison with an established standard method. However, reports in journal articles often omit the adequate incorporation of the intraindividual design into the graphic representation. This article illustrates the drawbacks and the possible erroneous conclusions caused by this misleading practice in terms of recent method comparison data resulting from axial length measurement in 220 consecutive patients by both applanation ultrasound and partial coherence interferometry. Graphic representation of such method comparison data should be based on boxplots for intraindividual differences or on Bland-Altman plots. Otherwise, severe deviations between the measurement devices could be erroneously ignored and false-positive conclusions on the concordance of the instruments could result. Graphic representation of method comparison data should sensitively incorporate the underlying study design for intraindividual comparison.

Biomedical Impact in Implantable Devices-The Transcatheter Aortic Valve as an example

NASA Astrophysics Data System (ADS)

Anastasiou, Alexandros; Saatsakis, George

2015-09-01

Objective: To update of the scientific community about the biomedical engineering involvement in the implantable devices chain. Moreover the transcatheter Aortic Valve (TAV) replacement, in the field of cardiac surgery, will be analyzed as an example of contemporary implantable technology. Methods: A detailed literature review regarding biomedical engineers participating in the implantable medical product chain, starting from the design of the product till the final implantation technique. Results: The scientific role of biomedical engineers has clearly been established. Certain parts of the product chain are implemented almost exclusively by experienced biomedical engineers such as the transcatheter aortic valve device. The successful professional should have a multidisciplinary knowledge, including medicine, in order to pursue the challenges for such intuitive technology. This clearly indicates that biomedical engineers are among the most appropriate scientists to accomplish such tasks. Conclusions: The biomedical engineering involvement in medical implantable devices has been widely accepted by the scientific community, worldwide. Its important contribution, starting from the design and extended to the development, clinical trials, scientific support, education of other scientists (surgeons, cardiologists, technicians etc.), and even to sales, makes biomedical engineers a valuable player in the scientific arena. Notably, the sector of implantable devices is constantly raising, as emerging technologies continuously set up new targets.

Initial experience with teriparatide in the United States.

PubMed

Gold, Deborah T; Pantos, Barbara S; Masica, Daniel N; Misurski, Derek A; Marcus, Robert

2006-04-01

Teriparatide has been commercially available in the United States (US) for over 3 years. This summary spans the early experience with this therapy. As of December 31, 2005, over 235 000 patients had filled a prescription for teriparatide world-wide. Data collected from July to December 2004, from 15,000 retail pharmacies in the US, indicated that the mean age of patients was 67.5 years, and more recent data collected from January through October 2005 indicated that 90% of patients were female. According to market research conducted with prescribing physicians from February through March of 2005, it is estimated that over 80% of patients receiving prescriptions for teriparatide had already experienced one or more prior fractures. Since teriparatide is administered subcutaneously, it is important that patients receive training on the use of the teriparatide injection device (i.e., the pen device). Educational programs are available for those who have been prescribed teriparatide therapy. Patients may also contact a customer care program regarding a variety of topics, including pen device use. Based on patient feedback, design changes have been implemented in the pen device to facilitate optimal use. Updates have also been made to the prescribing information to reflect the post-marketing surveillance experience. Adverse experiences reported to date have been consistent with the current product label and with cumulative teriparatide clinical trial experience. As of December 31, 2005 no reports of pathology-confirmed osteosarcoma have been received for individuals who have been treated with teriparatide, either with the commercially available drug or in clinical trials. We are unaware of any reports of osteosarcoma in association with other preparations of teriparatide, or other peptides of parathyroid hormone, either in the setting of clinical trials or from marketed drug experience.

A multispectral, high-speed, low-cost device in the UV-MWIR spectral range

NASA Astrophysics Data System (ADS)

Svensson, Thomas; Lindell, Roland; Carlsson, Leif

2011-10-01

This paper presents the design and performance of a multispectral, high-speed, low-cost device. It is composed of six separate single element detectors covering the spectral range from UV to MWIR. Due to the wide spectral ranges of the detectors, these are used in conjunction with spectral filters. The device is a tool to spectrally and temporally resolve large field of view angularly integrated signatures from very fast events and get a total amplitude measure. One application has been to determine the maximal amplitude signal in muzzle flashes. Since the pulse width of a muzzle flash is on the order of 1 ms, a sensor with a bandwidth significantly higher than 1000 Hz is needed to resolve the flash. Examples from experimental trials are given.

Review of MRI positioning devices for guiding focused ultrasound systems.

PubMed

Yiallouras, C; Damianou, C

2015-06-01

This article contains a review of positioning devices that are currently used in the area of magnetic resonance imaging (MRI) guided focused ultrasound surgery (MRgFUS). The paper includes an extensive review of literature published since the first prototype system was invented in 1991. The technology has grown into a fast developing area with application to any organ accessible to ultrasound. The initial design operated using hydraulic principles, while the latest technology incorporates piezoelectric motors. Although, in the beginning there were fears regarding MRI safety, during recent years, the deployment of MR-safe positioning devices in FUS has become routine. Many of these positioning devices are now undergoing testing in clinical trials. Existing MRgFUS systems have been utilized mostly in oncology (fibroids, brain, liver, kidney, bone, pancreas, eye, thyroid, and prostate). It is anticipated that, in the near future, there will be a positioning device for every organ that is accessible by focused ultrasound. Copyright © 2014 John Wiley & Sons, Ltd.

Portable electronic vision enhancement systems in comparison with optical magnifiers for near vision activities: an economic evaluation alongside a randomized crossover trial.

PubMed

Bray, Nathan; Brand, Andrew; Taylor, John; Hoare, Zoe; Dickinson, Christine; Edwards, Rhiannon T

2017-08-01

To determine the incremental cost-effectiveness of portable electronic vision enhancement system (p-EVES) devices compared with optical low vision aids (LVAs), for improving near vision visual function, quality of life and well-being of people with a visual impairment. An AB/BA randomized crossover trial design was used. Eighty-two participants completed the study. Participants were current users of optical LVAs who had not tried a p-EVES device before and had a stable visual impairment. The trial intervention was the addition of a p-EVES device to the participant's existing optical LVA(s) for 2 months, and the control intervention was optical LVA use only, for 2 months. Cost-effectiveness and cost-utility analyses were conducted from a societal perspective. The mean cost of the p-EVES intervention was £448. Carer costs were £30 (4.46 hr) less for the p-EVES intervention compared with the LVA only control. The mean difference in total costs was £417. Bootstrapping gave an incremental cost-effectiveness ratio (ICER) of £736 (95% CI £481 to £1525) for a 7% improvement in near vision visual function. Cost per quality-adjusted life year (QALY) ranged from £56 991 (lower 95% CI = £19 801) to £66 490 (lower 95% CI = £23 055). Sensitivity analysis varying the commercial price of the p-EVES device reduced ICERs by up to 75%, with cost per QALYs falling below £30 000. Portable electronic vision enhancement system (p-EVES) devices are likely to be a cost-effective use of healthcare resources for improving near vision visual function, but this does not translate into cost-effective improvements in quality of life, capability or well-being. © 2016 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation and European Association for Vision & Eye Research.

Clinical efficacy and effectiveness of 3D printing: a systematic review

PubMed Central

Diment, Laura E; Thompson, Mark S; Bergmann, Jeroen H M

2017-01-01

Objective To evaluate the clinical efficacy and effectiveness of using 3D printing to develop medical devices across all medical fields. Design Systematic review compliant with Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Data sources PubMed, Web of Science, OVID, IEEE Xplore and Google Scholar. Methods A double-blinded review method was used to select all abstracts up to January 2017 that reported on clinical trials of a three-dimensional (3D)-printed medical device. The studies were ranked according to their level of evidence, divided into medical fields based on the International Classification of Diseases chapter divisions and categorised into whether they were used for preoperative planning, aiding surgery or therapy. The Downs and Black Quality Index critical appraisal tool was used to assess the quality of reporting, external validity, risk of bias, risk of confounding and power of each study. Results Of the 3084 abstracts screened, 350 studies met the inclusion criteria. Oral and maxillofacial surgery contained 58.3% of studies, and 23.7% covered the musculoskeletal system. Only 21 studies were randomised controlled trials (RCTs), and all fitted within these two fields. The majority of RCTs were 3D-printed anatomical models for preoperative planning and guides for aiding surgery. The main benefits of these devices were decreased surgical operation times and increased surgical accuracy. Conclusions All medical fields that assessed 3D-printed devices concluded that they were clinically effective. The fields that most rigorously assessed 3D-printed devices were oral and maxillofacial surgery and the musculoskeletal system, both of which concluded that the 3D-printed devices outperformed their conventional comparators. However, the efficacy and effectiveness of 3D-printed devices remain undetermined for the majority of medical fields. 3D-printed devices can play an important role in healthcare, but more rigorous and long-term assessments are needed to determine if 3D-printed devices are clinically relevant before they become part of standard clinical practice. PMID:29273650

Single incision device (TVT Secur) versus retropubic tension-free vaginal tape device (TVT) for the management of stress urinary incontinence in women: a randomized clinical trial.

PubMed

Ross, Sue; Tang, Selphee; Schulz, Jane; Murphy, Magnus; Goncalves, Jose; Kaye, Stephen; Dederer, Lorel; Robert, Magali

2014-12-22

In 2006, Ethicon Inc. introduced a new minimally invasive single incision sling device for the surgical treatment of stress urinary incontinence, the Gynecare TVT Secur®. For device licensing, no new evidence of TVT Secur efficacy and safety was needed: rather evidence was provided of the long-term follow-up of patients who had a procedure using a predecate retropubic tension-free vaginal tape device. Before adopting TVT Secur into our routine clinical practice, we decided to evaluate it. The objective of our Canadian multi-centre pragmatic randomized controlled trial was to compare the effectiveness of the new single-incision device, TVT Secur, to the established TVT device, in terms of objective cure of stress urinary incontinence (SUI) at 12 months postoperatively. Other outcomes included: complications, symptoms, and incontinence-related quality of life. The sample size estimate for our trial was 300, but the trial stopped early because of poor recruitment. 74 women participated (40 allocated to TVT Secur, 34 to TVT). At 12 months postoperatively, 27/33(82%) of TVT Secur group were cured, compared with 25/28(89%) of the TVT group (relative risk 0.92, 95% confidence interval 0.75 to 1.13, p=0.49). Most women reported little or no SUI symptoms (35/37(95%) vs 29/30(97%), >0.999). Quality of life improved significantly from baseline for both groups (IIQ-7 mean change -25 for both groups) but did not differ between groups (p=0.880). Our small randomized trial did not find statistically significant differences in outcomes between women allocated to the TVT Secur device versus those allocated to the TVT device for stress urinary incontinence. Despite the discontinuation of TVT Secur in March 2013 for commercial reasons, the importance of our study lies in making evidence available for the many women who had a TVT Secur device implanted and their physicians who may be considering alternative treatments. Our experience illustrates the difficulty of undertaking research on new licensed devices in a rapidly changing surgical specialty, and further highlights the need for research before licensing if surgeons and their patients are to be confident in the effectiveness and safety of new surgical devices. ClinicalTrials.gov NCT00685217, 22 May 2008.

Independent Evaluators of Federal Programs: Approaches, Devices, and Examples

DTIC Science & Technology

2010-08-16

rehabilitation of the disorder; the status of studies and clinical trials involving innovative treatments; a description of each treatment program and a...Transit Administration ( FTA ), a part of the Department of Transportation (DOT), oversees the safety and security of rail transit agencies which...an oversight body for each jurisdiction. The program is designed, according to a GAO summary, “as one in which FTA , other federal agencies, states

PHIT for Duty, a Personal Health Intervention Tool for Psychological Health and Traumatic Brain Injury

DTIC Science & Technology

2016-06-01

smartphone or tablet computer platforms, including both Google Android™ and Apple iOS based devices. Recruiting for the pilot study was very...framework design.. 15. SUBJECT TERMS PTSD, post-traumatic stress disorder, mobile health, self-help, iOS , Android, mindfulness, relaxation... study and subsequent randomized controlled trial (RCT) with post-deployed personnel; and (5) adapting the developed system for several popular

Oscillating devices for airway clearance in people with cystic fibrosis.

PubMed

Morrison, Lisa; Innes, Stephanie

2017-05-04

Chest physiotherapy is widely prescribed to assist the clearance of airway secretions in people with cystic fibrosis. Oscillating devices generate intra- or extra-thoracic oscillations orally or external to the chest wall. Internally they create variable resistances within the airways, generating controlled oscillating positive pressure which mobilises mucus. Extra-thoracic oscillations are generated by forces outside the respiratory system, e.g. high frequency chest wall oscillation. This is an update of a previously published review. To identify whether oscillatory devices, oral or chest wall, are effective for mucociliary clearance and whether they are equivalent or superior to other forms of airway clearance in the successful management of secretions in people with cystic fibrosis. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and hand searches of relevant journals and abstract books of conference proceedings. Latest search of the Cystic Fibrosis Trials Register: 27 April 2017.In addition we searched the trials databases ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform. Latest search of trials databases: 26 April 2017. Randomised controlled studies and controlled clinical studies of oscillating devices compared with any other form of physiotherapy in people with cystic fibrosis. Single-treatment interventions (therapy technique used only once in the comparison) were excluded. Two authors independently applied the inclusion criteria to publications and assessed the quality of the included studies. The searches identified 76 studies (302 references); 35 studies (total of 1138 participants) met the inclusion criteria. Studies varied in duration from up to one week to one year; 20 of the studies were cross-over in design. The studies also varied in type of intervention and the outcomes measured, data were not published in sufficient detail in most of these studies, so meta-analysis was limited. Few studies were considered to have a low risk of bias in any domain. It is not possible to blind participants and clinicians to physiotherapy interventions, but 11 studies did blind the outcome assessors.Forced expiratory volume in one second was the most frequently measured outcome. One long-term study (seven months) compared oscillatory devices with either conventional physiotherapy or breathing techniques and found statistically significant differences in some lung function parameters in favour of oscillating devices. One study identified an increase in frequency of exacerbations requiring antibiotics whilst using high frequency chest wall oscillation when compared to positive expiratory pressure. There were some small but significant changes in secondary outcome variables such as sputum volume or weight, but not wholly in favour of oscillating devices. Participant satisfaction was reported in 15 studies but this was not specifically in favour of an oscillating device, as some participants preferred breathing techniques or techniques used prior to the study interventions. The results for the remaining outcome measures were not examined or reported in sufficient detail to provide any high level evidence. There was no clear evidence that oscillation was a more or less effective intervention overall than other forms of physiotherapy; furthermore there was no evidence that one device is superior to another. The findings from one study showing an increase in frequency of exacerbations requiring antibiotics whilst using an oscillating device compared to positive expiratory pressure may have significant resource implications. More adequately-powered long-term randomised controlled trials are necessary and outcomes measured should include frequency of exacerbations, individual preference, adherence to therapy and general satisfaction with treatment. Increased adherence to therapy may then lead to improvements in other parameters, such as exercise tolerance and respiratory function. Additional evidence is needed to evaluate whether oscillating devices combined with other forms of airway clearance is efficacious in people with cystic fibrosis.There may also be a requirement to consider the cost implication of devices over other forms of equally advantageous airway clearance techniques. Using the GRADE method to assess the quality of the evidence, we judged this to be low or very low quality, which suggests that further research is very likely to have an impact on confidence in any estimate of effect generated by future interventions.

Regulatory issues relating to therapies for periodontal regeneration.

PubMed

Singleton, D G; Torres-Cabassa, A

1997-03-01

The Food and Drug Administration (FDA) has regulated medical devices since May 1976, when the Medical Device Amendments were enacted. The clinical trial requirements for the marketing of periodontal regeneration devices have been dependent, in part, on the degree of their similarity to devices marketed prior to the legislative enactment date in terms of materials, indication statements, and labeling claims. Nonresorbable barriers were allowed to be marketed based on their equivalence to devices marketed prior to the enactment date based on biocompatability and clinical trial data under the premarket notification requirements section of the law. Bone filling materials such as hydroxyapatite were first marketed based on the finding of equivalence to predicate devices. Newer technologies such as bioabsorbable barriers have also been reviewed under the premarket notification provisions of the law, but manufacturers have been required to provide more extensive safety and effectiveness data to establish equivalence to pre-Amendments devices. Data to answer questions related to the potential toxicity of breakdown products, period of absorption, and ultimate clinical effectiveness needed to be answered prior to marketing. New devices that incorporate technologies that are not substantially equivalent to predicate devices must proceed through the premarket approval route to marketing. For new devices considered a potential significant risk to the patient population, clinical trials are conducted via the investigational device exemption (IDE) requirements that specify the means by which trials will proceed in order to protect the rights of patients. New devices of organic origin, such as bone morphogenic protein, have followed the premarket approval route with IDE requirements instituted as a condition for their path to the marketplace. Issues associated with immediate and long-term contact including potential toxicity, tumorigenicity, and sensitization need to be addressed with appropriate animal models.

Wheels, skills and thrills: a social marketing trial to reduce aggressive driving from young men in deprived areas.

PubMed

Tapp, Alan; Pressley, Ashley; Baugh, Mike; White, Paul

2013-09-01

Young men from poorer backgrounds are associated with high road traffic collision levels. However, solving this problem has proven very difficult. Hence this paper summarises the findings of a UK government funded two-year trial of a cross-discipline intervention to reduce aggressive driving amongst this group. The intervention reported on here departed from traditional approaches such as fear appeals, stand-alone educational approaches, or punitive measures. Instead, the discipline of social marketing was used to provide overarching direction and structure for the trial, with a key focus on motivation and engagement. The project rested on a strong education and training platform and included a bespoke coaching programme, incentives, and an in-vehicle measurement and feedback device. The project had three development phases leading to the final trial. First, a literature and case study review identified possible design strategies. Second, these strategies were explored using primary research in the form of a qualitative inquiry. Third, a pre-trial design phase sought to introduce key components of the intervention to the trial cohort, retaining some flexibility before committing to the final design. Young males with a history of challenging behaviour (e.g. criminal records, driving convictions) from an economically deprived area within a UK city were recruited. Of 42 recruits, 23 successfully completed the trial. Behaviour changes were measured pre-, during and post-trial through a combination of driver performance data measured by in-vehicle data recorders (IVDRs), assessments of driving undertaken by trained observers, and self-assessment surveys and interviews with trial participants. Results indicate a significant average improvement in driving skills amongst participants who completed the trial. Given the difficulty in engaging and changing behaviour of this specific group, this is regarded as a significant finding. In summary the study provides an indication of proof of concept for the intervention in improving driving skills. However the limited sample size and lack of control group mean that further work will be required to validate these findings. It is recommended that a feasibility study with higher cohort volumes is undertaken, before attempting a full scale trial. Copyright © 2013 Elsevier Ltd. All rights reserved.

Bi-modal stimulation in the treatment of tinnitus: a study protocol for an exploratory trial to optimise stimulation parameters and patient subtyping.

PubMed

D'Arcy, Shona; Hamilton, Caroline; Hughes, Stephen; Hall, Deborah A; Vanneste, Sven; Langguth, Berthold; Conlon, Brendan

2017-10-25

Tinnitus is the perception of sound in the absence of a corresponding external acoustic stimulus. Bimodal neuromodulation is emerging as a promising treatment for this condition. The main objectives of this study are to investigate the relevance of interstimulus timing and the choices of acoustic and tongue stimuli for a proprietary bimodal (auditory and somatosensory) neuromodulation device, as well as to explore whether specific subtypes of patients are differentially responsive to this novel intervention for reducing the symptoms of chronic tinnitus. This is a two-site, randomised, triple-blind, exploratory study of a proprietary neuromodulation device with a pre-post and 12-month follow-up design. Three different bimodal stimulation parameter sets will be examined. The study will enrol 342 patients, split 80:20 between two sites (Dublin, Ireland and Regensburg, Germany), to complete 12 weeks of treatment with the device. Patients will be allocated to one of three arms using a stepwise stratification according to four binary categories: tinnitus tonality, sound level tolerance (using loudness discomfort level of <60 dB SL as an indicator for hyperacusis), hearing thresholds and presence of a noise-induced audiometric profile. The main indicators of relative clinical efficacy for the three different parameter sets are two patient-reported outcomes measures, the Tinnitus Handicap Inventory and the Tinnitus Functional Index, after 12 weeks of intervention. Clinical efficacy will be further explored in a series of patient subtypes, split by the stratification variables and by presence of a somatic tinnitus. Evidence for sustained effects on the psychological and functional impact of tinnitus will be followed up for 12 months. Safety data will be collected and reported. A number of feasibility measures to inform future trial design include: reasons for exclusion, completeness of data collection, attrition rates, patient's adherence to the device usage as per manufacturer's instructions and evaluation of alternative methods for estimating tinnitus impact and tinnitus loudness. This study protocol is approved by the Tallaght Hospital/St. James's Hospital Joint Research Ethics Committee in Dublin, Ireland, and by the Ethics Committee of the University Clinic Regensburg, Germany. Findings will be disseminated to relevant research, clinical, health service and patient communities through publications in peer-reviewed and popular science journals and presentations at scientific and clinical conferences. The trial is registered on ClinicalTrials.gov (NCT02669069) Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

The Role of Computational Modeling and Simulation in the Total Product Life Cycle of Peripheral Vascular Devices

PubMed Central

Morrison, Tina M.; Dreher, Maureen L.; Nagaraja, Srinidhi; Angelone, Leonardo M.; Kainz, Wolfgang

2018-01-01

The total product life cycle (TPLC) of medical devices has been defined by four stages: discovery and ideation, regulatory decision, product launch, and postmarket monitoring. Manufacturers of medical devices intended for use in the peripheral vasculature, such as stents, inferior vena cava (IVC) filters, and stent-grafts, mainly use computational modeling and simulation (CM&S) to aid device development and design optimization, supplement bench testing for regulatory decisions, and assess postmarket changes or failures. For example, computational solid mechanics and fluid dynamics enable the investigation of design limitations in the ideation stage. To supplement bench data in regulatory submissions, manufactures can evaluate the effects of anatomical characteristics and expected in vivo loading environment on device performance. Manufacturers might also harness CM&S to aid root-cause analyses that are necessary when failures occur postmarket, when the device is exposed to broad clinical use. Once identified, CM&S tools can then be used for redesign to address the failure mode and re-establish the performance profile with the appropriate models. The Center for Devices and Radiological Health (CDRH) wants to advance the use of CM&S for medical devices and supports the development of virtual physiological patients, clinical trial simulations, and personalized medicine. Thus, the purpose of this paper is to describe specific examples of how CM&S is currently used to support regulatory submissions at different phases of the TPLC and to present some of the stakeholder-led initiatives for advancing CM&S for regulatory decision-making. PMID:29479395

The Role of Computational Modeling and Simulation in the Total Product Life Cycle of Peripheral Vascular Devices.

PubMed

Morrison, Tina M; Dreher, Maureen L; Nagaraja, Srinidhi; Angelone, Leonardo M; Kainz, Wolfgang

2017-01-01

The total product life cycle (TPLC) of medical devices has been defined by four stages: discovery and ideation, regulatory decision, product launch, and postmarket monitoring. Manufacturers of medical devices intended for use in the peripheral vasculature, such as stents, inferior vena cava (IVC) filters, and stent-grafts, mainly use computational modeling and simulation (CM&S) to aid device development and design optimization, supplement bench testing for regulatory decisions, and assess postmarket changes or failures. For example, computational solid mechanics and fluid dynamics enable the investigation of design limitations in the ideation stage. To supplement bench data in regulatory submissions, manufactures can evaluate the effects of anatomical characteristics and expected in vivo loading environment on device performance. Manufacturers might also harness CM&S to aid root-cause analyses that are necessary when failures occur postmarket, when the device is exposed to broad clinical use. Once identified, CM&S tools can then be used for redesign to address the failure mode and re-establish the performance profile with the appropriate models. The Center for Devices and Radiological Health (CDRH) wants to advance the use of CM&S for medical devices and supports the development of virtual physiological patients, clinical trial simulations, and personalized medicine. Thus, the purpose of this paper is to describe specific examples of how CM&S is currently used to support regulatory submissions at different phases of the TPLC and to present some of the stakeholder-led initiatives for advancing CM&S for regulatory decision-making.

Patient-centered clinical trials.

PubMed

Chaudhuri, Shomesh E; Ho, Martin P; Irony, Telba; Sheldon, Murray; Lo, Andrew W

2018-02-01

We apply Bayesian decision analysis (BDA) to incorporate patient preferences in the regulatory approval process for new therapies. By assigning weights to type I and type II errors based on patient preferences, the significance level (α) and power (1-β) of a randomized clinical trial (RCT) for a new therapy can be optimized to maximize the value to current and future patients and, consequently, to public health. We find that for weight-loss devices, potentially effective low-risk treatments have optimal αs larger than the traditional one-sided significance level of 5%, whereas potentially less effective and riskier treatments have optimal αs below 5%. Moreover, the optimal RCT design, including trial size, varies with the risk aversion and time-to-access preferences and the medical need of the target population. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Regulatory Perspectives on Endoscopic Devices for Obesity.

PubMed

Marrone, April K; Antonino, Mark J; Silverstein, Joshua S; Betz, Martha W; Venkataraman-Rao, Priya; Golding, Martin; Cordray, Diane; Cooper, Jeffrey W

2017-04-01

The recent increase in US Food and Drug Administration-approved weight-loss devices has diversified obesity treatment options. The regulatory pathways for endoscopically placed weight-loss devices and considerations for clinical trials are discussed, including the benefit-risk paradigm intended to aid in weight-loss-device trial development. Also discussed is the benefit-risk analysis of recently approved endoscopic devices. A strategic priority of the FDA Center for Devices and Radiological Health is to increase the use of patient input in decision making. Thus, we consider how endoscopic weight-loss devices with profiles similar to those that have been approved may be viewed in a patient preference study. Published by Elsevier Inc.

The design, effectiveness and acceptability of the arm sleeve for the prevention of body fluid contamination during obstetric procedures.

PubMed

Kabukoba, J J; Pearce, J M

1993-08-01

1. To design a device that would reduce contamination of staff during obstetric procedures. 2. To undertake clinical trials to assess the effectiveness and acceptability of such a device. A prospective study. The arm sleeve is made of a nonwoven material laminated on polyethylene film making it waterproof. It has an elastomeric cuff with adhesive that ensures a watertight seal between it and the glove. Delivery suite in a teaching hospital. Doctors and midwives were requested to wear the sleeve on top of the standard gown and gloves. Each user was assessed for blood contamination at the end of the procedure and a questionnaire detailing the extent of contamination and the views of the user was completed. Eighty questionnaires were completed. The contamination of arms and hands was 3.8% and 5%, respectively. Eighty-nine percent thought the sleeve had served its purpose and 76% said they would use it regularly. The sleeve is an effective protective device which complements the glove and gown. We recommend that it should be used during all obstetric procedures.

Using e-technologies in clinical trials

PubMed Central

Rosa, Carmen; Campbell, Aimee N. C.; Miele, Gloria M.; Brunner, Meg; Winstanley, Erin L.

2015-01-01

Clinical trials have been slow to incorporate e-technology (digital and electronic technology that utilizes mobile devices or the Internet) into the design and execution of studies. In the meantime, individuals and corporations are relying more on electronic platforms and most have incorporated such technology into their daily lives. This paper provides a general overview of the use of e-technologies in clinical trials research, specifically within the last decade, marked by rapid growth of mobile and Internet-based tools. Benefits of and challenges to the use of e-technologies in data collection, recruitment and retention, delivery of interventions, and dissemination are provided, as well as a description of the current status of regulatory oversight of e-technologies in clinical trials research. As an example of ways in which e-technologies can be used for intervention delivery, a summary of e-technologies for treatment of substance use disorders is presented. Using e-technologies to design and implement clinical trials has the potential to reach a wide audience, making trials more efficient while also reducing costs; however, researchers should be cautious when adopting these tools given the many challenges in using new technologies, as well as threats to participant privacy/confidentiality. Challenges of using e-technologies can be overcome with careful planning, useful partnerships, and forethought. The role of web- and smartphone-based applications is expanding, and the increasing use of those platforms by scientists and the public alike make them tools that cannot be ignored. PMID:26176884

Using e-technologies in clinical trials.

PubMed

Rosa, Carmen; Campbell, Aimee N C; Miele, Gloria M; Brunner, Meg; Winstanley, Erin L

2015-11-01

Clinical trials have been slow to incorporate e-technology (digital and electronic technology that utilizes mobile devices or the Internet) into the design and execution of studies. In the meantime, individuals and corporations are relying more on electronic platforms and most have incorporated such technology into their daily lives. This paper provides a general overview of the use of e-technologies in clinical trials research, specifically within the last decade, marked by rapid growth of mobile and Internet-based tools. Benefits of and challenges to the use of e-technologies in data collection, recruitment and retention, delivery of interventions, and dissemination are provided, as well as a description of the current status of regulatory oversight of e-technologies in clinical trials research. As an example of ways in which e-technologies can be used for intervention delivery, a summary of e-technologies for treatment of substance use disorders is presented. Using e-technologies to design and implement clinical trials has the potential to reach a wide audience, making trials more efficient while also reducing costs; however, researchers should be cautious when adopting these tools given the many challenges in using new technologies, as well as threats to participant privacy/confidentiality. Challenges of using e-technologies can be overcome with careful planning, useful partnerships, and forethought. The role of web- and smartphone-based applications is expanding, and the increasing use of those platforms by scientists and the public alike make them tools that cannot be ignored. Published by Elsevier Inc.

Bone stimulation for fracture healing: What's all the fuss?

PubMed Central

Victoria, Galkowski; Petrisor, Brad; Drew, Brian; Dick, David

2009-01-01

Approximately 10% of the 7.9 million annual fracture patients in the United States experience nonunion and/or delayed unions, which have a substantial economic and quality of life impact. A variety of devices are being marketed under the name of “bone growth stimulators.” This article provides an overview of electrical and electromagnetic stimulation, ultrasound, and extracorporeal shock waves. More research is needed for knowledge of appropriate device configurations, advancement in the field, and encouragement in the initiation of new trials, particularly large multicenter trials and randomized control trials that have standardized device and protocol methods. PMID:19838359

Immediate vs. delayed insertion of intrauterine contraception after second trimester abortion: study protocol for a randomized controlled trial

PubMed Central

2011-01-01

Background We describe the rationale and protocol for a randomized controlled trial (RCT) to assess whether intrauterine contraception placed immediately after a second trimester abortion will result in fewer pregnancies than current recommended practice of intended placement at 4 weeks post-abortion. Decision analysis suggests the novel strategy could substantially reduce subsequent unintended pregnancies and abortions. This paper highlights considerations of design, implementation and evaluation of a trial expected to provide rigorous evidence for appropriate insertion timing and health economics of intrauterine contraception after second trimester abortion. Methods/Design Consenting women choosing to use intrauterine contraception after abortion for a pregnancy of 12 to 24 weeks will be randomized to insertion timing groups either immediately (experimental intervention) or four weeks (recommended care) post abortion. Primary outcome measure is pregnancy rate at one year. Secondary outcomes include: cumulative pregnancy rates over five year follow-up period, comprehensive health economic analyses comparing immediate and delayed insertion groups, and device retention rates, complication rates (infection, expulsion) and, contraceptive method satisfaction. Web-based Contraception Satisfaction Questionnaires, clinical records and British Columbia linked health databases will be used to assess primary and secondary outcomes. Enrolment at all clinics in the province performing second trimester abortions began in May 2010 and is expected to complete in late 2011. Data on one year outcomes will be available for analysis in 2014. Discussion The RCT design combined with access to clinical records at all provincial abortion clinics, and to information in provincial single-payer linked administrative health databases, birth registry and hospital records, offers a unique opportunity to evaluate such an approach by determining pregnancy rate at one through five years among enrolled women. We highlight considerations of design, implementation and evaluation of a trial expected to provide rigorous evidence for appropriate insertion timing and health economics of intrauterine contraception after second trimester abortion. Trial registration Current Controlled Trials ISRCTN19506752 PMID:21672213

En Route Air Traffic Control Input Devices for the Next Generation

NASA Technical Reports Server (NTRS)

Mainini, Matthew J.

2010-01-01

The purpose of this study was to investigate the usefulness of different input device configurations when trial planning new routes for aircraft in an advanced simulation of the en route workstation. The task of trial planning is one of the futuristic tools that is performed by the graphical manipulation of an aircraft's trajectory to reroute the aircraft without voice communication. In this study with two input devices, the FAA's current trackball and a basic optical computer mouse were evaluated with "pick" button in a click-and-hold state and a click-and-release state while the participant dragged the trial plan line. The trial plan was used for three different conflict types: Aircraft Conflicts, Weather Conflicts, and Aircraft + Weather Conflicts. Speed and accuracy were the primary dependent variables. Results indicate that the mouse conditions were significantly faster than the trackball conditions overall with no significant loss of accuracy. Several performance ratings and preference ratings were analyzed from post-run and post-simulation questionnaires. The release conditions were significantly more useful and likable than the hold conditions. The results suggest that the mouse in the release button state was the fastest and most well liked device configuration for trial planning in the en route workstation. Keywords-input devices, en route, controller, workstation, mouse, trackball, NextGen

[The modeling of the ricochet shot fired from a light weapon].

PubMed

Gusentsov, A O; Chuchko, V A; Kil'dyushev, E M; Tumanov, E V

The objective of the present study was to choose the optimal method for the modeling of the glance of a bullet after hitting a target under conditions of the laboratory experiment. The study required the designing and construction of an original device for the modeling of the rebound effect of a light-firearm shot under experimental conditions. The device was tested under conditions of the laboratory experiment. The trials have demonstrated the possibility of using barriers of different weight and dimensions in the above device, their positioning and fixation depending on the purpose of the experiment, dynamic alteration of its conditions with due regard for the safety and security arrangements to protect the health and life of the experimenters without compromising the statistical significance and scientific validity of the results of the experiments.

Securing All intraVenous devices Effectively in hospitalised patients—the SAVE trial: study protocol for a multicentre randomised controlled trial

PubMed Central

Rickard, Claire M; Marsh, Nicole; Webster, Joan; Playford, E Geoffrey; McGrail, Matthew R; Larsen, Emily; Keogh, Samantha; McMillan, David; Whitty, Jennifer A; Choudhury, Md Abu; Dunster, Kimble R; Reynolds, Heather; Marshall, Andrea; Crilly, Julia; Young, Jeanine; Thom, Ogilvie; Gowardman, John; Corley, Amanda; Fraser, John F

2015-01-01

Introduction Over 70% of all hospital admissions have a peripheral intravenous device (PIV) inserted; however, the failure rate of PIVs is unacceptably high, with up to 69% of these devices failing before treatment is complete. Failure can be due to dislodgement, phlebitis, occlusion/infiltration and/or infection. This results in interrupted medical therapy; painful phlebitis and reinsertions; increased hospital length of stay, morbidity and mortality from infections; and wasted medical/nursing time. Appropriate PIV dressing and securement may prevent many cases of PIV failure, but little comparative data exist regarding the efficacy of various PIV dressing and securement methods. This trial will investigate the clinical and cost-effectiveness of 4 methods of PIV dressing and securement in preventing PIV failure. Methods and analysis A multicentre, parallel group, superiority randomised controlled trial with 4 arms, 3 experimental groups (tissue adhesive, bordered polyurethane dressing, sutureless securement device) and 1 control (standard polyurethane dressing) is planned. There will be a 3-year recruitment of 1708 adult patients, with allocation concealment until randomisation by a centralised web-based service. The primary outcome is PIV failure which includes any of: dislodgement, occlusion/infiltration, phlebitis and infection. Secondary outcomes include: types of PIV failure, PIV dwell time, costs, device colonisation, skin colonisation, patient and staff satisfaction. Relative incidence rates of device failure per 100 devices and per 1000 device days with 95% CIs will summarise the impact of each dressing, and test differences between groups. Kaplan-Meier survival curves (with log-rank Mantel-Cox test) will compare device failure over time. p Values of <0.05 will be considered significant. Secondary end points will be compared between groups using parametric or non-parametric techniques appropriate to level of measurement. Ethics and dissemination Ethical approval has been received from Queensland Health (HREC/11/QRCH/152) and Griffith University (NRS/46/11/HREC). Results will be published according to the CONSORT statement and presented at relevant conferences. Trial registration number Australian New Zealand Clinical Trial Registry (ACTRN); 12611000769987. PMID:26399574

A meta-analysis of comparative outcomes following cervical arthroplasty or anterior cervical fusion: results from 4 prospective multicenter randomized clinical trials and up to 1226 patients.

PubMed

McAfee, Paul C; Reah, Chris; Gilder, Kye; Eisermann, Lukas; Cunningham, Bryan

2012-05-15

Meta-analysis of 4 prospective randomized controlled Food and Drug Administration (FDA) Investigational Device Exemption (IDE) clinical trials. To maximize the information available from 4 IDE studies by analyzing the combined outcomes of cervical arthroplasty versus fusion at 24-month follow-up. To date, 4 randomized clinical trials have been completed in the United States under FDA IDE protocols to study cervical arthroplasty. Each trial reported arthroplasty to be at least as successful as fusion controls based on noninferiority trial designs. However, sample sizes in any given trial may not be sufficient to demonstrate superiority of treatment effect. Meta-analysis enables pooling of results from comparable trials, which may lead to more precise and statistically significant estimates of treatment effect. Four cervical arthroplasty randomized clinical trials with comparable enrollment criteria and outcome measures were conducted independently by 3 separate sponsors to study the following devices: Bryan, Prestige, ProDisc-C, and PCM cervical disc replacements. A total of 1608 patients were treated across 98 investigative sites. Data were available for 1352 treated patients, of which 1226 were evaluable at 24 months. Assessments included clinical success definitions based on neck disability index, maintenance or improvement of neurological status, subsequent surgery or intervention at the index level (survivorship), and a composite score comprising these as well as serious device-related adverse events. Trial endpoint comparisons were made at 24 months postoperatively. For each endpoint, a random-effects meta-analysis was performed to compare the success rates of cervical arthroplasty with anterior cervical discectomy and fusion (ACDF). Also, supportive frequentist and bayesian analyses were performed. The pooled primary overall success results indicated a statistically significant treatment effect favoring arthroplasty compared with ACDF. Overall success was achieved by 77.6% of the arthroplasty patients and by 70.8% of the ACDF patients (pooled odds ratio [OR]: 0.699, 95% confidence interval [CI]: 0.539-0.908, P = 0.007). The results of the individual subcomponent meta-analyses, all of which favored arthroplasty, were neck disability index success (OR: 0.786, 95% CI: 0.589-1.050, P = 0.103), neurological status (OR: 0.552, 95% CI: 0.364-0.835, P = 0.005), and survivorship (OR: 0.510, 95% CI: 0.275-0.946, P = 0.033). Only the survivorship endpoint suggested low heterogeneity. These findings suggest that cervical arthroplasty is superior to ACDF in overall success, neurological success, and survivorship outcomes at 24 months postoperatively.

[Differences between clinical trials according to the German law on pharmaceuticals (Arzneimittelgesetz) and trials according to the German law on medical products (Medizinproduktegesetz)].

PubMed

Krummenauer, F

2003-02-01

Similar to the registration process for pharmaceutical agents, medical devices have to undergo standardized clinical evaluation before being marketed and used in routine therapy or diagnostics. However, conduction, submission, and reporting of such clinical evaluations to authorities has to follow the German law on medical products(Medizinproduktegesetz,MPG), which in some central aspects differs remarkably from the German law on pharmaceuticals (Arzneimittelgesetz,AMG). Relevant deviations of MPG requirements from those of the AMG are reviewed with particular emphasis on submission, conduction, and reporting of trials to the authorities in charge. Whereas AMG-based trials focus on the proof of efficacy of pharmaceutical agents, the MPG demands instead proof of functionality of the medical devices; the MPG therefore concentrates more on technically satisfactory results in the context of function and patient safety. The aim of MPG trials is thus CE marking instead of AMG-based registration. However, this focus on functionality implies that medical devices need not necessarily be tested in a clinical trial--in some settings evidence-based evaluation alone will be sufficient. The decision on the necessity of a clinical trial is based mainly on the risk profile and invasive character of the device at hand. The early consideration of differences between AMG and MPG concerning the role and conduction of clinical trials will remarkably increase the (CE) certification process's outcome quality and juridical validity.

Assessing the Usability of Six Data Entry Mobile Interfaces for Caregivers: A Randomized Trial.

PubMed

Ehrler, Frederic; Haller, Guy; Sarrey, Evelyne; Walesa, Magali; Wipfli, Rolf; Lovis, Christian

2015-12-15

There is an increased demand in hospitals for tools, such as dedicated mobile device apps, that enable the recording of clinical information in an electronic format at the patient's bedside. Although the human-machine interface design on mobile devices strongly influences the accuracy and effectiveness of data recording, there is still a lack of evidence as to which interface design offers the best guarantee for ease of use and quality of recording. Therefore, interfaces need to be assessed both for usability and reliability because recording errors can seriously impact the overall level of quality of the data and affect the care provided. In this randomized crossover trial, we formally compared 6 handheld device interfaces for both speed of data entry and accuracy of recorded information. Three types of numerical data commonly recorded at the patient's bedside were used to evaluate the interfaces. In total, 150 health care professionals from the University Hospitals of Geneva volunteered to record a series of randomly generated data on each of the 6 interfaces provided on a smartphone. The interfaces were presented in a randomized order as part of fully automated data entry scenarios. During the data entry process, accuracy and effectiveness were automatically recorded by the software. Various types of errors occurred, which ranged from 0.7% for the most reliable design to 18.5% for the least reliable one. The length of time needed for data recording ranged from 2.81 sec to 14.68 sec, depending on the interface. The numeric keyboard interface delivered the best performance for pulse data entry with a mean time of 3.08 sec (SD 0.06) and an accuracy of 99.3%. Our study highlights the critical impact the choice of an interface can have on the quality of recorded data. Selecting an interface should be driven less by the needs of specific end-user groups or the necessity to facilitate the developer's task (eg, by opting for default solutions provided by commercial platforms) than by the level of speed and accuracy an interface can provide for recording information. An important effort must be made to properly validate mobile device interfaces intended for use in the clinical setting. In this regard, our study identified the numeric keyboard, among the proposed designs, as the most accurate interface for entering specific numerical values. This is an important step toward providing clearer guidelines on which interface to choose for the appropriate use of handheld device interfaces in the health care setting.

Assessing the Usability of Six Data Entry Mobile Interfaces for Caregivers: A Randomized Trial

PubMed Central

Haller, Guy; Sarrey, Evelyne; Walesa, Magali; Wipfli, Rolf; Lovis, Christian

2015-01-01

Background There is an increased demand in hospitals for tools, such as dedicated mobile device apps, that enable the recording of clinical information in an electronic format at the patient’s bedside. Although the human-machine interface design on mobile devices strongly influences the accuracy and effectiveness of data recording, there is still a lack of evidence as to which interface design offers the best guarantee for ease of use and quality of recording. Therefore, interfaces need to be assessed both for usability and reliability because recording errors can seriously impact the overall level of quality of the data and affect the care provided. Objective In this randomized crossover trial, we formally compared 6 handheld device interfaces for both speed of data entry and accuracy of recorded information. Three types of numerical data commonly recorded at the patient’s bedside were used to evaluate the interfaces. Methods In total, 150 health care professionals from the University Hospitals of Geneva volunteered to record a series of randomly generated data on each of the 6 interfaces provided on a smartphone. The interfaces were presented in a randomized order as part of fully automated data entry scenarios. During the data entry process, accuracy and effectiveness were automatically recorded by the software. Results Various types of errors occurred, which ranged from 0.7% for the most reliable design to 18.5% for the least reliable one. The length of time needed for data recording ranged from 2.81 sec to 14.68 sec, depending on the interface. The numeric keyboard interface delivered the best performance for pulse data entry with a mean time of 3.08 sec (SD 0.06) and an accuracy of 99.3%. Conclusions Our study highlights the critical impact the choice of an interface can have on the quality of recorded data. Selecting an interface should be driven less by the needs of specific end-user groups or the necessity to facilitate the developer’s task (eg, by opting for default solutions provided by commercial platforms) than by the level of speed and accuracy an interface can provide for recording information. An important effort must be made to properly validate mobile device interfaces intended for use in the clinical setting. In this regard, our study identified the numeric keyboard, among the proposed designs, as the most accurate interface for entering specific numerical values. This is an important step toward providing clearer guidelines on which interface to choose for the appropriate use of handheld device interfaces in the health care setting. PMID:27025648

Connecting Health and Technology (CHAT): protocol of a randomized controlled trial to improve nutrition behaviours using mobile devices and tailored text messaging in young adults

PubMed Central

2012-01-01

Background Increasing intakes of fruits and vegetables intake, in tandem with reducing consumption of energy-dense and nutrient poor foods and beverages are dietary priorities to prevent chronic disease. Although most adults do not eat enough fruit and vegetables, teenagers and young adults tend to have the lowest intakes. Young adults typically consume a diet which is inconsistent with the dietary recommendations. Yet little is known about the best approaches to improve dietary intakes and behaviours among this group. This randomised controlled trial aims to evaluate the effectiveness of using a mobile device to assess dietary intake, provide tailored dietary feedback and text messages to motivate changes in fruit, vegetable and junk food consumption among young adults. Methods/design The CHAT project will involve the development of the mobile device food record (MDFR), and evaluation of dietary feedback and implementation of a 6-month intervention in young adults aged 18 to 30 years. The participants will be randomly assigned to one of three groups (1) Intervention Group 1: MDFR + Text Messages + Dietary Feedback; (2) Intervention Group 2: MDFR + Dietary Feedback; (3) Control Group 3: MDFR, no feedback. All groups will undertake a 3-day dietary record using the MDFR but only the Intervention Groups 1 and 2 will receive tailored dietary feedback at baseline and at 6-months which will consist of assessment of serves of fruits, vegetables and junk food in comparison to dietary recommendations. Tailored nutrition text messages will be sent to Intervention Group 1 over the 6 months. Data will be collected at baseline and again at the 6-month completion. Discussion This trial will test if applications running on mobile devices have potential to assess diet, provide tailored feedback and nutrition messages as an effective way of improving fruit and vegetable consumption and reducing energy-dense nutrient poor foods in young adults. The CHAT project will assess the impact of the intervention on behavioural intention to eat a more healthful diet. This innovative approach if successful may provide a means to deliver a low cost health promotion program that has the potential to reach large groups, particularly young adults. Trial registration Australian and New Zealand Clinical Trials Registry ACTRN12612000250831 PMID:22726532

Impact of Hearing Aid Technology on Outcomes in Daily Life II: Speech Understanding and Listening Effort.

PubMed

Johnson, Jani A; Xu, Jingjing; Cox, Robyn M

2016-01-01

Modern hearing aid (HA) devices include a collection of acoustic signal-processing features designed to improve listening outcomes in a variety of daily auditory environments. Manufacturers market these features at successive levels of technological sophistication. The features included in costlier premium hearing devices are designed to result in further improvements to daily listening outcomes compared with the features included in basic hearing devices. However, independent research has not substantiated such improvements. This research was designed to explore differences in speech-understanding and listening-effort outcomes for older adults using premium-feature and basic-feature HAs in their daily lives. For this participant-blinded, repeated, crossover trial 45 older adults (mean age 70.3 years) with mild-to-moderate sensorineural hearing loss wore each of four pairs of bilaterally fitted HAs for 1 month. HAs were premium- and basic-feature devices from two major brands. After each 1-month trial, participants' speech-understanding and listening-effort outcomes were evaluated in the laboratory and in daily life. Three types of speech-understanding and listening-effort data were collected: measures of laboratory performance, responses to standardized self-report questionnaires, and participant diary entries about daily communication. The only statistically significant superiority for the premium-feature HAs occurred for listening effort in the loud laboratory condition and was demonstrated for only one of the tested brands. The predominant complaint of older adults with mild-to-moderate hearing impairment is difficulty understanding speech in various settings. The combined results of all the outcome measures used in this research suggest that, when fitted using scientifically based practices, both premium- and basic-feature HAs are capable of providing considerable, but essentially equivalent, improvements to speech understanding and listening effort in daily life for this population. For HA providers to make evidence-based recommendations to their clientele with hearing impairment it is essential that further independent research investigates the relative benefit/deficit of different levels of hearing technology across brands and manufacturers in these and other real-world listening domains.

Reminder packaging for improving adherence to self-administered long-term medications.

PubMed

Heneghan, C J; Glasziou, P; Perera, R

2006-01-25

Current methods of improving medication adherence for health problems are mostly complex, labour-intensive, and not reliably effective. Medication 'reminder packaging' which incorporates a date or time for a medication to be taken in the packaging, can act as a reminder system to improve adherence. The objective of this review was to determine the effects of reminder packaging to enhance patient adherence with self-administered medications taken for one month or more. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) and the Database of Abstracts of Reviews of Effects (DARE) (The Cochrane Library Issue 3, 2004), MEDLINE, EMBASE, CINAHL and PsycINFO from the start of the databases to 1 September 2004. We also searched the internet, contacted packaging manufacturers, and checked abstracts from the Pharm-line database and reference lists from relevant articles. We did not apply any language restrictions. We selected randomised controlled trials with at least 80% follow up, comparing a reminder packaging device with no device in participants taking self-administered medications for a minimum of one month. Two reviewers independently assessed studies for inclusion, assessed quality, and extracted data from included studies. Where considered appropriate, data were combined for meta-analysis, or were reported and discussed in a narrative. Eight studies containing data on 1,137 participants were included. Six intervention groups in four trials provided data on the percentage of pills taken. Reminder packaging showed a significant increase in the percentage of pills taken, weighted mean difference 11% (95% confidence interval (CI) 6% to 17%). Notable heterogeneity occurred among these trials I(2 )= 96.3%. Two trials provided data for the proportion of self-reported adherent patients, reporting a reduction in the intervention group which was not statistically significant, odds ratio = 0.89 (95% CI 0.56 to 1.40). No appropriate data were available for meta-analysis of different clinical outcomes, the most common of these being blood pressure (three out of eight trials). Other clinical outcomes reported were glycated haemoglobin, serum Vitamin C and E levels, and self-reported psychological symptoms (one trial each). Reminder packing may represent a simple method for improving adherence for patients with selected conditions examined to date. Further research is warranted to improve the design and targeting of these devices.

The STENTYS self-apposing stent technology in coronary artery disease: literature review and future directions.

PubMed

Lu, Huangling; de Winter, Robbert J; Koch, Karel T

2018-06-21

Coronary stent designs have been through extensive developments in the past few decades. Since the first introduction of the self-apposing STENTYS stent, several theoretical advantages of its nitinol platform have been clinically evaluated. This paper reviews the current status, ongoing work and future directions of this device. Areas covered: The OPEN (STENTYS Coronary Bifurcation Stent System fOr the PErcutaNeous treatment of de novo lesions in native bifurcated coronary arteries) trials revealed high technical success rates of the STENTYS performance in bifurcation lesions. The APPOSITION (Assessment of the Safety and Performance of the STENTYS self-expanding Coronary Stent in Acute Myocardial Infarction) trials demonstrated the safety and feasibility of the device in patients with acute myocardial infarction. Optical coherence tomography showed better short-term strut apposition in patients treated with the STENTYS stent in APPOSITION IV. The clinical outcomes of the device in saphenous vein graft lesions and left main coronary artery disease are favourable. Expert Commentary: Despite numerous theoretical advantages of the nitinol platform, superiority of the STENTYS self-apposing stent over currently available DES has not yet been proven. However, the ongoing registries evaluating the performance of the STENTYS Xposition will provide more insights in its clinical performance.

Design and usability evaluation of user-centered and visual-based aids for dietary food measurement on mobile devices in a randomized controlled trial.

PubMed

Liu, Ying-Chieh; Chen, Chien-Hung; Lee, Chien-Wei; Lin, Yu-Sheng; Chen, Hsin-Yun; Yeh, Jou-Yin; Chiu, Sherry Yueh-Hsia

2016-12-01

We designed and developed two interactive apps interfaces for dietary food measurements on mobile devices. The user-centered designs of both the IPI (interactive photo interface) and the SBI (sketching-based interface) were evaluated. Four types of outcomes were assessed to evaluate the usability of mobile devices for dietary measurements, including accuracy, absolute weight differences, and the response time to determine the efficacy of food measurements. The IPI presented users with images of pre-determined portion sizes of a specific food and allowed users to scan and then select the most representative image matching the food that they were measuring. The SBI required users to relate the food shape to a readily available comparator (e.g., credit card) and scribble to shade in the appropriate area. A randomized controlled trial was conducted to evaluate their usability. A total of 108 participants were randomly assigned into the following three groups: the IPI (n=36) and SBI (n=38) experimental groups and the traditional life-size photo (TLP) group as the control. A total of 18 types of food items with 3-4 different weights were randomly selected for assessment by each type. The independent Chi-square test and t-test were performed for the dichotomous and continuous variable analyses, respectively. The total accuracy rates were 66.98%, 44.15%, and 72.06% for the IPI, SBI, and TLP, respectively. No significant difference was observed between the IPI and TLP, regardless of the accuracy proportion or weight differences. The SBI accuracy rates were significantly lower than the IPI and TLP accuracy rates, especially for several spooned, square cube, and sliced pie food items. The time needed to complete the operation assessment by the user was significantly lower for the IPI than for the SBI. Our study corroborates that the user-centered visual-based design of the IPI on a mobile device is comparable the TLP in terms of the usability for dietary food measurements. However, improvements are needed because both the IPI and TLP accuracies associated with some food shapes were lower than 60%. The SBI is not yet a viable aid. This innovative alternative required further improvements to the user interface. Copyright © 2016 Elsevier Inc. All rights reserved.

Real-life efficacy and reliability of training a hearing aid.

PubMed

Keidser, Gitte; Alamudi, Karima

2013-09-01

Commercial trainable hearing aids (HA) (i.e., devices that for a period are adjusted by the user in different acoustic environments and that subsequently with changing environments automatically adapt to the user's preferred settings), are readily available; however, little information exists about the efficacy of training a HA. The purpose of this study was to investigate the efficacy and reliability of training a HA in everyday environments. The participants were 26 hearing-impaired volunteers with a median age of 79 years and an average pure-tone average of 53 dB HL. Test devices were commercial, multimemory, prototype devices that enabled training of the compression characteristics in four frequency bands and in six sound classes. Participants wore the National Acoustic Laboratories nonlinear fitting procedure version 2 prescription for 3 weeks and trained the devices from the prescribed response for 3 weeks, before comparing their trained response with the prescription for 2 weeks. The devices were reset to the prescription, and 19 participants repeated the training and comparison trials. During the comparison trial, participants made daily diary ratings of their satisfaction with the programs, and a structured interview was completed at the end of the comparison trial. The participants displayed different needs for changing the prescription, with more daily adjustments leading to training across more sound classes. Unreliable observations were obtained from 8 participants after each of the test and retest comparison trials. Of the 10 participants who made sufficient changes to the prescription during the first trial, 80% preferred their trained response. The 8 "low trainers" reported no preference, and also reported lower overall satisfaction with the device. Fewer adjustments were made during the repeat trial, resulting in less training. Significant correlations between trained variations were seen for 63% of 19 participants. Of the 10 participants who provided valid data after both comparison trials, those who trained the device consistently generally showed consistent preferences, and vice versa. For those who wanted a change to the prescription, training was mostly effective. Limited data on reliability showed reasonable consistency in training outcomes and preferences. Findings, in particular on reliability, should be verified in larger populations. A guideline on how to clinically manage training with clients is presented.

Safety of an intra-oral hearing device utilizing a split-mouth research design.

PubMed

Miller, Ross; Hujoel, Philippe; Murray, Michael; Popelka, Gerald R

2011-01-01

The auditory deficits of Single Sided Deafness (SSD) can be treated effectively with a novel device, SoundBite, that delivers sound by applying imperceptible vibratory signals to the teeth (hereafter referred to as an intra-oral hearing device). The intra-oral hearing device is placed around two maxillary teeth and is similar to a small partial denture or retainer. The goal of this study was to report how this removable hearing device affects the oral structures. Twenty-two SSD patients wearing an intra-oral hearing device were enrolled in a prospective study for six months. Differences (delta) between the device-anchoring teeth and the equivalent contralateral non-device teeth were evaluated with four dental parameters using a paired t-test. Hearing thresholds were evaluated as a function of alveolar bone support using linear regression. Compared to the non-device teeth, the hearing device teeth did not exhibit any increased recession (delta = 0.1 mm, p-value = 0.48), increased pocket depth (delta = 0.0 mm, p-value = 0.48), increased root resorption (delta = 4%, p-value = 0.43), or increased alveolar bone loss (delta = 0.0 %, p-value = 0.43). There was no association between the amount of alveolar support and hearing thresholds (delta = 0.2, p-value = 0.34). The intra-oral component of the hearing device did not adversely affect the dental structures of the subjects in this trial.

Utilizing national and international registries to enhance pre-market medical device regulatory evaluation.

PubMed

Yue, Lilly Q; Campbell, Gregory; Lu, Nelson; Xu, Yunling; Zuckerman, Bram

2016-01-01

Regulatory decisions are made based on the assessment of risk and benefit of medical devices at the time of pre-market approval and subsequently, when post-market risk-benefit balance needs reevaluation. Such assessments depend on scientific evidence obtained from pre-market studies, post-approval studies, post-market surveillance studies, patient perspective information, as well as other real world data such as national and international registries. Such registries provide real world evidence and are playing a more and more important role in enhancing the safety and effectiveness evaluation of medical devices. While these registries provide large quantities of data reflecting real world practice and can potentially reduce the cost of clinical trials, challenges arise concerning (1) data quality adequate for regulatory decision-making, (2) bias introduced at every stage and aspect of study, (3) scientific validity of study designs, and (4) reliability and interpretability of study results. This article will discuss related statistical and regulatory challenges and opportunities with examples encountered in medical device regulatory reviews.

Implementing bright light treatment for MSFC payload operations shiftworkers

NASA Technical Reports Server (NTRS)

Hayes, Benita C.; Stewart, Karen T.; Eastman, Charmane I.

1994-01-01

Intense light can phase-shift circadian rhythms and improve performance, sleep, and wellbeing during shiftwork simulations, but to date there have been very few attempts to administer light treatment to real shiftworkers. We have developed procedures for implementing light treatment and have conducted controlled trials of light treatment for MSFC Payload Operations staff during the USML-1 mission. We found that treatment had beneficial effects on fatigue, alertness, self-rated job performance, sleep, mood, and work attendance. Although there are portable bright light boxes commercially available, there is no testing protocol and little performance information available. We measure the illuminance of two candidate boxes for use in this study and found that levels were consistently lower than those advertised by manufacturers. A device was developed to enhance the illuminance output of such units. This device increased the illuminance by at least 60 % and provided additional improvements in visual comfort and overall exposure. Both the design of this device and some suggested procedures for evaluating light devices are presented.

Optical diagnosis of testicular torsion: feasibility and methodology

NASA Astrophysics Data System (ADS)

Shadgan, Babak; Macnab, Andrew; Stothers, Lynn; Kajbafzadeh, A. M.

2014-03-01

Background: Torsion of the testis compromises blood flow through the spermatic cord; testicular ischemia results which if not diagnosed promptly and corrected surgically irrevocably damages the testis. Current diagnostic modalities aimed at rationalizing surgical exploration by demonstrating interruption of spermatic cord blood flow or testicular ischemia have limited applicability. Near infrared spectroscopy (NIRS) offers a non-invasive optical method for detection of ischemia; continuous wave and frequency domain devices have been used experimentally; no device customized for clinical use has been designed. Methods: A miniature spatially resolved NIRS device with light emitting diode light source was applied over the right and left spermatic cord and the difference in oxygen saturation between the two sides measured. Results: In a 14-month old boy with a history of unilateral testicular pain color Doppler ultrasonography was equivocal but the NIRS-derived tissue oxygen saturation index (TSI) was significantly reduced on the left side. Confirmation of torsion of the left testicle was made surgically. Conclusions: Spatially resolved NIRS monitoring of spermatic cord oxygen saturation is feasible in children, adding to prior studies of testicular oxygen saturation in adults. Customized device design and further clinical trials would enhance the applicability of NIRS as a diagnostic entity for torsion.

The EpiNo® Device: Efficacy, Tolerability, and Impact on Pelvic Floor—Implications for Future Research

PubMed Central

Kavvadias, Tilemachos; Hoesli, Irene

2016-01-01

Aims. The aim of this review is to provide a comprehensive overview of the available literature on preventing perineal trauma with the EpiNo. Methods. We perfomed a literature research in the MedLine and EMBASE databases for studies referring to EpiNo published between 1990 and 2014, without restrictions for language and study type. Results. Five published studies were identified, regarding the effect of EpiNo on the rate of episiotomy and perineal tears, pelvic floor muscle function, and fetal outcome. The device seems to reduce episiotomy and perineal tears' rate, as well as the risk for levator ani microtrauma and avulsion, though not always statistically significant. It does not seem to have an effect on duration of second stage of labour and fetal outcome. The device is well tolerated and the adverse events are rare and mild. However, design and reporting bias in the reviewed articles do not allow evidence based conclusions. Conclusions. The EpiNo device seems to be promising, with potential positive effects on natural birth, while being uncomplicated to use and without major complications. Well designed, randomized trials are needed in order to understand the effects of EpiNo on pelvic floor and make evidence based recommendations on its use. PMID:26981126

Study protocol for a randomized controlled pilot-trial on the semiocclusive treatment of fingertip amputation injuries using a novel finger cap

PubMed Central

Schultz, Jurek; Leupold, Susann; Grählert, Xina; Pfeiffer, Roland; Schwanebeck, Uta; Schröttner, Percy; Djawid, Barbara; Artsimovich, Wladislav; Kozak, Karol; Fitze, Guido

2017-01-01

Abstract Introduction: Fingertip amputation injuries are common in all ages. Conservatively treated fingertips can regenerate skin and soft tissues to form a functionally and cosmetically excellent new fingertip. Little is known about this ability that, in humans, is confined to the fingertips. Even less is known about the role of the bacteria that regularly colonize these wounds without negative impact on regeneration and healing. As an alternative to surgery, self-adhesive film dressings are commonly used to establish a wet chamber around the injury. These dressings leak malodorous wound fluid eventually until the wound is dry. Having that into consideration, we have therefore developed a silicone finger cap that forms a mechanically protected, wet chamber around the injury for optimal regeneration conditions. It contains a puncturable reservoir for excess wound fluid, which can be thus routinely analyzed for diagnostic and research purposes. This study protocol explains the first randomized controlled trial (RCT) on the semiocclusive treatment of fingertip amputations in both children and adults comparing traditional film dressings with the novel silicone finger cap. Being the first RCT using 2 medical devices not yet certified for this indication, it will gather valuable information for the understanding of fingertip regeneration and the design of future definitive studies. Methods and analysis: By employing an innovative pseudo-cross-over-design with a dichotomous primary endpoint based on patients preference, this pilot study will gain statistically significant data with a very limited sample size. Our RCT will investigate acceptance, safety, effectiveness, and efficacy of this novel medical device while gathering information on the clinical course and outcome of conservatively treated fingertip injuries. A total of 22 patients older than 2 years will be randomly assigned to start the conservative treatment with either the traditional film-dressing or the novel finger cap. The treatment will be changed to the other alternative for another 2 weeks before the patient or the guardian is confronted with the decision of which method they would prefer for the rest of the treatment (if required). Ethics and dissemination: Ethical approval (EK 148042015) of the study protocol has been obtained from Institutional Review Board at the TU Dresden. The trial is registered at the European Database on Medical Devices (EUDAMED-No.: CIV-15-03-013246) and at ClinicalTrials.gov (NCT03089060). PMID:29019891

Transcatheter aortic valve replacement: historical perspectives, current evidence, and future directions.

PubMed

Horne, Aaron; Reineck, Elizabeth A; Hasan, Rani K; Resar, Jon R; Chacko, Matthews

2014-10-01

Severe aortic stenosis (AS) results in considerable morbidity and mortality without aortic valve replacement and is expected to increase in prevalence with the aging population. Because AS primarily affects the elderly, many patients with comorbidities are poor candidates for surgical aortic valve replacement (SAVR) and may not be referred. Transcatheter aortic valve replacement (TAVR) has emerged as transformative technology for the management of AS over the past decade. Randomized trials have established the safety and efficacy of TAVR with improved mortality and quality of life compared with medical therapy in inoperable patients, while demonstrating noninferiority and even superiority to SAVR among high-risk operative candidates. However, early studies demonstrated an early penalty of stroke and vascular complications with TAVR as well as increased paravalvular leak as compared with SAVR. Two device platforms have been evaluated and approved for use in the United States: the Edwards SAPIEN and the Medtronic CoreValve. Early studies also suggest cost-effectiveness for TAVR. Ongoing studies are evaluating new iterations of the aforementioned TAVR devices, novel device designs, and applications of TAVR in expanded populations of patients including those with lower risk profiles as well as those with comorbidities that were excluded from early clinical trials. Future improvements in TAVR technology will likely reduce periprocedural and long-term complications. Further studies are needed to confirm device durability over long-term follow-up and explore the applicability of TAVR to broader AS patient populations. Copyright © 2014 Mosby, Inc. All rights reserved.

Rehabilitation for Chronic Ankle Instability With or Without Destabilization Devices: A Randomized Controlled Trial

PubMed Central

Donovan, Luke; Hart, Joseph M.; Saliba, Susan A.; Park, Joseph; Feger, Mark Anthony; Herb, Christopher C.; Hertel, Jay

2016-01-01

Context:  Individuals with chronic ankle instability (CAI) have deficits in neuromuscular control and altered movement patterns. Ankle-destabilization devices have been shown to increase lower extremity muscle activity during functional tasks and may be useful tools for improving common deficits and self-reported function. Objective:  To determine whether a 4-week rehabilitation program that includes destabilization devices has greater effects on self-reported function, range of motion (ROM), strength, and balance than rehabilitation without devices in patients with CAI. Design:  Randomized controlled clinical trial. Setting:  Laboratory. Patients or Other Participants:  A total of 26 patients with CAI (7 men, 19 women; age = 21.34 ± 3.06 years, height = 168.96 ± 8.77 cm, mass = 70.73 ± 13.86 kg). Intervention(s):  Patients completed baseline measures and were randomized into no-device and device groups. Both groups completed 4 weeks of supervised, impairment-based progressive rehabilitation with or without devices and then repeated baseline measures. Main Outcome Measure(s):  We assessed self-reported function using the Foot and Ankle Ability Measure. Ankle ROM was measured with an inclinometer. Ankle strength was assessed using a handheld dynamometer during maximal voluntary isometric contractions. Balance was measured using a composite score of 3 reach directions from the Star Excursion Balance Test and a force plate to calculate center of pressure during eyes-open and eyes-closed single-limb balance. We compared each dependent variable using a 2 × 2 (group × time) analysis of variance and post hoc tests as appropriate and set an a priori α level at .05. The Hedges g effect sizes and associated 95% confidence intervals were calculated. Results:  We observed no differences between the no-device and device groups for any measure. However, both groups had large improvements in self-reported function and ankle strength. Conclusions:  Incorporating destabilization devices into rehabilitation did not improve ankle function more effectively than traditional rehabilitation tools because both interventions resulted in similar improvements. Impairment-based progressive rehabilitation improved clinical outcomes associated with CAI. PMID:26934211

First-in-Human Trial of a Novel Suprachoroidal Retinal Prosthesis

PubMed Central

Ayton, Lauren N.; Blamey, Peter J.; Guymer, Robyn H.; Luu, Chi D.; Nayagam, David A. X.; Sinclair, Nicholas C.; Shivdasani, Mohit N.; Yeoh, Jonathan; McCombe, Mark F.; Briggs, Robert J.; Opie, Nicholas L.; Villalobos, Joel; Dimitrov, Peter N.; Varsamidis, Mary; Petoe, Matthew A.; McCarthy, Chris D.; Walker, Janine G.; Barnes, Nick; Burkitt, Anthony N.; Williams, Chris E.; Shepherd, Robert K.; Allen, Penelope J.

2014-01-01

Retinal visual prostheses (“bionic eyes”) have the potential to restore vision to blind or profoundly vision-impaired patients. The medical bionic technology used to design, manufacture and implant such prostheses is still in its relative infancy, with various technologies and surgical approaches being evaluated. We hypothesised that a suprachoroidal implant location (between the sclera and choroid of the eye) would provide significant surgical and safety benefits for patients, allowing them to maintain preoperative residual vision as well as gaining prosthetic vision input from the device. This report details the first-in-human Phase 1 trial to investigate the use of retinal implants in the suprachoroidal space in three human subjects with end-stage retinitis pigmentosa. The success of the suprachoroidal surgical approach and its associated safety benefits, coupled with twelve-month post-operative efficacy data, holds promise for the field of vision restoration. Trial Registration Clinicaltrials.gov NCT01603576 PMID:25521292

Mail-Order Microfluidics: Evaluation of Stereolithography for the Production of Microfluidic Devices

PubMed Central

Au, Anthony K.; Lee, Wonjae; Folch, Albert

2015-01-01

The vast majority of microfluidic devices are developed in PDMS by molding (“soft lithography”) because PDMS is an inexpensive material, has physicochemical properties that are well suited for biomedical and physical sciences applications, and design cycle lengths are generally adequate for prototype development. However, PDMS molding is tediously slow and thus cannot provide the high- or medium-volume production required for the commercialization of devices. While high-throughput plastic molding techniques (e.g. injection molding) exist, the exorbitant cost of the molds and/or the equipment can be a serious obstacle for device commercialization, especially for small startups. High-volume production is not required to reach niche markets such as clinical trials, biomedical research supplies, customized research equipment, and classroom projects. Crucially, both PDMS and plastic molding are layer-by-layer techniques where each layer is produced as a result of physicochemical processes not specified in the initial photomask(s) and where the final device requires assembly by bonding, all resulting in a cost that is very hard to predict at the start of the project. By contrast, stereolithography (SL) is an automated fabrication technique that allows for the production of quasi-arbitrary 3D shapes in a single polymeric material at medium-volume throughputs (ranging from a single part to hundreds of parts). Importantly, SL devices can be designed between several groups using CAD tools, conveniently ordered by mail, and their cost precisely predicted via a web interface. Here we evaluate the resolution of an SL mail-order service and the main causes of resolution loss; the optical clarity of the devices and how to address the lack of clarity for imaging in the channels; and the future role that SL could play in the commercialization of microfluidic devices. PMID:24510161

Mail-order microfluidics: evaluation of stereolithography for the production of microfluidic devices.

PubMed

Au, Anthony K; Lee, Wonjae; Folch, Albert

2014-04-07

The vast majority of microfluidic devices are developed in PDMS by molding ("soft lithography") because PDMS is an inexpensive material, has physicochemical properties that are well suited for biomedical and physical sciences applications, and design cycle lengths are generally adequate for prototype development. However, PDMS molding is tediously slow and thus cannot provide the high- or medium-volume production required for the commercialization of devices. While high-throughput plastic molding techniques (e.g. injection molding) exist, the exorbitant cost of the molds and/or the equipment can be a serious obstacle for device commercialization, especially for small startups. High-volume production is not required to reach niche markets such as clinical trials, biomedical research supplies, customized research equipment, and classroom projects. Crucially, both PDMS and plastic molding are layer-by-layer techniques where each layer is produced as a result of physicochemical processes not specified in the initial photomask(s) and where the final device requires assembly by bonding, all resulting in a cost that is very hard to predict at the start of the project. By contrast, stereolithography (SL) is an automated fabrication technique that allows for the production of quasi-arbitrary 3D shapes in a single polymeric material at medium-volume throughputs (ranging from a single part to hundreds of parts). Importantly, SL devices can be designed between several groups using CAD tools, conveniently ordered by mail, and their cost precisely predicted via a web interface. Here we evaluate the resolution of an SL mail-order service and the main causes of resolution loss; the optical clarity of the devices and how to address the lack of clarity for imaging in the channels; and the future role that SL could play in the commercialization of microfluidic devices.

Notebook input devices put to the age test: the usability of trackpoint and touchpad for middle-aged adults.

PubMed

Armbrüster, C; Sutter, C; Ziefle, M

2007-03-01

In two experiments, the usability of input devices integrated into computer notebooks was under study. The most common input devices, touchpad (experiment 1) and trackpoint (experiment 2) were examined. So far, the evaluation of mobile input devices has been restricted to younger users. However, due to ongoing demographic change, the main target group of mobile devices will be older users. Therefore, the present study focused on ageing effects. A total of 14 middle-aged (40-65 years) and 20 younger (20-32 years) users were compared regarding speed and accuracy of cursor control in a point-click and a point-drag-drop task. Moreover, the effects of training were addressed by examining the performance increase over time. In total, 640 trials per task and input device were executed. The results show that ageing is a central factor to be considered in input device design. Middle-aged users were significantly slower than younger users when executing the different tasks. Over time, a significant training effect was observed for both devices and both age groups, although the benefit of training was greater for the middle-aged group. Generally, the touchpad performance was higher than the trackpoint performance in both age groups, but the age-related performance decrements were less distinct when using the touchpad.

Design and validation of a method for evaluation of interocular interaction.

PubMed

Lai, Xin Jie Angela; Alexander, Jack; Ho, Arthur; Yang, Zhikuan; He, Mingguang; Suttle, Catherine

2012-02-01

To design a simple viewing system allowing dichoptic masking, and to validate this system in adults and children with normal vision. A Trial Frame Apparatus (TFA) was designed to evaluate interocular interaction. This device consists of a trial frame, a 1 mm pinhole in front of the tested eye and a full or partial occluder in front of the non-tested eye. The difference in visual function in one eye between the full- and partial-occlusion conditions was termed the Interaction Index. In experiment 1, low-contrast acuity was measured in six adults using five types of partial occluder. Interaction Index was compared between these five, and the occluder showing the highest Index was used in experiment 2. In experiment 2, low-contrast acuity, contrast sensitivity, and alignment sensitivity were measured in the non-dominant eye of 45 subjects (15 older adults, 15 young adults, and 15 children), using the TFA and an existing well-validated device (shutter goggles) with full and partial occlusion of the dominant eye. These measurements were repeated on 11 subjects of each group using TFA in the partial-occlusion condition only. Repeatability of visual function measurements using TFA was assessed using the Bland-Altman method and agreement between TFA and goggles in terms of visual functions and interactions was assessed using the Bland-Altman method and t-test. In all three subject groups, the TFA showed a high level of repeatability in all visual function measurements. Contrast sensitivity was significantly poorer when measured using TFA than using goggles (p < 0.05). However, Interaction Index of all three visual functions showed acceptable agreement between TFA and goggles (p > 0.05). The TFA may provide an acceptable method for the study of some forms of dichoptic masking in populations where more complex devices (e.g., shutter goggles) cannot be used.

Trials of transvaginal mesh devices for pelvic organ prolapse: a systematic database review of the US FDA approval process.

PubMed

Heneghan, Carl J; Goldacre, Ben; Onakpoya, Igho; Aronson, Jeffrey K; Jefferson, Tom; Pluddemann, Annette; Mahtani, Kamal R

2017-12-06

Transvaginal mesh devices are approved in the USA by the Food and Drug Administration (FDA), through the 510(k) system. However, there is uncertainty about the benefit to harm balance of mesh approved for pelvic organ prolapse. We, therefore, assessed the evidence at the time of approval for transvaginal mesh products and the impact of safety studies the FDA mandated in 2012 because of emerging harms. We used FDA databases to determine the evidence for approval of transvaginal mesh. To create a 'family tree' of device equivalence, we used the 510(k) regulatory approval of the 1985 Mersilene Mesh (Ethicon) and the 1996 ProteGen Sling (Boston Scientific), searched for all subsequently related device approvals, and for the first published randomised trial evidence. We assessed compliance with all FDA 522 orders issued in 2012 requiring postmarketing surveillance studies. We found 61 devices whose approval ultimately relied on claimed equivalence to the Mersilene Mesh and the ProteGen Sling. We found no clinical trials evidence for these 61 devices at the time of approval. Publication of randomised clinical trials occurred at a median of 5 years after device approval (range 1-14 years). Analysis of 119 FDA 522 orders revealed that in 79 (66%) the manufacturer ceased market distribution of the device, and in 26 (22%) the manufacturer had changed the indication. Only seven studies (six cohorts and new randomised controlled trial) covering 11 orders were recruiting participants (none had reported outcomes). Transvaginal mesh products for pelvic organ prolapse have been approved on the basis of weak evidence over the last 20 years. Devices have inherited approval status from a few products. A publicly accessible registry of licensed invasive devices, with details of marketing status and linked evidence, should be created and maintained at the time of approval. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Patient safety and efficacy as measured by clinical trials and regulatory policy.

PubMed

Harvey, B E; Alpert, S

1997-01-01

Virtual Reality and other technological innovations in medicine provide new challenges to the regulatory framework of the premarket review process for medical devices. By reinventing the government-academia-industry partnership, clinical trial data necessary for a medical device to enter the market can be more efficiently obtained.

Building the bionic eye: an emerging reality and opportunity.

PubMed

Merabet, Lotfi B

2011-01-01

Once the topic of folklore and science fiction, the notion of restoring vision to the blind is now approaching a tractable reality. Technological advances have inspired numerous multidisciplinary groups worldwide to develop visual neuroprosthetic devices that could potentially provide useful vision and improve the quality of life of profoundly blind individuals. While a variety of approaches and designs are being pursued, they all share a common principle of creating visual percepts through the stimulation of visual neural elements using appropriate patterns of electrical stimulation. Human clinical trials are now well underway and initial results have been met with a balance of excitement and cautious optimism. As remaining technical and surgical challenges continue to be solved and clinical trials move forward, we now enter a phase of development that requires careful consideration of a new set of issues. Establishing appropriate patient selection criteria, methods of evaluating long-term performance and effectiveness, and strategies to rehabilitate implanted patients will all need to be considered in order to achieve optimal outcomes and establish these devices as viable therapeutic options. Copyright © 2011 Elsevier B.V. All rights reserved.

Robot-Assisted Fracture Surgery: Surgical Requirements and System Design.

PubMed

Georgilas, Ioannis; Dagnino, Giulio; Tarassoli, Payam; Atkins, Roger; Dogramadzi, Sanja

2018-03-09

The design of medical devices is a complex and crucial process to ensure patient safety. It has been shown that improperly designed devices lead to errors and associated accidents and costs. A key element for a successful design is incorporating the views of the primary and secondary stakeholders early in the development process. They provide insights into current practice and point out specific issues with the current processes and equipment in use. This work presents how information from a user-study conducted in the early stages of the RAFS (Robot Assisted Fracture Surgery) project informed the subsequent development and testing of the system. The user needs were captured using qualitative methods and converted to operational, functional, and non-functional requirements based on the methods derived from product design and development. This work presents how the requirements inform a new workflow for intra-articular joint fracture reduction using a robotic system. It is also shown how the various elements of the system are developed to explicitly address one or more of the requirements identified, and how intermediate verification tests are conducted to ensure conformity. Finally, a validation test in the form of a cadaveric trial confirms the ability of the designed system to satisfy the aims set by the original research question and the needs of the users.

A haptic-robotic platform for upper-limb reaching stroke therapy: Preliminary design and evaluation results

PubMed Central

Lam, Paul; Hebert, Debbie; Boger, Jennifer; Lacheray, Hervé; Gardner, Don; Apkarian, Jacob; Mihailidis, Alex

2008-01-01

Background It has been shown that intense training can significantly improve post-stroke upper-limb functionality. However, opportunities for stroke survivors to practice rehabilitation exercises can be limited because of the finite availability of therapists and equipment. This paper presents a haptic-enabled exercise platform intended to assist therapists and moderate-level stroke survivors perform upper-limb reaching motion therapy. This work extends on existing knowledge by presenting: 1) an anthropometrically-inspired design that maximizes elbow and shoulder range of motions during exercise; 2) an unobtrusive upper body postural sensing system; and 3) a vibratory elbow stimulation device to encourage muscle movement. Methods A multi-disciplinary team of professionals were involved in identifying the rehabilitation needs of stroke survivors incorporating these into a prototype device. The prototype system consisted of an exercise device, postural sensors, and a elbow stimulation to encourage the reaching movement. Eight experienced physical and occupational therapists participated in a pilot study exploring the usability of the prototype. Each therapist attended two sessions of one hour each to test and evaluate the proposed system. Feedback about the device was obtained through an administered questionnaire and combined with quantitative data. Results Seven of the nine questions regarding the haptic exercise device scored higher than 3.0 (somewhat good) out of 4.0 (good). The postural sensors detected 93 of 96 (97%) therapist-simulated abnormal postures and correctly ignored 90 of 96 (94%) of normal postures. The elbow stimulation device had a score lower than 2.5 (neutral) for all aspects that were surveyed, however the therapists felt the rehabilitation system was sufficient for use without the elbow stimulation device. Conclusion All eight therapists felt the exercise platform could be a good tool to use in upper-limb rehabilitation as the prototype was considered to be generally well designed and capable of delivering reaching task therapy. The next stage of this project is to proceed to clinical trials with stroke patients. PMID:18498641

Integration of Stable Droplet Formation on a CD Microfluidic Device for Extreme Point of Care Applications

NASA Astrophysics Data System (ADS)

Ganesh, Shruthi Vatsyayani

With the advent of microfluidic technologies for molecular diagnostics, a lot of emphasis has been placed on developing diagnostic tools for resource poor regions in the form of Extreme Point of Care devices. To ensure commercial viability of such a device there is a need to develop an accurate sample to answer system, which is robust, portable, isolated yet highly sensitive and cost effective. This need has been a driving force for research involving integration of different microsystems like droplet microfluidics, Compact-disc (CD)microfluidics along with sample preparation and detection modules on a single platform. This work attempts to develop a proof of concept prototype of one such device using existing CD microfluidics tools to generate stable droplets used in point of care diagnostics (POC diagnostics). Apart from using a fairly newer technique for droplet generation and stabilization, the work aims to develop this method focused towards diagnostics for rural healthcare. The motivation for this work is first described with an emphasis on the current need for diagnostic testing in rural health-care and the general guidelines prescribed by WHO for such a sample to answer system. Furthermore, a background on CD and droplet microfluidics is presented to understand the merits and de-merits of each system and the need for integrating the two. This phase of the thesis also includes different methods employed/demonstrated to generate droplets on a spinning platform. An overview on the detection platforms is also presented to understand the challenges involved in building an extreme point of care device. In the third phase of the thesis, general manufacturing techniques and materials used to accomplish this work is presented. Lastly, design trials for droplet generation is presented. The shortcomings of these trials are solved by investigating mechanisms pertaining to design modification and use of agarose based droplet generation to ensure a more robust sample processing method. This method is further characterized and compared with non-agarose based system and the results are analyzed. In conclusion, future prospects of this work are discussed in relation to extreme POC applications.

Holding Area LINQ Trial (HALT).

PubMed

Lee, John J; Weitz, Daniel; Anand, Rishi

Recent studies have shown that insertable cardiac monitors (ICMs) can be implanted out of the traditional hospital setting and efforts are being made to explore the feasibility of implanting these devices in a specific standardized location other than the operating room or a cardiac catherization/electrophysiology lab. This was a prospective, non-randomized, single center post-market clinical trial designed to occur in the holding area of a hospital operating room or cardiac catheterization/electrophysiology laboratory. The Medtronic Reveal LINQ ICM was implanted and patients were followed for 90 days post implant. This study was designed to observe any procedure related adverse events stemming from the holding area implantation. Twenty patients were implanted at our hospital in a holding room not traditionally associated with the electrophysiology/cardiac/operatory labs. One patient was lost to the 90-day follow up. In one case, ICM implantation led to diagnosis requiring removal of ICM before the 90 day follow up and insertion of a biventricular implantable cardioverter defibrillator (ICD). In the remaining 18 patients, there were no serious complications such as minor skin infections, systemic infections or procedure-related adverse events requiring device explant. When following a standardized protocol with attention to sterile technique, it is feasible to implant ICMs in a holding area with no procedure related adverse events (AE). Copyright © 2017 Indian Heart Rhythm Society. Production and hosting by Elsevier B.V. All rights reserved.

Rationale and design of the multicenter randomized trial investigating the effects of levosimendan pretreatment in patients with low ejection fraction (≤40 %) undergoing CABG with cardiopulmonary bypass (LICORN study).

PubMed

Caruba, Thibaut; Hourton, Delphine; Sabatier, Brigitte; Rousseau, Dominique; Tibi, Annick; Hoffart-Jourdain, Cécile; Souag, Akim; Freitas, Nelly; Yjjou, Mounia; Almeida, Carla; Gomes, Nathalie; Aucouturier, Pascaline; Djadi-Prat, Juliette; Menasché, Philippe; Chatellier, Gilles; Cholley, Bernard

2016-08-05

Patients with a left ventricular ejection fraction (LVEF) of less than 40 % are at high risk of developing postoperative low cardiac output syndrome (LCOS). Despite actual treatments (inotropic agents and/or mechanical assist devices), the mortality rate of such patients remains very high (13 to 24 %). The LICORN trial aims at assessing the efficacy of a preoperative infusion of levosimendan in reducing postoperative LCOS in patients with poor LVEF undergoing coronary artery bypass grafting (CABG). LICORN study is a multicenter, randomized double-blind, placebo-controlled trial in parallel groups. 340 patients with LVEF ≤40 %, undergoing CABG will be recruited from 13 French hospitals. The study drug will be started after anaesthesia induction and infused over 24 h (0.1 μg/kg/min). The primary outcome (postoperative LCOS) is evaluated using a composite criterion composed of: 1) need for inotropic agents beyond 24 h following discontinuation of the study drug; 2) need for post-operative mechanical assist devices or failure to wean from these techniques when inserted pre-operatively; 3) need for renal replacement therapy. Secondary outcomes include: 1) mortality at Day 28 and Day 180; 2) each item of the composite criterion of the primary outcome; 3) the number of "ventilator-free" days and "out of intensive care unit" days at Day 28. The usefulness of levosimendan in the perioperative period has not yet been documented with a high level of evidence. The LICORN study is the first randomized controlled trial evaluating the clinical value of preoperative levosimendan in high risk cardiac surgical patients undergoing CABG. NCT02184819 (ClinicalTrials.gov).

Effectiveness of robot-assisted therapy on ankle rehabilitation – a systematic review

PubMed Central

2013-01-01

Objective The aim of this study was to provide a systematic review of studies that investigated the effectiveness of robot-assisted therapy on ankle motor and function recovery from musculoskeletal or neurologic ankle injuries. Methods Thirteen electronic databases of articles published from January, 1980 to June, 2012 were searched using keywords ‘ankle*’, ‘robot*’, ‘rehabilitat*’ or ‘treat*’ and a free search in Google Scholar based on effects of ankle rehabilitation robots was also conducted. References listed in relevant publications were further screened. Eventually, twenty-nine articles were selected for review and they focused on effects of robot-assisted ankle rehabilitation. Results Twenty-nine studies met the inclusion criteria and a total of 164 patients and 24 healthy subjects participated in these trials. Ankle performance and gait function were the main outcome measures used to assess the therapeutic effects of robot-assisted ankle rehabilitation. The protocols and therapy treatments were varied, which made comparison among different studies difficult or impossible. Few comparative trials were conducted among different devices or control strategies. Moreover, the majority of study designs met levels of evidence that were no higher than American Academy for Cerebral Palsy (CP) and Developmental Medicine (AACPDM) level IV. Only one study used a Randomized Control Trial (RCT) approach with the evidence level being II. Conclusion All the selected studies showed improvements in terms of ankle performance or gait function after a period of robot-assisted ankle rehabilitation training. The most effective robot-assisted intervention cannot be determined due to the lack of universal evaluation criteria for various devices and control strategies. Future research into the effects of robot-assisted ankle rehabilitation should be carried out based on universal evaluation criteria, which could determine the most effective method of intervention. It is also essential to conduct trials to analyse the differences among different devices or control strategies. PMID:23517734

Field assessment of a novel household-based water filtration device: a randomised, placebo-controlled trial in the Democratic Republic of Congo.

PubMed

Boisson, Sophie; Kiyombo, Mbela; Sthreshley, Larry; Tumba, Saturnin; Makambo, Jacques; Clasen, Thomas

2010-09-10

Household water treatment can improve the microbiological quality of drinking water and may prevent diarrheal diseases. However, current methods of treating water at home have certain shortcomings, and there is evidence of bias in the reported health impact of the intervention in open trial designs. We undertook a randomised, double-blinded, placebo-controlled trial among 240 households (1,144 persons) in rural Democratic Republic of Congo to assess the field performance, use and effectiveness of a novel filtration device in preventing diarrhea. Households were followed up monthly for 12 months. Filters and placebos were monitored for longevity and for microbiological performance by comparing thermotolerant coliform (TTC) levels in influent and effluent water samples. Mean longitudinal prevalence of diarrhea was estimated among participants of all ages. Compliance was assessed through self-reported use and presence of water in the top vessel of the device at the time of visit. Over the 12-month follow-up period, data were collected for 11,236 person-weeks of observation (81.8% total possible). After adjusting for clustering within the household, the longitudinal prevalence ratio of diarrhoea was 0.85 (95% confidence interval: 0.61-1.20). The filters achieved a 2.98 log reduction in TTC levels while, for reasons that are unclear, the placebos achieved a 1.05 log reduction (p<0.0001). After 8 months, 68% of intervention households met the study's definition of current users, though most (73% of adults and 95% of children) also reported drinking untreated water the previous day. The filter maintained a constant flow rate over time, though 12.4% of filters were damaged during the course of the study. While the filter was effective in improving water quality, our results provide little evidence that it was protective against diarrhea. The moderate reduction observed nevertheless supports the need for larger studies that measure impact against a neutral placebo. Current Controlled Trials ISRCTN03844341.

Randomised comparison of the effectiveness of the laryngeal mask airway supreme, i-gel and current practice in the initial airway management of prehospital cardiac arrest (REVIVE-Airways): a feasibility study research protocol

PubMed Central

Benger, Jonathan Richard; Voss, Sarah; Coates, David; Greenwood, Rosemary; Nolan, Jerry; Rawstorne, Steven; Rhys, Megan; Thomas, Matthew

2013-01-01

Introduction Effective cardiopulmonary resuscitation with appropriate airway management improves outcomes following out-of-hospital cardiac arrest (OHCA). Historically, tracheal intubation has been accepted as the optimal form of OHCA airway management in the UK. The Joint Royal Colleges Ambulance Liaison Committee recently concluded that newer supraglottic airway devices (SADs) are safe and effective devices for hospital procedures and that their use in OHCA should be investigated. This study will address an identified gap in current knowledge by assessing whether it is feasible to use a cluster randomised design to compare SADs with current practice, and also to each other, during OHCA. Methods and analysis The primary objective of this study is to assess the feasibility of a cluster randomised trial to compare the ventilation success of two newer SADs: the i-gel and the laryngeal mask airway supreme to usual practice during the initial airway management of OHCA. The secondary objectives are to collect data on ventilation success, further airway interventions required, loss of a previously established airway during transport, airway management on arrival at hospital (or termination of the resuscitation attempt), initial resuscitation success, survival to intensive care admission, survival to hospital discharge and patient outcome at 3 months. Ambulance paramedics will be randomly allocated to one of the three methods of airway management. Adults in medical OHCA attended by a trial paramedic will be eligible for the study. Ethics and dissemination Approval for the study has been obtained from a National Health Service Research Ethics Committee with authority to review proposals for trials of a medical device in incapacitated adults. The results will be made publicly available on an open access website, and we will publish the findings in appropriate journals and present them at national and international conferences relevant to the subject field. Trial registration ISRCTN: 18528625. PMID:23408081

Smart Technology in Lung Disease Clinical Trials.

PubMed

Geller, Nancy L; Kim, Dong-Yun; Tian, Xin

2016-01-01

This article describes the use of smart technology by investigators and patients to facilitate lung disease clinical trials and make them less costly and more efficient. By "smart technology" we include various electronic media, such as computer databases, the Internet, and mobile devices. We first describe the use of electronic health records for identifying potential subjects and then discuss electronic informed consent. We give several examples of using the Internet and mobile technology in clinical trials. Interventions have been delivered via the World Wide Web or via mobile devices, and both have been used to collect outcome data. We discuss examples of new electronic devices that recently have been introduced to collect health data. While use of smart technology in clinical trials is an exciting development, comparison with similar interventions applied in a conventional manner is still in its infancy. We discuss advantages and disadvantages of using this omnipresent, powerful tool in clinical trials, as well as directions for future research. Published by Elsevier Inc.

Battery thermal management unit

NASA Astrophysics Data System (ADS)

Sanders, Nicholas A.

1989-03-01

A battery warming device has been designed which uses waste heat from an operating internal combustion engine to warm a battery. A portion of the waste heat is stored in the sensible and latent heat of a phase change type material for use in maintaining the battery temperature after the engine is shut off. The basic design of the device consists of a Phase Change Material (PCM) reservoir and a simple heat exchanger connected to the engineer's cooling system. Two types of units were built, tested and field trialed. A strap-on type which was strapped to the side of an automotive battery and was intended for the automotive after-market and a tray type on which a battery or batteries sat. This unit was intended for the heavy duty truck market. It was determined that both types of units increased the average cranking power of the batteries they were applied to. Although there were several design problems with the units such as the need for an automatic thermostatically controlled bypass valve, the overall feeling is that there is a market opportunity for both the strap-on and tray type battery warming units.

Field Assessment of a Novel Household-Based Water Filtration Device: A Randomised, Placebo-Controlled Trial in the Democratic Republic of Congo

PubMed Central

Boisson, Sophie; Kiyombo, Mbela; Sthreshley, Larry; Tumba, Saturnin; Makambo, Jacques; Clasen, Thomas

2010-01-01

Background Household water treatment can improve the microbiological quality of drinking water and may prevent diarrheal diseases. However, current methods of treating water at home have certain shortcomings, and there is evidence of bias in the reported health impact of the intervention in open trial designs. Methods and Findings We undertook a randomised, double-blinded, placebo-controlled trial among 240 households (1,144 persons) in rural Democratic Republic of Congo to assess the field performance, use and effectiveness of a novel filtration device in preventing diarrhea. Households were followed up monthly for 12 months. Filters and placebos were monitored for longevity and for microbiological performance by comparing thermotolerant coliform (TTC) levels in influent and effluent water samples. Mean longitudinal prevalence of diarrhea was estimated among participants of all ages. Compliance was assessed through self-reported use and presence of water in the top vessel of the device at the time of visit. Over the 12-month follow-up period, data were collected for 11,236 person-weeks of observation (81.8% total possible). After adjusting for clustering within the household, the longitudinal prevalence ratio of diarrhoea was 0.85 (95% confidence interval: 0.61–1.20). The filters achieved a 2.98 log reduction in TTC levels while, for reasons that are unclear, the placebos achieved a 1.05 log reduction (p<0.0001). After 8 months, 68% of intervention households met the study's definition of current users, though most (73% of adults and 95% of children) also reported drinking untreated water the previous day. The filter maintained a constant flow rate over time, though 12.4% of filters were damaged during the course of the study. Conclusions While the filter was effective in improving water quality, our results provide little evidence that it was protective against diarrhea. The moderate reduction observed nevertheless supports the need for larger studies that measure impact against a neutral placebo. Trial Registration Current Controlled Trials ISRCTN03844341 PMID:20856584

Launching a Novel Preclinical Infrastructure: Comparative Oncology Trials Consortium Directed Therapeutic Targeting of TNFα to Cancer Vasculature

PubMed Central

Mazcko, Christina; Hanna, Engy; Kachala, Stefan; LeBlanc, Amy; Newman, Shelley; Vail, David; Henry, Carolyn; Thamm, Douglas; Sorenmo, Karin; Hajitou, Amin; Pasqualini, Renata; Arap, Wadih

2009-01-01

Background Under the direction and sponsorship of the National Cancer Institute, we report on the first pre-clinical trial of the Comparative Oncology Trials Consortium (COTC). The COTC is a novel infrastructure to integrate cancers that naturally develop in pet dogs into the development path of new human drugs. Trials are designed to address questions challenging in conventional preclinical models and early phase human trials. Large animal spontaneous cancer models can be a valuable addition to successful studies of cancer biology and novel therapeutic drug, imaging and device development. Methodology/Principal Findings Through this established infrastructure, the first trial of the COTC (COTC001) evaluated a targeted AAV-phage vector delivering tumor necrosis factor (RGD-A-TNF) to αV integrins on tumor endothelium. Trial progress and data was reviewed contemporaneously using a web-enabled electronic reporting system developed for the consortium. Dose-escalation in cohorts of 3 dogs (n = 24) determined an optimal safe dose (5×1012 transducing units intravenous) of RGD-A-TNF. This demonstrated selective targeting of tumor-associated vasculature and sparing of normal tissues assessed via serial biopsy of both tumor and normal tissue. Repetitive dosing in a cohort of 14 dogs, at the defined optimal dose, was well tolerated and led to objective tumor regression in two dogs (14%), stable disease in six (43%), and disease progression in six (43%) via Response Evaluation Criteria in Solid Tumors (RECIST). Conclusions/Significance The first study of the COTC has demonstrated the utility and efficiency of the established infrastructure to inform the development of new cancer drugs within large animal naturally occurring cancer models. The preclinical evaluation of RGD-A-TNF within this network provided valuable and necessary data to complete the design of first-in-man studies. PMID:19330034

Broad Band Antireflection Coating on Zinc Sulphide Window for Shortwave infrared cum Night Vision System

NASA Astrophysics Data System (ADS)

Upadhyaya, A. S.; Bandyopadhyay, P. K.

2012-11-01

In state of art technology, integrated devices are widely used or their potential advantages. Common system reduces weight as well as total space covered by its various parts. In the state of art surveillance system integrated SWIR and night vision system used for more accurate identification of object. In this system a common optical window is used, which passes the radiation of both the regions, further both the spectral regions are separated in two channels. ZnS is a good choice for a common window, as it transmit both the region of interest, night vision (650 - 850 nm) as well as SWIR (0.9 - 1.7 μm). In this work a broad band anti reflection coating is developed on ZnS window to enhance the transmission. This seven layer coating is designed using flip flop design method. After getting the final design, some minor refinement is done, using simplex method. SiO2 and TiO2 coating material combination is used for this work. The coating is fabricated by physical vapour deposition process and the materials were evaporated by electron beam gun. Average transmission of both side coated substrate from 660 to 1700 nm is 95%. This coating also acts as contrast enhancement filter for night vision devices, as it reflect the region of 590 - 660 nm. Several trials have been conducted to check the coating repeatability, and it is observed that transmission variation in different trials is not very much and it is under the tolerance limit. The coating also passes environmental test for stability.

The "Healthy Habits, Healthy Girls" randomized controlled trial for girls: study design, protocol, and baseline results.

PubMed

Leme, Ana Carolina Barco; Philippi, Sonia Tucunduva

2015-07-01

The purpose of this article is to describe the study design, protocol, and baseline results of the "Healthy Habits, Healthy Girls" program. The intervention is being evaluated through a randomized controlled trial in 10 public schools in the city of São Paulo, Brazil. Data on the following variables were collected and assessed at baseline and will be reevaluated at 7 and 12 months: body mass index, waist circumference, dietary intake, nutrition, physical activity, social cognitive mediators, physical activity level, sedentary behaviors, self-rated physical status, and overall self-esteem. According to the baseline results, 32.4% and 23.4% of girls were overweight in the intervention and control groups, respectively, and in both groups a higher percentage failed to meet daily recommendations for moderate and vigorous physical activity and maximum screen time (TV, computer, mobile devices). There were no significant differences between the groups for most of the variables, except age (p = 0.000) and waist circumference (p = 0.014). The study showed a gap in the Brazilian literature on protocols for randomized controlled trials to prevent obesity among youth. The current study may thus be an important initial contribution to the field.

Randomized trial of the ForeseeHome monitoring device for early detection of neovascular age-related macular degeneration. The HOme Monitoring of the Eye (HOME) study design - HOME Study report number 1.

PubMed

Chew, Emily Y; Clemons, Traci E; Bressler, Susan B; Elman, Michael J; Danis, Ronald P; Domalpally, Amitha; Heier, Jeffrey S; Kim, Judy E; Garfinkel, Richard A

2014-03-01

To evaluate the effects of a home-monitoring device with tele-monitoring compared with standard care in detection of progression to choroidal neovascularization (CNV) associated with age-related macular degeneration (AMD), the leading cause of blindness in the US. Participants, aged 55 to 90 years, at high risk of developing CNV associated with AMD were recruited to the HOme Monitoring of Eye (HOME) Study, an unmasked, multi-center, randomized trial of the ForeseeHome (FH) device plus standard care vs. standard care alone. The FH device utilizes preferential hyperacuity perimetry and tele-monitoring to detect changes in vision function associated with development of CNV, potentially prior to symptom and visual acuity loss. After establishing baseline measurements, subsequent changes on follow-up are detected by the device, causing the monitoring center to alert the clinical center to recall participants for an exam. Standard care consists of instructions for self-monitoring visual changes with subsequent self-report to the clinical center. The primary objective of this study is to determine whether home monitoring plus standard care in comparison with standard care alone, results in earlier detection of incident CNV with better present visual acuity. The primary outcome is the decline in visual acuity at CNV diagnosis from baseline. Detection of CNV prior to substantial vision loss is critical as vision outcome following anti-angiogenic therapy is dependent on the visual acuity at initiation of treatment. HOME Study is the first large scale study to test the use of home tele-monitoring system in the management of AMD patients. Published by Elsevier Inc.

Multicenter clinical trial of a home-use nonablative fractional laser device for wrinkle reduction.

PubMed

Leyden, James; Stephens, Thomas J; Herndon, James H

2012-11-01

Until now, nonablative fractional treatments could only be delivered in an office setting by trained professionals. The goal of this work was to perform clinical testing of a nonablative fractional laser device designed for home-use. This multicenter trial consisted of two clinical studies with slightly varying treatment protocols in which subjects performed at-home treatments of periorbital wrinkles using a handheld nonablative fractional laser. Both studies included an active treatment phase (daily treatments) and a maintenance phase (twice-weekly treatments). In all, 36 subjects were followed up for as long as 5 months after completion of the maintenance phase and 90 subjects were followed up until the completion of the maintenance phase. Evaluations included in-person investigator assessment, independent blinded review of high-resolution images using the Fitzpatrick Wrinkle Scale, and subject self-assessment. All 124 subjects who completed the study were able to use the device following written instructions for use. Treatments were well tolerated with good protocol compliance. Independent blinded evaluations by a panel of physicians showed Fitzpatrick Wrinkle Scale score improvement by one or more grades in 90% of subjects at the completion of the active phase and in 79% of subjects at the completion of the maintenance phase. The most prevalent side effect was transient posttreatment erythema. Lack of a control group and single-blinded study groups were limitations. Safety testing with self-applications by users demonstrated the utility of the device for home use. Independent blinded review of clinical images confirmed the device's proficiency for improving periorbital wrinkles. Copyright © 2012 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

Electrophoresis in space.

PubMed

Bauer, J; Hymer, W C; Morrison, D R; Kobayashi, H; Seaman, G V; Weber, G

1999-01-01

Programs for free flow electrophoresis in microgravity over the past 25 years are reviewed. Several studies accomplished during 20 spaceflight missions have demonstrated that sample throughput is significantly higher in microgravity than on the ground. Some studies have shown that resolution is also increased. However, many cell separation trials have fallen victim to difficulties associated with experimenting in the microgravity environment such as microbial contamination, air bubbles in electrophoresis chambers, and inadequate facilities for maintaining cells before and after separation. Recent studies suggest that the charge density of cells at their surface may also be modified in microgravity. If this result is confirmed, a further cellular mechanism of "sensing" the low gravity environment will have been found. Several free fluid electrophoresis devices are now available. Most have been tried at least once in microgravity. Newer units not yet tested in spaceflight have been designed to accommodate problems associated with space processing. The USCEPS device and the Japanese FFEU device are specifically designed for sterile operations, whereas the Octopus device is designed to reduce electroosmotic and electrohydrodynamic effects, which become dominant and detrimental in microgravity. Some of these devices will also separate proteins by zone electrophoresis, isotachophoresis, or isoelectric focusing in a single unit. Separation experiments with standard test particles are useful and necessary for testing and optimizing new space hardware. A cohesive free fluid electrophoresis program in the future will obviously require (1) flight opportunities and funding, (2) identification of suitable cellular and macromolecular candidate samples, and (3) provision of a proper interface of electrophoresis processing equipment with biotechnological facilities--equipment like bioreactors and protein crystal growth chambers. The authors feel that such capabilities will lead to the production of commercially useful quantities of target products and to an accumulation of new knowledge relating to the complexities of electrostatic phenomena at the cell surface.

Cerebral oximetry in cardiac and major vascular surgery.

PubMed

Fischer, G W; Silvay, G

2010-01-01

We describe the development and current applications of cerebral oximetry (based on near-infrared reflectance spectroscopy) that can be used during cardiac and major vascular surgery to determined brain tissue oxygen saturation. There are presently three cerebral oximetry devices with FDA approval in the United States to measure and monitor cerebral tissue oxygen saturation. 1. INVOS (Somanetics Corporation, Troy, MI - recently COVIDIEN, Boulder, CO); FORE-SIGHT (CAS Medical Systems, Inc. Branford, CT); EQUANOX (Nonin Medical Inc.Minnesota, MN). All devices are portable, non-invasive and easy to use in operating room and intensive care unit. The data provided in these communication may provided information for improvement of perioperative neuromonitoring techniques, and may be crucial in the design of future clinical trials.

HairMax LaserComb laser phototherapy device in the treatment of male androgenetic alopecia: A randomized, double-blind, sham device-controlled, multicentre trial.

PubMed

Leavitt, Matt; Charles, Glenn; Heyman, Eugene; Michaels, David

2009-01-01

The use of low levels of visible or near infrared light for reducing pain, inflammation and oedema, promoting healing of wounds, deeper tissue and nerves, and preventing tissue damage has been known for almost 40 years since the invention of lasers. The HairMax LaserComb is a hand-held Class 3R lower level laser therapy device that contains a single laser module that emulates 9 beams at a wavelength of 655 nm (+/-5%). The device uses a technique of parting the user's hair by combs that are attached to the device. This improves delivery of distributed laser light to the scalp. The combs are designed so that each of the teeth on the combs aligns with a laser beam. By aligning the teeth with the laser beams, the hair can be parted and the laser energy delivered to the scalp of the user without obstruction by the individual hairs on the scalp. The primary aim of the study was to assess the safety and effectiveness of the HairMax LaserComb laser phototherapy device in the promotion of hair growth and in the cessation of hair loss in males diagnosed with androgenetic alopecia (AGA). This double-blind, sham device-controlled, multicentre, 26-week trial randomized male patients with Norwood-Hamilton classes IIa-V AGA to treatment with the HairMax LaserComb or the sham device (2 : 1). The sham device used in the study was identical to the active device except that the laser light was replaced by a non-active incandescent light source. Of the 110 patients who completed the study, subjects in the HairMax LaserComb treatment group exhibited a significantly greater increase in mean terminal hair density than subjects in the sham device group (p < 0.0001). Consistent with this evidence for primary effectiveness, significant improvements in overall hair regrowth were demonstrated in terms of patients' subjective assessment (p < 0.015) at 26 weeks over baseline. The HairMax LaserComb was well tolerated with no serious adverse events reported and no statistical difference in adverse effects between the study groups. The results of this study suggest that the HairMax LaserComb is an effective, well tolerated and safe laser phototherapy device for the treatment of AGA in males.

Randomized Clinical Trial: The Use of SpeechEasy® in Stuttering Treatment

ERIC Educational Resources Information Center

Ritto, Ana Paula; Juste, Fabiola Staróbole; Stuart, Andrew; Kalinowski, Joseph; de Andrade, Claudia Regina Furquim

2016-01-01

Background: Numerous studies have demonstrated the benefit of devices delivering altered auditory feedback (AAF) as a therapeutic alternative for those who stutter. Aims: The effectiveness of a device delivering AAF (SpeechEasy®) was compared with behavioural techniques in the treatment of stuttering in a randomized clinical trial. Methods &…

Development of an encapsulated stem cell-based therapy for diabetes.

PubMed

Tomei, Alice Anna; Villa, Chiara; Ricordi, Camillo

2015-01-01

Islet transplantation can treat the most severe cases of type 1 diabetes but it currently requires deceased donor pancreata as an islet source and chronic immunosuppression to prevent rejection and recurrence of autoimmunity. Stem cell-derived insulin-producing cells may address the shortage of organ donors, whereas cell encapsulation may reduce or eliminate the requirement for immunosuppression, minimizing the risks associated with the islet transplantation procedure, and potentially prolonging graft survival. This review focuses on the design principles for immunoisolation devices and on stem cell differentiation into insulin-producing cell products. The reader will gain understanding of the different types of immunoisolation devices and the key parameters that affect the outcome of the encapsulated graft. Progresses in stem cell differentiation towards mature endocrine islet cells, including the most recent clinical trials and the challenges associated with the application of immunoisolation devices designed for primary islets to stem-cell products, are also discussed. Recent advancements in the field of stem cell-derived islet cell products and immunoisolation strategies hold great promise for type 1 diabetes. However, a combination product including both cells and an immunoisolation strategy still needs to be optimized and tested for safety and efficacy.

The efficiency of gravity distribution devices for on-site wastewater treatment systems.

PubMed

Patel, T; O'Luanaigh, N; Gill, L W

2008-01-01

A detailed analysis of different types of gravity distribution devices, designed to split on-site wastewater effluent equally between percolation trenches, has been carried out both in the laboratory and also in the field under realistic loading conditions. Five different types of distribution device have been compared: a V-notch distribution box, stilling chamber box, T-splitters with and without baffles and tipping bucket device. The trials carried out in the laboratory with clean water showed that flow distribution for all devices was sensitive to both the off-level installation angles and variable flow rates, with the most stable performance achieved using the T-splitters with baffles and tipping bucket devices. In parallel to this, the on-site flow regime experienced at two sites was continuously monitored using a tipping bucket and data-logger over eighteen month periods, finding that the most common flow rates at the distribution unit were in the range of 0.1-2.5 L/min. The on-site performance of these devices receiving both septic tank and secondary treated effluent showed that significant solid deposition and biofilm development had severely affected the equal distribution between the trenches, hence highlighting the need for regular maintenance to ensure efficient performance over time after installation. IWA Publishing 2008.

Securing All intraVenous devices Effectively in hospitalised patients--the SAVE trial: study protocol for a multicentre randomised controlled trial.

PubMed

Rickard, Claire M; Marsh, Nicole; Webster, Joan; Playford, E Geoffrey; McGrail, Matthew R; Larsen, Emily; Keogh, Samantha; McMillan, David; Whitty, Jennifer A; Choudhury, Md Abu; Dunster, Kimble R; Reynolds, Heather; Marshall, Andrea; Crilly, Julia; Young, Jeanine; Thom, Ogilvie; Gowardman, John; Corley, Amanda; Fraser, John F

2015-09-23

Over 70% of all hospital admissions have a peripheral intravenous device (PIV) inserted; however, the failure rate of PIVs is unacceptably high, with up to 69% of these devices failing before treatment is complete. Failure can be due to dislodgement, phlebitis, occlusion/infiltration and/or infection. This results in interrupted medical therapy; painful phlebitis and reinsertions; increased hospital length of stay, morbidity and mortality from infections; and wasted medical/nursing time. Appropriate PIV dressing and securement may prevent many cases of PIV failure, but little comparative data exist regarding the efficacy of various PIV dressing and securement methods. This trial will investigate the clinical and cost-effectiveness of 4 methods of PIV dressing and securement in preventing PIV failure. A multicentre, parallel group, superiority randomised controlled trial with 4 arms, 3 experimental groups (tissue adhesive, bordered polyurethane dressing, sutureless securement device) and 1 control (standard polyurethane dressing) is planned. There will be a 3-year recruitment of 1708 adult patients, with allocation concealment until randomisation by a centralised web-based service. The primary outcome is PIV failure which includes any of: dislodgement, occlusion/infiltration, phlebitis and infection. Secondary outcomes include: types of PIV failure, PIV dwell time, costs, device colonisation, skin colonisation, patient and staff satisfaction. Relative incidence rates of device failure per 100 devices and per 1000 device days with 95% CIs will summarise the impact of each dressing, and test differences between groups. Kaplan-Meier survival curves (with log-rank Mantel-Cox test) will compare device failure over time. p Values of <0.05 will be considered significant. Secondary end points will be compared between groups using parametric or non-parametric techniques appropriate to level of measurement. Ethical approval has been received from Queensland Health (HREC/11/QRCH/152) and Griffith University (NRS/46/11/HREC). Results will be published according to the CONSORT statement and presented at relevant conferences. Australian New Zealand Clinical Trial Registry (ACTRN); 12611000769987. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Mobile applications for handheld devices to screen and randomize acute stroke patients in clinical trials.

PubMed

Qureshi, Ai; Connelly, B; Abbott, Ei; Maland, E; Kim, J; Blake, J

2012-08-01

The availability of internet connectivity and mobile application software used by low-power handheld devices makes smart phones of unique value in time-sensitive clinical trials. Trial-specific applications can be downloaded by investigators from various mobile software distribution platforms or web applications delivered over HTTP. The Antihypertensive Treatment in Acute Cerebral Hemorrhage (ATACH) II investigators in collaboration with MentorMate released the ATACH-II Patient Recruitment mobile application available on iPhone, Android, and Blackberry in 2011. The mobile application provides tools for pre-screening, assessment of eligibility, and randomization of patients. Since the release of ATACH-II mobile application, the CLEAR-IVH (Clot Lysis Evaluating Accelerated Resolution of Intraventricular Hemorrhage) trial investigators have also adopted such a mobile application. The video-conferencing capabilities of the most recent mobile devices open up additional opportunities to involve central coordinating centers in the recruitment process in real time.

Development of Stabilimax NZ From Biomechanical Principles.

PubMed

Panjabi, Manohar M; Timm, Jens Peter

2007-01-01

Traditionally, spinal degeneration and injury have been associated with abnormal intervertebral motion; thus, treatment for lowback pain has centered on prevention of motion through spinal fusion. Although the rate of successful spinal fusions is improving, complications such as adjacent-level syndrome emphasize the need to develop alternatives for treating spinal degeneration. In an effort to improve the clinical outcomes associated with such treatment, we hypothesized that spinal stabilization and a consequent reduction in symptoms is achievable without the harsh restrictions to spinal motion imposed by fusion. This idea was based on the principle of the neutral zone and the neutral zone hypothesis of back pain. Performance requirements for a novel device were determined through a series of biomechanical experiments. From these data, the Stabilimax NZ was developed to provide stabilization to a degenerated or surgically destabilized spine while maintaining the maximum possible total range of motion. Applied Spine Technologies Inc has tested 70 bilateral assemblies of the final design of the Stabilimax NZ, and all exceeded the biomechanical, static, fatigue, wear, and histological requirements necessary to initiate clinical investigation. The Stabilimax NZ device has been systematically designed and tested under protocols developed by Applied Spine Technologies in conjunction with Panjabi, Patwardhan, and Goel. The device decreased the neutral zone in destabilized spines while maintaining substantial range of motion. Development testing has been submitted to the US Food and Drug Administration and permission obtained to initiate an investigational device exemption trial to clinically investigate the efficacy of the Stabilimax NZ device.

Glocal clinical registries: pacemaker registry design and implementation for global and local integration--methodology and case study.

PubMed

da Silva, Kátia Regina; Costa, Roberto; Crevelari, Elizabeth Sartori; Lacerda, Marianna Sobral; de Moraes Albertini, Caio Marcos; Filho, Martino Martinelli; Santana, José Eduardo; Vissoci, João Ricardo Nickenig; Pietrobon, Ricardo; Barros, Jacson V

2013-01-01

The ability to apply standard and interoperable solutions for implementing and managing medical registries as well as aggregate, reproduce, and access data sets from legacy formats and platforms to advanced standard formats and operating systems are crucial for both clinical healthcare and biomedical research settings. Our study describes a reproducible, highly scalable, standard framework for a device registry implementation addressing both local data quality components and global linking problems. We developed a device registry framework involving the following steps: (1) Data standards definition and representation of the research workflow, (2) Development of electronic case report forms using REDCap (Research Electronic Data Capture), (3) Data collection according to the clinical research workflow and, (4) Data augmentation by enriching the registry database with local electronic health records, governmental database and linked open data collections, (5) Data quality control and (6) Data dissemination through the registry Web site. Our registry adopted all applicable standardized data elements proposed by American College Cardiology / American Heart Association Clinical Data Standards, as well as variables derived from cardiac devices randomized trials and Clinical Data Interchange Standards Consortium. Local interoperability was performed between REDCap and data derived from Electronic Health Record system. The original data set was also augmented by incorporating the reimbursed values paid by the Brazilian government during a hospitalization for pacemaker implantation. By linking our registry to the open data collection repository Linked Clinical Trials (LinkedCT) we found 130 clinical trials which are potentially correlated with our pacemaker registry. This study demonstrates how standard and reproducible solutions can be applied in the implementation of medical registries to constitute a re-usable framework. Such approach has the potential to facilitate data integration between healthcare and research settings, also being a useful framework to be used in other biomedical registries.

Mitigating adverse event reporting bias in spine surgery.

PubMed

Auerbach, Joshua D; McGowan, Kevin B; Halevi, Marci; Gerling, Michael C; Sharan, Alok D; Whang, Peter G; Maislin, Greg

2013-08-21

Recent articles in the lay press and literature have raised concerns about the ability to report honest adverse event data from industry-sponsored spine surgery studies. To address this, clinical trials may utilize an independent Clinical Events Committee (CEC) to review adverse events and readjudicate the severity and relatedness accordingly. We are aware of no prior study that has quantified either the degree to which investigator bias is present in adverse event reporting or the effect that an independent CEC has on mitigating this potential bias. The coflex Investigational Device Exemption study is a prospective randomized controlled trial comparing coflex (Paradigm Spine) stabilization with lumbar spinal fusion to treat spinal stenosis and spondylolisthesis. Investigators classified the severity of adverse events (mild, moderate, or severe) and their relationship to the surgery and device (unrelated, unlikely, possibly, probably, or definitely). An independent CEC, composed of three spine surgeons without affiliation to the study sponsor, reviewed and reclassified all adverse event reports submitted by the investigators. The CEC reclassified the level of severity, relation to the surgery, and/or relation to the device in 394 (37.3%) of 1055 reported adverse events. The proportion of adverse events that underwent reclassification was similar in the coflex and fusion groups (37.9% compared with 36.0%, p = 0.56). The CEC was 5.3 (95% confidence interval [CI], 2.6 to 10.7) times more likely to upgrade than downgrade the adverse event. The CEC was 7.3 (95% CI, 5.1 to 10.6) times more likely to upgrade than downgrade the relationship to the surgery and 11.6 (95% CI, 7.5 to 18.8) times more likely to upgrade than downgrade the relationship to the device. The status of the investigator's financial interest in the company had little effect on the reclassification of adverse events. Thirty-seven percent of adverse events were reclassified by the CEC; the large majority of the reclassifications were an upgrade in the level of severity or a designation of greater relatedness to the surgery or device. An independent CEC can identify and mitigate potential inherent investigator bias and facilitate an accurate assessment of the safety profile of an investigational device, and a CEC should be considered a requisite component of future clinical trials.

FemCap with removal strap: ease of removal, safety and acceptability.

PubMed

Mauck, Christine K; Weiner, Debra H; Creinin, Mitchell D; Archer, David F; Schwartz, Jill L; Pymar, Helen C; Ballagh, Susan A; Henry, Deborah M; Callahan, Marianne M

2006-01-01

FemCap is a silicone-rubber barrier contraceptive approved for marketing in the United States. To address reported problems with removal and dislodgment, the device's developer added a strap to the device and increased the height of the brim. This trial assessed whether the new design reduced removal difficulties and had any effects on dislodgment, genital pain/discomfort, safety, and acceptability. Women used the strapped device for 8 weeks with follow-up visits at 2 and 8 weeks. Outcome measures were obtained through diary cards, questionnaires, and naked eye examination. Data from these 120 women were compared with data from 419 women who used the unstrapped FemCap in a previous contraceptive effectiveness study. The strapped device was not significantly easier for users to remove than the unstrapped device. Similar odds of dislodgment and cervical/vaginal irritation were seen with the two devices. Both female and male participants were significantly more likely to report pain/discomfort with use of the strapped device. Female users of the strapped device were significantly more likely to say they disliked their device. In six weeks, two pregnancies were observed, but pregnancy was not an endpoint in the study and no conclusions should be drawn regarding pregnancy rates. The modifications to the FemCap did not significantly improve the ease of device removal and appears to have resulted in significantly more female and male partner pain/discomfort and decreased acceptability, compared with the unstrapped device.

Effectivity of artrihpi irrigation for diabetic ulcer healing: A randomized controlled trial

NASA Astrophysics Data System (ADS)

Gayatri, Dewi; Asmorohadi, Aries; Dahlia, Debie

2018-02-01

The healing process of diabetic ulcer is often impeded by inflammation, infection, and decreased immune state. High pressure irrigation (10-15 psi) may be used to control the infection level. This research was designed to identify the effectiveness of artrihpi irrigation device towards diabetic ulcers in public hospitals in the Central Java. This research is a randomized control trial with cross over design. Sixty four subjects were selected using block randomization technique, and were divided into control and intervention group. The intervention was given in 6 days along with wound healing evaluation in every 3 days. The results demonstrated that there was a significant difference decrease scoring healing after treatment, even though the difference scoring healing between both groups was not statistically significant. However, it means difference was found that in the intervention artrihpi the wound healing was better than the spuit. These results illustrates the artrihpi may be solution of using high pressure irrigation to help healing process diabetic ulcers.

Clinical Validation Trial of a Diagnostic for Ebola Zaire Antigen Detection: Design Rationale and Challenges to Implementation

PubMed Central

Schieffelin, John; Moses, Lina M; Shaffer, Jeffrey; Goba, Augustine; Grant, Donald S

2015-01-01

The current Ebola outbreak in West Africa has affected more people than all previous outbreaks combined. The current diagnostic method of choice, quantitative polymerase chain reaction, requires specialized conditions as well as specially trained technicians. Insufficient testing capacity has extended the time from sample collection to results. These delays have led to further delays in the transfer and treatment to Ebola Treatment Units. A sensitive and specific point-of-care device that could be used reliably in low resource settings by healthcare workers with minimal training would increase the efficiency of triage and appropriate transfer of care. This article describes a study designed to validate the sensitivity and specificity of the ReEBOVTM RDT using venous whole blood and capillary blood obtained via fingerprick. We present the scientific and clinical rationale for the decisions made in the design of a diagnostic validation study to be conducted in an outbreak setting. The multi-site strategy greatly complicated implementation. In addition, a decrease in cases in one geographic area along with a concomitant increase in other areas made site selection challenging. Initiation of clinical trials during rapidly evolving outbreaks requires significant cooperation on a national level between research teams implementing studies and clinical care providers. Coordination and streamlining of approval process is essential if trials are to be implemented in a timely fashion. PMID:26768566

Low dose intranasal oxytocin delivered with Breath Powered device dampens amygdala response to emotional stimuli: A peripheral effect-controlled within-subjects randomized dose-response fMRI trial.

PubMed

Quintana, Daniel S; Westlye, Lars T; Alnæs, Dag; Rustan, Øyvind G; Kaufmann, Tobias; Smerud, Knut T; Mahmoud, Ramy A; Djupesland, Per G; Andreassen, Ole A

2016-07-01

It is unclear if and how exogenous oxytocin (OT) reaches the brain to improve social behavior and cognition and what is the optimal dose for OT response. To better understand the delivery routes of intranasal OT administration to the brain and the dose-response, we compared amygdala response to facial stimuli by means of functional magnetic resonance imaging (fMRI) in four treatment conditions, including two different doses of intranasal OT using a novel Breath Powered device, intravenous (IV) OT, which provided similar concentrations of blood plasma OT, and placebo. We adopted a randomized, double-blind, double-dummy, crossover design, with 16 healthy male adults administering a single-dose of these four treatments. We observed a treatment effect on right amygdala activation during the processing of angry and happy face stimuli, with pairwise comparisons revealing reduced activation after the 8IU low dose intranasal treatment compared to placebo. These data suggest the dampening of amygdala activity in response to emotional stimuli occurs via direct intranasal delivery pathways rather than across the blood-brain barrier via systemically circulating OT. This trial is registered at the U.S. National Institutes of Health clinical trial registry (www.clinicaltrials.gov; NCT01983514) and as EudraCT no. 2013-001608-12. Copyright © 2016 Elsevier Ltd. All rights reserved.

Clinically Significant Pocket Hematoma Increases Long-Term Risk of Device Infection: BRUISE CONTROL INFECTION Study.

PubMed

Essebag, Vidal; Verma, Atul; Healey, Jeff S; Krahn, Andrew D; Kalfon, Eli; Coutu, Benoit; Ayala-Paredes, Felix; Tang, Anthony S; Sapp, John; Sturmer, Marcio; Keren, Arieh; Wells, George A; Birnie, David H

2016-03-22

The BRUISE CONTROL trial (Bridge or Continue Coumadin for Device Surgery Randomized Controlled Trial) demonstrated that a strategy of continued warfarin during cardiac implantable electronic device surgery was safe and reduced the incidence of clinically significant pocket hematoma (CSH). CSH was defined as a post-procedure hematoma requiring further surgery and/or resulting in prolongation of hospitalization of at least 24 h, and/or requiring interruption of anticoagulation. Previous studies have inconsistently associated hematoma with the subsequent development of device infection; reasons include the retrospective nature of many studies, lack of endpoint adjudication, and differing subjective definitions of hematoma. The BRUISE CONTROL INFECTION (Bridge or Continue Coumadin for Device Surgery Randomized Controlled Trial Extended Follow-Up for Infection) prospectively examined the association between CSH and subsequent device infection. The study included 659 patients with a primary outcome of device-related infection requiring hospitalization, defined as 1 or more of the following: pocket infection; endocarditis; and bloodstream infection. Outcomes were verified by a blinded adjudication committee. Multivariable analysis was performed to identify predictors of infection. The overall 1-year device-related infection rate was 2.4% (16 of 659). Infection occurred in 11% of patients (7 of 66) with previous CSH and in 1.5% (9 of 593) without CSH. CSH was the only independent predictor and was associated with a >7-fold increased risk of infection (hazard ratio: 7.7; 95% confidence interval: 2.9 to 20.5; p < 0.0001). Empiric antibiotics upon development of hematoma did not reduce long-term infection risk. CSH is associated with a significantly increased risk of infection requiring hospitalization within 1 year following cardiac implantable electronic device surgery. Strategies aimed at reducing hematomas may decrease the long-term risk of infection. (Bridge or Continue Coumadin for Device Surgery Randomized Controlled Trial [BRUISE CONTROL]; NCT00800137). Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Reading aids for adults with low vision.

PubMed

Virgili, Gianni; Acosta, Ruthy; Bentley, Sharon A; Giacomelli, Giovanni; Allcock, Claire; Evans, Jennifer R

2018-04-17

The purpose of low-vision rehabilitation is to allow people to resume or to continue to perform daily living tasks, with reading being one of the most important. This is achieved by providing appropriate optical devices and special training in the use of residual-vision and low-vision aids, which range from simple optical magnifiers to high-magnification video magnifiers. To assess the effects of different visual reading aids for adults with low vision. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2017, Issue 12); MEDLINE Ovid; Embase Ovid; BIREME LILACS, OpenGrey, the ISRCTN registry; ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). The date of the search was 17 January 2018. This review includes randomised and quasi-randomised trials that compared any device or aid used for reading to another device or aid in people aged 16 or over with low vision as defined by the study investigators. We did not compare low-vision aids with no low-vision aid since it is obviously not possible to measure reading speed, our primary outcome, in people that cannot read ordinary print. We considered reading aids that maximise the person's visual reading capacity, for example by increasing image magnification (optical and electronic magnifiers), augmenting text contrast (coloured filters) or trying to optimise the viewing angle or gaze position (such as prisms). We have not included studies investigating reading aids that allow reading through hearing, such as talking books or screen readers, or through touch, such as Braille-based devices and we did not consider rehabilitation strategies or complex low-vision interventions. We used standard methods expected by Cochrane. At least two authors independently assessed trial quality and extracted data. The primary outcome of the review was reading speed in words per minute. Secondary outcomes included reading duration and acuity, ease and frequency of use, quality of life and adverse outcomes. We graded the certainty of the evidence using GRADE. We included 11 small studies with a cross-over design (435 people overall), one study with two parallel arms (37 participants) and one study with three parallel arms (243 participants). These studies took place in the USA (7 studies), the UK (5 studies) and Canada (1 study). Age-related macular degeneration (AMD) was the most frequent cause of low vision, with 10 studies reporting 50% or more participants with the condition. Participants were aged 9 to 97 years in these studies, but most were older (the median average age across studies was 71 years). None of the studies were masked; otherwise we largely judged the studies to be at low risk of bias. All studies reported the primary outcome: results for reading speed. None of the studies measured or reported adverse outcomes.Reading speed may be higher with stand-mounted closed circuit television (CCTV) than with optical devices (stand or hand magnifiers) (low-certainty evidence, 2 studies, 92 participants). There was moderate-certainty evidence that reading duration was longer with the electronic devices and that they were easier to use. Similar results were seen for electronic devices with the camera mounted in a 'mouse'. Mixed results were seen for head-mounted devices with one study of 70 participants finding a mouse-based head-mounted device to be better than an optical device and another study of 20 participants finding optical devices better (low-certainty evidence). Low-certainty evidence from three studies (93 participants) suggested no important differences in reading speed, acuity or ease of use between stand-mounted and head-mounted electronic devices. Similarly, low-certainty evidence from one study of 100 participants suggested no important differences between a 9.7'' tablet computer and stand-mounted CCTV in reading speed, with imprecise estimates (other outcomes not reported).Low-certainty evidence showed little difference in reading speed in one study with 100 participants that added electronic portable devices to preferred optical devices. One parallel-arm study in 37 participants found low-certainty evidence of higher reading speed at one month if participants received a CCTV at the initial rehabilitation consultation instead of a standard low-vision aids prescription alone.A parallel-arm study including 243 participants with AMD found no important differences in reading speed, reading acuity and quality of life between prism spectacles and conventional spectacles. One study in 10 people with AMD found that reading speed with several overlay coloured filters was no better and possibly worse than with a clear filter (low-certainty evidence, other outcomes not reported). There is insufficient evidence supporting the use of a specific type of electronic or optical device for the most common profiles of low-vision aid users. However, there is some evidence that stand-mounted electronic devices may improve reading speeds compared with optical devices. There is less evidence to support the use of head-mounted or portable electronic devices; however, the technology of electronic devices may have improved since the studies included in this review took place, and modern portable electronic devices have desirable properties such as flexible use of magnification. There is no good evidence to support the use of filters or prism spectacles. Future research should focus on assessing sustained long-term use of each device and the effect of different training programmes on its use, combined with investigation of which patient characteristics predict performance with different devices, including some of the more costly electronic devices.

Effects of an Elastic Hamstring Assistance Device During Downhill Running

PubMed Central

Aldret, Randy L; Trahan, Brittany A; Davis, Greggory; Campbell, Brian; Bellar, David M

2017-01-01

Abstract The purpose of this study was to determine the appropriateness of using an elastic hamstring assistance device to reduce perceived levels of soreness, increase isometric strength, increase passive range of motion, and decrease biomarkers of muscle damage after eccentric exercise, specifically, downhill running This study was conducted in a university exercise physiology laboratory placing sixteen apparently healthy males (X = 21.6 ± 2.5 years) into two groups using a pre-test/post-test design. Pre-intervention measures taken included participants’ body height, body mass, body fat, capillary blood samples, VO2max, isometric hamstring strength at 45 and 90 degrees of flexion and passive hamstring range of motion. Post-intervention measures included blood biomarkers, passive range of motion, the perceived level of soreness and isometric strength. An analysis of normality of data was initially conducted followed by multivariate analysis of variance (MANOVA) of hamstring strength at 45 and 90 degrees of flexion, blood myoglobin and passive range of motion of the hamstrings. Statistically significant changes were noted in subject-perceived muscle soreness and isometric strength at 90 degrees at the 24-hour post-exercise trial measure between the two groups. Results would suggest the findings could be explained by the decrease in muscle soreness from utilizing the device during the exercise trial. Further research should be conducted to address sample size issues and to determine if the results are comparable on different surfaces. PMID:28713460

Frequency of pneumothorax and haemothorax after primary open versus closed implantation strategies for insertion of a totally implantable venous access port in oncological patients: study protocol for a randomised controlled trial.

PubMed

Hüttner, Felix J; Bruckner, Tom; Alldinger, Ingo; Hennes, Roland; Ulrich, Alexis; Büchler, Markus W; Diener, Markus K; Knebel, Phillip

2015-03-31

The insertion of central venous access devices, such as totally implantable venous access ports (TIVAPs), is routine in patients who need a safe and permanent venous access. The number of port implantations is increasing due to the development of innovative adjuvant and neo-adjuvant therapies. Currently, two different strategies are being routinely used: surgical cut-down of the cephalic vein (vena section) and direct puncture of the subclavian vein. The aim of this trial is to identify the strategy for the implantation of TIVAPs with the lowest risk of pneumothorax and haemothorax. The PORTAS-3 trial is designed as a multicentre, randomised controlled trial to compare two implantation strategies. A total of 1,154 patients will be randomised after giving written informed consent. Patients must be over 18 years of age and scheduled for primary implantation of a TIVAP on the designated side. The primary endpoint will be the frequency of pneumothorax and haemothorax after insertion of a TIVAP by one of two different strategies. The experimental intervention is as follows: open strategy, defined as surgical cut-down of the cephalic vein, supported by a rescue technique if necessary, and in the case of failure, direct puncture of the subclavian vein. The control intervention is as follows: direct puncture of the subclavian vein using the Seldinger technique guided by sonography, fluoroscopy or landmark technique. The trial duration is approximately 36 months, with a recruitment period of 18 months and a follow-up period of 30 days. The PORTAS-3 trial will compare two different TIVAP implantation strategies with regard to their individual risk of postoperative pneumothorax and haemothorax. Since TIVAP implantation is one of the most common procedures in general surgery, the results will be of interest for a large community of surgeons as well as oncologists and general practitioners. The pragmatic trial design ensures that the results will be generalizable to a wide range of patients. The trial protocol was registered on 28 August 2014 with the German Clinical Trials Register (DRKS00004900) . The World Health Organization's Universal Trial Number is U1111-1142-4420.

Synthetic devices for reconstructive surgery of the cruciate ligaments: a systematic review.

PubMed

Batty, Lachlan M; Norsworthy, Cameron J; Lash, Nicholas J; Wasiak, Jason; Richmond, Anneka K; Feller, Julian A

2015-05-01

The role of synthetic devices in the management of the cruciate ligament-injured knee remains controversial. The aim of this systematic review was to assess the safety and efficacy of synthetic devices in cruciate ligament surgery. A systematic review of the electronic databases Medline, Embase, and The Cochrane Library (issue 1, 2014) on January 13, 2014, was performed to identify controlled and uncontrolled trials. Trials that assessed the safety and efficacy of synthetic devices for cruciate ligament surgery were included. The main variables assessed included rates of failure, revision, and noninfective effusion and synovitis. Patient-reported outcome assessments and complications were also assessed where reported. From 511 records screened, we included 85 articles published between 1985 and 2013 reporting on 6 synthetic devices (ligament augmentation and reconstruction system [Ligament Augmentation and Reconstruction System (LARS; Surgical Implants and Devices, Arc-sur-Tille, France)]; Leeds-Keio [Xiros (formerly Neoligaments), Leeds, England]; Kennedy ligament augmentation device [3M, St Paul, MN]; Dacron [Stryker, Kalamazoo, MI]; Gore-Tex [W.L. Gore and Associates, Flagstaff, AZ]; and Trevira [Telos (limited liability company), Marburg, Germany]). The heterogeneity of the included studies precluded meta-analysis. The results were analyzed by device and then type of reconstruction (anterior cruciate ligament [ACL]/posterior cruciate ligament [PCL]/combined ACL and PCL). The lowest cumulative rates of failure were seen with the LARS device (2.6% for ACL and 1% for PCL surgery). The highest failure rate was seen in the Dacron ACL group (cumulative rate, 33.6%). Rates of noninfective synovitis and effusion ranged from 0.2% in the LARS ACL group to 27.6% in the Gore-Tex ACL group. Revision rates ranged from 2.6% (LARS) to 11.8% (Trevira-Hochfest; Telos). Recent designs, specifically the LARS, showed good improvement in the outcome scores. The mean preoperative and postoperative Lysholm knee scores were 54 and 88, respectively; the mean preoperative and postoperative Tegner activity scale scores were 3.3 and 6, respectively. Preliminary results for newer-generation devices, specifically the LARS, show lower reported rates of failure, revision, and sterile effusion/synovitis when compared with older devices. Level IV, systematic review of Level II through IV studies. Copyright © 2015 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Effectiveness of a lumbopelvic monitor and feedback device to change postural behaviour: a protocol for the ELF cluster randomised controlled trial

PubMed Central

Milosavljevic, Stephan

2017-01-01

Introduction Low back pain (LBP) is the most common, costly and disabling musculoskeletal disorder worldwide, and is prevalent in healthcare workers. Posture is a modifiable risk factor for LBP shown to reduce the prevalence of LBP. Our feasibility research suggests that postural feedback might help healthcare workers avoid hazardous postures. The Effectiveness of Lumbopelvic Feedback (ELF) trial will investigate the extent to which postural monitor and feedback (PMF) can reduce exposure to hazardous posture associated with LBP. Methods This is a participant-blinded, randomised controlled trial with blocked cluster random allocation. Participants will include volunteer healthcare workers recruited from aged care institutions and hospitals. A postural monitoring and feedback device will monitor and record lumbopelvic forward bending posture, and provide audio feedback whenever the user sustains a lumbopelvic forward bending posture that exceeds predefined thresholds. The primary outcome measure will be postural behaviour (exceeding thresholds). Secondary outcome measures will be incidence of LBP, participant-reported disability and adherence. Following baseline assessment, we will randomly assign participants to 1 of 2 intervention arms: a feedback group and a no-feedback control group. We will compare between-group differences of changes in postural behaviour by using a repeated measures mixed-effect model analysis of covariance (ANCOVA) at 6 weeks. Postural behaviour baseline scores, work-related psychosocial factors and disability scores will be input as covariates into the statistical models. We will use logistic mixed model analysis and Cox's proportional hazards for assessing the effect of a PMF on LBP incidence between groups. Discussion Posture is a modifiable risk factor for low back disorders. Findings from the ELF trial will inform the design of future clinical trials assessing the effectiveness of wearable technology on minimising hazardous posture during daily living activities in patients with low back disorders. Trial registration number ACTRN12616000449437. PMID:28073798

Electromechanical-assisted training for walking after stroke.

PubMed

Mehrholz, Jan; Elsner, Bernhard; Werner, Cordula; Kugler, Joachim; Pohl, Marcus

2013-07-25

Electromechanical and robotic-assisted gait training devices are used in rehabilitation and might help to improve walking after stroke. This is an update of a Cochrane Review first published in 2007. To investigate the effects of automated electromechanical and robotic-assisted gait training devices for improving walking after stroke. We searched the Cochrane Stroke Group Trials Register (last searched April 2012), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 2), MEDLINE (1966 to November 2012), EMBASE (1980 to November 2012), CINAHL (1982 to November 2012), AMED (1985 to November 2012), SPORTDiscus (1949 to September 2012), the Physiotherapy Evidence Database (PEDro, searched November 2012) and the engineering databases COMPENDEX (1972 to November 2012) and INSPEC (1969 to November 2012). We handsearched relevant conference proceedings, searched trials and research registers, checked reference lists and contacted authors in an effort to identify further published, unpublished and ongoing trials. We included all randomised and randomised cross-over trials consisting of people over 18 years old diagnosed with stroke of any severity, at any stage, or in any setting, evaluating electromechanical and robotic-assisted gait training versus normal care. Two review authors independently selected trials for inclusion, assessed methodological quality and extracted the data. The primary outcome was the proportion of participants walking independently at follow-up. In this update of our review, we included 23 trials involving 999 participants. Electromechanical-assisted gait training in combination with physiotherapy increased the odds of participants becoming independent in walking (odds ratio (OR) (random effects) 2.39, 95% confidence interval (CI) 1.67 to 3.43; P < 0.00001; I² = 0%) but did not significantly increase walking velocity (mean difference (MD) = 0.04 metres/s, 95% CI -0.03 to 0.11; P = 0.26; I² = 73%) or walking capacity (MD = 3 metres walked in six minutes, 95% CI -29 to 35; P = 0.86; I² = 70%). The results must be interpreted with caution because (1) some trials investigated people who were independent in walking at the start of the study, (2) we found variations between the trials with respect to devices used and duration and frequency of treatment, and (3) some trials included devices with functional electrical stimulation. Our planned subgroup analysis suggests that people in the acute phase may benefit but people in the chronic phase may not benefit from electromechanical-assisted gait training. Post hoc analysis showed that people who are non-ambulatory at intervention onset may benefit but ambulatory people may not benefit from this type of training. Post hoc analysis showed no differences between the types of devices used in studies regarding ability to walk, but significant differences were found between devices in terms of walking velocity. People who receive electromechanical-assisted gait training in combination with physiotherapy after stroke are more likely to achieve independent walking than people who receive gait training without these devices. Specifically, people in the first three months after stroke and those who are not able to walk seem to benefit most from this type of intervention. The role of the type of device is still not clear. Further research should consist of a large definitive, pragmatic, phase III trial undertaken to address specific questions such as the following: What frequency or duration of electromechanical-assisted gait training might be most effective? How long does the benefit last?

[Experiences and recommendations of the German Federal Institute for Drugs and Medical Devices (BfArM) concerning clinical investigation of medical devices and the evaluation of serious adverse events (SAE)].

PubMed

Renisch, B; Lauer, W

2014-12-01

An integral part of the conformity assessment process for medical devices is a clinical evaluation based on clinical data. Particularly in the case of implantable devices and products of risk class III clinical trials must be performed. Since March 2010 applications for the authorization of clinical trials as well as for the waiver of the authorization requirement must be submitted centrally in Germany to the appropriate federal authority, the Federal Institute for Drugs and Medical Devices (BfArM) or the Paul Ehrlich Institute (PEI). In addition to authorization, approval by the responsible ethics committee is also required under law in order to begin clinical testing of medical devices in Germany. In this paper, the legal framework for the clinical testing of medical devices as well as those involved and possible procedures including evaluation criteria for the initial application of a trial and subsequent amendments are presented in detail. In addition, the reporting requirements for serious adverse events (SAEs) are explained and possible consequences of the evaluation are presented. Finally, a summary of application and registration numbers for all areas of extensive experience of the BfArM as well as requests and guidance for applicants are presented.

Use of mobile devices to answer online surveys: implications for research.

PubMed

Cunningham, John A; Neighbors, Clayton; Bertholet, Nicolas; Hendershot, Christian S

2013-07-08

There is a growing use of mobile devices to access the Internet. We examined whether participants who used a mobile device to access a brief online survey were quicker to respond to the survey but also, less likely to complete it than participants using a traditional web browser. Using data from a recently completed online intervention trial, we found that participants using mobile devices were quicker to access the survey but less likely to complete it compared to participants using a traditional web browser. More concerning, mobile device users were also less likely to respond to a request to complete a six week follow-up survey compared to those using traditional web browsers. With roughly a third of participants using mobile devices to answer an online survey in this study, the impact of mobile device usage on survey completion rates is a concern. ClinicalTrials.gov: NCT01521078.

An Implementation-Focused Bio/Algorithmic Workflow for Synthetic Biology.

PubMed

Goñi-Moreno, Angel; Carcajona, Marta; Kim, Juhyun; Martínez-García, Esteban; Amos, Martyn; de Lorenzo, Víctor

2016-10-21

As synthetic biology moves away from trial and error and embraces more formal processes, workflows have emerged that cover the roadmap from conceptualization of a genetic device to its construction and measurement. This latter aspect (i.e., characterization and measurement of synthetic genetic constructs) has received relatively little attention to date, but it is crucial for their outcome. An end-to-end use case for engineering a simple synthetic device is presented, which is supported by information standards and computational methods and focuses on such characterization/measurement. This workflow captures the main stages of genetic device design and description and offers standardized tools for both population-based measurement and single-cell analysis. To this end, three separate aspects are addressed. First, the specific vector features are discussed. Although device/circuit design has been successfully automated, important structural information is usually overlooked, as in the case of plasmid vectors. The use of the Standard European Vector Architecture (SEVA) is advocated for selecting the optimal carrier of a design and its thorough description in order to unequivocally correlate digital definitions and molecular devices. A digital version of this plasmid format was developed with the Synthetic Biology Open Language (SBOL) along with a software tool that allows users to embed genetic parts in vector cargoes. This enables annotation of a mathematical model of the device's kinetic reactions formatted with the Systems Biology Markup Language (SBML). From that point onward, the experimental results and their in silico counterparts proceed alongside, with constant feedback to preserve consistency between them. A second aspect involves a framework for the calibration of fluorescence-based measurements. One of the most challenging endeavors in standardization, metrology, is tackled by reinterpreting the experimental output in light of simulation results, allowing us to turn arbitrary fluorescence units into relative measurements. Finally, integration of single-cell methods into a framework for multicellular simulation and measurement is addressed, allowing standardized inspection of the interplay between the carrier chassis and the culture conditions.

Improving academic leadership and oversight in large industry-sponsored clinical trials: the ARO-CRO model

PubMed Central

Goldenberg, Neil A.; Spyropoulos, Alex C.; Halperin, Jonathan L.; Kessler, Craig M.; Schulman, Sam; Turpie, Alexander G. G.; Skene, Allan M.; Cutler, Neal R.

2011-01-01

Standards for clinical trial design, execution, and publication have increased in recent years. However, the current structure for interaction among the pharmaceutical sponsor funding a drug or device development program, the contract research organization (CRO) that typically assists in executing the trial, regulatory agencies, and academicians, provides inadequate leadership and oversight of the development process. Conventional academic steering committees are not provided with the independent infrastructure by which to verify statistical analyses and conclusions regarding safety and efficacy. We propose an alternative approach centered on partnerships between CROs and university-based academic research organizations (AROs). In this model, the ARO takes responsibility for processes that address journal requirements and regulatory expectations for independent academic oversight (including oversight of Steering Committee and Data and Safety Monitoring Board activities), whereas the CRO provides infrastructure for efficient trial execution, site monitoring, and data management. The ARO engages academic experts throughout the trial process and minimizes conflicts of interest in individual industry relationships via diversification of sponsors, agents, and therapeutic areas. Although numerous models can be entertained, the ARO-CRO model is uniquely structured to meet the demand for greater assurance of integrity in clinical trials and the needs of each stakeholder in the process. PMID:21068436

Three upper limb robotic devices for stroke rehabilitation: a review and clinical perspective.

PubMed

Bishop, Lauri; Stein, Joel

2013-01-01

Stroke is a leading cause of disability worldwide. Many survivors of stroke remain with residual disabilities, even years later. Advances in technology have led to the development of a variety of robotic devices for use in rehabilitation. The integration of robotics in the delivery of neurorehabilitation is promising, but still not widely used in clinical settings. The aim of this review is to discuss the general design of three typical upper limb robotic devices, and examine the practical considerations for their use in a clinical environment. Each device is described, the available clinical literature is reviewed and a clinical perspective is given on the usefulness of these robotic devices in rehabilitation of this population. Current literature supports the use of robotics in the clinical environment. However, claims that robotic therapy is more effective than traditional treatment is not substantially supported. The majority of clinical trials reported are small, and lack the use of a control group for comparison treatment. The use of robotics in stroke rehabilitation is still a relatively new treatment platform, and still evolving. As technological advances are made, there is much potential for growth in this field.

Investigation of phononic crystals for dispersive surface acoustic wave ozone sensors

NASA Astrophysics Data System (ADS)

Westafer, Ryan S.

The object of this research was to investigate dispersion in surface phononic crystals (PnCs) for application to a newly developed passive surface acoustic wave (SAW) ozone sensor. Frequency band gaps and slow sound already have been reported for PnC lattice structures. Such engineered structures are often advertised to reduce loss, increase sensitivity, and reduce device size. However, these advances have not yet been realized in the context of surface acoustic wave sensors. In early work, we computed SAW dispersion in patterned surface structures and we confirmed that our finite element computations of SAW dispersion in thin films and in one dimensional surface PnC structures agree with experimental results obtained by laser probe techniques. We analyzed the computations to guide device design in terms of sensitivity and joint spectral operating point. Next we conducted simulations and experiments to determine sensitivity and limit of detection for more conventional dispersive SAW devices and PnC sensors. Finally, we conducted extensive ozone detection trials on passive reflection mode SAW devices, using distinct components of the time dispersed response to compensate for the effect of temperature. The experimental work revealed that the devices may be used for dosimetry applications over periods of several days.

Using off-the-shelf medical devices for biomedical signal monitoring in a telemedicine system for emergency medical services.

PubMed

Thelen, Sebastian; Czaplik, Michael; Meisen, Philipp; Schilberg, Daniel; Jeschke, Sabina

2015-01-01

In order to study new methods of telemedicine usage in the context of emergency medical services, researchers need to prototype integrated telemedicine systems. To conduct a one-year trial phase-intended to study a new application of telemedicine in German emergency medical services-we used off-the-shelf medical devices and software to realize real-time patient monitoring within an integrated telemedicine system prototype. We demonstrate its feasibility by presenting the integrated real-time patient monitoring solution, by studying signal delay and transmission robustness regarding changing communication channel characteristics, and by evaluating issues reported by the physicians during the trial phase. Where standards like HL7 and the IEEE 11073 family are intended to enable interoperability of product grade medical devices, we show that research prototypes benefit from the use of web technologies and simple device interfaces, as they simplify product development for a manufacturer and ease integration efforts for research teams. Embracing this approach for the development of new medical devices eases the constraint to use off-the-shelf products for research trials investigating innovative use of telemedicine.

Nine Year Follow-up of a Ceramic-on-Ceramic Bearing Total Hip Arthroplasty Utilizing a Layered Monoblock Acetabular Component

PubMed Central

Mayor, David; Patel, Savan; Perry, Clayton; Walter, Norman; Burton, Stephen; Atkinson, Theresa

2014-01-01

Introduction Early ceramic bearing systems in total hip arthoplasty (THA) sought to provide long term wear improvement over traditional metal on polyethylene systems. However, previous designs exhibited fractures of the ceramic acetabular liner, leading to the development of the Implex Hedrocel ceramic bearing THA system where the ceramic liner was supported on a layer of polyethylene intended to transition liner loads to the metal shell, a so-called “sandwich” design. Unfortunately, the device trial was stopped to further enrollment when liner fractures were reported. The current study examines nearly 10-year follow-up on 28 devices implanted by two surgeons at one institution in order to document ceramic bearing system performance over a longer time period. Methods Radiographic and patient reported outcomes, in the form of Harris Hip Scores (HHS) and 12-Item Short Form Health Survey (sF-12), were collected. Results During the study period two cups were replaced, one at three years and a second at seven years. At the five year follow-up HHS were similar to those reported in the literature for devices with traditional metal-on-polyethylene bearing surfaces and for other sandwich ceramic bearing designs. At the nine year follow-up, the HHS had not changed significantly and SF-12 scores measuring overall physical and mental health were higher than age matched national norms (p<0.001). There were no signs of cup migration, stem subsidence, osteolysis or cup loosening at any time up to the last follow-up in this patient cohort. The 89% survivorship rate and device revisions due to delamination of the liner observed in this group were similar to those reported earlier for this device and for other “sandwich design” ceramic bearing systems. Discussion This cohort did not exhibit new failure modes and HHS and SF-12 scores indicated high functionality for the majority of patients. These data suggest that a focus on preventing ceramic liner fracture through design and/or materials improvements may result in a device with long-term functionality. PMID:25328464

The Manumeter: A non-obtrusive wearable device for monitoring spontaneous use of the wrist and fingers

PubMed Central

Rowe, Justin B.; Friedman, Nizan; Bachman, Mark; Reinkensmeyer, David J.

2014-01-01

This paper describes the design and pilot testing of a novel device for unobtrusive monitoring of wrist and hand movement through a sensorized watch and a magnetic ring system called the manumeter. The device senses the magnetic field of the ring through two triaxial magnetometers and records the data to onboard memory which can be analyzed later by connecting the watch unit to a computer. Wrist and finger joint angles are estimated using a radial basis function network. We compared joint angle estimates collected using the manumeter to direct measurements taken using a passive exoskeleton and found that after a 60 minute trial, 95% of the radial/ulnar deviation, wrist flexion/extension and finger flexion/extension estimates were within 2.4, 5.8, and 4.7 degrees of their actual values respectively. The device measured angular distance traveled for these three joints within 10.4%, 4.5%, and 14.3 % of their actual values. The manumeter has potential to improve monitoring of real world use of the hand after stroke and in other applications. PMID:24187216

UV Waterworks Outreach Support. Final Report

DOE R&D Accomplishments Database

Miller, P.

1998-05-01

A recently invented device uses UV light (254 nm) to inexpensively disinfect community drinking water supplies. Its novel features are: low cost (about US $600), robust design, rapid disinfection (12 seconds), low electricity use (40W), low maintenance (every 6 months), high flow rate (15 l/min) and ability to work with unpressurized water sources. The device could service a community of 1,000 persons, at an annual total cost of 14 cents US per person. This device has been tested in a number of independent laboratories worldwide. The laboratory tests have confirmed that the unit is capable of disinfecting waters to drinking water standards for bacteria and viruses. An extended field trial of the device began in South Africa in February 1997, with lab testing at the municipal water utility. A unit installed at the first field site, an AIDS hospice near Durban, has been in continuous operation since August, 1997. Additional test sites are being identified. The author describes the results of the initial lab tests, reports the most recent findings from the ongoing field test-monitoring program, and discusses plans for future tests.

Test-Retest Reliability of a Novel Isokinetic Squat Device With Strength-Trained Athletes.

PubMed

Bridgeman, Lee A; McGuigan, Michael R; Gill, Nicholas D; Dulson, Deborah K

2016-11-01

Bridgeman, LA, McGuigan, MR, Gill, ND, and Dulson, DK. Test-retest reliability of a novel isokinetic squat device with strength-trained athletes. J Strength Cond Res 30(11): 3261-3265, 2016-The aim of this study was to investigate the test-retest reliability of a novel multijoint isokinetic squat device. The subjects in this study were 10 strength-trained athletes. Each subject completed 3 maximal testing sessions to assess peak concentric and eccentric force (N) over a 3-week period using the Exerbotics squat device. Mean differences between eccentric and concentric force across the trials were calculated. Intraclass correlation coefficients (ICCs) and coefficients of variation (CVs) for the variables of interest were calculated using an excel reliability spreadsheet. Between trials 1 and 2 an 11.0 and 2.3% increase in mean concentric and eccentric forces, respectively, was reported. Between trials 2 and 3 a 1.35% increase in the mean concentric force production and a 1.4% increase in eccentric force production was reported. The mean concentric peak force CV and ICC across the 3 trials was 10% (7.6-15.4) and 0.95 (0.87-0.98) respectively. However, the mean eccentric peak force CV and ICC across the trials was 7.2% (5.5-11.1) and 0.90 (0.76-0.97), respectively. Based on these findings it is suggested that the Exerbotics squat device shows good test-retest reliability. Therefore practitioners and investigators may consider its use to monitor changes in concentric and eccentric peak force.

Radiographic evaluation of vessel count and density with quantitative magnetic resonance imaging during external breast expansion in Asian women: A prospective clinical trial.

PubMed

Myung, Yujin; Kwon, Heeyeon; Pak, Changsik; Lee, Hobin; Jeong, Jae Hoon; Heo, Chan Yeong

2016-12-01

Breast augmentation with fat transfer does not bear the risks associated with silicone implantation. The method can potentially be especially useful in Asian women, who often reject augmentation mammoplasty with implants. This prospective clinical trial evaluated the effects of external breast expansion on breast density and vessel count using magnetic resonance imaging. Thirty-four enrolled patients were instructed to apply one of two devices, the conventional BRAVA device (used in the AESTES trial) or a novel external expansion device (EVERA) designed for Asian women, continuously for 8 h per day for 12 weeks. For external expansion, the pressure was set to 25 mmHg. Follow-up examinations were performed for 4 weeks after completion of the expansion. The ratio between the fibroglandular and adipose tissues of the breast was measured using T1-weighted MRI, and the number of vessels in the breast tissue was determined before and after the treatment by contrast MRI. Additionally, the volume of the breast was measured by laser scanning before, during, and after the device application. The obtained measurements were compared within and between the groups at different time points. Six patients dropped out, while 28 completed the trial without major side effects or adverse events. External expansion significantly increased breast vessel count in both the EVERA and AESTES groups (p = 0.019, p = 0.022). However, it did not significantly change breast density in either group (p = 0.186, p = 0.638). No significant intergroup differences were noted in vessel count (p = 0.874) or density (p = 0.482). Breast volume increases after 12 weeks of application were statistically significant in both groups, with mean changes of 81 ± 22 cc (AESTES) and 98 ± 30 cc (EVERA) (p < 0.001 in both cases). External expansion resulted in a marked increase in breast vessel count but did not affect breast density. The observed increase in breast volume can be considered substantial for Asian women. Level II, therapeutic study. Copyright © 2016 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Are Locking Constructs in Distal Femoral Fractures Always Best? A Prospective Multicenter Randomized Controlled Trial Comparing the Less Invasive Stabilization System With the Minimally Invasive Dynamic Condylar Screw System.

PubMed

2016-01-01

The purpose of this clinical study is to determine whether the rate of fracture healing and fracture union, repaired with a locked device, will be as good as or better than standard nonlocking bicortical fixation in distal femoral fractures. Institutional review board-approved, multicenter prospective randomized controlled trial. Seven level 1 trauma centers across Canada. Fifty-two patients with distal femoral fractures (AO/OTA 33A1 to 33C2) were enrolled in the randomized trial. Twelve AO/OTA 33C3 fractures were excluded from the randomized trial but followed up as a nonrandomized cohort. Patients were treated through a standardized minimally invasive approach. Fractures were randomized 1:1 to treatment with the locked Less Invasive Stabilization System (LISS; Synthes, Paoli, PA) or the dynamic condylar screw (DCS). The nonrandomized cohort was treated at the surgeon's discretion. Primary outcomes were time to radiological union and number of delayed/nonunions at 12 months. Secondary outcomes were postoperative function and complications. Fifty-two patients were randomized including 34 women and 18 men. The mean age was 59 years. Twenty-eight patients were treated with the LISS and 24 with the DCS. There was no statistically significant difference between the LISS and the DCS in terms of the number of fractures healed, time to union, or functional scores. Complications and revisions were more common in the LISS group. There were 7 reoperations in the LISS group and one in the DCS group. Only 52% of the LISS group healed without intervention by 12 months compared with 91% in the DCS group. There was no advantage to the locking plate design in the management of distal femoral fractures in this study. The higher cost of the locking plates, challenges in technique, and lack of superiority have led the authors to discontinue the use of this lateral unicortical locking device in favor of other devices that allow locked or nonlocked bicortical fixation, articular compression, and bridging of the comminuted fracture segments. The cost-effective treatment for a subgroup or periarticular fractures may be a fixed-angle nonlocked device in patients with reasonable bone quality. Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Negative pressure wound therapy for skin grafts and surgical wounds healing by primary intention.

PubMed

Webster, Joan; Scuffham, Paul; Stankiewicz, Monica; Chaboyer, Wendy P

2014-10-07

Indications for the use of negative pressure wound therapy (NPWT) are broadening with a range of systems now available on the market, including those designed for use on clean, closed incisions and skin grafts. Reviews have concluded that the evidence for the effectiveness of NPWT remains uncertain, however, it is a rapidly evolving therapy. Consequently, an updated systematic review of the evidence for the effects of NPWT on postoperative wounds expected to heal by primary intention is required. To assess the effects of NPWT on surgical wounds (primary closure, skin grafting or flap closure) that are expected to heal by primary intention. We searched the following electronic databases to identify reports of relevant randomised clinical trials: the Cochrane Wounds Group Specialised Register (searched 28 January 2014); the Cochrane Central Register of Controlled Trials (CENTRAL; 2013, issue 12); Database of Abstracts of Reviews of Effects (2013, issue 12); Ovid MEDLINE (2011 to January 2014); Ovid MEDLINE (In-Process & Other Non-Indexed Citations 24 January 2014); Ovid EMBASE (2011 to January 2014 Week 44); and EBSCO CINAHL (2011 to January 2014). We conducted a separate search to identify economic evaluations. We included trials if they allocated patients to treatment randomly and compared NPWT with any other type of wound dressing, or compared one type of NPWT with a different type of NPWT. We assessed trials for their appropriateness for inclusion and for their quality. This was done by three review authors working independently, using pre-determined inclusion and quality criteria. In this first update, we included an additional four trials, taking the total number of trials included to nine (785 participants). Three trials involved skin grafts, four included orthopaedic patients and two included general surgery and trauma surgery patients; all the included trials had unclear or high risk of bias for one or more of the quality indicators we assessed. Seven trials compared NPWT with a standard dressing (two of these were 'home-made' NPWT devices), one trial compared one 'home-made' NPWT with a commercially available device. In trials where the individual was the unit of randomisation, there were no differences in the incidence of surgical site infections (SSI); wound dehiscence, re-operation (in incisional wounds); seroma/haematoma; or failed skin grafts. Lower re-operation rates were observed among skin graft patients in the 'home-made' NPWT group (7/65; 10.8%) compared to the standard dressing group (17/66; 25.8%) (risk ratio (RR) 0.42; 95% CI 0.19 to 0.92). The mean cost to supply equipment for VAC® therapy was USD 96.51/day compared to USD 4.22/day for one of the 'home-made' devices (P value 0.01); labour costs for dressing changes were similar for both treatments. Pain intensity score was also reported to be lower in the 'home-made' group when compared with the VAC® group (P value 0.02). One of the trials in orthopaedic patients was stopped early because of a high incidence of fracture blisters in the NPWT group (15/24; 62.5%) compared with the standard dressing group (3/36; 8.3%) (RR 7.50; 95% CI 2.43 to 23.14). Evidence for the effects of negative pressure wound therapy (NPWT) for reducing SSI and wound dehiscence remains unclear, as does the effect of NPWT on time to complete healing. Rates of graft loss may be lower when NPWT is used, but hospital-designed and built products are as effective in this area as commercial applications. There are clear cost benefits when non-commercial systems are used to create the negative pressure required for wound therapy, with no evidence of a negative effect on clinical outcome. In one study, pain levels were also rated lower when a 'home-made' system was compared with a commercial counterpart. The high incidence of blisters occurring when NPWT is used following orthopaedic surgery suggests that the therapy should be limited until safety in this population is established. Given the cost and widespread use of NPWT, there is an urgent need for suitably powered, high-quality trials to evaluate the effects of the newer NPWT products that are designed for use on clean, closed surgical incisions. Such trials should focus initially on wounds that may be difficult to heal, such as sternal wounds or incisions on obese patients.

A Step Made Toward Designing Microelectromechanical System (MEMS) Structures With High Reliability

NASA Technical Reports Server (NTRS)

Nemeth, Noel N.

2003-01-01

The mechanical design of microelectromechanical systems-particularly for micropower generation applications-requires the ability to predict the strength capacity of load-carrying components over the service life of the device. These microdevices, which typically are made of brittle materials such as polysilicon, show wide scatter (stochastic behavior) in strength as well as a different average strength for different sized structures (size effect). These behaviors necessitate either costly and time-consuming trial-and-error designs or, more efficiently, the development of a probabilistic design methodology for MEMS. Over the years, the NASA Glenn Research Center s Life Prediction Branch has developed the CARES/Life probabilistic design methodology to predict the reliability of advanced ceramic components. In this study, done in collaboration with Johns Hopkins University, the ability of the CARES/Life code to predict the reliability of polysilicon microsized structures with stress concentrations is successfully demonstrated.

A systematic review and meta-analysis of mobile devices and weight loss with an intervention content analysis.

PubMed

Lyzwinski, Lynnette Nathalie

2014-06-30

Overweight and obesity constitute leading global public health challenges. Tackling overweight and obesity by influencing human behaviour is a complex task, requiring novel emerging health psychology interventions. The aims of this review will be to determine whether mobile devices induce weight loss and improvements in diet and physical activity levels when compared with standard controls without a weight loss intervention or controls allocated to non-mobile device weight loss interventions. A systematic review on mobile devices and weight loss was conducted. The inclusion criteria were all randomized controlled trials with baseline and post-intervention weight measures in adult subjects >18 years of age without pre-specified co-morbidities. Mobile device specifications included modern, portable devices in the form of smartphones, PDAs, iPods, and Mp3 players. Cohen's d for standardized differences in mean weight loss was calculated. A random effects meta-analysis was generated using Comprehensive meta-analysis software. Theories and intervention content were coded and analysed. A total of 17 studies were identified, of which 12 were primary trials and 5 were secondary analyses. The meta-analysis generated a medium significant effect size of 0.430 (95% CI 0.252-0.609) (p-value ≤ 0.01), favouring mobile interventions. Throughout the systematic review, mobile devices were found to induce weight loss relative to baseline weight. When comparing them with standard no intervention controls as well as controls receiving non-mobile weight loss interventions, results favoured mobile devices for weight loss. Reductions in Body mass index, waist circumference, and percentage body fat were also found in the review. Improvements in the determinants of weight loss in the form of improved dietary intake and physical activity levels were also found. Theory appears to largely inform intervention design, with the most common theories being Social Cognitive Theory, Elaboration Likelihood Theory, Control Theory, and Goal Theory. The use of behavioural change techniques was widespread across the studies, with a minimum of five per intervention. Mobile devices appear to induce positive changes in the behavioural determinants of weight and subsequently are associated with weight loss. Mobile device interventions are heavily informed by theory and behaviour change techniques. The use of theory appears to effectively enhance levels of constructs targeted by interventions.

The impact of automatic devices for capillary blood collection on efficiency and pain response in newborns: A randomized controlled trial.

PubMed

Sorrentino, G; Fumagalli, M; Milani, S; Cortinovis, I; Zorz, A; Cavallaro, G; Mosca, F; Plevani, L

2017-07-01

The heel stick is the method of choice in most neonatal units for capillary blood sampling, and it represents the most common event among all painful procedures performed on newborns. The type and design of heel stick device and the clinical procedure to collect a blood sample may have an impact on newborn pain response as well. To compare the pain response and efficiency of different automated devices for capillary blood collection in newborns. Randomized clinical trial. Postnatal ward of a tertiary-care university hospital in Italy. Newborn infants at gestational age ≥34 weeks undergoing the metabolic screening test after the 49th hour of life. A total of 762 neonates were recruited and randomized into 6 groups (127 babies in each group) assigned to 6 different capillary blood collection devices (Ames Minilet™ Lancet; Cardinal Health Gentleheel ® ; Natus Medical NeatNick™; BD Quikheel™ Lancet; Vitrex Steriheel ® Baby Lancet; Accriva Diagnostics Tenderfoot ® ). The following data were collected and assessed for each of the 6 groups evaluated: a) number of heel sticks, b) pain score according to the Neonatal Infant Pain Scale (NIPS) and c) need to squeeze the heel. The Ames Minilet™ Lancet device was found to perform by far the worst compared to the five device underexamination: it required the highest number of sticks (mean=3.91; 95% CI: 3.46-4.36), evoked the most intense pain (mean=3.98; 95% CI: 3.77-4.20), and most frequently necessitated squeezing the heel (92.9%; 95% CI: 86.9-96.3). The five devices under examination appeared to be similar in terms of the number of sticks required, but differed slightly in NIPS score and in need to squeeze the heel. The Accriva Diagnostics Tenderfoot ® device demonstrated the greatest efficiency for blood sampling and evoked the least pain. With this device, the metabolic screening test could be performed with a single skin incision in the large majority of infants (98.4%), heel squeezing was limited to only 6.3% of infants, and the NIPS score turns out to be lower than other devices in our study (1.22; 95% CI 1.05-1.39). Copyright © 2017 Elsevier Ltd. All rights reserved.

A Systematic Review and Meta-Analysis of Mobile Devices and Weight Loss with an Intervention Content Analysis

PubMed Central

Lyzwinski, Lynnette Nathalie

2014-01-01

Introduction: Overweight and obesity constitute leading global public health challenges. Tackling overweight and obesity by influencing human behaviour is a complex task, requiring novel emerging health psychology interventions. The aims of this review will be to determine whether mobile devices induce weight loss and improvements in diet and physical activity levels when compared with standard controls without a weight loss intervention or controls allocated to non-mobile device weight loss interventions. Methods: A systematic review on mobile devices and weight loss was conducted. The inclusion criteria were all randomized controlled trials with baseline and post-intervention weight measures in adult subjects >18 years of age without pre-specified co-morbidities. Mobile device specifications included modern, portable devices in the form of smartphones, PDAs, iPods, and Mp3 players. Cohen’s d for standardized differences in mean weight loss was calculated. A random effects meta-analysis was generated using Comprehensive meta-analysis software. Theories and intervention content were coded and analysed. Results: A total of 17 studies were identified, of which 12 were primary trials and 5 were secondary analyses. The meta-analysis generated a medium significant effect size of 0.430 (95% CI 0.252–0.609) (p-value ≤ 0.01), favouring mobile interventions. Throughout the systematic review, mobile devices were found to induce weight loss relative to baseline weight. When comparing them with standard no intervention controls as well as controls receiving non-mobile weight loss interventions, results favoured mobile devices for weight loss. Reductions in Body mass index, waist circumference, and percentage body fat were also found in the review. Improvements in the determinants of weight loss in the form of improved dietary intake and physical activity levels were also found. Theory appears to largely inform intervention design, with the most common theories being Social Cognitive Theory, Elaboration Likelihood Theory, Control Theory, and Goal Theory. The use of behavioural change techniques was widespread across the studies, with a minimum of five per intervention. Conclusion: Mobile devices appear to induce positive changes in the behavioural determinants of weight and subsequently are associated with weight loss. Mobile device interventions are heavily informed by theory and behaviour change techniques. The use of theory appears to effectively enhance levels of constructs targeted by interventions. PMID:25563356

A pneumatic Bionic Voice prosthesis-Pre-clinical trials of controlling the voice onset and offset.

PubMed

Ahmadi, Farzaneh; Noorian, Farzad; Novakovic, Daniel; van Schaik, André

2018-01-01

Despite emergent progress in many fields of bionics, a functional Bionic Voice prosthesis for laryngectomy patients (larynx amputees) has not yet been achieved, leading to a lifetime of vocal disability for these patients. This study introduces a novel framework of Pneumatic Bionic Voice Prostheses as an electronic adaptation of the Pneumatic Artificial Larynx (PAL) device. The PAL is a non-invasive mechanical voice source, driven exclusively by respiration with an exceptionally high voice quality, comparable to the existing gold standard of Tracheoesophageal (TE) voice prosthesis. Following PAL design closely as the reference, Pneumatic Bionic Voice Prostheses seem to have a strong potential to substitute the existing gold standard by generating a similar voice quality while remaining non-invasive and non-surgical. This paper designs the first Pneumatic Bionic Voice prosthesis and evaluates its onset and offset control against the PAL device through pre-clinical trials on one laryngectomy patient. The evaluation on a database of more than five hours of continuous/isolated speech recordings shows a close match between the onset/offset control of the Pneumatic Bionic Voice and the PAL with an accuracy of 98.45 ±0.54%. When implemented in real-time, the Pneumatic Bionic Voice prosthesis controller has an average onset/offset delay of 10 milliseconds compared to the PAL. Hence it addresses a major disadvantage of previous electronic voice prostheses, including myoelectric Bionic Voice, in meeting the short time-frames of controlling the onset/offset of the voice in continuous speech.

A pneumatic Bionic Voice prosthesis—Pre-clinical trials of controlling the voice onset and offset

PubMed Central

Noorian, Farzad; Novakovic, Daniel; van Schaik, André

2018-01-01

Despite emergent progress in many fields of bionics, a functional Bionic Voice prosthesis for laryngectomy patients (larynx amputees) has not yet been achieved, leading to a lifetime of vocal disability for these patients. This study introduces a novel framework of Pneumatic Bionic Voice Prostheses as an electronic adaptation of the Pneumatic Artificial Larynx (PAL) device. The PAL is a non-invasive mechanical voice source, driven exclusively by respiration with an exceptionally high voice quality, comparable to the existing gold standard of Tracheoesophageal (TE) voice prosthesis. Following PAL design closely as the reference, Pneumatic Bionic Voice Prostheses seem to have a strong potential to substitute the existing gold standard by generating a similar voice quality while remaining non-invasive and non-surgical. This paper designs the first Pneumatic Bionic Voice prosthesis and evaluates its onset and offset control against the PAL device through pre-clinical trials on one laryngectomy patient. The evaluation on a database of more than five hours of continuous/isolated speech recordings shows a close match between the onset/offset control of the Pneumatic Bionic Voice and the PAL with an accuracy of 98.45 ±0.54%. When implemented in real-time, the Pneumatic Bionic Voice prosthesis controller has an average onset/offset delay of 10 milliseconds compared to the PAL. Hence it addresses a major disadvantage of previous electronic voice prostheses, including myoelectric Bionic Voice, in meeting the short time-frames of controlling the onset/offset of the voice in continuous speech. PMID:29466455

How to: evaluate a diagnostic test.

PubMed

Leeflang, Mariska M G; Allerberger, Franz

2018-06-12

The development of an in vitro diagnostic test from a good idea to a clinically relevant tool takes several steps, with more stringent requirements at every step. This article aims to summarize the necessary questions to be asked about a test and to illustrate study designs answering these questions. We also aim to relate the Regulation (EU) 2017/746 to the needs of evidence-based diagnostic testing, where applicable. We used literature on evidence-based diagnostics, a text book on clinical trials in the development and marketing of medical devices and the English version of Regulation 2017/746 of the European Parliament and of the Council on in vitro diagnostic medical devices. The combination of different test uses and different stages of development determine the required test characteristics and suitability of study designs. In an earlier stage of test development it may be crucial to know whether a test can differentiate diseased persons from healthy controls, while this tells us little about how a test will perform in practice. Later stages focus on the diagnostic accuracy of a test in a clinically relevant situation. However, a test that perfectly distinguishes between patients with and without a certain condition may still have little effect on patient outcomes. Therefore, randomized controlled trials of testing may be needed, as well as post-marketing monitoring. Both researchers and users of tests need to be aware of the limitations of diagnostic test accuracy and realize that accuracy is only indirectly linked to people's health status. Copyright © 2018. Published by Elsevier Ltd.

FDA perspective on objective performance goals and clinical trial design for evaluating catheter-based treatment of critical limb ischemia.

PubMed

Kumar, Allison; Brooks, Steven S; Cavanaugh, Kenneth; Zuckerman, Bram

2009-12-01

The article by Conte et al.(1) on behalf of the Society for Vascular Surgery (SVS) in this issue of the Journal of Vascular Surgery provides guidelines for improving the consistency and interpretability of clinical trials intended to evaluate treatment options for patients with critical limb ischemia (CLI). This article identifies a number of key challenges with conducting and comparing CLI trials, including the wide spectrum of clinical presentations that CLI encompasses, the use of disparate eligibility criteria and endpoint measurements, and logistical and economic considerations that can limit study initiation and completion. The authors propose definitions for a number of performance goals derived from historical surgical literature as a means of reducing the negative impact of these factors. The current editorial reviews aspects of this proposal from the perspective of the authors in terms of their understanding of the statutory obligations of the U.S. Food and Drug Administration (FDA) to regulate the marketing of cardiovascular devices based on valid scientific evidence.

The European "clinical trial" regulation; relationship with the Jardé Act: a Giens workshop.

PubMed

Lemaire, François; Marchenay, Brigitte; Chassany, Olivier; Barthélémy, Philippe; Bouzzagou, Mohamed; Comet, Denis; Delval, Cécile; Dubray, Claude; Fouret, Cécile; Frija-Orvoen, Elisabeth; Gambotti, Laetitia; Lamarque, Véronique; d'Orsay, Geneviève; Plattner, Valérie; Sibenaler, Claire; Roux, Jacques; Thoby, Frédérique

2015-01-01

In May 2014, the European Union Parliament and Council published a new regulation on clinical trials on medicinal products for human use, which is designed to replace Directive 2001/20/EC. It will not come into effect until 2016. Nevertheless, it is essential to examine its relationship with national legislation, i.e. the Jardé Act, whose implementation has been delayed pending publication of the European regulation. The Giens workshop identified and examined the various issues that this relationship is bound to raise. In particular, it looked at trial methodology assessment procedures, the working relationship between the French National Agency of Drug Safety and Health Products (Agence Nationale de Sécurité du Médicament et des Produits de Santé, ANSM) and ethics committees during the authorization application evaluation phase, review of post-authorization/registration studies on medicinal products and medical devices, and data transparency. © 2015 Société Française de Pharmacologie et de Thérapeutique.

Spatial Discrimination Reversal and Incremental Repeated Acquisition in Adolescent and Adult BALB/c Mice

PubMed Central

Shen, Andrew Nathanael; Pope, Derek A.; Hutsell, Blake A.; Newland, M. Christopher

2015-01-01

Adolescence is characterized by neural and behavior development that includes increases in novel experiences and impulsive choice. Experimental rodent models can characterize behavior phenotypes that typify adolescence. The present experiment was designed to characterize differences between adolescent (post-natal day (PND) 34 - 60) and adult (PND 70 - 96) BALB/c mice using a response-initiated spatial discrimination reversal (SDR) and incremental repeated acquisition of response chains (IRA) procedures. During SDR, adolescents omitted more trials and were slower to initiate trials than adults, but the age groups did not differ on accuracy and perseveration measures. During IRA, adolescents displayed poorer overall performance (measured by progress quotient), lower accuracy at individual chain links, and completed fewer long response chains (>3 links) than adults. In both procedures (SDR and IRA), the poorer performance of adolescents appeared to be related to the use of a response device that was spatially removed from reinforcer delivery. These results indicate that SDR and IRA performance can be established during the brief rodent adolescent period but that these two age groups’ performances differ. We hypothesize that adolescent behavior is more sensitive than adult behavior to the spatiotemporal distance between response device and location of reinforcer delivery. PMID:26051193

Development of Uniform Protocol for Alopecia Areata Clinical Trials.

PubMed

Solomon, James A

2015-11-01

Developing a successful treatment for alopecia areata (AA), clearly has not been at the forefront of the agenda for new drug/device development among the pharmaceutical and medical device industry. The National Alopecia Areata Foundation (NAAF), a patient advocacy group, initiated a plan to facilitate and drive clinical research toward finding safe and efficacious treatments for AA. As such, Alopecia Areata Uniform Protocols for clinical trials to test new treatments for AA were developed. The design of the uniform protocol is to accomplish the development of a plug-and-play template as well as to provide a framework wherein data from studies utilizing the uniform protocol can be compared through consistency of inclusions/exclusions, safety, and outcome assessment measures. A core uniform protocol for use by pharmaceutical companies in testing proof of concept for investigational products to treat AA. The core protocol includes standardized title, informed consent, inclusion/exclusion criteria, disease outcome assessments, and safety assessments. The statistical methodology to assess successful outcomes will also be standardized. The protocol as well as the informed consent form has been approved in concept by Liberty IRB and is ready to present to pharmaceutical companies.

Theoretical design and discovery of the most-promising, previously overlooked hybrid perovskite compounds

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zunger, Alex; Kazmerski, Lawrence L.; Dalpian, Gustavo M.

The material class of hybrid organic-inorganic perovskites (AMX3) has risen rapidly from a virtually unknown material in photovoltaic applications a short 8-years ago into 20-23% efficient thin-film solar cell devices. As promising as this class of materials is, however, there are limitations associated with its poor long-term stability, non-optimal band gap, and the presence of toxic Pb atom on the metalloid site. An Edisonian laboratory exploration (i.e., growth + characterization) via trial-and-error processes of all other candidate materials, is unpractical. Our approach uses high speed computational design and discovery to screen the ‘best of class” candidates based upon optimal functionalities.

Thermophysiological responses induced by a body heat removal system with Peltier devices in a hot environment.

PubMed

Suzurikawa, Jun; Fujimoto, Sho; Mikami, Kousei; Jonai, Hiroshi; Inoue, Takenobu

2013-01-01

Individuals with spinal cord injuries often experience thermoregulation disorders as well as sensory and motor disabilities. In order to prevent such individuals from becoming hyperthermic, we developed a body heat removal system (BHRS) with thermoelectric devices. Our BHRS comprises four Peltier devices mounted on a wheelchair backrest and continuously transfers body heat through the contacting interface to the external environment. Here, we characterized thermophysiological responses induced by this novel contact-type cooling system. A cooling experiment in a hot environment with five able-bodied subjects demonstrated that sweating and systolic blood pressure in the back-cooling (BC) trial were significantly suppressed compared with those in no-cooling (NC) trial, while no difference was found in oral and skin temperatures. A correlation was observed between chest skin temperature and blood flow in the NC trial; this was not observed in the BC trial. These results suggest that BHRS modulates normal thermoregulatory responses, including sweating and vascular dilation and has the capability to partly replace these functions.

Rapid prototyping of flexible intrafascicular electrode arrays by picosecond laser structuring.

PubMed

Mueller, Matthias; de la Oliva, Natalia; Del Valle, Jaume; Delgado-Martínez, Ignacio; Navarro, Xavier; Stieglitz, Thomas

2017-12-01

Interfacing the peripheral nervous system can be performed with a large variety of electrode arrays. However, stimulating and recording a nerve while having a reasonable amount of channels limits the number of available systems. Translational research towards human clinical trial requires device safety and biocompatibility but would benefit from design flexibility in the development process to individualize probes. We selected established medical grade implant materials like precious metals and Parylene C to develop a rapid prototyping process for novel intrafascicular electrode arrays using a picosecond laser structuring. A design for a rodent animal model was developed in conjunction with an intrafascicular implantation strategy. Electrode characterization and optimization was performed first in saline solution in vitro before performance and biocompatibility were validated in sciatic nerves of rats in chronic implantation. The novel fabrication process proved to be suitable for prototyping and building intrafascicular electrode arrays. Electrochemical properties of the electrode sites were enhanced and tested for long-term stability. Chronic implantation in the sciatic nerve of rats showed good biocompatibility, selectivity and stable stimulation thresholds. Established medical grade materials can be used for intrafascicular nerve electrode arrays when laser structuring defines structure size in the micro-scale. Design flexibility reduces re-design cycle time and material certificates are beneficial support for safety studies on the way to clinical trials.

Promoting weight loss through diet and exercise in overweight or obese breast cancer survivors (InForma): study protocol for a randomized controlled trial.

PubMed

Gnagnarella, Patrizia; Dragà, Daniele; Baggi, Federica; Simoncini, Maria Claudia; Sabbatini, Annarita; Mazzocco, Ketti; Bassi, Fabio Domenico; Pravettoni, Gabriella; Maisonneuve, Patrick

2016-07-28

Most women with breast cancer experience a progressive weight gain during and after treatment. Obesity is associated with an increased risk of recurrence, contralateral breast cancer, and death. Physical activity after cancer diagnosis has been reported to have positive effects on body composition and quality of life. We present the protocol of the InForma study, a trial testing the efficacy of an intervention on weight loss (≥5 % of the baseline body weight) in a group of overweight or obese breast cancer survivors. This is a four-arm randomized controlled trial. Patients will receive a 6-month intervention and be followed for a further 18 months. Intervention is designed to improve adherence to a healthy diet and/or to increase physical activity, taking advantage of a wrist-based activity monitor. Participants will be recruited among overweight or obese breast cancer patients treated at the European Institute of Oncology, after completion of eventual adjuvant chemotherapy and/or radiotherapy. It is envisaged that 260 patients will be randomized into four arms: Dietary Intervention; Physical Activity Intervention; Physical Activity and Dietary Intervention; and Less Intensive Intervention. Women will be offered individualized counseling consisting of face-to face discussion and phone calls in addition to group meetings. A motivational interviewing approach will be used to encourage health behavior change. All participants will be given a pedometer device to monitor their physical activity. Participants' dietary intake will be repeatedly assessed using a validated food frequency questionnaire. Participants' quality of life and anxiety will be assessed with the Functional Assessment of Cancer Therapy-Breast and the State-Trait Anxiety Inventory questionnaires. Blood samples will be collected at baseline and follow-up visits to assess lipid and hormone profiles. Body composition will be repeatedly assessed using bioelectrical impedance vector analysis for identifying changes of fat and fat-free mass. Women allocated to the less intensive intervention arm will be considered as the control group. While there is a rising concern about the role of obesity in cancer recurrence and survival, this trial with its multi-arm design, motivational approach and use of a pedometer device will provide important insights regarding the most effective approach in promoting weight control in breast cancer survivors. ISRCTN53325751 (registration date: 16 October 2015); ClinicalTrials.gov NCT02622711 (registration date: 2 December 2015).

Development and Evaluation of a New Technological Way of Engaging Patients and Enhancing Understanding of Drug Tolerability in Early Clinical Development: PROACT.

PubMed

Hughes, Andrew; Landers, Donal; Arkenau, Hendrik-Tobias; Shah, Saj; Stephens, Richard; Mahal, Amrik; Simmons, Matthew; Lemech, Charlotte; Royle, Jennifer

2016-06-01

During early clinical testing of a new medication, it is critical to understand and characterise patient tolerability. However, in early clinical studies, it is difficult for patients to contribute directly to the sponsors' understanding of a new compound. Patient reported opinions about clinical tolerability (PROACT) provides a new, simple and innovative way in which patients can collaborate using an application downloaded to a mobile computer or smartphone. PROACT was designed with special consideration given to patient confidentiality, patient engagement and data security. A pilot study was conducted to investigate patient uptake of PROACT and to characterize clinical trial information it captured. Patients recruited to Phase I oncology trials at a UK center were eligible to participate but were required to have a tablet computer or smartphone. Patients used PROACT to upload audio/video messages that became available instantly to their clinical team, who were able to reply to the patient within PROACT. The patient's message was also analyzed, personally-identifiable information removed and anonymized information then made available to the sponsor in an analytics module for decision-making. In parallel, a patient focus group was engaged to provide feedback on communication needs during early clinical trials and the PROACT concept. Of the 16 patients informed of PROACT, 8 had a smart device and consented to take part. Use of PROACT varied and all messages volunteered were relevant and informative for drug development. Topics disclosed included tolerability impacts, study design, and drug formulation. Alignment with the clinical study data provided a richer understanding of tolerability and treatment consequences. This information was available to be shared among the clinical team and the sponsor, to improve patient support and experience. Patient forum feedback endorsed the concept and provided further information to enhance the application. Overall, PROACT achieved proof of concept in this small pilot study and delivered a secure end-to-end system that protected patient privacy and provided preliminary insight into patient experiences beyond the usual clinical trial data set. The use of mobile devices to interact actively with participants in clinical trials may be a new way of engaging and empowering patients. Further validation of this technology in larger patient cohorts is ongoing. AstraZeneca.

A Discussion of Possibility of Reinforcement Learning Using Event-Related Potential in BCI

NASA Astrophysics Data System (ADS)

Yamagishi, Yuya; Tsubone, Tadashi; Wada, Yasuhiro

Recently, Brain computer interface (BCI) which is a direct connecting pathway an external device such as a computer or a robot and a human brain have gotten a lot of attention. Since BCI can control the machines as robots by using the brain activity without using the voluntary muscle, the BCI may become a useful communication tool for handicapped persons, for instance, amyotrophic lateral sclerosis patients. However, in order to realize the BCI system which can perform precise tasks on various environments, it is necessary to design the control rules to adapt to the dynamic environments. Reinforcement learning is one approach of the design of the control rule. If this reinforcement leaning can be performed by the brain activity, it leads to the attainment of BCI that has general versatility. In this research, we paid attention to P300 of event-related potential as an alternative signal of the reward of reinforcement learning. We discriminated between the success and the failure trials from P300 of the EEG of the single trial by using the proposed discrimination algorithm based on Support vector machine. The possibility of reinforcement learning was examined from the viewpoint of the number of discriminated trials. It was shown that there was a possibility to be able to learn in most subjects.

Effect of Compression Devices on Preventing Deep Vein Thrombosis Among Adult Trauma Patients: A Systematic Review.

PubMed

Ibrahim, Mona; Ahmed, Azza; Mohamed, Warda Yousef; El-Sayed Abu Abduo, Somaya

2015-01-01

Trauma is the leading cause of death in Americans up to 44 years old each year. Deep vein thrombosis (DVT) is a significant condition occurring in trauma, and prophylaxis is essential to the appropriate management of trauma patients. The incidence of DVT varies in trauma patients, depending on patients' risk factors, modality of prophylaxis, and methods of detection. However, compression devices and arteriovenous (A-V) foot pumps prophylaxis are recommended in trauma patients, but the efficacy and optimal use of it is not well documented in the literature. The aim of this study was to review the literature on the effect of compression devices in preventing DVT among adult trauma patients. We searched through PubMed, CINAHL, and Cochrane Central Register of Controlled Trials for eligible studies published from 1990 until June 2014. Reviewers identified all randomized controlled trials that satisfied the study criteria, and the quality of included studies was assessed by Cochrane risk of bias tool. Five randomized controlled trials were included with a total of 1072 patients. Sequential compression devices significantly reduced the incidence of DVT in trauma patients. Also, foot pumps were more effective in reducing incidence of DVT compared with sequential compression devices. Sequential compression devices and foot pumps reduced the incidence of DVT in trauma patients. However, the evidence is limited to a small sample size and did not take into account other confounding variables that may affect the incidence of DVT in trauma patients. Future randomized controlled trials with larger probability samples to investigate the optimal use of mechanical prophylaxis in trauma patients are needed.

A Novel Small-Specimen Planar Biaxial Testing System With Full In-Plane Deformation Control.

PubMed

Potter, Samuel; Graves, Jordan; Drach, Borys; Leahy, Thomas; Hammel, Chris; Feng, Yuan; Baker, Aaron; Sacks, Michael S

2018-05-01

Simulations of soft tissues require accurate and robust constitutive models, whose form is derived from carefully designed experimental studies. For such investigations of membranes or thin specimens, planar biaxial systems have been used extensively. Yet, all such systems remain limited in their ability to: (1) fully prescribe in-plane deformation gradient tensor F2D, (2) ensure homogeneity of the applied deformation, and (3) be able to accommodate sufficiently small specimens to ensure a reasonable degree of material homogeneity. To address these issues, we have developed a novel planar biaxial testing device that overcomes these difficulties and is capable of full control of the in-plane deformation gradient tensor F2D and of testing specimens as small as ∼4 mm × ∼4 mm. Individual actuation of the specimen attachment points, combined with a robust real-time feedback control, enabled the device to enforce any arbitrary F2D with a high degree of accuracy and homogeneity. Results from extensive device validation trials and example tissues illustrated the ability of the device to perform as designed and gather data needed for developing and validating constitutive models. Examples included the murine aortic tissues, allowing for investigators to take advantage of the genetic manipulation of murine disease models. These capabilities highlight the potential of the device to serve as a platform for informing and verifying the results of inverse models and for conducting robust, controlled investigation into the biomechanics of very local behaviors of soft tissues and membrane biomaterials.

Natriuretic Peptides, 6-Min Walk Test, and Quality-of-Life Questionnaires as Clinically Meaningful Endpoints in HF Trials.

PubMed

Ferreira, João Pedro; Duarte, Kevin; Graves, Todd L; Zile, Michael R; Abraham, William T; Weaver, Fred A; Lindenfeld, JoAnn; Zannad, Faiez

2016-12-20

The Expedited Access for Premarket Approval and De Novo Medical Devices Intended for Unmet Medical Need for Life Threatening or Irreversibly Debilitating Diseases or Conditions document was issued as a guidance for industry and for the Food and Drug Administration. The Expedited Access Pathway was designed as a new program for medical devices that demonstrated the potential to address unmet medical needs for life threatening or irreversibly debilitating conditions. The Food and Drug Administration would consider assessments of a device's effect on intermediate endpoints that, when improving in a congruent fashion, are reasonably likely to predict clinical benefit. The purpose of this review is to provide evidence to support the use of 3 such intermediate endpoints: natriuretic peptides, such as N-terminal pro-B-type natriuretic peptide/B-type natriuretic peptide, the 6-min walk test distance, and health-related quality of life in heart failure. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

ABSORB II randomized controlled trial: a clinical evaluation to compare the safety, efficacy, and performance of the Absorb everolimus-eluting bioresorbable vascular scaffold system against the XIENCE everolimus-eluting coronary stent system in the treatment of subjects with ischemic heart disease caused by de novo native coronary artery lesions: rationale and study design.

PubMed

Diletti, Roberto; Serruys, Patrick W; Farooq, Vasim; Sudhir, Krishnankutty; Dorange, Cecile; Miquel-Hebert, Karine; Veldhof, Susan; Rapoza, Richard; Onuma, Yoshinobu; Garcia-Garcia, Hector M; Chevalier, Bernard

2012-11-01

Currently, no data are available on the direct comparison between the Absorb everolimus-eluting bioresorbable vascular scaffold (Absorb BVS) and conventional metallic drug-eluting stents. The ABSORB II study is a randomized, active-controlled, single-blinded, multicenter clinical trial aiming to compare the second-generation Absorb BVS with the XIENCE everolimus-eluting metallic stent. Approximately 501 subjects will be enrolled on a 2:1 randomization basis (Absorb BVS/XIENCE stent) in approximately 40 investigational sites across Europe and New Zealand. Treated lesions will be up to 2 de novo native coronary artery lesions, each located in different major epicardial vessels, all with an angiographic maximal luminal diameter between 2.25 and 3.8 mm as estimated by online quantitative coronary angiography (QCA) and a lesion length of ≤48 mm. Clinical follow-up is planned at 30 and 180 days and at 1, 2, and 3 years. All subjects will undergo coronary angiography, intravascular ultrasound (IVUS) and IVUS-virtual histology at baseline (pre-device and post-device implantation) and at 2-year angiographic follow-up. The primary end point is superiority of the Absorb BVS vs XIENCE stent in terms of vasomotor reactivity of the treated segment at 2 years, defined as the QCA quantified change in the mean lumen diameter prenitrate and postnitrate administration. The coprimary end point is the noninferiority (reflex to superiority) of the QCA-derived minimum lumen diameter at 2 years postnitrate minus minimum lumen diameter postprocedure postnitrate by QCA. In addition, all subjects allocated to the Absorb BVS group will undergo multislice computed tomography imaging at 3 years. The ABSORB II randomized controlled trial (ClinicalTrials.gov NCT01425281) is designed to compare the safety, efficacy, and performance of Absorb BVS against the XIENCE everolimus-eluting stent in the treatment of de novo native coronary artery lesions. Copyright © 2012 Mosby, Inc. All rights reserved.

A Mechanomodulatory Device to Minimize Incisional Scar Formation

PubMed Central

Wong, Victor W.; Beasley, Bill; Zepeda, John; Dauskardt, Reinhold H.; Yock, Paul G.; Longaker, Michael T.; Gurtner, Geoffrey C.

2013-01-01

Objective To mechanically control the wound environment and prevent cutaneous scar formation. Approach We subjected various material substrates to biomechanical testing to investigate their ability to modulate skin behavior. Combinations of elastomeric materials, adhesives, and strain applicators were evaluated to develop topical stress-shielding devices. Noninvasive imaging modalities were utilized to characterize anatomic site-specific differences in skin biomechanical properties in humans. The devices were tested in a validated large animal model of hypertrophic scarring. Phase I within-patient controlled clinical trials were conducted to confirm their safety and efficacy in scar reduction in patients undergoing abdominoplasty surgery. Results Among the tested materials and device applicators, a polymer device was developed that effectively off-loaded high tension wounds and blocked pro-fibrotic pathways and excess scar formation in red Duroc swine. In humans, different anatomic sites exhibit unique biomechanical properties that may correlate with the propensity to form scars. In the clinical trial, utilization of this device significantly reduced incisional scar formation and improved scar appearance for up to 12 months compared with control incisions that underwent routine postoperative care. Innovation This is the first device that is able to precisely control the mechanical environment of incisional wounds and has been demonstrated in multiple clinical trials to significantly reduce scar formation after surgery. Conclusion Mechanomodulatory strategies to control the incisional wound environment can significantly reduce pathologic scarring and fibrosis after surgery. PMID:24527342

A Modern Magnetic Implant for Gastroesophageal Reflux Disease.

PubMed

Ganz, Robert A

2017-09-01

A magnetic implant for the treatment of gastroesophageal reflux disease (GERD) was Food and Drug Administration-approved in 2012 and has been extensively evaluated. The device is a ring of magnets that are placed around the gastroesophageal junction, augmenting the native lower esophageal sphincter and preventing reflux yet preserving lower esophageal sphincter physiologic function and allowing belching and vomiting. Magnetic force is advantageous, being permanent and precise, and forces between magnets decrease with esophageal displacement. Multiple patient cohorts have been studied using the magnetic device, and trials establish consistent, long-term improvement in pH data, GERD symptom scores, and proton-pump inhibitor use. A 5-year Food and Drug Administration trial demonstrated that most patients achieved normal pH scores, 85% stopped proton-pump inhibitors, and GERD health-related quality of life symptom scores improved from 27 to 4 at 5 years. Seven studies have compared magnetic augmentation with laparoscopic Nissen fundoplication and demonstrated that the magnetic device achieved comparable efficacy with regard to proton-pump inhibitor cessation, GERD symptom score improvement, and heartburn and regurgitation scores. However, to date there have been no randomized, controlled trials comparing the 2 techniques, and the study cohorts are not necessarily comparable regarding hiatal hernia size, severity of reflux, body mass index scores, or esophagitis scores. Dysphagia incidence was similar in both groups. Reoperation rates and safety profiles were also comparable, but the magnetic device demonstrated significant beneficial differences in allowing belching and vomiting. The magnetic device is safe, with the main adverse event being dysphagia with an approximate 3%-5% chronic incidence. Device removals in clinical trials have been between 0% and 7% and were uneventful. There have been no erosions, perforations, or infections in FDA clinical trials; erosions have rarely been noted in practice. Magnetic augmentation of the lower esophageal sphincter is a safe and effective operation for GERD, and should be considered a surgical option for those seeking a fundic-sparing operation, particularly those with parameters consistent with study cohorts. Additional randomized, controlled trials are underway. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

Rigor and reproducibility in research with transcranial electrical stimulation: An NIMH-sponsored workshop.

PubMed

Bikson, Marom; Brunoni, Andre R; Charvet, Leigh E; Clark, Vincent P; Cohen, Leonardo G; Deng, Zhi-De; Dmochowski, Jacek; Edwards, Dylan J; Frohlich, Flavio; Kappenman, Emily S; Lim, Kelvin O; Loo, Colleen; Mantovani, Antonio; McMullen, David P; Parra, Lucas C; Pearson, Michele; Richardson, Jessica D; Rumsey, Judith M; Sehatpour, Pejman; Sommers, David; Unal, Gozde; Wassermann, Eric M; Woods, Adam J; Lisanby, Sarah H

Neuropsychiatric disorders are a leading source of disability and require novel treatments that target mechanisms of disease. As such disorders are thought to result from aberrant neuronal circuit activity, neuromodulation approaches are of increasing interest given their potential for manipulating circuits directly. Low intensity transcranial electrical stimulation (tES) with direct currents (transcranial direct current stimulation, tDCS) or alternating currents (transcranial alternating current stimulation, tACS) represent novel, safe, well-tolerated, and relatively inexpensive putative treatment modalities. This report seeks to promote the science, technology and effective clinical applications of these modalities, identify research challenges, and suggest approaches for addressing these needs in order to achieve rigorous, reproducible findings that can advance clinical treatment. The National Institute of Mental Health (NIMH) convened a workshop in September 2016 that brought together experts in basic and human neuroscience, electrical stimulation biophysics and devices, and clinical trial methods to examine the physiological mechanisms underlying tDCS/tACS, technologies and technical strategies for optimizing stimulation protocols, and the state of the science with respect to therapeutic applications and trial designs. Advances in understanding mechanisms, methodological and technological improvements (e.g., electronics, computational models to facilitate proper dosing), and improved clinical trial designs are poised to advance rigorous, reproducible therapeutic applications of these techniques. A number of challenges were identified and meeting participants made recommendations made to address them. These recommendations align with requirements in NIMH funding opportunity announcements to, among other needs, define dosimetry, demonstrate dose/response relationships, implement rigorous blinded trial designs, employ computational modeling, and demonstrate target engagement when testing stimulation-based interventions for the treatment of mental disorders. Published by Elsevier Inc.

Rigor and reproducibility in research with transcranial electrical stimulation: An NIMH-sponsored workshop

PubMed Central

Bikson, Marom; Brunoni, Andre R.; Charvet, Leigh E.; Clark, Vincent P.; Cohen, Leonardo G.; Deng, Zhi-De; Dmochowski, Jacek; Edwards, Dylan J.; Frohlich, Flavio; Kappenman, Emily S.; Lim, Kelvin O.; Loo, Colleen; Mantovani, Antonio; McMullen, David P.; Parra, Lucas C.; Pearson, Michele; Richardson, Jessica D.; Rumsey, Judith M.; Sehatpour, Pejman; Sommers, David; Unal, Gozde; Wassermann, Eric M.; Woods, Adam J.; Lisanby, Sarah H.

2018-01-01

Background Neuropsychiatric disorders are a leading source of disability and require novel treatments that target mechanisms of disease. As such disorders are thought to result from aberrant neuronal circuit activity, neuromodulation approaches are of increasing interest given their potential for manipulating circuits directly. Low intensity transcranial electrical stimulation (tES) with direct currents (transcranial direct current stimulation, tDCS) or alternating currents (transcranial alternating current stimulation, tACS) represent novel, safe, well-tolerated, and relatively inexpensive putative treatment modalities. Objective This report seeks to promote the science, technology and effective clinical applications of these modalities, identify research challenges, and suggest approaches for addressing these needs in order to achieve rigorous, reproducible findings that can advance clinical treatment. Methods The National Institute of Mental Health (NIMH) convened a workshop in September 2016 that brought together experts in basic and human neuroscience, electrical stimulation biophysics and devices, and clinical trial methods to examine the physiological mechanisms underlying tDCS/tACS, technologies and technical strategies for optimizing stimulation protocols, and the state of the science with respect to therapeutic applications and trial designs. Results Advances in understanding mechanisms, methodological and technological improvements (e.g., electronics, computational models to facilitate proper dosing), and improved clinical trial designs are poised to advance rigorous, reproducible therapeutic applications of these techniques. A number of challenges were identified and meeting participants made recommendations made to address them. Conclusions These recommendations align with requirements in NIMH funding opportunity announcements to, among other needs, define dosimetry, demonstrate dose/response relationships, implement rigorous blinded trial designs, employ computational modeling, and demonstrate target engagement when testing stimulation-based interventions for the treatment of mental disorders. PMID:29398575

Funding source and the quality of reports of chronic wounds trials: 2004 to 2011

PubMed Central

2014-01-01

Background Critical commentaries suggest that wound care randomised controlled trials (RCTs) are often poorly reported with many methodological flaws. Furthermore, interventions in chronic wounds, rather than being drugs, are often medical devices for which there are no requirements for RCTs to bring products to market. RCTs in wounds trials therefore potentially represent a form of marketing. This study presents a methodological overview of chronic wound trials published between 2004 and 2011 and investigates the influence of industry funding on methodological quality. Methods A systematic search for RCTs for the treatment of chronic wounds published in the English language between 2004 and 2011 (inclusive) in the Cochrane Wounds Group Specialised Register of Trials was carried out. Data were extracted on aspects of trial design, conduct and quality including sample size, duration of follow-up, specification of a primary outcome, use of surrogate outcomes, and risks of bias. In addition, the prevalence of industry funding was assessed and its influence on the above aspects of trial design, conduct and quality was assessed. Results A total of 167 RCTs met our inclusion criteria. We found chronic wound trials often have short durations of follow-up (median 12 weeks), small sample sizes (median 63), fail to define a primary outcome in 41% of cases, and those that do define a primary outcome, use surrogate measures of healing in 40% of cases. Only 40% of trials used appropriate methods of randomisation, 25% concealed allocation and 34% blinded outcome assessors. Of the included trials, 41% were wholly or partially funded by industry, 33% declared non-commercial funding and 26% did not report a funding source. Industry funding was not statistically significantly associated with any measure of methodological quality, though this analysis was probably underpowered. Conclusions This overview confirms concerns raised about the methodological quality of RCTs in wound care and illustrates that greater efforts must be made to follow international standards for conducting and reporting RCTs. There is currently minimal evidence of an influence of industry funding on methodological quality although analyses had limited power and funding source was not reported for a quarter of studies. PMID:24422753

Funding source and the quality of reports of chronic wounds trials: 2004 to 2011.

PubMed

Hodgson, Robert; Allen, Richard; Broderick, Ellen; Bland, J Martin; Dumville, Jo C; Ashby, Rebecca; Bell-Syer, Sally; Foxlee, Ruth; Hall, Jill; Lamb, Karen; Madden, Mary; O'Meara, Susan; Stubbs, Nikki; Cullum, Nicky

2014-01-14

Critical commentaries suggest that wound care randomised controlled trials (RCTs) are often poorly reported with many methodological flaws. Furthermore, interventions in chronic wounds, rather than being drugs, are often medical devices for which there are no requirements for RCTs to bring products to market. RCTs in wounds trials therefore potentially represent a form of marketing. This study presents a methodological overview of chronic wound trials published between 2004 and 2011 and investigates the influence of industry funding on methodological quality. A systematic search for RCTs for the treatment of chronic wounds published in the English language between 2004 and 2011 (inclusive) in the Cochrane Wounds Group Specialised Register of Trials was carried out.Data were extracted on aspects of trial design, conduct and quality including sample size, duration of follow-up, specification of a primary outcome, use of surrogate outcomes, and risks of bias. In addition, the prevalence of industry funding was assessed and its influence on the above aspects of trial design, conduct and quality was assessed. A total of 167 RCTs met our inclusion criteria. We found chronic wound trials often have short durations of follow-up (median 12 weeks), small sample sizes (median 63), fail to define a primary outcome in 41% of cases, and those that do define a primary outcome, use surrogate measures of healing in 40% of cases. Only 40% of trials used appropriate methods of randomisation, 25% concealed allocation and 34% blinded outcome assessors. Of the included trials, 41% were wholly or partially funded by industry, 33% declared non-commercial funding and 26% did not report a funding source. Industry funding was not statistically significantly associated with any measure of methodological quality, though this analysis was probably underpowered. This overview confirms concerns raised about the methodological quality of RCTs in wound care and illustrates that greater efforts must be made to follow international standards for conducting and reporting RCTs. There is currently minimal evidence of an influence of industry funding on methodological quality although analyses had limited power and funding source was not reported for a quarter of studies.

Effectiveness of an annular closure device in a "real-world" population: stratification of registry data using screening criteria from a randomized controlled trial.

PubMed

Kuršumović, Adisa; Rath, Stefan A

2018-01-01

Increased focus has been put on the use of "'real-world" data to support randomized clinical trial (RCT) evidence for clinical decision-making. The objective of this study was to assess the performance of an annular closure device (ACD) after stratifying a consecutive series of "real-world" patients by the screening criteria of an ongoing RCT. This was a single-center registry analysis of 164 subjects who underwent limited discectomy combined with ACD for symptomatic lumbar disc herniation. Patients were stratified into two groups using the selection criteria of a pivotal RCT on the same device: Trial (met inclusion; n=44) or non-Trial (did not meet inclusion; n=120). Patient-reported outcomes, including Oswestry Disability Index (ODI) and visual analog scale (VAS) for leg and back pain, and adverse events were collected from baseline to last follow-up (mean: Trial - 15.6 months; non-Trial - 14.6 months). Statistical analyses were performed with significance set at p <0.05. Patient-reported outcomes were not significantly different between groups at last ( p ≥0.15) and clinical success (≥15-point improvement in ODI score; ≥20-point improvement in VAS scores) was achieved in both the groups. Three non-Trial (2.5%) and three Trial (6.8%) patients experienced symptomatic reherniation ( p =0.34). Rates of reoperation, ACD mesh dislocation/separation, and other radiographic findings were similar between groups ( p =1.00). Outcomes with the ACD appeared advantageous in both the groups, particularly in comparison with historical reherniation rates reported in the same high-risk, large annular defect population. Stratification of this "real-world" series on the basis of RCT screening criteria did not result in significant between-group differences. These findings suggest that the efficacy of the ACD extends beyond the strictly defined patient population being studied in the RCT of this device. Furthermore, reducing the reherniation rate following lumbar discectomy has positive clinical and economic implications.

Using Fitness Trackers and Smartwatches to Measure Physical Activity in Research: Analysis of Consumer Wrist-Worn Wearables

PubMed Central

Haugen Mikalsen, Martin; Woldaregay, Ashenafi Zebene; Muzny, Miroslav; Hartvigsen, Gunnar; Hopstock, Laila Arnesdatter; Grimsgaard, Sameline

2018-01-01

Background New fitness trackers and smartwatches are released to the consumer market every year. These devices are equipped with different sensors, algorithms, and accompanying mobile apps. With recent advances in mobile sensor technology, privately collected physical activity data can be used as an addition to existing methods for health data collection in research. Furthermore, data collected from these devices have possible applications in patient diagnostics and treatment. With an increasing number of diverse brands, there is a need for an overview of device sensor support, as well as device applicability in research projects. Objective The objective of this study was to examine the availability of wrist-worn fitness wearables and analyze availability of relevant fitness sensors from 2011 to 2017. Furthermore, the study was designed to assess brand usage in research projects, compare common brands in terms of developer access to collected health data, and features to consider when deciding which brand to use in future research. Methods We searched for devices and brand names in six wearable device databases. For each brand, we identified additional devices on official brand websites. The search was limited to wrist-worn fitness wearables with accelerometers, for which we mapped brand, release year, and supported sensors relevant for fitness tracking. In addition, we conducted a Medical Literature Analysis and Retrieval System Online (MEDLINE) and ClinicalTrials search to determine brand usage in research projects. Finally, we investigated developer accessibility to the health data collected by identified brands. Results We identified 423 unique devices from 132 different brands. Forty-seven percent of brands released only one device. Introduction of new brands peaked in 2014, and the highest number of new devices was introduced in 2015. Sensor support increased every year, and in addition to the accelerometer, a photoplethysmograph, for estimating heart rate, was the most common sensor. Out of the brands currently available, the five most often used in research projects are Fitbit, Garmin, Misfit, Apple, and Polar. Fitbit is used in twice as many validation studies as any other brands and is registered in ClinicalTrials studies 10 times as often as other brands. Conclusions The wearable landscape is in constant change. New devices and brands are released every year, promising improved measurements and user experience. At the same time, other brands disappear from the consumer market for various reasons. Advances in device quality offer new opportunities for research. However, only a few well-established brands are frequently used in research projects, and even less are thoroughly validated. PMID:29567635

Electromechanical-assisted training for walking after stroke.

PubMed

Mehrholz, Jan; Thomas, Simone; Werner, Cordula; Kugler, Joachim; Pohl, Marcus; Elsner, Bernhard

2017-05-10

Electromechanical- and robotic-assisted gait-training devices are used in rehabilitation and might help to improve walking after stroke. This is an update of a Cochrane Review first published in 2007. To investigate the effects of automated electromechanical- and robotic-assisted gait-training devices for improving walking after stroke. We searched the Cochrane Stroke Group Trials Register (last searched 9 August 2016), the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2016, Issue 8), MEDLINE in Ovid (1950 to 15 August 2016), Embase (1980 to 15 August 2016), CINAHL (1982 to 15 August 2016), AMED (1985 to 15 August 2016), Web of Science (1899 to 16 August 2016), SPORTDiscus (1949 to 15 September 2012), the Physiotherapy Evidence Database (PEDro) (searched 16 August 2016), and the engineering databases COMPENDEX (1972 to 16 November 2012) and Inspec (1969 to 26 August 2016). We handsearched relevant conference proceedings, searched trials and research registers, checked reference lists, and contacted authors in an effort to identify further published, unpublished, and ongoing trials. We included all randomised controlled trials and randomised controlled cross-over trials in people over the age of 18 years diagnosed with stroke of any severity, at any stage, in any setting, evaluating electromechanical- and robotic-assisted gait training versus normal care. Two review authors independently selected trials for inclusion, assessed methodological quality and risk of bias, and extracted the data. The primary outcome was the proportion of participants walking independently at follow-up. We included 36 trials involving 1472 participants in this review update. Electromechanical-assisted gait training in combination with physiotherapy increased the odds of participants becoming independent in walking (odds ratio (random effects) 1.94, 95% confidence interval (CI) 1.39 to 2.71; P < 0.001; I² = 8%; moderate-quality evidence) but did not significantly increase walking velocity (mean difference (MD) 0.04 m/s, 95% CI 0.00 to 0.09; P = 0.08; I² = 65%; low-quality evidence) or walking capacity (MD 5.84 metres walked in 6 minutes, 95% CI -16.73 to 28.40; P = 0.61; I² = 53%; very low-quality evidence). The results must be interpreted with caution because 1) some trials investigated people who were independent in walking at the start of the study, 2) we found variations between the trials with respect to devices used and duration and frequency of treatment, and 3) some trials included devices with functional electrical stimulation. Our planned subgroup analysis suggested that people in the acute phase may benefit, but people in the chronic phase may not benefit from electromechanical-assisted gait training. Post hoc analysis showed that people who are non-ambulatory at intervention onset may benefit, but ambulatory people may not benefit from this type of training. Post hoc analysis showed no differences between the types of devices used in studies regarding ability to walk, but significant differences were found between devices in terms of walking velocity. People who receive electromechanical-assisted gait training in combination with physiotherapy after stroke are more likely to achieve independent walking than people who receive gait training without these devices. We concluded that seven patients need to be treated to prevent one dependency in walking. Specifically, people in the first three months after stroke and those who are not able to walk seem to benefit most from this type of intervention. The role of the type of device is still not clear. Further research should consist of large definitive pragmatic phase III trials undertaken to address specific questions about the most effective frequency and duration of electromechanical-assisted gait training as well as how long any benefit may last.

Investigational Clinical Trial of a Prototype Optoelectronic Computer-Aided Navigation Device for Dental Implant Surgery.

PubMed

Jokstad, Asbjørn; Winnett, Brenton; Fava, Joseph; Powell, David; Somogyi-Ganss, Eszter

New digital technologies enable real-time computer-aided (CA) three-dimensional (3D) guidance during dental implant surgery. The aim of this investigational clinical trial was to demonstrate the safety and effectiveness of a prototype optoelectronic CA-navigation device in comparison with the conventional approach for planning and effecting dental implant surgery. Study participants with up to four missing teeth were recruited from the pool of patients referred to the University of Toronto Graduate Prosthodontics clinic. The first 10 participants were allocated to either a conventional or a prototype device study arm in a randomized trial. The next 10 participants received implants using the prototype device. All study participants were restored with fixed dental prostheses after 3 (mandible) or 6 (maxilla) months healing, and monitored over 12 months. The primary outcome was the incidence of any surgical, biologic, or prosthetic adverse events or device-related complications. Secondary outcomes were the incidence of positioning of implants not considered suitable for straightforward prosthetic restoration (yes/no); the perception of the ease of use of the prototype device by the two oral surgeons, recorded by use of a Likert-type questionnaire; and the clinical performance of the implant and superstructure after 1 year in function. Positioning of the implants was appraised on periapical radiographs and clinical photographs by four independent blinded examiners. Peri-implant bone loss was measured on periapical radiographs by a blinded examiner. No adverse events occurred related to placing any implants. Four device-related complications led to a switch from using the prototype device to the conventional method. All implants placed by use of the prototype device were in a position considered suitable for straightforward prosthetic restoration (n = 21). The qualitative evaluation by the surgeons was generally positive, although ergonomic challenges were identified. All study participants were present for the 1-year examination (n = 20 patients, 41 implants, 32 superstructures), and no complications or failures with any implants or superstructures were revealed. The peri-implant bone loss was less than 1 mm for all implants. Within the limitations of this trial, the prototype device provided placement of dental implants without adverse events.

A Movement Monitor Based on Magneto-Inertial Sensors for Non-Ambulant Patients with Duchenne Muscular Dystrophy: A Pilot Study in Controlled Environment.

PubMed

Le Moing, Anne-Gaëlle; Seferian, Andreea Mihaela; Moraux, Amélie; Annoussamy, Mélanie; Dorveaux, Eric; Gasnier, Erwan; Hogrel, Jean-Yves; Voit, Thomas; Vissière, David; Servais, Laurent

2016-01-01

Measurement of muscle strength and activity of upper limbs of non-ambulant patients with neuromuscular diseases is a major challenge. ActiMyo® is an innovative device that uses magneto-inertial sensors to record angular velocities and linear accelerations that can be used over long periods of time in the home environment. The device was designed to insure long-term stability and good signal to noise ratio, even for very weak movements. In order to determine relevant and pertinent clinical variables with potential for use as outcome measures in clinical trials or to guide therapy decisions, we performed a pilot study in non-ambulant neuromuscular patients. We report here data from seven Duchenne Muscular Dystrophy (DMD) patients (mean age 18.5 ± 5.5 years) collected in a clinical setting. Patients were assessed while wearing the device during performance of validated tasks (MoviPlate, Box and Block test and Minnesota test) and tasks mimicking daily living. The ActiMyo® sensors were placed on the wrists during all the tests. Software designed for use with the device computed several variables to qualify and quantify muscular activity in the non-ambulant subjects. Four variables representative of upper limb activity were studied: the rotation rate, the ratio of the vertical component in the overall acceleration, the hand elevation rate, and an estimate of the power of the upper limb. The correlations between clinical data and physical activity and the ActiMyo® movement parameters were analyzed. The mean of the rotation rate and mean of the elevation rate appeared promising since these variables had the best reliability scores and correlations with task scores. Parameters could be computed even in a patient with a Brooke functional score of 6. The variables chosen are good candidates as potential outcome measures in non-ambulant patients with Duchenne Muscular Dystrophy and use of the ActiMyo® is currently being explored in home environment. ClinicalTrials.gov NCT01611597.

A randomized clinical trial of the effectiveness of an acupressure device (relief brief) for managing symptoms of dysmenorrhea.

PubMed

Taylor, Diana; Miaskowski, Christine; Kohn, Joel

2002-06-01

To develop and test the safety and effectiveness of an acupressure garment (the Relief Brief) in decreasing the pain and symptom distress associated with dysmenorrhea. A randomized clinical trial applied a 2 (Relief Brief use or control group) x 3 (baseline and two treatment measurement occasions) mixed factorial design. Sixty-one (61) women with moderately severe primary dysmenorrhea were randomly assigned to the standard treatment control group or the Relief Brief acupressure device group after one pretreatment menses, with 58 women reporting the effect on their pain during two post-treatment menstrual cycles. The acupressure garment: The Relief Brief is a cotton Lycra panty brief with a fixed number of lower abdominal and lower back latex foam acupads that provide pressure to dysmenorrhea-relieving Chinese acupressure points. Menstrual pain severity (worst pain and symptom intensity), pain medication use, and adverse effects were analyzed using between-groups and repeated measures analyses of treatment effects. Statistical and clinical significance criteria were applied a priori. For pain measures and pain medication use, the group main effect, time main effect and group x time interaction were statistically significant. Median pain medication use, the same for both groups at baseline (6 pills per day), dropped to 2 pills per day for the Relief Brief group but remained at 6 pills for the control group at the second treatment cycle. Predicted clinical significance criteria were surpassed: almost all (90%) women wearing the Relief Brief obtained at least a 25% reduction in menstrual pain severity (a 2-3 point drop) compared to only 8% of the control group (z = 6.07; p < 0.05). Relief Brief use was associated with at least a 50% decline in menstrual pain symptom intensity in more than two thirds of the women. An acupressure device is an effective and safe nonpharmacologic strategy for the treatment of primary dysmenorrhea. With design modifications, it could serve as a main treatment modality for women who suffer from primary dysmenorrhea and do not wish to or cannot use the conventional pharmacologic agents. In addition, this acupressure device may serve as an adjuvant therapy to medication in more severe cases of dysmenorrhea.

Parylene as a new membrane material for BioMEMS applications

NASA Astrophysics Data System (ADS)

Lu, Bo

The work in this thesis aims to use MEMS and microfabrication technologies to develop two types of parylene membrane devices for biomedical applications. The first device is the parylene membrane filter for cancer detection. The presence of circulating tumor cells (CTC) in patient blood is an important sign of cancer metastasis. However, currently there are two big challenges for CTC detection. First, CTCs are extremely rare, especially at the early stage of cancer metastasis. Secondly, CTCs are very fragile, and are very likely to be damaged during the capturing process. By using size-based membrane filtration through the specially designed parylene filters, together with a constant-pressure filtration system, we are able to capture the CTCs from patient blood with high capture efficiency, high viability, moderate enrichment, and high throughput. Both immunofluorescence enumeration and telomerase activity detection have been used to detect and differentiate the captured CTCs. The feasibility of further cell culture of the captured CTCs has also been demonstrated, which could be a useful way to increase the number of CTCs for future studies. Models of the time-dependent cell membrane damage are developed to predict and prevent CTC damage during this detection process. The results of clinical trials further demonstrate that the parylene membrane filter is a promising device for cancer detection. The second device is the parylene artificial Bruch's membrane for age-related macular degeneration (AMD). AMD is usually characterized by an impaired Bruch's membrane with much lowered permeability, which impedes the transportation of nutrients from choroid vessels to nourish the retinal pigment epithelial (RPE) cells and photoreceptors. Parylene is selected as a substitute material because of its good mechanical properties, transparency, biocompatibility, and machinability. More importantly, it is found that the permeability of submicron parylene is very similar to that of healthy human Bruch's membrane. A mesh-supported submicron parylene membrane structure has been designed and its feasibility as an artificial Bruch's membrane has been demonstrated by diffusion experiments, cell perfusion culture, and pressure deflection tests. RPE cells are able to adhere, proliferate and develop into normal in vivo-like morphology and functions. Currently this artificial membrane is under clinical trials.

Improving treatment for obese women with early stage cancer of the uterus: rationale and design of the levonorgestrel intrauterine device ± metformin ± weight loss in endometrial cancer (feMME) trial.

PubMed

Hawkes, A L; Quinn, M; Gebski, V; Armes, J; Brennan, D; Janda, M; Obermair, A

2014-09-01

Endometrial adenocarcinoma (EC) is the most common gynaecologic cancer. Up to 90% of EC patients are obese which poses a health threat to patients post-treatment. Standard treatment for EC includes hysterectomy, although this has significant side effects for obese women at high risk of surgical complications and for women of childbearing age. This trial investigates the effectiveness of non-surgical or conservative treatment options for obese women with early stage EC. The primary aim is to determine the efficacy of: levonorgestrel intrauterine device (LNG-IUD); with or without metformin (an antidiabetic drug); and with or without a weight loss intervention to achieve a pathological complete response (pCR) in EC at six months from study treatment initiation. The secondary aim is to enhance understanding of the molecular processes and to predict a treatment response by investigating EC biomarkers. An open label, three-armed, randomised, phase-II, multi-centre trial of LNG-IUD ± metformin ± weight loss intervention. 165 participants from 28 centres are randomly assigned in a 3:3:5 ratio to the treatment arms. Clinical, quality of life and health behavioural data will be collected at baseline, six weeks, three and six months. EC biomarkers will be assessed at baseline, three and six months. There is limited prospective evidence for conservative treatment for EC. Trial results could benefit patients and reduce health system costs through a reduction in hospitalisations and through lower incidence of adverse events currently observed with standard treatment. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

Immunological Challenges Facing Translation of Alginate Encapsulated Porcine Islet Xenotransplantation to Human Clinical Trials.

PubMed

Krishnan, Rahul; Ko, David; Foster, Clarence E; Liu, Wendy; Smink, A M; de Haan, Bart; De Vos, Paul; Lakey, Jonathan R T

2017-01-01

Transplantation of alginate-encapsulated islets has the potential to treat patients suffering from type I diabetes, a condition characterized by an autoimmune attack against insulin-secreting beta cells. However, there are multiple immunological challenges associated with this procedure, all of which must be adequately addressed prior to translation from trials in small animal and nonhuman primate models to human clinical trials. Principal threats to graft viability include immune-mediated destruction triggered by immunogenic alginate impurities, unfavorable polymer composition and surface characteristics, and release of membrane-permeable antigens, as well as damage associated molecular patterns (DAMPs) by the encapsulated islets themselves. The lack of standardization of significant parameters of bioencapsulation device design and manufacture (i.e., purification protocols, surface-modification grafting techniques, alginate composition modifications) between labs is yet another obstacle that must be overcome before a clinically effective and applicable protocol for encapsulating islets can be implemented. Nonetheless, substantial progress is being made, as is evident from prolonged graft survival times and improved protection from immune-mediated graft destruction reported by various research groups, but also with regard to discoveries of specific pathways involved in explaining observed outcomes. Progress in the latter is essential for a comprehensive understanding of the mechanisms responsible for the varying levels of immunogenicity of certain alginate devices. Successful translation of encapsulated islet transplantation from in vitro and animal model testing to human clinical trials hinges on application of this knowledge of the pathways and interactions which comprise immune-mediated rejection. Thus, this review not only focuses on the different factors contributing to provocation of the immune reaction by encapsulated islets, but also on the defining characteristics of the response itself.

Cost-Effectiveness of Implantable Pulmonary Artery Pressure Monitoring in Chronic Heart Failure.

PubMed

Sandhu, Alexander T; Goldhaber-Fiebert, Jeremy D; Owens, Douglas K; Turakhia, Mintu P; Kaiser, Daniel W; Heidenreich, Paul A

2016-05-01

This study aimed to evaluate the cost-effectiveness of the CardioMEMS (CardioMEMS Heart Failure System, St Jude Medical Inc, Atlanta, Georgia) device in patients with chronic heart failure. The CardioMEMS device, an implantable pulmonary artery pressure monitor, was shown to reduce hospitalizations for heart failure and improve quality of life in the CHAMPION (CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in NYHA Class III Heart Failure Patients) trial. We developed a Markov model to determine the hospitalization, survival, quality of life, cost, and incremental cost-effectiveness ratio of CardioMEMS implantation compared with usual care among a CHAMPION trial cohort of patients with heart failure. We obtained event rates and utilities from published trial data; we used costs from literature estimates and Medicare reimbursement data. We performed subgroup analyses of preserved and reduced ejection fraction and an exploratory analysis in a lower-risk cohort on the basis of the CHARM (Candesartan in Heart failure: Reduction in Mortality and Morbidity) trials. CardioMEMS reduced lifetime hospitalizations (2.18 vs. 3.12), increased quality-adjusted life-years (QALYs) (2.74 vs. 2.46), and increased costs ($176,648 vs. $156,569), thus yielding a cost of $71,462 per QALY gained and $48,054 per life-year gained. The cost per QALY gained was $82,301 in patients with reduced ejection fraction and $47,768 in those with preserved ejection fraction. In the lower-risk CHARM cohort, the device would need to reduce hospitalizations for heart failure by 41% to cost <$100,000 per QALY gained. The cost-effectiveness was most sensitive to the device's durability. In populations similar to that of the CHAMPION trial, the CardioMEMS device is cost-effective if the trial effectiveness is sustained over long periods. Post-marketing surveillance data on durability will further clarify its value. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Low-level laser/light therapy for androgenetic alopecia.

PubMed

Gupta, Aditya K; Lyons, Danika C A; Abramovits, William

2014-01-01

Androgenetic alopecia (AGA) is a persistent and pervasive condition that affects men worldwide. Some common treatment options for AGA include hair prosthetics, oral and topical medications, and surgical hair restoration (SHR). Pharmaceutical and SHR treatments are associated with limitations including adverse side effects and significant financial burden. Low-level laser or light (LLL) devices offer alternative treatment options that are not typically associated with adverse side effects or significant costs. There are clinic- and home-based LLL devices. One home-based laser comb device has set a standard for others; however, this device requires time devoted to carefully moving the comb through the hair to allow laser penetration to the scalp. A novel helmet-like LLL device for hair growth has proven effective in preliminary trials and allows for hands-free use. Regardless, there are few clinical trials that have been conducted regarding LLL devices for AGA and results are mixed. Further research is required to establish the true efficacy of these devices for hair growth in comparison to existing alternative therapies.

ICONE: An International Consortium of Neuro Endovascular Centres.

PubMed

Raymond, J; White, P; Kallmes, D F; Spears, J; Marotta, T; Roy, D; Guilbert, F; Weill, A; Nguyen, T; Molyneux, A J; Cloft, H; Cekirge, S; Saatci, I; Bracard, S; Meder, J F; Moret, J; Cognard, C; Qureshi, A I; Turk, A S; Berenstein, A

2008-06-30

The proliferation of new endovascular devices and therapeutic strategies calls for a prudentand rational evaluation of their clinical benefit. This evaluation must be done in an effective manner and in collaboration with industry. Such research initiative requires organisation a land methodological support to survive and thrive in a competitive environment. We propose the formation of an international consortium, an academic alliance committed to the pursuit of effective neurovascular therapies. Such a consortium would be dedicated to the designand execution of basic science, device developmentand clinical trials. The Consortium is owned and operated by its members. Members are international leaders in neurointerventional research and clinical practice. The Consortium brings competency, knowledge, and expertise to industry as well as to its membership across aspectrum of research initiatives such as: expedited review of clinical trials, protocol development, surveys and systematic reviews; laboratory expertise and support for research design and grant applications to public agencies. Once objectives and protocols are approved, the Consortium provides a stable network of centers capable of timely realization of clinical trials or pre clinical investigations in an optimal environment. The Consortium is a non-profit organization. The potential revenue generated from clientsponsored financial agreements will be redirected to the academic and research objectives of the organization. The Consortium wishes to work inconcert with industry, to support emerging trends in neurovascular therapeutic development. The Consortium is a realistic endeavour optimally structured to promote excellence through scientific appraisal of our treatments, and to accelerate technical progress while maximizing patients' safety and welfare.

Direct comparison of the short-term clinical performance of Z Guidant and Taxus stents.

PubMed

Guildford, Anna; Colombo, Paola; Bruschi, Giuseppe; Bonacina, Edgardo; Klugmann, Silvio; Santin, Matteo

2010-12-03

The recent introduction of drug-eluting stents in angioplasty of atherosclerotic blood vessels has significantly reduced the risks of in-stent restenosis (ISR) [1]. Indeed, it is known that in conventional stents ISR takes place in over 20% of the cases and up to 60% when implanted in diabetic patients. Conversely, clinical trials have shown that drug-eluting stents have significantly reduced ISR. Among the drug-eluting stents available on the market, Taxus stents (Tax, Boston Scientific, USA) are among the most used devices [2]. Tax are stainless-steel stents coated with Translute, a poly(styrene-b-isobutylene-b-styrene) polymer (PSIBS) eluting Placlitaxel, an anti-mitotic drug. Clinical trials on this type of drug-eluting stents have shown an incidence of restenosis of approximately 4%. The majority of these trials were randomized studies where conventional stents and drug-eluting devices have been implanted in separate patients' cohorts. Such a randomized design, although fundamental to collect statistically-relevant data, does not allow a direct histological comparison of different stent types when implanted in the same patient and do not show the individual susceptibility to the host response especially at short-term implantation times. Here, an interesting case study is presented where two chrome-cobalt stents (Z Guidant, ZG, Guidant Corp.) and a Tax have been simultaneously implanted in the same patient in three separate coronary arteries, retrieved after only 8 weeks and histologically analysed. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.

Pulsed Electromagnetic Fields in the treatment of fresh scaphoid fractures. A multicenter, prospective, double blind, placebo controlled, randomized trial

PubMed Central

2011-01-01

Background The scaphoid bone is the most commonly fractured of the carpal bones. In the Netherlands 90% of all carpal fractures is a fracture of the scaphoid bone. The scaphoid has an essential role in functionality of the wrist, acting as a pivot. Complications in healing can result in poor functional outcome. The scaphoid fracture is a troublesome fracture and failure of treatment can result in avascular necrosis (up to 40%), non-union (5-21%) and early osteo-arthritis (up to 32%) which may seriously impair wrist function. Impaired consolidation of scaphoid fractures results in longer immobilization and more days lost at work with significant psychosocial and financial consequences. Initially Pulsed Electromagnetic Fields was used in the treatment of tibial pseudoarthrosis and non-union. More recently there is evidence that physical forces can also be used in the treatment of fresh fractures, showing accelerated healing by 30% and 71% reduction in nonunion within 12 weeks after initiation of therapy. Until now no double blind randomized, placebo controlled trial has been conducted to investigate the effect of this treatment on the healing of fresh fractures of the scaphoid. Methods/Design This is a multi center, prospective, double blind, placebo controlled, randomized trial. Study population consists of all patients with unilateral acute scaphoid fracture. Pregnant women, patients having a life supporting implanted electronic device, patients with additional fractures of wrist, carpal or metacarpal bones and pre-existing impairment in wrist function are excluded. The scaphoid fracture is diagnosed by a combination of physical and radiographic examination (CT-scanning). Proven scaphoid fractures are treated with cast immobilization and a small Pulsed Electromagnetic Fields bone growth stimulating device placed on the cast. Half of the devices will be disabled at random in the factory. Study parameters are clinical consolidation, radiological consolidation evaluated by CT-scanning, functional status of the wrist, including assessment by means of the patient rated wrist evaluation (PRWE) questionnaire and quality of life using SF-36 health survey questionnaire. Primary endpoint is number of scaphoid unions at six weeks, secondary endpoints are time interval to clinical and radiological consolidation, number of non-unions, functional status at 52 weeks and non-adherence to the treatment protocol. Trial registration Netherlands Trial Register (NTR): NTR2064 PMID:21548951

Characterization and Compensation of Network-Level Anomalies in Mixed-Signal Neuromorphic Modeling Platforms

PubMed Central

Petrovici, Mihai A.; Vogginger, Bernhard; Müller, Paul; Breitwieser, Oliver; Lundqvist, Mikael; Muller, Lyle; Ehrlich, Matthias; Destexhe, Alain; Lansner, Anders; Schüffny, René; Schemmel, Johannes; Meier, Karlheinz

2014-01-01

Advancing the size and complexity of neural network models leads to an ever increasing demand for computational resources for their simulation. Neuromorphic devices offer a number of advantages over conventional computing architectures, such as high emulation speed or low power consumption, but this usually comes at the price of reduced configurability and precision. In this article, we investigate the consequences of several such factors that are common to neuromorphic devices, more specifically limited hardware resources, limited parameter configurability and parameter variations due to fixed-pattern noise and trial-to-trial variability. Our final aim is to provide an array of methods for coping with such inevitable distortion mechanisms. As a platform for testing our proposed strategies, we use an executable system specification (ESS) of the BrainScaleS neuromorphic system, which has been designed as a universal emulation back-end for neuroscientific modeling. We address the most essential limitations of this device in detail and study their effects on three prototypical benchmark network models within a well-defined, systematic workflow. For each network model, we start by defining quantifiable functionality measures by which we then assess the effects of typical hardware-specific distortion mechanisms, both in idealized software simulations and on the ESS. For those effects that cause unacceptable deviations from the original network dynamics, we suggest generic compensation mechanisms and demonstrate their effectiveness. Both the suggested workflow and the investigated compensation mechanisms are largely back-end independent and do not require additional hardware configurability beyond the one required to emulate the benchmark networks in the first place. We hereby provide a generic methodological environment for configurable neuromorphic devices that are targeted at emulating large-scale, functional neural networks. PMID:25303102

Characterization and compensation of network-level anomalies in mixed-signal neuromorphic modeling platforms.

PubMed

Petrovici, Mihai A; Vogginger, Bernhard; Müller, Paul; Breitwieser, Oliver; Lundqvist, Mikael; Muller, Lyle; Ehrlich, Matthias; Destexhe, Alain; Lansner, Anders; Schüffny, René; Schemmel, Johannes; Meier, Karlheinz

2014-01-01

Advancing the size and complexity of neural network models leads to an ever increasing demand for computational resources for their simulation. Neuromorphic devices offer a number of advantages over conventional computing architectures, such as high emulation speed or low power consumption, but this usually comes at the price of reduced configurability and precision. In this article, we investigate the consequences of several such factors that are common to neuromorphic devices, more specifically limited hardware resources, limited parameter configurability and parameter variations due to fixed-pattern noise and trial-to-trial variability. Our final aim is to provide an array of methods for coping with such inevitable distortion mechanisms. As a platform for testing our proposed strategies, we use an executable system specification (ESS) of the BrainScaleS neuromorphic system, which has been designed as a universal emulation back-end for neuroscientific modeling. We address the most essential limitations of this device in detail and study their effects on three prototypical benchmark network models within a well-defined, systematic workflow. For each network model, we start by defining quantifiable functionality measures by which we then assess the effects of typical hardware-specific distortion mechanisms, both in idealized software simulations and on the ESS. For those effects that cause unacceptable deviations from the original network dynamics, we suggest generic compensation mechanisms and demonstrate their effectiveness. Both the suggested workflow and the investigated compensation mechanisms are largely back-end independent and do not require additional hardware configurability beyond the one required to emulate the benchmark networks in the first place. We hereby provide a generic methodological environment for configurable neuromorphic devices that are targeted at emulating large-scale, functional neural networks.

Validating models of target acquisition performance in the dismounted soldier context

NASA Astrophysics Data System (ADS)

Glaholt, Mackenzie G.; Wong, Rachel K.; Hollands, Justin G.

2018-04-01

The problem of predicting real-world operator performance with digital imaging devices is of great interest within the military and commercial domains. There are several approaches to this problem, including: field trials with imaging devices, laboratory experiments using imagery captured from these devices, and models that predict human performance based on imaging device parameters. The modeling approach is desirable, as both field trials and laboratory experiments are costly and time-consuming. However, the data from these experiments is required for model validation. Here we considered this problem in the context of dismounted soldiering, for which detection and identification of human targets are essential tasks. Human performance data were obtained for two-alternative detection and identification decisions in a laboratory experiment in which photographs of human targets were presented on a computer monitor and the images were digitally magnified to simulate range-to-target. We then compared the predictions of different performance models within the NV-IPM software package: Targeting Task Performance (TTP) metric model and the Johnson model. We also introduced a modification to the TTP metric computation that incorporates an additional correction for target angular size. We examined model predictions using NV-IPM default values for a critical model constant, V50, and we also considered predictions when this value was optimized to fit the behavioral data. When using default values, certain model versions produced a reasonably close fit to the human performance data in the detection task, while for the identification task all models substantially overestimated performance. When using fitted V50 values the models produced improved predictions, though the slopes of the performance functions were still shallow compared to the behavioral data. These findings are discussed in relation to the models' designs and parameters, and the characteristics of the behavioral paradigm.

Home tele-rehabilitation for rheumatic patients: impact and satisfaction of care analysis.

PubMed

Pani, D; Piga, M; Barabino, G; Crabolu, M; Uras, S; Mathieu, A; Raffo, L

2017-02-01

Introduction In this paper, we evaluated patients' perspectives on the use of a system for home tele-rehabilitation, designed for subjects with low computer literacy suffering hand impairment due to rheumatic diseases. Methods After a clinical trial assessing device effectiveness, the Psychosocial Impact of Assistive Devices Scale (PIADS), Quebec User Evaluation of Satisfaction with Assistive Technology (QUEST) and Individually Prioritised Problem Assessment (IPPA) questionnaires were administered to evaluate the system's impact on each patient's life, and the results were correlated with clinical indices. Patients were asked to continue self-administered rehabilitation with common objects. One year later, a semi-structured telephone interview gathered data on their experience. Results The system received a positive QUEST score (4.5 ± 0.3) and a modest PIADS score (0.84 ± 0.8) due to the small impact on adaptability and self-esteem. The IPPA (3.7 ± 3.4) revealed improvement in the ability to perform tasks considered important, which was significantly correlated ( r = 0.60; p < 0.02) with the clinical Health Assessment Questionnaire (HAQ) index improvement. The interviews revealed a positive engagement effect, enhanced by the need to develop skills to be able to use the device (technological challenge) and by the perception of more attention by the medical staff. This may explain the significant dropout rate (80%) from the post-trial rehabilitation of the patients who used the device. Discussion The system was largely accepted by the patients. The results suggest that the need for information on their rehabilitation progress and the technological challenge deserves further study to make patients more autonomous in cases of continuous rehabilitation.

C-MAC compared with direct laryngoscopy for intubation in patients with cervical spine immobilization: A manikin trial.

PubMed

Smereka, Jacek; Ladny, Jerzy R; Naylor, Amanda; Ruetzler, Kurt; Szarpak, Lukasz

2017-08-01

The aim of this study was to compare C-MAC videolaryngoscopy with direct laryngoscopy for intubation in simulated cervical spine immobilization conditions. The study was designed as a prospective randomized crossover manikin trial. 70 paramedics with <5years of medical experience participated in the study. The paramedics attempted to intubate manikins in 3 airway scenarios: normal airway without cervical immobilization (Scenario A); manual inline cervical immobilization (Scenario B); cervical immobilization using cervical extraction collar (Scenario C). Scenario A: Nearly all participants performed successful intubations with both MAC and C-MAC on the first attempt (95.7% MAC vs. 100% C-MAC), with similar intubation times (16.5s MAC vs. 18s C-MAC). Scenario B: The results with C-MAC were significantly better than those with MAC (p<0.05) for the time of intubation (23 s MAC vs. 19 s C-MAC), success of the first intubation attempt (88.6% MAC vs. 100% C-MAC), Cormack-Lehane grade, POGO score, severity of dental compression, device difficulty score, and preferred airway device. Scenario C: The results with C-MAC were significantly better than those with MAC (p<0.05) for all the analysed variables: success of the first attempt (51.4% MAC vs. 100% C-MAC), overall success rate, intubation time (27 s MAC vs. 20.5 s C-MAC), Cormack-Lehane grade, POGO score, dental compression, device difficulty score and the preferred airway device. The C-MAC videolaryngoscope is an excellent alternative to the MAC laryngoscope for intubating manikins with cervical spine immobilization. Copyright © 2017 Elsevier Inc. All rights reserved.

Alternative approaches to ventilator-associated pneumonia prevention.

PubMed

Berra, L; Sampson, J; Fumagalli, J; Panigada, M; Kolobow, T

2011-03-01

Ventilator-associated pneumonia (VAP), which develops in patients receiving mechanical ventilation, is the most common nosocomial infection in patients with acute respiratory failure. The major mechanism of lower respiratory tract colonization is aspiration of bacteria-colonized secretions from the oropharynx into the lower airways. The hydrostatic pressure of the secretions that collect in the subglottic space, which is the area above the endotracheal tube (ETT) cuff, or aerosolization of bacteria from the secretions collected within the respiratory tubing may facilitate the leakage into the lower airways. Ideally, the elimination of the mechanisms responsible for aspiration would decrease the incidence of VAP. Several preventive measures have been tested in clinical trials with little success.Here we present the results of our efforts to develop novel approaches for the prevention of VAP. Specifically, we found that keeping ventilated patients in a lateral position, which eliminates gravitational forces, is feasible and possibly advantageous. Additionally, several novel medical devices have been recently developed to prevent bacterial biofilm formation from the ETT and breathing tubing. These devices include coated ETTs, mucus shavers and mucus slurpers. Prevention of ETT bacterial colonization showed decreased bacterial colonization of the respiratory circuit and of the lower respiratory tract in laboratory studies and clinical trials. Future large studies should be designed to test the hypothesis that VAP can be prevented with these novel strategies. While there is a current focus on the use of respiratory devices to prevent biofilm formation and microaspiration, it is important to remember that lower respiratory tract colonization is multifactorial. Prevention of VAP cannot be achieved solely by eliminating bacterial biofilm on respiratory devices, and more comprehensive care of the intubated patient needs to be implemented.

Retinal Implants for Blind Patients

NASA Astrophysics Data System (ADS)

Rothermel, Albrecht

Recently, very promising results have been obtained in clinical trials with eye-prostheses for the blind. There is a chance that advances in surgical techniques, microelectronics design, and material science may lead to the first really useful applications of retinal implants in the near future. This chapter will focus on the actual status of subretinal surgery and implant technologies. Opportunities and limitations of the different technologies will be discussed in terms of patients benefit and technological challenges. Finally, a vision on how the devices may work and look like in the future will be given.

A Randomized, Crossover Clinical Trial of Exoskeletal-Assisted Walking to Improve Mobility, Bowel Function, and Cardiometabolic Profiles in Persons with SCI

DTIC Science & Technology

2015-10-01

comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS...participants and at three study sites. It is also designed to determine if the body composition and bowel function benefits that were observed with as few...demonstrated that ten participants were able to use the device to successfully walk for four to six hours per week for three months. It is unknown if a

Existing reporting guidelines for clinical trials are not completely relevant for implantable medical devices: a systematic review.

PubMed

Motte, Anne-France; Diallo, Stéphanie; van den Brink, Hélène; Châteauvieux, Constance; Serrano, Carole; Naud, Carole; Steelandt, Julie; Alsac, Jean-Marc; Aubry, Pierre; Cour, Florence; Pellerin, Olivier; Pineau, Judith; Prognon, Patrice; Borget, Isabelle; Bonan, Brigitte; Martelli, Nicolas

2017-11-01

The aim of this study was to determine relevant items for reporting clinical trials on implantable medical devices (IMDs) and to identify reporting guidelines which include these items. A panel of experts identified the most relevant items for evaluating IMDs from an initial list based on reference papers. We then conducted a systematic review of articles indexed in MEDLINE. We retrieved reporting guidelines from the EQUATOR network's library for health research reporting. Finally, we screened these reporting guidelines to find those using our set of reporting items. Seven relevant reporting items were selected that related to four topics: randomization, learning curve, surgical setting, and device information. A total of 348 reporting guidelines were identified, among which 26 met our inclusion criteria. However, none of the 26 reporting guidelines presented all seven items together. The most frequently reported item was timing of randomization (65%). On the contrary, device information and learning curve effects were poorly specified. To our knowledge, this study is the first to identify specific items related to IMDs in reporting guidelines for clinical trials. We have shown that no existing reporting guideline is totally suitable for these devices. Copyright © 2017 Elsevier Inc. All rights reserved.

Lessons Learned From The Investigational Device Exemption (IDE) Review of Children's Oncology Group Trial AAML1031

PubMed Central

Meshinchi, Soheil; Hunger, Stephen P.; Aplenc, Richard; Adamson, Peter C.; Jessup, J. Milburn

2012-01-01

The FDA is now exerting its regulatory authority over molecular diagnostics and their assays used for medical-decision making in clinical trials by performing pre-Investigational Device Exemption (IDE) reviews in all phases of clinical trials. This review assesses the analytical performance of the assay for the diagnostic and considers how that performance affects the diagnostic and the patient and their risks and benefits from treatment. This manuscript reviews the process of the first review that was performed on a new Children's Oncology Group (COG) Phase III trial in Acute Myelogenous Leukemia. The lessons learned and recommendations for how to prepare for and incorporate this new level of regulatory review into the protocol development process are presented. PMID:22422407

Assessment of hydraulic performance and biocompatibility of a MagLev centrifugal pump system designed for pediatric cardiac or cardiopulmonary support.

PubMed

Dasse, Kurt A; Gellman, Barry; Kameneva, Marina V; Woolley, Joshua R; Johnson, Carl A; Gempp, Thomas; Marks, John D; Kent, Stella; Koert, Andrew; Richardson, J Scott; Franklin, Steve; Snyder, Trevor A; Wearden, Peter; Wagner, William R; Gilbert, Richard J; Borovetz, Harvey S

2007-01-01

The treatment of children with life-threatening cardiac and cardiopulmonary failure is a large and underappreciated public health concern. We have previously shown that the CentriMag is a magnetically levitated centrifugal pump system, having the utility for treating adults and large children (1,500 utilized worldwide). We present here the PediVAS, a pump system whose design was modified from the CentriMag to meet the physiological requirements of young pediatric and neonatal patients. The PediVAS is comprised of a single-use centrifugal blood pump, reusable motor, and console, and is suitable for right ventricular assist device (RVAD), left ventricular assist device (LVAD), biventricular assist device (BVAD), or extracorporeal membrane oxygenator (ECMO) applications. It is designed to operate without bearings, seals and valves, and without regions of blood stasis, friction, or wear. The PediVAS pump is compatible with the CentriMag hardware, although the priming volume was reduced from 31 to 14 ml, and the port size reduced from 3/8 to (1/4) in. For the expected range of pediatric flow (0.3-3.0 L/min), the PediVAS exhibited superior hydraulic efficiency compared with the CentriMag. The PediVAS was evaluated in 14 pediatric animals for up to 30 days, demonstrating acceptable hydraulic function and hemocompatibility. The current results substantiate the performance and biocompatibility of the PediVAS cardiac assist system and are likely to support initiation of a US clinical trial in the future.

A prospective randomized trial examining health care utilization in individuals using multiple smartphone-enabled biosensors.

PubMed

Bloss, Cinnamon S; Wineinger, Nathan E; Peters, Melissa; Boeldt, Debra L; Ariniello, Lauren; Kim, Ju Young; Sheard, Judith; Komatireddy, Ravi; Barrett, Paddy; Topol, Eric J

2016-01-01

Background. Mobile health and digital medicine technologies are becoming increasingly used by individuals with common, chronic diseases to monitor their health. Numerous devices, sensors, and apps are available to patients and consumers-some of which have been shown to lead to improved health management and health outcomes. However, no randomized controlled trials have been conducted which examine health care costs, and most have failed to provide study participants with a truly comprehensive monitoring system. Methods. We conducted a prospective randomized controlled trial of adults who had submitted a 2012 health insurance claim associated with hypertension, diabetes, and/or cardiac arrhythmia. The intervention involved receipt of one or more mobile devices that corresponded to their condition(s) (hypertension: Withings Blood Pressure Monitor; diabetes: Sanofi iBGStar Blood Glucose Meter; arrhythmia: AliveCor Mobile ECG) and an iPhone with linked tracking applications for a period of 6 months; the control group received a standard disease management program. Moreover, intervention study participants received access to an online health management system which provided participants detailed device tracking information over the course of the study. This was a monitoring system designed by leveraging collaborations with device manufacturers, a connected health leader, health care provider, and employee wellness program-making it both unique and inclusive. We hypothesized that health resource utilization with respect to health insurance claims may be influenced by the monitoring intervention. We also examined health-self management. Results & Conclusions. There was little evidence of differences in health care costs or utilization as a result of the intervention. Furthermore, we found evidence that the control and intervention groups were equivalent with respect to most health care utilization outcomes. This result suggests there are not large short-term increases or decreases in health care costs or utilization associated with monitoring chronic health conditions using mobile health or digital medicine technologies. Among secondary outcomes there was some evidence of improvement in health self-management which was characterized by a decrease in the propensity to view health status as due to chance factors in the intervention group.

A prospective randomized trial examining health care utilization in individuals using multiple smartphone-enabled biosensors

PubMed Central

Peters, Melissa; Boeldt, Debra L.; Ariniello, Lauren; Kim, Ju Young; Sheard, Judith; Komatireddy, Ravi; Barrett, Paddy

2016-01-01

Background. Mobile health and digital medicine technologies are becoming increasingly used by individuals with common, chronic diseases to monitor their health. Numerous devices, sensors, and apps are available to patients and consumers–some of which have been shown to lead to improved health management and health outcomes. However, no randomized controlled trials have been conducted which examine health care costs, and most have failed to provide study participants with a truly comprehensive monitoring system. Methods. We conducted a prospective randomized controlled trial of adults who had submitted a 2012 health insurance claim associated with hypertension, diabetes, and/or cardiac arrhythmia. The intervention involved receipt of one or more mobile devices that corresponded to their condition(s) (hypertension: Withings Blood Pressure Monitor; diabetes: Sanofi iBGStar Blood Glucose Meter; arrhythmia: AliveCor Mobile ECG) and an iPhone with linked tracking applications for a period of 6 months; the control group received a standard disease management program. Moreover, intervention study participants received access to an online health management system which provided participants detailed device tracking information over the course of the study. This was a monitoring system designed by leveraging collaborations with device manufacturers, a connected health leader, health care provider, and employee wellness program–making it both unique and inclusive. We hypothesized that health resource utilization with respect to health insurance claims may be influenced by the monitoring intervention. We also examined health-self management. Results & Conclusions. There was little evidence of differences in health care costs or utilization as a result of the intervention. Furthermore, we found evidence that the control and intervention groups were equivalent with respect to most health care utilization outcomes. This result suggests there are not large short-term increases or decreases in health care costs or utilization associated with monitoring chronic health conditions using mobile health or digital medicine technologies. Among secondary outcomes there was some evidence of improvement in health self-management which was characterized by a decrease in the propensity to view health status as due to chance factors in the intervention group. PMID:26788432

The British antibiotic and silver-impregnated catheters for ventriculoperitoneal shunts multi-centre randomised controlled trial (the BASICS trial): study protocol

PubMed Central

2014-01-01

Background Insertion of a ventriculoperitoneal shunt (VPS) for the treatment of hydrocephalus is one of the most common neurosurgical procedures in the UK, but failures caused by infection occur in approximately 8% of primary cases. VPS infection is associated with considerable morbidity and mortality and its management results in substantial cost to the health service. Antibiotic-impregnated (rifampicin and clindamycin) and silver-impregnated VPS have been developed to reduce infection rates. Whilst there is some evidence showing that such devices may lead to a reduction in VPS infection, there are no randomised controlled trials (RCTs) to support their routine use. Methods/design Overall, 1,200 patients will be recruited from 17 regional neurosurgical units in the UK and Ireland. Patients of any age undergoing insertion of their first VPS are eligible. Patients with previous indwelling VPS, active and on-going cerebrospinal fluid (CSF) or peritoneal infection, multiloculated hydrocephalus requiring multiple VPS or neuroendoscopy, and ventriculoatrial or ventriculopleural shunt planned will be excluded. Patients will be randomised 1:1:1 to either standard silicone (comparator), antibiotic-impregnated, or silver-impregnated VPS. The primary outcome measure is time to VPS infection. Secondary outcome measures include time to VPS failure of any cause, reason for VPS failure (infection, mechanical failure, or patient failure), types of bacterial VPS infection (organism type and antibiotic resistance), and incremental cost per VPS failure averted. Discussion The British antibiotic and silver-impregnated catheters for ventriculoperitoneal shunts multi-centre randomised controlled trial (the BASICS trial) is the first multi-centre RCT designed to determine whether antibiotic or silver-impregnated VPS reduce early shunt infection compared to standard silicone VPS. The results of this study will be used to inform current neurosurgical practice and may potentially benefit patients undergoing shunt surgery in the future. Trial registration International Standard Randomised Controlled Trial Number: ISRCTN49474281. PMID:24383496

A randomised clinical trial of comprehensive cardiac rehabilitation versus usual care for patients treated for infective endocarditis—the CopenHeartIE trial protocol

PubMed Central

Rasmussen, Trine Bernholdt; Zwisler, Ann-Dorthe; Sibilitz, Kirstine Lærum; Risom, Signe Stelling; Bundgaard, Henning; Gluud, Christian; Moons, Philip; Winkel, Per; Thygesen, Lau Caspar; Hansen, Jane Lindschou; Norekvål, Tone Merete; Berg, Selina Kikkenborg

2012-01-01

Introduction Infective endocarditis (IE) is among the most serious infectious diseases in the western world. Treatment requires lengthy hospitalisation, high-dosage antibiotic therapy and possible valve replacement surgery. Despite advances in treatment, the 1-year mortality remains at 20–40%. Studies indicate that patients experience persisting physical symptoms, diminished quality of life and difficulties returning to work up to a year postdischarge. No studies investigating the effects of rehabilitation have been published. We present the rationale and design of the CopenHeartIE trial, which investigates the effect of comprehensive cardiac rehabilitation versus usual care for patients treated for IE. Methods and analysis We will conduct a randomised clinical trial to investigate the effects of comprehensive cardiac rehabilitation versus usual care on the physical and psychosocial functioning of patients treated for IE. The trial is a multicentre, parallel design trial with 1 : 1 individual randomisation to either the intervention or control group. The intervention consists of five psychoeducational consultations provided by specialised nurses and a 12-week exercise training programme. The primary outcome is mental health (MH) measured by the standardised Short Form 36 (SF-36). The secondary outcome is peak oxygen uptake measured by the bicycle ergospirometry test. Furthermore, a number of exploratory analyses will be performed. Based on sample size calculation, 150 patients treated for left-sided (native or prosthetic valve) or cardiac device endocarditis will be included in the trial. A qualitative and a survey-based complementary study will be undertaken, to investigate postdischarge experiences of the patients. A qualitative postintervention study will explore rehabilitation participation experiences. Ethics and dissemination The study complies with the Declaration of Helsinki and was approved by the regional research ethics committee (no H-1-2011-129) and the Danish Data Protection Agency (no 2007-58-0015). Study findings will be disseminated widely through peer-reviewed publications and conference presentations. Registration Clinicaltrials.gov identifier: NCT01512615. PMID:23175738

A randomised clinical trial of comprehensive cardiac rehabilitation versus usual care for patients treated for infective endocarditis--the CopenHeartIE trial protocol.

PubMed

Rasmussen, Trine Bernholdt; Zwisler, Ann-Dorthe; Sibilitz, Kirstine Lærum; Risom, Signe Stelling; Bundgaard, Henning; Gluud, Christian; Moons, Philip; Winkel, Per; Thygesen, Lau Caspar; Hansen, Jane Lindschou; Norekvål, Tone Merete; Berg, Selina Kikkenborg

2012-01-01

Infective endocarditis (IE) is among the most serious infectious diseases in the western world. Treatment requires lengthy hospitalisation, high-dosage antibiotic therapy and possible valve replacement surgery. Despite advances in treatment, the 1-year mortality remains at 20-40%. Studies indicate that patients experience persisting physical symptoms, diminished quality of life and difficulties returning to work up to a year postdischarge. No studies investigating the effects of rehabilitation have been published. We present the rationale and design of the CopenHeart(IE) trial, which investigates the effect of comprehensive cardiac rehabilitation versus usual care for patients treated for IE. We will conduct a randomised clinical trial to investigate the effects of comprehensive cardiac rehabilitation versus usual care on the physical and psychosocial functioning of patients treated for IE. The trial is a multicentre, parallel design trial with 1 : 1 individual randomisation to either the intervention or control group. The intervention consists of five psychoeducational consultations provided by specialised nurses and a 12-week exercise training programme. The primary outcome is mental health (MH) measured by the standardised Short Form 36 (SF-36). The secondary outcome is peak oxygen uptake measured by the bicycle ergospirometry test. Furthermore, a number of exploratory analyses will be performed. Based on sample size calculation, 150 patients treated for left-sided (native or prosthetic valve) or cardiac device endocarditis will be included in the trial. A qualitative and a survey-based complementary study will be undertaken, to investigate postdischarge experiences of the patients. A qualitative postintervention study will explore rehabilitation participation experiences. The study complies with the Declaration of Helsinki and was approved by the regional research ethics committee (no H-1-2011-129) and the Danish Data Protection Agency (no 2007-58-0015). Study findings will be disseminated widely through peer-reviewed publications and conference presentations. Clinicaltrials.gov identifier: NCT01512615.

An Everting Ureteral Access Sheath: Concepts and In Vitro Testing

NASA Astrophysics Data System (ADS)

Lee, Keith L.; Stoller, Marshall L.

2007-04-01

Ureteral access sheaths have been a recent innovation in facilitating ureteral stone surgery. Once properly placed, access sheaths allow the movement of ureteroscopes and other instruments through the ureter with minimal injury to the urothelium. However, there are shortcomings of the current device designs. Initial sheath placement requires significant force, and shear stress can injure the ureter. In addition, inadvertent advancement of the outer sheath without the inner introducer stylet can tear and avulse the ureter. A novel eversion design incorporating a lubricous film provides marked improvement over current access sheaths. In bench top and animal models, the eversion shealths require less force during advancement, cause less injury to the urothelial tissue, and have a lower potential of introducing extraneous materials (e.g., microbes) into a simulated urinary tract. While, the everting design provides important advantages over traditional non-everting designs, further preclinical and clinical trials are required.

Designing effective drug and device development programs for hospitalized heart failure: A proposal for pretrial registries

PubMed Central

Greene, Stephen J.; Shah, Ami N.; Butler, Javed; Ambrosy, Andrew P.; Anker, Stefan D.; Chioncel, Ovidiu; Collins, Sean P.; Dinh, Wilfried; Dunnmon, Preston M.; Fonarow, Gregg C.; Lam, Carolyn S. P.; Mentz, Robert J.; Pieske, Burkert; Roessig, Lothar; Rosano, Giuseppe M. C.; Sato, Naoki; Vaduganathan, Muthiah; Gheorghiade, Mihai

2014-01-01

Recent international phase III clinical trials of novel therapies for hospitalized heart failure (HHF) have failed to improve the unacceptably high postdischarge event rate. These large studies have demonstrated notable geographic and site-specific variation in patient profiles and enrollment. Possible contributors to the lack of success in HHF outcome trials include challenges in selecting clinical sites capable of (1) providing adequate numbers of appropriately selected patients and (2) properly executing the study protocol. We propose a “pretrial registry” as a novel tool for improving the efficiency and quality of international HHF trials by focusing on the selection and cultivation of high-quality sites. A pretrial registry may help assess a site’s ability to achieve adequate enrollment of the target patient population, integrate protocol requirements into clinical workflow, and accomplish appropriate follow-up. Although such a process would be associated with additional upfront resource investment, this appropriation may be modest in comparison with the downstream costs associated with maintenance of poorly performing sites, failed clinical trials, and the global health and economic burden of HHF. This review is based on discussions between scientists, clinical trialists, and regulatory representatives regarding methods for improving international HHF trials that took place at the United States Food and Drug Administration on January 12th, 2012. PMID:25066552

Testing an attachment method for solar-powered tracking devices on a long-distance migrating shorebird

USGS Publications Warehouse

Chan, Ying-Chi; Brugge, Martin; Tibbitts, T. Lee; Dekinga, Anne; Porter, Ron; Klaassen, Raymond H. G.; Piersma, Theunis

2016-01-01

Small solar-powered satellite transmitters and GPS data loggers enable continuous, multi-year, and global tracking of birds. What is lacking, however, are reliable methods to attach these tracking devices to small migratory birds so that (1) flight performance is not impacted and (2) tags are retained during periods of substantial mass change associated with long-distance migration. We developed a full-body harness to attach tags to Red Knots (Calidris canutus), a medium-sized shorebird (average mass 124 g) that undertakes long-distance migrations. First, we deployed dummy tags on captive birds and monitored them over a complete migratory fattening cycle (February–July 2013) during which time they gained and lost 31–110 g and underwent a pre-alternate moult of body feathers. Using each individual’s previous year fattening and moult data in captivity as controls, we compared individual mass and moult differences between years between the tagged and reference groups, and concluded that the attachment did not impact mass and moult cycles. However, some birds shed feathers under the tags and under the polyester harness line commonly used in avian harnesses. Feather shedding was alleviated by switching to smoothed-bottom tags and monofilament harness lines. To field-trial this design, we deployed 5-g satellite transmitters on ten Red Knots released on 3 October 2013 in the Dutch Wadden Sea. Bird movements and tag performance appeared normal. However, nine tags stopped transmitting 11–170 days post-release which was earlier than expected. We attribute this to bird mortality rather than failure of the attachments or transmitters and suggest that the extra weight and drag caused by the tag and its feather-blocking shield increased the chance of depredation by the locally common Peregrine Falcons (Falco peregrinus). Our results demonstrate that species- and place-specific contexts can strongly determine tagging success. While captive trials are an important first step in developing an attachment method, field trials are essential to fully assess attachment designs.

Protection or nonprotection in carotid stent angioplasty: the influence of interventional techniques on outcome data from the SPACE Trial.

PubMed

Jansen, Olav; Fiehler, Jens; Hartmann, Marius; Brückmann, Hartmut

2009-03-01

The use of protection devices (PDs) and stents with different cell designs in carotid artery stenting (CAS) is a subject of controversy, and no data on their benefit are available from independently controlled multi-center studies. We analyzed data from the prospective randomized SPACE trial, which included 563 patients randomized to CAS and treated per protocol. A total of 145 patients were treated with a PD and 418 without. Of the patients, 436 were treated with an open cell stent and 127 with a closed cell stent. Use of PDs and choice of device was chosen at the individual discretion of the interventionalist. The outcome event (OE) of the analysis (ipsilateral stroke or ipsilateral stroke death within 30 days) was reached in 26/418 patients (6.2%, 95% CI: 4.1 to 9.0%) in the nonprotection [corrected] group and in 12/145 (8.3%, 95% CI: 4.3 to 14.0%) patients in the protection [corrected] group (P=0.40). The OE rate was significantly lower in patients treated with a closed cell stent (5.6% [95% CI: 3.7 to 8.2%]) than in those treated with an open cell stent.(11.0%, 95% CI: 6.2 to 17.8%; P=0.029). Predilatation showed a tendency to but no significant reduction of OE rate. Overall, 49% of all OEs occurred directly periinterventionally, 10% during the navigation procedure and 41% postinterventionally, including 10% of hyperperfusion syndromes. Time point of the event was not influenced by the use of a PD. This secondary analysis of data from the SPACE trial does not support the need for a PD in CAS. Stent design seems to have an impact on the OE rate. Our analysis demonstrates that the choice of the interventional material may have an impact on the periprocedural complication rate in CAS and that the development of more specific stent systems for the treatment of carotid stenosis may reduce the complication rate significantly.

Validating the Accuracy of Reaction Time Assessment on Computer-Based Tablet Devices.

PubMed

Schatz, Philip; Ybarra, Vincent; Leitner, Donald

2015-08-01

Computer-based assessment has evolved to tablet-based devices. Despite the availability of tablets and "apps," there is limited research validating their use. We documented timing delays between stimulus presentation and (simulated) touch response on iOS devices (3rd- and 4th-generation Apple iPads) and Android devices (Kindle Fire, Google Nexus, Samsung Galaxy) at response intervals of 100, 250, 500, and 1,000 milliseconds (ms). Results showed significantly greater timing error on Google Nexus and Samsung tablets (81-97 ms), than Kindle Fire and Apple iPads (27-33 ms). Within Apple devices, iOS 7 obtained significantly lower timing error than iOS 6. Simple reaction time (RT) trials (250 ms) on tablet devices represent 12% to 40% error (30-100 ms), depending on the device, which decreases considerably for choice RT trials (3-5% error at 1,000 ms). Results raise implications for using the same device for serial clinical assessment of RT using tablets, as well as the need for calibration of software and hardware. © The Author(s) 2015.

A Prospective Evaluation of a Protocol for Magnetic Resonance Imaging of Patients With Implanted Cardiac Devices

PubMed Central

Nazarian, Saman; Hansford, Rozann; Roguin, Ariel; Goldsher, Dorith; Zviman, Menekhem M.; Lardo, Albert C.; Caffo, Brian S.; Frick, Kevin D.; Kraut, Michael A.; Kamel, Ihab R.; Calkins, Hugh; Berger, Ronald D.; Bluemke, David A.; Halperin, Henry R.

2015-01-01

Background Magnetic resonance imaging (MRI) is avoided in most patients with implanted cardiac devices because of safety concerns. Objective To define the safety of a protocol for MRI at the commonly used magnetic strength of 1.5 T in patients with implanted cardiac devices. Design Prospective nonrandomized trial. (ClinicalTrials.gov registration number: NCT01130896) Setting One center in the United States (94% of examinations) and one in Israel. Patients 438 patients with devices (54% with pacemakers and 46% with defibrillators) who underwent 555 MRI studies. Intervention Pacing mode was changed to asynchronous for pacemaker-dependent patients and to demand for others. Tachy-arrhythmia functions were disabled. Blood pressure, electrocardiography, oximetry, and symptoms were monitored by a nurse with experience in cardiac life support and device programming who had immediate backup from an electrophysiologist. Measurements Activation or inhibition of pacing, symptoms, and device variables. Results In 3 patients (0.7% [95% CI, 0% to 1.5%]), the device reverted to a transient back-up programming mode without long-term effects. Right ventricular (RV) sensing (median change, 0 mV [interquartile range {IQR}, −0.7 to 0 V]) and atrial and right and left ventricular lead impedances (median change, −2 Ω[IQR, −13 to 0 Ω], −4 Ω [IQR, −16 to 0 Ω], and −11 Ω [IQR, −40 to 0 Ω], respectively) were reduced immediately after MRI. At long-term follow-up (61% of patients), decreased RV sensing (median, 0 mV, [IQR, −1.1 to 0.3 mV]), decreased RV lead impedance (median, −3 Ω, [IQR, −29 to 15 Ω]), increased RV capture threshold (median, 0 V, IQR, [0 to 0.2 Ω]), and decreased battery voltage (median, −0.01 V, IQR, −0.04 to 0 V) were noted. The observed changes did not require device revision or reprogramming. Limitations Not all available cardiac devices have been tested. Long-term in-person or telephone follow-up was unavailable in 43 patients (10%), and some data were missing. Those with missing long-term capture threshold data had higher baseline right atrial and right ventricular capture thresholds and were more likely to have undergone thoracic imaging. Defibrillation threshold testing and random assignment to a control group were not performed. Conclusion With appropriate precautions, MRI can be done safely in patients with selected cardiac devices. Because changes in device variables and programming may occur, electrophysiologic monitoring during MRI is essential. Primary Funding Source National Institutes of Health. PMID:21969340

Challenges to clinical deployment of upper limb neuroprostheses.

PubMed

Triolo, R; Nathan, R; Handa, Y; Keith, M; Betz, R R; Carroll, S; Kantor, C

1996-04-01

The technology for functional neuromuscular stimulation (FNS) as a means of providing upper limb function to people with tetraplegia has been under development by three clinical research groups for almost two decades. This paper presents the current status of the clinical trials of three FNS systems: a noninvasive system built into a cosmetic forearm splint, a 30-channel percutaneous system, and an 8-channel implantable system. The complexity of FNS systems and the unique characteristics of the individuals to whom they are applied combine to create many clinical and technical challenges that must be addressed before the devices can be deployed. The emerging challenges to widespread clinical introduction of FNS systems for hand and arm function are identified and analyzed. In addition to the demands of designed and conducting the clinical trials to satisfy regulatory requirements, the lack of knowledge, skepticism, and the complacency on the part of potential FNS recipients, as well as of rehabilitation professionals, must be overcome through education and careful consideration of economic and societal factors in the design of clinical systems.

Results of the ANSWER Trial Using the PulseRider for the Treatment of Broad-Necked, Bifurcation Aneurysms.

PubMed

Spiotta, Alejandro M; Derdeyn, Colin P; Tateshima, Satoshi; Mocco, Jay; Crowley, R Webster; Liu, Kenneth C; Jensen, Lee; Ebersole, Koji; Reeves, Alan; Lopes, Demetrius K; Hanel, Ricardo A; Sauvageau, Eric; Duckwiler, Gary; Siddiqui, Adnan; Levy, Elad; Puri, Ajit; Pride, Lee; Novakovic, Roberta; Chaudry, M Imran; Turner, Raymond D; Turk, Aquilla S

2017-07-01

The safety and probable benefit of the PulseRider (Pulsar Vascular, Los Gatos, California) for the treatment of broad-necked, bifurcation aneurysms was studied in the context of the prospective, nonrandomized, single arm clinical trial-the Adjunctive Neurovascular Support of Wide-neck aneurysm Embolization and Reconstruction (ANSWER) Trial. To present the results of the United States cases employing the PulseRider device as part of the ANSWER clinical trial. Aneurysms treated with the PulseRider device among sites enrolling in the ANSWER trial were prospectively studied and the results are summarized. Aneurysms arising at either the carotid terminus or basilar apex that were relatively broad necked were considered candidates for inclusion into the ANSWER study. Thirty-four patients were enrolled (29 female and 5 male) with a mean age of 60.9 years (27 basilar apex and 7 carotid terminus). Mean aneurysm height ranged from 2.4 to 15.9 mm with a mean neck size of 5.2 mm (range 2.3-11.6 mm). In all patients, the device was delivered and deployed. Immediate Raymond I or II occlusion was achieved in 82.4% and progressed to 87.9% at 6-month follow-up. A modified Rankin Score of 2 or less was seen in 94% of patients at 6 months. The results from the ANSWER trial demonstrate that the PulseRider device is safe and offers probable benefit as for the treatment of bifurcation aneurysms arising at the basilar apex or carotid terminus. As such, it represents a useful addition to the armamentarium of the neuroendovascular specialist. Copyright © 2017 by the Congress of Neurological Surgeons

Selection of and Evidentiary Considerations for Wearable Devices and Their Measurements for Use in Regulatory Decision Making: Recommendations from the ePRO Consortium.

PubMed

Byrom, Bill; Watson, Chris; Doll, Helen; Coons, Stephen Joel; Eremenco, Sonya; Ballinger, Rachel; Mc Carthy, Marie; Crescioni, Mabel; O'Donohoe, Paul; Howry, Cindy

2018-06-01

Wearable devices offer huge potential to collect rich sources of data to provide insights into the effects of treatment interventions. Despite this, at the time of writing this report, limited regulatory guidance on the use of wearables in clinical trial programs has been published. To present recommendations from the Critical Path Institute's Electronic Patient-Reported Outcome Consortium regarding the selection and evaluation of wearable devices and their measurements for use in regulatory trials and to support labeling claims. The evaluation group was composed of Critical Path Institute's clinical outcome assessment (COA) scientists and COA specialists from pharmaceutical trial eCOA solution providers, including COA development and validation specialists. The resulting recommendations were drawn from a broad range of backgrounds, perspectives, and expertise that enriched the development of this report. Recommendations were developed through analysis of existing regulatory guidance relating to COA development and use in clinical trials, medical device certification/clearance regulations, literature-reported best practice, and practical experience of wearable technology application in clinical trials. We identify the essential properties of fit-for-purpose wearables and propose evidence needed to support their use. In addition, we overview the activities required to establish clinical endpoints derived from wearables data. Using this framework, we believe there is enough current understanding to promote the appropriate use of wearables in study protocols. We hope this will provide a basis for discussion among clinical trial stakeholders and catalyze the development of more robust regulatory guidance. Copyright © 2018 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Anatomic suitability of aortoiliac aneurysms for next generation branched systems.

PubMed

Pearce, Benjamin J; Varu, Vinit N; Glocker, Roan; Novak, Zdenek; Jordan, William D; Lee, Jason T

2015-01-01

Preservation of internal iliac flow is an important consideration to prevent ischemic complications during endovascular aneurysm repair. We sought to determine the suitability of aortoiliac aneurysms for off-the-shelf iliac branched systems currently in clinical trial. Patients undergoing abdominal aortic aneurysm repair from 2004 to 2013 at 2 institutions were reviewed. Centerline diameters and lengths of aortoiliac morphology were measured using three-dimensional workstations and compared with inclusion/exclusion criteria for both Cook and Gore iliac branch devices. Of the nearly 2,400 aneurysm repairs performed during the study period, 99 patients had common iliac aneurysms suitable for imaging review. Eighteen of the 99 (18.2%) patients and 25/99 (25.3%) patients fit the inclusion criteria and would have been able to be treated using the Cook and Gore iliac branch devices, respectively. The most common reason for exclusion from Cook was internal iliac diameter of <6 or >9 mm (68/99, 68.7%). The most common reason for exclusion from Gore was proximal common iliac diameter of <17 mm (39/99, 39.4%) and inadequate internal iliac artery diameter of <6.5 or >13.5 mm (37/99, 37.3%). Comparing the included patients across both devices, a total of 35/99 (35.4%) of patients would be eligible for the treatment of aortoiliac aneurysms based on anatomic criteria. Only 35% of the aneurysm repairs involving common iliac arteries would have been candidates for the 2 iliac branch devices currently in trial based on anatomic criteria. The major common reason for exclusion is the internal iliac landing zone for both devices. Design modifications for future generation iliac branch technology should focus on diameter accommodations for the hypogastric branch stent and proximal and distal sizes of the iliac branch components. Familiarity with alternate branch preserving techniques is still needed in the majority of cases. Copyright © 2015 Elsevier Inc. All rights reserved.

Participants’ Perceptions on the Use of Wearable Devices to Reduce Sitting Time: Qualitative Analysis

PubMed Central

Lewars, Brittany; Hurst, Samantha; Crist, Katie; Nebeker, Camille; Madanat, Hala; Nichols, Jeanne; Rosenberg, Dori E; Kerr, Jacqueline

2018-01-01

Background Recent epidemiological evidence indicates that, on average, people are sedentary for approximately 7.7 hours per day. There are deleterious effects of prolonged sedentary behavior that are separate from participation in physical activity and include increased risk of weight gain, cancer, metabolic syndrome, diabetes, and heart disease. Previous trials have used wearable devices to increase physical activity in studies; however, additional research is needed to fully understand how this technology can be used to reduce sitting time. Objective The purpose of this study was to explore the potential of wearable devices as an intervention tool in a larger sedentary behavior study through a general inductive and deductive analysis of focus group discussions. Methods We conducted four focus groups with 15 participants to discuss 7 different wearable devices with sedentary behavior capabilities. Participants recruited for the focus groups had previously participated in a pilot intervention targeting sedentary behavior over a 3-week period and were knowledgeable about the challenges of reducing sitting time. During the focus groups, participants commented on the wearability, functionality, and feedback mechanism of each device and then identified their two favorite and two least favorite devices. Finally, participants designed and described their ideal or dream wearable device. Two researchers, who have expertise analyzing qualitative data, coded and analyzed the data from the focus groups. A thematic analysis approach using Dedoose software (SocioCultural Research Consultants, LLC version 7.5.9) guided the organization of themes that reflected participants’ perspectives. Results Analysis resulted in 14 codes that we grouped into themes. Three themes emerged from our data: (1) features of the device, (2) data the device collected, and (3) how data are displayed. Conclusions Current wearable devices for increasing physical activity are insufficient to intervene on sitting time. This was especially evident when participants voted, as several participants reported using a “process of elimination” as opposed to choosing favorites because none of the devices were ideal for reducing sitting time. To overcome the limitations in current devices, future wearable devices designed to reduce sitting time should include the following features: waterproof, long battery life, accuracy in measuring sitting time, real time feedback on progress toward sitting reduction goals, and flexible options for prompts to take breaks from sitting. PMID:29599105

Evaluation of the acoustic coordinated reset (CR®) neuromodulation therapy for tinnitus: study protocol for a double-blind randomized placebo-controlled trial.

PubMed

Hoare, Derek J; Pierzycki, Robert H; Thomas, Holly; McAlpine, David; Hall, Deborah A

2013-07-10

Current theories of tinnitus assume that the phantom sound is generated either through increased spontaneous activity of neurons in the auditory brain, or through pathological temporal firing patterns of the spontaneous neuronal discharge, or a combination of both factors. With this in mind, Tass and colleagues recently tested a number of temporally patterned acoustic stimulation strategies in a proof of concept study. Potential therapeutic sound regimes were derived according to a paradigm assumed to disrupt hypersynchronous neuronal activity, and promote plasticity mechanisms that stabilize a state of asynchronous spontaneous activity. This would correspond to a permanent reduction of tinnitus. The proof of concept study, conducted in Germany, confirmed the safety of the acoustic stimuli for use in tinnitus, and exploratory results indicated modulation of tinnitus-related pathological synchronous activity with potential therapeutic benefit. The most effective stimulation paradigm is now in clinical use as a sound therapy device, the acoustic coordinated reset (CR®) neuromodulation (Adaptive Neuromodulation GmbH (ANM), Köln, Germany). To measure the efficacy of CR® neuromodulation, we devised a powered, two-center, randomized controlled trial (RCT) compliant with the reporting standards defined in the Consolidated Standards of Reporting Trials (CONSORT) Statement. The RCT design also addresses the recent call for international standards within the tinnitus community for high-quality clinical trials. The design uses a between-subjects comparison with minimized allocation of participants to treatment and placebo groups. A minimization approach was selected to ensure that the two groups are balanced with respect to age, gender, hearing, and baseline tinnitus severity. The protocol ensures double blinding, with crossover of the placebo group to receive the proprietary intervention after 12 weeks. The primary endpoints are the pre- and post-treatment measures that provide the primary measures of efficacy, namely a validated and sensitive questionnaire measure of the functional impact of tinnitus. The trial is also designed to capture secondary changes in tinnitus handicap, quality (pitch, loudness, bandwidth), and changes in tinnitus-related pathological synchronous brain activity using electroencephalography (EEG). This RCT was designed to provide a confident high-level estimate of the efficacy of sound therapy using CR® neuromodulation compared to a well-matched placebo intervention, and uniquely in terms of sound therapy, examine the physiological effects of the intervention against its putative mechanism of action. ClinicalTrials.gov, NCT01541969.

Registry Assessment of Peripheral Interventional Devices (RAPID)　- Registry Assessment of Peripheral Interventional Devices Core Data Elements.

PubMed

Jones, W Schuyler; Krucoff, Mitchell W; Morales, Pablo; Wilgus, Rebecca W; Heath, Anne H; Williams, Mary F; Tcheng, James E; Marinac-Dabic, J Danica; Malone, Misti L; Reed, Terrie L; Fukaya, Rie; Lookstein, Robert; Handa, Nobuhiro; Aronow, Herbert D; Bertges, Daniel J; Jaff, Michael R; Tsai, Thomas T; Smale, Joshua A; Zaugg, Margo J; Thatcher, Robert J; Cronenwett, Jack L; Nc, Durham; Md, Silver Spring; Japan, Tokyo; Ny, New York; Ri, Providence; Vt, Burlington; Mass, Newton; Colo, Denver; Ariz, Tempe; Calif, Santa Clara; Minn, Minneapolis; Nh, Lebanon

2018-01-25

The current state of evaluating patients with peripheral artery disease and more specifically of evaluating medical devices used for peripheral vascular intervention (PVI) remains challenging because of the heterogeneity of the disease process, the multiple physician specialties that perform PVI, the multitude of devices available to treat peripheral artery disease, and the lack of consensus about the best treatment approaches. Because PVI core data elements are not standardized across clinical care, clinical trials, and registries, aggregation of data across different data sources and physician specialties is currently not feasible.Methods and Results:Under the auspices of the U.S. Food and Drug Administration's Medical Device Epidemiology Network initiative-and its PASSION (Predictable and Sustainable Implementation of the National Registries) program, in conjunction with other efforts to align clinical data standards-the Registry Assessment of Peripheral Interventional Devices (RAPID) workgroup was convened. RAPID is a collaborative, multidisciplinary effort to develop a consensus lexicon and to promote interoperability across clinical care, clinical trials, and national and international registries of PVI. The current manuscript presents the initial work from RAPID to standardize clinical data elements and definitions, to establish a framework within electronic health records and health information technology procedural reporting systems, and to implement an informatics-based approach to promote the conduct of pragmatic clinical trials and registry efforts in PVI. Ultimately, we hope this work will facilitate and improve device evaluation and surveillance for patients, clinicians, health outcomes researchers, industry, policymakers, and regulators.

Progressive Staging of Pilot Studies to Improve Phase III Trials for Motor Interventions

PubMed Central

Dobkin, Bruce H.

2014-01-01

Based on the suboptimal research pathways that finally led to multicenter randomized clinical trials (MRCTs) of treadmill training with partial body weight support and of robotic assistive devices, strategically planned successive stages are proposed for pilot studies of novel rehabilitation interventions Stage 1, consideration-of-concept studies, drawn from animal experiments, theories, and observations, delineate the experimental intervention in a small convenience sample of participants, so the results must be interpreted with caution. Stage 2, development-of-concept pilots, should optimize the components of the intervention, settle on most appropriate outcome measures, and examine dose-response effects. A well-designed study that reveals no efficacy should be published to counterweight the confirmation bias of positive trials. Stage 3, demonstration-of-concept pilots, can build out from what has been learned to test at least 15 participants in each arm, using random assignment and blinded outcome measures. A control group should receive an active practice intervention aimed at the same primary outcome. A third arm could receive a substantially larger dose of the experimental therapy or a combinational intervention. If only 1 site performed this trial, a different investigative group should aim to reproduce positive outcomes based on the optimal dose of motor training. Stage 3 studies ought to suggest an effect size of 0.4 or higher, so that approximately 50 participants in each arm will be the number required to test for efficacy in a stage 4, proof-of-concept MRCT. By developing a consensus around acceptable and necessary practices for each stage, similar to CONSORT recommendations for the publication of phase III clinical trials, better quality pilot studies may move quickly into better designed and more successful MRCTs of experimental interventions. PMID:19240197

PediaFlow™ Maglev Ventricular Assist Device: A Prescriptive Design Approach.

PubMed

Antaki, James F; Ricci, Michael R; Verkaik, Josiah E; Snyder, Shaun T; Maul, Timothy M; Kim, Jeongho; Paden, Dave B; Kameneva, Marina V; Paden, Bradley E; Wearden, Peter D; Borovetz, Harvey S

2010-03-01

This report describes a multi-disciplinary program to develop a pediatric blood pump, motivated by the critical need to treat infants and young children with congenital and acquired heart diseases. The unique challenges of this patient population require a device with exceptional biocompatibility, miniaturized for implantation up to 6 months. This program implemented a collaborative, prescriptive design process, whereby mathematical models of the governing physics were coupled with numerical optimization to achieve a favorable compromise among several competing design objectives. Computational simulations of fluid dynamics, electromagnetics, and rotordynamics were performed in two stages: first using reduced-order formulations to permit rapid optimization of the key design parameters; followed by rigorous CFD and FEA simulations for calibration, validation, and detailed optimization. Over 20 design configurations were initially considered, leading to three pump topologies, judged on the basis of a multi-component analysis including criteria for anatomic fit, performance, biocompatibility, reliability, and manufacturability. This led to fabrication of a mixed-flow magnetically levitated pump, the PF3, having a displaced volume of 16.6 cc, approximating the size of a AA battery and producing a flow capacity of 0.3-1.5 L/min. Initial in vivo evaluation demonstrated excellent hemocompatibility after 72 days of implantation in an ovine. In summary, combination of prescriptive and heuristic design principles have proven effective in developing a miniature magnetically levitated blood pump with excellent performance and biocompatibility, suitable for integration into chronic circulatory support system for infants and young children; aiming for a clinical trial within 3 years.

Parabolic dish collectors - A solar option

NASA Astrophysics Data System (ADS)

Truscello, V. C.

1981-05-01

A description is given of several parabolic-dish high temperature solar thermal systems currently undergoing performance trials. A single parabolic dish has the potential for generating 20 to 30 kW of electricity with fluid temperatures from 300 to 1650 C. Each dish is a complete power-producing unit, and may function either independently or as part of a group of linked modules. The two dish designs under consideration are of 11 and 12 meter diameters, yielding receiver operating temperatures of 925 and 815 C, respectively. The receiver designs described include (1) an organic working fluid (toluene) Rankine cycle engine; (2) a Brayton open cycle unit incorporating a hybrid combustion chamber and nozzle and a shaft-coupled permanent magnet alternator; and (3) a modified Stirling cycle device originally designed for automotive use. Also considered are thermal buffer energy storage and thermochemical transport and storage.

Women in Clinical Trials

MedlinePlus

... your healthcare provider if a clinical trial is right for you. Are Women in Clinical Trials? Yes. Women are already in ... how drugs and devices work. FDA Office of Women’s ... should not feel pressured to join. You have the right to quit at any time. There are rules ...

The effect of providing feedback on inhaler technique and adherence from an electronic audio recording device, INCA®, in a community pharmacy setting: study protocol for a randomised controlled trial.

PubMed

O'Dwyer, Susan Mary; MacHale, Elaine; Sulaiman, Imran; Holmes, Martin; Hughes, Cian; D'Arcy, Shona; Rapcan, Viliam; Taylor, Terence; Boland, Fiona; Bosnic-Anticevich, Sinthia; Reilly, Richard B; Ryder, Sheila A; Costello, Richard W

2016-05-04

Poor adherence to inhaled medication may lead to inadequate symptom control in patients with respiratory disease. In practice it can be difficult to identify poor adherence. We designed an acoustic recording device, the INCA® (INhaler Compliance Assessment) device, which, when attached to an inhaler, identifies and records the time and technique of inhaler use, thereby providing objective longitudinal data on an individual's adherence to inhaled medication. This study will test the hypothesis that providing objective, personalised, visual feedback on adherence to patients in combination with a tailored educational intervention in a community pharmacy setting, improves adherence more effectively than education alone. The study is a prospective, cluster randomised, parallel-group, multi-site study conducted over 6 months. The study is designed to compare current best practice in care (i.e. routine inhaler technique training) with the use of the INCA® device for respiratory patients in a community pharmacy setting. Pharmacies are the unit of randomisation and on enrolment to the study they will be allocated by the lead researcher to one of the three study groups (intervention, comparator or control groups) using a computer-generated list of random numbers. Given the nature of the intervention neither pharmacists nor participants can be blinded. The intervention group will receive feedback from the acoustic recording device on inhaler technique and adherence three times over a 6-month period along with inhaler technique training at each of these times. The comparator group will also receive training in inhaler use three times over the 6-month study period but no feedback on their habitual performance. The control group will receive usual care (i.e. the safe supply of medicines and advice on their use). The primary outcome is the rate of participant adherence to their inhaled medication, defined as the proportion of correctly taken doses of medication at the correct time relative to the prescribed interval. Secondary outcomes include exacerbation rates and quality of life measures. Differences in the timing and technique of inhaler use as altered by the interventions will also be assessed. Data will be analysed on an intention-to-treat and a per-protocol basis. Sample size has been calculated with reference to comparisons to be made between the intervention and comparator clusters and indicates 75 participants per cluster. With an estimated 10 % loss to follow-up we will be able to show a 20 % difference between the population means of the intervention and comparator groups with a power of 0.8. The Type I error probability associated with the test of the null hypothesis is 0.05. This clinical trial will establish whether providing personalised feedback to individuals on their inhaler use improves adherence. It may also be possible to enhance the role of pharmacists in clinical care by identifying patients in whom alteration of either therapy or inhaler device is appropriate. ClinicalTrials.gov NCT02203266 .

Simple Circumcision Device: Proof-of-Concept for a Single-visit, Adjustable Device to Facilitate Safe Adult Male Circumcision

PubMed Central

Hotaling, James M; Leddy, Laura S; Haider, Mahum A; Mossanen, Matthew; Bailey, Michael R; MacConaghy, Brian; Olson, Francis; Krieger, John N

2014-01-01

Objective To conduct a proof-of-concept study to determine the potential utility of a novel, adjustable single-visit, disposable device to facilitate rapid adult circumcision. Design Prospective pilot trial of a novel surgical device Setting Tertiary care Veterans Administration medical center Patients 5 adult males Interventions Circumcisions performed by junior trainees using an adjustable, single-size surgical-assist device constructed by the University of Washington Applied Physics Laboratory. Main Outcome Measure(s) The attending surgeon and trainees completed standardized forms after each procedure to assess technical problems and ease of use. Follow-up visits were scheduled to evaluate adverse events, post-operative pain, cosmetic outcomes and participant satisfaction at 3, 8, 30 and 90 days post-operatively. Results The average operative time was 16.4 minutes. All cases were performed with local anesthesia and no case required electrocautery or conversion to standard surgery. At the post-operative day 3 visit all subjects were happy with their results and would recommend the procedure to another patient. One participant had a minor wound separation noted at the 30-day visit that resolved during follow-up. There were no wound infections, hematomas or other adverse events. Conclusions This proof-of-study suggests that the Simple Circumcision Device (SCD) may facilitate delivery of safe adult male circumcision services. PMID:24613534

Stepping on Obstacles with a Sensory Substitution Device on the Lower Leg: Practice without Vision Is More Beneficial than Practice with Vision

PubMed Central

Lobo, Lorena; Travieso, David; Barrientos, Antonio; Jacobs, David M.

2014-01-01

Practice is essential for an adapted use of sensory substitution devices. Understanding the learning process is therefore a fundamental issue in this field of research. This study presents a novel sensory substitution device worn on the lower leg and uses the device to study learning. The device includes 32 vibrotactile actuators that each vibrate as a function of the distance to the nearest surface in a particular direction. Participants wearing the device were asked to approach an object and to step on the object. Two 144-trial practice conditions were compared in a pretest-practice-posttest design. Participants in the first condition practiced with vibrotactile stimulation while blindfolded. Participants in the second condition practiced with vibrotactile stimulation along with normal vision. Performance was relatively successful, both types of practice led to improvements in performance, and practice without vision led to a larger reduction in the number of errors than practice with vision. These results indicate that distance-based sensory substitution is promising in addition to the more traditional light-intensity-based sensory substitution and that providing appropriate sensorimotor couplings is more important than applying the stimulation to highly sensitive body parts. The observed advantage of practice without vision over practice with vision is interpreted in terms of the guidance hypothesis of feedback and learning. PMID:24901843

Global cardiovascular device innovation: Japan-USA synergies: Harmonization by Doing (HBD) program, a consortium of regulatory agencies, medical device industry, and academic institutions.

PubMed

Uchida, Takahiro; Ikeno, Fumiaki; Ikeda, Koji; Suzuki, Yuka; Todaka, Koji; Yokoi, Hiroyoshi; Thompson, Gary; Krucoff, Mitchel; Saito, Shigeru

2013-01-01

Global medical devices have become more popular, but investment money for medical device development is not easily available in the market. Worldwide health-care budget constraints mean that efficient medical device development has become essential. To achieve efficient development, globalization is a key to success. Spending large amounts of money in different regions for medical device development is no longer feasible. In order to streamline processes of global medical device development, an academic, governmental, and industrial consortium, called the Harmonization by Doing program, has been set up. The program has been operating between Japan and the USA since 2003. The program has 4 working groups: (1) Global Cardiovascular Device Trials; (2) Study on Post-Market Registry; (3) Clinical Trials; and (4) Infrastructure and Methodology Regulatory Convergence and Communication. Each working group has as its goals the achievement of speedy and efficient medical device development in Japan and the USA. The program has held multiple international meetings to deal with obstacles against efficient medical device development. This kind of program is very important to deliver novel medical devices. Involvement of physicians in this type of activity is also very helpful to achieve these goals.

Experiment on a novel user input for computer interface utilizing tongue input for the severely disabled.

PubMed

Kencana, Andy Prima; Heng, John

2008-11-01

This paper introduces a novel passive tongue control and tracking device. The device is intended to be used by the severely disabled or quadriplegic person. The main focus of this device when compared to the other existing tongue tracking devices is that the sensor employed is passive which means it requires no powered electrical sensor to be inserted into the user's mouth and hence no trailing wires. This haptic interface device employs the use of inductive sensors to track the position of the user's tongue. The device is able perform two main PC functions that of the keyboard and mouse function. The results show that this device allows the severely disabled person to have some control in his environment, such as to turn on and off or control daily electrical devices or appliances; or to be used as a viable PC Human Computer Interface (HCI) by tongue control. The operating principle and set-up of such a novel passive tongue HCI has been established with successful laboratory trials and experiments. Further clinical trials will be required to test out the device on disabled persons before it is ready for future commercial development.

Mobile-Based Video Learning Outcomes in Clinical Nursing Skill Education

PubMed Central

Lee, Nam-Ju; Chae, Sun-Mi; Kim, Haejin; Lee, Ji-Hye; Min, Hyojin Jennifer; Park, Da-Eun

2016-01-01

Mobile devices are a regular part of daily life among the younger generations. Thus, now is the time to apply mobile device use to nursing education. The purpose of this study was to identify the effects of a mobile-based video clip on learning motivation, competence, and class satisfaction in nursing students using a randomized controlled trial with a pretest and posttest design. A total of 71 nursing students participated in this study: 36 in the intervention group and 35 in the control group. A video clip of how to perform a urinary catheterization was developed, and the intervention group was able to download it to their own mobile devices for unlimited viewing throughout 1 week. All of the students participated in a practice laboratory to learn urinary catheterization and were blindly tested for their performance skills after participation in the laboratory. The intervention group showed significantly higher levels of learning motivation and class satisfaction than did the control. Of the fundamental nursing competencies, the intervention group was more confident in practicing catheterization than their counterparts. Our findings suggest that video clips using mobile devices are useful tools that educate student nurses on relevant clinical skills and improve learning outcomes. PMID:26389858

Trial of a novel endoscopic tattooing biopsy forceps on animal model

PubMed Central

Si, Jian-Min; Sun, Lei-Min; Fan, Yu-Jing; Wang, Liang-Jing

2005-01-01

AIM: To tattoo gastric mucosa with a novel medical device which could be used to monitor and follow-up gastric mucosal lesions. METHODS: Combining endoscopic biopsy with sclerotherapy injection, we designed a new device that could perform biopsy and injection simultaneously. We performed endoscopies on a pig by using a novel endoscope tattoo biopsy forceps for 15 mo. At the same time, we used two-step method combining sclerotherapy injection needle with endoscopic biopsy. The acuity, inflammation and duration of endoscopy were compared between two methods. RESULTS: Compared with the old two-step method, although the inflammation induced by our new device was similar, the duration of procedure was markedly decreased and the acuity of tattooing was better than the old two-step method. All characteristics of the novel device complied with national safety guidelines. Follow-up gastroscopy after 15 mo showed the stained site with injection of 1:100 0.5 mL of India ink was still markedly visible with little inflammatory reaction. CONCLUSION: Endoscopic tattooing biopsy forceps can be widely used in monitoring precancerous lesions. Its safety and effectiveness has been established in animals. PMID:15793881

Commentary: physical approaches for the treatment of epilepsy: electrical and magnetic stimulation and cooling.

PubMed

Löscher, Wolfgang; Cole, Andrew J; McLean, Michael J

2009-04-01

Physical approaches for the treatment of epilepsy currently under study or development include electrical or magnetic brain stimulators and cooling devices, each of which may be implanted or applied externally. Some devices may stimulate peripheral structures, whereas others may be implanted directly into the brain. Stimulation may be delivered chronically, intermittently, or in response to either manual activation or computer-based detection of events of interest. Physical approaches may therefore ultimately be appropriate for seizure prophylaxis by causing a modification of the underlying substrate, presumably with a reduction in the intrinsic excitability of cerebral structures, or for seizure termination, by interfering with the spontaneous discharge of pathological neuronal networks. Clinical trials of device-based therapies are difficult due to ethical issues surrounding device implantation, problems with blinding, potential carryover effects that may occur in crossover designs if substrate modification occurs, and subject heterogeneity. Unresolved issues in the development of physical treatments include optimization of stimulation parameters, identification of the optimal volume of brain to be stimulated, development of adequate power supplies to stimulate the necessary areas, and a determination that stimulation itself does not promote epileptogenesis or adverse long-term effects on normal brain function.

Field evaluation of the Off! Clip-on Mosquito Repellent (metofluthrin) against Aedes albopictus and Aedes taeniorhynchus (Diptera: Culicidae) in northeastern Florida.

PubMed

Xue, Rui-De; Qualls, Whitney A; Smith, Michael L; Gaines, Marcia K; Weaver, James H; Debboun, Mustapha

2012-05-01

Repellent efficacy of the Off! Clip-on Mosquito Repellent device (S. C. Johnson and Son, Inc., Racine, WI) containing Metofluthrin was evaluated on six human volunteers against the container-breeding mosquito Aedes albopictus (Skuse) and the salt marsh mosquito Aedes taeniorhynchus (Wiedemann) at two field locations in northeastern Florida. The device repelled mosquitoes by releasing a vaporized form of the pyrethroid insecticide metofluthrin ([AI] 31.2%) and provided 70% protection from Ae. albopictus bites for > 3 h. For the second field trial, a repellent device that was used in the first trial was tested after being open for >1 wk. This device provided 79% protection from Ae. taeniorhynchus bites for 3 h. Our field results showed that the repellent device was 70 and 79% effective at repelling Ae. albopictus and Ae. taeniorhynchus from human test subjects in both field locations in northeastern Florida.

Stent Thrombosis With Drug-Eluting Stents and Bioresorbable Scaffolds: Evidence From a Network Meta-Analysis of 147 Trials.

PubMed

Kang, Si-Hyuck; Chae, In-Ho; Park, Jin-Joo; Lee, Hak Seung; Kang, Do-Yoon; Hwang, Seung-Sik; Youn, Tae-Jin; Kim, Hyo-Soo

2016-06-27

This study sought to perform a systematic review and network meta-analysis to compare the relative safety and efficacy of contemporary DES and BVS. To improve outcomes of patients undergoing percutaneous coronary revascularization, there have been advances in the design of drug-eluting stents (DES), including the development of drug-eluting bioresorbable vascular scaffolds (BVS). Prospective, randomized, controlled trials comparing bare-metal stents (BMS), paclitaxel-eluting stents (PES), sirolimus-eluting stents (SES), Endeavor zotarolimus-eluting stents (E-ZES), cobalt-chromium (CoCr) everolimus-eluting stents (EES), platinum-chromium (PtCr)-EES, biodegradable polymer (BP)-EES, Resolute zotarolimus-eluting stents (R-ZES), BP biolimus-eluting stents (BP-BES), hybrid sirolimus-eluting stents (H [Orsiro]-SES), polymer-free sirolimus- and probucol-eluting stents, or BVS were searched in online databases. The primary endpoint was definite or probable stent thrombosis at 1 year. A total of 147 trials including 126,526 patients were analyzed in this study. All contemporary DES were superior to BMS and PES in terms of definite or probable stent thrombosis at 1 year. CoCr-EES, PtCr-EES, and H-SES were associated with significantly lower risk than BVS. CoCr-EES and H-SES were superior to SES and BP-BES. The risk of myocardial infarction was significantly lower with H-SES than with BVS. There were no significant differences regarding all-cause or cardiac mortality. Contemporary devices including BVS showed comparably low risks of repeat revascularization. Contemporary DES, including biocompatible DP-DES, BP-DES, and polymer-free DES, showed a low risk of definite or probable stent thrombosis at 1 year. BVS had an increased risk of device thrombosis compared with CoCr-EES, PtCr-EES, and H-SES. Data from extended follow-up are warranted to confirm the long-term safety of contemporary coronary devices. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Glocal Clinical Registries: Pacemaker Registry Design and Implementation for Global and Local Integration – Methodology and Case Study

PubMed Central

da Silva, Kátia Regina; Costa, Roberto; Crevelari, Elizabeth Sartori; Lacerda, Marianna Sobral; de Moraes Albertini, Caio Marcos; Filho, Martino Martinelli; Santana, José Eduardo; Vissoci, João Ricardo Nickenig; Pietrobon, Ricardo; Barros, Jacson V.

2013-01-01

Background The ability to apply standard and interoperable solutions for implementing and managing medical registries as well as aggregate, reproduce, and access data sets from legacy formats and platforms to advanced standard formats and operating systems are crucial for both clinical healthcare and biomedical research settings. Purpose Our study describes a reproducible, highly scalable, standard framework for a device registry implementation addressing both local data quality components and global linking problems. Methods and Results We developed a device registry framework involving the following steps: (1) Data standards definition and representation of the research workflow, (2) Development of electronic case report forms using REDCap (Research Electronic Data Capture), (3) Data collection according to the clinical research workflow and, (4) Data augmentation by enriching the registry database with local electronic health records, governmental database and linked open data collections, (5) Data quality control and (6) Data dissemination through the registry Web site. Our registry adopted all applicable standardized data elements proposed by American College Cardiology / American Heart Association Clinical Data Standards, as well as variables derived from cardiac devices randomized trials and Clinical Data Interchange Standards Consortium. Local interoperability was performed between REDCap and data derived from Electronic Health Record system. The original data set was also augmented by incorporating the reimbursed values paid by the Brazilian government during a hospitalization for pacemaker implantation. By linking our registry to the open data collection repository Linked Clinical Trials (LinkedCT) we found 130 clinical trials which are potentially correlated with our pacemaker registry. Conclusion This study demonstrates how standard and reproducible solutions can be applied in the implementation of medical registries to constitute a re-usable framework. Such approach has the potential to facilitate data integration between healthcare and research settings, also being a useful framework to be used in other biomedical registries. PMID:23936257

Randomised comparison of the effectiveness of the laryngeal mask airway supreme, i-gel and current practice in the initial airway management of prehospital cardiac arrest (REVIVE-Airways): a feasibility study research protocol.

PubMed

Benger, Jonathan Richard; Voss, Sarah; Coates, David; Greenwood, Rosemary; Nolan, Jerry; Rawstorne, Steven; Rhys, Megan; Thomas, Matthew

2013-01-01

Effective cardiopulmonary resuscitation with appropriate airway management improves outcomes following out-of-hospital cardiac arrest (OHCA). Historically, tracheal intubation has been accepted as the optimal form of OHCA airway management in the UK. The Joint Royal Colleges Ambulance Liaison Committee recently concluded that newer supraglottic airway devices (SADs) are safe and effective devices for hospital procedures and that their use in OHCA should be investigated. This study will address an identified gap in current knowledge by assessing whether it is feasible to use a cluster randomised design to compare SADs with current practice, and also to each other, during OHCA. The primary objective of this study is to assess the feasibility of a cluster randomised trial to compare the ventilation success of two newer SADs: the i-gel and the laryngeal mask airway supreme to usual practice during the initial airway management of OHCA. The secondary objectives are to collect data on ventilation success, further airway interventions required, loss of a previously established airway during transport, airway management on arrival at hospital (or termination of the resuscitation attempt), initial resuscitation success, survival to intensive care admission, survival to hospital discharge and patient outcome at 3 months. Ambulance paramedics will be randomly allocated to one of the three methods of airway management. Adults in medical OHCA attended by a trial paramedic will be eligible for the study. Approval for the study has been obtained from a National Health Service Research Ethics Committee with authority to review proposals for trials of a medical device in incapacitated adults. The results will be made publicly available on an open access website, and we will publish the findings in appropriate journals and present them at national and international conferences relevant to the subject field. ISRCTN: 18528625.

External trial deep brain stimulation device for the application of desynchronizing stimulation techniques.

PubMed

Hauptmann, C; Roulet, J-C; Niederhauser, J J; Döll, W; Kirlangic, M E; Lysyansky, B; Krachkovskyi, V; Bhatti, M A; Barnikol, U B; Sasse, L; Bührle, C P; Speckmann, E-J; Götz, M; Sturm, V; Freund, H-J; Schnell, U; Tass, P A

2009-12-01

In the past decade deep brain stimulation (DBS)-the application of electrical stimulation to specific target structures via implanted depth electrodes-has become the standard treatment for medically refractory Parkinson's disease and essential tremor. These diseases are characterized by pathological synchronized neuronal activity in particular brain areas. We present an external trial DBS device capable of administering effectively desynchronizing stimulation techniques developed with methods from nonlinear dynamics and statistical physics according to a model-based approach. These techniques exploit either stochastic phase resetting principles or complex delayed-feedback mechanisms. We explain how these methods are implemented into a safe and user-friendly device.

The impact of a point-of-care testing device on CVD risk assessment completion in New Zealand primary-care practice: A cluster randomised controlled trial and qualitative investigation.

PubMed

Wells, Sue; Rafter, Natasha; Kenealy, Timothy; Herd, Geoff; Eggleton, Kyle; Lightfoot, Rose; Arcus, Kim; Wadham, Angela; Jiang, Yannan; Bullen, Chris

2017-01-01

To assess the effect of a point of care (POC) device for testing lipids and HbA1c in addition to testing by community laboratory facilities (usual practice) on the completion of cardiovascular disease (CVD) risk assessments in general practice. We conducted a pragmatic, cluster randomised controlled trial in 20 New Zealand general practices stratified by size and rurality and randomised to POC device plus usual practice or usual practice alone (controls). Patients aged 35-79 years were eligible if they met national guideline criteria for CVD risk assessment. Data on CVD risk assessments were aggregated using a web-based decision support programme common to each practice. Data entered into the on-line CVD risk assessment form could be saved pending blood test results. The primary outcome was the proportion of completed CVD risk assessments. Qualitative data on practice processes for CVD risk assessment and feasibility of POC testing were collected at the end of the study by interviews and questionnaire. The POC testing was supported by a comprehensive quality assurance programme. A CVD risk assessment entry was recorded for 7421 patients in 10 POC practices and 6217 patients in 10 control practices; 99.5% of CVD risk assessments had complete data in both groups (adjusted odds ratio 1.02 [95%CI 0.61-1.69]). There were major external influences that affected the trial: including a national performance target for CVD risk assessment and changes to CVD guidelines. All practices had invested in systems and dedicated staff time to identify and follow up patients to completion. However, the POC device was viewed by most as an additional tool rather than as an opportunity to review practice work flow and leverage the immediate test results for patient education and CVD risk management discussions. Shortly after commencement, the trial was halted due to a change in the HbA1c test assay performance. The trial restarted after the manufacturing issue was rectified but this affected the end use of the device. Performance incentives and external influences were more powerful modifiers of practice behaviours than the POC device in relation to CVD risk assessment completion. The promise of combining risk assessment, communication and management within one consultation was not realised. With shifts in policy focus, the utility of POC devices for patient engagement in CVD preventive care may be demonstrated if fully integrated into the clinical setting. Australian New Zealand Clinical Trials Registry ACTRN12613000607774.

Assistive acting movement therapy devices with pneumatic rotary-type soft actuators.

PubMed

Wilkening, André; Baiden, David; Ivlev, Oleg

2012-12-01

Inherent compliance and assistive behavior are assumed to be essential properties for safe human-robot interaction. Rehabilitation robots demand the highest standards in this respect because the machine interacts directly with weak persons who are often sensitive to pain. Using novel soft fluidic actuators with rotary elastic chambers (REC actuators), compact, lightweight, and cost-effective therapeutic devices can be developed. This article describes modular design and control strategies for new assistive acting robotic devices for upper and lower extremities. Due to the inherent compliance and natural back-drivability of pneumatic REC actuators, these movement therapy devices provide gentle treatment, whereby the interaction forces between humans and the therapy device are estimated without the use of expensive force/torque sensors. An active model-based gravity compensation based on separated models of the robot and of the individual patient's extremity provides the basis for effective assistive control. The utilization of pneumatic actuators demands a special safety concept, which is merged with control algorithms to provide a sufficient level of safeness and to catch any possible system errors and/or emergency situations. A self-explanatory user interface allows for easy, intuitive handling. Prototypes are very comfortable for use due to several control routines that work in the background. Assistive devices have been tested extensively with several healthy persons; the knee/hip movement therapy device is now under clinical trials at the Clinic for Orthopaedics and Trauma Surgery at the Klinikum Stuttgart.

Renal denervation therapy for hypertension: pathways for moving development forward.

PubMed

White, William B; Galis, Zorina S; Henegar, Jeffrey; Kandzari, David E; Victor, Ronald; Sica, Domenic; Townsend, Raymond R; Turner, J Rick; Virmani, Renu; Mauri, Laura

2015-05-01

This scientific statement provides a summary of presentations and discussions at a cardiovascular Think Tank co-sponsored by the American Society of Hypertension (ASH), the United States Food and Drug Administration (FDA), and the National Heart, Lung, and Blood Institute (NHLBI) held in North Bethesda, Maryland, on June 26, 2014. Studies of device therapies for the treatment of hypertension are requested by regulators to evaluate their safety and efficacy during their development programs. Think Tank participants thought that important considerations in undertaking such studies were: (1) Preclinical assessment: how likely it is that both efficacy and safety data indicating benefit in humans will be obtained, and/or whether a plausible mechanism of action for efficacy can be identified; (2) Early human trial(s): the ability to determine that the device has an acceptable benefit-to-risk balance for its use in the intended patient population and without the influence of drug therapy during a short-term follow-up period; and (3) Pivotal Phase III trial(s): the ability to prove the effectiveness of the device in a broad population in which the trial can be made as non-confounded as possible while still allowing for the determination for benefits when added to antihypertensive therapies. Copyright © 2015 American Society of Hypertension. All rights reserved.

NHLBI's program for VAD therapy for moderately advanced heart failure: the REVIVE-IT pilot trial.

PubMed

Baldwin, J Timothy; Mann, Douglas L

2010-11-01

Ventricular assist devices (VADs) are used to bridge heart failure patients to transplantation, to allow their own hearts to recover, or as permanent ("destination") therapy. To date, the use of VADs has been limited to late-stage heart failure patients because of the associated device risks. In 2008, a National Heart, Lung, and Blood Institute (NHLBI) working group met to evaluate the treatment of heart failure using VADs and to advise the institute on how therapy for heart failure may be best advanced by clinical trials involving the devices. Recognizing the improvements in VAD technology and in patient care and selection over the past decade, the working group recommended that a trial be performed to assess the use of chronic VAD therapy in patients who are less ill than those currently eligible for destination therapy. The hypothesis proposed for the trial is that VAD therapy may improve both survival and quality of life in moderately advanced heart failure patients who are neither inotrope-dependent nor exercise-intolerant and have not yet developed serious consequences such as malnourishment, end-organ damage, and immobility. Based on the group's recommendations, NHLBI issued an RFP in 2009 for the REVIVE-IT Pilot Trail, which will serve to test the hypothesis and inform the pivotal trial. Published by Elsevier Inc.

Update on Tissue Tightening

PubMed Central

2010-01-01

A variety of medical devices are described under the heading of tissue tightening devices. This article reviews the tissue tightening devices currently available in the United States and some that may receive clearance in the upcoming year. These include the various radiofrequency devices as well as the pulsed light devices that achieve similar end results. The one noticeable factor seen with this group of devices is the paucity of large, clinical, controlled trials that appear in the medical literature for this group of medical devices as a whole. PMID:20725568

Safety evaluation of large external fixation clamps and frames in a magnetic resonance environment.

PubMed

Luechinger, Roger; Boesiger, Peter; Disegi, John A

2007-07-01

Large orthopedic external fixation clamps and related components were evaluated for force, torque, and heating response when subjected to the strong electromagnetic fields of magnetic-resonance (MR) imaging devices. Forces induced by a 3-Tesla (T) MR scanner were compiled for newly designed nonmagnetic clamps and older clamps that contained ferromagnetic components. Heating trials were performed in a 1.5 and in a 3 T MR scanner with two assembled external fixation frames. Forces of the newly designed clamps were more than a factor 2 lower as the gravitational force on the device whereas, magnetic forces on the older devices showed over 10 times the force induced by earth acceleration of gravity. No torque effects could be found for the newly designed clamps. Temperature measurements at the tips of Schanz screws in the 1.5 T MR scanner showed a rise of 0.7 degrees C for a pelvic frame and of 2.1 degrees C for a diamond knee bridge frame when normalized to a specific absorption rate (SAR) of 2 W/kg. The normalized temperature increases in the 3 T MR scanner were 0.9 degrees C for the pelvic frame and 1.1 degrees C for the knee bridge frame. Large external fixation frames assembled with the newly designed clamps (390 Series Clamps), carbon fiber reinforced rods, and implant quality 316L stainless steel Schanz screws met prevailing force and torque limits when tested in a 3-T field, and demonstrated temperature increase that met IEC-60601 guidelines for extremities. The influence of frame-induced eddy currents on the risk of peripheral nerve stimulation was not investigated. Copyright 2006 Wiley Periodicals, Inc.

Structuring communication relationships for interprofessional teamwork (SCRIPT): a cluster randomized controlled trial

PubMed Central

Zwarenstein, Merrick; Reeves, Scott; Russell, Ann; Kenaszchuk, Chris; Conn, Lesley Gotlib; Miller, Karen-Lee; Lingard, Lorelei; Thorpe, Kevin E

2007-01-01

Background Despite a burgeoning interest in using interprofessional approaches to promote effective collaboration in health care, systematic reviews find scant evidence of benefit. This protocol describes the first cluster randomized controlled trial (RCT) to design and evaluate an intervention intended to improve interprofessional collaborative communication and patient-centred care. Objectives The objective is to evaluate the effects of a four-component, hospital-based staff communication protocol designed to promote collaborative communication between healthcare professionals and enhance patient-centred care. Methods The study is a multi-centre mixed-methods cluster randomized controlled trial involving twenty clinical teaching teams (CTTs) in general internal medicine (GIM) divisions of five Toronto tertiary-care hospitals. CTTs will be randomly assigned either to receive an intervention designed to improve interprofessional collaborative communication, or to continue usual communication practices. Non-participant naturalistic observation, shadowing, and semi-structured, qualitative interviews were conducted to explore existing patterns of interprofessional collaboration in the CTTs, and to support intervention development. Interviews and shadowing will continue during intervention delivery in order to document interactions between the intervention settings and adopters, and changes in interprofessional communication. The primary outcome is the rate of unplanned hospital readmission. Secondary outcomes are length of stay (LOS); adherence to evidence-based prescription drug therapy; patients' satisfaction with care; self-report surveys of CTT staff perceptions of interprofessional collaboration; and frequency of calls to paging devices. Outcomes will be compared on an intention-to-treat basis using adjustment methods appropriate for data from a cluster randomized design. Discussion Pre-intervention qualitative analysis revealed that a substantial amount of interprofessional interaction lacks key core elements of collaborative communication such as self-introduction, description of professional role, and solicitation of other professional perspectives. Incorporating these findings, a four-component intervention was designed with a goal of creating a culture of communication in which the fundamentals of collaboration become a routine part of interprofessional interactions during unstructured work periods on GIM wards. Trial registration Registered with National Institutes of Health as NCT00466297. PMID:17877830

Rapid prototyping of flexible intrafascicular electrode arrays by picosecond laser structuring

NASA Astrophysics Data System (ADS)

Mueller, Matthias; de la Oliva, Natalia; del Valle, Jaume; Delgado-Martínez, Ignacio; Navarro, Xavier; Stieglitz, Thomas

2017-12-01

Objective. Interfacing the peripheral nervous system can be performed with a large variety of electrode arrays. However, stimulating and recording a nerve while having a reasonable amount of channels limits the number of available systems. Translational research towards human clinical trial requires device safety and biocompatibility but would benefit from design flexibility in the development process to individualize probes. Approach. We selected established medical grade implant materials like precious metals and Parylene C to develop a rapid prototyping process for novel intrafascicular electrode arrays using a picosecond laser structuring. A design for a rodent animal model was developed in conjunction with an intrafascicular implantation strategy. Electrode characterization and optimization was performed first in saline solution in vitro before performance and biocompatibility were validated in sciatic nerves of rats in chronic implantation. Main results. The novel fabrication process proved to be suitable for prototyping and building intrafascicular electrode arrays. Electrochemical properties of the electrode sites were enhanced and tested for long-term stability. Chronic implantation in the sciatic nerve of rats showed good biocompatibility, selectivity and stable stimulation thresholds. Significance. Established medical grade materials can be used for intrafascicular nerve electrode arrays when laser structuring defines structure size in the micro-scale. Design flexibility reduces re-design cycle time and material certificates are beneficial support for safety studies on the way to clinical trials.

Acceptability and Feasibility of Real-Time Antiretroviral Therapy Adherence Interventions in Rural Uganda: Mixed-Method Pilot Randomized Controlled Trial

PubMed Central

Atukunda, Esther C; Tumuhimbise, Wilson; Pisarski, Emily E; Tam, Melanie; Wyatt, Monique A; Ware, Norma C; Haberer, Jessica E

2018-01-01

Background Wireless electronic adherence monitors can detect antiretroviral therapy (ART) adherence lapses and trigger interventions in real time, thus potentially avoiding unnecessary HIV viremia. Evidence about the acceptability and feasibility of these monitors and associated interventions, however, is limited. Objective The aim of this study was to assess the acceptability and feasibility of real-time adherence monitoring linked to text messaging (short message service, SMS) reminders and notifications to support adherence among individuals living with HIV who are taking ART in rural southwestern Uganda. Methods Individuals living with HIV who were initiating ART were enrolled in a pilot randomized controlled trial and followed up for 9 months. Participants received a real-time adherence monitor and were randomized to one of the following study arms: (1) scheduled SMS, (2) SMS triggered by missed or delayed doses, or (3) no SMS. SMS notifications were also sent to 45 patient-identified social supporters for sustained adherence lapses in the scheduled SMS and triggered SMS arms. Study participants and social supporters participated in qualitative semistructured in-depth interviews on acceptability and feasibility of this technology. An inductive, content analytic approach, framed by the unified theory of acceptance and use of technology model, was used to analyze qualitative data. Quantitative feasibility data, including device functionality and SMS tracking data, were recorded based upon device metrics collected electronically and summarized descriptively. Results A total of 63 participants participated in the study. Participants reported that real-time monitoring intervention linked to SMS reminders and notifications are generally acceptable; the predominant feedback was perceived utility—the intervention was beneficial in motivating and reminding patients to take medication, as well as enabling provision of social support. The intervention was found to be technically feasible, as data were obtained from most participants as expected most of the time. Potential challenges included the impact of the technology on confidentiality, shared phone ownership, usability skills, and availability of electricity. Conclusions Real-time adherence monitoring integrated with SMS reminders and social support notifications is a generally acceptable (based primarily on perceived utility) and feasible intervention in a resource-limited country. Future efforts should focus on optimized device design, user training to overcome the challenges we encountered, cost effectiveness studies, as well as studying the monitoring aspect of the device without accompanying interventions. Trial Registration ClinicalTrials.gov NCT01957865; https://clinicaltrials.gov/ct2/show/NCT01957865 (Archived by WebCite at http://www.webcitation.org/6zFiDlXDa) PMID:29773527

Efficacy and Safety of Three Cryotherapy Devices for Wart Treatment: A Randomized, Controlled, Investigator-Blinded, Comparative Study.

PubMed

Walczuk, Imko; Eertmans, Frank; Rossel, Bart; Cegielska, Agnieszka; Stockfleth, Eggert; Antunes, Andre; Adriaens, Els

2018-06-01

Cutaneous warts are common skin lesions, caused by human papillomavirus. For years, liquid nitrogen is the cryogen of choice for wart treatment. Alternatively, several cryogenic devices for home treatment are commercially available. The present trial assessed efficacy and safety of a novel nitrous oxide-based cryogenic device for home use (EndWarts Freeze ® in Europe, Compound W ® Nitro-Freeze in the USA). This investigator-blinded, controlled, randomized study compared the nitrous oxide device (test product) with a dimethylether propane-based product (Wartner ® ; comparator 1). Subjects with common or plantar warts (50/50 ratio) were randomized into two groups (n = 58, test product; n = 40, comparator 1). Sequentially, an extra treatment arm (n = 40) was added to compare with a dimethylether-based product with metal nib (Wortie ® ; comparator 2). Main objective implied comparison of the percentage cured subjects after one to maximum three treatments. Efficacy and safety was evaluated by a blinded investigator. After a maximum of three applications, a significantly (p = 0.001) higher cure rate of 70.7% (Intention-to-Treat analysis) was observed with test product versus 46.2% (comparator 1) and 47.5% (comparator 2). Almost three times more subjects were cured after 1 test product application (29.3%), versus comparator 1 (10.4%) and comparator 2 (12.5%). Reported side effects were transient and typical of cryotherapy. All treatments were well-tolerated. The superior cure rates for the test product versus two comparators can be explained by its design. Combination of nitrous oxide (cooling agent), the specific activation method (holding the liquid coolant in the cap), and skin-conforming polyurethane foam, results in higher cooling efficiency (- 80 °C) and more effective wart freezing. This trial demonstrated that the nitrous oxide device is a safe, user-friendly and effective wart treatment for home use, comparing favourably to dimethylether (propane) devices with higher freezing temperature, regardless of the applicator type. Oystershell Laboratories. Clinicaltrials.gov identifier, NCT03129373.

Randomized controlled trial in rural Ethiopia to assess a portable water treatment device.

PubMed

Boisson, Sophie; Schmidt, Wolf-Peter; Berhanu, Tsegahiwot; Gezahegn, Henock; Clasen, Thomas

2009-08-01

We conducted a randomized controlled trial to assess the Lifestraw Personal pipe-style water treatment device among a rural population in Ethiopia. A total of 313 households (including 1516 persons) were randomly assigned either to an intervention group in which each householder received a Lifestraw Personal or a control. Households were visited fortnightly over a five-month intervention period and asked to report any episode of diarrhea during the previous week. A random sample of 160 devices was tested each month to assess the presence of thermotolerant coliforms (TTC) and residual iodine in treated water and to measure flow rate under simulated use. Members of the intervention group had 25% fewer weeks with diarrhea than those of the control group (longitudinal prevalence ratio = 0.75; 95% CI 0.60; 0.95). All 718 filtered water samples were free of TTC, were free of detectable iodine disinfectant, and showed a constant flow rate over time. After the five-month intervention period, 34% of participants reported use of device in the preceding week and 13% reported consistent use. While the device was associated with a 25% reduction in longitudinal prevalence of diarrhea, low levels of use suggest that much of this effect is likely to be attributable to reporting bias that is common in open trials with nonobjective outcomes.

Globally optimal trial design for local decision making.

PubMed

Eckermann, Simon; Willan, Andrew R

2009-02-01

Value of information methods allows decision makers to identify efficient trial design following a principle of maximizing the expected value to decision makers of information from potential trial designs relative to their expected cost. However, in health technology assessment (HTA) the restrictive assumption has been made that, prospectively, there is only expected value of sample information from research commissioned within jurisdiction. This paper extends the framework for optimal trial design and decision making within jurisdiction to allow for optimal trial design across jurisdictions. This is illustrated in identifying an optimal trial design for decision making across the US, the UK and Australia for early versus late external cephalic version for pregnant women presenting in the breech position. The expected net gain from locally optimal trial designs of US$0.72M is shown to increase to US$1.14M with a globally optimal trial design. In general, the proposed method of globally optimal trial design improves on optimal trial design within jurisdictions by: (i) reflecting the global value of non-rival information; (ii) allowing optimal allocation of trial sample across jurisdictions; (iii) avoiding market failure associated with free-rider effects, sub-optimal spreading of fixed costs and heterogeneity of trial information with multiple trials. Copyright (c) 2008 John Wiley & Sons, Ltd.

Novel Platform for MRI-Guided Convection-Enhanced Delivery of Therapeutics: Preclinical Validation in Nonhuman Primate Brain

PubMed Central

Richardson, R. Mark; Kells, Adrian P.; Martin, Alastair J.; Larson, Paul S.; Starr, Philip A.; Piferi, Peter G.; Bates, Geoffrey; Tansey, Lisa; Rosenbluth, Kathryn H.; Bringas, John R.; Berger, Mitchel S.; Bankiewicz, Krystof S.

2011-01-01

Background/Aims A skull-mounted aiming device and integrated software platform has been developed for MRI-guided neurological interventions. In anticipation of upcoming gene therapy clinical trials, we adapted this device for real-time convection-enhanced delivery of therapeutics via a custom-designed infusion cannula. The targeting accuracy of this delivery system and the performance of the infusion cannula were validated in nonhuman primates. Methods Infusions of gadoteridol were delivered to multiple brain targets and the targeting error was determined for each cannula placement. Cannula performance was assessed by analyzing gadoteridol distributions and by histological analysis of tissue damage. Results The average targeting error for all targets (n = 11) was 0.8 mm (95% CI = 0.14). For clinically relevant volumes, the distribution volume of gadoteridol increased as a linear function (R2 = 0.97) of the infusion volume (average slope = 3.30, 95% CI = 0.2). No infusions in any target produced occlusion, cannula reflux or leakage from adjacent tracts, and no signs of unexpected tissue damage were observed. Conclusions This integrated delivery platform allows real-time convection-enhanced delivery to be performed with a high level of precision, predictability and safety. This approach may improve the success rate for clinical trials involving intracerebral drug delivery by direct infusion. PMID:21494065

Chinese medicine shenfu injection for heart failure: a systematic review and meta-analysis.

PubMed

Wen-Ting, Song; Fa-Feng, Cheng; Li, Xu; Cheng-Ren, Lin; Jian-Xun, Liu

2012-01-01

Objective. Heart failure (HF) is a global public health problem. Early literature studies manifested that Shenfu injection (SFI) is one of the most commonly used traditional Chinese patent medicine for HF in China. This article intended to systematically evaluate the efficacy and safety of SFI for HF. Methods. An extensive search was performed within 6 English and Chinese electronic database up to November 2011. Ninety-nine randomized controlled trails (RCTs) were collected, irrespective of languages. Two authors extracted data and assessed the trial quality independently. RevMan 5.0.2 was used for data analysis. Results. Compared with routine treatment and/or device support, SFI combined with routine treatment and/or device support showed better effect on clinical effect rate, mortality, heart rate, NT-proBNP and 6-minute walk distance. Results in ultrasonic cardiography also showed that SFI combined with routine treatment improved heart function of HF patients. There were no significant difference in blood pressure between SFI and routine treatment groups. Adverse events were reported in thirteen trails with thirteen specific symptoms, while no serious adverse effect was reported. Conclusion. SFI appear to be effective for treating HF. However, further rigorously designed RCTs are warranted because of insufficient methodological rigor in the majority of included trials.

Percutaneous Creation of a Central Iliac Arteriovenous Anastomosis for the Treatment of Arterial Hypertension.

PubMed

Bertog, Stefan C; Sobotka, Nathan A; Sobotka, Paul A; Lobo, Melvin D; Sievert, Kolja; Vaskelyte, Laura; Sievert, Horst; Schmieder, Roland E

2018-03-19

Provision of a summary on the physiologic effects of arteriovenous fistula creation and description of previously published human data on the efficacy of a percutaneously implanted device creating an arteriovenous fistula. Though antihypertensive therapy is effective, some patient's blood pressure remains poorly controlled despite adherence to optimal medical therapy. Moreover, some patients are not compliant with recommended medical therapy due to side effects or personal decision. This has prompted exploration of alternative, device-based antihypertensive therapies including, among others, the percutaneous creation of an arteriovenous fistula. An arteriovenous fistula is accompanied by a number of favorable physiologic changes that may lower blood pressure. These physiologic changes, conduction of the procedure, and previously published human experience are summarized in this review article. The results of a recently published trial comparing arteriovenous fistula creation and standard antihypertensive therapy versus standard antihypertensive therapy alone are summarized. Creation of an arteriovenous fistula is accompanied by a significant blood pressure reduction likely related to a reduction in total arterial resistance, perhaps blood volume reduction, inhibition of the baroreceptor reflex, and release of natriuretic peptides. These findings foster further interest in studying the impact of an arteriovenous fistula and arterial blood pressure. The design of a large randomized trial comparing arteriovenous fistula creation to sham control is outlined.

Resuscitation Outcomes Consortium (ROC) PRIMED Cardiac Arrest Trial Methods, Part 1: Rationale and Methodology for the Impedance Threshold Device (ITD) Protocol

PubMed Central

Aufderheide, Tom P.; Kudenchuk, Peter J.; Hedges, Jerris R.; Nichol, Graham; Kerber, Richard E.; Dorian, Paul; Davis, Daniel P.; Idris, Ahamed H.; Callaway, Clifton W.; Emerson, Scott; Stiell, Ian G.; Terndrup, Thomas E.

2013-01-01

Aim The primary aim of this study is to compare survival to hospital discharge with a modified Rankin score (MRS) ≤3 between standard cardiopulmonary resuscitation (CPR) plus an active impedance threshold device (ITD) versus standard CPR plus a sham ITD in patients with out-of-hospital cardiac arrest. Secondary aims are to compare functional status and depression at discharge and at 3 and 6 months post discharge in survivors. Materials and Methods Design Prospective, double-blind, randomized, controlled, clinical trial. Population Patients with non-traumatic out-of-hospital cardiac arrest treated by emergency medical services (EMS) providers. Setting EMS systems participating in the Resuscitation Outcomes Consortium. Sample Size Based on a one-sided significance level of 0.025, power = 0.90, a survival with MRS ≤ 3 to discharge rate of 5.33% with standard CPR and sham ITD, and two interim analyses, a maximum of 14,742 evaluable patients are needed to detect a 6.69% survival with MRS ≤ 3 to discharge with standard CPR and active ITD (1.36% absolute survival difference). Conclusion If the ITD demonstrates the hypothesized improvement in survival, it is estimated that2,700 deaths from cardiac arrest per year would be averted in North America alone. PMID:18487005

Robotic assistants in personal care: A scoping review.

PubMed

Bilyea, A; Seth, N; Nesathurai, S; Abdullah, H A

2017-11-01

The aim of this study is to present an overview of the technological advances in the field of robotics developed for assistance with activities of daily living (ADL), and to present areas where further research is required. Four databases were searched for articles presenting either a novel design of one of these personal care robotic system or trial results relating to these systems. Articles presenting nine different robotic personal care systems were examined, six of which had been developed after 2005. These six also all have publications relating to their trials. In the majority of trials, patient independence was improved with operation of the robotic device for a specific subset of ADL. A map of the current state of the field of personal care robotics is presented in this study. Areas requiring further research include improving feedback and awareness, as well as refining control methods and pre-programmed behaviors. Developing an affordable, easy to use system would help fill the current gap in the commercial market. Copyright © 2017 IPEM. Published by Elsevier Ltd. All rights reserved.

Safety and Efficacy of Solitaire Stent Thrombectomy: Individual Patient Data Meta-Analysis of Randomized Trials.

PubMed

Campbell, Bruce C V; Hill, Michael D; Rubiera, Marta; Menon, Bijoy K; Demchuk, Andrew; Donnan, Geoffrey A; Roy, Daniel; Thornton, John; Dorado, Laura; Bonafe, Alain; Levy, Elad I; Diener, Hans-Christoph; Hernández-Pérez, María; Pereira, Vitor Mendes; Blasco, Jordi; Quesada, Helena; Rempel, Jeremy; Jahan, Reza; Davis, Stephen M; Stouch, Bruce C; Mitchell, Peter J; Jovin, Tudor G; Saver, Jeffrey L; Goyal, Mayank

2016-03-01

Recent positive randomized trials of endovascular therapy for ischemic stroke used predominantly stent retrievers. We pooled data to investigate the efficacy and safety of stent thrombectomy using the Solitaire device in anterior circulation ischemic stroke. Patient-level data were pooled from trials in which the Solitaire was the only or the predominant device used in a prespecified meta-analysis (SEER Collaboration): Solitaire FR With the Intention for Thrombectomy as Primary Endovascular Treatment (SWIFT PRIME), Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times (ESCAPE), Extending the Time for Thrombolysis in Emergency Neurological Deficits-Intra-Arterial (EXTEND-IA), and Randomized Trial of Revascularization With Solitaire FR Device Versus Best Medical Therapy in the Treatment of Acute Stroke Due to Anterior Circulation Large Vessel Occlusion Presenting Within Eight Hours of Symptom Onset (REVASCAT). The primary outcome was ordinal analysis of modified Rankin Score at 90 days. The primary analysis included all patients in the 4 trials with 2 sensitivity analyses: (1) excluding patients in whom Solitaire was not the first device used and (2) including the 3 Solitaire-only trials (excluding ESCAPE). Secondary outcomes included functional independence (modified Rankin Score 0-2), symptomatic intracerebral hemorrhage, and mortality. The primary analysis included 787 patients: 401 randomized to endovascular thrombectomy and 386 to standard care, and 82.6% received intravenous thrombolysis. The common odds ratio for modified Rankin Score improvement was 2.7 (2.0-3.5) with no heterogeneity in effect by age, sex, baseline stroke severity, extent of computed tomography changes, site of occlusion, or pretreatment with alteplase. The number needed to treat to reduce disability was 2.5 and for an extra patient to achieve independent outcome was 4.25 (3.29-5.99). Successful revascularization occurred in 77% treated with Solitaire device. The rate of symptomatic intracerebral hemorrhage and overall mortality did not differ between treatment groups. Solitaire thrombectomy for large vessel ischemic stroke was safe and highly effective with substantially reduced disability. Benefits were consistent in all prespecified subgroups. © 2016 The Authors.

A new paradigm for obtaining marketing approval for pediatric-sized prosthetic heart valves.

PubMed

Yoganathan, Ajit P; Fogel, Mark; Gamble, Susan; Morton, Michael; Schmidt, Paul; Secunda, Jeff; Vidmar, Sara; Del Nido, Pedro

2013-10-01

Congenital heart valve disease is one of the most common abnormalities in children. There are limited technological solutions available for treating children with congenital heart valve diseases. The aim of this study is to provide the details of the consensus reached in terms of pediatric definitions, design approach, in vitro testing, and clinical trials, which may be used as guidance for developing prosthetic heart valves for the pediatric indication. In stark contrast to the various designs of adult-sized replacement valves available in the market, there are no Food and Drug Administration (FDA)-approved prosthetic heart valves available for use in the pediatric population. There is a pressing need for FDA-approved pediatric valve devices in the United States. The pediatric patient population has been typically excluded from replacement heart valve trials for several reasons. In January 2010, heart valve manufacturers and pediatric clinicians collaborated with academicians and FDA staff in a workshop to suggest ways to successfully evaluate pediatric prosthetic valves and conduct pediatric clinical trials to provide acceptable heart valve replacement options for this patient population. Recommendations, derived from ISO 5840:2005 and the 2010 FDA Draft Replacement Heart Valve Guidance, are provided for hydrodynamic, durability, and fatigue testing. The article specifically addresses in vitro and premarket and postmarket approval clinical studies that should be considered by a heart valve manufacturer for obtaining regulatory approval of pediatric sizes of prosthetic heart valve designs that are already approved for adult clinical use. Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

HeartMate II left ventricular assist system: from concept to first clinical use.

PubMed

Griffith, B P; Kormos, R L; Borovetz, H S; Litwak, K; Antaki, J F; Poirier, V L; Butler, K C

2001-03-01

The HeartMate II left ventricular assist device (LVAD) (ThermoCardiosystems, Inc, Woburn, MA) has evolved from 1991 when a partnership was struck between the McGowan Center of the University of Pittsburgh and Nimbus Company. Early iterations were conceptually based on axial-flow mini-pumps (Hemopump) and began with purge bearings. As the project developed, so did the understanding of new bearings, computational fluid design and flow visualization, and speed control algorithms. The acquisition of Nimbus by ThermoCardiosystems, Inc (TCI) sped developments of cannulas, controller, and power/monitor units. The system has been successfully tested in more than 40 calves since 1997 and the first human implant occurred in July 2000. Multicenter safety and feasibility trials are planned for Europe and soon thereafter a trial will be started in the United States to test 6-month survival in end-stage heart failure.

Dealing with the genetic load in bacterial synthetic biology circuits: convergences with the Ohm's law

PubMed Central

Carbonell-Ballestero, M.; Garcia-Ramallo, E.; Montañez, R.; Rodriguez-Caso, C.; Macía, J.

2016-01-01

Synthetic biology seeks to envision living cells as a matter of engineering. However, increasing evidence suggests that the genetic load imposed by the incorporation of synthetic devices in a living organism introduces a sort of unpredictability in the design process. As a result, individual part characterization is not enough to predict the behavior of designed circuits and thus, a costly trial-error process is eventually required. In this work, we provide a new theoretical framework for the predictive treatment of the genetic load. We mathematically and experimentally demonstrate that dependences among genes follow a quantitatively predictable behavior. Our theory predicts the observed reduction of the expression of a given synthetic gene when an extra genetic load is introduced in the circuit. The theory also explains that such dependence qualitatively differs when the extra load is added either by transcriptional or translational modifications. We finally show that the limitation of the cellular resources for gene expression leads to a mathematical formulation that converges to an expression analogous to the Ohm's law for electric circuits. Similitudes and divergences with this law are outlined. Our work provides a suitable framework with predictive character for the design process of complex genetic devices in synthetic biology. PMID:26656950

The life cycles of six multi-center adaptive clinical trials focused on neurological emergencies developed for the Advancing Regulatory Science initiative of the National Institutes of Health and US Food and Drug Administration: Case studies from the Adaptive Designs Accelerating Promising Treatments Into Trials Project.

PubMed

Guetterman, Timothy C; Fetters, Michael D; Mawocha, Samkeliso; Legocki, Laurie J; Barsan, William G; Lewis, Roger J; Berry, Donald A; Meurer, William J

2017-01-01

Clinical trials are complicated, expensive, time-consuming, and frequently do not lead to discoveries that improve the health of patients with disease. Adaptive clinical trials have emerged as a methodology to provide more flexibility in design elements to better answer scientific questions regarding whether new treatments are efficacious. Limited observational data exist that describe the complex process of designing adaptive clinical trials. To address these issues, the Adaptive Designs Accelerating Promising Treatments Into Trials project developed six, tailored, flexible, adaptive, phase-III clinical trials for neurological emergencies, and investigators prospectively monitored and observed the processes. The objective of this work is to describe the adaptive design development process, the final design, and the current status of the adaptive trial designs that were developed. To observe and reflect upon the trial development process, we employed a rich, mixed methods evaluation that combined quantitative data from visual analog scale to assess attitudes about adaptive trials, along with in-depth qualitative data about the development process gathered from observations. The Adaptive Designs Accelerating Promising Treatments Into Trials team developed six adaptive clinical trial designs. Across the six designs, 53 attitude surveys were completed at baseline and after the trial planning process completed. Compared to baseline, the participants believed significantly more strongly that the adaptive designs would be accepted by National Institutes of Health review panels and non-researcher clinicians. In addition, after the trial planning process, the participants more strongly believed that the adaptive design would meet the scientific and medical goals of the studies. Introducing the adaptive design at early conceptualization proved critical to successful adoption and implementation of that trial. Involving key stakeholders from several scientific domains early in the process appears to be associated with improved attitudes towards adaptive designs over the life cycle of clinical trial development.

A personalized 3D-printed prosthetic joint replacement for the human temporomandibular joint: From implant design to implantation.

PubMed

Ackland, David C; Robinson, Dale; Redhead, Michael; Lee, Peter Vee Sin; Moskaljuk, Adrian; Dimitroulis, George

2017-05-01

Personalized prosthetic joint replacements have important applications in cases of complex bone and joint conditions where the shape and size of off-the-shelf components may not be adequate. The objective of this study was to design, test and fabricate a personalized 3D-printed prosthesis for a patient requiring total joint replacement surgery of the temporomandibular joint (TMJ). The new 'Melbourne' prosthetic TMJ design featured a condylar component sized specifically to the patient and fixation screw positions that avoid potential intra-operative damage to the mandibular nerve. The Melbourne prosthetic TMJ was developed for a 58-year-old female recipient with end-stage osteoarthritis of the TMJ. The load response of the prosthesis during chewing and a maximum-force bite was quantified using a personalized musculoskeletal model of the patient's masticatory system developed using medical images. The simulations were then repeated after implantation of the Biomet Microfixation prosthetic TMJ, an established stock device. The maximum condylar stresses, screw stress and mandibular stress at the screw-bone interface were lower in the Melbourne prosthetic TMJ (259.6MPa, 312.9MPa and 198.4MPa, respectively) than those in the Biomet Microfixation device (284.0MPa, 416.0MPa and 262.2MPa, respectively) during the maximum-force bite, with similar trends also observed during the chewing bite. After trialing surgical placement and evaluating prosthetic TMJ stability using cadaveric specimens, the prosthesis was fabricated using 3D printing, sterilized, and implanted into the female recipient. Six months post-operatively, the prosthesis recipient had a normal jaw opening distance (40.0 mm), with no complications identified. The new design features and immediate load response of the Melbourne prosthetic TMJ suggests that it may provide improved clinical and biomechanical joint function compared to a commonly used stock device, and reduce risk of intra-operative nerve damage during placement. The framework presented may be useful for designing and testing customized devices for the treatment of debilitating bone and joint conditions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Dose-dependent social-cognitive effects of intranasal oxytocin delivered with novel Breath Powered device in adults with autism spectrum disorder: a randomized placebo-controlled double-blind crossover trial

PubMed Central

Quintana, D S; Westlye, L T; Hope, S; Nærland, T; Elvsåshagen, T; Dørum, E; Rustan, Ø; Valstad, M; Rezvaya, L; Lishaugen, H; Stensønes, E; Yaqub, S; Smerud, K T; Mahmoud, R A; Djupesland, P G; Andreassen, O A

2017-01-01

The neuropeptide oxytocin has shown promise as a treatment for symptoms of autism spectrum disorders (ASD). However, clinical research progress has been hampered by a poor understanding of oxytocin’s dose–response and sub-optimal intranasal delivery methods. We examined two doses of oxytocin delivered using a novel Breath Powered intranasal delivery device designed to improve direct nose-to-brain activity in a double-blind, crossover, randomized, placebo-controlled trial. In a randomized sequence of single-dose sessions, 17 male adults with ASD received 8 international units (IU) oxytocin, 24IU oxytocin or placebo followed by four social-cognitive tasks. We observed an omnibus main effect of treatment on the primary outcome measure of overt emotion salience as measured by emotional ratings of faces (η2=0.18). Compared to placebo, 8IU treatment increased overt emotion salience (P=0.02, d=0.63). There was no statistically significant increase after 24IU treatment (P=0.12, d=0.4). The effects after 8IU oxytocin were observed despite no significant increase in peripheral blood plasma oxytocin concentrations. We found no significant effects for reading the mind in the eyes task performance or secondary outcome social-cognitive tasks (emotional dot probe and face-morphing). To our knowledge, this is the first trial to assess the dose-dependent effects of a single oxytocin administration in autism, with results indicating that a low dose of oxytocin can significantly modulate overt emotion salience despite minimal systemic exposure. PMID:28534875

Healthcare Applications of Smart Watches

PubMed Central

Lu, Tsung-Chien; Fu, Chia-Ming; Ma, Matthew Huei-Ming; Fang, Cheng-Chung

2016-01-01

Summary Objective The aim of this systematic review is to synthesize research studies involving the use of smart watch devices for healthcare. Materials and Methods The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was chosen as the systematic review methodology. We searched PubMed, CINAHL Plus, EMBASE, ACM, and IEEE Xplore. In order to include ongoing clinical trials, we also searched ClinicalTrials.gov. Two investigators evaluated the retrieved articles for inclusion. Discrepancies between investigators regarding article inclusion and extracted data were resolved through team discussion. Results 356 articles were screened and 24 were selected for review. The most common publication venue was in conference proceedings (13, 54%). The majority of studies were published or presented in 2015 (19, 79%). We identified two registered clinical trials underway. A large proportion of the identified studies focused on applications involving health monitoring for the elderly (6, 25%). Five studies focused on patients with Parkinson’s disease and one on cardiac arrest. There were no studies which reported use of usability testing before implementation. Discussion Most of the reviewed studies focused on the chronically ill elderly. There was a lack of detailed description of user-centered design or usability testing before implementation. Based on our review, the most commonly used platform in healthcare research was that of the Android Wear. The clinical application of smart watches as assistive devices deserves further attention. Conclusion Smart watches are unobtrusive and easy to wear. While smart watch technology supplied with biosensors has potential to be useful in a variety of healthcare applications, rigorous research with their use in clinical settings is needed. PMID:27623763

Healthcare Applications of Smart Watches. A Systematic Review.

PubMed

Lu, Tsung-Chien; Fu, Chia-Ming; Ma, Matthew Huei-Ming; Fang, Cheng-Chung; Turner, Anne M

2016-09-14

The aim of this systematic review is to synthesize research studies involving the use of smart watch devices for healthcare. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was chosen as the systematic review methodology. We searched PubMed, CINAHL Plus, EMBASE, ACM, and IEEE Xplore. In order to include ongoing clinical trials, we also searched ClinicalTrials.gov. Two investigators evaluated the retrieved articles for inclusion. Discrepancies between investigators regarding article inclusion and extracted data were resolved through team discussion. 356 articles were screened and 24 were selected for review. The most common publication venue was in conference proceedings (13, 54%). The majority of studies were published or presented in 2015 (19, 79%). We identified two registered clinical trials underway. A large proportion of the identified studies focused on applications involving health monitoring for the elderly (6, 25%). Five studies focused on patients with Parkinson's disease and one on cardiac arrest. There were no studies which reported use of usability testing before implementation. Most of the reviewed studies focused on the chronically ill elderly. There was a lack of detailed description of user-centered design or usability testing before implementation. Based on our review, the most commonly used platform in healthcare research was that of the Android Wear. The clinical application of smart watches as assistive devices deserves further attention. Smart watches are unobtrusive and easy to wear. While smart watch technology supplied with biosensors has potential to be useful in a variety of healthcare applications, rigorous research with their use in clinical settings is needed.

Conceptual model for heart failure disease management.

PubMed

Andrikopoulou, Efstathia; Abbate, Kariann; Whellan, David J

2014-03-01

The objective of this review is to propose a conceptual model for heart failure (HF) disease management (HFDM) and to define the components of an efficient HFDM plan in reference to this model. Articles that evaluated 1 or more of the following aspects of HFDM were reviewed: (1) outpatient clinic follow-up; (2) self-care interventions to enhance patient skills; and (3) remote evaluation of worsening HF either using structured telephone support (STS) or by monitoring device data (telemonitoring). The success of programs in reducing readmissions and mortality were mixed. Outpatient follow-up programs generally resulted in improved outcomes, including decreased readmissions. Based on 1 meta-analysis, specialty clinics improved outcomes and nonspecialty clinics did not. Results from self-care programs were inconsistent and might have been affected by patient cognitive status and educational level, and intervention intensity. Telemonitoring, despite initially promising meta-analyses demonstrating a decrease in the number and duration of HF-related readmissions and all-cause mortality rates at follow-up, has not been shown in randomized trials to consistently reduce readmissions or mortality. However, evidence from device monitoring trials in particular might have been influenced by technology and design issues that might be rectified in future trials. Results from the literature suggest that the ideal HFDM plan would include outpatient follow-up at an HF specialty clinic and continuous education to improve patient self-care. The end result of this plan would lead to better understanding on the part of the patient and improved patient ability to recognize and respond to signs of decompensation. Copyright © 2014 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Dose-dependent social-cognitive effects of intranasal oxytocin delivered with novel Breath Powered device in adults with autism spectrum disorder: a randomized placebo-controlled double-blind crossover trial.

PubMed

Quintana, D S; Westlye, L T; Hope, S; Nærland, T; Elvsåshagen, T; Dørum, E; Rustan, Ø; Valstad, M; Rezvaya, L; Lishaugen, H; Stensønes, E; Yaqub, S; Smerud, K T; Mahmoud, R A; Djupesland, P G; Andreassen, O A

2017-05-23

The neuropeptide oxytocin has shown promise as a treatment for symptoms of autism spectrum disorders (ASD). However, clinical research progress has been hampered by a poor understanding of oxytocin's dose-response and sub-optimal intranasal delivery methods. We examined two doses of oxytocin delivered using a novel Breath Powered intranasal delivery device designed to improve direct nose-to-brain activity in a double-blind, crossover, randomized, placebo-controlled trial. In a randomized sequence of single-dose sessions, 17 male adults with ASD received 8 international units (IU) oxytocin, 24IU oxytocin or placebo followed by four social-cognitive tasks. We observed an omnibus main effect of treatment on the primary outcome measure of overt emotion salience as measured by emotional ratings of faces (η 2 =0.18). Compared to placebo, 8IU treatment increased overt emotion salience (P=0.02, d=0.63). There was no statistically significant increase after 24IU treatment (P=0.12, d=0.4). The effects after 8IU oxytocin were observed despite no significant increase in peripheral blood plasma oxytocin concentrations. We found no significant effects for reading the mind in the eyes task performance or secondary outcome social-cognitive tasks (emotional dot probe and face-morphing). To our knowledge, this is the first trial to assess the dose-dependent effects of a single oxytocin administration in autism, with results indicating that a low dose of oxytocin can significantly modulate overt emotion salience despite minimal systemic exposure.

StereoTactic radiotherapy for wet Age-Related macular degeneration (STAR): study protocol for a randomised controlled clinical trial.

PubMed

Neffendorf, James E; Desai, Riti; Wang, Yanzhong; Kelly, Joanna; Murphy, Caroline; Reeves, Barnaby C; Chakravarthy, Usha; Wordsworth, Sarah; Lewis, Cornelius; Peacock, Janet; Uddin, Shahir; O'Sullivan, Joe M; Jackson, Timothy L

2016-11-24

The standard of care for neovascular age-related macular degeneration (nAMD) involves ongoing intravitreal injections of anti-angiogenic drugs targeting vascular endothelial growth factor (VEGF). The most commonly used anti-VEGF drugs are ranibizumab, bevacizumab and aflibercept. The main objective of the STAR trial is to determine if stereotactic radiotherapy can reduce the number of anti-VEGF injections that patients with nAMD require. STAR is a multicentre, double-masked, randomised, sham-controlled clinical trial. It evaluates a new device (manufactured by Oraya, Newark, CA, USA) designed to deliver stereotactic radiotherapy (SRT) to nAMD lesions. The trial enrols participants with chronic, active nAMD. Participants receive a single SRT treatment (16 Gy or sham) with a concomitant baseline intravitreal injection of 0.5 mg ranibizumab. Thereafter, they attend every month for 24 months, and ranibizumab is administered at the visit if retreatment criteria are met. The primary outcome is the number of pro re nata ranibizumab injections during the first 24 months. Secondary outcomes include visual acuity, lesion morphology, quality of life and safety. Additional visits occur at 36 and 48 months to inspect for radiation retinopathy. The target sample size of 411 participants (randomised 2:1 in favour of radiation) is designed to detect a reduction of 2.5 injections against ranibizumab monotherapy, at 90% power, and a significance level (alpha) of 0.025 (one-sided two-sample t test). This gives 97% power to detect non-inferiority of visual acuity at a five-letter margin. The primary analyses will be by intention to treat. The safety and efficacy outcomes will help determine the role of SRT in the management of chronic, active nAMD. International Standard Randomised Controlled Trial Number: ISRCTN12884465. Registered on 28 November 2014. ClinicalTrials.gov: NCT02243878 . Registered on 17 September 2014.

Registry Assessment of Peripheral Interventional Devices (RAPID): Registry assessment of peripheral interventional devices core data elements.

PubMed

Jones, W Schuyler; Krucoff, Mitchell W; Morales, Pablo; Wilgus, Rebecca W; Heath, Anne H; Williams, Mary F; Tcheng, James E; Marinac-Dabic, J Danica; Malone, Misti L; Reed, Terrie L; Fukaya, Rie; Lookstein, Robert A; Handa, Nobuhiro; Aronow, Herbert D; Bertges, Daniel J; Jaff, Michael R; Tsai, Thomas T; Smale, Joshua A; Zaugg, Margo J; Thatcher, Robert J; Cronenwett, Jack L

2018-02-01

The current state of evaluating patients with peripheral artery disease and more specifically of evaluating medical devices used for peripheral vascular intervention (PVI) remains challenging because of the heterogeneity of the disease process, the multiple physician specialties that perform PVI, the multitude of devices available to treat peripheral artery disease, and the lack of consensus about the best treatment approaches. Because PVI core data elements are not standardized across clinical care, clinical trials, and registries, aggregation of data across different data sources and physician specialties is currently not feasible. Under the auspices of the U.S. Food and Drug Administration's Medical Device Epidemiology Network initiative-and its PASSION (Predictable and Sustainable Implementation of the National Registries) program, in conjunction with other efforts to align clinical data standards-the Registry Assessment of Peripheral Interventional Devices (RAPID) workgroup was convened. RAPID is a collaborative, multidisciplinary effort to develop a consensus lexicon and to promote interoperability across clinical care, clinical trials, and national and international registries of PVI. The current manuscript presents the initial work from RAPID to standardize clinical data elements and definitions, to establish a framework within electronic health records and health information technology procedural reporting systems, and to implement an informatics-based approach to promote the conduct of pragmatic clinical trials and registry efforts in PVI. Ultimately, we hope this work will facilitate and improve device evaluation and surveillance for patients, clinicians, health outcomes researchers, industry, policymakers, and regulators. Copyright © 2017 Society for Vascular Surgery. All rights reserved.

Using Bayesian Adaptive Trial Designs for Comparative Effectiveness Research: A Virtual Trial Execution.

PubMed

Luce, Bryan R; Connor, Jason T; Broglio, Kristine R; Mullins, C Daniel; Ishak, K Jack; Saunders, Elijah; Davis, Barry R

2016-09-20

Bayesian and adaptive clinical trial designs offer the potential for more efficient processes that result in lower sample sizes and shorter trial durations than traditional designs. To explore the use and potential benefits of Bayesian adaptive clinical trial designs in comparative effectiveness research. Virtual execution of ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) as if it had been done according to a Bayesian adaptive trial design. Comparative effectiveness trial of antihypertensive medications. Patient data sampled from the more than 42 000 patients enrolled in ALLHAT with publicly available data. Number of patients randomly assigned between groups, trial duration, observed numbers of events, and overall trial results and conclusions. The Bayesian adaptive approach and original design yielded similar overall trial conclusions. The Bayesian adaptive trial randomly assigned more patients to the better-performing group and would probably have ended slightly earlier. This virtual trial execution required limited resampling of ALLHAT patients for inclusion in RE-ADAPT (REsearch in ADAptive methods for Pragmatic Trials). Involvement of a data monitoring committee and other trial logistics were not considered. In a comparative effectiveness research trial, Bayesian adaptive trial designs are a feasible approach and potentially generate earlier results and allocate more patients to better-performing groups. National Heart, Lung, and Blood Institute.

Mechanical Validation of an MRI Compatible Stereotactic Neurosurgery Robot in Preparation for Pre-Clinical Trials.

PubMed

Nycz, Christopher J; Gondokaryono, Radian; Carvalho, Paulo; Patel, Nirav; Wartenberg, Marek; Pilitsis, Julie G; Fischer, Gregory S

2017-09-01

The use of magnetic resonance imaging (MRI) for guiding robotic surgical devices has shown great potential for performing precisely targeted and controlled interventions. To fully realize these benefits, devices must work safely within the tight confines of the MRI bore without negatively impacting image quality. Here we expand on previous work exploring MRI guided robots for neural interventions by presenting the mechanical design and assessment of a device for positioning, orienting, and inserting an interstitial ultrasound-based ablation probe. From our previous work we have added a 2 degree of freedom (DOF) needle driver for use with the aforementioned probe, revised the mechanical design to improve strength and function, and performed an evaluation of the mechanism's accuracy and effect on MR image quality. The result of this work is a 7-DOF MRI robot capable of positioning a needle tip and orienting it's axis with accuracy of 1.37 ± 0.06 mm and 0.79° ± 0.41°, inserting it along it's axis with an accuracy of 0.06 ± 0.07 mm , and rotating it about it's axis to an accuracy of 0.77° ± 1.31°. This was accomplished with no significant reduction in SNR caused by the robot's presence in the MRI bore, ≤ 10.3% reduction in SNR from running the robot's motors during a scan, and no visible paramagnetic artifacts.

A pilot single-blind multicentre randomized controlled trial to evaluate the potential benefits of computer-assisted arm rehabilitation gaming technology on the arm function of children with spastic cerebral palsy.

PubMed

Preston, Nick; Weightman, Andrew; Gallagher, Justin; Levesley, Martin; Mon-Williams, Mark; Clarke, Mike; O'Connor, Rory J

2016-10-01

To evaluate the potential benefits of computer-assisted arm rehabilitation gaming technology on arm function of children with spastic cerebral palsy. A single-blind randomized controlled trial design. Power calculations indicated that 58 children would be required to demonstrate a clinically important difference. Intervention was home-based; recruitment took place in regional spasticity clinics. A total of 15 children with cerebral palsy aged five to 12 years were recruited; eight to the device group. Both study groups received 'usual follow-up treatment' following spasticity treatment with botulinum toxin; the intervention group also received a rehabilitation gaming device. ABILHAND-kids and Canadian Occupational Performance Measure were performed by blinded assessors at baseline, six and 12 weeks. An analysis of covariance showed no group differences in mean ABILHAND-kids scores between time points. A non-parametric analysis of variance on Canadian Occupational Performance Measure scores showed a statistically significant improvement across time points (χ 2 (2,15) = 6.778, p = 0.031), but this improvement did not reach minimal clinically important difference. Mean daily device use was seven minutes. Recruitment did not reach target owing to unanticipated staff shortages in clinical services. Feedback from children and their families indicated that the games were not sufficiently engaging to promote sufficient use that was likely to result in functional benefits. This study suggests that computer-assisted arm rehabilitation gaming does not benefit arm function, but a Type II error cannot be ruled out. © The Author(s) 2015.

Practical characteristics of adaptive design in phase 2 and 3 clinical trials.

PubMed

Sato, A; Shimura, M; Gosho, M

2018-04-01

Adaptive design methods are expected to be ethical, reflect real medical practice, increase the likelihood of research and development success and reduce the allocation of patients into ineffective treatment groups by the early termination of clinical trials. However, the comprehensive details regarding which types of clinical trials will include adaptive designs remain unclear. We examined the practical characteristics of adaptive design used in clinical trials. We conducted a literature search of adaptive design clinical trials published from 2012 to 2015 using PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials, with common search terms related to adaptive design. We systematically assessed the types and characteristics of adaptive designs and disease areas employed in the adaptive design trials. Our survey identified 245 adaptive design clinical trials. The number of trials by the publication year increased from 2012 to 2013 and did not greatly change afterwards. The most frequently used adaptive design was group sequential design (n = 222, 90.6%), especially for neoplasm or cardiovascular disease trials. Among the other types of adaptive design, adaptive dose/treatment group selection (n = 21, 8.6%) and adaptive sample-size adjustment (n = 19, 7.8%) were frequently used. The adaptive randomization (n = 8, 3.3%) and adaptive seamless design (n = 6, 2.4%) were less frequent. Adaptive dose/treatment group selection and adaptive sample-size adjustment were frequently used (up to 23%) in "certain infectious and parasitic diseases," "diseases of nervous system," and "mental and behavioural disorders" in comparison with "neoplasms" (<6.6%). For "mental and behavioural disorders," adaptive randomization was used in two trials of eight trials in total (25%). Group sequential design and adaptive sample-size adjustment were used frequently in phase 3 trials or in trials where study phase was not specified, whereas the other types of adaptive designs were used more in phase 2 trials. Approximately 82% (202 of 245 trials) resulted in early termination at the interim analysis. Among the 202 trials, 132 (54% of 245 trials) had fewer randomized patients than initially planned. This result supports the motive to use adaptive design to make study durations shorter and include a smaller number of subjects. We found that adaptive designs have been applied to clinical trials in various therapeutic areas and interventions. The applications were frequently reported in neoplasm or cardiovascular clinical trials. The adaptive dose/treatment group selection and sample-size adjustment are increasingly common, and these adaptations generally follow the Food and Drug Administration's (FDA's) recommendations. © 2017 John Wiley & Sons Ltd.

[Trial of eye drops recognizer for visually disabled persons].

PubMed

Okamoto, Norio; Suzuki, Katsuhiko; Mimura, Osamu

2009-01-01

The development of a device to enable the visually disabled to differentiate eye drops and their dose. The new instrument is composed of a voice generator and a two-dimensional bar-code reader (LS9208). We designed voice outputs for the visually disabled to state when (number of times) and where (right, left, or both) to administer eye drops. We then determined the minimum bar-code size that can be recognized. After attaching bar-codes of the appropriate size to the lateral or bottom surface of the eye drops container, the readability of the bar-codes was compared. The minimum discrimination bar-code size was 6 mm high x 8.5 mm long. Bar-codes on the bottom surface could be more easily recognized than bar-codes on the side. Our newly-developed device using bar-codes enables visually disabled persons to differentiate eye drops and their doses.

Utilization of a New Intracranial Support Catheter as an Intermediate Aspiration Catheter in the Treatment of Acute Ischemic Stroke: Technical Report on Initial Experience.

PubMed

Lozano, J Diego; Massari, Francesco; Howk, Mary C; de Macedo Rodrigues, Katyucia; Brooks, Christopher; Perras, Mary; Rex, David E; Wakhloo, Ajay K; Kühn, Anna Luisa; Puri, Ajit S

2016-05-21

The endovascular management of acute ischemic stroke (AIS) due to emergency large vessel occlusion (ELVO) has become the standard of care after the recent publication of landmark randomized, controlled trials. Mechanical thrombectomy, in addition to intravenous thrombolysis (within 4.5 hours when eligible), is now part of the algorithm of the standard of care when treating AIS in patients with ELVO in the anterior circulation up to six hours after symptom onset. A newly introduced device, the Arc™ intracranial support catheter (Medtronic, Irvine, USA), is specifically designed for the introduction of neurointerventional devices into the cerebral vasculature and facilitates the delivery of microcatheters into smaller, more distal intracranial vessels. This technical report describes the use of the Arc™ intracranial support catheter in the setting of AIS.

Utilization of a New Intracranial Support Catheter as an Intermediate Aspiration Catheter in the Treatment of Acute Ischemic Stroke: Technical Report on Initial Experience

PubMed Central

Lozano, J. Diego; Massari, Francesco; Howk, Mary C; de Macedo Rodrigues, Katyucia; Brooks, Christopher; Perras, Mary; Rex, David E; Wakhloo, Ajay K; Kühn, Anna Luisa

2016-01-01

The endovascular management of acute ischemic stroke (AIS) due to emergency large vessel occlusion (ELVO) has become the standard of care after the recent publication of landmark randomized, controlled trials. Mechanical thrombectomy, in addition to intravenous thrombolysis (within 4.5 hours when eligible), is now part of the algorithm of the standard of care when treating AIS in patients with ELVO in the anterior circulation up to six hours after symptom onset. A newly introduced device, the Arc™ intracranial support catheter (Medtronic, Irvine, USA), is specifically designed for the introduction of neurointerventional devices into the cerebral vasculature and facilitates the delivery of microcatheters into smaller, more distal intracranial vessels. This technical report describes the use of the Arc™ intracranial support catheter in the setting of AIS. PMID:27382525

Oscillating devices for airway clearance in people with cystic fibrosis.

PubMed

Morrison, Lisa; Agnew, Jennifer

2014-07-20

Chest physiotherapy is widely prescribed to assist the clearance of airway secretions in people with cystic fibrosis. Oscillating devices generate intra- or extra-thoracic oscillations orally or external to the chest wall. Internally they create variable resistances within the airways, generating controlled oscillating positive pressure which mobilises mucus. Extra-thoracic oscillations are generated by forces outside the respiratory system, e.g. high frequency chest wall oscillation. To identify whether oscillatory devices, oral or chest wall, are effective for mucociliary clearance and whether they are equivalent or superior to other forms of airway clearance in the successful management of secretions in people with cystic fibrosis. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and hand searches of relevant journals and abstract books of conference proceedings. Latest search of the Cystic Fibrosis Trials Register: 13 January 2014. Randomised controlled studies and controlled clinical studies of oscillating devices compared with any other form of physiotherapy in people with cystic fibrosis. Single-treatment interventions (therapy technique used only once in the comparison) were excluded. Two authors independently applied the inclusion criteria to publications and assessed the quality of the included studies. The searches identified 68 studies with a total of 288 references; 35 studies (total of 1050 participants) met the inclusion criteria. Studies varied in duration from up to one week to one year; 20 of the studies were cross-over in design. The studies also varied in type of intervention and the outcomes measured, furthermore data were not published in sufficient detail in most of these studies, so meta-analysis was limited. Few studies were considered to have a low risk of bias in any domain. It is not possible to blind participants and clinicians to physiotherapy interventions, but 10 studies did blind the outcome assessors.Forced expiratory volume in one second was the most frequently measured outcome. One long-term study (seven months) compared oscillatory devices with either conventional physiotherapy or breathing techniques and found statistically significant differences in some lung function parameters in favour of oscillating devices. One study identified an increase in frequency of exacerbations requiring antibiotics whilst using high frequency chest wall oscillation when compared to positive expiratory pressure. There were some small but significant changes in secondary outcome variables such as sputum volume or weight, but not wholly in favour of oscillating devices. Participant satisfaction was reported in 15 studies but this was not specifically in favour of an oscillating device, as some participants preferred breathing techniques or techniques used prior to the study interventions. The results for the remaining outcome measures were not examined or reported in sufficient detail to provide any high level evidence. There was no clear evidence that oscillation was a more or less effective intervention overall than other forms of physiotherapy; furthermore there was no evidence that one device is superior to another. The findings from one study showing an increase in frequency of exacerbations requiring antibiotics whilst using an oscillating device compared to positive expiratory pressure may have significant resource implications. More adequately-powered long-term randomised controlled trials are necessary and outcomes measured should include frequency of exacerbations, patient preference, adherence to therapy and general satisfaction with treatment. Increased adherence to therapy may then lead to improvements in other parameters, such as exercise tolerance and respiratory function. Additional evidence is needed to evaluate whether oscillating devices combined with other forms of airway clearance is efficacious in people with cystic fibrosis.

Development and feasibility testing of decision support for patients who are candidates for a prophylactic implantable defibrillator: a study protocol for a pilot randomized controlled trial

PubMed Central

2013-01-01

Background Patients, identified to be at risk for but who have never experienced a potentially lethal cardiac arrhythmia, have the option of receiving an implantable cardioverter defibrillator (ICD) as prophylaxis against sudden cardiac death - a primary prevention indication. In Canada, there is no clear framework to support patients’ decision-making for these devices. Decision support, using a decision aid, could moderate treatment-related uncertainty and prepare patients to make well-informed decisions. Patient decision aids provide information on treatment options, risks, and benefits, to help patients clarify their values for outcomes of treatment options. The objectives of this research are: 1) develop a decision aid, 2) evaluate the decision aid, and 3) determine the feasibility of conducting a trial. Methods/design A development panel comprised of the core investigative team, health service researchers, decision science experts, cardiovascular healthcare practitioners, and ICD patient representatives will collaborate to provide input on the content and format of the aid. To generate probabilities to include in the aid, we will synthesize primary prevention ICD evidence. To obtain anonymous input about the facts and content, we will employ a modified Delphi process. To evaluate the draft decision aid will invite ICD patients and their families (n = 30) to rate its acceptability. After we evaluate the aid, to determine the feasibility, we will conduct a feasibility pilot randomized controlled trial (RCT) in new ICD candidates (n = 80). Participants will be randomized to receive a decision aid prior to specialist consultation versus usual care. Results from the pilot RCT will determine the feasibility of research processes; inform sample size calculation, measure decision quality (knowledge, values, decision conflict) and the influence of health related quality of life on decision-making. Discussion Our study seeks to develop a decision aid, for patients offered their first ICD for prophylaxis against sudden cardiac death. This paper outlines the background and methods of a pilot randomized trial which will inform a larger multicenter trial. Ultimately, decision support prior to specialist consultation could enhance the decision-making process between patients, physicians, and families, associated with life-prolonging medical devices like the ICD. Trial registration ClinicalTrials.gov: NCT01876173 PMID:24148851

Assessment of Hydraulic Performance and Biocompatibility of a MagLev Centrifugal Pump System Designed for Pediatric Cardiac or Cardiopulmonary Support

PubMed Central

Dasse, Kurt A.; Gellman, Barry; Kameneva, Marina V.; Woolley, Joshua R.; Johnson, Carl A.; Gempp, Thomas; Marks, John D.; Kent, Stella; Koert, Andrew; Richardson, J. Scott; Franklin, Steve; Snyder, Trevor A.; Wearden, Peter; Wagner, William R.; Gilbert, Richard J.; Borovetz, Harvey S.

2011-01-01

The treatment of children with life-threatening cardiac and cardiopulmonary failure is a large and underappreciated public health concern. We have previously shown that the CentriMag is a magnetically levitated centrifugal pump system, having the utility for treating adults and large children (1,500 utilized worldwide). We present here the Pedi-VAS, a pump system whose design was modified from the CentriMag to meet the physiological requirements of young pediatric and neonatal patients. The PediVAS is comprised of a single-use centrifugal blood pump, reusable motor, and console, and is suitable for right ventricular assist device (RVAD), left ventricular assist device (LVAD), biventricular assist device (BVAD), or extracorporeal membrane oxygenator (ECMO) applications. It is designed to operate without bearings, seals and valves, and without regions of blood stasis, friction, or wear. The PediVAS pump is compatible with the CentriMag hardware, although the priming volume was reduced from 31 to 14 ml, and the port size reduced from 3/8 to ¼ in. For the expected range of pediatric flow (0.3–3.0 L/min), the PediVAS exhibited superior hydraulic efficiency compared with the CentriMag. The PediVAS was evaluated in 14 pediatric animals for up to 30 days, demonstrating acceptable hydraulic function and hemocompatibility. The current results substantiate the performance and biocompatibility of the PediVAS cardiac assist system and are likely to support initiation of a US clinical trial in the future. PMID:18043164

Determining Desirable Cursor Control Device Characteristics for NASA Exploration Missions

NASA Technical Reports Server (NTRS)

Sandor, Aniko; Holden, Kritina

2007-01-01

The Crew Exploration Vehicle (CEV) that will travel to the moon and Mars, and all future Exploration vehicles and habitats will be highly computerized, necessitating an accurate method of interaction with the computers. The design of a cursor control device will have to take into consideration g-forces, vibration, gloved operations, and the specific types of tasks to be performed. The study described here is being undertaken to begin identifying characteristics of cursor control devices that will work well for the unique Exploration mission environments. The objective of the study is not to identify a particular device, but to begin identifying design characteristics that are usable and desirable for space missions. Most cursor control devices have strengths and weaknesses; they are more appropriate for some tasks and less suitable for others. The purpose of this study is to collect some initial usability data on a large number of commercially available and proprietary cursor control devices. A software test battery was developed for this purpose. Once data has been collected using these low-level, basic point/click/drag tasks, higher fidelity, scenario-driven evaluations will be conducted with a reduced set of devices. The standard tasks used for testing cursor control devices are based on a model of human movement known as Fitts law. Fitts law predicts that the time to acquire a target is logarithmically related to the distance over the target size. To gather data for analysis with this law, fundamental, low-level tasks are used such as dragging or pointing at various targets of different sizes from various distances. The first four core tasks for the study were based on the ISO 9241-9:(2000) document from the International Organization for Standardization that contains the requirements for non-keyboard input devices. These include two pointing tasks, one dragging and one tracking task. The fifth task from ISO 9241-9, the circular tracking task was not used because it is a movement that is not applicable to most of the applications used on aviation displays. Additionally, we opted to add a multi-size and multi-distance pointing task, and two ecologically more valid tasks which included text selection, and interaction with drop down menus, sliders, and checkboxes. The Visual Basic test battery tracks the task and trial numbers, measures the pointing, tracking or dragging time, as well as the number and types of errors. The testing session includes a practice set for each input device, then the randomized 7 tasks, and finally a questionnaire about the device. This is repeated for all the devices tested within a session. The experiment is a within-subjects design, with participants returning for multiple sessions to test additional devices. The input devices will be compared based on objective performance data from the tasks, as well as subjective feedback and ratings on the questionnaire.

Determining the feasibility of objective adherence measurement with blister packaging smart technology.

PubMed

van Onzenoort, Hein A; Neef, Cees; Verberk, Willem W; van Iperen, H Peter; de Leeuw, Peter W; van der Kuy, Paul-Hugo M

2012-05-15

The results of a feasibility study of blister-pack smart technology for monitoring medication adherence are reported. Research in the area of objective therapy compliance measurement has led to the development of microprocessor-driven systems that record the time a unit dose is removed from blister packaging. One device under development is the Smart Blister-a label imprinted with event-detection circuitry that can be affixed to standard commercial blister cards. In the first trial of the device in actual clinical practice, 115 community-dwelling Dutch patients receiving valsartan maintenance therapy (160 mg once daily) were given 14-day blister packages equipped with the Smart Blister. On the return of empty blister cards to the 20 participating community pharmacies, the stored information was scanned and downloaded for data analysis and patient counseling purposes. A total of 245 Smart Blister-equipped packages were used by valsartan recipients during the eight-month study. The device was largely effective in recording patient and blister-card identification data and other desired information. However, in 17% of cases, the Smart Blister system registered multiple tablet-removal events at the same time, presumably indicating unintentional breakage of nearby conductive circuits and the need for design refinements. The Smart Blister-equipped medication cards were generally well received by patients and pharmacies. An evaluation of the functionality and robustness of the Smart Blister in a real-world clinical practice situation yielded some promising results, but the findings also indicated a need for design refinements and additional performance testing of the device.

Current UK practice of pediatric supraglottic airway devices - a survey of members of the Association of Paediatric Anaesthetists of Great Britain and Ireland.

PubMed

Bradley, Anthony E D; White, Michelle C; Engelhardt, Thomas; Bayley, Guy; Beringer, Richard M

2013-11-01

Over half of general anesthetics in the UK involve supraglottic airway devices (SADs). The National Audit Project 4 undertaken by the Royal College of Anaesthetists demonstrated that aspiration was the most frequent complication relating to SAD use. SADs designed to reduce this risk (second-generation devices) are increasingly recommended in both adults and children. As well as routine use, SADs are recommended for use in cases of 'difficult airway'. This survey assessed current usage of SADs in routine practice and difficult airways. Sixteen questions, approved by the Association of Paediatric Anaesthetists of Great Britain and Ireland (APAGBI) survey committee, were distributed to all its members. Two hundred and forty-four members responded. Eighty-eight percent preferentially use first-generation rather than second-generation devices. The most important design feature was the availability of a complete range of sizes (84%). Seventy-seven percent felt that randomized controlled trials assessing SAD safety in children are needed. In cases of failed intubation, classically shaped SADs are preferred (79%). Three percent of responders intubate via an SAD routinely. Eighteen percent have employed this technique in an emergency. Thirty-six percent of responders have found an SAD to function poorly. Pediatric anesthesiologists appear slow to embrace second-generation SADs. The role of SADs in the management of difficult airways is widely accepted. Research currently has little influence over the choice of which SAD to use, which is more likely determined by personal choice and departmental preference. There is a risk that some SADs are unsafe. © 2013 John Wiley & Sons Ltd.

What is the Optimal Strategy for Adaptive Servo-Ventilation Therapy?

PubMed

Imamura, Teruhiko; Kinugawa, Koichiro

2018-05-23

Clinical advantages in the adaptive servo-ventilation (ASV) therapy have been reported in selected heart failure patients with/without sleep-disorder breathing, whereas multicenter randomized control trials could not demonstrate such advantages. Considering this discrepancy, optimal patient selection and device setting may be a key for the successful ASV therapy. Hemodynamic and echocardiographic parameters indicating pulmonary congestion such as elevated pulmonary capillary wedge pressure were reported as predictors of good response to ASV therapy. Recently, parameters indicating right ventricular dysfunction also have been reported as good predictors. Optimal device setting with appropriate pressure setting during appropriate time may also be a key. Large-scale prospective trial with optimal patient selection and optimal device setting is warranted.

Technology evaluation: VEGF165 gene therapy, Valentis Inc.

PubMed

Morse, M A

2001-02-01

Valentis Inc, formerly GeneMedicine, is developing a vascular endothelial growth factor (VEGF165) non-viral gene therapy using its proprietary PINC polymer for plasmid condensation. Two physician-initiated phase II angioplasty trials are ongoing, one for treating peripheral vascular disease and one for treating coronary artery disease [281714], [347153]. In February 2000, the trials were expected to be completed in the fourth quarter of 2000 [356225]; however, in October 2000, it was reported that the trial for peripheral vascular disease would be completed in the first quarter of 2001 [385232]. In March 2000, Valentis initiated a trial incorporating Valentis's DOTMA-based cationic lipid gene delivery system and the VEGF165 gene with Eurogene's local collar-reservoir delivery device. The trial is designed to demonstrate that the VEGF165 gene, delivered locally to the outside surface of a blood vessel, will transfect and express in the smooth muscle cells of the vessel wall [360683]. In March 1999, Valentis was awarded with a Phase II SBIR grant of $686,260. The aim of grant was to advance the development of non-viral gene therapies for ischemia. Specifically, Valentis intended to select an optimal promoter to be used with the VEGF expression plasmid. Valentis also intended to evaluate the gene therapy system in a rabbit ischemia model and complete the necessary preclinical studies for submission of an IND [318137].

A Targeted Infection Prevention Intervention in Nursing Home Residents With Indwelling Devices

PubMed Central

Mody, Lona; Krein, Sarah L.; Saint, Sanjay K.; Min, Lillian C.; Montoya, Ana; Lansing, Bonnie; McNamara, Sara E.; Symons, Kathleen; Fisch, Jay; Koo, Evonne; Rye, Ruth Anne; Galecki, Andrzej; Kabeto, Mohammed U.; Fitzgerald, James T.; Olmsted, Russell N.; Kauffman, Carol A.; Bradley, Suzanne F.

2015-01-01

IMPORTANCE Indwelling devices (eg, urinary catheters and feeding tubes) are often used in nursing homes (NHs). Inadequate care of residents with these devices contributes to high rates of multidrug-resistant organisms (MDROs) and device-related infections in NHs. OBJECTIVE To test whether a multimodal targeted infection program (TIP) reduces the prevalence of MDROs and incident device-related infections. DESIGN, SETTING, AND PARTICIPANTS Randomized clinical trial at 12 community-based NHs from May 2010 to April 2013. Participants were high-risk NH residents with urinary catheters, feeding tubes, or both. INTERVENTIONS Multimodal, including preemptive barrier precautions, active surveillance for MDROs and infections, and NH staff education. MAIN OUTCOMES AND MEASURES The primary outcome was the prevalence density rate of MDROs, defined as the total number of MDROs isolated per visit averaged over the duration of a resident's participation. Secondary outcomes included new MDRO acquisitions and new clinically defined device-associated infections. Data were analyzed using a mixed-effects multilevel Poisson regression model (primary outcome) and a Cox proportional hazards model (secondary outcome), adjusting for facility-level clustering and resident-level variables. RESULTS In total, 418 NH residents with indwelling devices were enrolled, with 34 174 device-days and 6557 anatomic sites sampled. Intervention NHs had a decrease in the overall MDRO prevalence density (rate ratio, 0.77; 95% CI, 0.62–0.94). The rate of new methicillin-resistant Staphylococcus aureus acquisitions was lower in the intervention group than in the control group (rate ratio, 0.78; 95% CI, 0.64–0.96). Hazard ratios for the first and all (including recurrent) clinically defined catheter-associated urinary tract infections were 0.54 (95% CI, 0.30–0.97) and 0.69 (95% CI, 0.49–0.99), respectively, in the intervention group and the control group. There were no reductions in new vancomycin-resistant enterococci or resistant gram-negative bacilli acquisitions or in new feeding tube–associated pneumonias or skin and soft-tissue infections. CONCLUSIONS AND RELEVANCE Our multimodal TIP intervention reduced the overall MDRO prevalence density, new methicillin-resistant S aureus acquisitions, and clinically defined catheter-associated urinary tract infection rates in high-risk NH residents with indwelling devices. Further studies are needed to evaluate the cost-effectiveness of this approach as well as its effects on the reduction of MDRO transmission to other residents, on the environment, and on referring hospitals. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01062841 PMID:25775048

Controlling Motion Sickness and Spatial Disorientation and Enhancing Vestibular Rehabilitation with a User-Worn See-Through Display

PubMed Central

Krueger, Wesley W.O.

2010-01-01

Objectives/Hypotheses An eyewear mounted visual display (“User-worn see-through display”) projecting an artificial horizon aligned with the user's head and body position in space can prevent or lessen motion sickness in susceptible individuals when in a motion provocative environment as well as aid patients undergoing vestibular rehabilitation. In this project, a wearable display device, including software technology and hardware, was developed and a phase I feasibility study and phase II clinical trial for safety and efficacy were performed. Study Design Both phase I and phase II were prospective studies funded by the NIH. The phase II study used repeated measures for motion intolerant subjects and a randomized control group (display device/no display device) pre-post test design for patients in vestibular rehabilitation. Methods Following technology and display device development, 75 patients were evaluated by test and rating scales in the phase II study; 25 subjects with motion intolerance used the technology in the display device in provocative environments and completed subjective rating scales while 50 patients were evaluated before and after vestibular rehabilitation (25 using the display device and 25 in a control group) using established test measures. Results All patients with motion intolerance rated the technology as helpful for nine symptoms assessed, and 96% rated the display device as simple and easy to use. Duration of symptoms significantly decreased with use of the technology displayed. In patients undergoing vestibular rehabilitation, there were no significant differences in amount of change from pre- to post-therapy on objective balance tests between display device users and controls. However, those using the technology required significantly fewer rehabilitation sessions to achieve those outcomes than the control group. Conclusions A user-worn see-through display, utilizing a visual fixation target coupled with a stable artificial horizon and aligned with user movement, has demonstrated substantial benefit for individuals susceptible to motion intolerance and spatial disorientation and those undergoing vestibular rehabilitation. The technology developed has applications in any environment where motion sensitivity affects human performance. PMID:21181963

Rational In Silico Design of an Organic Semiconductor with Improved Electron Mobility.

PubMed

Friederich, Pascal; Gómez, Verónica; Sprau, Christian; Meded, Velimir; Strunk, Timo; Jenne, Michael; Magri, Andrea; Symalla, Franz; Colsmann, Alexander; Ruben, Mario; Wenzel, Wolfgang

2017-11-01

Organic semiconductors find a wide range of applications, such as in organic light emitting diodes, organic solar cells, and organic field effect transistors. One of their most striking disadvantages in comparison to crystalline inorganic semiconductors is their low charge-carrier mobility, which manifests itself in major device constraints such as limited photoactive layer thicknesses. Trial-and-error attempts to increase charge-carrier mobility are impeded by the complex interplay of the molecular and electronic structure of the material with its morphology. Here, the viability of a multiscale simulation approach to rationally design materials with improved electron mobility is demonstrated. Starting from one of the most widely used electron conducting materials (Alq 3 ), novel organic semiconductors with tailored electronic properties are designed for which an improvement of the electron mobility by three orders of magnitude is predicted and experimentally confirmed. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Adaptive design clinical trials: a review of the literature and ClinicalTrials.gov

PubMed Central

Bothwell, Laura E; Avorn, Jerry; Khan, Nazleen F; Kesselheim, Aaron S

2018-01-01

Objectives This review investigates characteristics of implemented adaptive design clinical trials and provides examples of regulatory experience with such trials. Design Review of adaptive design clinical trials in EMBASE, PubMed, Cochrane Registry of Controlled Clinical Trials, Web of Science and ClinicalTrials.gov. Phase I and seamless Phase I/II trials were excluded. Variables extracted from trials included basic study characteristics, adaptive design features, size and use of independent data monitoring committees (DMCs) and blinded interim analyses. We also examined use of the adaptive trials in new drug submissions to the Food and Drug Administration (FDA) and European Medicines Agency (EMA) and recorded regulators’ experiences with adaptive designs. Results 142 studies met inclusion criteria. There has been a recent growth in publicly reported use of adaptive designs among researchers around the world. The most frequently appearing types of adaptations were seamless Phase II/III (57%), group sequential (21%), biomarker adaptive (20%), and adaptive dose-finding designs (16%). About one-third (32%) of trials reported an independent DMC, while 6% reported blinded interim analysis. We found that 9% of adaptive trials were used for FDA product approval consideration, and 12% were used for EMA product approval consideration. International regulators had mixed experiences with adaptive trials. Many product applications with adaptive trials had extensive correspondence between drug sponsors and regulators regarding the adaptive designs, in some cases with regulators requiring revisions or alterations to research designs. Conclusions Wider use of adaptive designs will necessitate new drug application sponsors to engage with regulatory scientists during planning and conduct of the trials. Investigators need to more consistently report protections intended to preserve confidentiality and minimise potential operational bias during interim analysis. PMID:29440155

78 FR 58318 - Clinical Trial Design for Intravenous Fat Emulsion Products; Public Workshop

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-23

...] Clinical Trial Design for Intravenous Fat Emulsion Products; Public Workshop AGENCY: Food and Drug... announcing a 1-day public workshop entitled ``Clinical Trial Design for Intravenous Fat Emulsion Products.'' This workshop will provide a forum to discuss trial design of clinical trials intended to support...

Machines that go "ping" may improve balance but may not improve mobility or reduce risk of falls: a systematic review.

PubMed

Dennett, Amy M; Taylor, Nicholas F

2015-01-01

To determine the effectiveness of computer-based electronic devices that provide feedback in improving mobility and balance and reducing falls. Randomized controlled trials were searched from the earliest available date to August 2013. Standardized mean differences were used to complete meta-analyses, with statistical heterogeneity being described with the I-squared statistic. The GRADE approach was used to summarize the level of evidence for each completed meta-analysis. Risk of bias for individual trials was assessed with the (Physiotherapy Evidence Database) PEDro scale. Thirty trials were included. There was high-quality evidence that computerized devices can improve dynamic balance in people with a neurological condition compared with no therapy. There was low-to-moderate-quality evidence that computerized devices have no significant effect on mobility, falls efficacy and falls risk in community-dwelling older adults, and people with a neurological condition compared with physiotherapy. There is high-quality evidence that computerized devices that provide feedback may be useful in improving balance in people with neurological conditions compared with no therapy, but there is a lack of evidence supporting more meaningful changes in mobility and falls risk.

A systematic review of microwave-based therapy for axillary hyperhidrosis.

PubMed

Hsu, Tzu-Herng; Chen, Yu-Tsung; Tu, Yu-Kang; Li, Chien-Nien

2017-10-01

To systematically analyse the literature on the use of the microwave-based device for subdermal thermolysis of the axilla and its efficacy for the treatment of axillary hyperhidrosis. A systematic review was conducted using PubMed, Embase, SCOPUS and Cochrane databases on 2 June 2016. The inclusion criteria including: (1) studies with human subjects, (2) full-text articles published in English, (3) a microwave-based device used to treat axillary hyperhidrosis and (4) trials that precisely evaluated axillary hyperhidrosis. Exclusion criteria were the following: (1) studies that did not fit the inclusion criteria mentioned above and (2) case reports and reviews. We reviewed five clinical trials and 189 patients, all of which were published between 2012 and 2016. There was one randomized controlled trial, one retrospective study and the remainder were prospective studies. Although all of the studies were conducted with a small sample size, the results indicated that microwave-based device treatment of axillary hyperhidrosis had long-term efficacy with mild adverse effects. In addition, most patients were satisfied with the outcomes in these studies. Microwave-based device treatment may be an effective alternative treatment for axillary hyperhidrosis. However, further investigation is necessary to determine its long-term efficacy and safety.

Informed consent for clinical trials of deep brain stimulation in psychiatric disease: challenges and implications for trial design.

PubMed

Lipsman, Nir; Giacobbe, Peter; Bernstein, Mark; Lozano, Andres M

2012-02-01

Advances in neuromodulation and an improved understanding of the anatomy and circuitry of psychopathology have led to a resurgence of interest in surgery for psychiatric disease. Clinical trials exploring deep brain stimulation (DBS), a focally targeted, adjustable and reversible form of neurosurgery, are being developed to address the use of this technology in highly selected patient populations. Psychiatric patients deemed eligible for surgical intervention, such as DBS, typically meet stringent inclusion criteria, including demonstrated severity, chronicity and a failure of conventional therapy. Although a humanitarian device exemption by the US Food and Drug Administration exists for its use in obsessive-compulsive disorder, DBS remains a largely experimental treatment in the psychiatric context, with its use currently limited to clinical trials and investigative studies. The combination of a patient population at the limits of conventional therapy and a novel technology in a new indication poses interesting challenges to the informed consent process as it relates to clinical trial enrollment. These challenges can be divided into those that relate to the patient, their disease and the technology, with each illustrating how traditional conceptualisations of research consent may be inadequate in the surgical psychiatry context. With specific reference to risk analysis, patient autonomy, voluntariness and the duty of the clinician-researcher, this paper will discuss the unique challenges that clinical trials of surgery for refractory psychiatric disease present to the consent process. Recommendations are also made for an ethical approach to clinical trial consent acquisition in this unique patient population.

Stroke Treatment Academic Industry Roundtable Recommendations for Individual Data Pooling Analyses in Stroke.

PubMed

Lees, Kennedy R; Khatri, Pooja

2016-08-01

Pooled analysis of individual patient data from stroke trials can deliver more precise estimates of treatment effect, enhance power to examine prespecified subgroups, and facilitate exploration of treatment-modifying influences. Analysis plans should be declared, and preferably published, before trial results are known. For pooling trials that used diverse analytic approaches, an ordinal analysis is favored, with justification for considering deaths and severe disability jointly. Because trial pooling is an incremental process, analyses should follow a sequential approach, with statistical adjustment for iterations. Updated analyses should be published when revised conclusions have a clinical implication. However, caution is recommended in declaring pooled findings that may prejudice ongoing trials, unless clinical implications are compelling. All contributing trial teams should contribute to leadership, data verification, and authorship of pooled analyses. Development work is needed to enable reliable inferences to be drawn about individual drug or device effects that contribute to a pooled analysis, versus a class effect, if the treatment strategy combines ≥2 such drugs or devices. Despite the practical challenges, pooled analyses are powerful and essential tools in interpreting clinical trial findings and advancing clinical care. © 2016 American Heart Association, Inc.

The evaluation of off-loading using a new removable oRTHOsis in DIABetic foot (ORTHODIAB) randomized controlled trial: study design and rational.

PubMed

Mohammedi, Kamel; Potier, Louis; François, Maud; Dardari, Dured; Feron, Marilyne; Nobecourt-Dupuy, Estelle; Dolz, Manuel; Ducloux, Roxane; Chibani, Abdelkader; Eveno, Dominique-François; Crea Avila, Teresa; Sultan, Ariane; Baillet-Blanco, Laurence; Rigalleau, Vincent; Velho, Gilberto; Tubach, Florence; Roussel, Ronan; Dupré, Jean-Claude; Malgrange, Dominique; Marre, Michel

2016-01-01

Off-loading is essential for diabetic foot management, but remains understudied. The evaluation of Off-loading using a new removable oRTHOsis in DIABetic foot (ORTHODIAB) trial aims to evaluate the efficacy of a new removable device "Orthèse Diabète" in the healing of diabetic foot. ORTHODIAB is a French multi-centre randomized, open label trial, with a blinded end points evaluation by an adjudication committee according to the Prospective Randomized Open Blinded End-point. Main endpoints are adjudicated based on the analysis of diabetic foot photographs. Orthèse Diabète is a new removable off-loading orthosis (PROTEOR, France) allowing innovative functions including real-time evaluation of off-loading and estimation of patients' adherence. Diabetic patients with neuropathic plantar ulcer or amputation wounds (toes or transmetatarsal) are assigned to one of 2 parallel-groups: Orthèse Diabète or control group (any removable device) according to a central computer-based randomization. Study visits are scheduled for 6 months (days D7 and D14, and months M1, M2, M3, and M6). The primary endpoint is the proportion of patients whose principal ulcer is healed at M3. Secondary endpoints are: the proportion of patients whose principal ulcer is healed at M1, M2 and M6; the proportion of patients whose initial ulcers are all healed at M1, M2, M3, and M6; principal ulcer area reduction; time-related ulcer-free survival; development of new ulcers; new lower-extremity amputation; infectious complications; off-loading adherence; and patient satisfaction. The study protocol was approved by the French National Agency for Medicines and Health Products Safety, and by the ethics committee of Saint-Louis Hospital (Paris). Comprehensive study information including a Patient Information Sheet has been provided to each patient who must give written informed consent before enrolment. Monitoring, data management, and statistical analyses are providing by UMANIS Life Science (Paris), independently to the sponsor. Since 27/10/2013, 13 centres have agreed to participate in this study, 117 participants were included, and 70 have achieved the study schedules. The study completion is expected for the end of 2016, and the main results will be published in 2017. ORTHODIAB trial evaluates an innovating removable off-loading device, seeking to improve diabetic foot healing (ClinicalTrials.gov identifier: NCT01956162).

High-Fidelity 3D-Nanoprinting via Focused Electron Beams: Computer-Aided Design (3BID)

DOE PAGES

Fowlkes, Jason D.; Winkler, Robert; Lewis, Brett B.; ...

2018-02-14

Currently, there are few techniques that allow true 3D-printing on the nanoscale. The most promising candidate to fill this void is focused electron-beam-induced deposition (FEBID), a resist-free, nanofabrication compatible, direct-write method. The basic working principles of a computer-aided design (CAD) program (3BID) enabling 3D-FEBID is presented and simultaneously released for download. The 3BID capability significantly expands the currently limited toolbox for 3D-nanoprinting, providing access to geometries for optoelectronic, plasmonic, and nanomagnetic applications that were previously unattainable due to the lack of a suitable method for synthesis. In conclusion, the CAD approach supplants trial and error toward more precise/accurate FEBID requiredmore » for real applications/device prototyping.« less

High-Fidelity 3D-Nanoprinting via Focused Electron Beams: Computer-Aided Design (3BID)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fowlkes, Jason D.; Winkler, Robert; Lewis, Brett B.

Currently, there are few techniques that allow true 3D-printing on the nanoscale. The most promising candidate to fill this void is focused electron-beam-induced deposition (FEBID), a resist-free, nanofabrication compatible, direct-write method. The basic working principles of a computer-aided design (CAD) program (3BID) enabling 3D-FEBID is presented and simultaneously released for download. The 3BID capability significantly expands the currently limited toolbox for 3D-nanoprinting, providing access to geometries for optoelectronic, plasmonic, and nanomagnetic applications that were previously unattainable due to the lack of a suitable method for synthesis. In conclusion, the CAD approach supplants trial and error toward more precise/accurate FEBID requiredmore » for real applications/device prototyping.« less

Structuring Communication Relationships for Interprofessional Teamwork (SCRIPT): a cluster randomized controlled trial.

PubMed

Zwarenstein, Merrick; Reeves, Scott; Russell, Ann; Kenaszchuk, Chris; Conn, Lesley Gotlib; Miller, Karen-Lee; Lingard, Lorelei; Thorpe, Kevin E

2007-09-18

Despite a burgeoning interest in using interprofessional approaches to promote effective collaboration in health care, systematic reviews find scant evidence of benefit. This protocol describes the first cluster randomized controlled trial (RCT) to design and evaluate an intervention intended to improve interprofessional collaborative communication and patient-centred care. The objective is to evaluate the effects of a four-component, hospital-based staff communication protocol designed to promote collaborative communication between healthcare professionals and enhance patient-centred care. The study is a multi-centre mixed-methods cluster randomized controlled trial involving twenty clinical teaching teams (CTTs) in general internal medicine (GIM) divisions of five Toronto tertiary-care hospitals. CTTs will be randomly assigned either to receive an intervention designed to improve interprofessional collaborative communication, or to continue usual communication practices. Non-participant naturalistic observation, shadowing, and semi-structured, qualitative interviews were conducted to explore existing patterns of interprofessional collaboration in the CTTs, and to support intervention development. Interviews and shadowing will continue during intervention delivery in order to document interactions between the intervention settings and adopters, and changes in interprofessional communication. The primary outcome is the rate of unplanned hospital readmission. Secondary outcomes are length of stay (LOS); adherence to evidence-based prescription drug therapy; patients' satisfaction with care; self-report surveys of CTT staff perceptions of interprofessional collaboration; and frequency of calls to paging devices. Outcomes will be compared on an intention-to-treat basis using adjustment methods appropriate for data from a cluster randomized design. Pre-intervention qualitative analysis revealed that a substantial amount of interprofessional interaction lacks key core elements of collaborative communication such as self-introduction, description of professional role, and solicitation of other professional perspectives. Incorporating these findings, a four-component intervention was designed with a goal of creating a culture of communication in which the fundamentals of collaboration become a routine part of interprofessional interactions during unstructured work periods on GIM wards. Registered with National Institutes of Health as NCT00466297.

PediaFlow™ Maglev Ventricular Assist Device: A Prescriptive Design Approach

PubMed Central

Antaki, James F.; Ricci, Michael R.; Verkaik, Josiah E.; Snyder, Shaun T.; Maul, Timothy M.; Kim, Jeongho; Paden, Dave B.; Kameneva, Marina V.; Paden, Bradley E.; Wearden, Peter D.; Borovetz, Harvey S.

2010-01-01

This report describes a multi-disciplinary program to develop a pediatric blood pump, motivated by the critical need to treat infants and young children with congenital and acquired heart diseases. The unique challenges of this patient population require a device with exceptional biocompatibility, miniaturized for implantation up to 6 months. This program implemented a collaborative, prescriptive design process, whereby mathematical models of the governing physics were coupled with numerical optimization to achieve a favorable compromise among several competing design objectives. Computational simulations of fluid dynamics, electromagnetics, and rotordynamics were performed in two stages: first using reduced-order formulations to permit rapid optimization of the key design parameters; followed by rigorous CFD and FEA simulations for calibration, validation, and detailed optimization. Over 20 design configurations were initially considered, leading to three pump topologies, judged on the basis of a multi-component analysis including criteria for anatomic fit, performance, biocompatibility, reliability, and manufacturability. This led to fabrication of a mixed-flow magnetically levitated pump, the PF3, having a displaced volume of 16.6 cc, approximating the size of a AA battery and producing a flow capacity of 0.3–1.5 L/min. Initial in vivo evaluation demonstrated excellent hemocompatibility after 72 days of implantation in an ovine. In summary, combination of prescriptive and heuristic design principles have proven effective in developing a miniature magnetically levitated blood pump with excellent performance and biocompatibility, suitable for integration into chronic circulatory support system for infants and young children; aiming for a clinical trial within 3 years. PMID:20544002

Pain control in orthodontics using a micropulse vibration device: A randomized clinical trial.

PubMed

Lobre, Wendy D; Callegari, Brent J; Gardner, Gary; Marsh, Curtis M; Bush, Anneke C; Dunn, William J

2016-07-01

To investigate the relationship between a micropulse vibration device and pain perception during orthodontic treatment. This study was a parallel group, randomized clinical trial. A total of 58 patients meeting eligibility criteria were assigned using block allocation to one of two groups: an experimental group using the vibration device or a control group (n  =  29 for each group). Patients used the device for 20 minutes daily. Patients rated pain intensity on a visual analog scale at appropriate intervals during the weeks after the separator or archwire appointment. Data were analyzed using repeated measures analysis of variance at α  =  .05. During the 4-month test period, significant differences between the micropulse vibration device group and the control group for overall pain (P  =  .002) and biting pain (P  =  .003) were identified. The authors observed that perceived pain was highest at the beginning of the month, following archwire adjustment. The micropulse vibration device significantly lowered the pain scores for overall pain and biting pain during the 4-month study period.

The life cycles of six multi-center adaptive clinical trials focused on neurological emergencies developed for the Advancing Regulatory Science initiative of the National Institutes of Health and US Food and Drug Administration: Case studies from the Adaptive Designs Accelerating Promising Treatments Into Trials Project

PubMed Central

Guetterman, Timothy C; Fetters, Michael D; Mawocha, Samkeliso; Legocki, Laurie J; Barsan, William G; Lewis, Roger J; Berry, Donald A; Meurer, William J

2017-01-01

Objectives: Clinical trials are complicated, expensive, time-consuming, and frequently do not lead to discoveries that improve the health of patients with disease. Adaptive clinical trials have emerged as a methodology to provide more flexibility in design elements to better answer scientific questions regarding whether new treatments are efficacious. Limited observational data exist that describe the complex process of designing adaptive clinical trials. To address these issues, the Adaptive Designs Accelerating Promising Treatments Into Trials project developed six, tailored, flexible, adaptive, phase-III clinical trials for neurological emergencies, and investigators prospectively monitored and observed the processes. The objective of this work is to describe the adaptive design development process, the final design, and the current status of the adaptive trial designs that were developed. Methods: To observe and reflect upon the trial development process, we employed a rich, mixed methods evaluation that combined quantitative data from visual analog scale to assess attitudes about adaptive trials, along with in-depth qualitative data about the development process gathered from observations. Results: The Adaptive Designs Accelerating Promising Treatments Into Trials team developed six adaptive clinical trial designs. Across the six designs, 53 attitude surveys were completed at baseline and after the trial planning process completed. Compared to baseline, the participants believed significantly more strongly that the adaptive designs would be accepted by National Institutes of Health review panels and non-researcher clinicians. In addition, after the trial planning process, the participants more strongly believed that the adaptive design would meet the scientific and medical goals of the studies. Conclusion: Introducing the adaptive design at early conceptualization proved critical to successful adoption and implementation of that trial. Involving key stakeholders from several scientific domains early in the process appears to be associated with improved attitudes towards adaptive designs over the life cycle of clinical trial development. PMID:29085638

Reinventing clinical trials: a review of innovative biomarker trial designs in cancer therapies.

PubMed

Lin, Ja-An; He, Pei

2015-06-01

Recently, new clinical trial designs involving biomarkers have been studied and proposed in cancer clinical research, in the hope of incorporating the rapid growing basic research into clinical practices. Journal articles related to various biomarkers and their role in cancer clinical trial, articles and books about statistical issues in trial design, and regulatory website, documents, and guidance for submission of targeted cancer therapies. The drug development process involves four phases. The confirmatory Phase III is essential in regulatory approval of a special treatment. Regulatory agency has restrictions on confirmatory trials 'using adaptive designs'. No rule of thumb to pick the most appropriate design for biomarker-related trials. Statistical issues to solve in new designs. Regulatory acceptance of the 'newly proposed trial designs'. Biomarker-related trial designs that can resolve the statistical issues and satisfy the regulatory requirement. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

A Miniaturized, Programmable Deep-Brain Stimulator for Group-Housing and Water Maze Use

PubMed Central

Pinnell, Richard C.; Pereira de Vasconcelos, Anne; Cassel, Jean C.; Hofmann, Ulrich G.

2018-01-01

Pre-clinical deep-brain stimulation (DBS) research has observed a growing interest in the use of portable stimulation devices that can be carried by animals. Not only can such devices overcome many issues inherent with a cable tether, such as twisting or snagging, they can also be utilized in a greater variety of arenas, including enclosed or large mazes. However, these devices are not inherently designed for water-maze environments, and their use has been restricted to individually-housed rats in order to avoid damage from various social activities such as grooming, playing, or fighting. By taking advantage of 3D-printing techniques, this study demonstrates an ultra-small portable stimulator with an environmentally-protective device housing, that is suitable for both social-housing and water-maze environments. The miniature device offers 2 channels of charge-balanced biphasic pulses with a high compliance voltage (12 V), a magnetic switch, and a diverse range of programmable stimulus parameters and pulse modes. The device's capabilities have been verified in both chronic pair-housing and water-maze experiments that asses the effects of nucleus reuniens DBS. Theta-burst stimulation delivered during a reference-memory water-maze task (but not before) had induced performance deficits during both the acquisition and probe trials of a reference memory task. The results highlight a successful application of 3D-printing for expanding on the range of measurement modalities capable in DBS research. PMID:29706862

Elimination of laparoscopic lens fogging using directional flow of CO2.

PubMed

Calhoun, John Teague; Redan, Jay A

2014-01-01

Surgeons constantly struggle with the formation of condensation on the lens of a laparoscope, which prolongs procedures and reduces visibility of the abdominal cavity. The goal of this project was to build a device that would direct a flow of carbon dioxide (CO2) into an open chamber surrounding the lens of a laparoscope, acting to keep moisture away from the lens and eliminate condensation. The device isolates the lens of the laparoscope from the humid environment of the intraperitoneal cavity by creating a microenvironment of dry CO2. This was accomplished by building a communicating sleeve that created an open chamber around the distal 2 to 3 cm of the scope. Into this cavity, dry cool CO2 was pumped in from an insufflator so that the path of the gas would surround the lens of the scope and escape through a single outlet location through which the scope views the intraperitoneal cavity. This chamber is proposed to isolate the lens with a high percentage of dry CO2 and low humidity. The device was tested in 7 different adverse conditions that were meant to challenge the ability of the device to maintain the viewing field with no perceptible obstruction. In all of the conditions tested, 25 trials total, the device successfully prevented and/or eliminated laparoscopic lens fogging. The device designed for this project points to the potential of a simple and effective mechanical method for eliminating laparoscopic lens fogging.

Validity and reliability of the Ergomopro powermeter.

PubMed

Kirkland, A; Coleman, D; Wiles, J D; Hopker, J

2008-11-01

The aim of this investigation was to assess the validity and reliability of the Ergomopro powermeter. Nine participants completed trials on a Monark ergometer fitted with Ergomopro and SRM powermeters simultaneously recording power output. Each participant completed multiple trials at power outputs ranging from 50 to 450 W. The work stages recorded were 60 s in duration and were repeated three times. Participants also completed a single trial on a cycle ergometer designed to assess bilateral contributions to work output (Lode Excaliber Sport PFM). The power output during the trials was significantly different between all three systems, (p < 0.01) 231.2 +/- 114.2 W, 233.0 +/- 112.4 W, 227.8 +/- 108.8 W for the Monark, SRM and Ergomopro system, respectively. When the bilateral contributions were factored into the analysis, there were no significant differences between the powermeters (p = 0.58). The reliability of the Ergomopro system (CV%) was 2.31 % (95 % CI 2.13 - 2.52 %) compared to 1.59 % (95 % CI 1.47 to 1.74 %) for the Monark, and 1.37 % (95 % CI 1.26 - 1.50 %) for the SRM powermeter. These results indicate that the Ergomopro system has acceptable accuracy under these conditions. However, based on the reliability data, the increased variability of the Ergomopro system and bilateral balance issues have to be considered when using this device.

Differentiating closed-loop cortical intention from rest: building an asynchronous electrocorticographic BCI.

PubMed

Williams, Jordan J; Rouse, Adam G; Thongpang, Sanitta; Williams, Justin C; Moran, Daniel W

2013-08-01

Recent experiments have shown that electrocorticography (ECoG) can provide robust control signals for a brain-computer interface (BCI). Strategies that attempt to adapt a BCI control algorithm by learning from past trials often assume that the subject is attending to each training trial. Likewise, automatic disabling of movement control would be desirable during resting periods when random brain fluctuations might cause unintended movements of a device. To this end, our goal was to identify ECoG differences that arise between periods of active BCI use and rest. We examined spectral differences in multi-channel, epidural micro-ECoG signals recorded from non-human primates when rest periods were interleaved between blocks of an active BCI control task. Post-hoc analyses demonstrated that these states can be decoded accurately on both a trial-by-trial and real-time basis, and this discriminability remains robust over a period of weeks. In addition, high gamma frequencies showed greater modulation with desired movement direction, while lower frequency components demonstrated greater amplitude differences between task and rest periods, suggesting possible specialized BCI roles for these frequencies. The results presented here provide valuable insight into the neurophysiology of BCI control as well as important considerations toward the design of an asynchronous BCI system.

Differentiating closed-loop cortical intention from rest: building an asynchronous electrocorticographic BCI

NASA Astrophysics Data System (ADS)

Williams, Jordan J.; Rouse, Adam G.; Thongpang, Sanitta; Williams, Justin C.; Moran, Daniel W.

2013-08-01

Objective. Recent experiments have shown that electrocorticography (ECoG) can provide robust control signals for a brain-computer interface (BCI). Strategies that attempt to adapt a BCI control algorithm by learning from past trials often assume that the subject is attending to each training trial. Likewise, automatic disabling of movement control would be desirable during resting periods when random brain fluctuations might cause unintended movements of a device. To this end, our goal was to identify ECoG differences that arise between periods of active BCI use and rest. Approach. We examined spectral differences in multi-channel, epidural micro-ECoG signals recorded from non-human primates when rest periods were interleaved between blocks of an active BCI control task. Main Results. Post-hoc analyses demonstrated that these states can be decoded accurately on both a trial-by-trial and real-time basis, and this discriminability remains robust over a period of weeks. In addition, high gamma frequencies showed greater modulation with desired movement direction, while lower frequency components demonstrated greater amplitude differences between task and rest periods, suggesting possible specialized BCI roles for these frequencies. Significance. The results presented here provide valuable insight into the neurophysiology of BCI control as well as important considerations toward the design of an asynchronous BCI system.

Participants' Perceptions on the Use of Wearable Devices to Reduce Sitting Time: Qualitative Analysis.

PubMed

Takemoto, Michelle; Lewars, Brittany; Hurst, Samantha; Crist, Katie; Nebeker, Camille; Madanat, Hala; Nichols, Jeanne; Rosenberg, Dori E; Kerr, Jacqueline

2018-03-31

Recent epidemiological evidence indicates that, on average, people are sedentary for approximately 7.7 hours per day. There are deleterious effects of prolonged sedentary behavior that are separate from participation in physical activity and include increased risk of weight gain, cancer, metabolic syndrome, diabetes, and heart disease. Previous trials have used wearable devices to increase physical activity in studies; however, additional research is needed to fully understand how this technology can be used to reduce sitting time. The purpose of this study was to explore the potential of wearable devices as an intervention tool in a larger sedentary behavior study through a general inductive and deductive analysis of focus group discussions. We conducted four focus groups with 15 participants to discuss 7 different wearable devices with sedentary behavior capabilities. Participants recruited for the focus groups had previously participated in a pilot intervention targeting sedentary behavior over a 3-week period and were knowledgeable about the challenges of reducing sitting time. During the focus groups, participants commented on the wearability, functionality, and feedback mechanism of each device and then identified their two favorite and two least favorite devices. Finally, participants designed and described their ideal or dream wearable device. Two researchers, who have expertise analyzing qualitative data, coded and analyzed the data from the focus groups. A thematic analysis approach using Dedoose software (SocioCultural Research Consultants, LLC version 7.5.9) guided the organization of themes that reflected participants' perspectives. Analysis resulted in 14 codes that we grouped into themes. Three themes emerged from our data: (1) features of the device, (2) data the device collected, and (3) how data are displayed. Current wearable devices for increasing physical activity are insufficient to intervene on sitting time. This was especially evident when participants voted, as several participants reported using a "process of elimination" as opposed to choosing favorites because none of the devices were ideal for reducing sitting time. To overcome the limitations in current devices, future wearable devices designed to reduce sitting time should include the following features: waterproof, long battery life, accuracy in measuring sitting time, real time feedback on progress toward sitting reduction goals, and flexible options for prompts to take breaks from sitting. ©Michelle Takemoto, Brittany Lewars, Samantha Hurst, Katie Crist, Camille Nebeker, Hala Madanat, Jeanne Nichols, Dori E Rosenberg, Jacqueline Kerr. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 31.03.2018.

Enhancing clinical evidence by proactively building quality into clinical trials.

PubMed

Meeker-O'Connell, Ann; Glessner, Coleen; Behm, Mark; Mulinde, Jean; Roach, Nancy; Sweeney, Fergus; Tenaerts, Pamela; Landray, Martin J

2016-08-01

Stakeholders across the clinical trial enterprise have expressed concern that the current clinical trial enterprise is unsustainable. The cost and complexity of trials have continued to increase, threatening our ability to generate reliable evidence essential for making appropriate decisions concerning the benefits and harms associated with clinical interventions. Overcoming this inefficiency rests on improving protocol design, trial planning, and quality oversight. The Clinical Trials Transformation Initiative convened a project to evaluate methods to prospectively build quality into the scientific and operational design of clinical trials ("quality-by-design"), such that trials are feasible to conduct and important errors are prevented rather than remediated. A working group evaluated aspects of trial design and oversight and developed the Clinical Trials Transformation Initiative quality-by-design principles document, outlining a series of factors generally relevant to the reliability of trial conclusions and to patient safety. These principles were then applied and further refined during a series of hands-on workshops to evaluate their utility in facilitating proactive, cross-functional dialogue, and decision-making about trial design and planning. Following these workshops, independent qualitative interviews were conducted with 19 workshop attendees to explore the potential challenges for implementing a quality-by-design approach to clinical trials. The Clinical Trials Transformation Initiative project team subsequently developed recommendations and an online resource guide to support implementation of this approach. The Clinical Trials Transformation Initiative quality-by-design principles provide a framework for assuring that clinical trials adequately safeguard participants and provide reliable information on which to make decisions on the effects of treatments. The quality-by-design workshops highlighted the value of active discussions incorporating the different perspectives within and external to an organization (e.g. clinical investigators, research site staff, and trial participants) in improving trial design. Workshop participants also recognized the value of focusing oversight on those aspects of the trial where errors would have a major impact on participant safety and reliability of results. Applying the Clinical Trials Transformation Initiative quality-by-design recommendations and principles should enable organizations to prioritize the most critical determinants of a trial's quality, identify non-essential activities that can be eliminated to streamline trial conduct and oversight, and formulate appropriate plans to define, avoid, mitigate, monitor, and address important errors. © The Author(s) 2016.

Can emergency medicine research benefit from adaptive design clinical trials?

PubMed

Flight, Laura; Julious, Steven A; Goodacre, Steve

2017-04-01

Adaptive design clinical trials use preplanned interim analyses to determine whether studies should be stopped or modified before recruitment is complete. Emergency medicine trials are well suited to these designs as many have a short time to primary outcome relative to the length of recruitment. We hypothesised that the majority of published emergency medicine trials have the potential to use a simple adaptive trial design. We reviewed clinical trials published in three emergency medicine journals between January 2003 and December 2013. We determined the proportion that used an adaptive design as well as the proportion that could have used a simple adaptive design based on the time to primary outcome and length of recruitment. Only 19 of 188 trials included in the review were considered to have used an adaptive trial design. A total of 154/165 trials that were fixed in design had the potential to use an adaptive design. Currently, there seems to be limited uptake in the use of adaptive trial designs in emergency medicine despite their potential benefits to save time and resources. Failing to take advantage of adaptive designs could be costly to patients and research. It is recommended that where practical and logistical considerations allow, adaptive designs should be used for all emergency medicine clinical trials. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Devices and dressings to secure peripheral venous catheters to prevent complications.

PubMed

Marsh, Nicole; Webster, Joan; Mihala, Gabor; Rickard, Claire M

2015-06-12

A peripheral venous catheter (PVC) is typically used for short-term delivery of intravascular fluids and medications. It is an essential element of modern medicine and the most frequent invasive procedure performed in hospitals. However, PVCs often fail before intravenous treatment is completed: this can occur because the device is not adequately attached to the skin, allowing the PVC to fall out, leading to complications such as phlebitis (irritation or inflammation to the vein wall), infiltration (fluid leaking into surrounding tissues) or occlusion (blockage). An inadequately secured PVC also increases the risk of catheter-related bloodstream infection (CRBSI), as the pistoning action (moving back and forth in the vein) of the catheter can allow migration of organisms along the catheter and into the bloodstream. Despite the many dressings and securement devices available, the impact of different securement techniques for increasing PVC dwell time is still unclear; there is a need to provide guidance for clinicians by reviewing current studies systematically. To assess the effects of PVC dressings and securement devices on the incidence of PVC failure. We searched the following electronic databases to identify reports of relevant randomised controlled trials (RCTs): the Cochrane Wounds Group Register (searched 08 April 2015): The Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 3), Ovid MEDLINE (1946 to March 7 2015); Ovid MEDLINE (In-Process & Other Non-Indexed Citations, March 7 2015); Ovid EMBASE (1974 to March 7 2015); and EBSCO CINAHL (1982 to March 8 2015). RCTs or cluster RCTs comparing different dressings or securement devices for the stabilisation of PVCs. Cross-over trials were ineligible for inclusion, unless data for the first treatment period could be obtained. Two review authors independently selected studies, assessed trial quality and extracted data. We contacted study authors for missing information. We used standard methodological procedures expected by Cochrane. We included six RCTs (1539 participants) in this review. Trial sizes ranged from 50 to 703 participants. These six trials made four comparisons, namely: transparent dressings versus gauze; bordered transparent dressings versus a securement device; bordered transparent dressings versus tape; and transparent dressing versus sticking plaster. There is very low quality evidence of fewer catheter dislodgements or accidental removals with transparent dressings compared with gauze (two studies, 278 participants, RR 0.40; 95% CI 0.17 to 0.92, P = 0.03%). The relative effects of transparent dressings and gauze on phlebitis (RR 0.89; 95% CI 0.47 to 1.68) and infiltration (RR 0.80; 95% CI 0.48 to 1.33) are unclear. The relative effects on PVC failure of a bordered transparent dressing and a securement device have been assessed in only one small study and these were unclear. There was very low quality evidence from the same single study of less frequent dislodgement or accidental catheter removal with bordered transparent dressings than securement devices (RR 0.14, 95% CI 0.03 to 0.63) but more phlebitis with bordered dressings (RR 8.11, 95% CI 1.03 to 64.02) (very low quality evidence). A small single study compared bordered transparent dressings with tape and found very low quality evidence of more PVC failure with the bordered dressing (RR 1.84, 95% CI 1.08 to 3.11) but the relative effects on dislodgement were not clear (very low quality evidence). The relative effects of transparent dressings and a sticking plaster have only been compared in one small study and are unclear. More high quality RCTs are required to determine the relative effects of alternative PVC dressings and securement devices. It is not clear if any one dressing or securement device is better than any other in securing peripheral venous catheters. There is a need for further, independent high quality trials to evaluate the many traditional as well as the newer, high use products. Given the large cost differences between some different dressings and securement devices, future trials should include a robust cost-effectiveness analysis.

Immediate vs. delayed insertion of intrauterine contraception after second trimester abortion: study protocol for a randomized controlled trial.

PubMed

Norman, Wendy V; Kaczorowski, Janusz; Soon, Judith A; Brant, Rollin; Bryan, Stirling; Trouton, Konia J; Dicus, Lyda

2011-06-14

We describe the rationale and protocol for a randomized controlled trial (RCT) to assess whether intrauterine contraception placed immediately after a second trimester abortion will result in fewer pregnancies than current recommended practice of intended placement at 4 weeks post-abortion. Decision analysis suggests the novel strategy could substantially reduce subsequent unintended pregnancies and abortions. This paper highlights considerations of design, implementation and evaluation of a trial expected to provide rigorous evidence for appropriate insertion timing and health economics of intrauterine contraception after second trimester abortion. Consenting women choosing to use intrauterine contraception after abortion for a pregnancy of 12 to 24 weeks will be randomized to insertion timing groups either immediately (experimental intervention) or four weeks (recommended care) post abortion. Primary outcome measure is pregnancy rate at one year. Secondary outcomes include: cumulative pregnancy rates over five year follow-up period, comprehensive health economic analyses comparing immediate and delayed insertion groups, and device retention rates, complication rates (infection, expulsion) and, contraceptive method satisfaction. Web-based Contraception Satisfaction Questionnaires, clinical records and British Columbia linked health databases will be used to assess primary and secondary outcomes. Enrolment at all clinics in the province performing second trimester abortions began in May 2010 and is expected to complete in late 2011. Data on one year outcomes will be available for analysis in 2014. The RCT design combined with access to clinical records at all provincial abortion clinics, and to information in provincial single-payer linked administrative health databases, birth registry and hospital records, offers a unique opportunity to evaluate such an approach by determining pregnancy rate at one through five years among enrolled women. We highlight considerations of design, implementation and evaluation of a trial expected to provide rigorous evidence for appropriate insertion timing and health economics of intrauterine contraception after second trimester abortion.

Regulatory considerations in the design of comparative observational studies using propensity scores.

PubMed

Yue, Lilly Q

2012-01-01

In the evaluation of medical products, including drugs, biological products, and medical devices, comparative observational studies could play an important role when properly conducted randomized, well-controlled clinical trials are infeasible due to ethical or practical reasons. However, various biases could be introduced at every stage and into every aspect of the observational study, and consequently the interpretation of the resulting statistical inference would be of concern. While there do exist statistical techniques for addressing some of the challenging issues, often based on propensity score methodology, these statistical tools probably have not been as widely employed in prospectively designing observational studies as they should be. There are also times when they are implemented in an unscientific manner, such as performing propensity score model selection for a dataset involving outcome data in the same dataset, so that the integrity of observational study design and the interpretability of outcome analysis results could be compromised. In this paper, regulatory considerations on prospective study design using propensity scores are shared and illustrated with hypothetical examples.

Assessing the validity and reliability of self-report data on contraception use in the MObile Technology for Improved Family Planning (MOTIF) randomised controlled trial.

PubMed

Smith, Chris; Edwards, Phil; Free, Caroline

2018-03-15

A variety of different approaches to measuring contraceptive use have been used or proposed, either to assess current use or adherence over time, using subjective or objective measures. This paper reports an overview of approaches to measuring adherence to the oral contraceptive, intra-uterine device, sub-dermal implant, and injectable and describes how we assessed contraception use in the MObile Technology for Improved Family Planning (MOTIF) trial in Cambodia. We summarise and discuss advantages and disadvantages of different subjective and objective approaches to measuring adherence to the oral contraceptive, intra-uterine device, sub-dermal implant, and injectable such as self-reports, clinic records, electronic monitoring devices, clinical examination and biomarkers. For the MOTIF trial, we did not consider it feasible to measure objective contraception use as many participants lived a long distance from the clinic and we were concerned whether it was appropriate to ask women to return to clinic for a physical examination simply to verify self-report information already provided. We aimed to assess the validity of the four-month data with 50 participants, calculating the sensitivity and specificity of self-reported data compared with objective measurement. For the 46 valid measurements obtained, the sensitivity and specificity was 100% for self-reported contraception use compared to objective measurement but this study had some limitations. To assess reliability of self-report data we compared calendar data collected on effective contraception use at months 1-4 post-abortion, collected separately at four and 12 months. Agreement ranged from 80 to 84% with a kappa statistic ranging from 0·59 to 0·67 indicating fair to good agreement. There is no perfect method of assessing contraception use and researchers designing future studies should give consideration of what to measure, for example current use or detailed patterns of use over time, and remain mindful of what will be feasible and acceptable to the study population. Although self-reported data on contraception use are considered less reliable, and prone to social desirability bias, it is often the standard approach for contraception research and provides data comparable to previous studies. ClinicalTrials.gov Identifier: NCT01823861 . Registered: March 30, 2013.

The INNOVATION Trial: four-year safety and effectiveness of the INCRAFT® AAA Stent-Graft System for endovascular repair.

PubMed

Pratesi, Giovanni; Pratesi, Carlo; Chiesa, Roberto; Coppi, Gioacchino; Scheinert, Dierk; Brunkwall, Jan S; van der Meulen, Stefaan; Torsello, Giovanni

2017-10-01

This paper reports the 4-year safety and effectiveness of the INCRAFT® AAA Stent-Graft System (Cordis Corp., Milpitas, CA, USA), an ultra-low-profile device for the treatment of abdominal aortic aneurysms. The INNOVATION Trial is the prospective, first-in-human, multicenter trial to evaluate the safety and effectiveness of the INCRAFT® System. Patients underwent annual clinical and computed tomography angiography examination as part of the study protocol. The INCRAFT® AAA Stent-Graft System is a customizable tri-modular design, with an ultra-low profile (14-Fr) delivery system. Patient were treated under approved protocol, the prescribed clinical and imaging follow-up at annually through 5 years. Results analyzed and adjudicated by a clinical events committee, independent core laboratory, and a data safety and monitoring board. This manuscript reports results through 4 years of follow-up. A total of 60 patients were enrolled in the trial, all of whom were successfully treated. Follow-up rates at 1 and 4 years were 93% (56/60) and 85% (51/60), respectively. All-cause mortality at 4 years was 17.6% and no death was AAA-, device-, or procedure-related. The secondary reintervention rate at 1 year was 4.6%, primarily the result of stent thrombosis. In total, 10 patients required 13 post-procedure interventions within 4-years of follow-up (2 to repair a type I endoleak, 4 to repair a type II endoleak, 1 for stent thrombosis, 1 for renal stenosis, 1 for aneurysm enlargement, 2 for limb migration and 2 for prosthesis stenosis or occlusion). There were 4 cases (10%) of aneurysm enlargement reported at the 4 year follow-up. At 4 years, 38 out of 39 patients were free from type I and III endoleaks. There were no proximal type I or type III endoleaks at 4-year follow-up. Core laboratory evaluation of the postoperative imaging studies indicated absence of endograft migration while a single fracture was demonstrated without any clinical sequelae. The INCRAFT® AAA Stent-Graft System provides a minimally invasive and durable solution for patients undergoing EVAR that has been associated with a low frequency of device-related events through 4 years of follow-up.

Powered robotic exoskeletons in post-stroke rehabilitation of gait: a scoping review.

PubMed

Louie, Dennis R; Eng, Janice J

2016-06-08

Powered robotic exoskeletons are a potential intervention for gait rehabilitation in stroke to enable repetitive walking practice to maximize neural recovery. As this is a relatively new technology for stroke, a scoping review can help guide current research and propose recommendations for advancing the research development. The aim of this scoping review was to map the current literature surrounding the use of robotic exoskeletons for gait rehabilitation in adults post-stroke. Five databases (Pubmed, OVID MEDLINE, CINAHL, Embase, Cochrane Central Register of Clinical Trials) were searched for articles from inception to October 2015. Reference lists of included articles were reviewed to identify additional studies. Articles were included if they utilized a robotic exoskeleton as a gait training intervention for adult stroke survivors and reported walking outcome measures. Of 441 records identified, 11 studies, all published within the last five years, involving 216 participants met the inclusion criteria. The study designs ranged from pre-post clinical studies (n = 7) to controlled trials (n = 4); five of the studies utilized a robotic exoskeleton device unilaterally, while six used a bilateral design. Participants ranged from sub-acute (<7 weeks) to chronic (>6 months) stroke. Training periods ranged from single-session to 8-week interventions. Main walking outcome measures were gait speed, Timed Up and Go, 6-min Walk Test, and the Functional Ambulation Category. Meaningful improvement with exoskeleton-based gait training was more apparent in sub-acute stroke compared to chronic stroke. Two of the four controlled trials showed no greater improvement in any walking outcomes compared to a control group in chronic stroke. In conclusion, clinical trials demonstrate that powered robotic exoskeletons can be used safely as a gait training intervention for stroke. Preliminary findings suggest that exoskeletal gait training is equivalent to traditional therapy for chronic stroke patients, while sub-acute patients may experience added benefit from exoskeletal gait training. Efforts should be invested in designing rigorous, appropriately powered controlled trials before powered exoskeletons can be translated into a clinical tool for gait rehabilitation post-stroke.

Effects of standard training in the use of closed-circuit televisions in visually impaired adults: design of a training protocol and a randomized controlled trial.

PubMed

Burggraaff, Marloes C; van Nispen, Ruth M A; Melis-Dankers, Bart J M; van Rens, Ger H M B

2010-03-10

Reading problems are frequently reported by visually impaired persons. A closed-circuit television (CCTV) can be helpful to maintain reading ability, however, it is difficult to learn how to use this device. In the Netherlands, an evidence-based rehabilitation program in the use of CCTVs was lacking. Therefore, a standard training protocol needed to be developed and tested in a randomized controlled trial (RCT) to provide an evidence-based training program in the use of this device. To develop a standard training program, information was collected by studying literature, observing training in the use of CCTVs, discussing the content of the training program with professionals and organizing focus and discussion groups. The effectiveness of the program was evaluated in an RCT, to obtain an evidence-based training program. Dutch patients (n = 122) were randomized into a treatment group: normal instructions from the supplier combined with training in the use of CCTVs, or into a control group: instructions from the supplier only. The effect of the training program was evaluated in terms of: change in reading ability (reading speed and reading comprehension), patients' skills to operate the CCTV, perceived (vision-related) quality of life and tasks performed in daily living. The development of the CCTV training protocol and the design of the RCT in the present study may serve as an example to obtain an evidence-based training program. The training program was adjusted to the needs and learning abilities of individual patients, however, for scientific reasons it might have been preferable to standardize the protocol further, in order to gain more comparable results. http://www.trialregister.nl, identifier: NTR1031.

Therapeutic Devices for Epilepsy

PubMed Central

Fisher, Robert S.

2011-01-01

Therapeutic devices provide new options for treating drug-resistant epilepsy. These devices act by a variety of mechanisms to modulate neuronal activity. Only vagus nerve stimulation, which continues to develop new technology, is approved for use in the United States. Deep brain stimulation (DBS) of anterior thalamus for partial epilepsy recently was approved in Europe and several other countries. Responsive neurostimulation, which delivers stimuli to one or two seizure foci in response to a detected seizure, recently completed a successful multicenter trial. Several other trials of brain stimulation are in planning or underway. Transcutaneous magnetic stimulation (TMS) may provide a noninvasive method to stimulate cortex. Controlled studies of TMS split on efficacy, and may depend on whether a seizure focus is near a possible region for stimulation. Seizure detection devices in the form of “shake” detectors via portable accelerometers can provide notification of an ongoing tonic-clonic seizure, or peace of mind in the absence of notification. Prediction of seizures from various aspects of EEG is in early stages. Prediction appears to be possible in a subpopulation of people with refractory seizures and a clinical trial of an implantable prediction device is underway. Cooling of neocortex or hippocampus reversibly can attenuate epileptiform EEG activity and seizures, but engineering problems remain in its implementation. Optogenetics is a new technique that can control excitability of specific populations of neurons with light. Inhibition of epileptiform activity has been demonstrated in hippocampal slices, but use in humans will require more work. In general, devices provide useful palliation for otherwise uncontrollable seizures, but with a different risk profile than with most drugs. Optimizing the place of devices in therapy for epilepsy will require further development and clinical experience. PMID:22367987

Unique Study Designs in Nephrology: N-of-1 Trials and Other Designs.

PubMed

Samuel, Joyce P; Bell, Cynthia S

2016-11-01

Alternatives to the traditional parallel-group trial design may be required to answer clinical questions in special populations, rare conditions, or with limited resources. N-of-1 trials are a unique trial design which can inform personalized evidence-based decisions for the patient when data from traditional clinical trials are lacking or not generalizable. A concise overview of factorial design, cluster randomization, adaptive designs, crossover studies, and n-of-1 trials will be provided along with pertinent examples in nephrology. The indication for analysis strategies such as equivalence and noninferiority trials will be discussed, as well as analytic pitfalls. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Large - scale Rectangular Ruler Automated Verification Device

NASA Astrophysics Data System (ADS)

Chen, Hao; Chang, Luping; Xing, Minjian; Xie, Xie

2018-03-01

This paper introduces a large-scale rectangular ruler automated verification device, which consists of photoelectric autocollimator and self-designed mechanical drive car and data automatic acquisition system. The design of mechanical structure part of the device refer to optical axis design, drive part, fixture device and wheel design. The design of control system of the device refer to hardware design and software design, and the hardware mainly uses singlechip system, and the software design is the process of the photoelectric autocollimator and the automatic data acquisition process. This devices can automated achieve vertical measurement data. The reliability of the device is verified by experimental comparison. The conclusion meets the requirement of the right angle test procedure.

Noninvasive neuromodulation in migraine and cluster headache.

PubMed

Starling, Amaal

2018-06-01

The purpose of this narrative review is to provide an overview of the currently available noninvasive neuromodulation devices for the treatment of migraine and cluster headache. Over the last decade, several noninvasive devices have undergone development and clinical trials to evaluate efficacy and safety. Based on this body of work, single-pulse transcranial magnetic stimulation, transcutaneous supraorbital neurostimulation, and noninvasive vagal nerve stimulation devices have been cleared by the United States Food and Drug Administration and are available for clinical use for the treatment of primary headache disorders. Overall, these novel noninvasive devices appear to be safe, well tolerated, and have demonstrated promising results in clinical trials in both migraine and cluster headache. This narrative review will provide a summary and update of the proposed mechanisms of action, evidence, safety, and future directions of various currently available modalities of noninvasive neuromodulation for the treatment of migraine and cluster headache.

Effects of foot and ankle devices on balance, gait and falls in adults with sensory perception loss: a systematic review.

PubMed

Paton, Joanne; Hatton, Anna L; Rome, Keith; Kent, Bridie

2016-12-01

Foot and ankle devices are being developed as a method of preventing people with sensory perception loss sustaining a fall. Such devices are believed to work by reducing the likelihood of a fall by improving the balance and gait of the user. The objective of the review was to evaluate the effectiveness of foot and ankle devices for the prevention of falls and the improvement of balance and gait in adults with sensory perception loss. Participants were community-dwelling adults with bilateral pathological sensory perception loss. The current review evaluated any foot or ankle device, including but not restricted to, all types of footwear (therapeutic and retail), insoles (customized and prefabricated) and ankle-foot orthoses (AFOs). In the absence of randomized controlled trials (RCT), the review considered experimental and epidemiological study designs, except case series, individual case reports and descriptive cross-sectional studies. The primary outcome was number of falls. Secondary outcome measures were clinical or laboratory measures of balance or gait. A search for published and unpublished literature from inception to March 2015 written in the English language was conducted across a number of major electronic databases. A three-step search strategy was developed using MeSH terminology and keywords to ensure all that relevant materials are captured. Methodological quality of included studies was assessed by two reviewers, who appraised each study independently, using standardized Joanna Briggs Institute (JBI) critical appraisal tools. Quantitative data were extracted from the studies that were identified as meeting the criteria for methodological quality using the standardized JBI data extraction tools. Due to the heterogeneity of populations, interventions and outcome measures, meta-analyses were not possible and results are presented in narrative form. Nine trials (from 10 papers) involving 238 participants, (14 with multiple sclerosis and 16 with idiopathic peripheral neuropathy, 150 with diabetic neuropathy) and 58 controls were included in the review. No study reported falls as an outcome measure. The results of the included studies found that in people with sensory perception loss, postural sway improved with vibrating insoles and AFO, altering the softness and texture of the top cover had no effect on postural sway, wearing footwear over long distances or AFOs improved step-to-step consistency, and no foot and ankle device was reported to have a negative effect on the balance or gait of people with sensory perception loss. The methodological quality of the included studies was poor. No study used a randomized controlled trial (RCT) methodology. No study incorporated a follow-up period or tested the intervention within the context of the intended clinical environment. There is limited evidence to suggest that footwear and insole devices can artificially alter postural stability and may reduce the step-to-step variability in adults with sensory perception loss. Varying the material properties of an insole does not notably affect static balance or gait.

Personalised long-term follow-up of cochlear implant patients using remote care, compared with those on the standard care pathway: study protocol for a feasibility randomised controlled trial

PubMed Central

Kitterick, Padraig; DeBold, Lisa; Weal, Mark; Clarke, Nicholas; Newberry, Eva; Aubert, Lisa

2016-01-01

Introduction Many resources are required to provide postoperative care to patients who receive a cochlear implant. The implant service commits to lifetime follow-up. The patient commits to regular adjustment and rehabilitation appointments in the first year and annual follow-up appointments thereafter. Offering remote follow-up may result in more stable hearing, reduced patient travel expense, time and disruption, more empowered patients, greater equality in service delivery and more freedom to optimise the allocation of clinic resources. Methods and analysis This will be a two-arm feasibility randomised controlled trial (RCT) involving 60 adults using cochlear implants with at least 6 months device experience in a 6-month clinical trial of remote care. This project will design, implement and evaluate a person-centred long-term follow-up pathway for people using cochlear implants offering a triple approach of remote and self-monitoring, self-adjustment of device and a personalised online support tool for home speech recognition testing, information, self-rehabilitation, advice, equipment training and troubleshooting. The main outcome measure is patient activation. Secondary outcomes are stability and quality of hearing, stability of quality of life, clinic resources, patient and clinician experience, and any adverse events associated with remote care. We will examine the acceptability of remote care to service users and clinicians, the willingness of participants to be randomised, and attrition rates. We will estimate numbers required to plan a fully powered RCT. Ethics and dissemination Ethical approval was received from North West—Greater Manchester South Research Ethics Committee (15/NW/0860) and the University of Southampton Research Governance Office (ERGO 15329). Results Results will be disseminated in the clinical and scientific communities and also to the patient population via peer-reviewed research publications both online and in print, conference and meeting presentations, posters, newsletter articles, website reports and social media. Trial registration number ISRCTN14644286; Pre-results. PMID:27178980

Comparison of in-vivo failure of single-thread and dual-thread temporary anchorage devices over 18 months: A split-mouth randomized controlled trial.

PubMed

Durrani, Owais Khalid; Shaheed, Sohrab; Khan, Arsalan; Bashir, Ulfat

2017-10-01

The purpose of this study was to compare the in-vivo failure rates of single-thread and dual-thread temporary anchorage device (TAD) designs over 18 months. Thirty patients with skeletal Class II Division 1 malocclusion requiring anchorage from TADs for retraction of maxillary incisors into the extracted premolar space were recruited in this parallel group, split-mouth, randomized controlled trial. A block randomization sequence was generated with Random Allocation Software (version 2.0; Isfahan, Iran) with the allocations concealed in sequentially numbered, opaque, sealed envelopes. A total of 60 TADs (diameter, 2 mm; length, 10 mm) were placed in the maxillary arches of these patients with random allocation of the 2 types to the left and the right sides in a 1:1 ratio. All TADs were placed between the roots of the second premolar and the first molar and were immediately loaded. Patients were followed for a minimum of 12 months and a maximum of 18 months for the failure of the TADs. Data were analyzed blindly on an intention-to-treat basis. Four TADs (13.3%) failed in the single-thread group, and 6 TADs (20%) failed in the dual-thread group. The McNemar test showed an insignificant difference (P = 0.72) between the 2 groups. An odds ratio of 1.6 (95% confidence interval, 0.39-6.97) showed no significant associations among the variables. Most TADs failed in the first month after insertion (50%). The failure rate of dual-thread TADs compared with single-thread TADs is statistically insignificant when placed in the maxilla for retraction of the anterior segment. Registration: The trial was not registered before commencement. The protocol was not published before the trial. Copyright © 2016 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

A computerized handheld decision-support system to improve pulmonary embolism diagnosis: a randomized trial.

PubMed

Roy, Pierre-Marie; Durieux, Pierre; Gillaizeau, Florence; Legall, Catherine; Armand-Perroux, Aurore; Martino, Ludovic; Hachelaf, Mohamed; Dubart, Alain-Eric; Schmidt, Jeannot; Cristiano, Mirko; Chretien, Jean-Marie; Perrier, Arnaud; Meyer, Guy

2009-11-17

Testing for pulmonary embolism often differs from that recommended by evidence-based guidelines. To assess the effectiveness of a handheld clinical decision-support system to improve the diagnostic work-up of suspected pulmonary embolism among patients in the emergency department. Cluster randomized trial. Assignment was by random-number table, providers were not blinded, and outcome assessment was automated. (ClinicalTrials.gov registration number: NCT00188032). 20 emergency departments in France. 1103 and 1768 consecutive outpatients with suspected pulmonary embolism. After a preintervention period involving 20 centers and 1103 patients, in which providers grew accustomed to inputting clinical data into handheld devices and investigators assessed baseline testing, emergency departments were randomly assigned to activation of a decision-support system on the devices (10 centers, 753 patients) or posters and pocket cards that showed validated diagnostic strategies (10 centers, 1015 patients). Appropriateness of diagnostic work-up, defined as any sequence of tests that yielded a posttest probability less than 5% or greater than 85% (primary outcome) or as strict adherence to guideline recommendations (secondary outcome); number of tests per patient (secondary outcome). The proportion of patients who received appropriate diagnostic work-ups was greater during the trial than in the preintervention period in both groups, but the increase was greater in the computer-based guidelines group (adjusted mean difference in increase, 19.3 percentage points favoring computer-based guidelines [95% CI, 2.9 to 35.6 percentage points]; P = 0.023). Among patients with appropriate work-ups, those in the computer-based guidelines group received slightly fewer tests than did patients in the paper guidelines group (mean tests per patient, 1.76 [SD, 0.98] vs. 2.25 [SD, 1.04]; P < 0.001). The study was not designed to show a difference in the clinical outcomes of patients during follow-up. A handheld decision-support system improved diagnostic decision making for patients with suspected pulmonary embolism in the emergency department.

Peripherally InSerted CEntral catheter dressing and securement in patients with cancer: the PISCES trial. Protocol for a 2x2 factorial, superiority randomised controlled trial.

PubMed

Rickard, Claire M; Marsh, Nicole M; Webster, Joan; Gavin, Nicole C; Chan, Raymond J; McCarthy, Alexandra L; Mollee, Peter; Ullman, Amanda J; Kleidon, Tricia; Chopra, Vineet; Zhang, Li; McGrail, Matthew R; Larsen, Emily; Choudhury, Md Abu; Keogh, Samantha; Alexandrou, Evan; McMillan, David J; Mervin, Merehau Cindy; Paterson, David L; Cooke, Marie; Ray-Barruel, Gillian; Castillo, Maria Isabel; Hallahan, Andrew; Corley, Amanda; Geoffrey Playford, E

2017-06-15

Around 30% of peripherally inserted central catheters (PICCs) fail from vascular, infectious or mechanical complications. Patients with cancer are at highest risk, and this increases morbidity, mortality and costs. Effective PICC dressing and securement may prevent PICC failure; however, no large randomised controlled trial (RCT) has compared alternative approaches. We designed this RCT to assess the clinical and cost-effectiveness of dressing and securements to prevent PICC failure. Pragmatic, multicentre, 2×2 factorial, superiority RCT of (1) dressings (chlorhexidine gluconate disc (CHG) vs no disc) and (2) securements (integrated securement dressing (ISD) vs securement device (SED)). A qualitative evaluation using a knowledge translation framework is included. Recruitment of 1240 patients will occur over 3 years with allocation concealment until randomisation by a centralised service. For the dressing hypothesis, we hypothesise CHG discs will reduce catheter-associated bloodstream infection (CABSI) compared with no CHG disc. For the securement hypothesis, we hypothesise that ISD will reduce composite PICC failure (infection (CABSI/local infection), occlusion, dislodgement or thrombosis), compared with SED. types of PICC failure; safety; costs; dressing/securement failure; dwell time; microbial colonisation; reversible PICC complications and consumer acceptability. Relative incidence rates of CABSI and PICC failure/100 devices and/1000 PICC days (with 95% CIs) will summarise treatment impact. Kaplan-Meier survival curves (and log rank Mantel-Haenszel test) will compare outcomes over time. Secondary end points will be compared between groups using parametric/non-parametric techniques; p values <0.05 will be considered to be statistically significant. Ethical approval from Queensland Health (HREC/15/QRCH/241) and Griffith University (Ref. No. 2016/063). Results will be published. Trial registration number is: ACTRN12616000315415. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Transcatheter closure of patent foramen ovale for secondary prevention of ischemic stroke: Quantitative synthesis of pooled randomized trial data.

PubMed

Hakeem, Abdul; Cilingiroglu, Mehmet; Katramados, Angelos; Boudoulas, Konstantinos Dean; Iliescu, Cezar; Gundogdu, Betul; Marmagkiolis, Konstantinos

2018-01-14

To evaluate the safety and efficacy of percutaneous device closure of patent foramen ovale (PFO) for secondary prevention of ischemic stroke BACKGROUND: Stroke remains the leading cause of serious long-term disability in the United States. The effectiveness of a percutaneous PFO closure in the prevention of recurrent cryptogenic strokes has not been established. We performed a literature search using PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Google Scholar, and Internet-based sources from January 2003 to September 2017. Randomized controlled trails (RCTs) comparing percutaneous PFO closure to medical therapy alone. Five RCTs (CLOSURE I, PC Trial, REDUCE, RESPECT, and CLOSE) with 1,829 patients in the device group and 1,611 patients in the medical group met inclusion criteria. The cumulative incidence of recurrent stroke was 2.02% in the PFO closure arm and 4.4% in the medical therapy group (RR 0.42, 95%CI 0.20, 0.91; P = 0.03). There was no difference in the incidence of death [0.7% vs. 0.9%; RR 0.76 (95% CI 0.35, 1.64), P = 0.49] or adverse events during the follow-up period [24.6% vs. 23.7% (RR 1.03; 95% CI 0.91, 1.16), P = 0.65] between the closure and medical therapy groups. Incidence of atrial fibrillation was significantly higher in closure group compared to medical therapy [4% vs. 0.6% (RR 4.73; 95% CI 2.09, 10.70), P = 0.0002]. The comparative effectiveness of PFO closure (compared to medical therapy) was significantly more pronounced in those younger than 45 years, males, larger shunts and disc design platforms (P < 0.05). Based on the results of this analysis of randomized trial data, percutaneous PFO closure appears to be a safe and effective therapeutic option for the secondary prevention of ischemic stroke in patients with PFO and cryptogenic stroke. © 2018 Wiley Periodicals, Inc.

The LeucoPatch® system in the management of hard-to-heal diabetic foot ulcers: study protocol for a randomised controlled trial.

PubMed

Game, Frances; Jeffcoate, William; Tarnow, Lise; Day, Florence; Fitzsimmons, Deborah; Jacobsen, Judith

2017-10-10

Diabetic foot ulcers are a common and severe complication of diabetes mellitus. Standard treatment includes debridement, offloading, management of infection and revascularisation where appropriate, although healing times may be long. The LeucoPatch® device is used to generate an autologous platelet-rich fibrin and leucocyte wound dressing produced from the patient's own venous blood by centrifugation, but without the addition of any reagents. The final product comprises a thin, circular patch composed predominantly of fibrin together with living platelets and leucocytes. Promising results have been obtained in non-controlled studies this system, but this now needs to be tested in a randomised controlled trial (RCT). If confirmed, the LeucoPatch® may become an important new tool in the armamentarium in the management of diabetic foot ulcers which are hard-to-heal. People with diabetes and hard-to-heal ulcers of the foot will receive either pre-specified good standard care or good standard care supplemented by the application of the LeucoPatch® device. The primary outcome will be the percentage of ulcers healed within 20 weeks. Healing will be defined as complete epithelialisation without discharge that is maintained for 4 weeks and is confirmed by an observer blind to randomisation group. Ulcers of the foot are a major source of morbidity to patients with diabetes and costs to health care economies. The study population is designed to be as inclusive as possible with the aim of maximising the external validity of any findings. The primary outcome measure is healing within 20 weeks of randomisation and the trial also includes a number of secondary outcome measures. Among these are rate of change in ulcer area as a predictor of the likelihood of eventual healing, minor and major amputation of the target limb, the incidence of infection and quality of life. International Standard Randomised Controlled Trial, ISRCTN27665670 . Registered on 5 July 2013.

Balance Improvement Effects of Biofeedback Systems with State-of-the-Art Wearable Sensors: A Systematic Review.

PubMed

Ma, Christina Zong-Hao; Wong, Duo Wai-Chi; Lam, Wing Kai; Wan, Anson Hong-Ping; Lee, Winson Chiu-Chun

2016-03-25

Falls and fall-induced injuries are major global public health problems. Balance and gait disorders have been the second leading cause of falls. Inertial motion sensors and force sensors have been widely used to monitor both static and dynamic balance performance. Based on the detected performance, instant visual, auditory, electrotactile and vibrotactile biofeedback could be provided to augment the somatosensory input and enhance balance control. This review aims to synthesize the research examining the effect of biofeedback systems, with wearable inertial motion sensors and force sensors, on balance performance. Randomized and non-randomized clinical trials were included in this review. All studies were evaluated based on the methodological quality. Sample characteristics, device design and study characteristics were summarized. Most previous studies suggested that biofeedback devices were effective in enhancing static and dynamic balance in healthy young and older adults, and patients with balance and gait disorders. Attention should be paid to the choice of appropriate types of sensors and biofeedback for different intended purposes. Maximizing the computing capacity of the micro-processer, while minimizing the size of the electronic components, appears to be the future direction of optimizing the devices. Wearable balance-improving devices have their potential of serving as balance aids in daily life, which can be used indoors and outdoors.

Therapeutic orthosis and electrical stimulation for upper extremity hemiplegia after stroke: a review of effectiveness based on evidence.

PubMed

Aoyagi, Yoichiro; Tsubahara, Akio

2004-01-01

Upper extremity hemiplegia after stroke is common and disabling. Apart from conventional physical and occupational therapy, a number of additional approaches that use devices such as orthoses, prostheses, electrical stimulation, and robots have been introduced. The purpose of this review was to assess the clinical efficacy of such devices used for the affected upper extremities of acute, subacute, and chronic stroke patients. Assessments of their effectiveness and recommendations were based on the weight of published scientific evidence. The amount of evidence with respect to hand splints and shoulder slings is limited. Further study with a well-designed randomized controlled trial (RCT) is required to investigate accurately their short- and long-term efficacy. A number of studies suggested that the use of electrical stimulation for reducing shoulder subluxation or improving the function of wrist and finger extensors is effective during or shortly after the daily treatment period. The robotic approach to hemiplegic upper extremities appears to be a novel therapeutic strategy that may help improve hand and arm function. However, the longer term effectiveness after discontinuation as well as the motor recovery mechanism of electrical stimulation or robotic devices remains unclear. More research is needed to determine the evidence-based effectiveness of electrical stimulation or other devices for stroke survivors.

Balance Improvement Effects of Biofeedback Systems with State-of-the-Art Wearable Sensors: A Systematic Review

PubMed Central

Ma, Christina Zong-Hao; Wong, Duo Wai-Chi; Lam, Wing Kai; Wan, Anson Hong-Ping; Lee, Winson Chiu-Chun

2016-01-01

Falls and fall-induced injuries are major global public health problems. Balance and gait disorders have been the second leading cause of falls. Inertial motion sensors and force sensors have been widely used to monitor both static and dynamic balance performance. Based on the detected performance, instant visual, auditory, electrotactile and vibrotactile biofeedback could be provided to augment the somatosensory input and enhance balance control. This review aims to synthesize the research examining the effect of biofeedback systems, with wearable inertial motion sensors and force sensors, on balance performance. Randomized and non-randomized clinical trials were included in this review. All studies were evaluated based on the methodological quality. Sample characteristics, device design and study characteristics were summarized. Most previous studies suggested that biofeedback devices were effective in enhancing static and dynamic balance in healthy young and older adults, and patients with balance and gait disorders. Attention should be paid to the choice of appropriate types of sensors and biofeedback for different intended purposes. Maximizing the computing capacity of the micro-processer, while minimizing the size of the electronic components, appears to be the future direction of optimizing the devices. Wearable balance-improving devices have their potential of serving as balance aids in daily life, which can be used indoors and outdoors. PMID:27023558

Computational Analysis of Advanced Shape-Memory Alloy Devices Through a Robust Modeling Framework

NASA Astrophysics Data System (ADS)

Scalet, Giulia; Conti, Michele; Auricchio, Ferdinando

2017-06-01

Shape-memory alloys (SMA) provide significant advantages in various industrial fields, but their manufacturing and commercialization are currently hindered. This is attributed mainly to the poor knowledge of material behavior and the lack of standards in its mechanical characterization. SMA products are usually developed by trial-and-error testing to address specific design requirements, thus increasing costs and time. The development of simulation tools offers a possible solution to assist engineers and designers and allows to better understand SMA transformation phenomena. Accordingly, the purpose of the present paper is to numerically analyze and predict the response of spring-like actuators and septal occluders, which are industrial components exploiting the shape-memory and pseudoelastic properties of SMAs, respectively. The methodology includes two main stages: the implementation of the three-dimensional phenomenological model known as Souza- Auricchio model and the finite element modeling of the device. A discussion about the steps of each stage, as parameter identification and model generalizations, is provided. Validation results are presented through a comparison with the results of a performed experimental campaign. The framework proves good prediction capabilities and allows to reduce the number of experimental tests in the future.

A Wearable Multi-Site System for NMES-Based Hand Function Restoration.

PubMed

Crema, Andrea; Malesevic, Nebojsa; Furfaro, Ivan; Raschella, Flavio; Pedrocchi, Alessandra; Micera, Silvestro

2018-02-01

Reaching and grasping impairments significantly affect the quality of life for people who have experienced a stroke or spinal cord injury. The long-term well-being of patients varies greatly according to the restorable residual capabilities. Electrical stimulation could be a promising solution to restore motor functions in these conditions, but its use is not clinically widespread. Here, we introduce the HandNMES, an electrode array (EA) for neuromuscular electrical stimulation (NMES) aimed at grasp training and assistance. The device was designed to deliver electrical stimulation to extrinsic and intrinsic hand muscles. Six independent EAs, positioned on the user forearm and hand, deliver NMES pulses originating from an external stimulator equipped with demultiplexers for interfacing with a large number of electrodes. The garment was designed to be adaptable to user needs and anthropometric characteristics; size, shape, and contact materials can be customized, and stimulation characteristics such as intensity of stimulation and virtual electrode location, and size can be adjusted. We performed extensive tests with nine healthy subjects showing the efficacy of the HandNMES in terms of stimulation performance and personalization. Because encouraging results were achieved, in the coming months, the HandNMES device will be tested in pilot clinical trials.

A reanalysis of the Cu-7 intrauterine contraceptive device clinical trial and the incidence of pelvic inflammatory disease: a paradigm for assessing intrauterine contraceptive device safety.

PubMed

Roy, S; Azen, C

1994-06-01

We calculated and compared the incidence of pelvic inflammatory disease in a 10% random sample of the Cu-7 intrauterine contraceptive device (G.D. Searle & Co., Skokie, Ill.) clinical trial with the rates reported to the Food and Drug Administration and those in subsequent trials published in the world literature. A 10% random sample of the Cu-7 clinical trial was examined because calculations had demonstrated this random sample to be sufficient in size (n = 1614) to detect a difference in rates of pelvic inflammatory disease from those reported to the Food and Drug Administration. An audit of a subset of the patient files, compared with the original files in Skokie, Illinois, confirmed that the files available for analysis were complete. Standard definitions were used to identify cases of pelvic inflammatory disease and to calculate rates of pelvic inflammatory disease. The world literature on Cu-7 clinical trials was reviewed. The calculated crude and Pearl index rates of pelvic inflammatory disease were consistent with those rates previously reported to the Food and Drug Administration and published in the medical literature. Life-table pelvic inflammatory disease rates were not different between nulliparous and parous women and pelvic inflammatory disease did not differ from basal annual rates in fecund women. On the basis of the analysis of this 10% sample, the pelvic inflammatory disease patient rates reported to the Food and Drug Administration for the entire Cu-7 clinical trial are accurate and are similar to those published in the world literature.

Design of Phase II Non-inferiority Trials.

PubMed

Jung, Sin-Ho

2017-09-01

With the development of inexpensive treatment regimens and less invasive surgical procedures, we are confronted with non-inferiority study objectives. A non-inferiority phase III trial requires a roughly four times larger sample size than that of a similar standard superiority trial. Because of the large required sample size, we often face feasibility issues to open a non-inferiority trial. Furthermore, due to lack of phase II non-inferiority trial design methods, we do not have an opportunity to investigate the efficacy of the experimental therapy through a phase II trial. As a result, we often fail to open a non-inferiority phase III trial and a large number of non-inferiority clinical questions still remain unanswered. In this paper, we want to develop some designs for non-inferiority randomized phase II trials with feasible sample sizes. At first, we review a design method for non-inferiority phase III trials. Subsequently, we propose three different designs for non-inferiority phase II trials that can be used under different settings. Each method is demonstrated with examples. Each of the proposed design methods is shown to require a reasonable sample size for non-inferiority phase II trials. The three different non-inferiority phase II trial designs are used under different settings, but require similar sample sizes that are typical for phase II trials.

Adopting new technologies in stroke rehabilitation: the influence of the US health care system.

PubMed

Stein, J

2009-06-01

Stroke rehabilitation is entering a new era of technological innovation, including the development of robotic aids for therapy, peripheral electrical stimulation devices, and brain stimulation systems. These technologies have the potential to significantly improve the efficiency and efficacy of stroke rehabilitation. The United States health care system creates both opportunities for new technologies to be created and adopted, as well as important barriers. Inadequate support of clinical trials of the efficacy of new non-invasive devices is a particular concern for practitioners seeking to determine if new devices are clinically useful. Government support of clinical trials of efficacy, coupled with reform of FDA approval processes for novel therapies, is needed to create an evidence-based approach to improving stroke rehabilitation.

The optimal design of stepped wedge trials with equal allocation to sequences and a comparison to other trial designs.

PubMed

Thompson, Jennifer A; Fielding, Katherine; Hargreaves, James; Copas, Andrew

2017-12-01

Background/Aims We sought to optimise the design of stepped wedge trials with an equal allocation of clusters to sequences and explored sample size comparisons with alternative trial designs. Methods We developed a new expression for the design effect for a stepped wedge trial, assuming that observations are equally correlated within clusters and an equal number of observations in each period between sequences switching to the intervention. We minimised the design effect with respect to (1) the fraction of observations before the first and after the final sequence switches (the periods with all clusters in the control or intervention condition, respectively) and (2) the number of sequences. We compared the design effect of this optimised stepped wedge trial to the design effects of a parallel cluster-randomised trial, a cluster-randomised trial with baseline observations, and a hybrid trial design (a mixture of cluster-randomised trial and stepped wedge trial) with the same total cluster size for all designs. Results We found that a stepped wedge trial with an equal allocation to sequences is optimised by obtaining all observations after the first sequence switches and before the final sequence switches to the intervention; this means that the first sequence remains in the control condition and the last sequence remains in the intervention condition for the duration of the trial. With this design, the optimal number of sequences is [Formula: see text], where [Formula: see text] is the cluster-mean correlation, [Formula: see text] is the intracluster correlation coefficient, and m is the total cluster size. The optimal number of sequences is small when the intracluster correlation coefficient and cluster size are small and large when the intracluster correlation coefficient or cluster size is large. A cluster-randomised trial remains more efficient than the optimised stepped wedge trial when the intracluster correlation coefficient or cluster size is small. A cluster-randomised trial with baseline observations always requires a larger sample size than the optimised stepped wedge trial. The hybrid design can always give an equally or more efficient design, but will be at most 5% more efficient. We provide a strategy for selecting a design if the optimal number of sequences is unfeasible. For a non-optimal number of sequences, the sample size may be reduced by allowing a proportion of observations before the first or after the final sequence has switched. Conclusion The standard stepped wedge trial is inefficient. To reduce sample sizes when a hybrid design is unfeasible, stepped wedge trial designs should have no observations before the first sequence switches or after the final sequence switches.

The Barrel vascular reconstruction device for endovascular coiling of wide-necked intracranial aneurysms: a multicenter, prospective, post-marketing study.

PubMed

Gory, Benjamin; Blanc, Raphaël; Turjman, Francis; Berge, Jérôme; Piotin, Michel

2018-02-02

The Barrel vascular reconstruction device (Barrel VRD) is a novel stent with design features that allow endovascular coiling of wide-necked bifurcation aneurysms while preserving adjacent branches, without necessitating dual stent implantation. This study aimed to assess the safety and effectiveness of the Barrel VRD at 12-month follow-up. The Barrel VRD trial is a prospective, multicenter, observational post-marketing registry evaluating the use of the Barrel VRD for treatment of wide-necked bifurcation aneurysms. The primary effectiveness endpoint was successful aneurysm treatment measured by digital subtraction angiography with a Raymond-Roy occlusion grade of 1 or 2 in the absence of retreatment, parent artery stenosis (>50%), or target aneurysm rupture at 12 months. The primary safety endpoint was the absence of neurological death or major stroke at 12 months. Twenty patients were enrolled from December 2013 to December 2014. The device was implanted in 19 patients with 19 aneurysms (8 middle cerebral artery, 4 anterior communicating artery, 1 internal carotid artery terminus, 4 basilar artery aneurysms; mean dome height 5.7±1.91 mm; mean neck length 4.8±1.35 mm, mean dome-to-neck ratio 1.6±2.0). Coiling was performed in all cases. The primary effectiveness endpoint was achieved in 78.9% of subjects (15/19; 12 complete occlusions, 3 neck remnants), and the primary safety endpoint was 5.3% (1/19). This prospective study demonstrates that the Barrel VRD device resulted in ~80% occlusion rates and ~5% rates of neurological complications at 1 year after endovascular treatment of wide-necked bifurcation intracranial aneurysms. REGISTERED CLINICAL TRIAL: NCT02125097;Results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Penile measurements in Tanzanian males: guiding circumcision device design and supply forecasting.

PubMed

Chrouser, Kristin; Bazant, Eva; Jin, Linda; Kileo, Baldwin; Plotkin, Marya; Adamu, Tigistu; Curran, Kelly; Koshuma, Sifuni

2013-08-01

Voluntary medical male circumcision decreases the risk in males of HIV infection through heterosexual intercourse by about 60% in clinical trials and 73% at post-trial followup. In 2007 WHO and the Joint United Nations Programme on HIV/AIDS (UNAIDS) recommended that countries with a low circumcision rate and high HIV prevalence expand voluntary medical male circumcision programs as part of a national HIV prevention strategy. Devices for adult/adolescent male circumcision could accelerate the pace of scaling up voluntary medical male circumcision. Detailed penile measurements of African males are required for device development and supply size forecasting. Consenting males undergoing voluntary medical male circumcision at 3 health facilities in the Iringa region, Tanzania, underwent measurement of the penile glans, shaft and foreskin. Age, Tanner stage, height and weight were recorded. Measurements were analyzed by age categories. Correlations of penile parameters with height, weight and body mass index were calculated. In 253 Tanzanian males 10 to 47 years old mean ± SD penile length in adults was 11.5 ± 1.6 cm, mean shaft circumference was 8.7 ± 0.9 cm and mean glans circumference was 8.8 ± 0.9 cm. As expected, given the variability of puberty, measurements in younger males varied significantly. Glans circumference highly correlated with height (r = 0.80) and weight (r = 0.81, each p <0.001). Stretched foreskin diameter moderately correlated with height (r = 0.68) and weight (r = 0.71, each p <0.001). Our descriptive study provides penile measurements of males who sought voluntary medical male circumcision services in Iringa, Tanzania. To our knowledge this is the first study in a sub-Saharan African population that provides sufficiently detailed glans and foreskin dimensions to inform voluntary medical male circumcision device development and size forecasting. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

“Cold” X5 Hairlaser™ used to treat male androgenic alopecia and hair growth: an uncontrolled pilot study

PubMed Central

2014-01-01

Background Various trials have been conducted on the management and treatment of androgenic alopecia (AGA) or male pattern hair loss using a variety of laser and light sources. Methods For this feasibility study, the population was composed of males between the ages of 20 and 60 years who have been experiencing active hair loss within the last 12 months and the diagnosis of AGA. They also had a Norwood-Hamilton classification of 3, 3A, 3 V, 4, 4A, or 5 for the hair thinning patterns and skin type I, II, III, or IV on the Fitzpatrick skin type scale. This two-arm randomized, parallel group study design employed stratifying randomization to balance treatment assignment within three investigational centers with at least 2 subjects enrolled in each Fitzpatrick skin type. Results A statistically significant positive trend in hair growth was observed from this pilot study, to evaluate the efficacy of the novel cold X5 hairlaser device for treating male androgenic alopecia. From the repeated measures analysis of variance, difference in mean hair counts over time was statistically significant (F = 7.70; p-value < 0.0001). Subsequent, linear regression of mean hair counts at each time point was performed, and post-hoc analysis found an increasing trend of hair growth over time that was statistically significant (p-value < 0.0001) with the estimated slope of 1.406. Increased hair counts from the baseline to the end of the 26-week period were found to be strongly significant (p-value = 0.0003). Conclusion Albeit, sham device failure and resultant missing data from the control group, the positive trend hair growth, was observed due to the chronic use of X5hairlaser device. This positive benefit while in full agreement with other low laser hair devices requires intensive further investigation. Trial registration NCT02067260 PMID:24559020

Patient perception of Breezhaler® and Ellipta® device feedback mechanisms in COPD: The ADVANTAGE Study.

PubMed

Altman, Pablo; Bergna, Miguel A; Garcia, Gabriel R; Guerin, Tadhg; Pino, Andrea V; Whiteford, John L

2018-05-15

The primary objective of the ADVANTAGE study was to compare device-naïve chronic obstructive pulmonary disease (COPD) patients' perception of the Breezhaler ® and Ellipta ® devices' feedback mechanisms of dose delivery confirmation. The secondary objective was to assess comfort with the inhalers' mouthpiece in terms of ease to form a tight seal around the mouthpiece. These objectives were achieved by using a novel, patient perception of inhaler questionnaire developed and tested during cognitive interviews of patients by Evidera, London, United Kingdom. Ten COPD patients were interviewed to collect feedback on the interpretation, relevance and language of the questionnaire. This questionnaire was then used in ADVANTAGE to compare patients' perception (n = 100) of both devices. Patients completed the questionnaire after a single inhalation of placebo through each inhaler. Using the final questionnaire, patients reported being more confident of the feedback mechanism of Breezhaler than that of the Ellipta device (mean score 4.3 versus 3.6 respectively, estimated difference [95% CI]: 0.75 [0.51, 0.99], p < .0001). Patients also reported better comfort (ease to form a tight seal with the lips) with the Breezhaler mouthpiece than the Ellipta mouthpiece (mean score 4.3 versus 3.9 respectively, estimated difference [95% CI]: 0.41 [0.21, 0.61], p < .0001). There were no safety concerns associated with either device. COPD patients showed greater preference for the Breezhaler over the Ellipta inhaler for confidence of dose delivery and comfort of the mouthpiece. The trial is registered at ClinicalTrials.gov (ClinicalTrials.gov number NCT02551224).

A Stabilization Device That Promotes the Efficiency of Cardiopulmonary Resuscitation during Ambulance Transportation to the Level as under Non-Moving Conditions

PubMed Central

Foo, Ning-Ping; Chang, Jer-Hao; Su, Shih-Bin; Chen, Kow-Tong; Cheng, Ching-Fa; Chen, Pei-Chung

2014-01-01

Background The survival rate of patients with out-of-hospital cardiac arrest is low, and measures to improve the quality of cardiopulmonary resuscitation (CPR) during ambulance transportation are desirable. We designed a stabilization device, and in a randomized crossover trial we found performing CPR in a moving ambulance with the device (MD) could achieve better efficiency than that without the device (MND), but the efficiency was lower than that in a non-moving ambulance (NM). Purpose To evaluate whether a modified version of the stabilization device, can promote further the quality of CPR during ambulance transportation. Methods Participants of the previous study were recruited, and they performed CPR for 10 minutes in a moving ambulance with the modified version of the stabilization device (MVSD). The primary outcomes were effective chest compressions and no-flow fraction recorded by a skill-reporter manikin. The secondary outcomes included back pain, physiological parameters, and the participants' rating about the device after performing CPR. Results The overall effective compressions in 10 minutes were 86.4±17.5% for NM, 60.9±14.6% for MND, 69.7±22.4% for MD, and 86.6%±13.2% for MVSD (p<0.001). Whereas changes in back pain severity and physiology parameters were similar under all conditions, MVSD had the lowest no-flow fraction. Differences in effective compressions and the no-flow fraction between MVSD and NM did not reach statistical significance. Conclusions The use of the modified device can improve quality of CPR in a moving ambulance to a level similar to that in a non-moving condition without increasing the severity of back pain. PMID:25329643

First Australian experiences with an oral volume restriction device to change eating behaviors and assist with weight loss.

PubMed

McGee, Toni L; Grima, Mariee T; Hewson, Ian D; Jones, Kay M; Duke, Ellen B; Dixon, John B

2012-01-01

Eating behaviors impact satiety and caloric intake so should be considered in any weight-loss program. A novel custom-made oral device has been designed to be worn in the upper palate while eating in order to slow eating-rate and aid weight loss. The aim of this study was to assess the device's potential impact on weight-loss and gain first impressions among overweight/obese Australians. Twenty participants (M: 6, F: 14, mean age 36 years, BMI 27-33 kg/m(2)) were enrolled in a 4-month open-label trial. Each received a device and nutritionist-delivered diet plan. Weight, compliance, and acceptability were assessed fortnightly. Anthropometry, biochemical and clinical outcomes were measured at baseline and 16 weeks. Sixteen participants completed the study. Mean weight-loss was 4.9 ± 0.9 kg, or 5.2 ± 0.9% initial bodyweight (P < 0.001, n = 20, intention-to-treat). There were no significant adverse events (AEs), but 65% of participants required device adjustment by the dentist. Compliance (defined as >5 uses/week) was achieved by 80% of participants and correlated positively with weight-loss (R = 0.68, P = 0.001). All reported that the device was comfortable and reduced bite-size, promoted chewing and slowed eating-rate. Most observed either no change, or increased satiety, despite reduced meal sizes. For most, speech difficulties discouraged device use in social settings. All reported greater awareness of food choices, portion sizes and eating-rate. Subjective control of dietary behaviors, measured by the Three Factor Eating Questionnaire (TFEQ), improved significantly. The device should be explored as an adjunct to dietary composition change in weight-management programs, to assist patients to modify eating behaviors and achieve successful weight-loss.

A stabilization device that promotes the efficiency of cardiopulmonary resuscitation during ambulance transportation to the level as under non-moving conditions.

PubMed

Foo, Ning-Ping; Chang, Jer-Hao; Su, Shih-Bin; Chen, Kow-Tong; Cheng, Ching-Fa; Chen, Pei-Chung; Lin, Tsung-Yi; Guo, How-Ran

2014-01-01

The survival rate of patients with out-of-hospital cardiac arrest is low, and measures to improve the quality of cardiopulmonary resuscitation (CPR) during ambulance transportation are desirable. We designed a stabilization device, and in a randomized crossover trial we found performing CPR in a moving ambulance with the device (MD) could achieve better efficiency than that without the device (MND), but the efficiency was lower than that in a non-moving ambulance (NM). To evaluate whether a modified version of the stabilization device, can promote further the quality of CPR during ambulance transportation. Participants of the previous study were recruited, and they performed CPR for 10 minutes in a moving ambulance with the modified version of the stabilization device (MVSD). The primary outcomes were effective chest compressions and no-flow fraction recorded by a skill-reporter manikin. The secondary outcomes included back pain, physiological parameters, and the participants' rating about the device after performing CPR. The overall effective compressions in 10 minutes were 86.4±17.5% for NM, 60.9±14.6% for MND, 69.7±22.4% for MD, and 86.6%±13.2% for MVSD (p<0.001). Whereas changes in back pain severity and physiology parameters were similar under all conditions, MVSD had the lowest no-flow fraction. Differences in effective compressions and the no-flow fraction between MVSD and NM did not reach statistical significance. The use of the modified device can improve quality of CPR in a moving ambulance to a level similar to that in a non-moving condition without increasing the severity of back pain.

Spray System Trials in the Icing Research Tunnel

NASA Image and Video Library

1949-09-21

The spray bar system introduces water droplets into the Icing Research Tunnel’s air stream at the National Advisory Committee for Aeronautics (NACA) Lewis Flight Propulsion Laboratory. The icing tunnel was designed in the early 1940s to study ice accretion on airfoils and models. The Carrier Corporation designed a refrigeration system that reduced temperatures to -45° F. The tunnel’s drive fan generated speeds up to 400 miles per hour. The uniform injection of water droplets to the air was a key element of the facility’s operation. The system had to generate small droplets, distribute them uniformly throughout the airstream, and resist freezing and blockage. The Icing Research Tunnel’s designers struggled to develop a realistic spray system because they did not have access to data on the size of naturally occurring water droplets. For five years a variety of different designs were painstakingly developed and tested before the system was perfected. This photograph shows one of the trials using eight air-atomizing nozzles placed 48 feet upstream from the test section. A multi-cylinder device measured the size, liquid content, and distribution of the water droplets. The final system that was put into operation in 1950 included six horizontal spray bars with 80 nozzles that produced a 4- by 4-foot cloud in the test section. The Icing Research Tunnel produced excellent data throughout the 1950s and provided the basis for a hot air anti-icing system used on many transport aircraft.

Mobile access to virtual randomization for investigator-initiated trials.

PubMed

Deserno, Thomas M; Keszei, András P

2017-08-01

Background/aims Randomization is indispensable in clinical trials in order to provide unbiased treatment allocation and a valid statistical inference. Improper handling of allocation lists can be avoided using central systems, for example, human-based services. However, central systems are unaffordable for investigator-initiated trials and might be inaccessible from some places, where study subjects need allocations. We propose mobile access to virtual randomization, where the randomization lists are non-existent and the appropriate allocation is computed on demand. Methods The core of the system architecture is an electronic data capture system or a clinical trial management system, which is extended by an R interface connecting the R server using the Java R Interface. Mobile devices communicate via the representational state transfer web services. Furthermore, a simple web-based setup allows configuring the appropriate statistics by non-statisticians. Our comprehensive R script supports simple randomization, restricted randomization using a random allocation rule, block randomization, and stratified randomization for un-blinded, single-blinded, and double-blinded trials. For each trial, the electronic data capture system or the clinical trial management system stores the randomization parameters and the subject assignments. Results Apps are provided for iOS and Android and subjects are randomized using smartphones. After logging onto the system, the user selects the trial and the subject, and the allocation number and treatment arm are displayed instantaneously and stored in the core system. So far, 156 subjects have been allocated from mobile devices serving five investigator-initiated trials. Conclusion Transforming pre-printed allocation lists into virtual ones ensures the correct conduct of trials and guarantees a strictly sequential processing in all trial sites. Covering 88% of all randomization models that are used in recent trials, virtual randomization becomes available for investigator-initiated trials and potentially for large multi-center trials.

Patient Engagement in Neurological Clinical Trials Design: A Conference Summary.

PubMed

Cobb, Enesha M; Meurer, William; Harney, Deneil; Silbergleit, Robert; Lake, Bray Patrick; Clark, Christina; Gipson, Debbie; Barsan, William

2015-12-01

The conference objectives included educating patients and advocates about clinical trials, educating the clinical research community about patient perspectives on participating in clinical trial design, and identifying strategies to increase participation in clinical trial design for neurological disorders. Observations were noted during a 1-day conference attended by patients, patient advocates, clinical trial staff, and investigators. The conference offered didactic sessions, small, and large group discussions. Conference participants were patients, patient advocates, clinical trial staff, students, and investigators interested in engaging patients in clinical trial design for neurological disorders. Conference participants were asked to consider lessons learned that could increase patient engagement in clinical trial design. We found that there is growing interest in including patients in the design of clinical trials for neurological disorders. Several themes emerged on how to move forward: networking; the multifaceted roles of advocates in research; training and education; creating patient-researcher partnerships; and clinical trials regulation issues. The conference provided a forum for dialogue regarding stakeholder engagement in the design of clinical trials for neurological disorders. This experience provides a template for replication and dissemination of this conference and informs next steps to accelerate the pathway from dialogue to action. © 2015 Wiley Periodicals, Inc.

Test and evaluation of Japanese GPR-EMI dual sensor systems at Benkovac test site in Croatia

NASA Astrophysics Data System (ADS)

Ishikawa, J.; Furuta, K.; Pavković, Nikola

2007-04-01

This paper presents an experimental design and the evaluation result of a trial that were carried out from 1 February to 9 March 2006 using real PMA-1A and PMA-2 landmines at the Benkovac test site in Croatia. The objective of the Croatia- Japan joint trial is to evaluate dual sensor systems, which use both ground penetrating radar (GPR) and electromagnetic inductive (EMI) sensors. A comparative trial was also carried out by Croatian deminers using an existing EMI sensor, i.e., a metal detector (MD). The trial aims at evaluating differences in performance between dual sensors and MDs, especially in terms of discrimination of landmines from metal fragments and extension of detectable range in the depth direction. Devices evaluated here are 4 prototypes of anti-personnel landmine detection systems developed under a project of the Japan Science and Technology Agency (JST), the supervising authority of which is the Ministry of Education, Culture, Sports, Science and Technology (MEXT). The prototypes provide operators with subsurface images, and final decision whether a shadow in the image is a real landmine or not is left to the operator. This is similar to the way that medical doctors find cancer by reading CT images. Since operators' pre-knowledge of locations of buried targets significantly influences the test result, three test lanes, which have 3 different kinds of soils, have been designed to be suitable for blind tests. The result showed that the dual sensor systems have a potential to discriminate landmines from metal fragments and that probability of detection for small targets in mineralized soils can be improved by using GPR.

Study design and methodology for a multicentre, randomised controlled trial of transcranial direct current stimulation as a treatment for unipolar and bipolar depression.

PubMed

Alonzo, Angelo; Aaronson, Scott; Bikson, Marom; Husain, Mustafa; Lisanby, Sarah; Martin, Donel; McClintock, Shawn M; McDonald, William M; O'Reardon, John; Esmailpoor, Zeinab; Loo, Colleen

2016-11-01

Transcranial Direct Current Stimulation (tDCS) is a new, non-invasive neuromodulation approach for treating depression that has shown promising efficacy. The aim of this trial was to conduct the first international, multicentre randomised controlled trial of tDCS as a treatment for unipolar and bipolar depression. The study recruited 120 participants across 6 sites in the USA and Australia. Participants received active or sham tDCS (2.5mA, 20 sessions of 30min duration over 4weeks), followed by a 4-week open label active treatment phase and a 4-week taper phase. Mood and neuropsychological outcomes were assessed with the primary antidepressant outcome measure being the Montgomery-Asberg Depression Rating Scale (MADRS). A neuropsychological battery was administered to assess safety and examine cognitive effects. The study also investigated the possible influence of genetic polymorphisms on outcomes. The trial was triple-blinded. Participants, tDCS treaters and study raters were blinded to each participant's tDCS group allocation in the sham-controlled phase. Specific aspects of tDCS administration, device operation and group allocation were designed to optimise the integrity of blinding. Outcome measures will be tested using a mixed effects repeated measures analysis with the primary factors being Time as a repeated measure, tDCS condition (sham or active) and Diagnosis (unipolar or bipolar). A restricted number of random and fixed factors will be included as required to account for extraneous differences. As a promising treatment, tDCS has excellent potential for translation into widespread clinical use, being cost effective, portable, easy to operate and well tolerated. Copyright © 2016 Elsevier Inc. All rights reserved.

Rationale and design of a randomized trial of home electronic symptom and lung function monitoring to detect cystic fibrosis pulmonary exacerbations: the early intervention in cystic fibrosis exacerbation (eICE) trial.

PubMed

Lechtzin, N; West, N; Allgood, S; Wilhelm, E; Khan, U; Mayer-Hamblett, N; Aitken, M L; Ramsey, B W; Boyle, M P; Mogayzel, P J; Goss, C H

2013-11-01

Acute pulmonary exacerbations are central events in the lives of individuals with cystic fibrosis (CF). Pulmonary exacerbations lead to impaired lung function, worse quality of life, and shorter survival. We hypothesized that aggressive early treatment of acute pulmonary exacerbation may improve clinical outcomes. Describe the rationale of an ongoing trial designed to determine the efficacy of home monitoring of both lung function measurements and symptoms for early detection and subsequent early treatment of acute CF pulmonary exacerbations. A randomized, non-blinded, multi-center trial in 320 individuals with CF aged 14 years and older. The study compares usual care to a twice a week assessment of home spirometry and CF respiratory symptoms using an electronic device with data transmission to the research personnel to identify and trigger early treatment of CF pulmonary exacerbation. Participants will be enrolled in the study for 12 months. The primary endpoint is change in FEV1 (L) from baseline to 12 months determined by a linear mixed effects model incorporating all quarterly FEV1 measurements. Secondary endpoints include time to first acute protocol-defined pulmonary exacerbation, number of acute pulmonary exacerbations, number of hospitalization days for acute pulmonary exacerbation, time from the end of acute pulmonary exacerbation to onset of subsequent pulmonary exacerbation, change in health related quality of life, change in treatment burden, change in CF respiratory symptoms, and adherence to the study protocol. This study is a first step in establishing alternative approaches to the care of CF pulmonary exacerbations. We hypothesize that early treatment of pulmonary exacerbations has the potential to slow lung function decline, reduce respiratory symptoms and improve the quality of life for individuals with CF. © 2013.

Handheld vs. Laptop Computers for Electronic Data Collection in Clinical Research: A Crossover Randomized Trial

PubMed Central

Haller, Guy; Haller, Dagmar M.; Courvoisier, Delphine S.; Lovis, Christian

2009-01-01

Objective To compare users' speed, number of entry errors and satisfaction in using two current devices for electronic data collection in clinical research: handheld and laptop computers. Design The authors performed a randomized cross-over trial using 160 different paper-based questionnaires and representing altogether 45,440 variables. Four data coders were instructed to record, according to a random predefined and equally balanced sequence, the content of these questionnaires either on a laptop or on a handheld computer. Instructions on the kind of device to be used were provided to data-coders in individual sealed and opaque envelopes. Study conditions were controlled and the data entry process performed in a quiet environment. Measurements The authors compared the duration of the data recording process, the number of errors and users' satisfaction with the two devices. The authors divided errors into two separate categories, typing and missing data errors. The original paper-based questionnaire was used as a gold-standard. Results The overall duration of the recording process was significantly reduced (2.0 versus 3.3 min) when data were recorded on the laptop computer (p < 0.001). Data accuracy also improved. There were 5.8 typing errors per 1,000 entries with the laptop compared to 8.4 per 1,000 with the handheld computer (p < 0.001). The difference was even more important for missing data which decreased from 22.8 to 2.9 per 1,000 entries when a laptop was used (p < 0.001). Users found the laptop easier, faster and more satisfying to use than the handheld computer. Conclusions Despite the increasing use of handheld computers for electronic data collection in clinical research, these devices should be used with caution. They double the duration of the data entry process and significantly increase the risk of typing errors and missing data. This may become a particularly crucial issue in studies where these devices are provided to patients or healthcare workers, unfamiliar with Computer Technologies, for self-reporting or research data collection processes. PMID:19567799

Postapproval Development Options in COPD: A Case Study in Value-Based Healthcare Systems.

PubMed

Murphy, Michael F; Antonini, Paola; Lai, Zhihong Vicki

2011-01-01

Research and development activities in an era of globalization encounter a mosaic of providers, products, services, and intermediaries; regulatory and other government institutions; and consumers. The introduction of novel therapeutics into this environment mandates research programs that are relevant to the registration process, payers and purchasers, transparent pricing, and rule-driven business practices, while providing data relevant to marketing initiatives internationally. To outline an example for clinical development programs that incorporate the perspective of multiple stakeholders into a portfolio of study designs to provide optimal data platforms that can resonate with diverse recipients. A contract research organization directly involved in the design, execution, and analysis of clinical trials for new drugs and devices across pharmaceutical and biotechnology companies provides a unique perspective regarding opportunities and challenges within the international clinical research environment. Drs Murphy, Antonini, and Lai, representing Worldwide Clinical Trials, utilize chronic obstructive pulmonary disease as a demonstration project exploiting its prevalence, direct and indirect costs, and the rapid infusion/diffusion of innovative therapy into practice as a rationale for focus, and illustrate methods of informing registration and technology assessments during a prototypical development process. By virtue of its chronicity, prevalence, and pattern of healthcare utilization, chronic obstructive pulmonary disease provides an ideal case for illustrating the application of clinical trial methodology that can facilitate data evaluation through the prism of multiple stakeholders. Adding an international dimension exacerbates system complexity and serves to illustrate the breadth of issues that can be addressed within this therapeutic area.

Wire-Interwoven Nitinol Stent Outcome in the Superficial Femoral and Proximal Popliteal Arteries: Twelve-Month Results of the SUPERB Trial.

PubMed

Garcia, Lawrence; Jaff, Michael R; Metzger, Christopher; Sedillo, Gino; Pershad, Ashish; Zidar, Frank; Patlola, Raghotham; Wilkins, Robert G; Espinoza, Andrey; Iskander, Ayman; Khammar, George S; Khatib, Yazan; Beasley, Robert; Makam, Satyaprakash; Kovach, Richard; Kamat, Suraj; Leon, Luis R; Eaves, William Britton; Popma, Jeffrey J; Mauri, Laura; Donohoe, Dennis; Base, Carol C; Rosenfield, Kenneth

2015-05-01

Stent-based therapy in the superficial femoral and popliteal arteries in patients with peripheral artery disease is compromised by restenosis and risk of stent fracture or distortion. A novel self-expanding nitinol stent was developed that incorporates an interwoven-wire design (Supera stent, IDEV Technologies, Inc, Webster, TX) to confer greater radial strength, flexibility, and fracture resistance. This prospective, multicenter, investigational device exemption, single-arm trial enrolled 264 patients with symptomatic peripheral artery disease undergoing percutaneous treatment of de novo or restenotic lesions of the superficial femoral or proximal popliteal (femoropopliteal) artery. Freedom from death, target lesion revascularization, or any amputation of the index limb at 30 days (+ 7 days) postprocedure was achieved in 99.2% (258/260) of patients (P < 0.001). Primary patency at 12 months (360 ± 30 days) was achieved in 78.9% (180/228) of the population (P < 0.001). Primary patency by Kaplan-Meier analysis at 12 months (360 days) was 86.3%. No stent fracture was observed by independent core laboratory analysis in the 243 stents (228 patients) evaluated at 12 months. Clinical assessment at 12 months demonstrated improvement by at least 1 Rutherford-Becker category in 88.7% of patients. The SUPERB Trial, an investigational device exemption study using an interwoven nitinol wire stent in the femoropopliteal artery, achieved the efficacy and safety performance goals predesignated by the Food and Drug Administration. On the basis of the high primary patency rate, absence of stent fracture, and significant improvements in functional and quality-of-life measures, the Supera stent provides safe and effective treatment of femoropopliteal lesions in symptomatic patients with peripheral artery disease. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00933270. © 2015 American Heart Association, Inc.

Biomarker-Guided Non-Adaptive Trial Designs in Phase II and Phase III: A Methodological Review

PubMed Central

Antoniou, Miranta; Kolamunnage-Dona, Ruwanthi; Jorgensen, Andrea L.

2017-01-01

Biomarker-guided treatment is a rapidly developing area of medicine, where treatment choice is personalised according to one or more of an individual’s biomarker measurements. A number of biomarker-guided trial designs have been proposed in the past decade, including both adaptive and non-adaptive trial designs which test the effectiveness of a biomarker-guided approach to treatment with the aim of improving patient health. A better understanding of them is needed as challenges occur both in terms of trial design and analysis. We have undertaken a comprehensive literature review based on an in-depth search strategy with a view to providing the research community with clarity in definition, methodology and terminology of the various biomarker-guided trial designs (both adaptive and non-adaptive designs) from a total of 211 included papers. In the present paper, we focus on non-adaptive biomarker-guided trial designs for which we have identified five distinct main types mentioned in 100 papers. We have graphically displayed each non-adaptive trial design and provided an in-depth overview of their key characteristics. Substantial variability has been observed in terms of how trial designs are described and particularly in the terminology used by different authors. Our comprehensive review provides guidance for those designing biomarker-guided trials. PMID:28125057

A Critical Assessment of the Evidence for Low-Level Laser Therapy in the Treatment of Hair Loss.

PubMed

Gupta, Aditya K; Foley, Kelly A

2017-02-01

Low-level laser therapy (LLLT) is currently in use to stimulate hair growth and is quickly gaining in popularity due to the ease of use and absence of side effects. In 2015 alone, the number of LLLT devices with the Food and Drug Administration clearance has doubled. To consolidate evidence and establish which data are still required for the widespread acceptance of LLLT for hair loss therapy. A thorough search of the PubMed database was conducted to obtain studies investigating LLLT for androgenetic alopecia in men and women. Nine trials were identified for comb and helmet/cap devices, five of which were randomized controlled trials. Data comparison across LLLT trials and with traditional hair loss therapy (minoxidil, finasteride) was not straight forward because there was a lack of visual evidence, sample sizes were low, and there were large variations in study duration and efficacy measurements. There are a number of unanswered questions about the optimum treatment regimen, including maintenance treatment and the long-term consequences of LLLT use. Moving forward, protocols should be standardized across trials. Moreover, it is recommended that future trials include visual evidence and trial duration be expanded to 12 months.

Extracorporeal carbon dioxide removal for patients with acute respiratory failure secondary to the acute respiratory distress syndrome: a systematic review

PubMed Central

2014-01-01

Acute respiratory distress syndrome (ARDS) continues to have significant mortality and morbidity. The only intervention proven to reduce mortality is the use of lung-protective mechanical ventilation strategies, although such a strategy may lead to problematic hypercapnia. Extracorporeal carbon dioxide removal (ECCO2R) devices allow uncoupling of ventilation from oxygenation, thereby removing carbon dioxide and facilitating lower tidal volume ventilation. We performed a systematic review to assess efficacy, complication rates, and utility of ECCO2R devices. We included randomised controlled trials (RCTs), case–control studies and case series with 10 or more patients. We searched MEDLINE, Embase, LILACS (Literatura Latino Americana em Ciências da Saúde), and ISI Web of Science, in addition to grey literature and clinical trials registries. Data were independently extracted by two reviewers against predefined criteria and agreement was reached by consensus. Outcomes of interest included mortality, intensive care and hospital lengths of stay, respiratory parameters and complications. The review included 14 studies with 495 patients (two RCTs and 12 observational studies). Arteriovenous ECCO2R was used in seven studies, and venovenous ECCO2R in seven studies. Available evidence suggests no mortality benefit to ECCO2R, although post hoc analysis of data from the most recent RCT showed an improvement in ventilator-free days in more severe ARDS. Organ failure-free days or ICU stay have not been shown to decrease with ECCO2R. Carbon dioxide removal was widely demonstrated as feasible, facilitating the use of lower tidal volume ventilation. Complication rates varied greatly across the included studies, representing technological advances. There was a general paucity of high-quality data and significant variation in both practice and technology used among studies, which confounded analysis. ECCO2R is a rapidly evolving technology and is an efficacious treatment to enable protective lung ventilation. Evidence for a positive effect on mortality and other important clinical outcomes is lacking. Rapid technological advances have led to major changes in these devices and together with variation in study design have limited applicability of analysis. Further well-designed adequately powered RCTs are needed. PMID:25033302

A trial of an impedance threshold device in out-of-hospital cardiac arrest.

PubMed

Aufderheide, Tom P; Nichol, Graham; Rea, Thomas D; Brown, Siobhan P; Leroux, Brian G; Pepe, Paul E; Kudenchuk, Peter J; Christenson, Jim; Daya, Mohamud R; Dorian, Paul; Callaway, Clifton W; Idris, Ahamed H; Andrusiek, Douglas; Stephens, Shannon W; Hostler, David; Davis, Daniel P; Dunford, James V; Pirrallo, Ronald G; Stiell, Ian G; Clement, Catherine M; Craig, Alan; Van Ottingham, Lois; Schmidt, Terri A; Wang, Henry E; Weisfeldt, Myron L; Ornato, Joseph P; Sopko, George

2011-09-01

The impedance threshold device (ITD) is designed to enhance venous return and cardiac output during cardiopulmonary resuscitation (CPR) by increasing the degree of negative intrathoracic pressure. Previous studies have suggested that the use of an ITD during CPR may improve survival rates after cardiac arrest. We compared the use of an active ITD with that of a sham ITD in patients with out-of-hospital cardiac arrest who underwent standard CPR at 10 sites in the United States and Canada. Patients, investigators, study coordinators, and all care providers were unaware of the treatment assignments. The primary outcome was survival to hospital discharge with satisfactory function (i.e., a score of ≤3 on the modified Rankin scale, which ranges from 0 to 6, with higher scores indicating greater disability). Of 8718 patients included in the analysis, 4345 were randomly assigned to treatment with a sham ITD and 4373 to treatment with an active device. A total of 260 patients (6.0%) in the sham-ITD group and 254 patients (5.8%) in the active-ITD group met the primary outcome (risk difference adjusted for sequential monitoring, -0.1 percentage points; 95% confidence interval, -1.1 to 0.8; P=0.71). There were also no significant differences in the secondary outcomes, including rates of return of spontaneous circulation on arrival at the emergency department, survival to hospital admission, and survival to hospital discharge. Use of the ITD did not significantly improve survival with satisfactory function among patients with out-of-hospital cardiac arrest receiving standard CPR. (Funded by the National Heart, Lung, and Blood Institute and others; ROC PRIMED ClinicalTrials.gov number, NCT00394706.).

Effectiveness of a Smartphone application and wearable device for weight loss in overweight or obese primary care patients: protocol for a randomised controlled trial.

PubMed

Granado-Font, Esther; Flores-Mateo, Gemma; Sorlí-Aguilar, Mar; Montaña-Carreras, Xavier; Ferre-Grau, Carme; Barrera-Uriarte, Maria-Luisa; Oriol-Colominas, Eulàlia; Rey-Reñones, Cristina; Caules, Iolanda; Satué-Gracia, Eva-María

2015-06-04

To evaluate the effectiveness of an experimental intervention based on standard diet recommendations plus free Smartphone application (app) and wearable device for weight loss, compared with the standard diet intervention alone, in primary care patients aged 18 years or older who are overweight or obese. Multicentre randomized, controlled clinical trial. Primary health care centres in the city of Tarragona and surrounding areas. 70 primary care patients, aged 18 years or older, with body mass index of 25 g/m2 or greater who wish to lose weight. Description of the intervention: 12 months of standard diet recommendations without (n = 35) or with (n = 35) assistance of a free Smartphone app that allows the participant to maintain a record of dietary intake and a bracelet monitor that records physical activity. The outcomes will be weight loss at 12 months (primary outcome), changes in physical activity and cardiometabolic risk factors, frequency of app use, and participant satisfaction after 12 months. The results of our study will offer evidence of the effectiveness of an intervention using one of the most popular free apps and wearable devices in achieving weight loss among patients who are overweight or obese. If these new technologies are proven effective in our population, they could be readily incorporated into primary care interventions promoting healthy weight. The open design and study characteristics make it impossible for the participants and researchers to be blinded to study group assignment. Researchers responsible for data analysis will be blinded to participant allocation. Clinical Register: NCT02417623. Registered 26 March 2015.

Clinical trial quality: From supervision to collaboration and beyond.

PubMed

Meeker-O'Connell, Ann; Glessner, Coleen

2018-02-01

Over the past decade, clinical trial quality has evolved from an after-the-fact, reactive activity to one focused on the important work of evidence generation from well-designed trials. This article explores the role the Clinical Trials Transformation Initiative has played in advancing quality as a core element of clinical trial design, through project work that initially focused on monitoring but evolved into a holistic, prospective, and comprehensive quality by design approach to clinical trial design and conduct.

Programmable shunt valve interactions with osseointegrated hearing devices.

PubMed

Pierson, Matthew J; Wehrmann, Daniel; Albers, J Andrew; El Tecle, Najib E; Costa, Dary; Elbabaa, Samer K

2017-04-01

OBJECTIVE Patients with ventriculoperitoneal (VP) shunts with programmable valves who would benefit from osseointegrated hearing devices (OIHDs) represent a unique population. The aim of this study was to evaluate the magnetic field strengths of 4 OIHDs and their interactions with 5 programmable VP shunt valves. METHODS Magnetic field strength was measured as a function of distance for each hearing device (Cochlear Baha 5, Cochlear Baha BP110, Oticon Ponto Plus Power, and Medtronic Sophono) in the following modes: inactive, active in quiet, and active in 60 decibels of background noise in the sound booth. The hearing devices were introduced to each shunt valve (Aesculap proGAV, Aesculap proGAV 2.0, Codman Hakim, Codman Certas, and Medtronic Strata II) also as a function of distance in these identical 3 settings. Each trial was repeated 5 times. Between each trial, the valves were assessed for a change in setting. Finally, using a skull model, the devices were introduced to each other in standard anatomical locations and the valves were assessed for a change in settings. RESULTS The maximum magnetic field strengths generated by the Cochlear Baha 5, BP110, and Oticon OIHDs were 1.1, 36.2, and 48.7 gauss (G), respectively. The maximum strength generated by the Sophono device was > 800 G. The magnetic field strength of the hearing devices decreased markedly with increasing distance from the device. The strength of the Sophono's magnetic attachment decreased to 34.8 G at 5 mm. The Codman Hakim, Codman Certas, and Medtronic Strata II valve settings changed when rotating the valves next to the Sophono abutment. No other changes in valve settings occurred in the distance or anatomical models for any other trials. CONCLUSIONS This is the first study evaluating the interaction between OIHDs and programmable VP shunt valves. The findings suggest that it is safe to use these devices together without having to switch to a nonprogrammable valve or move the shunt valve to a more distant location. Still, care should be taken if the Sophono device is used to ensure that the valve is ≥ 5 mm away from the magnetic attachment.

Evaluating the Impact of Physical Activity Apps and Wearables: Interdisciplinary Review

PubMed Central

Rooksby, John; Gray, Cindy M

2018-01-01

Background Although many smartphone apps and wearables have been designed to improve physical activity, their rapidly evolving nature and complexity present challenges for evaluating their impact. Traditional methodologies, such as randomized controlled trials (RCTs), can be slow. To keep pace with rapid technological development, evaluations of mobile health technologies must be efficient. Rapid alternative research designs have been proposed, and efficient in-app data collection methods, including in-device sensors and device-generated logs, are available. Along with effectiveness, it is important to measure engagement (ie, users’ interaction and usage behavior) and acceptability (ie, users’ subjective perceptions and experiences) to help explain how and why apps and wearables work. Objectives This study aimed to (1) explore the extent to which evaluations of physical activity apps and wearables: employ rapid research designs; assess engagement, acceptability, as well as effectiveness; use efficient data collection methods; and (2) describe which dimensions of engagement and acceptability are assessed. Method An interdisciplinary scoping review using 8 databases from health and computing sciences. Included studies measured physical activity, and evaluated physical activity apps or wearables that provided sensor-based feedback. Results were analyzed using descriptive numerical summaries, chi-square testing, and qualitative thematic analysis. Results A total of 1829 abstracts were screened, and 858 articles read in full. Of 111 included studies, 61 (55.0%) were published between 2015 and 2017. Most (55.0%, 61/111) were RCTs, and only 2 studies (1.8%) used rapid research designs: 1 single-case design and 1 multiphase optimization strategy. Other research designs included 23 (22.5%) repeated measures designs, 11 (9.9%) nonrandomized group designs, 10 (9.0%) case studies, and 4 (3.6%) observational studies. Less than one-third of the studies (32.0%, 35/111) investigated effectiveness, engagement, and acceptability together. To measure physical activity, most studies (90.1%, 101/111) employed sensors (either in-device [67.6%, 75/111] or external [23.4%, 26/111]). RCTs were more likely to employ external sensors (accelerometers: P=.005). Studies that assessed engagement (52.3%, 58/111) mostly used device-generated logs (91%, 53/58) to measure the frequency, depth, and length of engagement. Studies that assessed acceptability (57.7%, 64/111) most often used questionnaires (64%, 42/64) and/or qualitative methods (53%, 34/64) to explore appreciation, perceived effectiveness and usefulness, satisfaction, intention to continue use, and social acceptability. Some studies (14.4%, 16/111) assessed dimensions more closely related to usability (ie, burden of sensor wear and use, interface complexity, and perceived technical performance). Conclusions The rapid increase of research into the impact of physical activity apps and wearables means that evaluation guidelines are urgently needed to promote efficiency through the use of rapid research designs, in-device sensors and user-logs to assess effectiveness, engagement, and acceptability. Screening articles was time-consuming because reporting across health and computing sciences lacked standardization. Reporting guidelines are therefore needed to facilitate the synthesis of evidence across disciplines. PMID:29572200

Task-dependent signal variations in EEG error-related potentials for brain-computer interfaces.

PubMed

Iturrate, I; Montesano, L; Minguez, J

2013-04-01

A major difficulty of brain-computer interface (BCI) technology is dealing with the noise of EEG and its signal variations. Previous works studied time-dependent non-stationarities for BCIs in which the user's mental task was independent of the device operation (e.g., the mental task was motor imagery and the operational task was a speller). However, there are some BCIs, such as those based on error-related potentials, where the mental and operational tasks are dependent (e.g., the mental task is to assess the device action and the operational task is the device action itself). The dependence between the mental task and the device operation could introduce a new source of signal variations when the operational task changes, which has not been studied yet. The aim of this study is to analyse task-dependent signal variations and their effect on EEG error-related potentials. The work analyses the EEG variations on the three design steps of BCIs: an electrophysiology study to characterize the existence of these variations, a feature distribution analysis and a single-trial classification analysis to measure the impact on the final BCI performance. The results demonstrate that a change in the operational task produces variations in the potentials, even when EEG activity exclusively originated in brain areas related to error processing is considered. Consequently, the extracted features from the signals vary, and a classifier trained with one operational task presents a significant loss of performance for other tasks, requiring calibration or adaptation for each new task. In addition, a new calibration for each of the studied tasks rapidly outperforms adaptive techniques designed in the literature to mitigate the EEG time-dependent non-stationarities.

Task-dependent signal variations in EEG error-related potentials for brain-computer interfaces

NASA Astrophysics Data System (ADS)

Iturrate, I.; Montesano, L.; Minguez, J.

2013-04-01

Objective. A major difficulty of brain-computer interface (BCI) technology is dealing with the noise of EEG and its signal variations. Previous works studied time-dependent non-stationarities for BCIs in which the user’s mental task was independent of the device operation (e.g., the mental task was motor imagery and the operational task was a speller). However, there are some BCIs, such as those based on error-related potentials, where the mental and operational tasks are dependent (e.g., the mental task is to assess the device action and the operational task is the device action itself). The dependence between the mental task and the device operation could introduce a new source of signal variations when the operational task changes, which has not been studied yet. The aim of this study is to analyse task-dependent signal variations and their effect on EEG error-related potentials.Approach. The work analyses the EEG variations on the three design steps of BCIs: an electrophysiology study to characterize the existence of these variations, a feature distribution analysis and a single-trial classification analysis to measure the impact on the final BCI performance.Results and significance. The results demonstrate that a change in the operational task produces variations in the potentials, even when EEG activity exclusively originated in brain areas related to error processing is considered. Consequently, the extracted features from the signals vary, and a classifier trained with one operational task presents a significant loss of performance for other tasks, requiring calibration or adaptation for each new task. In addition, a new calibration for each of the studied tasks rapidly outperforms adaptive techniques designed in the literature to mitigate the EEG time-dependent non-stationarities.

Opportunities and barriers in paediatric pulse oximetry for pneumonia in low-resource clinical settings: a qualitative evaluation from Malawi and Bangladesh

PubMed Central

Boyd, Nicholas; Walker, Isabeau; Zadutsa, Beatiwel; Baqui, Abdullah H; Ahmed, Salahuddin; Islam, Mazharul; Kainja, Esther; Nambiar, Bejoy; Wilson, Iain; McCollum, Eric D

2018-01-01

Objective To gain an understanding of what challenges pulse oximetry for paediatric pneumonia management poses, how it has changed service provision and what would improve this device for use across paediatric clinical settings in low-income countries. Design Focus group discussions (FGDs), with purposive sampling and thematic analysis using a framework approach. Setting Community, front-line outpatient, and hospital outpatient and inpatient settings in Malawi and Bangladesh, which provide paediatric pneumonia care. Participants Healthcare providers (HCPs) from Malawi and Bangladesh who had received training in pulse oximetry and had been using oximeters in routine paediatric care, including community healthcare workers, non-physician clinicians or medical assistants, and hospital-based nurses and doctors. Results We conducted six FGDs, with 23 participants from Bangladesh and 26 from Malawi. We identified five emergent themes: trust, value, user-related experience, sustainability and design. HCPs discussed the confidence gained through the use of oximeters, resulting in improved trust from caregivers and valuing the device, although there were conflicts between the weight given to clinical judgement versus oximeter results. HCPs reported the ease of using oximeters, but identified movement and physically smaller children as measurement challenges. Challenges in sustainability related to battery durability and replacement parts, however many HCPs had used the same device longer than 4 years, demonstrating robustness within these settings. Desirable features included back-up power banks and integrated respiratory rate and thermometer capability. Conclusions Pulse oximetry was generally deemed valuable by HCPs for use as a spot-check device in a range of paediatric low-income clinical settings. Areas highlighted as challenges by HCPs, and therefore opportunities for redesign, included battery charging and durability, probe fit and sensitivity in paediatric populations. Trial registration number NCT02941237. PMID:29382679

Analyses of power output of piezoelectric energy-harvesting devices directly connected to a load resistor using a coupled piezoelectric-circuit finite element method.

PubMed

Zhu, Meiling; Worthington, Emma; Njuguna, James

2009-07-01

This paper presents, for the first time, a coupled piezoelectric-circuit finite element model (CPC-FEM) to analyze the power output of a vibration-based piezoelectric energy-harvesting device (EHD) when it is connected to a load resistor. Special focus is given to the effect of the load resistor value on the vibrational amplitude of the piezoelectric EHD, and thus on the current, voltage, and power generated by the device, which are normally assumed to be independent of the load resistor value to reduce the complexity of modeling and simulation. The presented CPC-FEM uses a cantilever with a sandwich structure and a seismic mass attached to the tip to study the following characteristics of the EHD as a result of changing the load resistor value: 1) the electric outputs: the current through and voltage across the load resistor; 2) the power dissipated by the load resistor; 3) the displacement amplitude of the tip of the cantilever; and 4) the shift in the resonant frequency of the device. It is found that these characteristics of the EHD have a significant dependence on the load resistor value, rather than being independent of it as is assumed in most literature. The CPC-FEM is capable of predicting the generated output power of the EHD with different load resistor values while simultaneously calculating the effect of the load resistor value on the displacement amplitude of the tip of the cantilever. This makes the CPC-FEM invaluable for validating the performance of a designed EHD before it is fabricated and tested, thereby reducing the recurring costs associated with repeat fabrication and trials. In addition, the proposed CPC-FEM can also be used for producing an optimized design for maximum power output.

Safety and Efficacy of Solitaire Stent Thrombectomy

PubMed Central

Campbell, Bruce C.V.; Hill, Michael D.; Rubiera, Marta; Menon, Bijoy K.; Demchuk, Andrew; Donnan, Geoffrey A.; Roy, Daniel; Thornton, John; Dorado, Laura; Bonafe, Alain; Levy, Elad I.; Diener, Hans-Christoph; Hernández-Pérez, María; Pereira, Vitor Mendes; Blasco, Jordi; Quesada, Helena; Rempel, Jeremy; Jahan, Reza; Davis, Stephen M.; Stouch, Bruce C.; Mitchell, Peter J.; Jovin, Tudor G.; Saver, Jeffrey L.

2016-01-01

Background and Purpose— Recent positive randomized trials of endovascular therapy for ischemic stroke used predominantly stent retrievers. We pooled data to investigate the efficacy and safety of stent thrombectomy using the Solitaire device in anterior circulation ischemic stroke. Methods— Patient-level data were pooled from trials in which the Solitaire was the only or the predominant device used in a prespecified meta-analysis (SEER Collaboration): Solitaire FR With the Intention for Thrombectomy as Primary Endovascular Treatment (SWIFT PRIME), Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times (ESCAPE), Extending the Time for Thrombolysis in Emergency Neurological Deficits—Intra-Arterial (EXTEND-IA), and Randomized Trial of Revascularization With Solitaire FR Device Versus Best Medical Therapy in the Treatment of Acute Stroke Due to Anterior Circulation Large Vessel Occlusion Presenting Within Eight Hours of Symptom Onset (REVASCAT). The primary outcome was ordinal analysis of modified Rankin Score at 90 days. The primary analysis included all patients in the 4 trials with 2 sensitivity analyses: (1) excluding patients in whom Solitaire was not the first device used and (2) including the 3 Solitaire-only trials (excluding ESCAPE). Secondary outcomes included functional independence (modified Rankin Score 0–2), symptomatic intracerebral hemorrhage, and mortality. Results— The primary analysis included 787 patients: 401 randomized to endovascular thrombectomy and 386 to standard care, and 82.6% received intravenous thrombolysis. The common odds ratio for modified Rankin Score improvement was 2.7 (2.0–3.5) with no heterogeneity in effect by age, sex, baseline stroke severity, extent of computed tomography changes, site of occlusion, or pretreatment with alteplase. The number needed to treat to reduce disability was 2.5 and for an extra patient to achieve independent outcome was 4.25 (3.29–5.99). Successful revascularization occurred in 77% treated with Solitaire device. The rate of symptomatic intracerebral hemorrhage and overall mortality did not differ between treatment groups. Conclusions— Solitaire thrombectomy for large vessel ischemic stroke was safe and highly effective with substantially reduced disability. Benefits were consistent in all prespecified subgroups. PMID:26888532

Mechanical Validation of an MRI Compatible Stereotactic Neurosurgery Robot in Preparation for Pre-Clinical Trials

PubMed Central

Nycz, Christopher J; Gondokaryono, Radian; Carvalho, Paulo; Patel, Nirav; Wartenberg, Marek; Pilitsis, Julie G; Fischer, Gregory S

2018-01-01

The use of magnetic resonance imaging (MRI) for guiding robotic surgical devices has shown great potential for performing precisely targeted and controlled interventions. To fully realize these benefits, devices must work safely within the tight confines of the MRI bore without negatively impacting image quality. Here we expand on previous work exploring MRI guided robots for neural interventions by presenting the mechanical design and assessment of a device for positioning, orienting, and inserting an interstitial ultrasound-based ablation probe. From our previous work we have added a 2 degree of freedom (DOF) needle driver for use with the aforementioned probe, revised the mechanical design to improve strength and function, and performed an evaluation of the mechanism’s accuracy and effect on MR image quality. The result of this work is a 7-DOF MRI robot capable of positioning a needle tip and orienting it’s axis with accuracy of 1.37 ± 0.06mm and 0.79° ± 0.41°, inserting it along it’s axis with an accuracy of 0.06 ± 0.07mm, and rotating it about it’s axis to an accuracy of 0.77° ± 1.31°. This was accomplished with no significant reduction in SNR caused by the robot’s presence in the MRI bore, ≤ 10.3% reduction in SNR from running the robot’s motors during a scan, and no visible paramagnetic artifacts. PMID:29696097

Miniscrews for orthodontic anchorage: a review of available systems.

PubMed

Alkadhimi, Aslam; Al-Awadhi, Ebrahim A

2018-03-15

In recent years, extensive research has introduced novel ways of reinforcing orthodontic anchorage using a variety of devices temporarily anchored in bone (miniscrews). Currently, there are numerous manufacturers with different miniscrew designs on the market. The aim of this paper is to discuss the key design features of different miniscrew systems on the market. Furthermore, to present clinical selection criteria of miniscrews in different settings taking into account the determinant factors. Review of the literature was carried out using the following search methods: MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL). The search was focused on studies published until January 2018. We studied each individual miniscrew from all the identified manufacturers in details. All the features were then summarised and presented as a clinical guideline for the selection of miniscrews. In this article, we reviewed the development of miniscrews and outlined the general design features of miniscrews as well as specific design features of the current miniscrews in the market. Extensive research of the current products was carried out to help clinicians better understand the difference between the various designs of miniscrews that can be used.

Evidence for the Use of Hearing Assistive Technology by Adults: The Role of the FM System

PubMed Central

Chisolm, Theresa Hnath; Noe, Colleen M.; McArdle, Rachel; Abrams, Harvey

2007-01-01

Hearing assistive technologies include listening, alerting, and/or signaling devices that use auditory, visual, and/or tactile modalities to augment communication and/or facilitate awareness of environmental sounds. The importance of hearing assistive technologies in the management of adults with hearing loss was recently acknowledged in an evidence-based clinical practice guideline developed by the American Academy of Audiology. Most currently available evidence for hearing assistive technology use by adults focuses on frequency-modulated (FM) technology. Previous research is reviewed that demonstrates the efficacy of FM devices for adults in terms of laboratory measures of speech understanding in noise. Also reviewed are the outcomes from field trials of FM use by community-dwelling adults, which, to date, have been disappointing. Few to no individuals, in previous studies, elected to use FM devices at the end of the trial periods. Data are presented from a 1-group pretest-posttest study examining the role of extensive counseling, coaching, and instruction on FM use by adults. In addition, the potential influence of the cost of devices to the individual was eliminated by conducting the study with veterans who were eligible to receive FM systems through the Veterans Affairs National Hearing Aid Program. Positive outcomes were obtained at the end of a 6-week trial period and were found to remain 1 year after study completion. Implications for increasing the evidence base for the use of FM devices by adults are discussed. PMID:17494874

Fire/burn risk with electrosurgical devices and endoscopy fiberoptic cables.

PubMed

Smith, Lee P; Roy, Soham

2008-01-01

The purpose of the study was to systematically explore the fire and burn risk associated with fiberoptic cables and electrosurgical devices. A 300-W light source was connected to a standard gray fiberoptic light cable. The end of the cable was either rested atop or buried within a cotton towel or polypropylene drape in the presence or absence of 100% oxygen for up to 10 minutes. A monopolar electrosurgical device set at 1 W, 10 W, or 30 W was tested on a cotton towel or polypropylene drape for a period of 30 seconds. All trials were repeated. Resting the light cable on top of the cotton towel or polypropylene drape with or without oxygen produced no result. Burying the end of the cable within the drape produced a hole in the drape within 15 seconds both with and without oxygen. Burying the end of the cable within the cotton towel produced a yellow discoloration after 2 minutes both with and without oxygen. The monopolar electrosurgical device set at 30 W burned immediately through the polypropylene drape, producing a skin burn. All other trials with monopolar electrocautery produced no result. No flame or fire was produced in any trial. Fiberoptic cables and electrosurgical generators represent a serious burn risk for surgical patients, with operating room drapes and towels affording only limited protection. Otolaryngologists should be keenly aware of the risks that these devices represent because our specialty uses them frequently.

[Medical innovations in the area of conflict between certification and allowance].

PubMed

Möller, B; Stockheim, M; Kraus, T; Weber, A

2010-10-01

The medical technology industry is one of the most innovative industries in Germany. Once a medical product is developed, it will be certificated according to European harmonized guidelines and norms. The respective national regulations in Germany are stipulated in the Medical Devices Act (MPG). Part of the certification process is a clinical assessment with the aim to prove that the medical device complies with the so-called essential requirements concerning safety, performance and suitability for the intended use as defined by the manufacturer. A clinical trial may be necessary to establish compliance with these requirements. During this clinical trial the devices are being assessed in patients according to strict requirements by law. The main criticism by the funding agencies is that these trials do not sufficiently apply methods of evidence-based medicine. Thereby they are not useful for assessing the medical benefit of the devices. The manufacturers' counter-argument is that the products are bearing the CE mark, that they comply with the uniform European standards and that their quality therefore has been appropriately assessed. This discussion relates to the question about payment for the products, as according to the Fifth Social Act the funding agencies are only permitted to finance products with a scientifically proven medical benefit. The present article discusses both positions in the context of national and international legislation for the certification of medical devices and presents possible solutions. © Georg Thieme Verlag KG Stuttgart · New York.

Statistical power, the Belmont report, and the ethics of clinical trials.

PubMed

Vollmer, Sara H; Howard, George

2010-12-01

Achieving a good clinical trial design increases the likelihood that a trial will take place as planned, including that data will be obtained from a sufficient number of participants, and the total number of participants will be the minimal required to gain the knowledge sought. A good trial design also increases the likelihood that the knowledge sought by the experiment will be forthcoming. Achieving such a design is more than good sense-it is ethically required in experiments when participants are at risk of harm. This paper argues that doing a power analysis effectively contributes to ensuring that a trial design is good. The ethical importance of good trial design has long been recognized for trials in which there is risk of serious harm to participants. However, whether the quality of a trial design, when the risk to participants is only minimal, is an ethical issue is rarely discussed. This paper argues that even in cases when the risk is minimal, the quality of the trial design is an ethical issue, and that this is reflected in the emphasis the Belmont Report places on the importance of the benefit of knowledge gained by society. The paper also argues that good trial design is required for true informed consent.

Terminal illness and access to Phase 1 experimental agents, surgeries and devices: reviewing the ethical arguments.

PubMed

Schüklenk, Udo; Lowry, Christopher

2009-01-01

The advent of AIDS brought about a group of patients unwilling to accept crucial aspects of the methodological standards for clinical research investigating Phase 1 drugs, surgeries or devices. Their arguments against placebo controls in trials, which depended--at the time--on the terminal status of patient volunteers led to a renewed discussion of the ethics of denying patients with catastrophic illnesses access to last-chance experimental drugs, surgeries or devices. Existing ethics and health policy literature on the topic of access to experimental drugs. The positions of those arguing for or against free access to experimental drugs for terminally ill patients are irreconcilable. At stake are questions about the kinds of personal sacrifices society can reasonably expect patients in clinical trials to make to ensure statistically predictive results. These would benefit by necessity a much larger number of current and future patients--the conflict is about individual versus public interests. It is also about the question of whether or not the state can legitimately prevent patients with terminal illnesses from unfettered access to experimental drugs, surgeries or devices in order to motivate them to participate in clinical trials. We review the ethical arguments for and against the provision of access to Phase 1 agents for terminally ill patients. Finding a compromise between providing free or no access to Phase 1 drugs for terminally ill patients. We ought to investigate means to increase access to experimental drugs for terminally ill patients without sacrificing necessary clinical trials' sounds scientific methods.