Perspectives on alternatives to phthalate plasticized poly(vinyl chloride) in medical devices applications

Poly(vinyl chloride) (PVC) is one of the most important polymeric materials available today and is used to manufacture many items, ranging from packaging and toys to healthcare devices. PVC is per se a rigid material but it is made softer by compounding with plasticizers, particularly phthalate esters such as di-(2-ethylhexyl) phthalate (DEHP). In flexible plasticizer PVC (P-PVC), phthalates are not chemically bound to PVC and they are released into the external environment. In particular, prolonged contact of P-PVC based medical devices with body fluids or tissues has been shown to be associated with severe health risks. Major concerns regarding the safety of P-PVC in medical plastic items have been raised, and several alternatives to phthalates and to P-PVC itself as well as chemical/physical treatments of P-PVC to reduce DEHP migration have been proposed. This review outlines recent scientific approaches for preventing DEHP contamination of humans by P-PVC medical devices, highlighting the impact of the proposed alternative materials on human health and strategies for implementing them

Multicenter study of lumbar discectomy with Barricaid annular closure device for prevention of lumbar disc reherniation in US patients: A historically controlled post-market study protocol

BACKGROUND: Patients with large defects in the annulus fibrosus following lumbar discectomy have high rates of symptomatic reherniation. The Barricaid annular closure device provides durable occlusion of the annular defect and has been shown to significantly lower the risk of symptomatic reherniation in a large European randomized trial. However, the performance of the Barricaid device in a United States (US) population has not been previously reported. DESIGN AND METHODS: This is a historically controlled post-market multicenter study to determine the safety and efficacy of the Barricaid device when used in addition to primary lumbar discectomy in a US population. A total of 75 patients with large annular defects will receive the Barricaid device following lumbar discectomy at up to 25 sites in the US and will return for clinical and imaging follow-up at 4 weeks, 3 months, and 1 year. Trial oversight will be provided by a data safety monitoring board and imaging studies will be read by an independent imaging core laboratory. Patients treated with the Barricaid device in a previous European randomized trial with comparable eligibility criteria, surgical procedures, and outcome measures will serve as historical controls. Main outcomes will include back pain severity, leg pain severity, Oswestry Disability Index, health utility on the EuroQol-5 Dimension questionnaire, complications, symptomatic reherniation, and reoperation. Propensity score adjustment using inverse probability of treatment weighting will be used to adjust for differences in baseline patient characteristics between the US trial participants and European historical controls. ETHICS AND DISSEMINATION: This study was approved by a central institutional review board. The study results of this trial will be widely disseminated at conference proceedings and published in peer-reviewed journals. The outcomes of this study will have important clinical and economic implications for all stakeholders involved in treating patients with lumbar discectomy in the US. STUDY REGISTRATION: ClinicalTrials.gov (https://clinicaltrials.gov): NCT03986580. LEVEL OF EVIDENCE: 3

The structural properties and star formation history of Leo T from deep LBT photometry

We present deep, wide-field g and r photometry of the transition type dwarf galaxy Leo T, obtained with the blue arm of the Large Binocular Telescope. The data confirm the presence of both very young (5 Gyr) stars. We study the structural properties of the old and young stellar populations by preferentially selecting either population based on their color and magnitude. The young population is significantly more concentrated than the old population, with half-light radii of 104+-8 and 148+-16 pc respectively, and their centers are slightly offset. Approximately 10% of the total stellar mass is estimated to be represented by the young stellar population. Comparison of the color-magnitude diagram (CMD) with theoretical isochrones as well as numerical CMD-fitting suggest that star formation began over 10 Gyr ago and continued in recent times until at least a few hundred Myr ago. The CMD-fitting results are indicative of two distinct star formation bursts, with a quiescent period around 3 Gyr ago, albeit at low significance. The results are consistent with no metallicity evolution and [Fe/H] ~ -1.5 over the entire age of the system. Finally, the data show little if any sign of tidal distortion of Leo T.Comment: 8 pages, 9 figures, some small textual changes, accepted for publication in the Astrophysical Journa

Implantable loop recorder versus conventional diagnostic workup for unexplained recurrent syncope

Background The most recent syncope guideline recommends that implantable loop recorders (ILRs) are implanted in the early phase of evaluation of people with recurrent syncope of uncertain origin in the absence of high-risk criteria, and in high-risk patients after a negative evaluation. Observational and case-control studies have shown that loop recorders lead to earlier diagnosis and reduce the rate of unexplained syncopes, justifying their use in clinical practice. However, only randomised clinical trials with an emphasis on a primary outcome of specific ILR-guided diagnosis and therapy, rather than simply electrocardiogram (ECG) diagnosis, might change clinical practice. Objectives To assess the incidence of mortality, quality of life, adverse events and costs of ILRs versus conventional diagnostic workup in people with unexplained syncope. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 3, 2015), MEDLINE, EMBASE, ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) Search Portal in April 2015. No language restriction was applied. Selection criteria We included all randomised controlled trials of adult participants (i.e. >= 18 years old) with a diagnosis of unexplained syncope comparing ILR with standard diagnostic workup. Data collection and analysis Two independent review authors screened titles and abstracts of all potential studies we identified as a result of the literature search, extracted study characteristics and outcome data from included studies and assessed risk of bias for each study using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions. We contacted authors of trials for missing data. We analysed dichotomous data (all-cause mortality and aetiologic diagnosis) as risk ratios (RR) with 95% confidence intervals (CI). We used the Chi(2) test to assess statistical heterogeneity (with P < 0.1) and the I-2 statistic to measure heterogeneity among the trials. We created a 'Summary of findings' table using the five GRADE considerations (study limitations, consistency of effect, imprecision, indirectness and publication bias) to assess the quality of a body of evidence as it relates to the studies which contribute data to the meta-analyses for the prespecified outcomes. Main results We included four trials involving a total of 579 participants. With the limitation that only two studies reported data on mortality and none of them had considered death as a primary endpoint, the meta-analysis showed no evidence of a difference in the risk of long-term mortality between participants who received ILR and those who were managed conventionally at follow-up (RR 0.97, 95% CI 0.41 to 2.30; participants = 255; studies = 2; very low quality evidence) with no evidence of heterogeneity. No data on short term mortality were available. Two studies reported data on adverse events after ILR implant. Due to the lack of data on adverse events in one of the studies' arms, a formal meta-analysis was not performed for this outcome. Data from two trials seemed to show no difference in quality of life, although this finding was not supported by a formal analysis due to the differences in both the scores used and the way the data were reported. Data from two studies seemed to show a trend towards a reduction in syncope relapses after diagnosis in participants implanted with ILR. Cost analyses from two studies showed higher overall mean costs in the ILR group, if the costs incurred by the ILR implant were counted. The mean cost per diagnosis and the mean cost per arrhythmic diagnosis were lower for participants randomised to ILR implant. Participants who underwent ILR implantation experienced higher rates of diagnosis (RR (in favour of ILR) 0.61, 95% CI 0.54 to 0.68; participants = 579; studies = 4; moderate quality evidence), as compared to participants in the standard assessment group, with no evidence of heterogeneity. Authors' conclusions Our systematic review shows that there is no evidence that an ILR-based diagnostic strategy reduces long-term mortality as compared to a standard diagnostic assessment (very low quality evidence). No data were available for short-term all-cause mortality. Moderate quality evidence shows that an ILR-based diagnostic strategy increases the rate of aetiologic diagnosis as compared to a standard diagnostic pathway. No conclusive data were available on the other end-points analysed. Further trials evaluating the effect of ILRs in the diagnostic strategy of people with recurrent unexplained syncope are warranted. Future research should focus on the assessment of the ability of ILRs to change clinically relevant outcomes, such as quality of life, syncope relapse and costs

Mechanical energy recovery during walking in patients with Parkinson disease

The mechanisms of mechanical energy recovery during gait have been thoroughly investigated in healthy subjects, but never described in patients with Parkinson disease (PD). The aim of this study was to investigate whether such mechanisms are preserved in PD patients despite an altered pattern of locomotion. We consecutively enrolled 23 PD patients (mean age 64\ub19 years) with bilateral symptoms (H&amp;Y 65II) if able to walk unassisted in medication-off condition (overnight suspension of all dopaminergic drugs). Ten healthy subjects (mean age 62\ub13 years) walked both at their 'preferred' and 'slow' speeds, to match the whole range of PD velocities. Kinematic data were recorded by means of an optoelectronic motion analyzer. For each stride we computed spatio-temporal parameters, time-course and range of motion (ROM) of hip, knee and ankle joint angles. We also measured kinetic (Wk), potential (Wp), total (WtotCM) energy variations and the energy recovery index (ER). Along with PD progression, we found a significant correlation of WtotCM and Wp with knee ROM and in particular with knee extension in terminal stance phase. Wk and ER were instead mainly related to gait velocity. In PD subjects, the reduction of knee ROM significantly diminished both Wp and WtotCM. Rehabilitation treatments should possibly integrate passive and active mobilization of knee to prevent a reduction of gait-related energetic components