Enhancing the effectiveness of medical device incident reporting: final report of the EU pilot on the manufacturer incident reporting form (MIR form)

Aim of the report This report provides a final assessment by DG JRC of the 'EU MIR form pilot' project, concerning the use of nomenclature for manufacturer incident reporting. The purpose of this analysis is to exploit the submitted data in view of addressing the following key questions: 1. Is reporting of adverse events using nomenclature feasible and helpful? 2. Are existing nomenclatures relating to device problems and evaluations of causes adequate? 3. Is there a need for introducing new terms, e.g. to cover novel technologies? 4. What are the lessons learned from the pilot study in terms of international harmonisation of nomenclatures (IMDRF) and development of future reporting tools (e.g. EUDAMED)? Key findings This report focuses on the use of adverse 'event-type' and 'evaluation' terms which relate to problems with the medical device. The device-related terms were used in a 'Manufacturer Incident Report' form, which was designed for the pilot study, and was called the MIR pilot form. 786 forms, which were submitted by 13 manufacturers reporting from 15 European countries, were analysed. Concerning nomenclature usage, the report analyses whether incidents were reported adequately using (1) existing nomenclature (ISO/TS 19218), (2) newly introduced nomenclature (EDMA's IVD-related terms), and (3) newly proposed terms (by the participating manufacturers of the pilot study). The analysis has shown a number of important issues which concern five main topics: 1. Pilot data relate to approx. 50% of device categories on the market Due to voluntary participation, the submitted MIR pilot forms reflect only a certain proportion of medical devices on the market. This needs to be considered when interpreting and using the pilot data. 2. No participation of SMEs in the pilot project Additional bias may be due to (1) the absence of SME participation; and (2) a single manufacturer submitting >60% of the total number of forms (bias towards a particular device category). 3. Adequacy of term selection by manufacturers We assessed the adequacy of term use by comparing textual incident descriptions with the categorised terms chosen by reporters. It was based on a set of 100 randomly selected pilot forms representative of the pilot's overall device portfolio. Both, the event-type and evaluation terms chosen by manufacturers for reporting incidents were largely adequate. Moreover, the analysis shows that three choices per level to describe the incident (event-type terms) or final investigation (evaluation terms) appear sufficient. 4. Available terminology (ISO/TS 19218) is not fully adequate On the basis of the frequency of some proposed terms it appears that the existing ISO/TS 19218 terms are overall not sufficient. This is not surprising given the fact that the terms were derived from FDA's terminology in 2005 and have, since then, not been updated. To resolve the most frequently encountered issues in the analysis, the JRC has proposed several changes to terms used (cf. Fig. 18-24). 5. Proposals for new terms by manufacturers ISO/TS 19218 uses a 2-level hierarchical coding structure for reporting adverse events. Though the pilot study allowed for new proposals at these levels (level 1, 2), it was particularly designed for new proposals at an additional more granular third level. In line with this is the observation that the majority of new terms proposed concern level three terms. The analysis also showed that, although selection of existing terms was overall adequate, many of the new terms proposed by manufacturers are either redundant or do not reflect device problems but are, in fact, patient outcome terms. This clearly shows a need for reporters to have a better understanding of the terms and the reporting form used. Some of the confusion may stem from the simple fact that ISO's medical device problem terminology is called "Adverse Event Terms", i.e. seemingly suggesting that this nomenclature should be used to report adversity, i.e. clinical phenomena at patient / user level. In cases where level one event-type terms have been proposed, these related mainly (>80%) to the orthopaedic device category (cf. Fig. 13). It therefore appears that there is a need for a more elaborate nomenclature in this device category. Proposed terms that were deemed valid when compared with ISO/TS 19218 were subsequently compared with FDA's terms for device problems. This led to the identification of a number of proposed terms that could be proposed for incorporation into ongoing efforts in the development of a globally used nomenclature in the context of the work of the Adverse Event Terminology Working Group of IMDRF. EDMA has proposed new terms to cover specific needs of reporting incidents with in vitro diagnostic medical devices (IVDs). These were meant to complement the ISO/TS 19218 terms, and several of them have been used in the submissions. A closer look at the definitions of some of EDMA's terms does, however, show that they would need to be revised, for example four terms (corresponding to level 2) have identical definitions adding unnecessary ambiguity to their use. The report also provides in Annex I a summary of agreements reached during the workshop and topics that remain to be addressed when developing future tools for incident reporting including concerns voiced by stakeholders. Annex I also considers additional reflections made after the workshop and provides, as a synthesis, key recommendations for a way forward. In summary, this report shows that the outcome of the 'EU MIR form pilot' project has proven to be extremely useful for three reasons. 1. It confirmed the general feasibility of categorised reporting of incidents by manufacturers. 2. It identified inadequacies of the existing ISO/TS 19218 nomenclature suggesting the need for increased efforts into the development of freely available, scientifically and technically satisfying and, from a regulatory and end-user point of view, adequate nomenclature for adverse event reporting of incidents and events also in the pre-market space. 3. It led to the proposal of several potentially useful terms in view of future developments of nomenclature for incident / adverse event reporting.JRC.F.2-Consumer Products Safet

Normal and abnormal prosthetic valve function as assessed by doppler echocardiography

Doppler echocardiography was performed in 136 patients with a normally functioning prosthetic valve in the aortic (n = 59), mitral (n = 74) and tricuspid (n = 3) positions. These included patients with St. Jude (n = 82), Björk-Shiley (n = 18), Beall (n = 13), Starr-Edwards (n = 7) or tissue (n = 16) valves. Peak and mean pressure gradients across the prostheses were measured using the simplified Bernoulli equation. The prosthetic valve orifice (PVO, in square centimeters), only in the mitral position, was calculated by the equation: PVO = 220/pressure half-time.In the aortic position, the St. Jude valve had a lower peak velocity (2.3 ± 0.6 m/s, range 1.0 to 3.9), peak gradient (22 ± 12 mm Hg, range 4 to 61) and mean gradient (12 ± 7 mm Hg, range 2 to 32) than the other valves (p < 0.05 when compared with Starr-Edwards). In the mitral position, the St. Jude valve had the largest orifice (3.0 ± 0.6 cm2, range 1.8 to 5.0) (p < 0.0001 compared with all other valves). Insignificant regurgitation was commonly found by pulsed mode Doppler technique in patients with a St. Jude or Björk-Shiley valve in the aortic or mitral position and in patients with a Starr-Edwards or tissue valve in the aortic position. In 17 other patients with a malfunctioning prosthesis (four St. Jude, two Björk-Shiley, four Beall and seven tissue valves) proven by cardiac catheterization, surgery or autopsy, Doppler echocardiography correctly identified the complication (significant regurgitation or obstruction) in all but 2 patients who had a Beall valve.It is concluded that 1) the St. Jude valve appears to have the most optimal hemodynamics; mild regurgitation can be detected by the Doppler technique in normally functioning St. Jude and Björk-Shiley valves in the aortic or mitral position and in Starr-Edwards and tissue valves in the aortic position, and 2) Doppler echocardiography is a useful method for the detection of prosthetic valve malfunction, especially when the St. Jude, Björk-Shiley and tissue valves are assessed

The effect of sidewalls on rectangular jets

Effect of sidewalls Effect of Reynolds number a b s t r a c t An experimental study is presented regarding the influence of sidewalls on the turbulent free jet flow issuing from a smoothly contracting rectangular nozzle of aspect ratio 15. &apos;&apos;Sidewalls&quot; are two parallel plates, flush with each of the slots&apos; short sides, practically establishing bounding walls extending the nozzle sidewalls in the downstream direction. Measurements of the streamwise and lateral velocity mean and turbulent characteristics have been accomplished, with an x-sensor hot wire anemometer, up to an axial distance of 35 nozzle widths, for jets with identical inlet conditions with and without sidewalls. Centreline measurements for both configurations have been collected for three Reynolds numbers, Re D = 10,000, 20,000 and 30,000. For Re D = 20,000 measurements in the transverse direction were collected at 13 different downstream locations in the range, x = 0-35 nozzle widths, and in the spanwise direction at three different downstream locations, x = 2, 6 and 25 nozzle widths. Results indicate that, the two jet configurations (with and without sidewalls) produce statistically different flow fields. Sidewalls do not lead to the production of a 2D flow field as undulations in the spanwise mean velocity distribution indicate. They do increase the two-dimensionality of the jet increasing the longevity of 2D spanwise rollers structures formed in the initial stages of entrainment, which are responsible for the convection of longitudinal momentum towards the outer field, establishing larger streamwise mean velocities at the jet edges. In the near field, up to 25 nozzle widths, lower outward lateral velocities in the presence of the sidewalls are held responsible for the decrease of turbulent terms including rms of velocity fluctuations and Reynolds stresses. Skewness factors increase monotonically across the shear layers from negative values to positive forming sharp peaks at the outer edges of the jet, illustrative of the presence of well defined 2D roller structures in the jet with sidewalls

Joint Meeting of the Greek and Italian Sections of The Combustion Institute 1

ABSTRACT The effect of a secondary &quot;weak&quot; jet on a &quot;strong&quot; jet&apos;s flow field is of great importance for the evaluation of many staged combustion schemes. The present work is part of ongoing research on turbulent mixing characteristics of the interaction of a weak and a strong jet inside a confining area, with experimental and numerical tools. Preliminary experimental results, obtained with laser Doppler anemometry, will be presented. Measurements of mean and turbulent velocity statistics of a single turbulent axisymmetric jet are presented for reference. At a distance of thirty strong jet&apos;s diameters, mean and rms velocity profiles of jets&apos; merging are presented for isothermal conditions. In this test case momentum flux ratio of jets is rather high. Two local maximums corresponding to the central region of each jet are identified. A slight displacement of weak jet&apos;s maximum and a small increase of turbulent components at the edges of jets indicate early stages of mixing

A Rare Case of a Direct Incarcerated Inguinal Hernia Containing an Epiploic Appendage and a Literature Review

Inguinal hernias are a widespread condition, responsible for a large number of acute abdomen cases. Typically, indirect, rather than direct, hernias are the ones leading to complications, as a consequence of their narrower hernial defect. Our case concerns a rather rare incidence of a direct incarcerated hernia in a 71-year-old man who presented with acute pain in the left inguinal area. Upon clinical examination, an irreducible inguinal mass was palpated. Therefore, the existence of a complicated hernia was suspected. The patient underwent an emergency repair, during which it was established that the hernia was direct and incarcerated and that its sac contained an ischemic epiploic appendage. The hernia was successfully repaired with mesh, the patient recovered uneventfully and was discharged five days later. Despite the rarity of complicated direct inguinal hernias, they should always be included in the differential diagnosis of irreducible groin masses, because they can increase severe complications. Keywords: Direct inguinal hernia; Appendix epiploica

Vaspin: a novel adipokine, member of the family of serine protease inhibitors

In 2000, the novel adipokine vaspin, which belongs to the superfamily of serpins, was isolated from visceral adipose tissue. Vaspin is mainly produced in the visceral adipose tissue and is related to insulin resistance, blood glucose levels, sex hormones (women have higher levels compared to men) and nutritional status. Moreover, vaspin levels are modulated by weight loss and several agents, and it possibly constitutes a connecting link between obesity and its associated metabolic disorders. Many patients with polycystic ovary syndrome have insulin resistance, obesity (mostly visceral) and glucose intolerance, conditions associated with abnormalities in the production of vaspin. The role of vaspin in the regulation of human metabolism is unclear at present, but it appears that vaspin might represent a novel marker of obesity and insulin resistance. However, the controversial findings of existing studies on vaspin stress the need for further research in women with obesity and metabolic disorders in order to elucidate the role of this adipokine in these diseases and particularly in the polycystic ovary syndrome

The effects of obesity and polycystic ovary syndrome on serum lipocalin-2 levels: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Lipocalin-2 is a novel adipokine that appears to play a role in the development of insulin resistance. Serum lipocalin-2 levels are elevated in obese patients. Obesity and insulin resistance are cardinal characteristics of the polycystic ovary syndrome (PCOS). However, there are limited data on serum lipocalin-2 levels in patients with PCOS. The aim of the present study was to assess serum lipocalin-2 levels in PCOS.</p> <p>Methods</p> <p>We studied 200 patients with PCOS and 50 healthy female volunteers.</p> <p>Results</p> <p>Serum lipocalin-2 levels were slightly higher in women with PCOS compared with controls (65.4 +/- 34.3 vs. 60.3 +/- 26.0 ng/ml, respectively) but this difference did not reach statistical significance. In contrast, lipocalin-2 levels were higher in overweight/obese women with PCOS than in normal weight women with the syndrome (76.2 +/- 37.3 vs. 54.5 +/- 27.2 ng/ml, respectively; p < 0.001). Serum lipocalin-2 levels were also higher in overweight/obese controls compared with normal weight controls (70.1 +/- 24.9 vs. 50.5 +/- 23.7 ng/ml, respectively; p = 0.004). In the total study population (patients with PCOS and controls), lipocalin-2 levels were independently correlated with the body mass index (p < 0.001). In women with PCOS, lipocalin-2 levels were independently correlated with the waist (p < 0.001).</p> <p>Conclusions</p> <p>Obesity is associated with elevated serum lipocalin-2 levels. In contrast, PCOS does not appear to affect lipocalin-2 levels.</p

The impact of female obesity on the outcome of fertility treatment

Peer reviewedPublisher PD

Can dysglycemia in OGTT be predicted by baseline parameters in patients with PCOS?

BackgroundPolycystic ovary syndrome (PCOS) is considered a risk factor for the development of type 2 diabetes mellitus (T2DM). However, which is the most appropriate way to evaluate dysglycemia in women with PCOS and who are at increased risk are as yet unclear. Aim of the studyTo determine the prevalence of T2DM, impaired glucose tolerance (IGT), and impaired fasting glucose (IFG) in PCOS women and potential factors to identify those at risk. Subjects and methodsThe oral glucose tolerance test (OGTT), biochemical/hormonal profile, and ovarian ultrasound data from 1614 Caucasian women with PCOS and 362 controls were analyzed in this cross-sectional multicenter study. The data were categorized according to age and BMI. ResultsDysglycemia (T2DM, IGT, and IFG according to World Health Organization criteria) was more frequent in the PCOS group compared to controls: 2.2% vs 0.8%, P = 0.04; 9.5% vs 7.4%, P = 0.038; 14.2% vs 9.1%, P = 0.002, respectively. OGTT was essential for T2DM diagnosis, since in 88% of them basal glucose values were inconclusive for diagnosis. The presence of either T2DM or IFG was irrespective of age (P = 0.54) and BMI (P = 0.32), although the latter was associated with IGT (P = 0.021). There was no impact of age and BMI status on the prevalence of T2DM or IFG. Regression analysis revealed a role for age, BMI, fat deposition, androgens, and insulin resistance for dysglycemia. However, none of the factors prevailed as a useful marker employed in clinical practice. ConclusionsOne-third of our cohort of PCOS women with either T2DM or IGT displayed normal fasting glucose values but without confirming any specific predictor for dysglycemic condition. Hence, the evaluation of glycemic status using OGTT in all women with PCOS is strongly supported