Quality of reporting and fragility index for randomized controlled trials in the vesicoureteral reflux literature: where do we stand?

BACKGROUND/INTRODUCTION: Randomized controlled trials (RCTs) are considered the "gold standard" methodology for examining the effects of clinical interventions, yet only 1% of urology literature employs this design. The Consolidated Standards of Reporting Trials (CONSORT) statement contains a standardized checklist of 37 items to be included when reporting RCTs to ensure transparency and completeness of information [2]. Despite the robust design of RCTs, the number of events can greatly change the significance of the results, which can be represented by the fragility index (FI). OBJECTIVE: The objective was to assess the quality of reporting of RCTs in the pediatric vesicoureteral reflux (VUR) literature using the 2010 CONSORT statement and, for studies with significant positive findings, to determine the FI as a measure of robustness of the results. STUDY DESIGN: A comprehensive search was conducted through MEDLINE® and Embase® to identify RCTs in VUR literature from 2000 to 2016. Two reviewers independently selected articles, which were evaluated using the CONSORT checklist. An overall quality of reporting score (OQS) (%) was calculated by dividing the number of checklist items present in each study by the maximum possible score (34) and expressed as a percentage. Studies were classified as low (<40%), moderate (40-70%) and high quality (>70%) based on the modified assessing the methodological quality of systematic reviews (AMSTAR) checklist. Of the 2052 initial matches, 98% were excluded due to methodology or content, a further 28 studies were found not to meet inclusion criteria after full text review. The FI was calculated for the 7 studies that met inclusion criteria with significantly different results by manually adding events to the study groups until p>0.05. RESULTS: Twenty-two studies met inclusion criteria. The mean OQS was 46+17% with 9 (41%) identified as low quality (score <40%), 11 (50%) as moderate (40-70%) and 2 (9%) as high quality (>70%). There was no significant difference in OQS between RCTs with a sample size > 100 (n=15) versus <100 patients (n=7) (45+17% vs. 47+17%, p=0.7). However, we noted a difference when we compared RCTs with biostatistician support (n=4) vs. those without (n=18) (59+20% vs. 43+15%, p<0.05). Seven studies reported significant positive results making calculation of FI possible. The mean FI was 5.8+5.1 indicating that most studies were fragile. There was no correlation between the OQS and FI. DISCUSSION AND CONCLUSION: The mean OQS of VUR RCTs was suboptimal (46%), with most studies having low FI scores indicating the instability of the findings. The only variable that significantly impacted the OQS was biostatistician support. Implementation of the CONSORT checklist with a minimum of 50% inclusion as a prerequisite for submission of manuscripts may improve the quality and transparency of reporting. Calculation of the FI could provide readers with an objective measure of robustness for the published trials, allowing for appropriate interpretation of the results.

Is It Time to Re-Evaluate the Ethics Governance of Social Media Research?

This article reports on a U.K. workshop on social media research ethics held in May 2018. There were 10 expert speakers and an audience of researchers, research ethics committee members, and research institution representatives. Participants reviewed the current state of social media ethics, discussing well-rehearsed questions such as what needs consent in social media research, and how the public/private divide differs between virtual and real-life environments. The lack of answers to such questions was noted, along with the difficulties posed for ethical governance structures in general and the work of research ethics committees in particular. Discussions of these issues enabled the creation of two recommendations. The first is for research ethics committees and journal editors to add the category of 'data subject research' to the existing categories of 'text research' and 'human subject research'. This would reflect the fact that social media research does not fall into either of the existing categories and so needs a category of its own. The second is that ethical issues should be considered at all stages of social media research, up to and including aftercare. This acknowledges that social media research throws up a large number of ethical issues throughout the process which, under current arrangements for ethical research governance, risks remaining unaddressed.

[Evaluating the health target "Increasing health competence, strengthening patient sovereignty"]. / Ansätze zur Evaluation des Gesundheitsziels "Gesundheitliche Kompetenz erhöhen, Patient(inn)en-souveränität stärken".

Establishing citizen and patient orientation is a national objective of German health policy. The cooperation network gesundheitsziele.de has defined the target area "Increasing health competence, strengthening patient sovereignty", and its Working Group 8, which bears the same name, has identified four key areas for action: increasing transparency, developing competence, strengthening patients' rights, and improving complaint management. As in the case of all the other targets defined by gesundheitsziele.de, attention is drawn to the need to evaluate the effects and success of the targets and related measures. A group of experts was given the task of developing an evaluation strategy, defining success indicators, and examining the availability of data sources for evaluation. With regard to the health target "Increasing health competence, strengthening patient sovereignty", the evaluation is focusing on what effect the corresponding targets and measures are having on users and how they are perceived (summative evaluation), i.e., primarily on measuring outcomes at the population level. An examination of available studies and surveys shows that to date little is known about the expectations and assessments of health-service users. At the same time, the analysis makes it clear that priority should be given to using continuous data in order to arrive at a continuous and systematic evaluation of the "Increasing health competence, strengthening patient sovereignty" health target and the implementation of citizen and patient orientation in healthcare in general. It would also be useful to include all hitherto underrepresented indicator questions in these surveys and to also examine the implementation of the health target among vulnerable population groups, e.g., elderly people in nursing homes.

[The National Programme for Disease Management Guidelines. Goals, contents, patient involvement]. / Das Programm für Nationale VersorgungsLeitlinien von BAK, AWMF und KBV : Ziele, Inhalte, Patientenbeteiligung.

The Programme for National Disease Management Guidelines (German DM-CPG Programme) aims at the implementation of best practice recommendations for prevention, acute care, rehabilitation and chronic care. The programme, focussing on high priority healthcare topics, has been sponsored since 2003 by the German Medical Association (BAEK), the Association of the Scientific Medical Societies (AWMF), and by the National Association of Statutory Health Insurance Physicians (KBV). It is organised by the German Agency for Quality in Medicine, a founding member of the Guidelines International Network (G-I-N). The main objective of the programme is to establish consensus of the medical professions on evidence-based key recommendations covering all sectors of health care provision and facilitating the coordination of care for the individual patient through time and across disciplines. Within this framework experts from national patient self-help groups have been developing patient guidance based upon the recommendations for healthcare providers. The article describes goals, topics and selected contents of the DM-CPG programme - using asthma as an example.

[Evidence-based medicine for the public]. / Evidenzbasierte Medizin für den Bürger.

The methods of evidence-based medicine demand high quality and up-to-date medical information. Ideally, this information is based on data from controlled clinical trials. When such external evidence is available, it provides a base for an effective patient-physician consultation, and is also essential for the consumer friendly presentation of medical information. This article sketches the international and German developments and approaches to preparing and maintaining evidence-based patient information and its influences on the models of physician-patient communication.

[Well-informed on health matters--how well? The German 'Clearinghouse for Patient Information'--objective, background and methods]. / Gut informiert über Gesundheitsfragen, aber wie? Das Deutsche Clearingverfahren für Patienteninformationen--Zielsetzung, Hintergrund und Arbeitsweise.

OBJECTIVE: Health information for lay people in print or electronic form are internationally recognised as useful tools and as necessary in the decision-making process of individuals. The effectiveness of offered patient information depends on quality and accessibility. Because much of the available health information is significantly deficient, the Agency for Quality in Medicine developed a programme for assessing the quality of specialised health and medical information for all non-medically trained persons. The German 'Clearinghouse for Patient Information' project is an adjunct to the already established German 'Clearinghouse for Clinical Guidelines'. METHOD: The basis for quality improvement for specialised medical information consists 1. in the determination of demands on quality for patient information published in the German language, 2. development of a standardised instrument for assessing the quality of specialised medical information by non-medically trained persons, 3. establishment of an Internet portal for evaluated and rated material, and 4. the establishment and organisation of relevant partnerships with information providers and users of health and medical information. The principle building block to rate medical information for lay people are the DISCERN criteria for good patient information. The results of the quality rating of specialised medical information are made available to the public with emphasis on promoting transparency of the assessment and rating processes used. RESULTS: The Internet-based patient information service of the Agency for Quality in Medicine (www.patienten-information.de 19.06.02) has currently a selection of approximately 800 information items covering fifty disease topics with fully or partially evaluated and rated information. Partnerships to appropriate information providers and users are already established and have been tested in special single projects. CONCLUSION: To advance the process of quality improvement for medical information for non-medical and lay persons, it is essential to develop and to intensify the cooperation with stake holders and partners at different levels. Only through close cooperation with others it is possible to create a basis to continuously develop and improve the information quality assessment instrument further. In addition, effective strategies need to be developed to disseminate these endeavours to patients and consumers of health information in a user-friendly and transparent way.

Autologous plasma and platelet sequestration at the beginning of cardiopulmonary bypass: a pilot investigation in five patients undergoing extended vascular surgery in deep hypothermia.

Platelet dysfunction and loss of procoagulants and platelets leads to impaired hemostasis after cardiopulmonary bypass (CPB). Preoperative platelet sequestration delays surgery, and the large volume shifts, necessary to harvest therapeutically effective components, may be associated with hemodynamic instability. We performed platelet and plasma sequestration after the initiation of CPB during the cooling period in patients undergoing surgery in deep hypothermic cardiac arrest. Five patients who underwent major vascular surgery in deep hypothermia were enrolled in this pilot study. Platelet and plasma sequestration was performed during cooling with the CATS cell saver using the plasma sequestration set. Before processing, 2 x 1,000 ml of blood were concentrated by means of hemofiltration to reduce dilution effects of CPB. The autologous platelet concentrates were rotated at 24 degrees C, and the plasma was stored at room temperature. The harvested plasma and platelets were re-transfused during modified ultrafiltration after CPB. Platelet count, 20 mmol/L ADP stimulated platelet aggregation, and fibrinogen levels were measured preoperatively in the harvested material and in patient blood before and after transfusion. A heparinase thromboelastogram (TEG) was performed preoperatively before and after re-transfusion. There was a significant increase in the ADP stimulated platelet aggregation, platelet count, fibrinogen level, and maximum amplitude of the TEG after re-transfusion of the harvested material. No patient needed transfusion of fresh frozen plasma or random donor platelet concentrates. No patient needed re-exploration due to hemorrhage. The data presented provide evidence that autologous plasma and platelet sequestration during CPB initiation is effective. The harvested material reveals a high platelet count and fibrinogen level and preserves functional integrity.

[More power for patients: the patients' forum--a joint platform for the medical profession and patient self-help groups]. / Mehr Power für Patienten: Patientenforum--Gemeinsame Plattform von Arzteschaft und Patientenselbsthilfe.

New ways of cooperation between doctors and representatives of patients are followed with the help of the patients' forum which was founded on the initiative of the German Medical Association. Members of the German Association 'Help for the Handicapped People', the 'Forum of the Chronic Ill and Handicapped People' of the 'Equal Charitable Organisation' (Paritätischer Wohlfahrtsverband), the 'German Association of Self-Help Groups' as well as representatives of the committees and the management of the German Medical Association and the National Association of Statutory Health Insurance Physicians form the patients' forum. The major aim of this cooperation is to discuss the possibilities and the ways to improve the quality in health care. A direct participation of patients' representatives is for the moment planned in the evaluation of the quality of medical information for the lay public. In cooperation with the Agency for Quality in Medicine--a joint institution of the German Medical Association and the National Association of Statutory Health Insurance Physicians--the quality of information on health care that is published in the internet should be examined. The patients' information service which was developed by the Agency for Quality in Medicine and is found under www.patienten-information.de is the basis for this examination.

Prevention of venous graft sclerosis with clopidogrel and aspirin combined with a mesh tubing in a dog model of arteriovenous bypass grafting.

OBJECTIVE: to investigate the effect of clopidogrel combined with aspirin or aspirin alone on fibromyointimal hyperplasia (FIMH) in a bypass model with native vein grafts (NVG) and biocompound grafts (BCG). DESIGN: twelve Beagle dogs were randomised into two equal groups. In each animal NVG and a BCG were interposed in the common carotid arteries. Postoperatively, Group 1 received clopidogrel (200 mg/d) and aspirin (100 mg/d) and Group 2 received aspirin (100 mg/d) alone. METHODS: the BCG was constructed by sheathing the ipsilateral jugular vein with highly flexible metal mesh tubing. After 30 days the grafts were harvested and pressure fixed. FIMH was determined by morphometry. RESULTS: the average wall thickness of the BCG was significantly lower than that of the NVG in both groups (0.26 (SD)0.02 mm vs 0.47 (SD)0.15 mm, p = 0.04 and 0.28 (SD)0.05 mm vs 0.70 (SD)0.29 mm, p = 0.01, respectively). For BCG treated with aspirin, the wall cross section area was lower (5.0 (SD)0.6 mm(2)vs 9.1 (SD)3.3 mm(2), p = 0.02) and the lumen larger (25.2 (SD)5.9 mm(2)vs 9.7 (SD)3.4 mm(2), p < 0.01) than for the NVG. There was also a difference in the lumen cross section area of the NVG, which was larger after combined therapy with clopidogrel and aspirin (17.9 (SD)7.8 mm(2)vs 9.7 (SD)3.4 mm(2), p = 0.04). CONCLUSIONS: in this dog model the sheathing of vein grafts effectively prevents FIMH following bypass surgery. Clopidogrel is effective in NVG.

Inflammatory response after implantation of a left ventricular assist device: comparison between the axial flow MicroMed DeBakey VAD and the pulsatile Novacor device.

The implantation of a ventricular assist device (VAD) is associated with a stimulation of the inflammatory system. We compared changes in the inflammatory response after implantation of a pulsatile Novacor left (L) VAD and the axial flow MicroMed DeBakey VAD. Six consecutive patients after implantation of a Novacor LVAD (NC) and six patients after implantation of a MicroMed DeBakey VAD (MD) were included in the investigation. Patients received LVADs for medically non treatable end-stage heart failure. Tumor necrosis factor alpha (TNF), C3a, C5a, interleukin 6 (IL-6), and neutrophil elastase were measured twice a week over a period of 3 months after implantation of the device. All tests were performed with an enzyme-linked immunosorbent assay. There was no significant difference in the clinical course of the two groups. All inflammatory parameters were elevated in both groups during the entire period of the investigation. There was no difference in TNF, polynuclear leukocyte elastase, or C3a levels between the two groups; however, IL-6 (NC: 23.6+/-37.6 pg/ml vs. MD: 63+/-114 pg/ml, p < 0.001) and C5a (NC: 708+/-352 microg/L vs. MD: 1,745+/-1,305 microg/L, p < 0.001) were increased significantly more in patients following implantation of the axial flow MicroMed DeBakey VAD. Compared with the pulsatile Novacor device, the implantation of the axial flow MicroMed DeBakey LVAD seems to be associated with an increased stimulation of one part of the inflammatory system. Further investigations are necessary for evaluation of the pathophysiologic mechanism and clinical implications of these findings.

Inhibition of shock-induced foot tapping behaviour in the gerbil by a tachykinin NK1 receptor antagonist.

The selective tachykinin NK1 receptor antagonist, 2-(R)-(1-(R)-3,5-Bis(trifluoromethyl)phenylethoxy)-3-(S)-(4-fluoro)phenyl-4-(3-oxo-1,2,4-triazol-5-yl)methylmorpholine (MK-869), has been recently described as a novel therapeutic approach for anxiety/depression. A frequently used model to establish the central nervous system (CNS) activity of tachykinin NK1 receptor antagonists is the inhibition of NK1 agonist-induced foot tapping in gerbils. In the present study, we demonstrate that foot tapping can also be induced in most, but not all, gerbils by footshock and associated cues. MK-869 (0.3-3 mg/kg, i.p.) dose-dependently blocked this foot tapping response. This effect was further shown to be due to selective NK1 receptor blockade, since (2S,3S)-cis-3(2-methoxybenzylamino)-2-phenylpiperidine (CP-99,994; 3 mg/kg, i.p.) inhibited foot tapping, whereas its less active enantiomer (2R,3R)-cis-3(2-methoxybenzylamino)-2-phenylpiperidine (CP-100,263; 3 mg/kg, i.p.) had no effect. Diazepam (1-10 mg/kg, i.p.) also inhibited foot tapping, whereas fluoxetine (10-30 mg/kg, i.p.) markedly increased this behaviour. The present data support the view that foot tapping in the gerbil is a behavioural response to an aversive stimulus, and is robustly inhibited by two NK1 receptor antagonists. The data support a role for tachykinin NK1 receptor antagonists as novel anxiolytic/antidepressants.

Prevalence and persistence of heparin/platelet factor 4 antibodies in patients with heparin coated and noncoated ventricular assist devices.

Thromboembolism is a major complication in patients with ventricular assist devices (VAD). Anticoagulation with heparin, coumarin, and anti-platelet agents, particularly the development of biocompatible surfaces such as inner pseudo-endothelial layers or a coating with heparin, are intended to reduce these complications. However, the administration of heparin can lead to heparin induced thrombocytopenia type II (HIT II). Predominantly heparin/platelet factor 4 (HPF4) antibodies are responsible for the development of HIT II. The goal of the present investigation was to assess the prevalence of these antibodies in patients with heparin coated and noncoated VADs. Fifty-five patients were enrolled in the investigation. A heparin coated system was implanted in 30 patients, and a noncoated system was implanted in 25 patients. Antibodies were evaluated before, on days 7 and 14, and 3 months after implantation. Testing was performed with the Heparin/Platelet factor 4 enzyme-linked immunosorbent assay (ELISA) (Stago, France). In 40 of the 55 patients, the formation of HPF4 antibodies was observed (73%). In 35 of these patients (88%), HPF4 antibodies were present before surgery. There were no differences between the groups. In 11 patients (equal from both groups), the antibodies disappeared after termination of systemic heparinization. We conclude that in a rather high percentage of patients with VADs HPF4 antibodies are found. This finding may be explained by the repetitive and prolonged exposure of these patients to heparin. Immobilized heparin, as presently used in the carmeda coating, seems not to influence the formation and persistence of HPF4 antibodies. Further studies will have to prove whether HPF4 antibodies contribute to thromboembolic complications in these patients.