Clinical research projects at a German medical faculty: follow-up from ethical approval to publication and citation by others

BACKGROUND: Only data of published study results are available to the scientific community for further use such as informing future research and synthesis of available evidence. If study results are reported selectively, reporting bias and distortion of summarised estimates of effect or harm of treatments can occur. The publication and citation of results of clinical research conducted in Germany was studied. METHODS: The protocols of clinical research projects submitted to the research ethics committee of the University of Freiburg (Germany) in 2000 were analysed. Published full articles in several databases were searched and investigators contacted. Data on study and publication characteristics were extracted from protocols and corresponding publications. RESULTS: 299 study protocols were included. The most frequent study design was randomised controlled trial (141; 47%), followed by uncontrolled studies (61; 20%), laboratory studies (30; 10%) and non-randomised studies (29; 10%). 182 (61%) were multicentre studies including 97 (53%) international collaborations. 152 of 299 (51%) had commercial (co-)funding and 46 (15%) non-commercial funding. 109 of the 225 completed protocols corresponded to at least one full publication (total 210 articles); the publication rate was 48%. 168 of 210 identified publications (80%) were cited in articles indexed in the ISI Web of Science. The median was 11 citations per publication (range 0-1151). CONCLUSIONS: Results of German clinical research projects conducted are largely underreported. Barriers to successful publication need to be identified and appropriate measures taken. Close monitoring of projects until publication and adequate support provided to investigators may help remedy the prevailing underreporting of research.

Is there good simulation basic training for end-to-side vascular microanastomoses?

BACKGROUND Microvascular anastomosis is the cornerstone of free tissue transfers. Irrespective of the microsurgical technique that one seeks to integrate or improve, the time commitment in the laboratory is significant. After extensive previous training on several animal models, we sought to identify an animal model that circumvents the following issues: ethical rules, cost, time-consuming and expensive anesthesia, and surgical preparation of tissues required to access vessels before performing the microsurgical training, not to mention that laboratories are closed on weekends. METHODS Between January 2012 and April 2012, a total of 91 earthworms were used for 150 microsurgical training exercises to simulate vascular end-to-side microanastomosis. The training sessions were divided into ten periods of 7 days. Each training session included 15 simulations of end-to-side vascular microanastomoses: larger than 1.5 mm (n=5), between 1.0 and 1.5 mm (n=5), and smaller than 1.0 mm (n=5). A linear model with the main variables being the number of weeks (as a numerical covariate) and the size of the animal (as a factor) was used to determine the trend in time of anastomosis over subsequent weeks as well as the differences between the different size groups. RESULTS The linear model shows a significant trend (p<0.001) in time of anastomosis in the course of the training, as well as significant differences (p<0.001) between the groups of animals of different sizes. For microanastomoses larger than 1.5 mm, the mean anastomosis time decreased from 19.3±1.0 to 11.1±0.4 min between the first and last week of training (decrease of 42.5%). For training with smaller diameters, the results showed a decrease in execution time of 43.2% (diameter between 1.0 and 1.5 mm) and 40.9% (diameter<1.0 mm) between the first and last periods. The study demonstrates an improvement in the dexterity and speed of nodes execution. CONCLUSION The earthworm appears to be a reliable experimental model for microsurgical training of end-to-side microanastomoses. Its numerous advantages are discussed here and we predict training on earthworms will significantly grow and develop in the near future. LEVEL OF EVIDENCE III This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Toward global prevention of sexually transmitted infections (STIs): The need for STI vaccines.

An estimated 499 million curable sexually transmitted infections (STIs; gonorrhea, chlamydia, syphilis, and trichomoniasis) occurred globally in 2008. In addition, well over 500 million people are estimated to have a viral STI such as herpes simplex virus type 2 (HSV-2) or human papillomavirus (HPV) at any point in time. STIs result in a large global burden of sexual, reproductive, and maternal-child health consequences, including genital symptoms, pregnancy complications, cancer, infertility, and enhanced HIV transmission, as well as important psychosocial consequences and financial costs. STI control strategies based primarily on behavioral primary prevention and STI case management have had clear successes, but gains have not been universal. Current STI control is hampered or threatened by several behavioral, biological, and implementation challenges, including a large proportion of asymptomatic infections, lack of feasible diagnostic tests globally, antimicrobial resistance, repeat infections, and barriers to intervention access, availability, and scale-up. Vaccines against HPV and hepatitis B virus offer a new paradigm for STI control. Challenges to existing STI prevention efforts provide important reasons for working toward additional STI vaccines. We summarize the global epidemiology of STIs and STI-associated complications, examine challenges to existing STI prevention efforts, and discuss the need for new STI vaccines for future prevention efforts.

Health risk appraisal in older people 6: factors associated with self-reported poor vision and uptake of eye tests in older people

BACKGROUND Although free eye testing is available in the UK from a nation-wide network of optometrists, there is evidence of unrecognised, tractable vision loss amongst older people. A recent review identified this unmet need as a priority for further investigation, highlighting the need to understand public perceptions of eye services and barriers to service access and utilisation. This paper aims to identify risk factors for (1) having poor vision and (2) not having had an eyesight check among community-dwelling older people without an established ophthalmological diagnosis. METHODS Secondary analysis of self-reported data from the ProAge trial. 1792 people without a known ophthalmological diagnosis were recruited from three group practices in London. RESULTS Almost two in ten people in this population of older individuals without known ophthalmological diagnoses had self-reported vision loss, and more than a third of them had not had an eye test in the previous twelve months. In this sample, those with limited education, depressed mood, need for help with instrumental and basic activities of daily living (IADLs and BADLs), and subjective memory complaints were at increased risk of fair or poor self-reported vision. Individuals with basic education only were at increased risk for not having had an eye test in the previous 12 months (OR 1.52, 95% CI 1.17-1.98 p=0.002), as were those with no, or only one chronic condition (OR 1.850, 95% CI 1.382-2.477, p<0.001). CONCLUSIONS Self-reported poor vision in older people without ophthalmological diagnoses is associated with other functional losses, with no or only one chronic condition, and with depression. This pattern of disorders may be the basis for case finding in general practice. Low educational attainment is an independent determinant of not having had eye tests, as well as a factor associated with undiagnosed vision loss. There are other factors, not identified in this study, which determine uptake of eye testing in those with self-reported vision loss. Further exploration is needed to identify these factors and lead towards effective case finding.

From school to work: A comprehensive model of work-related motivation in the transition to working life.

Motivation is a core concept to understand work related outcomes and vocational pursuits. However, existing research mostly focused on specific aspects of motivation, such as goals or self-efficacy beliefs, while falling short of adequately addressing more complex and integrative notions of motivation. Advancing the current state of research, we draw from Motivational Systems Theory and a model of proactive motivation to propose a comprehensive model of work-related motivation. Specifically, we define motivation as a system of mutually related factors consisting of goals, emotions, and personal agency beliefs, comprised by capability beliefs and context evaluations. Adapting this model of motivation to the school-to-work transition, we postulate that this motivational system is affected by different social, personal, and environmental variables, for example social support, the presence of role-models, personality traits, and scholastic achievement. We further expect that students with more autonomous work-related goals, expectations of more positive emotional experiences in their future working life, fewer perceived barriers to their career development, and higher work-related self-efficacy beliefs would be more successful in their transition from school to work. We also propose that goal-directed engagement acts as a partial mediator in the relationship between motivation and a successful transition. Finally, we hypothesize that work-related motivation while in school will have meaningful effects on positive outcomes while in vocational training, as represented by more work engagement, higher career commitment, job satisfaction, and lower intentions to quit training. In sum, we advance the point that the adaptation of a broader concept of work-related motivation in the school-to-work transition would result in more powerful predictions of success in this transition and would enhance scientific research and interventions in career development and counselling practice.

Re-Conceptualizing the Global Digital Divide

The article seeks a re-conceptualization of the global digital divide debate. It critically explores the predominant notion, its evolution and measurement, as well as the policies that have been advanced to bridge the digital divide. Acknowledging the complexity of this inequality, the article aims at analyzing the disparities beyond the connectivity and skills barriers. Without understating the first two digital divides, it is argued that as the Internet becomes more sophisticated and more integrated into economic, social, and cultural processes, a “third” generation of divides becomes critical. These divides are drawn not at the entry to the net but within the net itself, and limit access to content. The increasing barriers to content, though of a diverse nature, all relate to some governance characteristics inherent in cyberspace, such as global spillover of local decisions, regulation through code, and proliferation of self- and co-regulatory models. It is maintained that as the practice of intervention intensifies in cyberspace, multiple and far-reaching points of control outside formal legal institutions are created, threatening the availability of public goods and making the pursuit of public objectives difficult. This is an aspect that is rarely addressed in the global digital divide discussions, even in comprehensive analyses and political initiatives such as the World Summit on the Information Society. Yet, the conceptualization of the digital divide as impeded access to content may be key in terms of ensuring real participation and catering for the long-term implications of digital technologies.

Trade-offs between voice and silence: a qualitative exploration of oncology staff's decisions to speak up about safety concerns

BACKGROUND Research suggests that "silence", i.e., not voicing safety concerns, is common among health care professionals (HCPs). Speaking up about patient safety is vital to avoid errors reaching the patient and thus to prevent harm and also to improve a culture of teamwork and safety. The aim of our study was to explore factors that affect oncology staff's decision to voice safety concerns or to remain silent and to describe the trade-offs they make. METHODS In a qualitative interview study with 32 doctors and nurses from 7 oncology units we investigated motivations and barriers to speaking up towards co-workers and supervisors. An inductive thematic content analysis framework was applied to the transcripts. Based on the individual experiences of participants, we conceptualize the choice to voice concerns and the trade-offs involved. RESULTS Preventing patients from serious harm constitutes a strong motivation to speaking up but competes with anticipated negative outcomes. Decisions whether and how to voice concerns involved complex considerations and trade-offs. Many respondents reflected on whether the level of risk for a patient "justifies" the costs of speaking up. Various barriers for voicing concerns were reported, e.g., damaging relationships. Contextual factors, such as the presence of patients and co-workers in the alarming situation, affect the likelihood of anticipated negative outcomes. Speaking up to well-known co-workers was described as considerably easier whereas "not knowing the actor well" increases risks and potential costs of speaking up. CONCLUSIONS While doctors and nurses felt strong obligation to prevent errors reaching individual patients, they were not engaged in voicing concerns beyond this immediacy. Our results offer in-depth insight into fears and conditions conducive of silence and voicing and can be used for educational interventions and leader reinforcement.

Psychosocial aspects in cardiac rehabilitation: From theory to practice. A position paper from the Cardiac Rehabilitation Section of the European Association of Cardiovascular Prevention and Rehabilitation of the European Society of Cardiology

A large body of empirical research shows that psychosocial risk factors (PSRFs) such as low socio-economic status, social isolation, stress, type-D personality, depression and anxiety increase the risk of incident coronary heart disease (CHD) and also contribute to poorer health-related quality of life (HRQoL) and prognosis in patients with established CHD. PSRFs may also act as barriers to lifestyle changes and treatment adherence and may moderate the effects of cardiac rehabilitation (CR). Furthermore, there appears to be a bidirectional interaction between PSRFs and the cardiovascular system. Stress, anxiety and depression affect the cardiovascular system through immune, neuroendocrine and behavioural pathways. In turn, CHD and its associated treatments may lead to distress in patients, including anxiety and depression. In clinical practice, PSRFs can be assessed with single-item screening questions, standardised questionnaires, or structured clinical interviews. Psychotherapy and medication can be considered to alleviate any PSRF-related symptoms and to enhance HRQoL, but the evidence for a definite beneficial effect on cardiac endpoints is inconclusive. A multimodal behavioural intervention, integrating counselling for PSRFs and coping with illness should be included within comprehensive CR. Patients with clinically significant symptoms of distress should be referred for psychological counselling or psychologically focused interventions and/or psychopharmacological treatment. To conclude, the success of CR may critically depend on the interdependence of the body and mind and this interaction needs to be reflected through the assessment and management of PSRFs in line with robust scientific evidence, by trained staff, integrated within the core CR team.

Reasons for late presentation to HIV care in Switzerland.

INTRODUCTION Late presentation to HIV care leads to increased morbidity and mortality. We explored risk factors and reasons for late HIV testing and presentation to care in the nationally representative Swiss HIV Cohort Study (SHCS). METHODS Adult patients enrolled in the SHCS between July 2009 and June 2012 were included. An initial CD4 count <350 cells/µl or an AIDS-defining illness defined late presentation. Demographic and behavioural characteristics of late presenters (LPs) were compared with those of non-late presenters (NLPs). Information on self-reported, individual barriers to HIV testing and care were obtained during face-to-face interviews. RESULTS Of 1366 patients included, 680 (49.8%) were LPs. Seventy-two percent of eligible patients took part in the survey. LPs were more likely to be female (p<0.001) or from sub-Saharan Africa (p<0.001) and less likely to be highly educated (p=0.002) or men who have sex with men (p<0.001). LPs were more likely to have their first HIV test following a doctor's suggestion (p=0.01), and NLPs in the context of a regular check-up (p=0.02) or after a specific risk situation (p<0.001). The main reasons for late HIV testing were "did not feel at risk" (72%), "did not feel ill" (65%) and "did not know the symptoms of HIV" (51%). Seventy-one percent of the participants were symptomatic during the year preceding HIV diagnosis and the majority consulted a physician for these symptoms. CONCLUSIONS In Switzerland, late presentation to care is driven by late HIV testing due to low risk perception and lack of awareness about HIV. Tailored HIV testing strategies and enhanced provider-initiated testing are urgently needed.

Ability to Work and Employment Rates in Human Immunodeficiency Virus (HIV)-1-Infected Individuals Receiving Combination Antiretroviral Therapy: The Swiss HIV Cohort Study

Background.  Limited data exist on human immunodeficiency virus (HIV)-infected individuals' ability to work after receiving combination antiretroviral therapy (cART). We aimed to investigate predictors of regaining full ability to work at 1 year after starting cART. Methods.  Antiretroviral-naive HIV-infected individuals <60 years who started cART from January 1998 through December 2012 within the framework of the Swiss HIV Cohort Study were analyzed. Inability to work was defined as a medical judgment of the patient's ability to work as 0%. Results.  Of 5800 subjects, 4382 (75.6%) were fully able to work, 471 (8.1%) able to work part time, and 947 (16.3%) were unable to work at baseline. Of the 947 patients unable to work, 439 (46.3%) were able to work either full time or part time at 1 year of treatment. Predictors of recovering full ability to work were non-white ethnicity (odds ratio [OR], 2.06; 95% confidence interval [CI], 1.20-3.54), higher education (OR, 4.03; 95% CI, 2.47-7.48), and achieving HIV-ribonucleic acid <50 copies/mL (OR, 1.83; 95% CI, 1.20-2.80). Older age (OR, 0.55; 95% CI, .42-.72, per 10 years older) and psychiatric disorders (OR, 0.24; 95% CI, .13-.47) were associated with lower odds of ability to work. Recovering full ability to work at 1 year increased from 24.0% in 1998-2001 to 41.2% in 2009-2012, but the employment rates did not increase. Conclusions.  Regaining full ability to work depends primarily on achieving viral suppression, absence of psychiatric comorbidity, and favorable psychosocial factors. The discrepancy between patients' ability to work and employment rates indicates barriers to reintegration of persons infected with HIV.

Using multiple landscape genetic approaches to test the validity of genetic clusters in a species characterized by an isolation-by-distance pattern

Bayesian clustering methods are typically used to identify barriers to gene flow, but they are prone to deduce artificial subdivisions in a study population characterized by an isolation-by-distance pattern (IbD). Here we analysed the landscape genetic structure of a population of wild boars (Sus scrofa) from south-western Germany. Two clustering methods inferred the presence of the same genetic discontinuity. However, the population in question was characterized by a strong IbD pattern. While landscape-resistance modelling failed to identify landscape features that influenced wild boar movement, partial Mantel tests and multiple regression of distance matrices (MRDMs) suggested that the empirically inferred clusters were separated by a genuine barrier. When simulating random lines bisecting the study area, 60% of the unique barriers represented, according to partial Mantel tests and MRDMs, significant obstacles to gene flow. By contrast, the random-lines simulation showed that the boundaries of the inferred empirical clusters corresponded to the most important genetic discontinuity in the study area. Given the degree of habitat fragmentation separating the two empirical partitions, it is likely that the clustering programs correctly identified a barrier to gene flow. The differing results between the work published here and other studies suggest that it will be very difficult to draw general conclusions about habitat permeability in wild boar from individual studies.

Role of alternative interventional procedures when endo- and epicardial catheter ablation attempts for ventricular arrhythmias fail.

BACKGROUND Ventricular tachycardia (VT) refractory to antiarrhythmic drugs and standard percutaneous catheter ablation techniques portends a poor prognosis. We characterized the reasons for ablation failure and describe alternative interventional procedures in this high-risk group. METHODS AND RESULTS Sixty-seven patients with VT refractory to 4±2 antiarrhythmic drugs and 2±1 previous endocardial/epicardial catheter ablation attempts underwent transcoronary ethanol ablation, surgical epicardial window (Epi-window), or surgical cryoablation (OR-Cryo; age, 62±11 years; VT storm in 52%). Failure of endo/epicardial ablation attempts was because of VT of intramural origin (35 patients), nonendocardial origin with prohibitive epicardial access because of pericardial adhesions (16), and anatomic barriers to ablation (8). In 8 patients, VT was of nonendocardial origin with a coexisting condition also requiring cardiac surgery. Transcoronary ethanol ablation alone was attempted in 37 patients, OR-Cryo alone in 21 patients, and a combination of transcoronary ethanol ablation and OR-Cryo (5 patients), or transcoronary ethanol ablation and Epi-window (4 patients), in the remainder. Overall, alternative interventional procedures abolished ≥1 inducible VT and terminated storm in 69% and 74% of patients, respectively, although 25% of patients had at least 1 complication. By 6 months post procedures, there was a significant reduction in defibrillator shocks (from a median of 8 per month to 1; P<0.001) and antiarrhythmic drug requirement although 55% of patients had at least 1 VT recurrence, and mortality was 17%. CONCLUSIONS A collaborative strategy of alternative interventional procedures offers the possibility of achieving arrhythmia control in high-risk patients with VT that is otherwise uncontrollable with antiarrhythmic drugs and standard percutaneous catheter ablation techniques.