Steps Back Research Articles

The advance of research governance in psychiatry: one step forward, two steps back

Purpose. To investigate the reasons behind difficulties in recruiting patients to randomized controlled trials (RCTs) in psychiatry and to examine a database of RCTs for differences between studies in mental health and other specialities. Methods. A discussion of recent changes in research governance in the UK and Europe followed by an examination of the database of all trials supported by the Health Technology Assessment programme of the National Institute of Health Research in the UK between 1993 and 2007 to determine if three different measures, (i) time between grant approval and study start date, (ii) percentage of additional time given to extend recruitment and (iii) percentage of planned recruitment achieved, changed over the time period studied and differed between mental health, cancer and other medical disciplines. Findings. Despite attempts in the UK to accelerate the process of clinical trials in recent years, there was a significant increase in the extension time for trials to be completed (p=0.038) and the percentage of planned recruitment to mental health studies (71%) was significantly less than for cancer (90.3%) and other studies (86.1%) (p=0.032). Summary. These results suggest that, despite the priority afforded to the advancement of RCTs in healthcare, such studies are encountering increasing difficulty in recruiting to time and target. We suggest that this difficulty can be attributed, at least in part, to the excessively byzantine regulation and governance processes for health research in the UK, and unnecessary bureaucracy in the current National Health Service system. Mental health studies appear particularly vulnerable to delay and better systems to facilitate recruitment are required urgently for the evidence base to be improved and facilitate new cost-effective interventions.

One Step Forward, Two Steps Back? Critical Observations on the Proposed Reform of the EU Data Protection Framework

Recent changes in market dynamics of electronic and mobile commerce mean that users of online services are no longer “passive agents of consumption”. Instead online business models increasingly provide a platform for user interaction while simultaneously relying on the contributions made by those users for the population of those spaces. Like many other online services that form part of the Web 2.0 economy, SNS, in the main, are offered free at the point of access. Instead of charging their users a monetary fee, most SNS providers generate revenue through payments they receive from third parties in exchange for the right directly to display advertising to their users or in exchange for providing aggregated data on those users’ behaviour, likes and dislikes. This means that users now “pay’” for online services with the personal information they disclose. Despite repeated announcements by members of the SNS industry that they are committed to the protection of their users’ online privacy, it can therefore not be denied that, in practice, a high level of privacy protection is likely to be in stark conflict with SNS providers’ business objectives and that, in reality, most SNS providers are entirely dependent for their market position on promoting an environment that encourages “openness” and widespread information-sharing by their users through the use of default privacy settings and the subtle encouragement of maximum disclosure in the form of financial and non-financial incentives (for example, additional “free” functionality). This article will examine the implications of these technical, economical and social developments of internet users’ rights to privacy under the current EU data protection framework and whether the changes to that framework proposed by the European Commission in 2012 are likely to address the policy issues identified.

Assessing the MGMT status in glioblastoma: one step forward, two steps back?

O6-methylguanin-DNA-methyltransferase (MGMT) would undoubtedly be the molecule of the decade in the field of glioblastoma. More than 15 years ago, the first reports indicated that high activity of this protein in glioma tissue was associated with limited benefit from alkylating-agent chemotherapy, at that time largely nitrosoureas1. In 2000, methylation of the promoter region of the MGMT gene was linked to improved outcomes in a small series of patients treated with whole-brain radiotherapy, bis-chloroethylnitrosourea, and platinum2. A few years later, in the context of the registration trial for temozolomide in newly diagnosed glioblastoma, a similar polymerase chain reaction (PCR)-based test identified a subpopulation of patients who particularly benefited from adding temozolomide to radiotherapy in the newly diagnosed setting3. In the ensuing years, two major notions became widely accepted in the neuro-oncology community: first, MGMT promoter methylation assessed by PCR is indeed a powerful prognostic marker in all malignant glioma patient series ever tested4, and second, no test other than PCR, including immunochemistry, has gained credibility for reliably predicting clinical benefit5. In the context of the phase III trial for the integrin antagonist cilengitide, CENTRIC, it has been recognized that even a centralized assessment of the MGMT status by methylation-specific PCR (MSP) has its inherent problems, supporting the notion that MGMT testing will be difficult to standardize. Finally, in 2012, the powerful value of MGMT promoter methylation to predict preferential benefit from temozolomide alone over radiotherapy alone in the NOA-08 and Nordic trials of elderly glioblastoma patients6,7 concluded the history of MGMT in a certain way: first, the results of these trials led to wide-spread acknowledgment that MGMT testing should now become the standard of care at least in the elderly, and second, it provided the neuro-oncology community with the challenge to introduce MGMT testing in a standardized and reliable manner in clinical practice8. In that regard, the article by Lalezari and colleagues9 in the present issue of Neuro-Oncology will be feared at first sight by many to be a step back rather than forward: after immunochemistry for MGMT had almost been declared dead5, these authors now try to make a case that double MGMT testing using MSP and immunochemistry is superior to MSP alone. They performed immunochemistry and MSP as well as bisulfite sequencing in a large group of non-study patients with newly diagnosed glioblastoma. Somewhat arbitrarily, they defined a cut-off for immunochemistry at 30% positively stained cells, stating that special care was given to avoid counting MGMT-positive non-neoplastic cells within the tumor tissues. This cut-off defined patients with differing progression-free survival durations of 10.9 vs 7.8 months and overall survival durations of 20.5 vs 16.7 months. These differences were significant, although they are less prominent than with MSP in this study9 or in other comparable series that based MGMT assessment on promoter methylation4. The authors report that they not only frequently saw low MGMT staining intensity in the absence of promoter methylation (23%) but also less frequently saw high MGMT staining in the presence of promoter methylation (8%). High protein levels were associated with poor outcome irrespective of the genetic MGMT status. In contrast, low protein was not associated with a favorable outcome compared with high protein in the absence of methylation. Still, the authors argue for introducing immunochemistry performed their way into the standard assessment of newly diagnosed glioblastoma. The authors acknowledge the previous skepticism regarding immunochemistry for MGMT assessment and try to explain why their immunochemistry correlated with outcome so much better than other previous efforts at using this technique4,5. They also acknowledge that before this method can assume broader relevance, it needs to be tested in a prospective fashion, preferably in the context of controlled clinical trials. Since immunochemistry is so much easier to perform than MSP on a community level and since calls for MGMT testing will get louder based on the results from the trials on the elderly6,7, it is of utmost importance to proceed with caution and not to base any clinical treatment decisions at present on immunochemistry alone based on this one publication. Admittedly, the very extensive and careful study presented by Lalezari and colleagues tells us that the MGMT assessment story is not over and that protein assessment may have to be revisited, albeit in a very careful and controlled manner.

The coronary slow flow phenomenon: one step forward, two steps back

The coronary slow flow phenomenon: one step forward, two steps back

One Step Forward, Two Steps Back: Biconvergence of Washed Harmonic Series

We examine variations of the harmonic series by grouping terms into “washings” that alternate sign with the number of terms in a washing growing exponentially with respect to a fixed base. The bases x = 1 and x = ∞ correspond to the alternating harmonic series and the usual harmonic series; we first consider other positive integral bases and further we consider positive real number bases with a unique way to make sense of adding a non-integral number of terms together. In both cases, we prove a remarkable result regarding the difference between the upper and lower convergent values of the series, and give some analysis of this behavior.

Patient Mobility Directive: One Step Forward or Two Steps Back for Cross-Border Health Care?

The European Parliament and the Council of the European Union have adopted, on 09 March 2011, Directive on the application of patients’ rights in cross-border healthcare. This Directive has emerged as a result of the Court of Justice jurisprudence on social security coverage of health care obtained outside the Member State of patient’ s social security protection, starting with the well known judgement in Raymond Kohll v. Union des caisses de maladie . The focus of the Court has been on developing a set of patients’ entitlements in cross-border health care, emphasising the individual needs and circumstances of patients seeking health care abroad. The aim of the paper is to investigate the Directive and determine whether it will add (once transposed into the national legal systems) to the current set of patient entitlements and make it easier for those patients to obtain socially covered health care outside the state of social protection, and to discuss the Directive’s application in Croatia, once the country joins the EU. The paper first briefly describes the most important principles that have evolved through the Court of Justice case-law, concerning both the application of freedoms guaranteed by EU primary law (namely, freedom to provide and receive cross-border health care services) and the secondary legislation on co-ordination of social security systems within the Union. This is followed by a detailed analysis of the Patient Mobility Directive, namely focusing on the issue whether the Directive actually contributes to patient mobility in the EU, as well as on its relationship with national social security legislation, especially the Croatian one (since Croatia is to become a Member State a few months before the end of the transposition period). Emphasis is placed on the interaction between the social aspects of national legal framework and the internal market as the cornerstone of the European integration. In the end, the paper submits that the Patient Mobility Directive’s impact on actual movement of patients across borders might prove to be, in some areas, counterproductive. Furthermore, the paper stresses the necessity of clarifying the EU legal framework and the need for closer co-operation and dialogue between the EU and the Member States’ relevant authorities, taking into account specificities of individual Member States, and the significance of the Patient Mobility Directive within the described context.

Three steps forward two steps back: implementing advance care planning across a health care system

Creating a system wide change in Advance Care Planning (ACP) has proven to be challenging. Sentara Healthcare is piloting multiple ACP projects across their health system; Home Care, Skilled Nursing...

Long Term Bisphosphonate Use in Osteoporotic Patients; A Step Forward, Two Steps Back

Bisphosphonates are the main class of drugs widely used in prevention and treatment of osteoporosis. Along with the beneficial effects, recent studies point to the harms of long-term treatment with bisphosphonates. The most relevant articles reporting serious adverse effects of bisphosphonates were selected and reviewed with the aim of assessing the risk-benefit of bisphosphonates. We searched PubMed, Web of Science, and Scopus using keywords bisphosphonates, risk of fracture, atrial fibrillation, osteonecrosis jaw, esophageal cancer, and adverse effects with no time limitation. We limited our s research to English articles. Our review shows that bisphosphonates reduce vertebral fractures in short term use while in long-term can cause osteonecrosis jaw, esophageal cancer, atrial fibrillation, and increase the risk of atypical fractures and probably adynamic bone disease. There is no consensus on the time limitation of bisphosphonate usage or its long term adverse effects. Thus, more studies on long-term side effects of bisphosphonates are highly recommended. In addition, new approaches for prevention and treatment of osteoporosis seem necessary. Prescribers should act cautionary and consider full assessment of risk-benefit and the duration of treatment.

HIV and infant feeding – one step forward, two steps back

The recent decision by the South African Health Department to withdraw the provision of free replacement (formula) feeds to HIV-exposed infants has hardly evoked any response from clinicians, health professionals or civil society groups. This paper argues that the decision is short-sighted, lacks an adequate evidence base, and is retrogressive and unconstitutional. Nine supporting arguments are presented and an alternative policy proposed.

Prevention of osteoporosis: one step forward, two steps back

For many years, hormone replacement therapy (HRT) was the mainstay for osteoporosis prevention in postmenopausal women until a large randomized clinical trial raised serious safety concerns. This resulted in a big drop in HRT use and its demotion by regulatory authorities to second-line treatment. Many clinicians now feel that HRT is not safe to use, and recommend various alternatives for the treatment of osteoporosis. But how effective are these alternative therapies, are they any safer than HRT, and how do their costs compare? This review questions the validity of the safety concerns about HRT, and highlights the safety concerns about alternative therapies. It concludes that HRT is as safe as the other treatment options, and its efficacy and low cost demand that it be restored as a first-line treatment for the prevention of postmenopausal osteoporosis. Other therapies are available for use in osteoporosis, and the bisphosphonates are particularly effective for the treatment of the established disease. However, they must be used selectively and with caution, and are best restricted to those patients who are elderly or have severe disease. New treatments are emerging, but again caution must be taken until any long-term adverse effects have been identified.

One Step Forward, Two Steps Back

Previous articleNext article No AccessOne Step Forward, Two Steps Back The Issue of “Behavioral Modernity” Again: A Comment on SheaMartin PorrMartin PorrArchaeology/Centre for Rock-Art Studies, M405, School of Social and Cultural Studies, University of Western Australia, Crawley, Western Australia 6009, Australia ([email protected]). 9 III 11 Search for more articles by this author PDFPDF PLUSFull Text Add to favoritesDownload CitationTrack CitationsPermissionsReprints Share onFacebookTwitterLinkedInRedditEmail SectionsMoreDetailsFiguresReferencesCited by Current Anthropology Volume 52, Number 4August 2011 Sponsored by the Wenner-Gren Foundation for Anthropological Research Article DOIhttps://doi.org/10.1086/660845 Views: 99Total views on this site Citations: 3Citations are reported from Crossref HistorySubmitted March 08, 2011Accepted March 09, 2011 © 2011 by The Wenner-Gren Foundation for Anthropological Research. All rights reserved.PDF download Crossref reports the following articles citing this article:Shumon T. Hussain Gazing at Owls? Human-strigiform Interfaces and their Role in the Construction of Gravettian Lifeworlds in East-Central Europe, Environmental Archaeology 48 (Feb 2018): 1–18.https://doi.org/10.1080/14614103.2018.1434854Martin Porr, Jacqueline M. Matthews Post-colonialism, human origins and the paradox of modernity, Antiquity 91, no.358358 (Aug 2017): 1058–1068.https://doi.org/10.15184/aqy.2017.82Terry Hopkinson ‘Man the symboller’. A contemporary origins myth, Archaeological Dialogues 20, no.22 (Nov 2013): 215–241.https://doi.org/10.1017/S138020381300024X

The fitness evaluation strategy in particle swarm optimization

The particle swarm optimization (PSO) computational method has recently become popular. However, it has limitations. It may trap into local optima and cause the premature convergence phenomenon, especially for multimodal and high-dimensional problems. In this paper, we focus on investigating the fitness evaluation in terms of a particle’s position. Particularly, we find that the fitness evaluation strategy in the standard PSO has two drawbacks, i.e., “two steps forward and one step back” and “two steps back and one step forward”. In addition, we propose a general fitness evaluation strategy (GFES), by which a particle is evaluated in multiple subspaces and different contexts in order to take diverse paces towards the destination position. As demonstrations of GFES, a series of PSOs with GFES are presented. Experiments are conducted on several benchmark optimization problems. The results show that GFES is effective at handling multimodal and high-dimensional problems.

One Step Forward and Two Steps Back: The Slow Process of Re-establishing Diplomatic Relations between Germany and Turkey after the First World War

The First World War greatly affected the balance of power in Europe and elsewhere. In the case of Turkey and Germany, diplomatic ties had been cut off in 1918, and afterwards both countries, which in the meantime had switched from monarchies to republics, had to forge a new relationship. This study focuses on the re-establishment of German–Turkish relations in a very delicate process which also depended on international developments.

One step forward, two steps back

Patients with heart failure (HF) fall into two categories—those who are stable and ambulatory with a relatively low event rate, and patients requiring hospitalization who are characterized by high post-discharge mortality and rates of rehospitalization. HF trials in 2010 contributed to the advancement of outpatient management, whereas the development of novel therapies with a survival benefit remains an unmet need in acute HF syndromes.

Leadership Teams: Developing and Sustaining High Performance

List of Figures Acknowledgments About the Authors Foreword Preface Conceptual Framework Mobilizing Confrontation Coming Together One Step Forward, Two Steps Back Behaving as One Facing the Future Grave under Pressure Index

The provisional diagnostic criteria for fibromyalgia: One step forward, two steps back: Comment on the article by Wolfe et al

The provisional diagnostic criteria for fibromyalgia: One step forward, two steps back: Comment on the article by Wolfe et al

One step forward, two steps back? The GMC, the common law and ‘informed’ consent

Until 2008, if doctors followed the General Medical Council's (GMC's) guidance on providing information prior to obtaining a patient's consent to treatment, they would be going beyond what was technically...

Which Socialism?

Every insurgency is a small advance toward the society of our dreams. Sometimes the small advances accumulate, as in the history of social democracy: two steps forward, one step back. Sometimes, as we all know, what happens is more like one step forward, two steps back. Things get better for some people in some places; persecuted, exploited, and oppressed groups learn to protect themselves and actually win effective protection. Some of these victories are permanent; some are not. We have to defend democracy, regulation, and welfare against constant erosion and adversarial capture; sometimes we do that well, sometimes not. The work is steady, the benefits come mostly in spurts. But the goodness is in the work as much as in the benefits—so it doesn't matter if the work goes on and on, as it does. It is important and worthwhile work because of its mutuality, because of the talents and capacities it calls forth, and because of the moral value it embodies. That work is socialism-in-the making, and that is the only socialism we will ever know.

Coercion and Community Treatment Orders (CTOs): One Step Forward, Two Steps Back?

The shift from hospital-based care to community-based programs for people with serious and persistent mental illnesses has led to the creation of numerous treatment programs, including the recent implementation of community treatment orders (CTOs). This form of mandated outpatient commitment is controversial because it is widely acknowledged to be a coercive intervention. Yet, there is little discussion about why this intervention is considered coercive and whether coercion is acceptable in the context of emerging commitments to recovery for people with serious and persistent mental illnesses. Moreover, there is a need to evaluate whether CTOs advance or undermine the interests of people who are diagnosed with mental illness. This paper seeks to contribute to a discussion of these issues by exploring coercion and its role in community mental health care, and how it may co-exist with recovery in the implementation of community treatment orders.

Gender Studies and Film Studies in France: Steps Forward and Back

AbstractFifteen years after the first translations of Anglo-American feminist film theories, this gender approach is finding it hard to gain acceptance in France. The main reason is the elitist view of cinema d’auteur that is still prevalent in academic circles, where the art is seen as a genius's creation outside social determinations in general and gender relations in particular.However, under the influence of historians and sociologists, who dominate gender research in France, French work on film privileges a historical and sociocultural approach, whereas American research is dominated by psychoanalytical approaches. French gender analyses privilege the expression of dominant relations but also of contradictions at work in the films, whether popular or by an auteur-e, as well as in the stars’ image or in tv fiction. Finally some research explores the changes brought about by the emergence of female film-makers on the French scene.