Deferred consent in a minimal-risk study involving critically ill subarachnoid hemorrhage patients

INTRODUCTION:

Alterations from first-party and surrogate decision-maker consent can enhance the feasibility of research involving critically ill patients.

OBJECTIVE:

To describe the use of a deferred-consent model to enable participation of critically ill patients in a minimal-risk biomarker study.

METHODS:

A prospective observational study was conducted in which serum biomarker samples were collected three times daily over the first 14 days following aneurysmal subarachnoid hemorrhage. Sample collection was initiated on intensive care unit admission and consent was obtained when research personnel could approach the patient or the patient’s surrogate decision maker.

RESULTS:

Twenty-seven patients were eligible for the study, of whom only five were capable of providing informed consent. Full consent was obtained for 21 (78%) patients through self- (n=4) and surrogate (n=17) consent. Partial consent or refusal (only permitting the collection of blood samples as a part of routine care or use of data) occurred in three patients. Among the 22 consents sought from surrogates, three (11%) refused participation. The refusals included the sickest patients in the cohort. Once consent was provided, no patient or surrogate withdrew consent before study completion.

DISCUSSION:

Use of a deferred consent model enabled participation of critically ill patients in a minimal-risk biomarker study with no withdrawals.

CONCLUSIONS:

Further research and enhanced awareness of the potential utility of hybrid models, including deferred consent in addition to patient or surrogate consent, in the conduct of low-risk and minimally interventional time-sensitive studies of critically ill patients are required.     

Majority Vote and Other Problems when using Computational Tools

Computational tools are essential for most of our research. To use these tools, one needs to know how they work. Problems in application of computational methods to variation analysis can appear at several stages and affect, for example, the interpretation of results. Such cases are discussed along with suggestions how to avoid them. The applications include incomplete reporting of methods, especially about the use of prediction tools; method selection on unscientific grounds and without consulting independent method performance assessments; extending application area of methods outside their intended purpose; use of the same data several times for obtaining majority vote; and filtering of datasets so that variants of interest are excluded. All these issues can be avoided by discontinuing the use software tools as black boxes.     

Alternatives assessment and informed substitution: A global landscape assessment of drivers,methods, policies and needs

There are increasing policy and market drivers for removing chemicals of concern from manufacturing processes and products. These drivers have centered primarily on developed countries. However, global activities through the United Nations, individual countries, and advocacy organizations are increasing concerns about chemical impacts in developing countries and economies in transition as well. While reducing the use of chemicals of concern is a primary goal, eliminating such substances without thoughtful consideration for their replacements can lead to regrettable substitutions. Against this backdrop there is growing attention to the identification, assessment, and adoption of safer chemicals, as well as product and process design alternatives. Informed substitution is a critical chemical risk management approach, focused on an intentional transition from chemicals of high concern to chemicals and technological processes of lower concern. Alternatives assessment, an interactive, step-defined process, has emerged as a critical approach to support informed substitution. Over the past decade, a number of tools, approaches, and case examples of alternatives assessment and informed substitution have emerged. Policies and practical experience have followed, improving the landscape of alternatives assessment and informed substitution. This article provides an assessment of the state-of-practice of both alternatives assessment and informed substitution methods, policies, and practices. We identify key needs and actions that can be taken by various stakeholder groups moving forward to advance the field. We conclude that there is a critical need for multi-stakeholder, multi-disciplinary collaboration at a global level to build capacity and support networks that can ensure the growth and success of informed substitution efforts in the future.     

Tropical countries may be willing to pay more to protect their forests

Inadequate funding from developed countries has hampered international efforts to conserve biodiversity in tropical forests. We present two complementary research approaches that reveal a significant increase in public demand for conservation within tropical developing countries as those countries reach upper-middle-income (UMI) status. We highlight UMI tropical countries because they contain nearly four-fifths of tropical primary forests, which are rich in biodiversity and stored carbon. The first approach is a set of statistical analyses of various cross-country conservation indicators, which suggests that protective government policies have lagged behind the increase in public demand in these countries. The second approach is a case study from Malaysia, which reveals in a more integrated fashion the linkages from rising household income to increased household willingness to pay for conservation, nongovernmental organization activity, and delayed government action. Our findings suggest that domestic funding in UMI tropical countries can play a larger role in (i) closing the funding gap for tropical forest conservation, and (ii) paying for supplementary conservation actions linked to international payments for reduced greenhouse gas emissions from deforestation and forest degradation in tropical countries.Primary forests—“forests of native species in which there are no clearly visible signs of past or present human activity” (ref. 1, p. 11)—are globally significant repositories of biodiversity (2) and carbon (3). The global area of these forests is declining at an annual percentage rate that is nearly triple the rate for total global forest area (ref. 1, tables 2.4 and 3.3). Virtually all of the loss is occurring in tropical countries (SI Text, section 1). Logging is the main cause of the loss (ref. 1, p. 27), but hunting threatens biodiversity even in primary forests with intact tree cover (4, 5).Protecting primary tropical forests is a core mission of several international institutions created since the early 1990s, including the Convention on Biological Diversity (CBD), the Global Environment Facility (GEF), and the UN Collaborative Program on Reducing Emissions from Deforestation and Forest Degradation in Developing Countries (REDD). However, the CBD failed to achieve its goal of significantly reducing biodiversity loss by 2010 (6); international funding for biodiversity protection through the GEF and other mechanisms is below commitments made at the 1992 Earth Summit (7) and the amounts required to achieve the CBD’s 2020 protection targets (8); and REDD has not advanced beyond a readiness phase (www.un-redd.org). Relying on international mechanisms to fund protection of primary tropical forests does not look like a winning strategy.Here, we argue that economic development during the past 20–25 y has raised public demand for forest protection within tropical countries, but the level of protection supplied by tropical country governments has not kept pace. We focus on the dynamics of conservation and development within relatively wealthier developing countries: The group that is classified by the World Bank as upper-middle income (UMI). As we will show, the majority of primary forest area in tropical countries is found in these countries. We hypothesize that public willingness to pay (WTP) to protect forests has reached a relatively high level in UMI countries, leading to greater support for local conservation nongovernmental organizations (NGOs) and prompting governments to boost forest protection efforts—but not as much as the public would like. This gap between domestic demand and domestic supply of forest protection has two important implications: Domestic funding might be sufficient to cover the costs of additional protection in some, and perhaps many, tropical countries; and international funding might be able to leverage more domestic funding than it currently does.Although many cross-country studies in the environmental Kuznets curve (EKC) literature have investigated the effect of rising national income on deforestation (9), none has considered the effect on primary forests. This gap matters because deforestation, unlike primary forest loss, results mainly from agricultural conversion, not logging (1, 10). A few cross-country studies have considered the effect of national income on creation of protected areas (11–16), but with mixed findings on the significance of the effect. A second and larger group of studies has used surveys to measure WTP for biodiversity conservation by domestic populations within particular countries. Most of these studies have failed to detect a significant income effect (P < 0.05) (17, 18). Metaanalyses of these studies estimate income effects that are generally positive (protection increases with income) but not necessarily statistically significant (17, 18).We extended this prior work by coupling two research approaches: a broad-brush statistical analysis of the association between a standard measure of economic development, i.e., per capita gross national income (GNI), and a large set of cross-country conservation indicators (CIs); and a focused investigation of forest protection in a particular UMI country, Malaysia. The statistical analysis spanned 12 indicators from 10 diverse sources (Materials and Methods and SI Text, section 1). The indicators pertained to public environmental preferences, conservation NGOs, and government action (conservation spending, protected area establishment). These indicators relate more directly to our hypothesis about domestic demand and domestic supply of forest protection than do the deforestation rates analyzed by EKC studies. We limited the samples to countries classified as tropical by the UN Food and Agriculture Organization Forestry Department (ref. 19, data table 2) and paid special attention to differences between tropical countries in the UMI group and ones in lower income groups.The Malaysian case study allowed us to examine more closely the linkages from rising household income to increased household WTP, NGO engagement, and government protective action, and thereby uncover reasons for the underprovision of forest protection relative to household preferences. The case concerned Belum–Temengor, a 300,000-ha forested region in the state of Perak (Fig. 1). This region contains the largest area of primary forest in Peninsular Malaysia outside a national park. Our research included a population-representative survey of 1,261 rural and urban households in the Malaysian state of Selangor and the federal territory of Kuala Lumpur during 2010 (Materials and Methods). We used choice experiments (20, 21) to estimate household WTP to protect Belum–Temengor against logging and poaching (SI Text, section 2). Information from the case study enabled us to compare the public’s aggregate WTP for protection to current protection expenditures and to discuss why there is a gap between the two.Open in a separate windowFig. 1.Locations of Belum–Temengor (site of forest protection plans in choice experiments) and Selangor and Kuala Lumpur (site of household survey; the black dot is Kuala Lumpur) within Peninsular Malaysia (light gray). Lines show Malaysian state boundaries. Sources: base map, GADM database (www.gadm.org); Belum–Temengor boundaries, Forest Research Institute Malaysia.     

Evaluation of an antipsychotic information sheet for patients

Introduction. The objective of this study was to develop a decision aid that patients and clinicians might use to help the patient in the process of selecting an antipsychotic medication. In addition, we aimed to determine the antipsychotic that patients would choose given the information contained in the leaflet. Method. We designed a questionnaire for patients to appraise the contents of the leaflet, their understanding of the leaflet and the potential impact of the leaflet on compliance and therapeutic relationship between patient and doctor. Results. We recruited 30 stable patients with a diagnosis of a psychotic illness to evaluate the leaflet and to determine patient choice. Over 90% of patients felt that the leaflet improved their knowledge of antipsychotic medication. Seventy-six percent of patients agreed that the leaflet contained the right type and amount of information. Seventy percent of respondents believed the leaflet would improve the trust between them and their doctors, and almost half (47%) stated they were more likely to take their medicine after reading the leaflet. Forty percent of patients would prefer to switch antipsychotic medication, with quetiapine being the most frequently preferred option. Conclusion. The results indicate that, for patients in the stable phase of their illness, the leaflet is a useful tool in selecting an antipsychotic medication and may represent a way forward in improving outcomes in patients with psychotic disorders. A larger study examining outcomes using this tool would establish its clinical utility.     

Polysialic acid expression is not necessary for motor neuron target selectivity

Introduction: Recovery after peripheral nerve lesions depends on guiding axons back to their targets. Polysialic acid upregulation by regrowing axons has been proposed recently as necessary for this target selectivity. Methods: We reexamined this proposition using a cross‐reinnervation model whereby axons from obturator motor neurons that do not upregulate polysialic acid regenerated into the distal femoral nerve. Our aim was to assess their target selectivity between pathways to muscle and skin. Results: After simple cross‐repair, obturator motor neurons showed no pathway preference, but the same repair with a shortened skin pathway resulted in selective targeting of these motor neurons to muscle by a polysialic acid–independent mechanism. Conclusion: The intrinsic molecular differences between motor neuron pools can be overcome by manipulation of their access to different peripheral nerve pathways such that obturator motor neurons preferentially project to a terminal nerve branch to muscle despite not upregulating the expression of polysialic acid. Muscle Nerve 47: 364–371, 2013     

Treatment preferences of originator versus biosimilar drugs in Crohn’s disease; discrete choice experiment among gastroenterologists

Objective. To explore preferences of gastroenterologists for biosimilar drugs in Crohn’s disease. Material and methods. Discrete choice experiment was carried out involving 51 Hungarian gastroenterologists in May 2014. The following attributes were used to describe hypothetical choice sets: 1) type of the treatment (biosimilar/originator), 2) severity of disease, 3) availability of continuous medicine supply, 4) frequency of the efficacy check-ups. Multinomial logit model was used to differentiate between three attitude types: 1) always opting for the originator, 2) willing to consider biosimilar for biological-naïve patients only, 3) willing to consider biosimilar treatment for both types of patients. Conditional logit model was used to estimate the probabilities of choosing a given profile. Results. Men, senior consultants, working in inflammatory bowel disease center and treating more patients were more likely willing to consider biosimilar for biological-naïve patients only. Treatment type (originator/biosimilar) was the most important determinant of choice for patients already treated with biologicals, and the availability of continuous medicine supply in case of biological-naïve patients. The probabilities of choosing the biosimilar with all the benefits offered over the originator under current reimbursement conditions are 89% versus 11% for new patients, and 44% versus 56% for patients already treated with biological. Conclusions. For gastroenterologist, the continuous medical supply would be one of the major benefits of biosimilars. However, benefits offered in the scenarios do not compensate for the change from the originator to the biosimilar treatment of patients already treated with biologicals.     

Preferences for symmetry in faces change across the menstrual cycle

Symmetry in human male faces may be a cue to heritable fitness benefits and is found attractive. Preferences for facial masculinity, another proposed marker of genetic quality, have been found to vary in ways that may maximise evolutionary relevant benefits and masculinity is found to be of increased attractiveness at peak fertility across the menstrual cycle. Here we show that women prefer more symmetric faces at peak fertility (Study 1) and that such shifting preferences may be potentially strategic preferences as we found them to occur only for judgements concerning short-term relations and when women already had a partner (Study 2). Such preferences potentially indicate a strategy that maximises the quality of extra-pair/short-term partners or a quality dependent response to hormones. Such strategic preferences for symmetry may support the role of symmetry in signalling potential good-gene benefits.