Should Research Ethics Encourage the Production of Cost-Effective Interventions?

This project considers whether and how research ethics can contribute to the provision of cost-effective medical interventions. Clinical research ethics represents an underexplored context for the promotion of cost-effectiveness. In particular, although scholars have recently argued that research on less-expensive, less-effective interventions can be ethical, there has been little or no discussion of whether ethical considerations justify curtailing research on more expensive, more effective interventions. Yet considering cost-effectiveness at the research stage can help ensure that scarce resources such as tissue samples or limited subject popula- tions are employed where they do the most good; can support parallel efforts by providers and insurers to promote cost-effectiveness; and can ensure that research has social value and benefits subjects. I discuss and rebut potential objections to the consideration of cost-effectiveness in research, including the difficulty of predicting effectiveness and cost at the research stage, concerns about limitations in cost-effectiveness analysis, and worries about overly limiting researchers’ freedom. I then consider the advantages and disadvantages of having certain participants in the research enterprise, including IRBs, advisory committees, sponsors, investigators, and subjects, consider cost-effectiveness. The project concludes by qualifiedly endorsing the consideration of cost-effectiveness at the research stage. While incorporating cost-effectiveness considerations into the ethical evaluation of human subjects research will not on its own ensure that the health care system realizes cost-effectiveness goals, doing so nonetheless represents an important part of a broader effort to control rising medical costs

Why do women invest in pre-pregnancy health and care? A qualitative investigation with women attending maternity services

Background Despite the importance attributed to good pre-pregnancy care and its potential to improve pregnancy and child health outcomes, relatively little is known about why women invest in pre-pregnancy health and care. We sought to gain insight into why women invested in pre-pregnancy health and care. Methods We carried out 20 qualitative in-depth interviews with pregnant or recently pregnant women who were drawn from a survey of antenatal clinic attendees in London, UK. Interviewees were purposively sampled to include high and low investors in pre-pregnancy health and care, with variation in age, partnership status, ethnicity and pre-existing medical conditions. Data analysis was conducted using the Framework method. Results We identified three groups in relation to pre-pregnancy health and care: 1) The “prepared” group, who had high levels of pregnancy planning and mostly positive attitudes to micronutrient supplementation outside of pregnancy, carried out pre-pregnancy activities such as taking folic acid and making changes to diet and lifestyle. 2) The “poor knowledge” group, who also had high levels of pregnancy planning, did not carry out pre-pregnancy activities and described themselves as having poor knowledge. Elsewhere in their interviews they expressed a strong dislike of micronutrient supplementation. 3) The “absent pre-pregnancy period” group, had the lowest levels of pregnancy planning and also expressed anti-supplement views. Even discussing the pre-pregnancy period with this group was difficult as responses to questions quickly shifted to focus on pregnancy itself. Knowledge of folic acid was poor in all groups. Conclusion Different pre-pregnancy care approaches are likely to be needed for each of the groups. Among the “prepared” group, who were proactive and receptive to health messages, greater availability of information and better response from health professionals could improve the range of pre-pregnancy activities carried out. Among the “poor knowledge” group, better response from health professionals might yield greater uptake of pre-pregnancy information. A different, general health strategy might be more appropriate for the “absent pre-pregnancy period” group. The fact that general attitudes to micronutrient supplementation were closely related to whether or not women invested in pre-pregnancy health and care was an unanticipated finding and warrants further investigation.This report is independent research commissioned and funded by the Department of Health Policy Research Programme Pre-Pregnancy Health and Care in England: Exploring Implementation and Public Health Impact, 006/0068

Staphylococcal Toxic Shock Syndrome 2000–2006: Epidemiology, Clinical Features, and Molecular Characteristics

Circulating strains of Staphylococcus aureus (SA) have changed in the last 30 years including the emergence of community-associated methicillin-resistant SA (MRSA). A report suggested staphylococcal toxic shock syndrome (TSS) was increasing over 2000-2003. The last population-based assessment of TSS was 1986.Population-based active surveillance for TSS meeting the CDC definition using ICD-9 codes was conducted in the Minneapolis-St. Paul area (population 2,642,056) from 2000-2006. Medical records of potential cases were reviewed for case criteria, antimicrobial susceptibility, risk factors, and outcome. Superantigen PCR testing and PFGE were performed on available isolates from probable and confirmed cases.Of 7,491 hospitalizations that received one of the ICD-9 study codes, 61 TSS cases (33 menstrual, 28 non-menstrual) were identified. The average annual incidence per 100,000 of all, menstrual, and non-menstrual TSS was 0.52 (95% CI, 0.32-0.77), 0.69 (0.39-1.16), and 0.32 (0.12-0.67), respectively. Women 13-24 years had the highest incidence at 1.41 (0.63-2.61). No increase in incidence was observed from 2000-2006. MRSA was isolated in 1 menstrual and 3 non-menstrual cases (7% of TSS cases); 1 isolate was USA400. The superantigen gene tst-1 was identified in 20 (80%) of isolates and was more common in menstrual compared to non-menstrual isolates (89% vs. 50%, p = 0.07). Superantigen genes sea, seb and sec were found more frequently among non-menstrual compared to menstrual isolates [100% vs 25% (p = 0.4), 60% vs 0% (p<0.01), and 25% vs 13% (p = 0.5), respectively].TSS incidence remained stable across our surveillance period of 2000-2006 and compared to past population-based estimates in the 1980s. MRSA accounted for a small percentage of TSS cases. tst-1 continues to be the superantigen associated with the majority of menstrual cases. The CDC case definition identifies the most severe cases and has been consistently used but likely results in a substantial underestimation of the total TSS disease burden

Evaluation and pharmacovigilance of projects promoting cultivation and local use of Artemisia annua for malaria

<p>Abstract</p> <p>Background</p> <p>Several non-governmental organisations (NGOs) are promoting the use of <it>Artemisia annua </it>teas as a home-based treatment for malaria in situations where conventional treatments are not available. There has been controversy about the effectiveness and safety of this approach, but no pharmacovigilance studies or evaluations have been published to date.</p> <p>Method</p> <p>A questionnaire about the cultivation of <it>A. annua</it>, treatment of patients, and side-effects observed, was sent to partners of the NGO Anamed in Kenya and Uganda. Some of the respondents were then selected purposively for more in-depth semi-structured interviews.</p> <p>Results</p> <p>Eighteen partners in Kenya and 21 in Uganda responded. 49% reported difficulties in growing the plant, mainly due to drought. Overall about 3,000 cases of presumed malaria had been treated with <it>A. annua </it>teas in the previous year, of which about 250 were in children and 54 were in women in the first trimester of pregnancy. The commonest problem observed in children was poor compliance due to the bitter taste, which was improved by the addition of sugar or honey. Two miscarriages were reported in pregnant patients. Only four respondents reported side-effects in other patients, the commonest of which was vomiting. 51% of respondents had started using <it>A. annua </it>tea to treat illnesses other than malaria.</p> <p>Conclusions</p> <p>Local cultivation and preparation of <it>A. annua </it>are feasible where growing conditions are appropriate. Few adverse events were reported even in children and pregnant women. Where ACT is in short supply, it would make sense to save it for young children, while using <it>A. annua </it>infusions to treat older patients who are at lower risk. An ongoing pharmacovigilance system is needed to facilitate reporting of any adverse events.</p

Children’s perceptions of dissimilarity in parenting styles are associated with internalizing and externalizing behavior

The purpose of this study was to examine the relationship between children’s perception of dissimilarity in parenting styles, and internalizing and externalizing problems in children. Children from the general population (n = 658) reported on the level of emotional warmth, rejection, and overprotection of both parents by filling out the child version of the Egna Minnen Beträffande Uppfostran (EMBU-C) and mothers completed the child behavior checklist (CBCL). Intraclass correlations were computed as measures of dissimilarity between parenting styles of mothers and fathers. Children’s perceived dissimilarity in parental emotional warmth is associated with internalizing and externalizing problems (β = 0.092, p < 0.05; β = 0.091, p < 0.05). Perceived dissimilarity between parents’ overprotection is associated with externalizing problems (β = 0.097, p < 0.05). Perceived dissimilarity between parenting styles is associated with externalizing and internalizing problems, over and above the effects of the level of the parenting styles. The results highlight the negative consequences of perceived dissimilarity between parents. To conclude, children have more internalizing and externalizing problems when they perceive their parents as more dissimilar in parenting styles

Robust Detection and Genotyping of Single Feature Polymorphisms from Gene Expression Data

It is well known that Affymetrix microarrays are widely used to predict genome-wide gene expression and genome-wide genetic polymorphisms from RNA and genomic DNA hybridization experiments, respectively. It has recently been proposed to integrate the two predictions by use of RNA microarray data only. Although the ability to detect single feature polymorphisms (SFPs) from RNA microarray data has many practical implications for genome study in both sequenced and unsequenced species, it raises enormous challenges for statistical modelling and analysis of microarray gene expression data for this objective. Several methods are proposed to predict SFPs from the gene expression profile. However, their performance is highly vulnerable to differential expression of genes. The SFPs thus predicted are eventually a reflection of differentially expressed genes rather than genuine sequence polymorphisms. To address the problem, we developed a novel statistical method to separate the binding affinity between a transcript and its targeting probe and the parameter measuring transcript abundance from perfect-match hybridization values of Affymetrix gene expression data. We implemented a Bayesian approach to detect SFPs and to genotype a segregating population at the detected SFPs. Based on analysis of three Affymetrix microarray datasets, we demonstrated that the present method confers a significantly improved robustness and accuracy in detecting the SFPs that carry genuine sequence polymorphisms when compared to its rivals in the literature. The method developed in this paper will provide experimental genomicists with advanced analytical tools for appropriate and efficient analysis of their microarray experiments and biostatisticians with insightful interpretation of Affymetrix microarray data

Democratization and the Diffusion of Shari'a Law: Comparative Insights from Indonesia

The democratization of politics has been accompanied by a rise of Islamic laws in many Muslim-majority countries. Despite a growing interest in the phenomenon, the Islamization of politics in democratizing Muslim-majority countries is rarely understood as a process that unfolds across space and time. Based on an original dataset established during years of field research in Indonesia, this article analyzes the spread of shari’a regulations across the world’s largest Muslim-majority democracy since 1998. The article shows that shari’a regulations in Indonesia diffused unevenly across space and time. Explanations put forward in the literature on the diffusion of morality policies in other countries such as geographic proximity, institutions, intergovernmental relations and economic conditions did not explain the patterns in the diffusion of shari’a regulations in Indonesia well. Instead, shari’a regulations in Indonesia were most likely to spread across jurisdictions where local Islamist groups situated outside the party system had an established presence. In short, the Islamization of politics was highly contingent on local conditions. Future research will need to pay more attention to local Islamist activists and networks situated outside formal politics as potential causes for the diffusion of shari’a law in democratizing Muslim-majority countries

Mechanical cleaning of graphene using in situ electron microscopy

Avoiding and removing surface contamination is a crucial task when handling specimens in any scientific experiment. This is especially true for two-dimensional materials such as graphene, which are extraordinarily affected by contamination due to their large surface area. While many efforts have been made to reduce and remove contamination from such surfaces, the issue is far from resolved. Here we report on an in situ mechanical cleaning method that enables the site-specific removal of contamination from both sides of two dimensional membranes down to atomic-scale cleanliness. Further, mechanisms of re-contamination are discussed, finding surface-diffusion to be the major factor for contamination in electron microscopy. Finally the targeted, electron-beam assisted synthesis of a nanocrystalline graphene layer by supplying a precursor molecule to cleaned areas is demonstrated