Theoretical model of critical issues in informed consent in HIV vaccine trials

The informed consent process (ICP) for HIV vaccine trials poses unique challenges and would benefit from improvements to its historically based structure and format. Here, we propose a theoretical framework that provides a basis for systematically evaluating and addressing these challenges. The proposed framework follows a linear pathway, starting with the precondition of voluntariness, three main variables of valid decision-making (competency, provision of information and understanding) and then the consequential outcome of either refusal or consent to participate. The existing literature reveals that culturally appropriate provision of information and resultant understanding by the vaccine trial participant are among the most significant factors influencing the authenticity of valid decision-making, though they may be overridden by other considerations, such as individual altruism, mistrust, and HIV-related stigma. Community collaborations to foster bidirectional transmission of information and more culturally tailored consenting materials, therefore, represent a key opportunity to enhance the ICP. By providing a visual synopsis of the issues most critical to IC effectiveness in a categorical and relational manner, the framework provided here presents HIV vaccine researchers a tool by which the ICP can be more systematically evaluated and consequently improved.     

Minimum depths to essential structures in a UK military population using computed tomography: application to stab-resistant body armour

International Journal of Legal Medicine - Edged weapons are a known domestic threat to the police forces of the UK. This threat is mitigated by wearing stab-resistant body armour that is either...     

Society of Abdominal Radiology (SAR) and European Society of Urogenital Radiology (ESUR) joint consensus statement for MR imaging of placenta accreta spectrum disorders

This study was conducted in order to establish the joint Society of Abdominal Radiology (SAR) and European Society of Urogenital Radiology (ESUR) guidelines on placenta accreta spectrum (PAS) disorders and propose strategies to standardize image acquisition, interpretation, and reporting for this condition with MRI. The published evidence-based data and the opinion of experts were combined using the RAND–UCLA Appropriateness Method and formed the basis for these consensus guidelines. The responses of the experts to questions regarding the details of patient preparation, MRI protocol, image interpretation, and reporting were collected, analyzed, and classified as “recommended” versus “not recommended” (if at least 80% consensus among experts) or uncertain (if less than 80% consensus among experts). Consensus regarding image acquisition, interpretation, and reporting was determined using the RAND–UCLA Appropriateness Method. The use of a tailored MRI protocol and standardized report was recommended. A standardized imaging protocol and reporting system ensures recognition of the salient features of PAS disorders. These consensus recommendations should be used as a guide for the evaluation of PAS disorders with MRI. • MRI is a powerful adjunct to ultrasound and provides valuable information on the topography and depth of placental invasion. • Consensus statement proposed a common lexicon to allow for uniformity in MRI acquisition, interpretation, and reporting of PAS disorders. • Seven MRI features, namely intraplacental dark T2 bands, uterine/placental bulge, loss of low T2 retroplacental line, myometrial thinning/disruption, bladder wall interruption, focal exophytic placental mass, and abnormal vasculature of the placental bed, reached consensus and are categorized as “recommended” for diagnosing PAS disorders.     

Comparing 3 Values Clarification Methods for Colorectal Cancer Screening Decision-Making: A Randomized Trial in the US and Australia

Purpose

To compare the effects of three methods of values clarification (VCM): balance sheet; rating and ranking; and a discrete choice experiment (DCE) on decision-making about colorectal cancer (CRC) screening among adults in the US and Australia.

Methods

Using online panels managed by a survey research organization in the US and Australia, we recruited adults ages 50–75 at average risk for CRC for an online survey. Those eligible were randomized to one of the three VCM tasks. CRC screening options were described in terms of five key attributes: reduction in risk of CRC incidence and mortality; nature of the screening test; screening frequency; complications from screening; and chance of requiring a colonoscopy (as initial or follow-up testing). Main outcomes included self-reported most important attribute and unlabeled screening test preference by VCM and by country, assessed after the VCM.

Results

A total of 920 participants were enrolled; 51 % were Australian; mean age was 59.0; 87.0 % were white; 34.2 % had a 4-year college degree; 42.8 % had household incomes less than $45,000 USD per year; 44.9 % were up to date with CRC screening. Most important attribute differed across VCM groups: the rating and ranking group was more likely to choose risk reduction as most important attribute (69.8 %) than the balance sheet group (54.7 %) or DCE (49.3 %), p < 0.0001; most important attribute did not vary by country (p = 0.236). The fecal occult blood test (FOBT)-like test was the most frequently preferred test overall (55.9 %). Unlabeled test choice did not differ meaningfully by VCM. Australians were more likely to prefer the FOBT (AU 66.2 % vs. US 45.1 %, OR 2.4, 95 % CI 1.8, 3.1). Few participants favored no screening (US: 9.2 %, AU: 6.2 %).

Conclusions

Screening test attribute importance varied by VCM, but not by country. FOBT was more commonly preferred by Australians than by Americans, but test preferences were heterogeneous in both countries.

Electronic supplementary material

The online version of this article (doi:10.1007/s11606-013-2701-0) contains supplementary material, which is available to authorized users.KEY WORDS: values clarification, colorectal cancer screening, patient decision support     

Haplotype-based study of the association of alcohol and acetaldehyde-metabolising genes with alcohol dependence (with or without comorbid anxiety symptoms) in a Cape Mixed Ancestry population

Alcohol dependence (AD) has a large heritable component. Genetic variation in genes involved in the absorption and elimination of ethanol have been associated with AD. However, some of these polymorphisms are not present in an African population. Previous studies have reported that a type of AD which is characterized by anxious behaviour may be a genetically specific subtype of AD. We investigated whether variation in genes encoding cytochrome P450 2E1 (CYP2E1) or acetaldehyde-metabolising enzymes (ALDH1A1, ALDH2) might alter the risk of AD, with and without symptoms of anxiety, in a Cape population with mixed ancestry. Eighty case control pairs (one with AD, one without AD) were recruited and individually matched for potential confounders. Genotype data were available for 29 single-nucleotide polymorphisms (SNPs) across the three genes. Linkage disequilibrium D′ values were evaluated for all pairwise comparisons. Allele and haplotype frequencies were compared between cases and controls using a χ ² test. The ACAG haplotype in block 4 of the ALDH1A1 gene provided evidence of an association with AD (p?=?0.03) and weak evidence of an association with AD without symptoms of anxiety (p?=?0.06). When a genetic score was constructed using SNPs showing nominal evidence of association with AD, every extra risk allele increased the odds of AD by 35 % (OR 1.35, 95%CI 1.08, 1.68, p?=?0.008) and the odds of having AD with anxiety symptoms increased by 53 % (OR 1.53, 95%CI 1.14, 2.05, p?=?0.004). Although our results are supported by previous studies in other populations, they must be interpreted with caution due to the small sample size and the potential influence of population stratification.     

Effect of Dosing Cup Size on the Aerosol Performance of High-Dose Carrier-Based Formulations in a Novel Dry Powder Inhaler

This study investigated how varying the dosing cup size of a novel reservoir dry powder inhaler (DPI) affects the detachment of a micronized active pharmaceutical ingredient from larger carrier particles, and the aerosol performance of a DPI carrier formulation. Three different-sized dosing cups were designed: 3D printed with cup volumes of 16.26 mm³, 55.99 mm³, and 133.04 mm³, and tested with five different carrier type formulations with beclomethasone dipropionate (BDP) concentrations between 1% and 30% (w/w). The morphology of the BDP attached to the carrier was investigated using scanning electron microscopy and the aerosol performance using the Next Generation Impactor. Increasing the volume of the dosing cup led to a reduction of BDP deposition in the Next Generation Impactor preseparator, and an increase in BDP detachment from the carrier was observed, leading to increased aerosol performance. The decreased amount of BDP attached to carrier after aerosolization was attributed to the increased dosing cup void volume. This may enable greater particle-particle and particle-wall collisions, with greater BDP detachment from the carrier and deagglomeration of smaller agglomerates. The dosing cup volume was observed to have significant influence on particle dispersion and the overall aerosol performance of a DPI.     

Klebsiella pneumoniae Bloodstream Infection: Epidemiology and Impact of Inappropriate Empirical Therapy

Multidrug resistance associated with extended-spectrum beta-lactamase (ESBL) and Klebsiella pneumoniae carbapenemase (KPC) among K. pneumoniae is endemic in southern Europe. We retrospectively analyzed the impact of resistance on the appropriateness of empirical therapy and treatment outcomes of K. pneumoniae bloodstream infections (BSIs) during a 2-year period at a 1420-bed tertiary-care teaching hospital in northern Italy. We identified 217 unique patient BSIs, including 92 (42%) KPC-positive, 49 (23%) ESBL-positive, and 1 (0.5%) metallo-beta-lactamase-positive isolates. Adequate empirical therapy was administered in 74% of infections caused by non-ESBL non-KPC strains, versus 33% of ESBL and 23% of KPC cases (p < 0.0001). To clarify the impact of resistance on BSI treatment outcomes, we compared several different models comprised of non-antibiotic treatment-related factors predictive of patients’ 30-day survival status. Acute Physiology and Chronic Health Evaluation (APACHE) II score determined at the time of positive blood culture was superior to other investigated models, correctly predicting survival status in 83% of the study cohort. In multivariate analysis accounting for APACHE II, receipt of inadequate empirical therapy was associated with nearly a twofold higher rate of death (adjusted hazard ratio 1.9, 95% confidence interval 1.1–3.4; p = 0.02). Multidrug-resistant K. pneumoniae accounted for two-thirds of all K. pneumoniae BSIs, high rates of inappropriate empirical therapy, and twofold higher rates of patient death irrespective of underlying illness.