Defining and measuring construct of interprofessional professionalism

The Interprofessional Professionalism Collaborative (IPC), convened in 2006, currently consists of 11 national organizations representing health professions programs at the doctoral entry level, and is developing a framework of "interprofessional professionalism" (IPP) around observable behaviors that illustrate what professionalism looks like in the context of interprofessional collaborations focused on patient-, client-, and family-centered care. IPC's goal is to create tools to foster and measure these behaviors in health professionals and students. This paper describes the work of IPC to date and its future plans.     

Immunization with apoptotic pseudovirus transduced cells induces both cellular and humoral responses: a proof of concept study in macaques

Dendritic cells are able to present viral antigens to T-cells after uptake of apoptotic bodies derived from virus-infected cells. Immunization with virus-infected apoptotic cells was previously shown to induce HIV-specific immune responses in mice. Here we evaluate the safety and immunogenicity of immunization with activated apoptotic cells in non-human primates using autologous T-cells infected with replication defective VSV pseudotyped SIV(mac239)Δenv. Animals were immunized with γ-irradiated activated T-cells carrying the VSVenvSIV(mac239)Δenv pseudovirus. SIV Gag-specific cellular immune responses were induced as early as two weeks after the first immunization eliciting a biased IFN-γ and IL-2 response. In addition, induction of SIV Gag-specific antibody responses and high titer neutralizing activity against the SIV pseudovirus harboring a VSV-env were detected after two immunizations. The vaccinated group and a control group of Chinese rhesus macaques were intravenously challenged with pathogenic SIV(mac251.) All animals became infected, but SIV-replication was effectively suppressed (below 100 copies/ml) in several animals in both groups. However the group immunized with apoptotic cells revealed better preservation of the gut CD4(+) T-cell compartment. Viral control was inversely correlated with an early (4 weeks) but transient increase in the percentage of Ki67(+)CD4(+) peripheral blood T-cells (Spearman -0.73). We here show that immunizations with activated apoptotic lymphocytes expressing transduced SIV genes result in induction of both cellular and humoral immune responses. This study provides evidence for an immunological principle demonstrating that certain apoptotic cells can be considered as carriers of antigens directing immune responses in macaques.     

Solutions to emergency department 'boarding' and crowding are underused and may need to be legislated

The practice of keeping admitted patients on stretchers in hospital emergency department hallways for hours or days, called "boarding," causes emergency department crowding and can be harmful to patients. Boarding increases patients' morbidity, lengths of hospital stay, and mortality. Strategies that optimize bed management reduce boarding by improving the efficiency of hospital patient flow, but these strategies are grossly underused. Convincing hospital leaders of the value of such solutions, and educating patients to advocate for such changes, may promote improvements. If these strategies do not work, legislation may be required to effect meaningful change.     

Epidemiological investigations of aircrew: an occupational group with low-level cosmic radiation exposure

Aircrew and passengers are exposed to low-level cosmic ionising radiation. Annual effective doses for flight crew have been estimated to be in the order of 2-5 mSv and can attain 75 mSv at career end. Epidemiological studies in this occupational group have been conducted over the last 15-20 years, usually with a focus on radiation-associated cancer. These studies are summarised in this note. Overall cancer risk was not elevated in most studies and subpopulations analysed, while malignant melanoma, other skin cancers and breast cancer in female aircrew have shown elevated incidence, with lesser risk elevations in terms of mortality. In some studies, including the large German cohort, brain cancer risk appears elevated. Cardiovascular mortality risks were generally very low. Dose information for pilots was usually derived from calculation procedures based on routine licence information, types of aircraft and routes/hours flown, but not on direct measurements. However, dose estimates have shown high validity when compared with measured values. No clear-cut dose-response patterns pointing to a higher risk for those with higher cumulative doses were found. Studies on other health outcomes have shown mixed results. Overall, aircrew are a highly selected group with many specific characteristics and exposures that might also influence cancers or other health outcomes. Radiation-associated health effects have not been clearly established in the studies available so far.     

In Vivo Evaluation of Candidate Allele-specific Mutant Huntingtin Gene Silencing Antisense Oligonucleotides

Huntington disease (HD) is a dominant, genetic neurodegenerative disease characterized by progressive loss of voluntary motor control, psychiatric disturbance, and cognitive decline, for which there is currently no disease-modifying therapy. HD is caused by the expansion of a CAG tract in the huntingtin (HTT) gene. The mutant HTT protein (muHTT) acquires toxic functions, and there is significant evidence that muHTT lowering would be therapeutically efficacious. However, the wild-type HTT protein (wtHTT) serves vital functions, making allele-specific muHTT lowering strategies potentially safer than nonselective strategies. CAG tract expansion is associated with single nucleotide polymorphisms (SNPs) that can be targeted by gene silencing reagents such as antisense oligonucleotides (ASOs) to accomplish allele-specific muHTT lowering. Here we evaluate ASOs targeted to HD-associated SNPs in acute in vivo studies including screening, distribution, duration of action and dosing, using a humanized mouse model of HD, Hu97/18, that is heterozygous for the targeted SNPs. We have identified four well-tolerated lead ASOs that potently and selectively silence muHTT at a broad range of doses throughout the central nervous system for 16 weeks or more after a single intracerebroventricular (ICV) injection. With further validation, these ASOs could provide a therapeutic option for individuals afflicted with HD.     

Pain,distress, and anticipated recovery for older versus younger emergency department patients after motor vehicle collision

There is a strong reciprocal association between two highly prevalent public health problems: intimate partner violence and heavy drinking, both of which remain major sources of morbidity and mortality. Brief interventions in the Emergency Department setting have been found to be effective in reducing alcohol-related injury but neither classic intimate partner violence nor substance abuse interventions have adequately integrated assessment and treatment for these co-occurring conditions. The overall goal of this study is to determine whether a motivational intervention delivered at the time of an Emergency Department visit will reduce heavy drinking and improve the safety of women experiencing intimate partner violence. We are completing data collection for a randomized controlled trial enrolling 600 female patients, age 18–64, presenting to one of two urban Emergency Departments, who self-disclose both problem drinking and intimate partner violence. Eligible patients are randomized to a brief manual-guided motivational intervention, and a phone booster at 10 days. The intervention, which is delivered by masters-level therapists during the Emergency Department visit, is recorded and monitored for fidelity. Primary outcomes are episodes of heavy drinking and incidents of intimate partner violence, assessed weekly by Interactive Voice Response System for 12 weeks and at 3, 6 and 12 months by interviewers blinded to group assignment. To identify the impact of assessment alone, we included a no-contact control group assessed only once at 3 months. Secondary outcomes include violence severity, changes in the Composite Abuse Scale and alcohol quantity/frequency, along with other health-related behaviors. The analysis will also explore the impact of likely mediators and moderators of the intervention. While screening and intervention for intimate partner violence is now recommended for women of child bearing age in health care settings, there is a need for rigorous evaluations of what works for whom. Upon completion, we will have high-quality evidence regarding the effectiveness of a low-intensity, brief motivational intervention, delivered by social workers in the Emergency Department setting, for decreasing episodes of heavy drinking and intimate partner violence. Ultimately, this is a model could be generalizable to other acute health care settings. ClinicalTrials.gov Registration Number: NCT01207258     

Cardiac function and plasma catecholamines during upright exercise in healthy young subjects

Radionuclide left ventricular ejection fraction, left ventricular volume changes and plasma catecholamines were recorded in six healthy untrained male subjects at rest and during upright exercise at increasing work loads. During mild submaximal exercise mean left ventricular ejection fraction increased 10% because of end-diastolic dilation, while a further 4% increase of left ventricular ejection fraction was recorded at heavy submaximal exercise mainly due to increased end-systolic contraction. Great individual changes were recorded during maximal exercise.

Alterations in plasma catecholamines were most pronounced at the high exercise levels indicating that changes in cardiac contractility are not linearly correlated with changes in sympathetic nervous activity.

Repeat studies showed only minor variations of mean left ventricular ejection fraction and plasma catecholamines indicating an acceptable reproducibility of the measurements. Variations of both left ventricular ejection fraction and catecholamines were smaller during exercise than at rest.     

Microarray-based classification of diffuse large B-cell lymphoma

OBJECTIVE: Hierarchical clusterings of diffuse large B-cell lymphoma (DLBCL) based on gene expression signatures have previously been used to classify DLBCL into Germinal Center B-cell (GCB) and Activated B-cell (ABC) types. To examine if it was feasible to perform a cross-platform validation on the Affymetrix HG-U133A oligonucleotide arrays and improve the classification, we determined the expression profiles of pretreatment, diagnostic samples from 52 primary nodal DLBCL. METHODS AND RESULTS: First, three previously published gene lists were converted to the HG-U133A probe sets and used for hierarchical clustering. In this way, three subtypes, including the GCB type (n = 20), the ABC type (n = 25) and an intermediate group, Type-3 (n = 5), were distinguished. The CD10 and Bcl-6 expression as well as t(14;18) translocation were prevalent, but not exclusive to the GCB type. By contrast, MUM1 was only expressed in the ABC and in Type-3 samples. The 5-year survival was similar between the groups, but GCB patients showed a better initial response to CHOP or CHOP-like regimens than the remaining patients and tended to have less advanced disease and lower IPI scores. As a next step, an improved set of classifier genes was generated by analysis of 34 patients that were consistently classified as GCB or ABC in the above analyses. Seventy-eight genes were selected and demonstrated on two previously published data sets (Shipp et al. Nat Med 2002;8:68-74 and Houldsworth et al. Blood 2004;103:1862-1868) to exhibit a higher specificity than the original gene lists. CONCLUSION: We conclude that gene expression profiling with Affymetrix Genechips is efficient to distinguish between GCB and ABC types of DLBCL and that these are likely to represent separate biological entities. The Genechip platform is highly standardised and therefore useful for future prospective investigations to establish the value of gene expression profiling in the clinical management of DLBCL.