Scholarly contributions of required senior research projects in a doctor of pharmacy curriculum.

OBJECTIVE: To determine dissemination outcomes and faculty perceptions of senior research projects conducted from 2008 to 2011 by PharmD students in a curricular pathway focused on direct patient care. METHODS: Preceptors' reported dissemination outcomes of research projects were surveyed and their perceptions of the precepting experience were rated using a web-based survey. Results were compared to those from an earlier pharmaceutical care cohort (2002-2007) and a combined cohort of 2, more research-intensive curricular pathways at the school. RESULTS: The overall response rate was 90.2%. Project dissemination included 61.3% at an institutional forum, 42.3% as a submitted publication, 37.8% as a poster, and 4.5% as an oral presentation. Projects completed from 2008-2011 were significantly more likely than those from 2002-2007 to be submitted for publication (42.3% vs 10.7%, p<0.001) and published (28.8% vs 5.3%, p<0.001). Most preceptors found their research projects valuable to them professionally (88.3%) and to their own or another institution (83.5% and 78.5%, respectively). Ninety-five percent of preceptors would precept again. CONCLUSION: Dissemination rates for pharmaceutical care projects increased over time. Despite modest dissemination levels, the majority of preceptors agreed that required student research projects provide a valuable learning experience for students.

CD8 T-cell reactivity to islet antigens is unique to type 1 while CD4 T-cell reactivity exists in both type 1 and type 2 diabetes.

Previous cross-sectional analyses demonstrated that CD8(+) and CD4(+) T-cell reactivity to islet-specific antigens was more prevalent in T1D subjects than in healthy donors (HD). Here, we examined T1D-associated epitope-specific CD4(+) T-cell cytokine production and autoreactive CD8(+) T-cell frequency on a monthly basis for one year in 10 HD, 33 subjects with T1D, and 15 subjects with T2D. Autoreactive CD4(+) T-cells from both T1D and T2D subjects produced more IFN-γ when stimulated than cells from HD. In contrast, higher frequencies of islet antigen-specific CD8(+) T-cells were detected only in T1D. These observations support the hypothesis that general beta-cell stress drives autoreactive CD4(+) T-cell activity while islet over-expression of MHC class I commonly seen in T1D mediates amplification of CD8(+) T-cells and more rapid beta-cell loss. In conclusion, CD4(+) T-cell autoreactivity appears to be present in both T1D and T2D while autoreactive CD8(+) T-cells are unique to T1D. Thus, autoreactive CD8(+) cells may serve as a more T1D-specific biomarker.

Temporal intra-individual variation of immunological biomarkers in type 1 diabetes patients: implications for future use in cross-sectional assessment.

Multiple immune parameters such as frequencies of autoreactive CD4(+), CD8(+) T-cells and CD4(+)CD25(+)Foxp3(+) T-cells have been explored as biomarkers in human T1D. However, intra-individual temporal variation of these parameters has not been assessed systematically over time. We determined the variation in each of these parameters in a cohort of T1D and healthy donors (HDs), at monthly intervals for one year. Despite low intra- and inter-assay co-efficient of variation (CV), mean CVs for each of the immune parameters were 119.1% for CD4(+) T-cell-derived IFN-γ, 50.44% for autoreactive CD8(+) T-cells, and 31.24% for CD4(+)CD25(+)Foxp3(+) T-cells. Further, both HDs and T1D donors had similar CVs. The variation neither correlated with BMI, age, disease duration or insulin usage, nor were there detectable cyclical patterns of variation. However, averaging results from multiple visits for an individual provided a better estimate of the CV between visits. Based on our data we predict that by averaging values from three visits a treatment effect on these parameters with a 50% effect size could be detected with the same power using 1.8-4-fold fewer patients within a trial compared to using values from a single visit. Thus, our present data contribute to a more robust, accurate endpoint design for future clinical trials in T1D and aid in the identification of truly efficacious therapies.

Telepsychiatry appointments in a continuing care setting: kept, cancelled and no-shows.

We reviewed the appointment data for a psychiatry service in California that provided consultations and also therapy through telepsychiatry. Over an 18-month period, there were 7523 telepsychiatry appointments and 115,148 conventional (face-to-face) appointments. A higher proportion of the telepsychiatry appointments was kept (92% telepsychiatry vs. 87% non-telepsychiatry). Also, telepsychiatry appointments were significantly less likely to be cancelled by patients (3.5% vs. 4.8%) and significantly less likely to be no-shows (4.2% vs. 7.8%). These findings were similar in three of the four counties where the service was delivered. However, one county was different, and further examination suggested that the morale of the staff and patients may have contributed to the unenthusiastic acceptance of telepsychiatry. We conclude that telepsychiatry can be used effectively in continuing care settings as well as in evaluation settings, and that staff and patient morale are important factors in successful telepsychiatry.

An iterative strategy combining biophysical criteria and duration hidden Markov models for structural predictions of Chlamydia trachomatis sigma66 promoters.

BACKGROUND: Promoter identification is a first step in the quest to explain gene regulation in bacteria. It has been demonstrated that the initiation of bacterial transcription depends upon the stability and topology of DNA in the promoter region as well as the binding affinity between the RNA polymerase sigma-factor and promoter. However, promoter prediction algorithms to date have not explicitly used an ensemble of these factors as predictors. In addition, most promoter models have been trained on data from Escherichia coli. Although it has been shown that transcriptional mechanisms are similar among various bacteria, it is quite possible that the differences between Escherichia coli and Chlamydia trachomatis are large enough to recommend an organism-specific modeling effort. RESULTS: Here we present an iterative stochastic model building procedure that combines such biophysical metrics as DNA stability, curvature, twist and stress-induced DNA duplex destabilization along with duration hidden Markov model parameters to model Chlamydia trachomatis sigma66 promoters from 29 experimentally verified sequences. Initially, iterative duration hidden Markov modeling of the training set sequences provides a scoring algorithm for Chlamydia trachomatis RNA polymerase sigma66/DNA binding. Subsequently, an iterative application of Stepwise Binary Logistic Regression selects multiple promoter predictors and deletes/replaces training set sequences to determine an optimal training set. The resulting model predicts the final training set with a high degree of accuracy and provides insights into the structure of the promoter region. Model based genome-wide predictions are provided so that optimal promoter candidates can be experimentally evaluated, and refined models developed. Co-predictions with three other algorithms are also supplied to enhance reliability. CONCLUSION: This strategy and resulting model support the conjecture that DNA biophysical properties, along with RNA polymerase sigma-factor/DNA binding collaboratively, contribute to a sequence's ability to promote transcription. This work provides a baseline model that can evolve as new Chlamydia trachomatis sigma66 promoters are identified with assistance from the provided genome-wide predictions. The proposed methodology is ideal for organisms with few identified promoters and relatively small genomes.

The effect of obesity on kidney length in a healthy pediatric population.

Over the past decade, the percentage of children who are obese has rapidly increased. As weight has been shown to correlate strongly with the size of various organs, we have observed that obese children have larger kidneys than their normal-weight counterparts. This study sought to quantify this observation by establishing the normal limits of renal length for this population. We examined 204 healthy patients seen for benign hematuria between January 2000 and May 2008. Both right and left kidney lengths significantly correlated with age, height, weight, body mass index and body surface area in our obese patients (n = 59). Height was also found to be a significant predictor of kidney length, in the obese group, by multiple linear regression analysis and was used to create renal length nomograms for the obese pediatric population (P < 0.01). According to this analysis, obese patients had significantly larger kidneys than those of normal-weight patients (P < 0.01). By defining the normal limits of renal length for this group, unnecessary evaluation for nephromegaly will be avoided.

Teaching psychiatry in primary care residencies: do training directors of primary care and psychiatry see eye to eye?

OBJECTIVE: This study compares the views of psychiatry residency training directors about psychiatry and mental health training in the primary care programs in their institutions with those of the primary care residency training directors. METHODS: A 16-item questionnaire surveying specific areas of training and perceived adequacy of current teaching was distributed to 1,544 U.S. primary care and psychiatry program directors. RESULTS: The response rate was 53%. Among psychiatry training directors, 85% responded that psychiatry training in their primary care programs was minimal to suboptimal, while 68% of family practice training directors responded that their psychiatry training was optimal to extensive. Among psychiatry training directors, 89% were dissatisfied with the psychiatry training in their primary care programs, and only 8% were satisfied. In contrast, almost half of primary care training directors were satisfied. However, within the primary care programs, there was a marked difference between family practice (majority satisfied) and the rest (internal medicine, obstetrics and gynecology, pediatrics, mostly unsatisfied). All primary care and psychiatry training directors agreed that most basic psychiatric skills and diagnoses were taught in the primary care programs. For all skills and syndromes examined, psychiatry training directors consistently and significantly rated the training to be less adequate than did primary care training directors. There was general agreement that primary care physicians should be able to treat most uncomplicated cases in patients with psychiatric disorders, and some but not other psychiatric conditions. CONCLUSION: Psychiatry and primary care training directors, except in family practice, generally agree that psychiatry training in primary care programs is inadequate and should be significantly enhanced. There should be more communication between psychiatry and primary care training programs for optimal curriculum development.

An iterative approach to class II predictions.

An iterative approach to resolving protein-peptide binding motifs is appropriate when the length of the binding protein is variable and a variety of amino acid residues may successfully occupy multiple positions. This chapter describes an iterative algorithm that first aligns binding peptides of variable lengths and then extracts a quantitative motif from the resulting alignment. Numerous examples are presented to illustrate the utility of the iterative process.

Mental health and psychiatry training in primary care residency programs. Part I. Who teaches, where, when and how satisfied?

OBJECTIVE: Some 40% of patients treated by primary care physicians have significant mental health problems. Only about half eventually receive mental health care, usually by the primary care physicians, often inadequately. Recently, there has been an increased attempt to incorporate psychiatry in primary care training programs. The authors sought to assess the current status of psychiatry training in Internal Medicine (IM), Family Practice (FP), Pediatrics (Peds) and Obstetrics and Gynecology (Ob/Gyn) residency programs. METHOD: All 1365 directors of accredited residency training programs in IM, FP, Ob/Gyn and Peds received a 16-item anonymous questionnaire in 2001-2002, collecting descriptive data concerning their psychiatry training. RESULTS: A great majority of IM (71%), Ob/Gyn (92%) and Peds (85%) training directors felt that the training was minimal or suboptimal, as compared to 41% of FP training directors (P<.001). Sixty-four percent of FP program directors were satisfied with their training (P<.001). In contrast, 54% of other PC program directors were dissatisfied with their psychiatry training. All programs utilized ambulatory care setting extensively. Family Practice programs had more types of mental health teachers, teaching formats and teaching settings (P<.001). A majority of IM (57%) and Peds (70%) residencies desired more psychiatry training in their programs compared to only a third of FP and 40% of Ob/Gyn programs (P<.001). Teaching in clinical settings was preferred by all except Ob/Gyn programs (P<.001). Psychiatry departments contributed more to IM and Peds programs than others. CONCLUSION: A majority of primary care training programs are dissatisfied with the current status of their psychiatric training except for FP programs. Family Practice programs have the most variety in training formats, venues and teachers. There are some specialty-specific differences in perceived needs and desires in psychiatric training.

Mental health and psychiatry training in primary care residency programs. Part II. What skills and diagnoses are taught, how adequate, and what affects training directors' satisfaction?

OBJECTIVE: The purpose of this study is to describe the psychiatric skills and diagnostic categories taught in primary care training programs, their adequacy, the perceived needs and desires for curriculum enhancement and the factors affecting training directors' satisfaction. METHOD: All 1365 directors of accredited residency training programs in Internal Medicine (IM), Family Practice (FP), Obstetrics and Gynecology (Ob/Gyn), Pediatrics (Peds) and psychiatry received a 16-item anonymous questionnaire about psychiatry training in their program. Responses to the questionnaire to items concerning the skills and diagnostic categories taught, assessment of adequacy of teaching and desires for curriculum enhancement for specific skills and diagnostic categories were analyzed. The factors affecting training directors' satisfaction were explored. RESULTS: Interviewing skills were taught by a majority of all training programs and were considered adequate by 81% of FP and 54% of IM programs, in contrast to less than a majority of Ob/Gyn and Peds programs (P<.001). A majority provided diagnostic interviewing and counseling training, but only FP considered it adequate. A majority taught psychopharmacology and various psychiatric diagnoses, but only in FP did a majority consider them adequate. Both Peds and FP programs teach child psychiatry; significantly, more Peds compared to FP consider their training to be adequate. A vast majority of IM, Ob/Gyn and Peds programs, and 50% of FP programs desired more training in interviewing techniques and diagnostic interview. A majority of all programs desired more counseling and psychopharmacology training and more training in disorders of childhood and adolescence. The overall satisfaction rate for psychiatric training across specialties was 46% (n=657). Sixty-four percent of FP programs were satisfied compared to 31% of non-FP programs. Satisfaction was associated with increased amount of psychiatric training, diversity of training formats, venues, faculty and settings, the amount of contribution to teaching by psychiatry departments and the presence of current teaching in interviewing skills. There were specialty-specific differences in factors associated with satisfaction. In general, a smaller size of residency program was associated with satisfaction except in IM, where larger size was associated with satisfaction. Satisfaction was associated with the opinion that primary care physician should be ready and willing to treat more psychiatric conditions. CONCLUSION: Most primary care training programs currently offer training in most psychiatric skills and disorders, but a majority of training directors are dissatisfied with their psychiatry training. There is a difference in the estimation of adequacy concerning training between FP, which consistently rates their teaching to be adequate, and all other primary care programs, which consider their teaching inadequate. This difference may be partly due to actual differences in amount and diversity of training as well as differences in the threshold for satisfaction. A vast majority of primary care training programs desire more training in almost all aspects of psychiatry, and there may be specialty-specific needs and areas of curriculum enhancement. To enhance satisfaction, we should improve the quality as well as the quantity of training, as well as the diversity in training formats, venues and faculty.

A consensus strategy for combining HLA-DR binding algorithms.

Diverse approaches have generated algorithms for predicting the binding of peptides and human leukocyte antigen DR (HLA-DR) molecules. As prediction tools appear online, interesting questions arise. Are the various predictions accurate? Do the predictions agree? Is there a value to combined results over individual predictions? Three directly accessible online HLA-DR binding prediction tools are evaluated here to address these questions. The three algorithms generate predictions for high affinity binding that partially agree. No one algorithm is consistently superior or inferior. When a consensus strategy provides a fourth prediction, it is consistently best or second best, regardless of the performance measure being utilized.