Curriculum mapping of accredited pharmacy programs in the United States.

INTRODUCTION: No current guidance exists to inform the content area credit hours for doctor of pharmacy (PharmD) programs in the United States (US). METHODS: Public websites were accessed for all Accreditation Council for Pharmacy Education (ACPE) accredited PharmD programs in the US to record the credit hours devoted to drug therapy, clinical skills, experiential learning, scholarship, social and administrative sciences, physiology/pathophysiology, pharmacogenomics, medicinal chemistry, pharmacology, pharmaceutics, and pharmacokinetics/pharmacodynamics in the didactic curricula. Due to the high prevalence of programs that integrate drug therapy, pharmacology, and medicinal chemistry into a single course, we subdivided programs based upon whether drug therapy courses were "integrated" or "non-integrated." A regression analyses was conducted to explore the relationship between each content area and North American Pharmacist Licensure Examination (NAPLEX) pass rates and residency match rates. RESULTS: Data were available for 140 accredited PharmD programs. Drug therapy had the highest credit hours in programs with both integrated and non-integrated drug therapy courses. Programs with integrated drug therapy courses had significantly more credit hours in experiential and scholarship and fewer credit hours in stand-alone courses for pathophysiology, medicinal chemistry, and pharmacology. Credit hours in content areas did not predict NAPLEX pass rate nor residency match success rate. CONCLUSIONS: This is the first comprehensive description of all ACPE accredited pharmacy schools with credit hours broken down by content areas. While content areas did not directly predict success criteria, these results may still be useful to describe curricular norms or inform the design of future pharmacy curricula.

Thyroid follicular adenomas and carcinomas: molecular profiling provides evidence for a continuous evolution.

Non-autonomous thyroid nodules are common in the general population with a proportion found to be cancerous. A current challenge in the field is to be able to distinguish benign adenoma (FA) from preoperatively malignant thyroid follicular carcinoma (FTC), which are very similar both histologically and genetically. One controversial issue, which is currently not understood, is whether both tumor types represent different molecular entities or rather a biological continuum. To gain a better insight into FA and FTC tumorigenesis, we defined their molecular profiles by mRNA and miRNA microarray. Expression data were analyzed, validated by qRT-PCR and compared with previously published data sets. The majority of deregulated mRNAs were common between FA and FTC and were downregulated, however FTC showed additional deregulated mRNA. Both types of tumors share deregulated pathways, molecular functions and biological processes. The additional deregulations in FTC include the lipid transport process that may be involved in tumor progression. The strongest candidate genes which may be able to discriminate follicular adenomas and carcinomas, CRABP1, FABP4 and HMGA2, were validated in independent samples by qRT-PCR and immunohistochemistry. However, they were not able to adequately classify FA or FTC, supporting the notion of continuous evolving tumors, whereby FA and FTC appear to show quantitative rather than qualitative changes. Conversely, miRNA expression profiles showed few dysregulations in FTC, and even fewer in FA, suggesting that miRNA play a minor, if any, role in tumor progression.

microRNA expression in autonomous thyroid adenomas: Correlation with mRNA regulation.

The objective of the study was to identify the deregulated miRNA in autonomous adenoma and to correlate the data with mRNA regulation. Seven autonomous adenoma with adjacent healthy thyroid tissues were investigated. Twelve miRNAs were downregulated and one was upregulated in the tumors. Combining bioinformatic mRNA target prediction and microarray data on mRNA regulations allowed to identify mRNA targets of our deregulated miRNAs. A large enrichment in mRNA encoding proteins involved in extracellular matrix organization and different phosphodiesterases were identified among these putative targets. The direct interaction between miR-101-3p and miR-144-3p and PDE4D mRNA was experimentally validated. The global miRNA profiles were not greatly modified, confirming the definition of these tumors as minimal deviation tumors. These results support a role for miRNA in the regulation of extracellular matrix proteins and tissue remodeling occurring during tumor development, and in the important negative feedback of the cAMP pathway, which limits the consequences of its constitutive activation in these tumors.

Adrenocortical tumors: improving the practice of the Weiss system through virtual microscopy: a National Program of the French Network INCa-COMETE.

The Weiss score is the reference method to distinguish between a benign and a malignant adrenocortical tumor (ACT). A program was initiated to improve the reproducibility of the pathologic diagnosis of ACTs in France through the National INCa-COMETE Network. Twelve pathologists from all Reference Centers of the Network analyzed 50 selected ACTs using a web-based virtual microscopy approach in a blind design, allowing to determine the intraobserver and interobserver reproducibilities of the Weiss system. All ACTs were read twice in random order before and after a coaching meeting organized to harmonize and improve analyses and create an online tutorial. The validity of the virtual approach was first established by comparing the 2 consensuses (virtual and microscopic) obtained for each tumor by 3 pathologists who performed the 2 approaches in a blinded manner. For the "dichotomized Weiss score" (separating malignant ≥3 from benign ≤2 tumors) interobserver reproducibility was "substantial" at the first "virtual" reading (κ = 0.70) and increased at the second "virtual" reading (κ = 0.75). In parallel, 7 of the 9 items of the Weiss system showed improvement. The diagnostic accuracy of the observers as a group, using the modal group score approach, showed an improved sensitivity from 86% to 95% for the diagnosis of malignant ACTs. We show the validity of the virtual microscopy approach and that the program improved the practice of the Weiss system reading and therefore the diagnosis of ACT. This tool can now be extended for other research and/or routine purposes in this rare cancer.

Scoring system for predicting recurrences in patients with papillary thyroid microcarcinoma.

CONTEXT: Papillary thyroid microcarcinomas (PMC) defined as tumors ≤10 mm in diameter (including pT1a and pT3 according to the latest pTNM classification) have good prognosis, although recurrence is possible. Clinicians are interested in using a scoring system for predicting recurrences. OBJECTIVE: To identify the prognostic factors for recurrence in patients with PMC and to develop a scoring system based on lymph node involvement, multifocality, and sex. To determine the impact of extrathyroidal invasion (ETI) and a threshold value for analyzing multifocality. METHODS: Single-center retrospective study of a cohort of 1669 patients with PMC managed from 1960 to 2007. The Kaplan-Meier survival rate and prognostic factors of events were analyzed using log-rank tests and uni- and multivariate Cox model-based analyses. A scoring system was proposed. RESULTS: Sixty-eight recurrences were observed. Initial lymph node metastases (P=0.0001), multifocality (P=0.05), and male sex (P=0.01) were significantly associated with recurrence, although there was a period effect (after 1990). PMC size was not a significant variable. Our scoring system allows us to separate patients into three risk groups according to their recurrence-free probability. For PMC Nx patients, total foci size of multifocal tumors >20 mm was significantly associated with recurrence (P<0.0001). Radioiodine (RAI) ablation was associated with better outcome only in PMC with ETI. CONCLUSION: Our scoring system classifies recurrence risk. In PMC Nx patients, multifocality is important in planning therapeutic strategies. Recurrence probability of pT3 PMC appears lower if RAI ablation is performed.

Translating standards into practice: experience and lessons learned at the Department of Veterans Affairs.

The increased need for interoperable electronic health records in health care organizations underscores the importance of standards. The US Department of Veterans Affairs (VA) has a long history of developing and adopting various types of health care data standards. The authors present in detail their experience in this domain. A formal organization within VA is responsible for helping to develop and implement standards. This group has produced a Standards Life Cycle (SLC) process endorsed by VA key business and information technology (IT) stakeholders. It coordinates the identification, description, and implementation of standards aligned with VA business requirements. In this paper, we review the adoption of four standards in the categories of security and privacy, terminology, health information exchange, and modeling tools; emphasizing the implementation approach used in each. In our experience, adoption is facilitated by internal staff with expertise in standards development and adoption. Use of processes such as an SLC and tools such as an enterprise requirement repository help formally track and ensure that IT development and acquisition incorporate these standards. An organization should adopt standards that are aligned with its business priorities and favor those that are more readily implementable. To assist with this final point, we offer a standard "Likelihood of Adoption Scale," which changes as standards specifications evolve from PDF documents only, to PDF documents with construction and testing tools, to fully functional reference implementations.

Clinical outcome after laparoscopic adrenalectomy for primary hyperaldosteronism: the role of pathology.

BACKGROUND: Primary hyperaldosteronism (PHA) is potentially curable by laparoscopic unilateral adrenalectomy (LUA). Pre-operative assessment rarely differentiates adrenal adenoma from hyperplasia. This study aimed to evaluate the results of LUA for PHA according to pathologic findings when an adrenal mass was identified unequivocally on a CT scan. METHODS: A retrospective analysis of LUA for PHA from July 1997 to May 2008 was performed. The minimal follow-up was 6 months. We considered hypertension to be cured in patients with normal blood pressure without antihypertensive medication (AM). Improvement was defined by a decrease of AM. RESULTS: Fifty-seven patients were included. Thirty-six patients (63%) had an adrenal adenoma and 21 (37%) a hyperplasia. The median follow-up was 6.4 years. Hypokalemia was cured in all patients, 33 patients (58%) were cured of their hypertension, and 23 (96% of the 24 noncured patients) were improved with a reduction of the number of AM. Predictive factors for a cure were: gender, age, BMI, duration of hypertension, number of pre-operative AMs, pre-operative arterial systolic blood pressure, creatinin and plasma renin activity. Postoperative predictive factors were pathology, size of the mass, and systolic and diastolic arterial pressures. In the multivariate analysis the only remaining factor was pathology. CONCLUSION: LUA for PHA cured all patients from their hypokalemia and cured or improved hypertension in 98%. Pre-operative diagnosis of adenoma or hyperplasia is not mandatory but it is important to warn patients that hypertension can persist after adrenalectomy, especially in case of adrenal hyperplasia, although this hypertension is easier to control.

An unusual clinical presentation of a rare tumor of the thyroid gland: report on one case of leiomyosarcoma and review of literature.

Primary muscle tumors of the thyroid gland are exceedingly rare. We report on the case of a patient with primary leiomyosarcoma of the thyroid gland and review the literature. An 83-year-old woman complaining of neuropathic pain in her left arm and enlargement of her anterior neck underwent multiple surgical biopsies of the thyroid gland. The tumor was composed of interlacing fascicles of spindle-shaped cells that expressed smooth muscle actin and vimentin but were negative for cytokeratins and thyroglobulin. Ultrastructurally, bundles of myofilaments were present. Magnetic resonance imaging showed a thyroid tumor that directly extended to the adjacent vertebra with an associated pachymeningitis. The patient died 2 months after surgery. The diagnosis of primary leiomyosarcoma of the thyroid gland is difficult and requires numerous clinical, radiologic, and pathologic data. To our knowledge, this case is the first one with such a locoregional extension.

Extensive thyroidectomy in Graves' disease.

BACKGROUND: The best surgical treatment for hyperthyroidism caused by Graves' disease remains a controversial subject. METHODS: Seven hundred fourteen consecutive patients underwent total or near-total thyroidectomy for Graves' disease in a 13-year period. In a first analysis, postoperative rates of suffocating hematoma, wound infection, recurrent laryngeal nerve (RLN) palsy, hypoparathyroidism, and persistence or recurrence of hyperthyroidism, were studied and compared with the same parameters in 4,426 patients who underwent bilateral thyroid gland resection for other conditions. A second analysis identified factors associated with postoperative complications among Graves' disease patients. RESULTS: Comparing Graves' disease patients with patients who had bilateral thyroid resection for other conditions, the transient morbidity rate was 13.3% versus 8.2% (p < 0.0001), with 10.2% versus 5.0% (p < 0.0001) hypoparathyroidism, 2.2% versus 1.7% (p = 0.35) RLN palsy, 1.7% versus 0.9% (p < 0.05) suffocating hematoma, and 0.3% versus 0.4% (p = 0.67) wound infection, respectively. Permanent morbidity rate was 2% versus 2.2% (p = 0.72), including 0.4% versus 0.6% RLN palsy and 1.5% versus 1.7% hypoparathyroidism. Among the Graves' disease patients, univariate analysis revealed that those who experienced postoperative complications had a higher weight resected thyroid gland (odds ratio = 1.5; 95% CI, 1.0-2.3) and a higher rate of total thyroidectomy (24.4% versus 19.5%, odds ratio = 2.2; 95% CI, 1.4-3.4) than patients without complications. In the multivariable model, these two factors remained independent. There was no recurrence of hyperthyroidism with a median followup of 6.7 years (interquartile range 4.1 to 10.1 years). Persistent hyperthyroidism developed in three patients. CONCLUSIONS: Total or near-total thyroidectomy is an effective and safe treatment for Graves' disease when performed by an experienced surgeon.

[An unusual cause of jejunal intussusception: heterotopic and hyperplastic Brunner's gland pseudo-tumor]. / Invagination intestinale aiguë de cause inhabituelle. Hyperplasie hétérotopique pseudo-tumorale des glandes de Brunner.

We report the first case of small-bowel intussusception caused by a tumour-like Brunner's gland hyperplasia in a 26 year old woman. The patient presented with intense abdominal pain. Abdominal and pelvic contrast enhanced CT-scan suggested small bowel intussusception involving the first jejunal loop. A 15 cm long polypoid mass was found in the jejunumectomy specimen (2nd and 3rd loops). Histological examination revealed Brunner's gland hyperplasia in the jejunal mucosa and submucosa. Considering the jejunal location of the lesion, it must be considered malformative and heterotopic Brunner's gland hyperplasia.

Prognostic factors associated with the survival of patients developing loco-regional recurrences of differentiated thyroid carcinomas.

To estimate survival of patients with loco-regional recurrences (LRRs) of differentiated thyroid carcinomas (DTCs) and to identify factors associated with survival after LRRs, we analyzed retrospective data of the 172 patients treated and followed up in our institution from 1958 to 2000 who had developed LRRs (6% of DTC patients). Ultrasound, when used, picked up 95% of the recurrences. Survival was estimated with the method of Kaplan-Meier, and associated prognostic features were studied in univariate and multivariate Cox model-based analyses. Cumulated survival rates 10 yr after LRRs were 49.1, 89.3, and 32.1% for all patients, patients aged less than 45 yr, and older patients, respectively. Multivariate analysis identified three features related to initial tumor (age >/= 45 yr, follicular histology, presence of thyroid capsular effraction), the absence of radioiodine ablation of thyroid remnants after initial surgery (10% of patients did not receive radioiodine), the presence of distant metastases before LRR diagnosis, and two features related to the LRRs (no radioiodine uptake and thyroid bed location) as significantly associated with a reduced survival. Our results underline the seriousness of LRRs of DTCs and could be used to identify patients who should benefit from a closer follow-up and especially reactive therapeutic intervention.

Inhibition of human plasma leucine5-enkephalin aminopeptidase hydrolysis by various endogenous peptides and a select number of clinically used drugs.

We identified a number of clinically used drugs and biologically active endogenous peptides able to significantly decrease the rate of human plasmatic aminopeptidase (AP) leucine-enkephalin (LEU) degradation. Bacitracin, bestatin, fluvoxamine, and each of 4 peptides tested significantly increased, in a dose-dependent manner (10-10 M), LEU degradation half-life (t1/2) in each of 5 plasma samples studied. Each sample was obtained by pooling equal volume of 6 randomly selected, individual plasmas (4 male and 2 female healthy, drug-free volunteers). Thirty subjects (20 females and 10 males) participated in this study. With the exception of fluvoxamine, this inhibitory effect was lacking in various other commonly used drugs with widely different chemical structures and pharmacological profiles, eg, antidepressants (SSRIs, imipramine-like tricyclics, MAOIs), acute antimigraine agents (triptan class drugs), the nonselective beta-adrenergic antagonist propranolol, and serotonin receptor agonists and antagonists. Agents (concentration 10 M used as illustration), listed in decreasing order of LEU-AP inhibitory activity: substance P > angiotensin III > methionine-enkephalin > angiotensin II > fluvoxamine > bestatin gave t1/2 values (+/- SD) of 39.3 +/- 1.1, 29.4 +/- 0.8, 28.3 +/- 0.8, 27.4 +/- 0.7, 24.5 +/- 1.5, and 23.6 +/- 0.9 minutes, respectively. Control, bacitracin, and fluphenazine (known LEU-AP inhibitors were used for comparison) values of 11.8 +/- 1.0, 31.3 +/- 0.7, and 19.6 +/- 1.0 minutes, respectively. As expected, these drugs significantly decreased the initial velocity of peptide degradation; Iv values (+/- SD) of: 0.17 +/- 0.1 (0.02 +/- 0.01), 0.23 +/- 0.2 (0.02 +/- 0.01), 0.25 +/- 0.2 (0.02 +/- 0.01), 0.26 +/- 0.2 (0.03 +/- 0.01), 0.31 +/- 0.1 (0.03 +/- 0.01), and 0.33 +/- 0.1 (0.03 +/- 0.01), respectively; control, bacitracin, and fluphenazine: 1.10 +/- 0.3 (0.12 +/- 0.03), 0.20 +/- 0.1 (0.02 +/- 0.01), and 0.82 +/- 0.2 (0.08 +/- 0.02) pg LEU/min (pg LEU/mg protein/min), respectively. Results emphasize the selective nature of chemical structures required to significantly inhibit AP activity and provided information that could help the rational design of agents with high specificity in a biologic milieu containing multiple peptidases. In this case, targeted modulation of the bioavailability of LEU and other endogenous AP-degraded hormonal and nonhormonal peptides could be useful in the treatment of the pathophysiology associated with various disease conditions. Whether their development could find useful pharmacological applications remains to be explored.

Interobserver and intraobserver reproducibility in the histopathology of follicular thyroid carcinoma.

We evaluated the interobserver and intraobserver reproducibility in the histopathology of follicular thyroid carcinoma (FTC). Forty-one anonymous FTC pathology slides were independently reviewed by 5 pathologists, and 31 of them were also evaluated twice by the same pathologist. A final consensus diagnosis (FCD) was made at the end of the study. Interobserver and intraobserver agreement was determined as the kappa statistic for qualitative data and intraclass correlation coefficient for quantitative data. The agreement between the 5 observers' initial diagnosis and the FCD was 0.69, 0.41, 0.35, 0.28 and 0.11, respectively, strongly suggesting a leadership phenomenon. The FCD classified 30 cases as malignant, including 24 cases diagnosed as FTC. There was unanimous agreement about 13 of the 24 FTCs. Diagnostic reproducibility was found to be acceptable for the nonminimally invasive FTC. Diagnostic discrepancies occurred in 57% of the seven cases classified as minimally invasive FTC by the FCD. FCD excluded malignancy in 11 cases including 6 atypical adenomas. Interobserver and intraobserver agreement for FTC diagnosis was 0.23 (standard error [SE], 0.04) and 0.68, respectively. Interobserver and intraobserver agreement for the presence of vascular invasion was 0.20 (SE, 0.04) and 0.51, respectively, contrasting with a moderate to substantial level of agreement when considering the number of vascular invasion. Interobserver and intraobserver agreement for nucleus optical clearing were slight and moderate, respectively. The importance of the study is the confirmation that diagnostic reproducibility of minimally invasive FTC is low and that this has clinical implications, and also implications for the design of studies into the treatment and outcome of FTC.

Effects of ursodeoxycholic acid (ursodiol) treatment on chronic viral hepatitis in heart transplant patients: results of a prospective, double-blind, placebo-randomized study.

BACKGROUND: Chronic viral hepatitis averages 15% to 20% in heart transplant patients. Several studies have shown that ursodiol may improve liver biochemistry in patients with chronic hepatitis. We used a double-blind randomized controlled trial to evaluate the effect of ursodiol in heart transplant patients with chronic viral hepatitis. METHODS: Thirty heart patients with chronic viral hepatitis B, C, or non-A-G received ursodiol, 800 mg per day (group 1), and 30 received placebo (group 2) for 12 months. Endpoints were improvement in liver biochemical tests and in total Knodell score. Intent-to-treat and per-protocol analyses were performed. RESULTS: At entry, both groups were comparable for all of the studied parameters. During the study period, serum alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transpeptidase variations were not different between group 1 and group 2 patients. Knodell score improved in 20% of group 1 patients and in 43% of group 2 patients (NS). Adverse events or mortality were not different in the two groups during the study period. Similar results were observed by intent-to-treat and per-protocol analyses. CONCLUSIONS: A 12-month course of ursodiol therapy had no effect on liver enzymes or liver histology in heart transplant patients with chronic hepatitis.

Selection of patients with solitary thyroid nodules for operation.

OBJECTIVE: To improve the preoperative selection for operation of patients with solitary thyroid nodules. DESIGN: Prospective cohort study. SETTING: University hospital, France. PATIENTS: 155 consecutive patients who presented with solitary thyroid nodules and were operated on. INTERVENTIONS: Clinical examination, ultrasound examination, fine needle aspiration biopsy, followed by total thyroid lobectomy with frozen section and final histological examination. MAIN OUTCOME MEASURE: Correct prediction of thyroid carcinoma or benign adenoma. RESULTS: A logistic regression analysis indicated that absence of rim (p < 0.002), solid and hypoechoic feature (p < 0.003) and malignant or suspicious fine needle aspiration biopsy results (p < 0.0001) were significantly associated with malignancy. Selection for operation by the logistic model would save 40 of 73 patients from operation and 40 of 59 from unnecessarily radical operation. It would detect a similar number of cancers as a strategy based solely on fine needle aspiration cytology. CONCLUSIONS: A combination of the available diagnostic methods provides substantial benefit in the preoperative selection of patients with an isolated thyroid nodule.