18F-DCFPyL PET/CT for Initially Diagnosed and Biochemically Recurrent Prostate Cancer: Prospective Trial with Pathologic Confirmation.

Background Prostate-specific membrane antigen (PSMA) PET is standard for newly diagnosed high-risk and biochemically recurrent (BCR) prostate cancer. Although studies suggest high specificity of 2-(3-{1-carboxy-5-[(6-[(18)F]fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid (DCFPyL) for targeting PSMA, false-positive findings have been identified and most studies lack histologic confirmation of malignancy. Purpose To estimate the positive predictive value (PPV) of DCFPyL PET/CT by providing histopathologic proof for DCFPyL-avid lesions suspected of being distant metastases at initial diagnosis and recurrence in BCR prostate cancer. Materials and Methods In this prospective trial, men with newly diagnosed high-risk prostate cancer (sample 1) or BCR prostate cancer and negative findings at conventional CT and/or bone scanning (sample 2) were enrolled between January and December 2021. All men underwent DCFPyL PET/CT. Suspected distant metastases and/or recurrences were biopsied. PPV was calculated. Results A total of 92 men with newly diagnosed prostate cancer (median age, 70 years; IQR, 64-75 years) (sample 1) and 92 men with BCR prostate cancer (median age, 71 years; IQR, 66-75 years) (sample 2) were enrolled. In sample 1, 25 of the 92 men (27%) demonstrated DCFPyL-avid lesions suspicious for distant metastases. Biopsy was performed in 23 of the 25 men (92%), with 17 of the 23 (74%) biopsies positive for malignancy and six (26%) benign. Of the six benign biopsies, three were solitary rib foci and three were solitary pelvic bone foci. In sample 2, 57 of the 92 men (62%) demonstrated DCFPyL-avid lesions suspicious for recurrence. Biopsy was performed in 37 of the 57 men (65%), with 33 of the 37 (89%) biopsies positive for malignancy and four (11%) benign. Of the four benign biopsies, two were subcentimeter pelvic nodes and/or nodules, one was a rib, and one was a pelvic bone focus. Conclusion PET/CT with 2-(3-{1-carboxy-5-[(6-[(18)F]fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid (DCFPyL) had a high biopsy-proven positive predictive value for distant metastases in newly diagnosed prostate cancer (74%) and for recurrence sites in men with biochemical recurrence (89%). However, there were DCFPyL-avid false-positive findings (particularly in ribs and pelvic bones). Solitary DCFPyL avidity in these locations should not be presumed as malignant. Biopsy may still be needed prior to therapy decisions. ClinicalTrials.gov registration no. NCT04700332 © RSNA, 2022 See also the editorial by Zukotynski and Kuo in this issue.

Effect of an Educational Video Miniseries on Interprofessional Preceptor Development.

OBJECTIVE: Experiential rotation preceptors may lack confidence in instructing interprofessional learners. This study examined the effect of a 12-episode, professionally produced video miniseries on attitudinal, satisfaction, and confidence outcomes in a cohort of interprofessional preceptors comprising pharmacy, medicine, nursing, and other allied health professionals. METHODS: An invitation to view the miniseries was distributed to all health science preceptors within 1 large, public health science university. Participants were asked survey questions addressing their attitudes toward the miniseries, their comfort in precepting, and their satisfaction with the miniseries. RESULTS: A total of 61 interprofessional preceptors enrolled in the study, with 33 completing the entire miniseries. Participants displayed highly positive attitudes toward the miniseries. In addition, members of all professions enrolled demonstrated an increase in precepting confidence after viewing the miniseries episodes (2.31 vs 2.7 on a 3-point Likert scale). Subgroup analyses demonstrated that preceptors with>10 years of professional experience displayed less positive attitudes toward the miniseries than those with 2-10 years of professional experience. CONCLUSION: The miniseries model proved effective as a preceptor development strategy for a group of health professional preceptors. Given the diversity of learners, a collection of training options that allows preceptor self-selection of programming may be beneficial.

A retrospective study of induction chemotherapy with docetaxel, cisplatinum, and 5-fluorouracil followed by concurrent radiotherapy with cetuximab in locally advanced head and neck cancer.

BACKGROUND: The objective was to study the results of induction chemotherapy followed by external beam radiation therapy with concurrent cetuximab in the treatment of locally advanced head and neck cancer. METHODS: Seventeen patients with stage III or IV squamous cell carcinomas of the head and neck who received docetaxel, cisplatinum, and 5-fluorouracil followed by radiation therapy with concurrent cetuximab were retrospectively analyzed. All radiation was delivered with image-guided intensity-modulated radiation treatments. Primary end points analyzed were local control and overall survival. RESULTS: With a median follow-up of 17 months, the approximate 2-year local control was 85%, with overall survival being 91%. At time of last follow-up, only 1 death was observed, with the cause of death unknown. Two local failures were observed, and the patients were under active management for their recurrences at time of last follow-up. No distant metastatic failures were noted among the patients. CONCLUSIONS: Induction chemotherapy with docetaxel, cisplatinum, and 5-fluorouracil followed by concurrent radiation with cetuximab provides for excellent locoregional control of disease. Future prospective studies can better establish the efficacy of this treatment regimen to current favored protocols.

Acute and delayed complications from surgery and adjuvant radiotherapy in the treatment of high-risk endometrial cancer.

OBJECTIVES: This retrospective study assessed the number and type of complications following surgery and adjuvant radiotherapy in the treatment of high-risk endometrial cancer. METHODS: Endometrial cancer patients who received surgery and postoperative radiotherapy (pelvic radiotherapy and/or vaginal brachytherapy) from April 1997 until October 2010 were evaluated. Short-term (≤6 months) and long-term (>6 months) complications (e.g., genitourinary/gastrointestinal complications) were comprehensively reviewed. RESULTS: We identified 109 high-risk endometrial cancer patients who completed adjuvant radiotherapy following either a total abdominal hysterectomy (TAH; n = 53) or minimally invasive hysterectomy (MIS; n = 56). The combined impact of surgery and radiotherapy on complication type did not reach statistical significance (p > 0.05). However, surgery type and the development of a complication were significantly related (p < 0.001). The MIS patients developed complications at a more accelerated rate compared to the TAH patients (21 vs. 45 months), although the incidence of toxicity of grade 3 or 4 was much higher in the TAH group. CONCLUSIONS: The impact of MIS and adjuvant radiotherapy may have adversely affected the development of complications compared to TAH patients who received adjuvant radiotherapy, although higher-grade patient toxicity was more prevalent in the TAH group.

The Status and Adequacy of Preceptor Orientation and Development Programs in US Pharmacy Schools.

Objective. To identify current preceptor orientation and development programs at US colleges and schools of pharmacy and propose future initiatives for preceptor programs. Methods. An anonymous 28-item survey was administered in January 2017 to 128 experiential education personnel at accredited US schools and colleges of pharmacy. Data from completed survey instruments were tabulated and qualitative responses to open-ended questions were examined using thematic analysis. Results. Eighty-five experiential education administrators participated in the survey (response rate=67%). Most preceptor orientation programs met the majority of requirements as outlined within the Accreditation Council for Pharmacy Education's Standard 20.3, although only 42% of programs mandated preceptor orientation prior to student placement. Two-thirds of respondents offered annual, live preceptor development, and 75% of programs used commercially available online products. Nearly 40% of respondents collaborated with other schools or professional organizations to offer preceptor training. Only 29% of programs had specific requirements for pharmacists to maintain their active preceptor status. Seventy percent of respondents reported spending over $2500 and 39% over $5000 annually on preceptor development. Programs with the highest monetary investment (>$10,000/year) in preceptor development offered multiple venues (live and online) for preceptor training. Programs with significant personnel commitment (≥0.5 FTE devoted to preceptor development) frequently had dedicated site visitors. Conclusion. Preceptor orientation programs at US schools of pharmacy are generally similar, but development programs vary significantly across the Academy. Highly invested programs featured live and online training or site visitors who provided individualized feedback or training. Future studies should explore the cost-effectiveness of program options and their impact on preceptor learning and behaviors.

Image-guided helical Tomotherapy for treatment of spine tumors.

OBJECTIVES: One of the most common indications for radiotherapy is treatment of the spine. The vast majority of cases are related to metastatic disease with primary tumors of the spine being rare. Conventional radiation therapy often plays an important role in the management of spine tumors although at times with significant side effects and disadvantages. Furthermore, retreatment of spine tumors is a challenge due to concerns over spinal cord toxicity. In this series, we examine the efficacy of using image-guided helical Tomotherapy and the possible advantages offered by this new technology. PATIENTS AND METHODS: Eight patients at Hoag Memorial Hospital Presbyterian were treated between November 2005 and November 2006. The median age was 66 years. Of the eight patients, seven had metastatic disease with one patient having a primary neuroendocrine tumor of the spine. Five patients were previously treated to the spine with conventional radiation planning. Two patients received single fraction stereotactic radiosurgery (15 Gy) while the remaining patients received hypofractionated stereotactic radiotherapy to a median total dose of 2,500 cGy in 500 cGy fractions. RESULTS: At the time of last follow-up, radiographic control was seen in all eight patients with a median local control rate of 2.5 months (range of 1-5.8 months). Four of the eight patients are still alive with median overall survival of 5.1 months (range 1.4-6.9 months). Acute toxicity ranged from Radiation Therapy Oncology Group (RTOG) score 0-2 and no patients experienced late complications of radiation myelitis. CONCLUSIONS: The TomoTherapy Hi-ART system can be an alternative treatment option for upfront or retreatment of spine tumors. Minimal acute and late toxicity were seen in patients treated with Tomotherapy. Intensity-modulated radiation delivery combined with megavoltage CT image guidance offered by the TomoTherapy Hi-ART system allows for set-up and delivery accuracy that is required for stereotactic treatment of spine tumors and eliminates the need for any internal or external fiducial marker placement.

National preceptor development program (PDP): Influential evidence and theory. The first of a 3-part series.

INTRODUCTION: Priority #3 of the Canadian Experiential Education Project for Pharmacy provided evidence-based guidance for the design and implementation of a national approach to preceptor development. In this first article (of three), findings from the project and recommendations to achieve a high-quality preceptor development program (PDP) are presented. METHODS: A multi-method approach including detailed semi-structured interviews, classic literature review, and advisory committee feedback was employed. The research team performed an integrated analysis of all data to achieve the objectives of Priority #3. RESULTS: Fifteen formal interviews, 167 articles and two stakeholder meetings informed findings. Experiential Education programs exhibited commonality in content and usually delivered programs online using modules or live lectures. Not all programs required preceptor education despite it being mandated by academic accreditors. Academics' perceptions varied regarding pharmacists' baseline knowledge, skills and attitudes prior to engaging in the preceptor role. A national approach to a PDP was desired if jurisdictional content was accommodated. Copious interprofessional literature of generally fair quality did not identify superior preceptor development approaches although there were numerous descriptions of interventions. Only 29 articles measured educational outcomes. Outcomes included satisfaction rates, self-efficacy and perceived knowledge, skill retention, skill implementation and participation rates. DISCUSSION AND CONCLUSIONS: Twelve recommendations were identified to guide successful development of a national PDP. In the absence of good evidence, adult educational theory provided a basis for an effective PDP. Findings from Priority #3 may be relevant not only to pharmacy in Canada but other health professions and counterparts in other western nations with similar approaches to professional education.

National preceptor development program (PDP) prototype. The third of a 3-part series.

INTRODUCTION: Preceptor development is critical to successful delivery of experiential learning. Although many preceptor development programs exist, a more individualized approach to training is needed. To accomplish this a national preceptor development program should be considered based on the continuing professional development model. A detailed prototype for this program has been described. METHODS: In this final installment of the series, the twelve evidence-based recommendations from the first installment were utilized to construct a prototype for a preceptor development program. Over a three-month period, investigators experimented with different designs and models before approving the final prototype. RESULTS: The prototype took the form of an electronic learning platform. Several categories were integral to the design and included sections entitled preceptor spotlight, mentorship, global outreach, choose your own adventure, continuing professional development, feedback, virtual online community, highlights/advertisements, what's new, competency assessment, and frequently asked questions. A graphic was developed to depict the process by which a preceptor would navigate through the web-based learning platform. DISCUSSION: The authors purposefully maintained a creative and unlimited vision for preceptor development. This conceptual model is intended to spark discussion and augment, refine, or develop entirely innovative ideas to meet preceptor needs. Development of a preceptor development platform could foster improved competency performance, enhanced interest in learning, and promote continuing professional development. CONCLUSION: With a greater focus on experiential education in pharmacy, the need for a national preceptor development resource is only expected to increase.

A Preceptor competency framework for pharmacists. Part 2 of a 3-part series.

BACKGROUND: Pharmacy faculties in Canada are transitioning to the doctor of pharmacy degree which will require approximately one-third of curricula contact time in experiential education. Preceptors will be responsible for delivering this experiential component and many have received little or no training in how to be an effective educator. Although training is mandated through accreditation standards, competencies to serve as a foundation for preceptor development have yet to be created. The objectives of this review were to develop core competencies of an effective preceptor and to identify performance indicators to guide preceptor growth METHODS: A literature review of teaching competencies from pharmacy, medicine, nursing, and higher education was completed. Competencies and performance indicators were extracted and analyzed for recurring themes. A framework was proposed and refined through consultation with Canadian and United States pharmacy stakeholder groups. RESULTS: Six-hundred and thirty-nine articles were identified through the review, of which only eight articles directly addressed preceptor competencies and/or related performance indicators. These articles were reviewed in detail. Regardless of discipline, several recurring themes emerged. Themes were collated and culminated in nine competencies and supporting performance indicators for preceptors. Competencies address important interpersonal, professional, and educational knowledge, skills, and attitudes of an effective educator. IMPLICATIONS: Defining competence and its performance indicators is essential to help preceptors effectively fulfill their professional responsibility of developing competent graduates. The competencies and performance indicators should be further refined through stakeholder engagement. This framework could be foundational to national preceptor development program, preceptor recruitment, and quality assurance programs.

Use of Entertainment Elements in an Online Video Mini-Series to Train Pharmacy Preceptors.

Objective. To create an entertaining approach to training pharmacy preceptors. Design. A training program was developed to provide an innovative, entertaining, and flexible continuing education program for pharmacy preceptors. Three instructional design principles - providing an authentic context, offering a diversity of content, and engaging and maintaining attention - were foundational to this concept. The mini-series consisted of 12 online video episodes. Participants completed three reflective questions and one evaluation after watching each episode. Three months following completion of the training, a survey was distributed to analyze the long-term impact of the mini-series on precepting skills. Assessment. Two hundred two participants completed all 12 episodes. After completing the training series, the participants' confidence level in their knowledge pertaining to the objectives was significantly greater than before they started. Among the 32% of participants who responded to the three-month follow-up survey, the mean score for precepting confidence was 6.8 on a scale of 1 to 10 on which 1=no increase to 10=big increase. Also, 99% of participants indicated they would complete a similar training program and recommend to others. Conclusions. Feedback from the mini-series provides evidence of the effectiveness of its delivery format and use as a preceptor learning tool.

Interprofessional objective structured teaching exercise (iOSTE) to train preceptors.

BACKGROUND AND PURPOSE: Interprofessional education (IPE) is important in the education of all health care students, yet limited IPE training has been provided to preceptors who train these students in the clinical setting. Simulation using the standardized student model has been used to train health care preceptors in medicine. To our knowledge, there are no reports utilizing interprofessional objective structured teaching exercises (iOSTE) to train pharmacy preceptors. The primary objectives of this pilot study were to evaluate the effects of iOSTE on the pharmacy preceptors' perceived importance of the Interprofessional Education Collaborative (IPEC) core competencies and confidence in precepting interprofessional students. Additionally, data were collected regarding pharmacy preceptors' prior experiences in simulation and debriefing. EDUCATIONAL ACTIVITY AND SETTING: Preceptors (n=23) participated in an iOSTE and debriefed with trained standardized nursing and pharmacy students caring for a trained standardized asthma patient. FINDINGS: Pre- versus post-iOSTE survey data showed statistically significant improvements in all self-confidence related items, including the following abilities: precept students from different disciplines (p=0.004), facilitate a simulation activity (p=0.001), conduct the debriefing process (p<0.001), and discuss with students the IPE core competencies (p=0.001). Additionally, responses to post-iOSTE survey questions assessing the learning activity showed high ratings (median=5, interquartile range=4 to 5). Pharmacy preceptors increased their teaching ability and confidence level in communicating with students from other health care professions. SUMMARY: These findings indicate that iOSTE is a useful and well-received method for preceptor development.

Lack of effect on coronary atherosclerotic disease biomarkers with modest dosing of an angiotensin-converting enzyme inhibitor, angiotensin II type-1 receptor blocker, and the combination.

BACKGROUND: Angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor blockers, used alone or in combination, have been shown to improve outcomes in certain populations, primarily when administered in high doses. For stable coronary atherosclerotic disease, however, the relative physiologic effect of these therapies is unclear. Furthermore, because of the notorious subtarget dosing of such agents in clinical practice, we explored the influence of a modest dosing of an angiotensin-converting enzyme inhibitor, angiotensin II type 1 receptor blockers, and the combination on common biologic markers of coronary atherosclerotic disease. METHODS: This randomized, cross-over study enrolled stable coronary atherosclerotic disease patients (n=20), each receiving three treatments: candesartan 16 mg daily, ramipril 5 mg daily, and candesartan 8 mg plus ramipril 2.5 mg daily. Treatments were administered for 2 weeks with a 2-week washout. Blood samples were collected before and after each treatment. Markers of endothelial function, fibrinolytic balance, and vascular inflammation were measured. RESULTS: No significant differences were observed in the pretreatment concentrations of angiotensin-converting enzyme or of any measured biologic marker. Relative to pretreatment levels, candesartan alone was the only therapy to exhibit an action on any measured biomarker--a trend toward increased nitric oxide concentrations (P=0.054). Otherwise, no effects on biologic markers were observed with the treatments. CONCLUSION: This study of various methods of the renin-angiotensin system inhibition in stable coronary atherosclerotic disease patients demonstrates negligible effects of a modest dosing of ramipril and the combination of ramipril plus candesartan on common biologic markers of coronary atherosclerotic disease. Candesartan at modest doses may favorably influence endothelial function. Overall, however, the results indicate that the commonly practiced subtarget dosing of such treatments provides little, if any, benefit pertaining to key physiologic components of coronary atherosclerotic disease.

Preventing contrast nephropathy: what is the best strategy? A review of the literature.

Patients receiving radiocontrast for diagnostic and interventional procedures are at risk for developing contrast nephropathy (CN). In fact, radiocontrast nephropathy is currently the third leading cause of hospital-acquired renal failure. Understanding that CN has been associated with increased length of hospitalization and mortality, determining the best prevention strategy is of utmost importance. Patients at the greatest risk for developing acute renal failure are patients with diabetes and underlying renal insufficiency. Several therapies have been investigated for the prevention of CN; unfortunately, very few have shown a consistent benefit. Therapies that have been studied include saline hydration, N-acetylcysteine (NAC), theophylline, calcium channel blockers, diuretics, dopamine, endothelin receptor antagonists, atrial natriuretic peptide, angiotensin-converting enzyme inhibitors, and prostaglandin E-1. Using adequate hydration, using low-osmolar dyes, and minimizing the dose of contrast have all been shown to be effective in reducing CN and are considered the standard of care. While trials with many pharmacologic agents have produced conflicting results, intervention with NAC has also been promising. This article reviews the pathophysiology, risk factors, and therapies that are currently available for the prevention of CN.

Pharmacologic blockade of the renin-angiotensin system: vascular benefits beyond commonly understood pharmacologic actions.

Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) are recognized primarily for their use in hypertension, in heart failure, and after myocardial infarction. New evidence, particularly with ACE inhibitors, has shown their ability to reduce acute coronary events associated with atherosclerosis in patients without a history of the aforementioned cardiac conditions. This is likely due to inhibitory effects on the renin-angiotensin system--a system that adversely influences fibrinolytic balance, vascular endothelial function, and vascular inflammation, all key components of atherosclerotic progression and adverse coronary outcomes. Results of various studies suggest favorable effects of ACE inhibitors and ARBs on markers of these components, including effects on plasminogen activator inhibitor-1, endothelin-1, and nitric oxide by ACE inhibitors, and effects on vascular cell adhesion molecule-1 and C-reactive protein by ARBs. Although early evidence suggests that ACE inhibitors may provide a greater beneficial effect on some of these markers compared with ARBs, and that certain ACE inhibitors may provide greater vascular benefits than others, further investigation is required to verify such findings. Overall, understanding the distinct coronary vascular benefits of these agents will emphasize the importance of using them, particularly ACE inhibitors, to improve outcomes in patients with coronary atherosclerotic disease.

Potential in vitro interaction between tenecteplase and unfractionated heparin.

STUDY OBJECTIVE: To explore the potential of a direct drug interaction between unfractionated heparin (UFH) and tenecteplase that lowers the pharmacologic propensity of UFH to prolong the activated partial thromboplastin time (aPTT). DESIGN: In vitro experiment. SETTING: Texas Tech University School of Pharmacy, with sample analysis performed at an independent, contract laboratory. Samples. Blood samples collected from healthy volunteers. INTERVENTION: Three separate in vitro experiments were conducted to explore the relative influence of various thrombolytic agents with and without UFH on aPTT prolongation. In each experiment, blood from healthy volunteers (12 for each experiment) was treated with different concentrations and combinations of tenecteplase and UFH. MEASUREMENTS AND MAIN RESULTS: When the effects of tenecteplase plus UFH versus UFH alone on aPTT prolongation were compared, each experiment demonstrated attenuation of aPTT with the combination versus UFH alone. In contrast, findings for other thrombolytic agents combined with UFH demonstrate elevation of the aPTT compared with UFH alone. CONCLUSION: The results indicate a possible drug interaction between tenecteplase and UFH, with tenecteplase attenuating the intensity of anticoagulation of UFH in vitro. Further investigation into this possible interaction is warranted in the clinical setting.

Antibiotic-induced cardiac arrhythmias.

This review aims to clarify the underlying risk of arrhythmia associated with the use of macrolides and fluoroquinolones antibiotics. Torsades de pointes (TdP) is a rare potential side effect of fluoroquinolones and macrolide antibiotics. However, the widespread use of these antibiotics compounds the problem. These antibiotics prolong the phase 3 of the action potential and cause early after depolarization and dispersion of repolarization that precipitate TdP. The potency of these drugs, as potassium channel blockers, is very low, and differences between them are minimal. Underlying impaired cardiac repolarization is a prerequisite for arrhythmia induction. Impaired cardiac repolarization can be congenital in the young or acquired in adults. The most important risk factors are a prolonged baseline QTc interval or a combination with class III antiarrhythmic drugs. Modifiable risk factors, including hypokalemia, hypomagnesemia, drug interactions, and bradycardia, should be corrected. In the absence of a major risk factor, the incidence of TdP is very low. The use of these drugs in the appropriate settings of infection should not be altered because of the rare risk of TdP, except among cases with high-risk factors.