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Corticosteroids are used for a multitude of indications in palliative patients. In this narrative review, we aim to review literature on the treatment and prevention of neuropsychiatric complications of steroids. For prevention, only lamotrigine had a positive effect in a small number of studies. For treatment, olanzapine appears to be nearly universally effective at low doses, but randomized trial evidence is lacking. Further randomized clinical trials are necessary to elucidate data-driven guidelines for prevention and treatment of corticosteroid-induced neuropsychiatric symptoms. Until further data are available, it is reasonable to consider low dose olanzapine for any patient taking 40 mg of prednisone or its equivalent, especially those with a history of depression or neuropsychiatric symptoms.

Objective To determine how passively providing informational handouts and/or drug disposal kits affects rates of leftover prescription opioid disposal. Design A multi-arm parallel-group randomized controlled trial with masked outcome assessment and computer-guided randomization. Setting Johns Hopkins Health System outpatient pharmacies. Subjects Individuals who filled ≥1 short-term prescription for an immediate-release opioid for themselves or a family member. Methods In June 2019, 499 individuals were randomized to receive an informational handout detailing U.S. Food and Drug Administration–recommended ways to properly dispose of leftover opioids (n = 188), the informational handout and a drug disposal kit with instructions on its use (n = 170), or no intervention (n = 141) at prescription pickup. Subjects were subsequently contacted by telephone, and outcomes were assessed by a standardized survey. The primary outcome was the use of a safe opioid disposal method. Results By 6 weeks after prescription pickup, 227 eligible individuals reported they had stopped taking prescription opioids to treat pain and had leftover medication. No difference in safe disposal was observed between the non-intervention group (10% [6/63]) and the group that received disposal kits (14% [10/73]) (risk ratio = 1.44; 95% confidence interval: 0.55 to 3.74) or the group that received a fact sheet (11% [10/91]) (risk ratio = 1.15; 95% confidence interval: 0.44 to 3.01). Conclusions These findings suggest that passive provision of a drug disposal kit at prescription pickup did not increase rates of leftover opioid disposal when compared with provision of a fact sheet alone or no intervention. Active interventions may deserve further investigation.

Objective: Over 80 percent of surgery patients experience acute post-operative pain and less than half feel their pain is adequately controlled. Patients receiving chronic opioids, including methadone, are at the highest risk of inadequate pain control. Guidelines do not provide specific recommendations for analgesia management in this population. The purpose of this study was to evaluate the association between post-operative methadone use and respiratory depression. Design: This study was a single center, retrospective, cohort study of adult patients. Setting: Patients included were admitted to a single academic medical center from July 2016 to September 2018. Participants: Medical records of adult inpatients with an operative procedure who received perioperative methadone were reviewed. Main outcome measures: Preoperative methadone use was evaluated for all patients. Post-operative methadone dosing was compared to preoperative methadone dosing. Post-operative respiratory depression was evaluated. Logistic regression was performed to identify risk factors for respiratory depression. Results: Two hundred ninety-eight patients were included in the study. Patients were divided into groups based on preoperative methadone use. Over 90 percent of patients were on preoperative methadone. There were no significant differences in baseline characteristics between groups. In the initial seven post-operative days, 14.8 percent of patients had documented respiratory depression. Respiratory depression was more common among patients who were newly initiated on methadone post-operatively. Factors associated with respiratory depression included male sex, increased age, and new post-operative methadone initiation. Conclusions: Most patients who were administered post-operative methadone were on preoperative methadone. New post-operative methadone initiation was a risk factor for respiratory depression.

Purpose The opioid epidemic continues to result in significant morbidity and mortality even within hospitals where opioids are the second most common cause of adverse events. Opioid stewardship represents one model for hospitals to promote safe and rational prescribing of opioids to mitigate preventable adverse events in alliance with new Joint Commission standards. The purpose of this study was to identify the prevalence of current hospital practices to improve opioid use. Methods A cross-sectional survey of hospital best practices for opioid use was electronically distributed via electronic listservs in March 2018 to examine the presence of an opioid stewardship program and related practices, including formulary restrictions, specialist involvement for high-risk patients, types of risk factors screened, and educational activities. Results Among 133 included hospitals, 23% reported a stewardship program and 14% reported a prospective screening process to identify patients at high risk of opioid-related adverse events (ORAEs). Among those with a prospective screening process, there was variability in ORAE risk factor screening. Formulary restrictions were dependent on specific opioids and formulations. Patient-controlled analgesia was restricted at 45% of hospitals. Most hospitals reported having a pain management service (90%) and a palliative care service providing pain management (67%). Conclusion The absence of opioid stewardship and prospectively screening ORAEs represents a gap in current practice at surveyed hospitals. Hospitals have an opportunity to implement and refine best practices such as access to pain management specialists, use of formulary restrictions, and retrospective and prospective monitoring of adverse events to improve opioid use.

PurposeMillions of Americans who undergo surgical procedures receive opioid prescriptions as they return home. While some derive great benefit from these medicines, others experience adverse events, convert to chronic opioid use, or have unused medicines that serve as a reservoir for potential nonmedical use. Our aim was to investigate concepts and methods relevant to optimal opioid prescribing and pain treatment in the perioperative period.MethodsWe reviewed existing literature for trials on factors that influence opioid prescribing and optimization of pain treatment for surgical procedures and generated a conceptual framework to guide future quality, safety, and research efforts.ResultsOpioid prescribing and pain treatment after discharge from surgery broadly consist of 3 key interacting perspectives, including those of the patient, the perioperative team, and, serving in an essential role for all patients, the pharmacist. Systems-based factors, ranging from the organizational environment’s ability to provide multimodal analgesia and participation in enhanced recovery after surgery programs to other healthcare system and macro-level trends, shape these interactions and influence opioid-related safety outcomes.ConclusionsThe severity and persistence of the opioid crisis underscore the urgent need for interventions to improve postoperative prescription opioid use in the United States. Such interventions are likely to be most effective, with the fewest unintended consequences, if based on sound evidence and built on multidisciplinary efforts that include pharmacists, nurses, surgeons, anesthesiologists, and the patient. Future studies have the potential to identify the optimal amount to prescribe, improve patient-focused safety and quality outcomes, and help curb the oversupply of opioids that contributes to the most pressing public health crisis of our time.

In recent years, the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Adult Cancer Pain have undergone substantial revisions focusing on the appropriate and safe prescription of opioid analgesics, optimization of nonopioid analgesics and adjuvant medications, and integration of nonpharmacologic methods of cancer pain management. This selection highlights some of these changes, covering topics on management of adult cancer pain including pharmacologic interventions, nonpharmacologic interventions, and treatment of specific cancer pain syndromes. The complete version of the NCCN Guidelines for Adult Cancer Pain addresses additional aspects of this topic, including pathophysiologic classification of cancer pain syndromes, comprehensive pain assessment, management of pain crisis, ongoing care for cancer pain, pain in cancer survivors, and specialty consultations.

Disclaimer In an effort to expedite the publication of articles related to the COVID-19 pandemic, AJHP is posting these manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Purpose To identify the proportion of patients with continued opioid use after total hip or knee arthroplasty. Methods This systematic review and meta-analysis searched Embase, MEDLINE, the Cochrane Central Register of Controlled Trials, and International Pharmaceutical Abstracts for articles published from January 1, 2009, to May 26, 2021. The search terms (opioid, postoperative, hospital discharge, total hip or knee arthroplasty, and treatment duration) were based on 5 key concepts. We included studies of adults who underwent total hip or knee arthroplasty, with at least 3 months postoperative follow-up. Results There were 30 studies included. Of these, 17 reported on outcomes of total hip arthroplasty and 19 reported on outcomes of total knee arthroplasty, with some reporting on outcomes of both procedures. In patients having total hip arthroplasty, rates of postoperative opioid use at various time points were as follows: at 3 months, 20% (95% CI, 13%-26%); at 6 months, 17% (95% CI, 12%-21%); at 9 months, 19% (95% CI, 13%-24%); and at 12 months, 16% (95% CI, 15%-16%). In patients who underwent total knee arthroplasty, rates of postoperative opioid use were as follows: at 3 months, 26% (95% CI, 19%-33%); at 6 months, 20% (95% CI, 17%-24%); at 9 months, 23% (95% CI, 17%-28%); and at 12 months, 21% (95% CI, 12%-29%). Opioid naïve patients were less likely to have continued postoperative opioid use than those who were opioid tolerant preoperatively. Conclusion Over 1 in 5 patients continued opioid use for longer than 3 months after total hip or knee arthroplasty. Clinicians should be aware of this trajectory of opioid consumption after surgery.

Foreword {#article-title-2} The ASHP Research and Education Foundation (“the Foundation”) is pleased to present the seventh edition of the annual Pharmacy Forecast . We are again pleased to disseminate the Pharmacy Forecast through AJHP, providing readers with easy access to the report. The

End-of-life decision making in cancer can be a complicated process. Patients and families encounter multiple providers throughout their cancer care. When the efforts of these providers are not well coordinated in teams, opportunities for high-quality, longitudinal goals of care discussions can be missed. This article reviews the case of a 55-year-old man with lung cancer, illustrating the barriers and missed opportunities for end-of-life decision making in his care through the lens of team leadership, a key principle in the science of teams. The challenges demonstrated in this case reflect the importance of the four functions of team leadership: information search and structuring, information use in problem solving, managing personnel resources, and managing material resources. Engaging in shared leadership of these four functions can help care providers improve their interactions with patients and families concerning end-of-life care decision making. This shared leadership can also produce a cohesive care plan that benefits from the expertise of the range of available providers while reflecting patient needs and preferences. Clinicians and researchers should consider the roles of team leadership functions and shared leadership in improving patient care when developing and studying models of cancer care delivery.

Opioids remain the mainstay of treatment for severe cancer pain, but up to 20% of patients have persistent or refractory pain despite rapid and aggressive opioid titration, or develop refractory pain after long-term opioid use. In these scenarios, alternative agents and mechanisms for analgesia should be considered. This case report describes a 28-year-old man with metastatic pancreatic neuroendocrine cancer with severe, intractable pain despite high-dose opioids including methadone and a hydromorphone patient-controlled analgesia (PCA). After treatment with short-course, low-dose ketamine, his opioid requirements decreased by 99% and pain ratings by 50%, with the majority of this decrease occurring in the first 48 hours. As this patient's pain and opioid regimen escalated, he likely experienced some component of central sensitization and hyperalgesia. Administration of ketamine reduced opioid consumption by 99% and potentially "reset" neuronal hyperexcitability and reduced pain signaling, allowing for improved pain control.

Palliative care arose from the modern hospice movement and has evolved significantly over the past 50 years.[1][1] Numerous definitions exist to describe palliative care, all of which focus on aggressively addressing suffering. The World Health Organization and the U.S. Department of Health and

Background One in 16 surgical patients prescribed opioids becomes a long-term user. Overprescribing opioids after surgery is common, and the lack of multidisciplinary procedure-specific guidelines contributes to the wide variation in opioid prescribing practices. We hypothesized that a single-institution, multidisciplinary expert panel can establish consensus on ideal opioid prescribing for select common surgical procedures. Study Design We used a 3-step modified Delphi method involving a multidisciplinary expert panel of 6 relevant stakeholder groups (surgeons, pain specialists, outpatient surgical nurse practitioners, surgical residents, patients, and pharmacists) to develop consensus ranges for outpatient opioid prescribing at the time of discharge after 20 common procedures in 8 surgical specialties. Prescribing guidelines were developed for opioid-naive adult patients without chronic pain undergoing uncomplicated procedures. The number of opioid tablets was defined using oxycodone 5 mg oral equivalents. Results For all 20 surgical procedures reviewed, the minimum number of opioid tablets recommended by the panel was 0. Ibuprofen was recommended for all patients unless medically contraindicated. The maximum number of opioid tablets varied by procedure (median 12.5 tablets), with panel recommendations of 0 opioid tablets for 3 of 20 (15%) procedures, 1 to 15 opioid tablets for 11 of 20 (55%) procedures, and 16 to 20 tablets for 6 of 20 (30%) procedures. Overall, patients who had the procedures voted for lower opioid amounts than surgeons who performed them. Conclusions Procedure-specific prescribing recommendations may help provide guidance to clinicians who are currently overprescribing opioids after surgery. Multidisciplinary, patient-centered consensus guidelines for more procedures are feasible and may serve as a tool in combating the opioid crisis.

Objective: To systematically assess benefits and harm of non-pharmacologic interventions for diabetic peripheral neuropathy (DPN) symptoms. Methods: MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched from 1966 to May 24, 2016 for randomized controlled trials. Two reviewers evaluated studies for eligibility, serially abstracted data, evaluated risk of bias, and graded strength of evidence (SOE) for critical outcomes (pain and quality-of-life). Results: Twenty-three trials were included. For pain, alpha-lipoic acid was more effective than placebo (moderate SOE) and frequency-modulated electromagnetic stimulation was more effective than sham (low SOE) in the short-term but not the long-term. Electrical stimulation (including transcutaneous) was not effective for pain (low SOE). Spinal cord stimulation was more effective than usual care for pain (low SOE), but had serious complications, and studies had no sham arm. Evidence for cognitive behavioral therapy and acupuncture was insufficient; no exercise or physical therapy trials met inclusion criteria. No interventions reported sufficient evidence on quality-of-life. Most studies were short-term with unclear risk of bias. Conclusions: Alpha-lipoic acid and spinal cord stimulation were effective for pain; studies were short-term with quality deficits. Spinal cord stimulation had serious adverse events. Further research should address long-term outcomes and other non-pharmacologic treatments.

Background: Caring for cancer patients with advanced and refractory disease requires communication about care preferences, particularly when patients become ill enough to be at risk for critical care interventions potentially inconsistent with their preferences. Aim: To describe the use of goals of care discussions in patients with advanced/refractory cancer at risk for critical care interventions and evaluate associations between these discussions and outcomes. Design: Cohort study describing patients/families’ perceptions of goals of care meetings and comparing health care utilization outcomes of patients who did and did not have discussions. Setting/participants: Inpatient units of an academic cancer center. Included patients had metastatic solid tumors or relapsed/refractory lymphoma or leukemia and were at risk for critical care, defined as requiring supplemental oxygen and/or cardiac monitor. Results: Of 86 patients enrolled, 34 (39%) had a reported goals of care discussion (study group). Patients/families reported their needs and goals were addressed moderately to quite a bit during the meetings. Patients in the study group were less likely to receive critical care (0% vs 22%, p = 0.003) and more likely to be discharged to hospice (48% vs 30%, p = 0.04) than the control group. Only one patient in the study group died during the index hospitalization (on comfort care) (3%) compared with 9(17%) in the control group ( p = 0.08). Conclusion: Goals of care meetings for advanced/refractory cancer inpatients at risk for critical care interventions can address patient and family goals and needs and improve health care utilization. These meetings should be part of routine care for these patients.

Objective: To present a framework for recognizing, appreciating, and applying the specific skills used during the processes of medication order screening and therapy monitoring in daily practice. Summary: The health care system in which the profession of pharmacy serves is undergoing significant change. The profession is continually reacting to this change. Recently these reactions have included a shift in focus from the medication order processing skills all pharmacists possess to such things as medication prescribing, clinical pathway development, and formulary management. Although some of these activities have merit, we believe that the disregard of pharmacy's traditional strengths applied to medication order processing may damage both patient care and the system in which we practice. Renewed focus must be applied to the development of practice models that include the application of unique pharmacist skills (e.g., optimizing drug doses, safety, routes of administration, and compliance) as integral components. Variances in knowledge and training among pharmacists may result in differences in the level of service provided to a given patient. However, all pharmacists are equipped to provide unique professional services at a level that has demonstrable impact on patient care. Conclusion: Pharmacists are uniquely skilled in ensuring the safe and effective use of medications. The authors believe that the specific skills applied during the processes of medication order screening and therapy monitoring can and should be incorporated into daily practice. Failure to do so will deprive patients of optimal care and pharmacists of professional satisfaction. We encourage pharmacists to recognize and develop their unique, traditional strengths, and subsequently allow these strengths to provide the health benefits for which they were intended.

Pain is a common symptom associated with cancer and its treatment. Pain management is an important aspect of oncologic care, and unrelieved pain significantly comprises overall quality of life. These NCCN Guidelines list the principles of management and acknowledge the range of complex decisions faced in the management oncologic pain. In addition to pain assessment techniques, these guidelines provide principles of use, dosing, management of adverse effects, and safe handling procedures of pharmacologic therapies and discuss a multidisciplinary approach for the management of cancer pain.

Objective. Improvements in clinical pain care have not matched advances in scientific knowledge, and innovations in medical education are needed. Several streams of evidence indicate that pain education needs to address both the affective and cognitive dimensions of pain. Our aim was to design and deliver a new course in pain establishing foundation-level knowledge while comprehensively addressing the emotional development needs in this area. Setting. One hundred eighteen first-year medical students at Johns Hopkins School of Medicine. Outcome Measures. Performance was measured by multiple-choice tests of pain knowledge, attendance, reflective pain portfolios, and satisfaction measures. Results. Domains of competence in pain knowledge included central and peripheral pain signalling, pharmacological management of pain with standard analgesic medications, neuromodulating agents, and opioids; cancer pain, musculoskeletal pain, nociceptive, inflammatory, neuropathic, geriatric, and pediatric pain. Socio-emotional development (portfolio) work focused on increasing awareness of pain affect in self and others, and on enhancing the commitment to excellence in pain care. Reflections included observations on a brief pain experience (cold pressor test), the multidimensionality of pain, the role of empathy and compassion in medical care, the positive characteristics of pain-care role models, the complex feelings engendered by pain and addiction including frustration and disappointment, and aspirations and commitments in clinical medicine. The students completing feedback expressed high levels of interest in pain medicine as a result of the course. Discussion. We conclude that a 4-day pain course incorporating sessions with pain specialists, pain medicine knowledge, and design-built elements to strengthen emotional skills is an effective educational approach. Summary. Innovations in medical education about pain are needed. Our aim was to design and deliver a new course for medical students addressing both the affective and cognitive dimensions of pain. Combining small-group sessions with pain specialists, active-learning approaches to pain knowledge, and design-built elements to strengthen emotional skills was highly effective.

Bone marrow aspiration and biopsy (BMAB) is painful when performed with only local anesthetic. Our objective was to determine whether viewing nature scenes and listening to nature sounds can reduce pain during BMAB.This was a randomized, controlled clinical trial. Adult patients undergoing outpatient BMAB with only local anesthetic were assigned to use either a nature scene with accompanying nature sounds, city scene with city sounds, or standard care. The primary outcome was a visual analog scale (0-10) of pain. Prespecified secondary analyses included categorizing pain as mild and moderate to severe and using multiple logistic regression to adjust for potential confounding variables.One hundred and twenty (120) subjects were enrolled: 44 in the Nature arm, 39 in the City arm, and 37 in the Standard Care arm. The mean pain scores, which were the primary outcome, were not significantly different between the three arms. A higher proportion in the Standard Care arm had moderate-to-severe pain (pain rating ≥4) than in the Nature arm (78.4% versus 60.5%), though this was not statistically significant (p = 0.097). This difference was statistically significant after adjusting for differences in the operators who performed the procedures (odds ratio = 3.71, p = 0.02).We confirmed earlier findings showing that BMAB is poorly tolerated. While mean pain scores were not significantly different between the study arms, secondary analyses suggest that viewing a nature scene while listening to nature sounds is a safe, inexpensive method that may reduce pain during BMAB. This approach should be considered to alleviate pain during invasive procedures.

Purpose. Ifosfamide is metabolized by the cytochrome P450 system to its active form, ifosforamide mustard. A potential side effect is neurotoxicity, often manifesting as confusion, hallucination, or seizure. Aprepitant, a neurokinin-1 inhibitor, is recommended for highly and moderately emetogenic chemotherapy regimens and may interfere with the metabolism of ifosfamide as it inhibits CYP3A4. The objective of the study is to identify if an increase in the incidence of neurotoxicity may be associated with the use of aprepitant with concomitant ifosfamide. Methods. A retrospective study of inpatients with sarcoma who received a two or four-day regimen of MAI (mesna, doxorubicin, and ifosfamide) between January 1, 2004 and December 31, 2006 was conducted. Data collection focused on characterizing neurotoxicity of patients receiving ifosfamide with or without aprepitant. Correlation between serum creatinine, albumin, liver function tests, age, gender, and total doses of ifosfamide was examined. Results. A total of 45 patients received ifosfamide of which 23 (51%) were male and 24 (53%) received aprepitant. All baseline characteristics were similar for those who received aprepitant versus those who did not. No significant differences were noted between patients with or without neurotoxicity for age, gender, or liver enzymes. Eight patients (18%) of 45 developed neurotoxicity of which six (75%) of those patients also received aprepitant. A trend of increased occurrence of neurotoxicity was noted with aprepitant administration (6 vs. 2 patients respectively, p = 0.176), although a statistical difference was not observed. A relative risk of 2.6 (95% CI, 0.47—26.6) was associated with the addition of aprepitant. Conclusions. An increased risk was identified for ifosfamide-induced neurotoxicity associated with aprepitant use; however, the observed difference was not statistically significant. The necessity of aprepitant given in association with ifosfamide may need to be reconsidered due to this risk. J Oncol Pharm Practice (2008) 14: 157—162.

The concept of opioid equianalgesia, limitations in current dose conversion systems, equianalgesic dose tables, and computer assisted dose conversions are discussed. Conversions for methadone, fentanyl and hydromorphone are described.

Cancer causes pain as it invades bone, compresses nerves, produces obstructive symptoms in the pulmonary, gastrointestinal, and genitourinary systems, and distends involved visceral organs. This manuscript reviews progress in cancer pain management during the past 2 decades. Since the 1980s, we have seen (1) genuine advances in research on the biology of pain, (2) new approaches to the treatment of cancer pain, and (3) important changes in the health-care system to ensure that pain is appropriately assessed and managed. Currently, clinicians have the appropriate diagnostic and therapeutic tools to ensure that the vast majority of patients with cancer pain can be comfortable during their illness. Nevertheless, too many patients with terminal malignancies continue to die in pain in nations around the globe. An effective strategy to make alleviating pain a major health-care priority remains the primary challenge to effectively palliating patients with cancer pain.

The agents used for sedation and analgesia during endoscopy have complex pharmacokinetic and pharmacodynamic properties. Knowledge of these characteristics is necessary for determining the proper agent and dose for specific patient needs. Short-acting agents, such as fentanyl, midazolam, and propofol, provide rapid sedation with a short duration of action that allows patients to return to normal functioning rapidly. When designing a dosing regimen with these agents, age and organ (liver, kidney) function of patients and concomitant medications that may interfere with metabolic and elimination pathways must be considered.

The efficacy of amphotericin B bladder irrigation at two concentrations was studied. Patients with funguria (> or =15,000 colony-forming units of yeast per milliliter of urine), an indwelling urinary catheter, and a physician order for amphotericin B continuous bladder irrigation were randomly assigned to receive 10 or 50 mg of amphotericin B per liter of sterile water as a continuous irrigation for 72 hours at the rate of 42 mL/hr. Before the bladder irrigation began, the indwelling catheter was changed to a three-way catheter. Repeat urine cultures were performed 24 hours after the irrigation was discontinued. A total of 28 patients were enrolled from November 1993 to May 1995. The rate of eradication of the infection was 100% in the 50-mg/L group and 67% in the 10-mg/ L group. Subject enrollment was stopped prematurely because all the treatment failures occurred in the 10-mg/L group. Dose was the only variable significantly associated with outcome. Bladder irrigation with amphotericin B was more effective when the drug concentration was 50 mg/L rather than 10 mg/L.

Pain and symptoms related to palliative care (pain and palliative care [PPC]) are often undertreated. This is largely owing to the complexity in the provision of care and the potential discrepancy in education among the various health care professionals required to deliver care. Pharmacists are frequently involved in the care of PPC patients, although pharmacy education currently does not offer or require a strong curriculum commitment to this area of practice. The Strategic Planning Summit for the Advancement of Pain and Palliative Care Pharmacy was convened to address opportunities to improve the education of pharmacists and pharmacy students on PPC. Six working groups were charged with objectives to address barriers and opportunities in the areas of student and professional assessment, model curricula, postgraduate training, professional education, and credentialing. Consensus was reached among the working groups and presented to the Summit Advisory Board for adoption. These recommendations will provide guidance on improving the care provided to PPC patients by pharmacists through integrating education at all points along the professional education continuum.