Malignant Transformation of Nonhealing Ulcer-Basal Cell Carcinoma.

We discuss the rare case of a 72-year-old female with a history of a nonhealing lower extremity ulcer that was biopsied, revealing malignant transformation to basal cell carcinoma (BCC). Although BCC is the most common malignancy worldwide, malignant transformation of nonhealing wounds is more often associated with squamous cell carcinoma. Current literature estimates the rate of BCC arising from venous stasis ulcer to occur between 1.5 and 15%. When diagnosed early, BCC can have cure rates of up to 95%. However, metastatic BCC has a median survival of roughly 8 months. We believe it is important to raise awareness of this rare, but often curable, clinical diagnosis to improve long-term outcomes.

Medication-related problems encountered in the Program of All-Inclusive Care for the Elderly: An observational study.

OBJECTIVE: To evaluate pharmacist-encountered medication-related problems (MRPs) among the participants of the Program of All-Inclusive Care for the Elderly (PACE). DESIGN: This was a retrospective analysis of proprietary pharmacy records detailing pharmacist encounters with PACE clinical staff. SETTING AND PARTICIPANTS: A national provider of pharmacy services to more than 75 PACE organizations. In total, 1057 PACE participants at 69 PACE sites across the United States with documented pharmacist encounters between March and May 2018. OUTCOME MEASURES: MRPs were classified using the Hepler-Strand taxonomy, and pharmacists' recommendations made to prescribers to resolve these MRPs were classified using a modified Hoth taxonomy. In addition, pharmacists' communication methods and prescribers' responses were analyzed. RESULTS: Overall, 2004 MRPs were encountered. The most frequent MRPs identified were related to medication safety concerns, including drug interactions (720, 35.9%), adverse drug reactions (ADRs, 356, 17.8%), high doses (270, 13.5%), and unindicated drugs (252, 12.6%). Drug interactions frequently involved competitive inhibition, 3 or more drugs, opioids, anticoagulants, antiplatelets, and antidepressants. Deprescribe medication (561, 24.8%), start alternative therapy (553, 24.4%), change doses (457, 20.2%), and monitor (243, 10.7%) were the top 4 types of recommendations made by pharmacists. Among 1730 responses obtained from PACE prescribers, 78.1% (n = 1351) of pharmacists' recommendations were accepted. Compared with electronic communication, telephonic communication was associated with more acceptance and less prescriber nonresponse (χ2 = 78.5, P < 0.001). CONCLUSION: Pharmacists identified a substantial number of MRPs in PACE, especially those related to medication safety such as drug interactions and ADRs. In this practice setting, significant collaboration occured between pharmacists and PACE prescribers, as evidenced by the rate of prescribers' acceptance of pharmacists' recommendations. Further research is needed to fully evaluate the economic, clinical, and humanistic outcomes associated with pharmacists' encounters in PACE.

Laparoscopy in penetrating abdominal trauma is a safe and effective alternative to laparotomy.

INTRODUCTION: Diagnostic laparoscopy (DL) is an increasingly used modality when approaching penetrating abdominal trauma (PAT). Trauma surgeons can utilize this minimally invasive technique to quickly assess for injury in hemodynamically stable patients. DL with a confirmed injury can be repaired through therapeutic laparoscopy (TL) or conversion to exploratory laparotomy (EL). This study analyzes the use of laparoscopy as a first-line therapy for hemodynamically stable patients with PAT. METHODS: Data were reviewed of patients presenting with PAT between December 2006 and September 2016. A retrospective analysis was conducted to analyze demographics, baseline presentations, treatment protocols and outcomes. RESULTS: A total of 56 patients with PAT were initially treated with laparoscopy. Injuries included stab wounds (n = 48) and gunshot wounds (n = 8). Patients were divided into three groups: DL, DL to TL, and DL to EL. Ten patients (17.9%) required conversion to laparotomy (DL to EL). Of the 46 patients who did not require conversion, 33 patients (71.7%) underwent DL, while 13 patients (28.3%) required TL (DL to TL). There were no differences in postoperative complication rates between the groups (p = 0.565). The mean lengths of hospital stay for DL, DL to TL, and DL to EL were 3.1, 2.7, and 8.1 days, respectively (p = 0.038). No missed injuries or mortalities occurred in any of the groups. CONCLUSION: Laparoscopy can be utilized for hemodynamically stable patients with PAT. DL can be converted to TL in the hands of a skilled laparoscopist. In this study, we analyze the use of DL over a 10-year period in patients who presented to our level 1 trauma center with PAT. We also provide a comprehensive review of literature to create clear definitions, and to clarify a systematic stepwise approach of how to effectively perform DL and TL. This study adds to the body of literature supporting the role of laparoscopy in PAT, and advances the discussion regarding management.

Implementation of a pharmacist-led pharmacogenomics service for the Program of All-Inclusive Care for the Elderly (PHARM-GENOME-PACE).

OBJECTIVES: To determine the feasibility of implementing a pharmacist-led pharmacogenomics (PGx) service for the Program of All-Inclusive Care for the Elderly (PACE). SETTING: A national centralized pharmacy providing PGx services to community-based PACE centers. PRACTICE DESCRIPTION: Individuals 55 years of age and older enrolled in PACE who underwent PGx testing as part of their medical care (n = 296). PRACTICE INNOVATION: Pharmacist-led PGx testing, interpreting, and consulting. EVALUATION: Implementation processes and roles were ascertained by reviewing policies and procedures for the PGx service and documented observations made by pharmacists providing the service. Genetic variants and drug-gene interactions (DGIs) were determined by interpretations of PGx test results. Types of recommendations provided by pharmacists were ascertained from PGx consultations. Prescribers' acceptance of recommendations were ascertained by documented responses or drug changes made after PGx consultations. RESULTS: Challenges to implementation included lack of systems interoperability, limited access to medical electronic health records, determining prescribers' responses, and knowledge and competency gaps in PGx. Pharmacist roles most essential to overcoming challenges were interpreting and applying PGx data, determining how to disseminate those data to prescribers, advocating for appropriate PGx testing, and educating about the application of test results to clinical practice. Participants frequently used drugs posing DGI risks, with the majority (73.6%) reporting more than 1 interaction. The overwhelming majority (89.0%) of pharmacists' recommendations to mitigate risks were accepted by referring prescribers. CONCLUSION: Implementing a pharmacist-led PGx service for PACE is feasible. Implementation of this service highlights the leadership role of pharmacists in moving PGx from research to practice.

Review of Proton Pump Inhibitor Overuse in the US Veteran Population.

Objective: A growing body of evidence provides proof that proton pump inhibitors (PPIs) are overused in the general population and that such use is associated with adverse risks and unnecessary costs. Our objective was to systematically evaluate PPI overuse in the veteran population. Data Sources: A literature search using MEDLINE and CINHAL databases (1946-December 2014) was performed using the search term proton pump inhibitors coupled with each of the following key words: inappropriate use, misuse, and overuse. Searches were limited to studies and reviews in English language and human subjects. Additional references were identified from a review of literature citations. Study Selection and Data Extraction: All articles that centrally addressed the issue of PPI overuse were evaluated, following the PRISMA guidelines for systematic reviews. Data were extracted into Microsoft Excel 2013. Articles that focused on the pediatric or non-US veteran populations were excluded. Data Synthesis: Among 30 articles included, 5 evaluated PPI overuse in veterans. The reported prevalence rate of PPI overuse in veterans ranged from 33% to 67%. Several cases reported PPI-associated Clostridium difficile-associated diarrhea and pneumonia. One Veterans Affairs center reported the total cost of PPI overuse to be more than $200 000 based on over-the-counter costs and more than $1.5 million based on average wholesale price cost. Conclusions: PPI overuse is common among veterans and exposes them to adverse risks and costs the system enormous dollars. Based on the findings of this review, we provide recommendations to curb PPI overuse among veterans and in the Veterans Affairs system.

Atomic structure of the nuclear pore complex targeting domain of a Nup116 homologue from the yeast, Candida glabrata.

The nuclear pore complex (NPC), embedded in the nuclear envelope, is a large, dynamic molecular assembly that facilitates exchange of macromolecules between the nucleus and the cytoplasm. The yeast NPC is an eightfold symmetric annular structure composed of ~456 polypeptide chains contributed by ~30 distinct proteins termed nucleoporins. Nup116, identified only in fungi, plays a central role in both protein import and mRNA export through the NPC. Nup116 is a modular protein with N-terminal "FG" repeats containing a Gle2p-binding sequence motif and a NPC targeting domain at its C-terminus. We report the crystal structure of the NPC targeting domain of Candida glabrata Nup116, consisting of residues 882-1034 [CgNup116(882-1034)], at 1.94 Å resolution. The X-ray structure of CgNup116(882-1034) is consistent with the molecular envelope determined in solution by small-angle X-ray scattering. Structural similarities of CgNup116(882-1034) with homologous domains from Saccharomyces cerevisiae Nup116, S. cerevisiae Nup145N, and human Nup98 are discussed.

Protein production and purification.

In selecting a method to produce a recombinant protein, a researcher is faced with a bewildering array of choices as to where to start. To facilitate decision-making, we describe a consensus 'what to try first' strategy based on our collective analysis of the expression and purification of over 10,000 different proteins. This review presents methods that could be applied at the outset of any project, a prioritized list of alternate strategies and a list of pitfalls that trip many new investigators.

Use of Drug Claims Data and a Medication Risk Score to Assess the Impact of CYP2D6 Drug Interactions among Opioid Users on Healthcare Costs.

Cytochrome P450 2D6 (CYP2D6) activity is highly variable due to several factors, including genetic polymorphisms and drug-drug-gene interactions. Hydrocodone, oxycodone, codeine, and tramadol the most commonly prescribed CYP2D6-activated opioids for pain. However, the co-administration of CYP2D6 interacting drugs can modulate CYP2D6-medicated activation of these opioids, affecting drug analgesia, effectiveness, and safety, and can impact healthcare costs. A retrospective, observational cohort analysis was performed in a large (n = 50,843) adult population. This study used drug claims data to derive medication risk scores and matching propensity scores to estimate the effects of opioid use and drug-drug interactions (DDIs) on medical expenditures. 4088 individuals were identified as opioid users; 95% of those were prescribed CYP2D6-activated opioids. Among those, 15% were identified as being at risk for DDIs. Opioid users had a significant increase in yearly medical expenditure compared to non-opioid users ($2457 vs. $1210). In matched individuals, average healthcare expenditures were higher for opioid users with DDIs compared to those without DDIs ($7841 vs. $5625). The derived medication risk score was higher in CYP2D6 opioid users with interacting drug(s) compared to no DDI (15 vs. 12). Higher costs associated with CYP2D6 opioid use under DDI conditions suggest inadequate CYP2D6 opioid prescribing practices. Efforts to improve chronic opioid use in adults should reduce interacting drug combinations, especially among patients using CYP2D6 activated opioids.

Cost avoidance related to a pharmacist-led pharmacogenomics service for the Program of All-inclusive Care for the Elderly.

Aim: Estimate cost avoidance of pharmacist recommendations for participants enrolled in the Program of All-inclusive Care for the Elderly. Materials & methods: Convenience sample of 200 pharmacogenomics consultations from the PHARM-GENOME-PACE study. Genetic variants, drug-gene interactions, drug-drug-gene interactions and phenoconversions were interrogated. Cost avoidance was estimated and adjusted for inflation. Results: In total, 165 participants had at least one actionable drug-gene pair totaling 429 drug-gene pairs, of which 158 (36.8%) were clinically actionable. Most (70.5%) pharmacists' recommendations were accepted. Estimated cost avoidance was $233,945 when all recommendations were included but conservatively $162,031 based on acceptance rates. Overall mean cost avoidance per actionable drug-gene pair was $1063 or $1983 per participant. Conclusion: Pharmacist-led pharmacogenomics services added to the traditional medication review can avoid substantial costs for payers. Clinical trial registration number: NCT03257605.

Opioids, Polypharmacy, and Drug Interactions: A Technological Paradigm Shift Is Needed to Ameliorate the Ongoing Opioid Epidemic.

Polypharmacy is a common phenomenon among adults using opioids, which may influence the frequency, severity, and complexity of drug-drug interactions (DDIs) experienced. Clinicians must be able to easily identify and resolve DDIs since opioid-related DDIs are common and can be life-threatening. Given that clinicians often rely on technological aids-such as clinical decision support systems (CDSS) and drug interaction software-to identify and resolve DDIs in patients with complex drug regimens, this narrative review provides an appraisal of the performance of existing technologies. Opioid-specific CDSS have several system- and content-related limitations that need to be overcome. Specifically, we found that these CDSS often analyze DDIs in a pairwise manner, do not account for relevant pharmacogenomic results, and do not integrate well with electronic health records. In the context of polypharmacy, existing systems may encourage inadvertent serious alert dismissal due to the generation of multiple incoherent alerts. Future technological systems should minimize alert fatigue, limit manual input, allow for simultaneous multidrug interaction assessments, incorporate pharmacogenomic data, conduct iterative risk simulations, and integrate seamlessly with normal workflow.

Prescriber-Initiated Engagement of Pharmacists for Information and Intervention in Programs of All-Inclusive Care for the Elderly.

Little is known about the types of drug information inquiries (DIIs) prescribers caring for older adults ask pharmacists during routine practice. The objective of this research was to analyze the types of DIIs prescribing clinicians of Programs of All-Inclusive Care for the Elderly (PACE) made to clinical pharmacists during routine patient care. This was a retrospective analysis of documented pharmacists' encounters with PACE prescribers between March through December, 2018. DIIs were classified using a developed taxonomy that describes prescribers' motivations for consulting with pharmacists and their drug information needs. Prescribers made 414 DIIs during the study period. Medication safety concerns motivated the majority of prescribers' inquiries (223, 53.9%). Inquiries received frequently involved modifying drug therapy (94, 22.7%), identifying or resolving adverse drug events (75, 18.1%), selecting or adjusting doses (61, 14.7%), selecting new drug therapies (57, 13.8%), and identifying or resolving drug interactions (52, 12.6%). Central nervous system medications (e.g., antidepressants and opioids), were involved in 38.6% (n = 160) of all DIIs. When answering DIIs, pharmacists made 389 recommendations. Start alternative medications (18.0%), start new medications (16.7%), and change doses (12.1%) were the most frequent recommendations rendered. Prescribers implemented at least 79.3% (n = 268) of recommendations based on pharmacy records (n = 338 verifiable recommendations). During clinical practice, PACE prescribers commonly ask pharmacists a variety of DIIs, largely related to medication safety concerns. In response to these DIIs, pharmacists provide medication management recommendations, which are largely implemented by prescribers.

Cytochrome P450 (CYP450) Interactions Involving Atypical Antipsychotics are Common in Community-Dwelling Older Adults Treated for Behavioral and Psychological Symptoms of Dementia.

Treatment of behavioral and psychological symptoms of dementia (BPSD) and comorbidities often necessitates the concomitant use of antipsychotics and non-antipsychotic drugs, thereby potentiating the risk for drug-drug interactions (DDIs).The primary objective of our study was to identify potentially clinically relevant cytochrome P450 (CYP)-mediated DDIs involving antipsychotics among participants enrolled in the Program of All-Inclusive Care for the Elderly (PACE) with BPSD. Additionally, we wanted to determine the prevalence of antipsychotic use in this population. The study included 10,001 PACE participants. The practice setting used a proprietary clinical decision support system (CDSS) to analyze simultaneous multidrug interactions. A retrospective analysis of pharmacy claims data was conducted to identify DDIs involving antipsychotics prescribed for BPSD, using snapshots of medication profiles paired with the CDSS. Of the participants who met inclusion criteria, 1190 (11.9%) were prescribed an antipsychotic; of those, 1071 (90.0%) were prescribed an atypical antipsychotic. Aripiprazole commonly caused (being a perpetrator drug 94.6% of the time) potential DDIs with antidepressants (e.g., duloxetine, venlafaxine, mirtazapine), opioids (e.g., hydrocodone, oxycodone, tramadol) and metoprolol via the CYP2D6 isoform. Risperidone commonly caused (85.7%) potential DDIs with donepezil, lamotrigine and trazodone via the CYP3A4 isoform. Quetiapine exclusively suffered (100%) from potential DDIs with amlodipine, buspirone, omeprazole or topiramate via the CYP3A4 isoform. Antipsychotics are commonly prescribed to PACE participants for BPSD treatment and they may interact with other drugs used to treat comorbidities. A thorough review of concomitant medications will help mitigate the likelihood of potentially dangerous CYP-mediated DDIs involving antipsychotics.

Precision medication: An illustrative case series guiding the clinical application of multi-drug interactions and pharmacogenomics.

Precision medication entails selecting the precise medication, dose, and timing of administration. Multi-drug interactions and genetics significantly affect precision medication. In this article, we present two simulated cases for real-world applications of precision medication. Clinicians may need to acquire additional skills to apply the principles illustrated by these cases.

Evolution of enzymatic activities in the enolase superfamily: stereochemically distinct mechanisms in two families of cis,cis-muconate lactonizing enzymes.

The mechanistically diverse enolase superfamily is a paradigm for elucidating Nature's strategies for divergent evolution of enzyme function. Each of the different reactions catalyzed by members of the superfamily is initiated by abstraction of the alpha-proton of a carboxylate substrate that is coordinated to an essential Mg(2+). The muconate lactonizing enzyme (MLE) from Pseudomonas putida, a member of a family that catalyzes the syn-cycloisomerization of cis,cis-muconate to (4S)-muconolactone in the beta-ketoadipate pathway, has provided critical insights into the structural bases for evolution of function within the superfamily. A second, divergent family of homologous MLEs that catalyzes anti-cycloisomerization has been identified. Structures of members of both families liganded with the common (4S)-muconolactone product (syn, Pseudomonas fluorescens, gi 70731221 ; anti, Mycobacterium smegmatis, gi 118470554 ) document that the conserved Lys at the end of the second beta-strand in the (beta/alpha)(7)beta-barrel domain serves as the acid catalyst in both reactions. The different stereochemical courses (syn and anti) result from different structural strategies for determining substrate specificity: although the distal carboxylate group of the cis,cis-muconate substrate attacks the same face of the proximal double bond, opposite faces of the resulting enolate anion intermediate are presented to the conserved Lys acid catalyst. The discovery of two families of homologous, but stereochemically distinct, MLEs likely provides an example of "pseudoconvergent" evolution of the same function from different homologous progenitors within the enolase superfamily, in which different spatial arrangements of active site functional groups and substrate specificity determinants support catalysis of the same reaction.

Computation-facilitated assignment of the function in the enolase superfamily: a regiochemically distinct galactarate dehydratase from Oceanobacillus iheyensis .

The structure of an uncharacterized member of the enolase superfamily from Oceanobacillus iheyensis (GI 23100298, IMG locus tag Ob2843, PDB entry 2OQY ) was determined by the New York SGX Research Center for Structural Genomics (NYSGXRC). The structure contained two Mg(2+) ions located 10.4 A from one another, with one located in the canonical position in the (beta/alpha)(7)beta-barrel domain (although the ligand at the end of the fifth beta-strand is His, unprecedented in structurally characterized members of the superfamily); the second is located in a novel site within the capping domain. In silico docking of a library of mono- and diacid sugars to the active site predicted a diacid sugar as a likely substrate. Activity screening of a physical library of acid sugars identified galactarate as the substrate (k(cat) = 6.8 s(-1), K(M) = 620 microM, k(cat)/K(M) = 1.1 x 10(4) M(-1) s(-1)), allowing functional assignment of Ob2843 as galactarate dehydratase (GalrD-II). The structure of a complex of the catalytically impaired Y90F mutant with Mg(2+) and galactarate allowed identification of a Tyr 164-Arg 162 dyad as the base that initiates the reaction by abstraction of the alpha-proton and Tyr 90 as the acid that facilitates departure of the beta-OH leaving group. The enzyme product is 2-keto-d-threo-4,5-dihydroxyadipate, the enantiomer of the product obtained in the GalrD reaction catalyzed by a previously characterized bifunctional l-talarate/galactarate dehydratase (TalrD/GalrD). On the basis of the different active site structures and different regiochemistries, we recognize that these functions represent an example of apparent, not actual, convergent evolution of function. The structure of GalrD-II and its active site architecture allow identification of the seventh functionally and structurally characterized subgroup in the enolase superfamily. This study provides an additional example in which an integrated sequence- and structure-based strategy employing computational approaches is a viable approach for directing functional assignment of unknown enzymes discovered in genome projects.

Hospice use among patients with heart failure.

BACKGROUND: Hospices provide end-of-life care for heart failure (HF) patients, but hospice is underused for these patients, and its use has not been well described. METHODS: We examined hospice use among 11,754 HF and 31,228 cancer patients. These patients were either discharged from hospice or died while in hospice between January 1, 2004, and June 30, 2005. RESULTS: The percentages of patients with HF and cancer who received hospice care for /=6 months (7.6% vs 1.1%; P < .001). Patients with HF were significantly more likely to be discharged from hospice alive (19.0% vs 11.3%; P < .001), as were African Americans with HF and those who were prescribed HF medications. CONCLUSION: Our study provides detailed estimates of hospice use and identifies potential areas of hospice care that are unique to HF patients. Our findings generate hypotheses about the Medicare Hospice Benefit, specifically whether changes to the 6-month prognosis criterion for hospice eligibility would result in increased hospice use for HF patients. We hope that our results will stimulate additional studies to elucidate differences in hospice use between HF and cancer patients, including patient perspectives of hospice care and clinician referral patterns.

Role of Opioid-Involved Drug Interactions in Chronic Pain Management.

The use of opioids for chronic pain management is extraordinarily common despite substantial evidence of only modest benefits, when compared with nonopioid analgesics. Opioid use is also associated with serious risks, including overdose and death. A growing body of evidence suggests that opioids are involved in significant drug interactions that often go unrecognized in clinical practice. Understanding opioid-involved drug interactions is of great practical importance for all health care professionals caring for patients with chronic pain. In this article, we describe the mechanisms of opioid-involved drug interactions and their potential consequences, which have major public health implications. Additionally, this article provides practical strategies to aid health care professionals in avoiding and mitigating opioid-involved drug interactions in order to obtain a favorable balance in the risk-benefit ratio associated with opioid use. These strategies include using osteopathic principles for chronic pain management, separating the times of administration of the opioid(s) from the nonopioid(s) involved in the interaction, changing the opioid(s) adversely affected by the interaction, changing the nonopioid(s) causing the interaction, and partnering with pharmacists in clinical practice.

Genetic variants and interactions from a pharmacist-led pharmacogenomics service for PACE.

Aim: Evaluate results of pharmacogenomics testing for participants enrolled in the Program of All-inclusive Care for the Elderly (PACE). Materials & methods: A convenience sample of 100 participants from the PHARM-GENOME-PACE study. Genetic variants were determined by pharmacogenomics testing. Drug-gene interactions (DGIs), drug-drug-gene interactions (DDGIs) and phenoconversions were interrogated from a clinical decision support system. Results: In total, 146 genetic variants, 169 DGIs and 125 DDGIs were detected. DGIs and DDGIs occurred most commonly with the CYP2D6 gene (36.1 and 39.2%, respectively). There were 280 instances of phenoconversions; majority (62.9%) affecting the CYP3A4 isoenzyme. Conclusion: Prevalence of exposures to DGIs and DDGIs among PACE participants is high. Pharmacists using a clinical decision support system can support PACE practitioners with assessing multidrug simultaneous interactions. Clinical trial registration: NCT03257605.

High throughput protein production and crystallization at NYSGXRC.

Phase II of the Protein Structure Initiative, funded by the NIH NIGMS (National Institute of General Medical Sciences), is a 5-year effort to determine thousands of protein structures. The New York SGX Research Center for Structural Genomics (NYSGXRC) is one of the four large-scale production centers tasked with determining 100-200 structures annually. Almost all protein production is carried out using the high throughput structural biology platform at SGX Pharmaceuticals (SGX), which supplies 120 or more ultrapure proteins per month for NYSGXRC crystallization and structure determination activities. Protocols for PCR, cloning, expression/solubility testing, fermentation, purification, and crystallization are described. General protocols and detailed experimental results for each target are updated weekly at the public PepcDB website (pepcdb.pdb.org/), and all NYSGXRC clones should be available in 2008 through the PlasmID resource operated by the Harvard Institute of Proteomics.

A systematic review of opioid conversion ratios used with methadone for the treatment of pain.

OBJECTIVE: Review and analyze the evidence base comprising methadone conversion methods and associated dosing ratios for the treatment of pain. DESIGN: Systematic review. METHODS: Clinical trials and retrospective analyses, case series, and case reports of human subjects published in the English language between January 1966 and June 2006 were included; review articles and reports with incomplete opioid data were excluded. Scatterplots displayed the relationship between previous morphine dose and final methadone dose and dose ratio. Correlation analyses were conducted using Pearson's and Spearman's correlation coefficient with a one-tailed test of significance. RESULTS: Twenty-two clinical studies and 19 case reports or series were reviewed (N = 730 patients). Methadone rotations were most common in cancer patients (N = 625, 88.9%) and those prescribed morphine (N = 259 patients, 41.7% of rotations where prerotation opioid was identified [N = 621]) or hydromorphone (N = 234 patients, 37.7% of rotations). In clinical studies, the most common reason for switching to methadone was a combination of inadequate analgesia and adverse effects (N = 254, 38.6%). Despite various approaches, 46-89% of rotations were successful. Overall, there was a relatively strong, positive correlation between the previous morphine dose and the final methadone dose and dose ratio, but ratios varied widely. CONCLUSIONS: There was no evidence to support the superiority of one method of rotation to methadone over another. Patients may be successfully rotated to methadone despite discrepancies between rotation ratios initially used and those associated with stabilization. Further research is needed to identify patient-level factors that may explain the wide variance in successful methadone rotations.