Changes in Quantity of Opioids Dispensed following Florida's Restriction Law for Acute Pain Prescriptions.

OBJECTIVE: To assess the impact of Florida's 3-day opioid prescription supply law, effective July 2018, on opioids dispensed for acute pain patients. METHODS: Pharmacy claims from a health plan serving a large Florida employer from January 2015 through March 2019 were analyzed. We used an interrupted time series study design accounting for autocorrelation of trends before and after policy change. Acute pain patients met inclusion criteria if they had not received any opioid containing medications in the past 180 days. Patients could contribute to additional new use time if subsequent opioid claims occurred ≥180 days since the previous claim. Outcomes included mean number of units dispensed of the initial opioid prescription, mean morphine milligram equivalents (MMEs) per day of initial prescription by month, and mean total MMEs per initial prescription by month. RESULTS: A total of 8,375 enrollees had 10,583 unique opioid starts in the given timeframe. Following the policy, there was an immediate significant decrease in the units dispensed per prescription of 4.9 (95% confidence interval [CI] -8.95, -.82 units). Additionally, there was a significant immediate reduction in total MMEs dispensed per prescription of 25.6 (95% CI -44.76, -6.44 MMEs). CONCLUSIONS: Among a group of privately-insured plan enrollees in Florida, and as a result of the law, there were significant decreases in the number of units dispensed, and total MMEs of opioid prescriptions. The immediate reduction in new opioid utilization following policy implementation suggests effective policy; however, impacts on chronic pain patients were not assessed.

Open Targets: a platform for therapeutic target identification and validation.

We have designed and developed a data integration and visualization platform that provides evidence about the association of known and potential drug targets with diseases. The platform is designed to support identification and prioritization of biological targets for follow-up. Each drug target is linked to a disease using integrated genome-wide data from a broad range of data sources. The platform provides either a target-centric workflow to identify diseases that may be associated with a specific target, or a disease-centric workflow to identify targets that may be associated with a specific disease. Users can easily transition between these target- and disease-centric workflows. The Open Targets Validation Platform is accessible at https://www.targetvalidation.org.

The melanoma-linked "redhead" MC1R influences dopaminergic neuron survival.

OBJECTIVE: Individuals with Parkinson disease are more likely to develop melanoma, and melanoma patients are reciprocally at higher risk of developing Parkinson disease. Melanoma is strongly tied to red hair/fair skin, a phenotype of loss-of-function polymorphisms in the MC1R (melanocortin 1 receptor) gene. Loss-of-function variants of MC1R have also been linked to increased risk of Parkinson disease. The present study is to investigate the role of MC1R in dopaminergic neurons in vivo. METHODS: Genetic and pharmacological approaches were employed to manipulate MC1R, and nigrostriatal dopaminergic integrity was determined by comprehensive behavioral, neurochemical, and neuropathological measures. RESULTS: MC1Re/e mice, which carry an inactivating mutation of MC1R and mimic the human redhead phenotype, have compromised nigrostriatal dopaminergic neuronal integrity, and they are more susceptible to dopaminergic neuron toxins 6-hydroxydopamine and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Furthermore, a selective MC1R agonist protects against MPTP-induced dopaminergic neurotoxicity. INTERPRETATION: Our findings reveal a protective role of MC1R in the nigrostriatal dopaminergic system, and they provide a rationale for MC1R as a potential therapeutic target for Parkinson disease. Together with its established role in melanoma, MC1R may represent a common pathogenic pathway for melanoma and Parkinson disease. Ann Neurol 2017;81:395-406.

DbVar and DGVa: public archives for genomic structural variation.

Much has changed in the last two years at DGVa (http://www.ebi.ac.uk/dgva) and dbVar (http://www.ncbi.nlm.nih.gov/dbvar). We are now processing direct submissions rather than only curating data from the literature and our joint study catalog includes data from over 100 studies in 11 organisms. Studies from human dominate with data from control and case populations, tumor samples as well as three large curated studies derived from multiple sources. During the processing of these data, we have made improvements to our data model, submission process and data representation. Additionally, we have made significant improvements in providing access to these data via web and FTP interfaces.

Anatomy and bronchoscopy of the porcine lung. A model for translational respiratory medicine.

The porcine model has contributed significantly to biomedical research over many decades. The similar size and anatomy of pig and human organs make this model particularly beneficial for translational research in areas such as medical device development, therapeutics and xenotransplantation. In recent years, a major limitation with the porcine model was overcome with the successful generation of gene-targeted pigs and the publication of the pig genome. As a result, the role of this model is likely to become even more important. For the respiratory medicine field, the similarities between pig and human lungs give the porcine model particular potential for advancing translational medicine. An increasing number of lung conditions are being studied and modeled in the pig. Genetically modified porcine models of cystic fibrosis have been generated that, unlike mouse models, develop lung disease similar to human cystic fibrosis. However, the scientific literature relating specifically to porcine lung anatomy and airway histology is limited and is largely restricted to veterinary literature and textbooks. Furthermore, methods for in vivo lung procedures in the pig are rarely described. The aims of this review are to collate the disparate literature on porcine lung anatomy, histology, and microbiology; to provide a comparison with the human lung; and to describe appropriate bronchoscopy procedures for the pig lungs to aid clinical researchers working in the area of translational respiratory medicine using the porcine model.

Cardiotoxicity and cardioprotection in childhood cancer.

Children diagnosed with cancer are now living longer as a result of advances in treatment. However, some commonly used anticancer drugs, although effective in curing cancer, can also cause adverse late effects. The cardiotoxic effects of anthracycline chemotherapy, such as doxorubicin, and radiation can cause persistent and progressive cardiovascular damage, emphasizing a need for effective prevention and treatment to reduce or avoid cardiotoxicity. Examples of risk factors for cardiotoxicity in children include higher anthracycline cumulative dose, higher dose of radiation, younger age at diagnosis, female sex, trisomy 21 and black race. However, not all who are exposed to toxic treatments experience cardiotoxicity, suggesting the possibility of a genetic predisposition. Cardioprotective strategies under investigation include the use of dexrazoxane, which provides short- and long-term cardioprotection in children treated with doxorubicin without interfering with oncological efficacy, the use of less toxic anthracycline derivatives and nutritional supplements. Evidence-based monitoring and screening are needed to identify early signs of cardiotoxicity that have been validated as surrogates of subsequent clinically significant cardiovascular disease before the occurrence of cardiac damage, in patients who may be at higher risk.

Mg(2+)-dependent gating of bacterial MgtE channel underlies Mg(2+) homeostasis.

The MgtE family of Mg(2+) transporters is ubiquitously distributed in all phylogenetic domains. Recent crystal structures of the full-length MgtE and of its cytosolic domain in the presence and absence of Mg(2+) suggested a Mg(2+)-homeostasis mechanism, in which the MgtE cytosolic domain acts as a 'Mg(2+) sensor' to regulate the gating of the ion-conducting pore in response to the intracellular Mg(2+) concentration. However, complementary functional analyses to confirm the proposed model have been lacking. Moreover, the limited resolution of the full-length structure precluded an unambiguous characterization of these regulatory divalent-cation-binding sites. Here, we showed that MgtE is a highly Mg(2+)-selective channel gated by Mg(2+) and elucidated the Mg(2+)-dependent gating mechanism of MgtE, using X-ray crystallographic, genetic, biochemical, and electrophysiological analyses. These structural and functional results have clarified the control of Mg(2+) homeostasis through cooperative Mg(2+) binding to the MgtE cytosolic domain.

The response of marine picoplankton to ocean acidification.

Since industrialization global CO(2) emissions have increased, and as a consequence oceanic pH is predicted to drop by 0.3-0.4 units before the end of the century - a process coined 'ocean acidification'. Consequently, there is significant interest in how pH changes will affect the ocean's biota and integral processes. We investigated marine picoplankton (0.2-2 µm diameter) community response to predicted end of century CO(2) concentrations, via a 'high-CO(2) ' (∼ 750 ppm) large-volume (11 000 l) contained seawater mesocosm approach. We found little evidence of changes occurring in bacterial abundance or community composition due to elevated CO(2) under both phytoplankton pre-bloom/bloom and post-bloom conditions. In contrast, significant differences were observed between treatments for a number of key picoeukaryote community members. These data suggested a key outcome of ocean acidification is a more rapid exploitation of elevated CO(2) levels by photosynthetic picoeukaryotes. Thus, our study indicates the need for a more thorough understanding of picoeukaryote-mediated carbon flow within ocean acidification experiments, both in relation to picoplankton carbon sources, sinks and transfer to higher trophic levels.

Microbial diversity and anaerobic hydrocarbon degradation potential in an oil-contaminated mangrove sediment.

BACKGROUND: Mangrove forests are coastal wetlands that provide vital ecosystem services and serve as barriers against natural disasters like tsunamis, hurricanes and tropical storms. Mangroves harbour a large diversity of organisms, including microorganisms with important roles in nutrient cycling and availability. Due to tidal influence, mangroves are sites where crude oil from spills farther away can accumulate. The relationship between mangrove bacterial diversity and oil degradation in mangrove sediments remains poorly understood. RESULTS: Mangrove sediment was sampled from 0-5, 15-20 and 35-40 cm depth intervals from the Suruí River mangrove (Rio de Janeiro, Brazil), which has a history of oil contamination. DGGE fingerprinting for bamA, dsr and 16S rRNA encoding fragment genes, and qPCR analysis using dsr and 16S rRNA gene fragment revealed differences with sediment depth. CONCLUSIONS: Analysis of bacterial 16S rRNA gene diversity revealed changes with depth. DGGE for bamA and dsr genes shows that the anaerobic hydrocarbon-degrading community profile also changed between 5 and 15 cm depth, and is similar in the two deeper sediments, indicating that below 15 cm the anaerobic hydrocarbon-degrading community appears to be well established and homogeneous in this mangrove sediment. qPCR analysis revealed differences with sediment depth, with general bacterial abundance in the top layer (0-5 cm) being greater than in both deeper sediment layers (15-20 and 35-40 cm), which were similar to each other.

Crystal structure of the CorA Mg2+ transporter.

The magnesium ion, Mg2+, is essential for myriad biochemical processes and remains the only major biological ion whose transport mechanisms remain unknown. The CorA family of magnesium transporters is the primary Mg2+ uptake system of most prokaryotes and a functional homologue of the eukaryotic mitochondrial magnesium transporter. Here we determine crystal structures of the full-length Thermotoga maritima CorA in an apparent closed state and its isolated cytoplasmic domain at 3.9 A and 1.85 A resolution, respectively. The transporter is a funnel-shaped homopentamer with two transmembrane helices per monomer. The channel is formed by an inner group of five helices and putatively gated by bulky hydrophobic residues. The large cytoplasmic domain forms a funnel whose wide mouth points into the cell and whose walls are formed by five long helices that are extensions of the transmembrane helices. The cytoplasmic neck of the pore is surrounded, on the outside of the funnel, by a ring of highly conserved positively charged residues. Two negatively charged helices in the cytoplasmic domain extend back towards the membrane on the outside of the funnel and abut the ring of positive charge. An apparent Mg2+ ion was bound between monomers at a conserved site in the cytoplasmic domain, suggesting a mechanism to link gating of the pore to the intracellular concentration of Mg2+.

Improvements to services at the European Nucleotide Archive.

The European Nucleotide Archive (ENA; http://www.ebi.ac.uk/ena) is Europe's primary nucleotide sequence archival resource, safeguarding open nucleotide data access, engaging in worldwide collaborative data exchange and integrating with the scientific publication process. ENA has made significant contributions to the collaborative nucleotide archival arena as an active proponent of extending the traditional collaboration to cover capillary and next-generation sequencing information. We have continued to co-develop data and metadata representation formats with our collaborators for both data exchange and public data dissemination. In addition to the DDBJ/EMBL/GenBank feature table format, we share metadata formats for capillary and next-generation sequencing traces and are using and contributing to the NCBI SRA Toolkit for the long-term storage of the next-generation sequence traces. During the course of 2009, ENA has significantly improved sequence submission, search and access functionalities provided at EMBL-EBI. In this article, we briefly describe the content and scope of our archive and introduce major improvements to our services.

Characteristics of academic medicine change agents as revealed by 4th-year medical students' reflections-on-practice.

PROBLEM: At present, formal training in adult learning principles, educational theories, and educational methods is not a core objective of most medical school curricula. As academic medical centers aim to develop the next generation of medical educators, students must be provided an opportunity to learn educational principles, engage in supervised teaching activities, and develop experiences in academic medicine to foster interest early in their development as educators. INTERVENTION: We developed a longitudinal medical education elective for fourth-year medical students, which was comprised of attending five seminars, leading 15 teaching sessions, formulating a medical education project, and writing a reflective essay. The seminars covered the history of medical education in the USA, adult learning theory and teaching principles, use of various teaching strategies and formats, construction and organization of curricula, effective models of evaluation and feedback provision, and principles of educational research. CONTEXT: This exploratory quasi-experiment incorporated a concurrent mixed methods data collection approach via pre- and post-seminar surveys and narrative reflection essay document analyses. IMPACT: Learners revealed favorable changes in their self-efficacy and self-perceived knowledge and attitudes towards medical education. A qualitative analysis of the reflective essays revealed five thematic categories (learning impacts, medical educator growth, leadership growth, medical school reflections, and future professional plans) and thirteen sub-categories. Students found many opportunities to implement high-quality educational projects, expressed commitment to pursuing teaching careers, and felt better equipped to assume a leadership role as change agents in academic medicine. LESSONS LEARNED: Findings are likely relevant to critical stakeholders who advocate for the inclusion of formal educational skills training into medical education curricula.

Too Hot to Handle: A Case of Fever of Unknown Origin.

Fever of unknown origin (FUO) is defined as a fever higher than 38.3ºC for at least three weeks. It remains a difficult diagnostic challenge and it carries well over 200 differential diagnoses, including infectious, rheumatologic and malignant etiologies. A methodological approach with clinical deductive reasoning and value-based investigative work-up can establish the diagnosis. This case is about a 76-year-old male with a past medical history of atrial fibrillation, bladder cancer treated with chemotherapy (now in remission) and hydronephrosis with recent ureteropelvic junction stent placement. He presented to the emergency department (ED) for worsening shortness of breath (SOB), weakness, and fevers. His initial workup was notable for a urinary tract infection which was treated with ceftriaxone. However, there was only a limited improvement in the fever. Diagnostic imaging was negative on initial review. He was evaluated by consultants of different specialities including infectious disease, rheumatology, and hematology. Ultimately, the decision was made to discharge the patient home on steroids with further outpatient workup. He returned four weeks later with worsening fever and was found to have new-onset mediastinal lymphadenopathy. A biopsy of an inguinal lymph node was obtained which showed high grade-B cell lymphoma. The patient was continued on prednisone and started on chemotherapeutic agents which included vincristine, rituximab and cyclophosphamide. Shortly after starting treatment, the patient and family elected for hospice. This case demonstrates the importance of continuously questioning the diagnosis at hand and of keeping an open mind when evaluating a patient with FUO.

Buprenorphine Use Trends Following Removal of Prior Authorization Policies for the Treatment of Opioid Use Disorder in 2 State Medicaid Programs.

Importance: State Medicaid programs have implemented initiatives to expand treatment coverage for opioid use disorder (OUD); however, some Medicaid programs still require prior authorizations (PAs) for filling buprenorphine prescriptions. Objective: To evaluate the changes in buprenorphine use for OUD among Medicaid enrollees in states that completely removed buprenorphine PA requirements. Design Setting and Participants: This retrospective cross-sectional study analyzed the immediate and trend changes on buprenorphine use during 2013 to 2020 associated with removal of PA requirements using a controlled interrupted time series analysis to account for autocorrelation. Data were collected from Medicaid State Drug Utilization Data for 2 states (California and Illinois) that completely removed a buprenorphine PA during the study period, and buprenorphine prescriptions for OUD treatment were identified among Medicaid enrollees. Main Outcomes and Measures: Quarterly total number of buprenorphine prescriptions for each state was calculated, and stratification analyses were conducted by dosage form (films and tablets). Results: Among the 2 state Medicaid programs (California and Illinois) that removed buprenorphine PAs, there was a total of 702 643 and 415 115 eligible buprenorphine prescription claims, respectively. After removing PA requirements for buprenorphine, there was an immediate increase that was not statistically significant (rate ratio [RR], 1.11; 95% CI, 0.76-1.61) in the number of all buprenorphine prescriptions in California and a statistically significant increase (RR, 6.99; 95% CI, 4.67-10.47) in the number of all buprenorphine prescriptions in Illinois relative to the change in the control states (Alabama, Florida, Idaho, Kansas, Mississippi, Nevada, South Dakota, and Wyoming). Additionally, there was a statistically significant decreasing trend in the number of all buprenorphine prescriptions in California (RR, 0.88; 95% CI, 0.82-0.94) and a statistically significant increasing trend in Illinois (RR, 1.11; 95% CI, 1.05-1.19) relative to the trend in control states. Conclusions and Relevance: In this cross-sectional study, removal of buprenorphine PA requirements was associated with a statistically significant increase in the number of buprenorphine prescription fills among Medicaid populations in 1 of the 2 included states.

NinaB is essential for Drosophila vision but induces retinal degeneration in opsin-deficient photoreceptors.

In animals, visual pigments are essential for photoreceptor function and survival. These G-protein-coupled receptors consist of a protein moiety (opsin) and a covalently bound 11-cis-retinylidene chromophore. The chromophore is derived from dietary carotenoids by oxidative cleavage and trans-to-cis isomerization of double bonds. In vertebrates, the necessary chemical transformations are catalyzed by two distinct but structurally related enzymes, the carotenoid oxygenase beta-carotenoid-15,15'-monooxygenase and the retinoid isomerase RPE65 (retinal pigment epithelium protein of 65 kDa). Recently, we provided biochemical evidence that these reactions in insects are catalyzed by a single enzyme family member named NinaB. Here we show that in the fly pathway, carotenoids are mandatory precursors of the chromophore. After chromophore formation, the retinoid-binding protein Pinta acts downstream of NinaB and is required to supply photoreceptors with chromophore. Like ninaE encoding the opsin, ninaB expression is eye-dependent and is activated as a downstream target of the eyeless/pax6 and sine oculis master control genes for eye development. The requirement for coordinated synthesis of chromophore and opsin is evidenced by analysis of ninaE mutants. Retinal degeneration in opsin-deficient photoreceptors is caused by the chromophore and can be prevented by restricting its supply as seen in an opsin and chromophore-deficient double mutant. Thus, our study identifies NinaB as a key component for visual pigment production and provides evidence that chromophore in opsin-deficient photoreceptors can elicit retinal degeneration.

The phage shock protein PspA facilitates divalent metal transport and is required for virulence of Salmonella enterica sv. Typhimurium.

The phage shock protein (Psp) system is induced by extracytoplasmic stress and thought to be important for the maintenance of proton motive force. We investigated the contribution of PspA to Salmonella virulence. A pspA deletion mutation significantly attenuates the virulence of Salmonella enterica serovar Typhimurium following intraperitoneal inoculation of C3H/HeN (Ity(r) ) mice. PspA was found to be specifically required for virulence in mice expressing the natural resistance-associated macrophage protein 1 (Nramp1) (Slc11a1) divalent metal transporter, which restricts microbial growth by limiting the availability of essential divalent metals within the phagosome. Salmonella competes with Nramp1 by expressing multiple metal uptake systems including the Nramp-homologue MntH, the ABC transporter SitABCD and the ZIP family transporter ZupT. PspA was found to facilitate Mn(2+) transport by MntH and SitABCD, as well as Zn(2+) and Mn(2+) transport by ZupT. In vitro uptake of (54) Mn(2+) by MntH and ZupT was reduced in the absence of PspA. Transport-deficient mutants exhibit reduced viability in the absence of PspA when grown under metal-limited conditions. Moreover, the ZupT transporter is required for Salmonella enterica serovar Typhimurium virulence in Nramp1-expressing mice. We propose that PspA promotes Salmonella virulence by maintaining proton motive force, which is required for the function of multiple transporters mediating bacterial divalent metal acquisition during infection.

Biomechanical evaluation of four different transosseous-equivalent/suture bridge rotator cuff repairs.

PURPOSE: Evaluate the biomechanical behavior of four variants of the transosseous-equivalent/suture bridge (TOE/SB) repair. METHODS: Four suture bridge (SB) constructs were created using 24 sheep infraspinatus tendon-humerus constructs (n = 6 per technique). The groups were (1) Knotted Standard Suture Bridge (Standard SB)--suture bridge with two medial mattress stitches, (2) Knotted Double Suture Bridge (Double SB)--four medial mattress stitches, (3) Untied Suture Bridge with Medial FT Anchors (Untied SB with FT)--two medial mattress stitches without knots, and (4) Untied Suture Bridge with PushLocks (Untied SB with Pushlocks)--two medial mattress stitches without knots. The contact area footprint was measured with an electronic pressure film prior to dynamic mechanical testing for gapping and testing to failure. RESULTS: The Double SB produced the greatest contact area footprint compared to the other techniques, which did not differ. The Double SB repair with a mean failure load of 456.9N was significantly stronger than the Untied SB with Pushlocks repair at 300N (P = 0.023), the standard SB repair at 295N (P = 0.019), and lastly the Untied SB with FT repair at 284N (P = 0.011). No differences were detected between the two mattress stitch standard SB repair with knots and the knotless two mattress stitch repairs (Untied SB with FT and Untied SB with Pushlocks). Gaps developed during cyclic loading in all repairs apart from the Double SB repair. CONCLUSIONS: The transosseous-equivalent/suture bridge repair with 4 stitches tied in the medial row and maximal lateral suture strand utilization (Double SB) outperformed all other repairs in terms of failure load, tendon-bone contact, and gapping characteristics. The presence of knots in the medial row did not change tendon fixation with respect to failure load, contact area or gapping characteristics.

Necrotic Ulcers Secondary to Apomorphine Infusion.

Background: Apomorphine is a potent dopamine agonist used in the treatment of advanced and fluctuating Parkinson's Disease. However the need for its subcutaneous infusion can lead to skin reactions. Phenomenology Shown: We illustrate necrotic ulcers at infusion sites as a rare event during continuous subcutaneous apomorphine infusion. Educational value: This case demonstrates the rare adverse event of necrotic ulcers in a patient with long term apomorphine infusion.

Trends in Use of Prescription Nonsteroidal Anti-inflammatory Medications Before vs After Implementation of a Florida Law Restricting Opioid Prescribing for Acute Pain.

Importance: Previous research has shown an immediate reduction in new opioid users and use after implementation of the opioid supply restriction laws. Assessment of the association between opioid restrictions and alternative treatment options, such as nonsteroidal anti-inflammatory drugs (NSAIDs), is needed to evaluate potential unintended consequences for patients requiring analgesia. Objective: To evaluate the association between an opioid restriction law in Florida and use of prescription NSAIDs. Design, Setting, and Participants: This quality improvement study used interrupted time series analyses accounting for autocorrelation to estimate immediate and trend changes in the prescribing and use of prescription NSAIDs in Florida before and after implementation of a state law limiting opioid prescriptions to a 3-day supply. Participants were enrollees in a single private health plan of a large university and health system employer in Florida from January 2015 to June 2019. Exposures: Prescriptions for NSAIDs, ascertained from pharmacy claims data. Main Outcomes and Measures: The following outcomes were calculated monthly per 1000 plan enrollees: (1) number of NSAID users; (2) mean days' supply of NSAIDs per prescription; and (3) mean number of NSAID prescriptions. Individuals were classified as NSAID users if they had at least 1 NSAID prescription in a given month. Analysis was stratified by route of NSAID administration (oral or nonoral). Results: Among 46 783 NSAID users with 79 089 NSAID prescriptions during the study period, the median age was 47 years (interquartile range, 35-57 years). After implementation of the opioid restriction law, the number of NSAID users immediately increased, but the difference was not significant (change, 0.82 per 1000 patients; 95% CI, -0.67 to 2.30 per 1000 patients). No significant change in the days' supply of oral NSAID users occurred (change, 0.21 days per prescription; 95% CI, -1.66 to 2.08 days per prescription). Before implementation of the law, there was a nonsignificant decreasing trend in NSAID prescriptions (rate of change, -0.03 per month per 1000 enrollees; 95% CI, -0.13 to 0.07 per month per 1000 enrollees; after implementation, there was a nonsignificant increase in the number of oral and nonoral NSAID prescriptions (change, 1.49 per 1000 enrollees; 95% CI, -3.38 to 6.37 per 1000 enrollees). Conclusions and Relevance: In this quality improvement study, prescribing and use of prescription NSAIDs did not increase after implementation of a law restricting opioid analgesic prescriptions in Florida. These findings suggest possible greater use of over-the-counter NSAIDs after implementation of the law, but further research is needed to evaluate changes in the use of nonopioid analgesics and alternative pain therapies.

Chronic Opioid Therapy: A Scoping Literature Review on Evolving Clinical and Scientific Definitions.

The management of chronic noncancer pain (CNCP) with chronic opioid therapy (COT) is controversial. There is a lack of consensus on how COT is defined resulting in unclear clinical guidance. This scoping review identifies and evaluates evolving COT definitions throughout the published clinical and scientific literature. Databases searched included PubMed, Embase, and Web of Science. A total of 227 studies were identified from 8,866 studies published between January 2000 and July 2019. COT definitions were classified by pain population of application and specific dosage/duration definition parameters, with results reported according to PRISMA-ScR. Approximately half of studies defined COT as "days' supply duration >90 days" and 9.3% defined as ">120 days' supply," with other days' supply cut-off points (>30, >60, or >70) each appearing in <5% of total studies. COT was defined by number of prescriptions in 63 studies, with 16.3% and 11.0% using number of initiations or refills, respectively. Few studies explicitly distinguished acute treatment and COT. Episode duration/dosage criteria was used in 90 studies, with 7.5% by Morphine Milligram Equivalents + days' supply and 32.2% by other "episode" combination definitions. COT definitions were applied in musculoskeletal CNCP (60.8%) most often, and typically in adults aged 18 to 64 (69.6%). The usage of ">90 days' supply" COT definitions increased from 3.2 publications/year before 2016 to 20.7 publications/year after 2016. An increasing proportion of studies define COT as ">90 days' supply." The most recent literature trends toward shorter duration criteria, suggesting that contemporary COT definitions are increasingly conservative. PERSPECTIVE: This study summarized the most common, current definition criteria for chronic opioid therapy (COT) and recommends adoption of consistent definition criteria to be utilized in practice and research. The most recent literature trends toward shorter duration criteria overall, suggesting that COT definition criteria are increasingly stringent.