Impact of CancelRx on discontinuation of controlled substance prescriptions: an interrupted time series analysis.

BACKGROUND: Prescription opioid misuse is a serious national crisis; in 2018 the top drugs involved in prescription overdose deaths included pain medications (opioids), benzodiazepines, and stimulants. Health information technology (health IT) provides a means to address this crisis through technologies that streamline the prescribing and discontinuation process. CancelRx is a health IT function that communicates when medications, such as controlled substances, are discontinued at the clinic and therefore should not be filled at the pharmacy. Prior to CancelRx, the communication of discontinued medications was a manual process, requiring the patient or a clinic staff member to personally contact the pharmacy to inform them of the change. The objective of this study was to assess how controlled substance medication discontinuations were communicated over time, before and after the implementation of CancelRx. METHODS: Secondary data from a midwestern academic health system electronic health record and pharmacy platform were collected 12-months prior to CancelRx implementation and for 12-months post implementation. The study utilized an interrupted time series analysis (ITSA) to capture the percentage of controlled substance medications that were discontinued in the clinic's electronic health record and discontinued in the pharmacy's dispensing software. The ITSA plotted the percentage of successful discontinuation messages over time, particularly after the health system's implementation of CancelRx, a novel technology. RESULTS: After CancelRx implementation there was an immediate (change = 77.7 percentage point) and significant (p < 0.001) increase in the number of controlled substance medications that were successfully discontinued at the pharmacy after being discontinued in the clinic. This change was sustained in the year following CancelRx (slope = 0.03 pp, 95% CI - 0.050 to 0.110) and did not revert to pre-CancelRx levels. The health IT functionality was able to effectively complete discontinuation tasks and potentially reduce workload for clinic staff. CONCLUSIONS: Overall, this study demonstrates the role that technology can play in promoting communication between clinics and pharmacies, especially when medications such as controlled substances are discontinued.

TNF inhibitor induced alopecia: an unusual form of psoriasiform alopecia that breaks the Renbök mold.

TNF-α-inhibitors are known to induce skin adverseeffects including psoriasis and alopecia areata. Here, wedescribe a unique pattern of hair loss that has psoriaticand alopecia areata-like features. Diagnosis requiresclinical-pathologic correlation and is supportedby increased catagen/telogen hairs, psoriasiformepidermal hyperplasia, perifollicular lymphocyticinfiltrate, and the presence of eosinophils and plasmacells. Although there are no treatment consensusguidelines, management options include stoppingtherapy, switching to a different TNF-α inhibitor orustekinumab (in severe cases), or continuing TNF-αinhibitor therapy with addition of topical, intralesional,or systemic immunosuppressants.

CancelRx: a health IT tool to reduce medication discrepancies in the outpatient setting.

OBJECTIVE: Medication list discrepancies between outpatient clinics and pharmacies can lead to medication errors. Within the last decade, a new health information technology (IT), CancelRx, emerged to send a medication cancellation message from the clinic's electronic health record (EHR) to the outpatient pharmacy's software. The objective of this study was to measure the impact of CancelRx on reducing medication discrepancies between the EHR and pharmacy dispensing software. MATERIALS AND METHODS: CancelRx was implemented in October 2017 at an academic health system. For 12 months prior, and 12 months after CancelRx implementation, data were collected on discontinued medications in the health system's EHR and whether those prescriptions were successfully discontinued in the pharmacy's dispensing software. An interrupted time series analysis was conducted to model the occurrence of prescriptions successfully discontinued over time. RESULTS: There was an immediate (lag = 0), significant (P < 0.001), and sustained (post-implementation slope 0.02) increase in the proportion of successful medication discontinuations after CancelRx implementation (from 34% to 93%). CancelRx had variable impact based on whether the clinic was primary care (71.4% change prepost) or specialty care (53.9% change prepost). CancelRx reduced the time between when a medication was discontinued in the clinic EHR and pharmacy dispensing software. CONCLUSION: CancelRx automated a manual process and illustrated the role for health IT in communicating medication discontinuations between clinics and pharmacies. Overall, CancelRx had a marked benefit on medication list discrepancies and illustrated how health IT can be used across different settings to improve patient care.

AMP-activated protein kinase suppresses LXR-dependent sterol regulatory element-binding protein-1c transcription in rat hepatoma McA-RH7777 cells.

AMP-activated protein kinase (AMPK) is an intracellular fuel sensor that plays a key role in regulating fatty acid synthesis in liver. Sterol regulatory element-binding protein (SREBP)-1c is a master regulator of hepatic lipogenic gene expression. It has long been documented that AMPK activation suppresses hepatic SREBP-1 mRNA and nuclear SREBP-1 protein. But the mechanism remains undefined. In this study we investigated the molecular mechanisms by which AMPK downregulates hepatic SREBP-1c mRNA using a novel model cell line McA-RH7777. We found that AMPK is robustly activated in rat hepatoma McA-RH7777 cells treated with two widely used AMPK activators, AICAR and metformin, and AMPK activation sharply suppresses SREBP-1c mRNA and nuclear SREBP-1c protein, but not SREBP-1a mRNA derived from the same gene. These inhibitory effects are reversed by the AMPK inhibitor Compound C or 8-BrAMP, demonstrating the requirement of AMPK in the suppression of SREBP-1c mRNA and nuclear SREBP-1c protein by AICAR and metformin. AMPK does not enhance SREBP-1c mRNA degradation in the presence of the general transcription inhibitor actinomycin D; instead it inhibits SREBP-1c promoter activity in a luciferase reporter assay. AMPK-mediated inhibition of SREBP-1c promoter activity can also be abrogated by the AMPK inhibitor Compound C. Furthermore AMPK activation significantly attenuates the synthetic liver X receptor (LXR) ligand T0901317-induced SREBP-1c promoter activity. AMPK also inhibits cleavage of LXR ligand-induced SREBP-1c precursor. We conclude that AMPK suppresses hepatic SREBP-1c mRNA expression by inhibiting LXR-dependent SREBP-1c transcription via inhibition of endogenous LXR ligand production and by inhibiting SREBP-1c processing in McA-RH7777 cells.

Chronic activation of AMP-activated protein kinase-alpha1 in liver leads to decreased adiposity in mice.

To assess the metabolic effects of chronic activation of AMP-activated protein kinase (AMPK) in liver, we generated a new transgenic (Tg) mouse model expressing constitutively active (CA)-AMPK-alpha1 in liver. In the short-term activation, the TgCA-AMPK-alpha1 mice exhibited minimal phenotype, but the Tg liver had elevated sterol regulatory element-binding protein (SREBP)-2 mRNA level and a parallel increase in transcripts of its target genes. UCP2 mRNA level was elevated. In the long-term activation, the TgCA-AMPK-alpha1 mice had markedly reduced white fat mass. The Tg liver had reduced mRNA expression of SREBP-1c and its target genes. Remarkably, the Tg mice were resistant to a high-fat diet-induced obesity. These data suggest that short-term chronic activation of AMPK-alpha1 in liver leads to compensatory increase in lipogenic gene expression due to increased SREBP-2 expression, and long-term chronic activation of AMPK-alpha1 decreases expression of SREBP-1c and its target genes, which results in reduced fat storage.

Mechanism of AMPK suppression of LXR-dependent Srebp-1c transcription.

Activation of AMP-activated protein kinase (AMPK) inhibits hepatic fatty acid synthesis by suppressing sterol regulatory element-binding protein (SREBP)-1c, a master regulator of hepatic lipogenic gene expression. Using a model cell line rat hepatoma McA-RH7777 (CRL-1601) that mimics the behavior of the intact liver by producing high levels of SREPB-1c mRNA and protein, we previously showed that AMPK suppresses hepatic Srebp-1c transcription by inhibiting endogenous liver X receptor (LXR) ligand production and SREBP-1c processing. However, whether AMPK directly inhibits ligand-induced LXR activity remained undetermined. In this study we used a series of mutant Srebp-1c promoter linked to a luciferase reporter to determine the inhibitory mechanism in rat hepatoma McA-RH7777 cells. AMPK activation by either AICAR or metformin decreases Srebp-1c promoter activity by about 75%. Normally, the synthetic LXR ligand T0901317 compound increases the wild-type Srebp-1c promoter activity by about 3-fold, which is similar to that observed in the presence of AICAR or metformin. When endogenous LXR ligand production was blocked by the potent HMG CoA reductase inhibitor compactin, T0901317-induced Srebp-1c promoter activity was decreased by AICAR or metformin treatment. In the mutant Srebp-1c promoter in which two LXR elements are intact but the sterol regulatory element (SRE) is disrupted, the fold inductions of the promoter activity by T0901317 without AMPK activators are significantly higher than those with AMPK activators. Furthermore, AMPK activation attenuates induction of endogenous SREBP-1c mRNA by T0901317. These results indicate that AMPK directly inhibits ligand-induced LXR activity in addition to blocking production of endogenous LXR ligands.