Journal of pharmacy practice最新文献

{"title":"Nationwide Survey to Characterize and Compare the Research Experiences of American Society of Health-System Pharmacists-Accredited Postgraduate Year One Pharmacy Residency Programs.","authors":"Andrea Dressler, Robert W Seabury, William Darko, Wesley D Kufel, Jeffrey M Steele, Courtney Kelly, Ryan Andrew, Zachary Hayes, Christopher D Miller, Katie A Parsels","doi":"10.1177/08971900241273223","DOIUrl":"10.1177/08971900241273223","url":null,"abstract":"<p><p><b>Background:</b> Many Postgraduate Year One (PGY1) Pharmacy residencies provide research training however, details of this training are not well described. Publication rates have been utilized to assess residency research learning experiences. Higher publication rates have been reported by programs that have implemented a structured research learning experience. <b>Objective:</b> The primary objective was to identify differences in the research learning experiences for American Society of Health-System Pharmacists (ASHP) accredited PGY1 Pharmacy residencies with reported resident publication rates of ≥20% vs <20%. <b>Methods:</b> This survey was distributed to PGY1 Pharmacy residency program directors (RPDs). Seven sections were analyzed to identify research learning experience differences between programs with reported publication rates of ≥20% vs <20%: (1) program characteristics/research outcomes; (2) involved individuals; (3) requirements; (4) learning experience structure; (5) educational methods; (6) formal education; (7) barriers/RPD perceptions. Variables with <i>P</i> < 0.05 on logistic regression were considered statistically significant. <b>Results:</b> The survey response rate was 31.3% (308/984). Significant positive predictors for reported publication rates of ≥20% were: involved individuals: research director/coordinator, individuals trained in statistics, non-pharmacy medical staff; requirements: Collaborative Institutional Training Initiative training, research seminars/training courses, research manuscript; learning experience structure: research committee; educational methods: didactic residency-led lectures/courses, formal workshops, self-taught online modules; and formal education: manuscript preparation. <b>Conclusion:</b> This study suggests there are differences in the research learning experiences at PGY1 Pharmacy residencies with reported resident publications rates of ≥20% vs <20%. We encourage PGY1 Pharmacy residency programs to consider implementing elements associated with reported resident publication rates of ≥20%.</p>","PeriodicalId":16818,"journal":{"name":"Journal of pharmacy practice","volume":" ","pages":"128-140"},"PeriodicalIF":1.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142008957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Pilot Study Describing DOAC Level Results and Association With Clinical Outcomes.","authors":"Brittni Gochnauer, Anne Rodino, Sarah Russell, Kristin Bradley","doi":"10.1177/08971900241262363","DOIUrl":"10.1177/08971900241262363","url":null,"abstract":"<p><p><b>Purpose:</b> Describe direct oral anticoagulant (DOAC) level ordering and interpretation practices in association with clinical outcomes at a vascular medicine clinic. <b>Methods:</b> This study was a retrospective, observational study including patients who had a DOAC level ordered and assessed while on DOAC therapy. The primary outcome was the proportion of DOAC levels within previously reported ranges. Secondary outcomes included thrombotic events, major and clinically relevant non-major bleeding events, and the proportion of DOAC level results which prompted a change in the therapeutic plan. <b>Results:</b> A total of 43 patients who had a DOAC level ordered while on DOAC therapy were included in the study. More patients were on apixaban than other DOACs, and the most common indication for anticoagulation was deep vein thrombosis (DVT) or pulmonary embolism (PE). The most common reasons for ordering DOAC levels included history of gastric bypass (n = 20) and drug-drug interactions (n = 8). Most patients on apixaban had in-range levels (n = 24) compared to out of-range levels (5 patients). More patients on rivaroxaban had a level out-of-range (n = 10) than in-range (n = 4). One patient had a DVT, resulting in hospitalization and change in DOAC therapy. Two patients had bleeding events, with 1 hospitalization and change in DOAC therapy. DOAC level results also prompted changes in therapeutic plans for 9 of the patients. <b>Conclusion:</b> DOAC level results did not always correlate with expected outcomes, and further research is warranted to clarify which clinical situations may benefit from ordering DOAC levels.</p>","PeriodicalId":16818,"journal":{"name":"Journal of pharmacy practice","volume":" ","pages":"149-154"},"PeriodicalIF":1.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141331223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diabetes Care in A Safety Net Hospital: Impact of a Pharmacist Transitional Care Service.","authors":"Shanelle M Murray, Laura M Traynor, Larissa Carli, Heather Rhodes, Ann M Brigino, Rajani M Wikelius","doi":"10.1177/08971900241256776","DOIUrl":"10.1177/08971900241256776","url":null,"abstract":"<p><p><b>Background:</b> Diabetes is associated with increased risk of hospital readmission and imposes a significant economic burden on patients and healthcare systems. Literature suggests that pharmacist-led transitions-of-care (TOC) services reduce hospital readmissions and improve patient outcomes and data within safety-net hospitals is limited. <b>Methods:</b> This was a single-center evaluation to assess the impact of pharmacist-led diabetes TOC services on hospital readmissions among diabetes patients vs standard care (SC). The evaluation included patients admitted from 11/1/2021-2/28/2022 and 10/19/2022-2/28/2023 who had a primary diagnosis of diabetes mellitus, were admitted for a diabetes-related reason, or were seen by the endocrine consult service during admission. The primary outcome was 30-day readmissions. Secondary outcomes included time to readmission, readmission diagnosis, changes in HbA1c, completion of follow-up visits, and number of pharmacist interventions at follow-up. <b>Results:</b> There were 109 patients included (TOC n = 65; SC n = 44) and 13.8% (9/65) of TOC and 18.2% (8/44) of SC patients readmitted within 30 days (<i>P</i> = .235). Average time to readmission was 15.3 days in the TOC and 10.4 days in the SC cohorts. There were no diabetes-related readmissions in the TOC cohort. Over 60% (5/8) of readmissions in the SC cohort were diabetes-related. The average change in HbA1c was -2.5% in the TOC cohort and -1.2% in the SC cohort, <i>P</i> = .046. Approximately 51% of TOC patients completed an outpatient follow-up visit and nearly 70% of those patients had an intervention made at that time. <b>Conclusion:</b> Pharmacist-led diabetes TOC services within a safety-net hospital may reduce hospital readmissions and improve clinical outcomes.</p>","PeriodicalId":16818,"journal":{"name":"Journal of pharmacy practice","volume":" ","pages":"122-127"},"PeriodicalIF":1.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141093613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alpha2 Agonist Use in Critically Ill Adults: A Focus on Sedation and Withdrawal Prevention.","authors":"Ashley Schuler, Connie H Yoon, Erica Caffarini, Alexander Heine, Alyssa Meester, Danielle Murray, Angela Harding","doi":"10.1177/08971900241263171","DOIUrl":"10.1177/08971900241263171","url":null,"abstract":"<p><p>The management of sedation in critically ill adults poses a unique challenge to clinicians. Dexmedetomidine, an α₂ agonist, has a unique mechanism and favorable pharmacokinetics, making it an attractive intravenous option for sedation and delirium in the intensive care unit. However, patients may be at risk for withdrawal with prolonged use, adding to the complexity of sedation and agitation management in this patient population. Enteral α₂ agents have the benefit of cost savings and ease of administration, thus playing a role in the ability to decrease intravenous sedative use and prevent dexmedetomidine withdrawal. Clonidine and guanfacine are the two most common enteral α₂ agents utilized for this purpose, however, there is a paucity of evidence regarding the comparative benefit between the two agents. The decision to use one vs the other agent should be determined based on their differing pharmacology, pharmacokinetics, and side effect profile. The most effective dosing strategy for these agents is also unknown. Ultimately, more robust literature is required to determine enteral α₂ agonists place in therapy. This narrative review evaluates the currently available literature on the use of α₂ agonists in critically ill adults with an emphasis on sedation, delirium, and withdrawal.</p>","PeriodicalId":16818,"journal":{"name":"Journal of pharmacy practice","volume":" ","pages":"155-167"},"PeriodicalIF":1.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141440546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a Medication-Use Evaluation Template for Andexanet Alfa in the Reversal of Anticoagulation With Factor Xa Inhibitors.","authors":"Toni Fera, Allison Burnett, Jessica Grandoni, Mary R Moore, Barbara B Nussbaum, Charles V Pollack, Anne E Rose, Sarah A Spinler, Michael B Streiff, Charles J Turck, John Fanikos","doi":"10.1177/08971900241263164","DOIUrl":"10.1177/08971900241263164","url":null,"abstract":"<p><p>Medication-use evaluations are meant to ensure that medication-use processes are consistent with prevailing standards of care, assure optimal use of therapy, and reduce the risk of medication-related problems. Reversal agents for direct oral anticoagulants are a worthy focus for medication-use evaluations for reasons of efficacy, safety, and cost. A multidisciplinary team of experts developed 2 medication-use evaluation templates illustrating the application of professional society guidelines to the appropriate use of andexanet alfa.</p>","PeriodicalId":16818,"journal":{"name":"Journal of pharmacy practice","volume":" ","pages":"7-12"},"PeriodicalIF":1.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11639411/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141731298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Temporal Effect of CYP3A4/5 Induction on Ticagrelor's Pharmacodynamic Effects: A Case Series.","authors":"Thomas W Szymanski, Matthew R Rockhold, Jordan L Lacoste","doi":"10.1177/08971900241273095","DOIUrl":"10.1177/08971900241273095","url":null,"abstract":"<p><p>Ticagrelor is contraindicated in combination with cytochrome P450 3A4 and 3A5 enzyme (CYP3A4/5) inducers due to increased clearance, causing diminished antiplatelet effects. The emergent nature of acute coronary syndromes (ACS) may preclude scrutinization of home medications before P2Y₁₂ inhibitor administration. The purpose of this case series is to establish the temporal impact of CYP3A4/5 enzyme induction on ticagrelor's pharmacodynamic effect by utilizing VerifyNow platelet aggregation studies. This was a retrospective case series of three patients who were taking a CYP3A4/5-inducing medication and loaded with ticagrelor for ACS. The duration of ticagrelor's antiplatelet effect was dramatically shortened in the presence of background CYP3A4/5 induction. The offset of antiplatelet effect, defined by platelet reactivity units (PRU), was 10-24 hours in the presence of CYP3A4/5 enzyme induction compared to the anticipated 36-48 hours. This was consistent across CYP3A4/5-inducing medications including carbamazepine, phenobarbital, and phenytoin. This study demonstrates rapid return of platelet function after a ticagrelor loading dose in the presence of CYP3A4/5-inducing medications. Monitoring of PRU every 6-12 hours with subsequent loading with clopidogrel or prasugrel should be considered. Larger scale studies are warranted to confirm these results.</p>","PeriodicalId":16818,"journal":{"name":"Journal of pharmacy practice","volume":" ","pages":"204-207"},"PeriodicalIF":1.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141988203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Clinical Pharmacists in the Inflammatory Bowel Disease Clinic.","authors":"Ashley Lopez, Melissa Snider, Allison McFerran, Ariel Holland, Aaron Bagnola, John Mellet, Junan Li, Madalina Butnariu","doi":"10.1177/08971900241264339","DOIUrl":"10.1177/08971900241264339","url":null,"abstract":"<p><p><b>Background:</b> Limited evidence exists regarding pharmacist involvement and impact in inflammatory bowel disease (IBD) interdisciplinary clinic care models. The purpose is to describe pharmacist utilization in an interdisciplinary IBD clinic and evaluate clinical impact on patient quality of life. <b>Methods:</b> This was a retrospective cohort study comparing outcomes in patients with Crohn's disease initiated on therapy when the implementation of pharmacy services began (Early Phase) to the expansion of pharmacy services (Recent Phase). The primary outcome compared the proportion of patients referred to a pharmacist and those achieving a Harvey-Bradshaw Index (HBI) reduction of ≥3 points after therapy initiation. <b>Results:</b> 50 patients were included in the Early Phase and 43 patients in the Recent Phase. Utilization in pharmacy referrals increased from 48% (n = 24) in the Early Phase to 72% (n = 31) in the Recent Phase (<i>P</i> = 0.03). The proportion of patients achieving a HBI reduction of ≥3 points increased from 35% (n = 14) in the Early Phase to 51% (n = 18) in the Recent Phase (<i>P</i> = 0.23). Results also found a greater proportion of patients remaining steroid free in the Recent Phase compared to the Early Phase (50% vs 63%; <i>P</i> = 0.01) and C-reactive protein (CRP) improved significantly in the Recent Phase (-11) compared to (-3) in the Early Phase (<i>P</i> = 0.006). <b>Conclusion:</b> The utilization of pharmacists in an interdisciplinary IBD clinic increased and showed to impact patient care through improving symptom relief as seen by the achievement rate of the HBI score reduction, reducing steroid use after therapy initiation, and making clinically significant interventions.</p>","PeriodicalId":16818,"journal":{"name":"Journal of pharmacy practice","volume":" ","pages":"52-59"},"PeriodicalIF":1.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141731299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Variability in Antimicrobial Prescribing Across Five Ambulatory Settings Within a Large Integrated Health System.","authors":"Alex D Taylor, Kaitlyn R Rivard, Andrea M Pallotta, Heather L Daniels, Thomas G Fraser, Baruch S Fertel, Simon Lam, Janet Y Wu","doi":"10.1177/08971900241271956","DOIUrl":"10.1177/08971900241271956","url":null,"abstract":"<p><p><b>Background:</b> Lack of access to timely, detailed antibiotic use data has limited ambulatory antibiotic stewardship efforts. Antibiotic utilization is tracked across ambulatory care sites and emergency departments (ED) within a large integrated health system. <b>Methods:</b> This is a retrospective cohort analysis from June 1, 2019 to May 31, 2020 comparing antibiotic prescribing for all patients with ICD-10 diagnosis codes for cystitis, otitis media, pharyngitis, sinusitis, and upper respiratory tract infections (URTIs) among five ambulatory care departments across northeast Ohio and southeast Florida locations: ED, Urgent Care (UC), On-Demand Telehealth (TEL), Pediatrics (PED), and Primary Care (PC). <b>Results:</b> A total of 261,947 encounters were included (ED:56,766, UC:92,749, TEL:8,783, PED:29,151, PC:74,498) for the treatment of cystitis (30,932), otitis media (22,094), pharyngitis (59,964), sinusitis (53,693), or URTI (95,264). The population was 63% female with a median age of 34.2 years [12.8-56.3]. A total of 17% of patients had documented penicillin allergies and 18% of patients with pharyngitis received Group A <i>Streptococcus</i> (GAS) testing. Antibiotics were prescribed in 44% of encounters (ED:21,746 [38%], UC:45,652 [49%], TEL:4,622 [53%], PED:10,909 [37%], PC:33,547 [45%]; <i>P</i> < 0.001). Guideline concordant antibiotics were prescribed in 65% of encounters (ED:14,338 [66%], UC:31,532 [69%], TEL:3,869 [84%], PED:8,212 [75%], PC:17,263 [51%]; <i>P</i> < 0.001). <b>Conclusions:</b> Observed rates of antibiotic and guideline concordant antibiotic prescribing were similar to national published rates of antibiotic prescribing in the ambulatory setting. The variability in antibiotic prescribing demonstrates opportunities for targeted outpatient stewardship efforts. Timely antibiotic tracking tools can facilitate ambulatory antimicrobial stewardship activities.</p>","PeriodicalId":16818,"journal":{"name":"Journal of pharmacy practice","volume":" ","pages":"60-68"},"PeriodicalIF":1.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Problematic Pharmacokinetics: A Case of Recurrent Pancreatitis Post Discontinuation of a Glucagon-Like Peptide 1 Receptor Agonists.","authors":"Zachary P Morehouse, Jack D Ledford","doi":"10.1177/08971900241273188","DOIUrl":"10.1177/08971900241273188","url":null,"abstract":"<p><p>Glucagon-like peptide 1 receptor agonists (GLP-1RA) are guideline recommended agents for the treatment of type 2 diabetes mellitus (T2DM) and select agents (liraglutide and semaglutide) are FDA approved as anti-obesity pharmacotherapy options. These drugs act on the incretin hormone system within the body to revive insulin excretion, delay gastric emptying, and inhibit the production of glucagon from pancreatic alpha cells. Acute pancreatitis is a serious condition that may have a fatal outcome. It has been shown, and is now part of the prescribing information label, that GLP-1RA agents can cause changes in the pancreas that may ultimately lead to pancreatitis. We describe the case of a 53-year-old female patient with uncontrolled type II diabetes mellitus, who experienced multiple episodes of pancreatitis, from what we suspect was due to repeated exposure to the GLP-1 RA agent, semaglutide. After discontinuation of semaglutide, our patient experienced another episode of pancreatitis roughly 15-week later; which we believe may be due to the patient experiencing the effects of a smoldering pancreas brought on by repeated injury and prolonged circulation of semaglutide post-discontinuation.</p>","PeriodicalId":16818,"journal":{"name":"Journal of pharmacy practice","volume":" ","pages":"187-192"},"PeriodicalIF":1.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141897660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Phenytoin Ataxia Enigma Unveiled \"A Case Report''.","authors":"Avinash Khadela, Bhavarth Dave, Yatvi Premal, Nishi Patel, Devang Sadhwani","doi":"10.1177/08971900241262379","DOIUrl":"10.1177/08971900241262379","url":null,"abstract":"<p><p><b>Background:</b> Phenytoin (PHT) has been approved for the treatment of epilepsy. It belongs to the category of medications with a limited therapeutic window and requires therapeutic drug monitoring (TDM). PTH has been observed to induce a variety of Adverse drug reactions (ADRs) including ataxia, dystonia, nystagmus, dyskinesia, etc. Phenytoin-induced ataxia is an uncommonly observed ADR of Phenytoin whose reports are extremely limited. <b>Case:</b> Herein, we present a case report of a 16-year-old Asian patient with a past history of epilepsy that was admitted to a tertiary care hospital due to the development of ataxia, giddiness, and vomiting when taking Phenytoin in addition to Oxcarbazepine, Clobazam, and Levetiracetam to treat seizures. On admission, Magnetic resonance imaging (MRI) findings revealed bilateral variable cerebrospinal fluid (CSF) lesions in the parieto-occipital region of the periventricular area (periventricular leukomalacia). Additionally, serum Phenytoin levels were observed to be in the toxic range (40 μg/mL) due to which physicians confirmed the ADR to be due to Phenytoin toxicity. Thus, the Phenytoin drug was discontinued in the patient gradually and he was continued on clobazam, oxcarbazepine, and brivaracetam which led to reversal of the ADR in the patient. <b>Conclusion:</b> In this case, ataxia resulted from Phenytoin overdose, as confirmed by MRI and serum tests suggesting that TDM of Phenytoin is essential to prevent ADRs. Given the scarcity of ataxia cases caused by Phenytoin, awareness is lacking within the scientific community. Our aim is to provide insights to promote better monitoring and patient-centered treatment outcomes for epileptic patients.</p>","PeriodicalId":16818,"journal":{"name":"Journal of pharmacy practice","volume":" ","pages":"180-186"},"PeriodicalIF":1.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141317573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}