Clinical Pharmacology : Advances and Applications最新文献

{"title":"Population pharmacokinetics of pomalidomide in patients with relapsed or refractory multiple myeloma with various degrees of impaired renal function.","authors":"Yan Li,&nbsp;Xiaomin Wang,&nbsp;Edward O'Mara,&nbsp;Meletios A Dimopoulos,&nbsp;Pieter Sonneveld,&nbsp;Katja C Weisel,&nbsp;Jeffrey Matous,&nbsp;David S Siegel,&nbsp;Jatin J Shah,&nbsp;Elisabeth Kueenburg,&nbsp;Lars Sternas,&nbsp;Chloe Cavanaugh,&nbsp;Mohamed Zaki,&nbsp;Maria Palmisano,&nbsp;Simon Zhou","doi":"10.2147/CPAA.S144606","DOIUrl":"https://doi.org/10.2147/CPAA.S144606","url":null,"abstract":"<p><p>Pomalidomide is an immunomodulatory drug for treatment of relapsed or refractory multiple myeloma (rrMM) in patients who often have comorbid renal conditions. To assess the impact of renal impairment on pomalidomide exposure, a population pharmacokinetics (PPK) model of pomalidomide in rrMM patients with various degrees of impaired renal function was developed. Intensive and sparse pomalidomide concentration data collected from two clinical studies in rrMM patients with normal renal function, moderately impaired renal function, severely impaired renal function not requiring dialysis, and with severely impaired renal function requiring dialysis were pooled over the dose range of 2 to 4 mg, to assess specifically the influence of the impaired renal function as a categorical variable and a continuous variable on pomalidomide clearance and plasma exposure. In addition, pomalidomide concentration data collected on dialysis days from both the withdrawal (arterial) side and from the returning (venous) side of the dialyzer, from rrMM patients with severely impaired renal function requiring dialysis, were used to assess the extent to which dialysis contributes to the removal of pomalidomide from blood circulation. PPK analyses demonstrated that moderate to severe renal impairment not requiring dialysis has no influence on pomalidomide clearance or plasma exposure, as compared to those patients with normal renal function, while pomalidomide exposure increased approximately 35% in patients with severe renal impairment requiring dialysis on nondialysis days. In addition, dialysis increased total body pomalidomide clearance from 5 L/h to 12 L/h, indicating that dialysis will significantly remove pomalidomide from the blood circulation. Thus, pomalidomide should be administered post-dialysis on the days of dialysis.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"9 ","pages":"133-145"},"PeriodicalIF":2.0,"publicationDate":"2017-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S144606","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35645647","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":"Assessment of prescribed medications and pattern of distribution for potential drug-drug interactions among chronic kidney disease patients attending the Nephrology Clinic of Lagos University Teaching Hospital in Sub-Saharan West Africa.","authors":"Olumuyiwa John Fasipe, Peter Ehizokhale Akhideno, Obiyo Nwaiwu, Alex Adedotun Adelosoye","doi":"10.2147/CPAA.S147835","DOIUrl":"10.2147/CPAA.S147835","url":null,"abstract":"<p><strong>Introduction: </strong>Life expectancy has increased significantly among chronic kidney disease (CKD) patients due to the extensive use of polypharmacy practice for medication prescriptions. This predisposes them to potential drug-drug interactions (DDIs), which can lead to an increase in morbidity, mortality, length of hospital stay, and health care cost.</p><p><strong>Methods: </strong>This was a 30-month retrospective study that reviewed the medical case records of consenting adult CKD patients from January 2014 to June 2016. The Medscape drug reference database was used to evaluate patients' medications for potential DDIs.</p><p><strong>Results: </strong>This study involved 123 adult CKD patients (63 [51.22%] males and 60 [48.78%] females) with a mean age of 53.81±16.03 years. The most common comorbid conditions were hypertension (112 [91.10%]) and diabetes mellitus (45 [36.60%]). Regarding the form of nephrological interventions being offered, the majority of the respondents - 66 (53.66%) were on maintenance dialysis, followed by 53 (43.09%) respondents on conservative care, while 4 (3.25%) respondents were on renal transplantation. A total of 1264 prescriptions were made, and the mean number of prescribed medications per patient was 10.28±3.85. The most frequently prescribed medications were furosemide (88 [71.6%]), heparin (67 [54.47%]), lisinopril (65 [52.9%]), oral calcium carbonate (CaCO₃) (63 [51.2%]), α-calcidol (62 [50.4%]), and erythropoietin (61 [49.6%]). A total number of 1851 potential DDIs were observed among 118 patients. The prevalence of potential DDIs in this study was 78.0%, while the mean DDI per prescription was 1.50. Among the potential DDIs observed, the severity was mild in 639 (34.5%) patients, moderate in 1160 (62.7%) patients, and major in 51 (2.8%) patients and only 1 (0.1%) patient was of contraindicated drug combination. The most frequent DDIs' pattern observed was between oral CaCO₃ and oral ferrous sulfate. There was a statistically significant association between the number of prescribed medications and the estimated glomerular filtration rate (eGFR; pre-ESRD and ESRD staging) with a <i>P</i>-value of 0.00000119. This implies that the number of prescribed medications increases as the eGFR declines in advance CKD stage patients.</p><p><strong>Conclusion: </strong>Most of these interactions have moderate severity and delayed onset, hence the need to follow-up these patients after prescription in order to reduce associated morbidity, mortality, length of hospital stay, and health care cost. Physicians and clinical pharmacists should utilise available interaction software to avoid harmful DDIs in these patients.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"9 ","pages":"125-132"},"PeriodicalIF":2.0,"publicationDate":"2017-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S147835","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35593255","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":"Possible involvement of ROS generation in vorinostat pretreatment induced enhancement of the antibacterial activity of ciprofloxacin.","authors":"Majed M Masadeh,&nbsp;Karem H Alzoubi,&nbsp;Sayer I Al-Azzam,&nbsp;Ahlam M Al-Buhairan","doi":"10.2147/CPAA.S148448","DOIUrl":"https://doi.org/10.2147/CPAA.S148448","url":null,"abstract":"<p><p>The mechanism underlying ciprofloxacin action involves interference with transcription and replication of bacterial DNA and, thus, the induction of double-strand breaks in DNA. It also involves elevated oxidative stress, which might contribute to bacterial cell death. Vorinostat was shown to induce oxidative DNA damage. The current work investigated a possible interactive effect of vorinostat on ciprofloxacin-induced cytotoxicity against a number of reference bacteria. Standard bacterial strains were <i>Escherichia coli</i> ATCC 35218, <i>Staphylococcus aureus</i> ATCC29213, <i>Pseudomonas aeruginosa</i> ATCC 9027, <i>Staphylococcus epidermidis</i> ATCC 12228, <i>Acinetobacter baumannii</i> ATCC 17978, <i>Proteus mirabilis</i> ATCC 12459, <i>Klebsiella pneumoniae</i> ATCC 13883, methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) (ATCC 43300), and <i>Streptococcus pneumoniae</i> (ATCC 25923). The antibacterial activity of ciprofloxacin, with or without pretreatment of bacterial cells by vorinostat, was examined using the disc diffusion procedure and determination of the minimum inhibitory concentration (MIC) and zones of inhibition of bacterial growth. All tested bacterial strains showed sensitivity to ciprofloxacin. When pretreated with vorinostat, significantly larger zones of inhibition and smaller MIC values were observed in all bacterial strains compared to those treated with ciprofloxacin alone. In correlation, generation of reactive oxygen species (ROS) induced by the antibacterial action of ciprofloxacin was enhanced by treatment of bacterial cells with vorinostat. Results showed the possible agonistic properties of vorinostat when used together with ciprofloxacin. This could be related to the ability of these agents to enhance oxidative stress in bacterial cells.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"9 ","pages":"119-124"},"PeriodicalIF":2.0,"publicationDate":"2017-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S148448","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35648751","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":"Practical recommendations for the use of therapeutic drug monitoring of biopharmaceuticals in inflammatory diseases.","authors":"Erwin Dreesen,&nbsp;Peter Bossuyt,&nbsp;Denis Mulleman,&nbsp;Ann Gils,&nbsp;Dora Pascual-Salcedo","doi":"10.2147/CPAA.S138414","DOIUrl":"https://doi.org/10.2147/CPAA.S138414","url":null,"abstract":"<p><p>Biopharmaceuticals directed against tumor necrosis factor-alpha, integrins, interleukins, interferons and their receptors have become key agents for the management of inflammatory diseases in the fields of gastroenterology, rheumatology, dermatology and neurology. However, response to these treatments is far from optimal. Therapeutic failure has been attributed in part to inadequate serum concentrations of the drug and the formation of antidrug antibodies (ADA). Therapeutic drug monitoring (TDM) based on drug concentrations and ADA represents a pharmacologically sound tool for guiding dosage adjustments to optimize exposure. Although becoming standard practice in tertiary care centers, the widespread accessibility and recognition of TDM is hindered by several hurdles, including a lack of education of health care providers on TDM. In this paper, the Monitoring of monoclonal Antibodies Group in Europe (MAGE) provides an introduction on the fundamental principles of the concept of TDM, aiming to educate clinicians and assist them in the process of implementing TDM of anti-inflammatory biopharmaceuticals.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"9 ","pages":"101-111"},"PeriodicalIF":2.0,"publicationDate":"2017-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S138414","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35524119","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":"Antipsychotic prescription to identify delirium: results from two cohorts.","authors":"Kristin M Zimmerman,&nbsp;Allison M Paquin,&nbsp;James L Rudolph","doi":"10.2147/CPAA.S138441","DOIUrl":"https://doi.org/10.2147/CPAA.S138441","url":null,"abstract":"<p><strong>Objectives: </strong>Detection of delirium in hospitalized patients remains challenging. The objective was to determine if the prescription of antipsychotic medications was associated with delirium.</p><p><strong>Patients and methods: </strong>Two patient cohorts were utilized from a tertiary Veterans Affairs hospital: a palliative care retrospective cohort and a prospective medical cohort. Patients prescribed outpatient antipsychotics were excluded. Retrospectively, delirium was identified using a validated medical record-review instrument. Prospectively, a clinical expert assessed patients for delirium daily using a standardized interview. Acute antipsychotic medication administration was recorded from the electronic medical record.</p><p><strong>Results: </strong>In the retrospective cohort (n=217), delirium was found in 31% (n=67) and antipsychotic use in 18% (n=40) of patients. Acute antipsychotic use indicated delirium with 54% sensitivity and 97% specificity. In the prospective cohort (n=100), delirium developed in 23% (n=23) and antipsychotics were used in 5% (n=5) of patients. The sensitivity and specificity of acute antipsychotic use was 22% and 100%, respectively.</p><p><strong>Conclusion: </strong>Hospitalized patients who are acutely prescribed antipsychotics are likely to have delirium, but not all patients with delirium will be identified with this method. In health systems, utilization of the prescription of acute antipsychotics can be an efficient and specific method to identify delirious patients for targeted intervention.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"9 ","pages":"113-117"},"PeriodicalIF":2.0,"publicationDate":"2017-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S138441","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35524120","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":"Etanercept (Enbrel^®) alternative storage at ambient temperature.","authors":"Edel Shannon, Joanne Daffy, Heather Jones, Andrea Paulson, Steven M Vicik","doi":"10.2147/CPAA.S131832","DOIUrl":"10.2147/CPAA.S131832","url":null,"abstract":"<p><strong>Background: </strong>Biologic disease-modifying antirheumatic drugs, including tumor necrosis factor inhibitors such as etanercept (Enbrel^®), have improved outcomes for patients with rheumatic and other inflammatory diseases, with sustained remission being the optimal goal for patients with rheumatoid arthritis. Flexible and convenient treatment options, compatible with modern lifestyle, are important in helping patients maintain treatment and manage their disease. Etanercept drug product (DP) is available in lyophilized powder (Lyo) for solution injection, prefilled syringe, and prefilled pen presentations and is typically stored under refrigerated conditions. We aimed to generate a comprehensive analytical data package from stability testing of key quality attributes, consistent with regulatory requirements, to determine whether the product profile of etanercept is maintained at ambient temperature.</p><p><strong>Methods: </strong>Test methods assessing key attributes of purity, quality, potency, and safety were performed over time, following storage of etanercept DP presentations under a range of conditions.</p><p><strong>Results: </strong>Results and statistical analysis from stability testing (based on size exclusion high-performance liquid chromatography, hydrophobic interaction chromatography, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis Coomassie) across all etanercept presentations (10 and 25 mg/vial Lyo DP; 25 and 50 mg prefilled syringe DP; 50 mg prefilled pen DP) showed key stability-indicating parameters were within acceptable limits through the alternative storage condition of 25°C±2°C for 1 month.</p><p><strong>Conclusion: </strong>Stability testing performed in line with regulatory requirements supports a single period of storage for etanercept DP at an alternative storage condition of 25°C±2°C for up to 1 month within the approved expiry of the product. This alternative storage condition represents further innovation in the etanercept product lifecycle, providing greater flexibility and enhanced overall convenience for patients.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"9 ","pages":"87-99"},"PeriodicalIF":3.1,"publicationDate":"2017-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/00/8b/cpaa-9-087.PMC5531722.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35303923","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":"NMDA receptors are important regulators of pancreatic cancer and are potential targets for treatment.","authors":"William G North,&nbsp;Fuli Liu,&nbsp;Liz Z Lin,&nbsp;Ruiyang Tian,&nbsp;Bonnie Akerman","doi":"10.2147/CPAA.S140057","DOIUrl":"https://doi.org/10.2147/CPAA.S140057","url":null,"abstract":"<p><p>Pancreatic cancer, particularly adenocarcinoma of the pancreas, is a common disease with a poor prognosis. In this study, the importance of N-methyl-D-aspartate (NMDA) receptors for the growth and survival of pancreatic cancer was investigated. Immunohistochemistry performed with antibodies against GluN1 and GluN2B revealed that all invasive adenocarcinoma and neuroendocrine pancreatic tumors likely express these two NMDA receptor proteins. These proteins were found to be membrane components of pancreatic cancer cell lines, and both channel-blocker antagonist and GluN2B antagonist significantly reduced cell viability in vitro. Both types of antagonists caused an internalization of the receptors. Dizocilpine maleate (MK-801) and ifenprodil hemitartrate both significantly inhibited the growth of pancreatic tumor xenografts in nu/nu mice. These findings predict that, as for other solid tumors investigated by us, pancreatic cancer could be successfully treated, alone or in combination, with NMDA receptor antagonists or other receptor-inhibiting blocking agents.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"9 ","pages":"79-86"},"PeriodicalIF":2.0,"publicationDate":"2017-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S140057","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35280322","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":"Adverse reactions in leprosy patients who underwent dapsone multidrug therapy: a retrospective study.","authors":"Sanjeev Guragain,&nbsp;Namrata Upadhayay,&nbsp;Bishwa Mohan Bhattarai","doi":"10.2147/CPAA.S135846","DOIUrl":"https://doi.org/10.2147/CPAA.S135846","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the occurrence and clinical characteristics of dapsone-related adverse drug reactions (ADRs) among leprosy patients who underwent multidrug therapy (MDT) from 2010 to 2013 in the western region of Nepal.</p><p><strong>Methods: </strong>A retrospective review was carried out in the rehabilitation center. Data were collected from the record files of the hospital.</p><p><strong>Results: </strong>From 2010 to 2013, there were 18 patients reported to have dapsone ADRs, with an occurrence rate of 0.82% in the 4-year duration. The maximum incidence of ADRs (1.043%) was in 2010 and the minimum incidence of ADRs (0.26%) was in 2013. Among two types of bacterial infections, 94.44% were of multibacillary and 5.56% were of paucibacillary type. The age range of patients with dapsone ADRs was 11-68 years. The male-to-female ratio was 1.25. The onset of dapsone ADRs after taking MDT was within a minimum of 3 weeks and a maximum of 21 weeks. There were 14 (77.77%) patients who presented with jaundice, 8 (44.44%) with exfoliative dermatitis, 5 (27.77%) with hemolytic anemia and 4 (22.22%) with fever and headache. The rare side effects (5.5%) found were agranulocytosis or toxic epidermal necrolysis. Three patients were cured; some were still on the treatment. Four patients died with dapsone ADRs.</p><p><strong>Conclusion: </strong>The common dapsone ADRs present in leprosy patients were jaundice, exfoliative dermatitis and hemolytic anemia in MDT-treated patients. Patients could be cured by managing the dapsone ADRs effectively on time. Some patients may die of dapsone ADRs if clinicians fail to manage the side effects on time.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"9 ","pages":"73-78"},"PeriodicalIF":2.0,"publicationDate":"2017-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S135846","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35180573","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":"Prediction of efficacy for conversion from adjunctive therapy to monotherapy with eslicarbazepine acetate 800 mg once daily for partial-onset epilepsy.","authors":"Soujanya Sunkaraneni,&nbsp;Julie A Passarell,&nbsp;Elizabeth A Ludwig,&nbsp;Jill Fiedler-Kelly,&nbsp;Janet K Pitner,&nbsp;Todd A Grinnell,&nbsp;David Blum","doi":"10.2147/CPAA.S133815","DOIUrl":"https://doi.org/10.2147/CPAA.S133815","url":null,"abstract":"<p><strong>Purpose: </strong>Eslicarbazepine acetate (ESL) is a once-daily (QD) oral antiepileptic drug (AED) indicated for partial-onset seizures (POS). Clinical studies of gradual conversion to ESL 1,200 and 1,600 mg QD monotherapies were previously conducted in patients with POS who were not well-controlled by 1 or 2 AEDs. This report describes modeling and simulation of plasma eslicarbazepine (primary active metabolite of ESL) concentrations and time to monotherapy study exit to predict efficacy for conversion to ESL monotherapy at a lower dose of 800 mg, as an option for patients requiring or not tolerating higher doses since this regimen is effective in adjunctive therapy for POS.</p><p><strong>Patients and methods: </strong>A previously developed population pharmacokinetic model for ESL monotherapy was used to predict minimum plasma eslicarbazepine concentration (<i>C</i>_min) in 1,500 virtual patients taking 1 (n=1,000) or 2 (n=500) AEDs at baseline, treated with ESL 400 mg QD for 1 week, followed by 800 mg QD for 17 weeks (similar to ESL monotherapy trials where the other AEDs were withdrawn during the first 6 weeks following titration to the randomized ESL dose). Model-predicted <i>C</i>_min as a time-varying covariate and number of baseline AEDs were used to determine the weekly probability of each patient meeting exit criteria (65.3% threshold) indicative of worsening seizure control in 500 simulated ESL monotherapy trials. A previously developed extended Cox proportional hazards exposure-response model was used to relate time-varying eslicarbazepine exposure to the time to study exit.</p><p><strong>Results: </strong>For virtual patients receiving ESL monotherapy (800 mg QD), the 95% upper prediction limit for exit rate at 112 days of 34.9% in patients taking 1 AED at baseline was well below the 65.3% threshold from historical control trials, while the estimate for patients taking 2 AEDs (70.6%) was slightly above the historical control threshold.</p><p><strong>Conclusion: </strong>This model-based assessment supports conversion to ESL 800 mg QD monotherapy for POS in adults taking 1 AED. For patients taking 2 concomitant AEDs, however, prescribers should consider maintenance doses of 1,200 or 1,600 mg ESL QD to reduce the likelihood of seizure worsening if conversion to ESL monotherapy is contemplated.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"9 ","pages":"65-72"},"PeriodicalIF":2.0,"publicationDate":"2017-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S133815","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35180572","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":"An integrated epidemiological and neural net model of the warfarin effect in managed care patients.","authors":"David M Jacobs,&nbsp;Filip Stefanovic,&nbsp;Greg Wilton,&nbsp;Andres Gomez-Caminero,&nbsp;Jerome J Schentag","doi":"10.2147/CPAA.S136243","DOIUrl":"https://doi.org/10.2147/CPAA.S136243","url":null,"abstract":"<p><strong>Introduction: </strong>Risk assessment tools are utilized to estimate the risk for stroke and need of anticoagulation therapy for patients with atrial fibrillation (AF). These risk stratification scores are limited by the information inputted into them and a reliance on time-independent variables. The objective of this study was to develop a time-dependent neural net model to identify AF populations at high risk of poor clinical outcomes and evaluate the discriminatory ability of the model in a managed care population.</p><p><strong>Methods: </strong>We performed a longitudinal, cohort study within a health-maintenance organization from 1997 to 2008. Participants were identified with incident AF irrespective of warfarin status and followed through their duration within the database. Three clinical outcome measures were evaluated including stroke, myocardial infarction, and hemorrhage. A neural net model was developed to identify patients at high risk of clinical events and defined to be an \"enriched\" patient. The model defines the enrichment based on the top 10 minimum mean square error output parameters that describe the three clinical outcomes. Cox proportional hazard models were utilized to evaluate the outcome measures.</p><p><strong>Results: </strong>Among 285 patients, the mean age was 74±12 years with a mean follow-up of 4.3±2.6 years, and 154 (54%) were treated with warfarin. After propensity score adjustment, warfarin use was associated with a slightly increased risk of adverse outcomes (including stroke, myocardial infarction, and hemorrhage), though it did not attain statistical significance (adjusted hazard ratio [aHR] =1.22; 95% confidence interval [CI] 0.75-1.97; <i>p</i>=0.42). Within the neural net model, subjects at high risk of adverse outcomes were identified and labeled as \"enriched.\" Following propensity score adjustment, enriched subjects were associated with an 81% higher risk of adverse outcomes as compared to nonenriched subjects (aHR=1.81; 95% CI, 1.15-2.88; <i>p</i>=0.01).</p><p><strong>Conclusion: </strong>Enrichment methodology improves the statistical discrimination of meaningful endpoints when used in a health records-based analysis.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"9 ","pages":"55-64"},"PeriodicalIF":2.0,"publicationDate":"2017-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S136243","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35053193","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}