S. Natale, J. Bradley, William Nguyen, T. Tran, P. Ny, Kirsten La, E. Vivian, J. Le
Limited data exist for appropriate drug dosing in obese children. This comprehensive review summarizes pharmacokinetic (PK) alterations that occur with age and obesity, and these effects on antimicrobial dosing. A thorough comparison of different measures of body weight and specific antimicrobial agents including cefazolin, cefepime, ceftazidime, daptomycin, doripenem, gentamicin, linezolid, meropenem, piperacillin‐tazobactam, tobramycin, vancomycin, and voriconazole is presented. PubMed (1966–July 2015) and Cochrane Library searches were performed using these key terms: children, pharmacokinetic, obesity, overweight, body mass index, ideal body weight, lean body weight, body composition, and specific antimicrobial drugs. PK studies in obese children and, if necessary, data from adult studies were summarized. Knowledge of PK alterations stemming from physiologic changes that occur with age from the neonate to adolescent, as well as those that result from increased body fat, become an essential first step toward optimizing drug dosing in obese children. Excessive amounts of adipose tissue contribute significantly to body size, total body water content, and organ size and function that may modify drug distribution and clearance. PK studies that evaluated antimicrobial dosing primarily used total (or actual) body weight (TBW) for loading doses and TBW or adjusted body weight for maintenance doses, depending on the drugs’ properties and dosing units. PK studies in obese children are imperative to elucidate drug distribution, clearance, and, consequently, the dose required for effective therapy in these children. Future studies should evaluate the effects of both age and obesity on drug dosing because the incidence of obesity is increasing in pediatric patients.
{"title":"Pediatric Obesity: Pharmacokinetic Alterations and Effects on Antimicrobial Dosing","authors":"S. Natale, J. Bradley, William Nguyen, T. Tran, P. Ny, Kirsten La, E. Vivian, J. Le","doi":"10.1002/phar.1899","DOIUrl":"https://doi.org/10.1002/phar.1899","url":null,"abstract":"Limited data exist for appropriate drug dosing in obese children. This comprehensive review summarizes pharmacokinetic (PK) alterations that occur with age and obesity, and these effects on antimicrobial dosing. A thorough comparison of different measures of body weight and specific antimicrobial agents including cefazolin, cefepime, ceftazidime, daptomycin, doripenem, gentamicin, linezolid, meropenem, piperacillin‐tazobactam, tobramycin, vancomycin, and voriconazole is presented. PubMed (1966–July 2015) and Cochrane Library searches were performed using these key terms: children, pharmacokinetic, obesity, overweight, body mass index, ideal body weight, lean body weight, body composition, and specific antimicrobial drugs. PK studies in obese children and, if necessary, data from adult studies were summarized. Knowledge of PK alterations stemming from physiologic changes that occur with age from the neonate to adolescent, as well as those that result from increased body fat, become an essential first step toward optimizing drug dosing in obese children. Excessive amounts of adipose tissue contribute significantly to body size, total body water content, and organ size and function that may modify drug distribution and clearance. PK studies that evaluated antimicrobial dosing primarily used total (or actual) body weight (TBW) for loading doses and TBW or adjusted body weight for maintenance doses, depending on the drugs’ properties and dosing units. PK studies in obese children are imperative to elucidate drug distribution, clearance, and, consequently, the dose required for effective therapy in these children. Future studies should evaluate the effects of both age and obesity on drug dosing because the incidence of obesity is increasing in pediatric patients.","PeriodicalId":19812,"journal":{"name":"Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy","volume":"37 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90303569","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}
S. Dorajoo, V. See, C. Chan, Joyce Zhen Yin Tan, D. Tan, Siti Maryam Binte Abdul Razak, Ting Ting. Ong, Narendran Koomanan, Chun Wei Yap, A. Chan
Stratifying patients according to 15‐day readmission risk would be useful in identifying those who may benefit from targeted interventions during and/or following hospital discharge that are designed to reduce the likelihood of readmission.
{"title":"Identifying Potentially Avoidable Readmissions: A Medication‐Based 15‐Day Readmission Risk Stratification Algorithm","authors":"S. Dorajoo, V. See, C. Chan, Joyce Zhen Yin Tan, D. Tan, Siti Maryam Binte Abdul Razak, Ting Ting. Ong, Narendran Koomanan, Chun Wei Yap, A. Chan","doi":"10.1002/phar.1896","DOIUrl":"https://doi.org/10.1002/phar.1896","url":null,"abstract":"Stratifying patients according to 15‐day readmission risk would be useful in identifying those who may benefit from targeted interventions during and/or following hospital discharge that are designed to reduce the likelihood of readmission.","PeriodicalId":19812,"journal":{"name":"Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy","volume":"33 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86334542","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}
Stephanie A. Flowers, S. Evans, Kristen M. Ward, M. McInnis, V. Ellingrod
The atypical antipsychotic (AAP) class is often associated with metabolic disease, but the mechanistic underpinnings of this risk are not understood. Due to reports linking gut bacteria function to metabolic disease, we hypothesize that AAP treatment in adults results in gut dysbiosis potentiating metabolic criteria. This report describes recent findings linking AAP treatment with differences in gut microbiota communities in a human cohort with bipolar disorder (BD).
{"title":"Interaction Between Atypical Antipsychotics and the Gut Microbiome in a Bipolar Disease Cohort","authors":"Stephanie A. Flowers, S. Evans, Kristen M. Ward, M. McInnis, V. Ellingrod","doi":"10.1002/phar.1890","DOIUrl":"https://doi.org/10.1002/phar.1890","url":null,"abstract":"The atypical antipsychotic (AAP) class is often associated with metabolic disease, but the mechanistic underpinnings of this risk are not understood. Due to reports linking gut bacteria function to metabolic disease, we hypothesize that AAP treatment in adults results in gut dysbiosis potentiating metabolic criteria. This report describes recent findings linking AAP treatment with differences in gut microbiota communities in a human cohort with bipolar disorder (BD).","PeriodicalId":19812,"journal":{"name":"Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy","volume":"37 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74370835","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}
Brandon R. Shank, Bryan Do, A. Sevin, Sheree E Chen, S. Neelapu, S. Horowitz
Patients with B‐cell hematologic malignancies who progress through first‐ or second‐line chemotherapy have a poor prognosis. Early clinical trials with autologous anti‐CD19 chimeric antigen receptor (CAR) T cells have demonstrated promising results for patients who have relapsed or refractory disease. Lymphodepleting conditioning regimens, including cyclophosphamide, fludarabine, pentostatin, bendamustine, interleukin‐2, and total body irradiation, are often administered before the infusion of CAR T cells, allowing for greater T‐cell expansion. The major toxicity associated with CAR T‐cell infusions is cytokine release syndrome (CRS), a potentially life‐threatening systemic inflammatory disorder. The quick onset and progression of CRS require rapid detection and intervention to reduce treatment‐related mortality. Management with tocilizumab can help ameliorate the symptoms of severe CRS, allowing steroids, which diminish the expansion and persistence of CAR T cells, to be reserved for tocilizumab‐refractory patients. Other toxicities of CAR T‐cell therapy include neutropenia and/or febrile neutropenia, infection, tumor lysis syndrome, neurotoxicity and nausea/vomiting. A review of patients’ medications is imperative to eliminate medications that may contribute to treatment‐related toxicities. Studies are ongoing to help optimize patient selection, preparation, safety, and management of individuals receiving CAR T cells. Long‐term follow‐up will help establish the place of CAR T cells in therapy.
{"title":"Chimeric Antigen Receptor T Cells in Hematologic Malignancies","authors":"Brandon R. Shank, Bryan Do, A. Sevin, Sheree E Chen, S. Neelapu, S. Horowitz","doi":"10.1002/phar.1900","DOIUrl":"https://doi.org/10.1002/phar.1900","url":null,"abstract":"Patients with B‐cell hematologic malignancies who progress through first‐ or second‐line chemotherapy have a poor prognosis. Early clinical trials with autologous anti‐CD19 chimeric antigen receptor (CAR) T cells have demonstrated promising results for patients who have relapsed or refractory disease. Lymphodepleting conditioning regimens, including cyclophosphamide, fludarabine, pentostatin, bendamustine, interleukin‐2, and total body irradiation, are often administered before the infusion of CAR T cells, allowing for greater T‐cell expansion. The major toxicity associated with CAR T‐cell infusions is cytokine release syndrome (CRS), a potentially life‐threatening systemic inflammatory disorder. The quick onset and progression of CRS require rapid detection and intervention to reduce treatment‐related mortality. Management with tocilizumab can help ameliorate the symptoms of severe CRS, allowing steroids, which diminish the expansion and persistence of CAR T cells, to be reserved for tocilizumab‐refractory patients. Other toxicities of CAR T‐cell therapy include neutropenia and/or febrile neutropenia, infection, tumor lysis syndrome, neurotoxicity and nausea/vomiting. A review of patients’ medications is imperative to eliminate medications that may contribute to treatment‐related toxicities. Studies are ongoing to help optimize patient selection, preparation, safety, and management of individuals receiving CAR T cells. Long‐term follow‐up will help establish the place of CAR T cells in therapy.","PeriodicalId":19812,"journal":{"name":"Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy","volume":"51 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81151595","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}
V. Bali, S. Chatterjee, Michael L. Johnson, Hua Chen, R. Carnahan, R. Aparasu
Among selective serotonin reuptake inhibitors (SSRIs), paroxetine is strongly anticholinergic and might lead to a higher risk of adverse outcomes such as mortality. This study examined the risk of mortality in depressed elderly nursing home patients using paroxetine and other SSRIs.
{"title":"Risk of Mortality in Elderly Nursing Home Patients with Depression Using Paroxetine","authors":"V. Bali, S. Chatterjee, Michael L. Johnson, Hua Chen, R. Carnahan, R. Aparasu","doi":"10.1002/phar.1898","DOIUrl":"https://doi.org/10.1002/phar.1898","url":null,"abstract":"Among selective serotonin reuptake inhibitors (SSRIs), paroxetine is strongly anticholinergic and might lead to a higher risk of adverse outcomes such as mortality. This study examined the risk of mortality in depressed elderly nursing home patients using paroxetine and other SSRIs.","PeriodicalId":19812,"journal":{"name":"Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74015931","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}
The direct acting oral anticoagulants (DOACs), including dabigatran, rivaroxaban, apixaban, and edoxaban, have favorable pharmacokinetic and pharmacodynamic properties and equal or superior efficacy and an improved safety profile compared with warfarin. Noted shortcomings with DOACs are shorter half‐lives requiring stricter adherence, lack of standardized laboratory monitoring, lack of anticoagulation reversal agents, and loss of routine coagulation monitoring leading to fewer patient–clinician interactions. This review addresses many of these limitations including monitoring of DOACs for efficacy and toxicity, an assessment of selected qualitative and quantitative tests, and development of monitoring strategies for special populations. Coagulation monitoring is generally recommended only in overdose situations, but once standardized assays are readily available, they could be helpful to ensure efficacy, assess bleeding, and aid in drug selection in a number of other patient scenarios. Coagulation tests that may provide qualitative assessment include activated partial thromboplastin time, prothrombin time, and thrombin time. Methods with potential utility for quantitative assessment of DOACs include plasma drug concentrations, ecarin clotting time, dilute thrombin time, and anti–factor Xa concentrations. Noncoagulation laboratory monitoring should include serum creatinine, liver function tests, and complete blood counts. Clinical monitoring of the DOAC‐treated patient should include routine assessment of adherence, bleeding risks, and drug interactions. Frequency of monitoring should be 1–3 months after initiation and then at least every 6 months, with more frequent follow‐up (i.e., 3 months) based on patient specific characteristics such as age, renal impairment, hepatic impairment, and concomitant drug therapy. The authors provide a practical tool to assist in DOAC monitoring and recommend that pharmacists collaborate with physicians in selecting appropriate patients and tailoring patient‐specific monitoring plans.
{"title":"Laboratory and Clinical Monitoring of Direct Acting Oral Anticoagulants: What Clinicians Need to Know","authors":"S. Conway, Andrew Y. Hwang, C. Ponte, J. Gums","doi":"10.1002/phar.1884","DOIUrl":"https://doi.org/10.1002/phar.1884","url":null,"abstract":"The direct acting oral anticoagulants (DOACs), including dabigatran, rivaroxaban, apixaban, and edoxaban, have favorable pharmacokinetic and pharmacodynamic properties and equal or superior efficacy and an improved safety profile compared with warfarin. Noted shortcomings with DOACs are shorter half‐lives requiring stricter adherence, lack of standardized laboratory monitoring, lack of anticoagulation reversal agents, and loss of routine coagulation monitoring leading to fewer patient–clinician interactions. This review addresses many of these limitations including monitoring of DOACs for efficacy and toxicity, an assessment of selected qualitative and quantitative tests, and development of monitoring strategies for special populations. Coagulation monitoring is generally recommended only in overdose situations, but once standardized assays are readily available, they could be helpful to ensure efficacy, assess bleeding, and aid in drug selection in a number of other patient scenarios. Coagulation tests that may provide qualitative assessment include activated partial thromboplastin time, prothrombin time, and thrombin time. Methods with potential utility for quantitative assessment of DOACs include plasma drug concentrations, ecarin clotting time, dilute thrombin time, and anti–factor Xa concentrations. Noncoagulation laboratory monitoring should include serum creatinine, liver function tests, and complete blood counts. Clinical monitoring of the DOAC‐treated patient should include routine assessment of adherence, bleeding risks, and drug interactions. Frequency of monitoring should be 1–3 months after initiation and then at least every 6 months, with more frequent follow‐up (i.e., 3 months) based on patient specific characteristics such as age, renal impairment, hepatic impairment, and concomitant drug therapy. The authors provide a practical tool to assist in DOAC monitoring and recommend that pharmacists collaborate with physicians in selecting appropriate patients and tailoring patient‐specific monitoring plans.","PeriodicalId":19812,"journal":{"name":"Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88784053","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}
Nicole E. Cieri, Kristen Kusmierski, C. Lackie, August Van Opdorp, Amany K. Hassan
To evaluate the occurrence of bleeding and venous thromboembolic (VTE) events in patients receiving rivaroxaban, warfarin, or warfarin with the addition of enoxaparin during the immediate postoperative period following major orthopedic surgery.
{"title":"Retrospective Evaluation of Postoperative Adverse Drug Events in Patients Receiving Rivaroxaban After Major Orthopedic Surgery Compared with Standard Therapy in a Community Hospital","authors":"Nicole E. Cieri, Kristen Kusmierski, C. Lackie, August Van Opdorp, Amany K. Hassan","doi":"10.1002/phar.1888","DOIUrl":"https://doi.org/10.1002/phar.1888","url":null,"abstract":"To evaluate the occurrence of bleeding and venous thromboembolic (VTE) events in patients receiving rivaroxaban, warfarin, or warfarin with the addition of enoxaparin during the immediate postoperative period following major orthopedic surgery.","PeriodicalId":19812,"journal":{"name":"Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy","volume":"61 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84576765","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}
C. Frei, Sylvie B. Rehani, Grace C. Lee, N. Boyd, Erene M. Attia, A. Pechal, Rachel S. Britt, E. Mortensen
To assess the impact of empiric Pseudomonas pharmacotherapy on 30‐day mortality in hospitalized patients with community‐onset pneumonia stratified according to their risk (low, medium, or high) of drug‐resistant pathogens.
{"title":"Application of a Risk Score to Identify Older Adults with Community‐Onset Pneumonia Most Likely to Benefit From Empiric Pseudomonas Therapy","authors":"C. Frei, Sylvie B. Rehani, Grace C. Lee, N. Boyd, Erene M. Attia, A. Pechal, Rachel S. Britt, E. Mortensen","doi":"10.1002/phar.1891","DOIUrl":"https://doi.org/10.1002/phar.1891","url":null,"abstract":"To assess the impact of empiric Pseudomonas pharmacotherapy on 30‐day mortality in hospitalized patients with community‐onset pneumonia stratified according to their risk (low, medium, or high) of drug‐resistant pathogens.","PeriodicalId":19812,"journal":{"name":"Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy","volume":"21 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86276492","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}
To evaluate the odds of achieving viral suppression in human immunodeficiency virus (HIV) patients using antiretroviral therapy as a single‐tablet regimen (STR) or multiple‐tablet regimen (MTR).
{"title":"Odds of Viral Suppression by Single‐Tablet Regimens, Multiple‐Tablet Regimens, and Adherence Level in HIV/AIDS Patients Receiving Antiretroviral Therapy","authors":"S. Sutton, J. Magagnoli, J. Hardin","doi":"10.1002/phar.1889","DOIUrl":"https://doi.org/10.1002/phar.1889","url":null,"abstract":"To evaluate the odds of achieving viral suppression in human immunodeficiency virus (HIV) patients using antiretroviral therapy as a single‐tablet regimen (STR) or multiple‐tablet regimen (MTR).","PeriodicalId":19812,"journal":{"name":"Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72995577","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}
Tyler K Liebenstein, Lucas T. Schulz, Chris Viesselmann, E. Bingen, Jackson S. Musuuza, N. Safdar, W. Rose
Because patients with abdominal solid organ transplants (SOTs) are at increased risk of polymicrobial intraabdominal infections (IAIs) following transplantation, the objective of this study was to compare the effectiveness and adverse event profile of tigecycline with those of other broad‐spectrum therapies for polymicrobial IAIs in this population.
{"title":"Effectiveness and Safety of Tigecycline Compared with Other Broad‐Spectrum Antimicrobials in Abdominal Solid Organ Transplant Recipients with Polymicrobial Intraabdominal Infections","authors":"Tyler K Liebenstein, Lucas T. Schulz, Chris Viesselmann, E. Bingen, Jackson S. Musuuza, N. Safdar, W. Rose","doi":"10.1002/phar.1883","DOIUrl":"https://doi.org/10.1002/phar.1883","url":null,"abstract":"Because patients with abdominal solid organ transplants (SOTs) are at increased risk of polymicrobial intraabdominal infections (IAIs) following transplantation, the objective of this study was to compare the effectiveness and adverse event profile of tigecycline with those of other broad‐spectrum therapies for polymicrobial IAIs in this population.","PeriodicalId":19812,"journal":{"name":"Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79197453","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}
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