Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 23
Filter
1.
medRxiv ; 2023 Oct 02.
Article in English | MEDLINE | ID: mdl-37503172

ABSTRACT

Heart failure (HF) is a complex trait, influenced by environmental and genetic factors, that affects over 30 million individuals worldwide. Historically, the genetics of HF have been studied in Mendelian forms of disease, where rare genetic variants have been linked to familial cardiomyopathies. More recently, genome-wide association studies (GWAS) have successfully identified common genetic variants associated with risk of HF. However, the relative importance of genetic variants across the allele-frequency spectrum remains incompletely characterized. Here, we report the results of common- and rare-variant association studies of all-cause heart failure, applying recently developed methods to quantify the heritability of HF attributable to different classes of genetic variation. We combine GWAS data across multiple populations including 207,346 individuals with HF and 2,151,210 without, identifying 176 risk loci at genome-wide significance (p < 5×10-8). Signals at newly identified common-variant loci include coding variants in Mendelian cardiomyopathy genes (MYBPC3, BAG3), as well as regulators of lipoprotein (LPL) and glucose metabolism (GIPR, GLP1R), and are enriched in cardiac, muscle, nerve, and vascular tissues, as well as myocyte and adipocyte cell types. Gene burden studies across three biobanks (PMBB, UKB, AOU) including 27,208 individuals with HF and 349,126 without uncover exome-wide significant (p < 3.15×10-6) associations for HF and rare predicted loss-of-function (pLoF) variants in TTN, MYBPC3, FLNC, and BAG3. Total burden heritability of rare coding variants (2.2%, 95% CI 0.99-3.5%) is highly concentrated in a small set of Mendelian cardiomyopathy genes, and is lower than heritability attributable to common variants (4.3%, 95% CI 3.9-4.7%) which is more diffusely spread throughout the genome. Finally, we demonstrate that common-variant background, in the form of a polygenic risk score (PRS), significantly modifies the risk of HF among carriers of pathogenic truncating variants in the Mendelian cardiomyopathy gene TTN. These findings suggest a significant polygenic component to HF exists that is not captured by current clinical genetic testing.

2.
Kidney360 ; 3(11): 1939-1941, 2022 11 24.
Article in English | MEDLINE | ID: mdl-36514404

ABSTRACT

This study confirms the safety of endovascular interventions for thrombosis of hemodialysis access in outpatient and office-based settings.Risk of death in the week after vascular access procedure was not associated with hemodialysis access type (fistula versus graft).


Subject(s)
Arteriovenous Shunt, Surgical , Thrombosis , Humans , Arteriovenous Shunt, Surgical/adverse effects , Outpatients , Renal Dialysis , Thrombosis/etiology
3.
Kidney Med ; 4(8): 100509, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35991693

ABSTRACT

Patients with kidney disease represent a medically complex group of patients with high medication burdens that could benefit from clinical pharmacy services as part of the interdisciplinary care team to optimize medication use. The "Advancing American Kidney Health" executive order includes new value-based reimbursement models to be tested by the Center for Medicare and Medicaid Innovation beginning January 2021 and January 2022. Advancing American Kidney Health executive order poses opportunities for the inclusion of comprehensive medication management. Following an iterative process integrating input from a diverse expert panel, published standards, clinical practice guidelines, peer review, and stakeholder feedback, our group developed practice standards for pharmacists caring for patients with kidney disease in health care settings. The standards focus on activities that are part of direct patient care and also include activities related to public health and advocacy, population health, leadership and management, and teaching, education and dissemination of knowledge. These standards are intended to be used by a variety of professionals, from pharmacists starting new practices to practice managers looking to add a pharmacist to the clinical team, to create standardization in services provided.

4.
Semin Dial ; 33(6): 449-456, 2020 Nov.
Article in English | MEDLINE | ID: mdl-33210373

ABSTRACT

People with end-stage kidney disease (ESKD) who require chronic dialysis are often reliant on complicated medication regimens to manage their health conditions. Due to the complexities of the advanced kidney disease, underlying comorbidities, and special instructions, medication regimens for patients on dialysis put patients at high risk for medication therapy problems related to safety, effectiveness, appropriateness, and adherence. This article explores the factors that affect optimal medication use for people on dialysis, including the broader drug use system, and offers recommendations around medication reconciliation, medication review, deprescribing, and considering social determinants of health to improve medication management among patients with ESKD.


Subject(s)
Kidney Diseases , Kidney Failure, Chronic , Humans , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/therapy , Medication Reconciliation , Medication Therapy Management , Renal Dialysis/adverse effects
5.
J Am Pharm Assoc (2003) ; 60(6): 957-962.e1, 2020.
Article in English | MEDLINE | ID: mdl-32811751

ABSTRACT

OBJECTIVES: Patients on hemodialysis have complicated medication regimens requiring the ability to accurately interpret medication information. Literacy and numeracy skills have been shown to differ by the types of materials provided to patients. The aims of this study were to determine prescription and over-the-counter medication label understanding and to assess the prevalence of low health literacy regarding medication labeling among in-center hemodialysis patients. DESIGN, SETTING AND PARTICIPANTS: The Medication Literacy and Numeracy in Dialysis (MedLitD) tool is an assessment of a person's ability to read and understand medication labels. A comparison with the Rapid Estimate of Adult Literacy in Medicine Short Form (REALM-SF), an established literacy tool, was conducted to determine if there were differences in the literacy results from the 2 tools that could be leveraged to target education initiatives for this specialized population. RESULTS: A total of 110 patients receiving hemodialysis from 3 dialysis facilities in the Capital Region of upstate New York were enrolled in the study. Most patients (77%) achieved a maximum REALM-SF score, indicating a high level of literacy proficiency; however, their MedLitD scores varied. Patients who were 65 years and older had lower scores on the MedLitD tool compared with younger patients. Gender, education, and the number of medications did not influence the MedLitD scores. Only 16% of all participants correctly answered the question asking for an indication of the phosphate binder (PB), although the most patients were currently taking PBs. CONCLUSION: A continuum of medication literacy levels exists among patients on hemodialysis. Appropriate evaluation of medication literacy should be done to better inform individualized education and counseling.


Subject(s)
Health Literacy , Literacy , Adult , Drug Labeling , Educational Status , Humans , New York , Renal Dialysis
7.
Curr Pharm Teach Learn ; 10(2): 185-194, 2018 02.
Article in English | MEDLINE | ID: mdl-29706274

ABSTRACT

BACKGROUND AND PURPOSE: Medication therapy management (MTM) is a comprehensive, patient-centered approach to improving medication use, reducing the risk of adverse events and improving medication adherence. Given the service delivery model and required outputs of MTM services, communication skills are of utmost importance. The objectives of this study were to identify and describe communication principles and instructional practices to enhance MTM training. EDUCATIONAL ACTIVITY AND SETTING: Drawing on formative assessment data from interviews of both pharmacy educators and alumni, this article identifies and describes communication principles and instructional practices that pharmacy educators can use to enhance MTM training initiatives to develop student communication strategies. FINDINGS: Analysis revealed five key communication challenges of MTM service delivery, two communication principles that pharmacy teachers and learners can use to address those challenges, and a range of specific strategies, derived from communication principles, that students can use when challenges emerge. Implications of the analysis for pharmacy educators and researchers are described. SUMMARY: Proactive communication training provided during MTM advanced pharmacy practice experiences enabled students to apply the principles and instructional strategies to specific patient interactions during the advanced pharmacy practice experiences and in their post-graduation practice settings.


Subject(s)
Communication , Community Pharmacy Services , Curriculum , Education, Pharmacy , Medication Therapy Management , Professional Competence , Students, Pharmacy , Humans , Pharmacists
8.
Pharmacy (Basel) ; 5(3)2017 Jul 11.
Article in English | MEDLINE | ID: mdl-28970451

ABSTRACT

To determine the impact of advanced pharmacy practice experiences (APPE) on student self-confidence related to medication therapy management (MTM), fourth-year pharmacy students were surveyed pre/post APPE to: identify exposure to MTM learning opportunities, assess knowledge of the MTM core components, and assess self-confidence performing MTM services. An anonymous electronic questionnaire administered pre/post APPE captured demographics, factors predicted to impact student self-confidence (Grade point average (GPA), work experience, exposure to MTM learning opportunities), MTM knowledge and self-confidence conducting MTM using a 5-point Likert scale (1 = Not at all Confident; 5 = Extremely Confident). Sixty-two students (26% response rate) responded to the pre-APPE questionnaire and n = 44 (18%) to the post-APPE. Over 90% demonstrated MTM knowledge and 68.2% completed MTM learning activities. APPE experiences significantly improved students' overall self-confidence (pre-APPE = 3.27 (0.85 SD), post-APPE = 4.02 (0.88), p < 0.001). Students engaging in MTM learning opportunities had higher self-confidence post-APPE (4.20 (0.71)) vs. those not reporting MTM learning opportunities (3.64 (1.08), p = 0.05). Post-APPE, fewer students reported MTM was patient-centric or anticipated engaging in MTM post-graduation. APPE learning opportunities increased student self-confidence to provide MTM services. However, the reduction in anticipated engagement in MTM post-graduation and reduction in sensing the patient-centric nature of MTM practice, may reveal a gap between practice expectations and reality.

10.
Drugs ; 77(11): 1155-1186, 2017 07.
Article in English | MEDLINE | ID: mdl-28584909

ABSTRACT

As kidney disease progresses, phosphorus retention also increases, and phosphate binders are used to treat hyperphosphatemia. Clinicians prescribe phosphate binders thinking that reducing total body burden of phosphorus may decrease risks of mineral and bone disorder, fractures, cardiovascular disease, progression of kidney disease, and mortality. Recent meta-analyses suggest that sevelamer use results in lower mortality than use of calcium-containing phosphate binders. However, studies included in meta-analyses show significant heterogeneity, and exclusion or inclusion of specific studies alters results. Since no long-term studies have been conducted to determine whether treatment with any phosphate binder is better than placebo on any hard clinical endpoint (including mortality), it is unclear whether possible benefit with sevelamer represents net benefit of sevelamer, net harm with calcium-containing phosphate binders, or both. Although one meta-analysis suggested that calcium acetate may be more efficacious gram for gram than calcium carbonate as a binder, calcium acetate did not reduce hypercalcemia, and gastrointestinal intolerance was higher. Data are insufficient to determine whether calcium acetate provides lower risk of vascular calcification than calcium carbonate. Fears of lanthanum accumulation in the central nervous system or bone with long-term treatment do not appear to be warranted. Newer iron-containing phosphate binders have potential benefits, such as lower pill burden (sucroferric oxyhydroxide) and improved iron parameters (ferric citrate). The biggest challenge to phosphate binder efficacy is non-adherence. This article reviews the current knowledge regarding safety, effectiveness, and adherence with currently marketed phosphate binders and those in development.


Subject(s)
Chelating Agents/therapeutic use , Hyperphosphatemia/drug therapy , Lanthanum/therapeutic use , Phosphates/metabolism , Renal Insufficiency, Chronic/drug therapy , Calcium Compounds/adverse effects , Calcium Compounds/metabolism , Calcium Compounds/therapeutic use , Chelating Agents/adverse effects , Chelating Agents/economics , Chelating Agents/pharmacology , Drug Costs , Ferric Compounds/adverse effects , Ferric Compounds/metabolism , Ferric Compounds/therapeutic use , Humans , Hyperphosphatemia/etiology , Lanthanum/metabolism , Lanthanum/pharmacology , Meta-Analysis as Topic , Phosphates/blood , Renal Insufficiency, Chronic/complications , Sevelamer/therapeutic use
11.
Res Social Adm Pharm ; 13(4): 738-745, 2017.
Article in English | MEDLINE | ID: mdl-27567742

ABSTRACT

OBJECTIVES: Patients with end-stage kidney disease (ESKD) typically have high medication burdens with numerous medications and specialized instructions. Limited data exist regarding ESKD patient perspectives on medication management. Why can some patients self-manage? Which organizational techniques are used? This project sought to determine experiences and attitudes regarding medication management among hemodialysis patients. METHODS: Group interviews were conducted with adult patients from 3 dialysis facilities. Semi-structured interviews solicited information about medication self-management and views on related services. Interviews were recorded and transcribed and data were analyzed using inductive, thematic coding. RESULTS: Participants reported medication regimens complicated by the dialysis schedule, co-morbid conditions and multiple prescribers. Patients engaged in various coping strategies, including reliance on activating social capital and/or family social support, to manage their medications and health. When described, most thought medication management services would be beneficial, but not necessarily for themselves, despite some having histories of medication mismanagement. DISCUSSION: Patients on hemodialysis often develop strategies for managing medications that rely heavily on a social network, and strategies may not be discussed with healthcare providers. Social capital is a useful framework for considering patients' lifestyles and support structure when designing a medication regimen. Future research should explore this idea more proactively.


Subject(s)
Health Knowledge, Attitudes, Practice , Kidney Failure, Chronic/therapy , Medication Therapy Management , Patients/psychology , Polypharmacy , Renal Dialysis , Self Care/methods , Social Capital , Activities of Daily Living , Adaptation, Psychological , Comorbidity , Cost of Illness , Group Processes , Humans , Interviews as Topic , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/psychology , Risk Factors , Social Support
12.
J Am Pharm Assoc (2003) ; 55(4): 390-7, 2015.
Article in English | MEDLINE | ID: mdl-26070138

ABSTRACT

OBJECTIVE: To determine views of staff of dialysis centers toward pharmacist-delivered medication therapy management (MTM) services. DESIGN: Focus group study. SETTING: Three private, nonprofit, outpatient dialysis facilities. PARTICIPANTS: Multidisciplinary dialysis staff. INTERVENTION: Two focus group sessions were conducted using a semistructured interview guide. MAIN OUTCOME MEASURES: Views of staff toward MTM services at a dialysis center. RESULTS: A total of 13 staff members of dialysis centers participated in the study. Participants included nurses, patient care technicians, a social worker, dietitian, and administrative personnel. Key themes included: the need for access to MTM services in dialysis facilities exists; services should include medication reconciliation and patient education; services should be proactive, consistent, individualized, and covered by insurance; and that pharmacists are uniquely suited to provide MTM services. CONCLUSION: Dialysis staff support the integration of MTM services in facilities. Further research is needed to identify barriers and opportunities in the implementation process, including patient perspectives.


Subject(s)
Ambulatory Care Facilities , Delivery of Health Care, Integrated , Medication Therapy Management , Pharmacists , Professional Role , Renal Dialysis , Adult , Attitude of Health Personnel , Clinical Competence , Cooperative Behavior , Female , Focus Groups , Health Knowledge, Attitudes, Practice , Humans , Interdisciplinary Communication , Male , Middle Aged , New York , Patient Care Team , Qualitative Research , Workforce
13.
BMC Nephrol ; 15: 204, 2014 Dec 20.
Article in English | MEDLINE | ID: mdl-25526750

ABSTRACT

BACKGROUND: The purpose of this study was to evaluate the feasibility of utilizing an in-vitro, closed loop hemodialysis system as a method to assess drug clearance. Secondarily, this study tested the influence of variables (blood flow rate, dialysate flow rate, and type of filter) in the hemodialysis procedure on the clearance of vancomycin and gentamicin. METHODS: An in-vitro, closed loop hemodialysis system was constructed. The vancomycin (30 mg/L) and gentamicin (25 mg/L) were added to a simulated blood system (SBS). Four conditions (C1-C4) were tested by defining the filter (Polyflux 170H or F180) and the blood and dialysate flow rates (BFR and DFR). All hemodialysis sessions were 3 hours in length and each condition was completed in duplicate. Dialysate effluent was collected in a 50 gallon polyethylene drum. Samples were collected (in duplicate) from the SBS and the dialysate effluent at baseline and at the end of the hemodialysis session. Samples were analyzed for vancomycin and gentamicin with an ultrahigh performance liquid chromatography/tandem mass spectrometry method. RESULTS: A total of eight 3-hour hemodialysis sessions were conducted. For all tested conditions (C1-C4), vancomycin was undetectable in the SBS at the end of dialysis. However, total vancomycin recovery in the dialysis effluent was 85±18%, suggesting that up to 15% may have adsorbed to the dialysis filter or tubing. Gentamicin clearance from SBS was >98% in all tested conditions. Average gentamicin recovery in the dialysate effluent was 99±15%. CONCLUSION: Both vancomycin and gentamicin were readily removed by high-flux hemodialysis under all conditions studied. No significant differences in drug clearance were observed between conditions used in this in vitro study. The clinical implications of changing these hemodialysis parameters are unknown.


Subject(s)
Gentamicins/pharmacokinetics , Renal Dialysis/methods , Vancomycin/pharmacokinetics , Dialysis Solutions/chemistry , Filtration/instrumentation , Gentamicins/analysis , Humans , In Vitro Techniques , Metabolic Clearance Rate , Renal Dialysis/instrumentation , Vancomycin/analysis
15.
J Antimicrob Chemother ; 69(7): 1873-6, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24722842

ABSTRACT

OBJECTIVES: The intent of this study was to evaluate the appropriateness of commonly used intravenous (iv) vancomycin dosing schemes in patients on automated peritoneal dialysis (APD) using population pharmacokinetic (PK) modelling and Monte Carlo simulation. METHODS: Data from a single-dose PK study of 10 non-infected APD patients ≥18 years old were analysed. Patients received iv vancomycin (15 mg/kg) followed by three cycler-assisted APD dwells over 8 h, followed by two 8 h dwells. Serum and dialysate samples were collected over the entire 24 h. A three-compartment model was fitted to the data with BigNPAG. Monte Carlo simulation was used to determine the probability of achieving an AUC/MIC ratio of >400 in both the serum and the peritoneal cavity for a variety of iv vancomycin dosing schemes (1-2 g every 24-48 h). RESULTS: In the probability of target attainment (PTA) analyses, only 2 g of iv vancomycin every 24 h conferred >90% probability of achieving an AUC/MIC ratio of >400 for MIC values <2 mg/L in the serum. However, this dosing regimen resulted in average trough concentrations >20 mg/L. In the peritoneal cavity, no regimen yielded PTA ≥90% for MIC values ≥0.5 mg/L. CONCLUSIONS: Although expert guidelines suggest iv vancomycin may be an acceptable empirical therapy for patients on APD with infection, these analyses indicate that iv vancomycin may not be effective for peritonitis but may be a viable option for non-peritoneal infections with MIC values ≤1 mg/L.


Subject(s)
Anti-Bacterial Agents/pharmacokinetics , Peritoneal Dialysis , Vancomycin/pharmacokinetics , Administration, Intravenous , Adolescent , Adult , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/pharmacology , Dialysis Solutions/chemistry , Female , Humans , Male , Microbial Sensitivity Tests , Middle Aged , Models, Statistical , Serum/chemistry , Vancomycin/administration & dosage , Vancomycin/pharmacology , Young Adult
16.
Antimicrob Agents Chemother ; 58(1): 19-26, 2014.
Article in English | MEDLINE | ID: mdl-24126585

ABSTRACT

While intraperitoneal (i.p.) ceftazidime is commonly used to treat continuous ambulatory peritoneal dialysis (CAPD)-related infections, the ability of i.p. regimens to achieve critical pharmacodynamic targets in both blood and dialysate has not been reported. To understand the pharmacodynamic profile of ceftazidime during CAPD, data were obtained from a single-dose pharmacokinetic (PK) i.p. ceftazidime study that included 10 CAPD patients who received i.p. ceftazidime at 15 mg/kg of body weight. The probability of target attainment (concentrations maintained above the MIC for >60% of the dosing interval [60% T > MIC]) was determined for six simulated regimens. A 3-compartment model with each dialysis dwell modeled as a separate differential equation was fit to ceftazidime concentrations using BigNPAG. Embedded with the final PK model, serum and dialysate concentration-time profiles of ceftazidime at 1, 1.5, and 2 g i.p. every 24 h (q24h) to q48h were simulated using ADAPT 5. The mean population pharmacokinetic parameters were as follows: apparent volume of the central compartment (Vc), 7.57 liter; apparent volume of the peritoneal cavity (Vpd), 2.44 liter; clearance from the central compartment (CL), 0.379 liter/h; intercompartmental transfer rate constants (first order) between the central and peripheral compartments (k12 and k21), 4.66 and 4.88 h(-1), respectively; and intercompartmental transfer rate constants (first order) between the central and peritoneal compartments (k13 and k31), 0.111 and 0.227 h(-1), respectively. In serum, the probability of target attainment for MICs of ≤8 mg/liter exceeded 90% for 1.5 to 2 g i.p. q24h to q48h. However, no tested regimen provided adequate dialysate exposure at MICs of ≥8 mg/liter on day 1 without the use of a 3-g loading dose (post hoc analysis). On day 2, 1.5 to 2 g i.p. q24h or 2 g i.p. q48h provided adequate exposure in the peritoneal cavity. These results should be validated in the presence of infection. Ceftazidime i.p. at 1.5 or 2 g q24h to q48h is recommended for nonperitoneal infections. For peritonitis, a 3-g load with maintenance dosing of 1 to 2 g i.p. q24h or 2 g i.p. q48h is recommended.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Ceftazidime/therapeutic use , Peritoneal Dialysis, Continuous Ambulatory/adverse effects , Adult , Anti-Bacterial Agents/administration & dosage , Ceftazidime/administration & dosage , Female , Humans , Male , Middle Aged , Monte Carlo Method , Peritonitis/drug therapy , Peritonitis/microbiology , Prospective Studies
17.
Clin J Am Soc Nephrol ; 8(11): 1988-99, 2013 Nov.
Article in English | MEDLINE | ID: mdl-23990162

ABSTRACT

Patients with ESRD undergoing dialysis have highly complex medication regimens and disproportionately higher total cost of care compared with the general Medicare population. As shown by several studies, dialysis-dependent patients are at especially high risk for medication-related problems. Providing medication reconciliation and therapy management services is critically important to avoid costs associated with medication-related problems, such as adverse drug events and hospitalizations in the ESRD population. The Medicare Modernization Act of 2003 included an unfunded mandate stipulating that medication therapy management be offered to high-risk patients enrolled in Medicare Part D. Medication management services are distinct from the dispensing of medications and involve a complete medication review for all disease states. The dialysis facility is a logical coordination center for medication management services, like medication therapy management, and it is likely the first health care facility that a patient will present to after a care transition. A dedicated and adequately trained clinician, such as a pharmacist, is needed to provide consistent, high-quality medication management services. Medication reconciliation and medication management services that could consistently and systematically identify and resolve medication-related problems would be likely to improve ESRD patient outcomes and reduce total cost of care. Herein, this work provides a review of available evidence and recommendations for optimal delivery of medication management services to ESRD patients in a dialysis facility-centered model.


Subject(s)
Delivery of Health Care, Integrated , Kidney Failure, Chronic/therapy , Medication Reconciliation , Medication Therapy Management , Pharmaceutical Services , Renal Dialysis , Cooperative Behavior , Cost Savings , Cost-Benefit Analysis , Delivery of Health Care, Integrated/economics , Drug Costs , Drug Interactions , Humans , Inappropriate Prescribing , Interdisciplinary Communication , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/diagnosis , Kidney Failure, Chronic/economics , Medication Reconciliation/economics , Medication Therapy Management/economics , Patient Care Team , Pharmaceutical Services/economics , Polypharmacy , Renal Dialysis/adverse effects , Renal Dialysis/economics , United States
18.
Antimicrob Agents Chemother ; 57(2): 864-72, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23208714

ABSTRACT

While the pharmacokinetic (PK) properties of daptomycin in hemodialysis (HD) patients have been evaluated previously by three groups, resultant dosing recommendations have varied. To address this clinical conundrum, this study combined concentration-time data from these PK evaluations and derived uniform dosing recommendations among patients on HD receiving daptomycin. A two-compartment model with separate HD and non-HD clearance terms was fit to the PK data from these studies by using BigNPAG. Embedded with PK parameters from the population PK analysis, 5,000-subject Monte Carlo simulations (MCS) were performed to identify HD dosing schemes that provided efficacy (cumulative and daily area under the concentration-time curve [AUC] values) and toxicity (trough concentrations of ≥ 24.3 mg/liter) profiles comparable to those from simulations employing the daptomycin PK model derived from the Staphylococcus aureus bacteremia-infective endocarditis (SAB-IE) study. Separate HD dosing schemes were sought for the two weekly interdialytic periods (48 and 72 h). For the 48-h interdialytic period, intra- and post-HD dosing provided the most isometric cumulative and daily AUCs. For the 72-h interdialytic period, all HD dosing schemes provided noncumulative AUC values from 48 to 72 h (AUC(48-72)) that were <50% of the SAB-IE AUC(48-72) values. Increasing the parent dose by 50% intra- or post-HD provided comparable AUC(48-72) values, while maintaining acceptable trough concentration (C(min)) values. When efficacy and toxicity profiles were evaluated for each individual study, higher probabilities for C(min) reaching ≥ 24.3 mg/liter were observed in one of the three studies. Given the high probability of C(min) being ≥ 24.3 mg/liter in one of the three studies, more intensive creatine phosphokinase (CPK) monitoring may be warranted in HD patients receiving daptomycin.


Subject(s)
Anti-Bacterial Agents/pharmacokinetics , Daptomycin/pharmacokinetics , Renal Dialysis , Staphylococcal Infections/drug therapy , Anti-Bacterial Agents/therapeutic use , Bacteremia/drug therapy , Bacteremia/microbiology , Creatine Kinase/blood , Daptomycin/therapeutic use , Endocarditis, Bacterial/drug therapy , Endocarditis, Bacterial/microbiology , Female , Humans , Male , Middle Aged , Monte Carlo Method , Staphylococcal Infections/microbiology , Staphylococcus aureus/drug effects
19.
Antimicrob Agents Chemother ; 56(2): 725-30, 2012 Feb.
Article in English | MEDLINE | ID: mdl-22083473

ABSTRACT

Scant data exist for the pharmacokinetics (PK) of ertapenem in patients on continuous ambulatory peritoneal dialysis (CAPD). The goals of this study were to characterize the PK profile of ertapenem during CAPD, determine the extent of ertapenem penetration into the peritoneal cavity, and quantify the probability of the target attainment (PTA) profile in the serum and peritoneal cavity. A single-dose PK study was conducted in seven patients on CAPD. Population PK modeling and Monte Carlo simulation determined the probability that ertapenem at 500 mg intravenously (i.v.) every 24 h (q24h) would achieve concentrations in excess of the MIC for 40% of the dosing interval (40% T>MIC, where T is time) in the serum and peritoneal cavity. Monte Carlo simulation was also used to calculate the peritoneal cavity/serum mean and median penetration ratios by estimating the area under the concentration-time curve in the peritoneal cavity and serum (AUC(Peritoneal) and AUC(Serum), respectively) from zero to infinity after a single simulated dose. The population mean (± standard deviation [SD]) values for the apparent volume in the central compartment, clearance, and apparent volume in the peritoneal cavity were 2.78 (0.62) liters, 0.24 (0.07) liters/hr, and 5.81 (2.05) liters, respectively. The mean (SD) AUC(Peritoneal)/AUC(Serum) ratio was 1.039 (0.861), and the median penetration ratio was 0.801 (interquartile range, 0.486 to 1.317). In both the serum and peritoneal cavity, ertapenem at 500 mg i.v. q24h was very likely (>90%) to achieve the pharmacodynamic target for MICs of ≤2 mg/liter. The simulations suggest that 500 mg of ertapenem i.v. q24h is very likely to achieve the exposure target associated with clinical efficacy in both the serum and peritoneal cavity against the range of MIC values deemed susceptible by the Clinical and Laboratory Standards Institute.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/pharmacokinetics , Peritoneal Dialysis, Continuous Ambulatory/methods , beta-Lactams/administration & dosage , beta-Lactams/pharmacokinetics , Adult , Aged , Anti-Bacterial Agents/blood , Anti-Bacterial Agents/urine , Area Under Curve , Chromatography, High Pressure Liquid , Ertapenem , Female , Humans , Male , Microbial Sensitivity Tests , Middle Aged , Models, Biological , Monte Carlo Method , Peritoneal Cavity/physiology , Urine/chemistry , beta-Lactams/blood , beta-Lactams/urine
20.
Hemodial Int ; 15(2): 234-42, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21395973

ABSTRACT

Medication regimen simplification may improve adherence in end-stage kidney disease. The effect of nocturnal home hemodialysis (NHHD) on medication burden is unknown. A retrospective pilot study of NHHD patients was conducted. Medication information was collected at baseline, NHHD start, and at 3, 6, 12, 18, and 24 months. SF-36 scores were collected at baseline, 6, 12, and 24 months. The number of medications, pill burden, and number of administrations per day were determined. Medication Regimen Complexity Index was used at each time point as a comparator. Medications for anemia, mineral and bone disorders (MBD), cardiovascular (CV) disease, infection, and vitamins were analyzed for number of medications and pill burden. Thirty-five patients were included. Patients used 10.5 ± 4.4 medications at baseline and 11.8 ± 4.7 at the end of the study (P=NS). Regarding the number of medications, anemia medications, anti-infectives, and vitamins increased; MBD and CV medications decreased by the end of the study. Total pill burden did not change over 24 months, nor did anemia pill burden. Mineral bone disorder and CV pill burden decreased, and vitamins and anti-infective pill burden increased. Daily medication administration times decreased significantly from 5.0 ± 1.5 to 3.6 ± 1.5 by 24 months. Switching to NHHD was associated with a significant increase in Medication Regimen Complexity Index at 24 months (P<0.05). SF-36 scores increased significantly once patients began on NHHD. No measure of medication regimen complexity was correlated with the SF-36 score. Medication burden changes over time after starting NHHD. It is unknown what effect NHHD has on adherence or medication costs, and warrants further study in a prospective comparative investigation.


Subject(s)
Hemodialysis, Home/methods , Hemodialysis, Home/standards , Kidney Failure, Chronic/therapy , Medication Adherence , Drug Administration Schedule , Female , Humans , Kidney Failure, Chronic/drug therapy , Male , Middle Aged , Practice Guidelines as Topic , Quality of Life , Retrospective Studies , Time Factors
SELECTION OF CITATIONS
SEARCH DETAIL
...