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Background Vaccination against hepatitis B virus (HBV) is recommended for dialysis patients. Two reports comparing seroprotection (SP) rates following HepB and HepB-CpG in vaccine-naïve patients with chronic kidney disease enrolled few dialysis patients (n = 122 combined). SP rates in a subset of dialysis patients were not reported or not powered to detect statistically significant differences. SP rates in those requiring additional vaccine series or booster doses are not known. Methods A retrospective cohort analysis including dialysis patients completing HepB or HepB-CpG vaccination between January 2019 and December 2020. Vaccine-naïve patients received a series of HepB or HepB-CpG (Series 1). A repeat series was given to nonresponders (Series 2). A booster regimen consists of one dose of either vaccine. Primary outcome was achieving SP (anti-HBs >10 mIU/mL) at least 60 days after the last HBV vaccine dose for Series 1 and Series 2, and achieving SP at least 3 weeks post-booster. Results For Series 1 (n = 3509), SP after HepB vaccination was significantly higher (62.9% versus 50.1% for HepB-CpG; P Conclusions SP rates in hepatitis B vaccine-naïve dialysis patients administered a recommended four doses of HepB were higher than those recommended two doses of HepB-CpG. SP rates were higher and achieved sooner if HepB-CpG was utilized initially and, if needed, for Series 2. Optimal HepB-CpG dosing deserves further study.

BackgroundPatients receiving maintenance dialysis represent a high risk, immune-compromised population with 15-25% COVID mortality rate who were unrepresented in clinical trials evaluated for mRNA vaccines’ emergency use authorization.MethodAll patients receiving maintenance dialysis that received two doses of SARS-CoV-2 mRNA vaccines with antibody test results drawn ≥14 days after the second dose, as documented in the electronic health record through March 18, 2021 were included. We report seroresponse based on levels of immunoglobulin-G against the receptor binding domain of the S1 subunit of SARS-CoV-2 spike antigen (seropositive ≥2) using FDA-approved semi-quantitative chemiluminescent assay (ADVIA Centaur® XP/XPT COV2G).ResultsAmong 186 dialysis patients from 32 clinics in 8 states tested 23±8 days after receiving 2 vaccine doses, mean age was 68±12 years, with 47% women, 21% Black, 26% residents in long-term care facilities and 97% undergoing in-center hemodialysis. Overall seropositive rate was 165/186 (88.7%) with 70% at maximum titer and with no significant difference in seropositivity between BNT162b2/Pfizer (N=148) and mRNA-1273/Moderna (N=18) vaccines (88.1% vs. 94.4%, p=0.42). Among patients with COVID-19 history, seropositive rate was 38/38 (100%) with 97% at maximum titer.ConclusionMost patients receiving maintenance dialysis were seropositive after two doses of BNT162b2/Pfizer or mRNA-1273/Moderna vaccine. Early evidence suggests that vaccinated dialysis patients with prior COVID-19 develop robust antibody response. These results support an equitable and aggressive vaccination strategy for eligible dialysis patients, regardless of age, sex, race, ethnicity, or disability, to prevent the extremely high morbidity and mortality associated with COVID-19 in this high risk population.SignificanceIn this retrospective observational evaluation of SARS-CoV-2 mRNA vaccine response defined by detectable levels of immunoglobulin-G against the receptor binding domain of the S1 subunit of SARS-CoV-2 spike antigen of ≥2 in serum of patients receiving maintenance dialysis, 165/186 (88.7%) were found to be seropositive (with 70% at maximum titer) at least 14 days after completing the second dose. No significant differences were observed by race or other subgroup or by vaccine manufacturer. Therefore, an equitable and aggressive vaccination strategy for all eligible maintenance dialysis patients, regardless of age, sex, race, ethnicity, or disability, is warranted to prevent the extremely high morbidity and mortality associated with COVID-19 in this high risk population.

Due to age and impaired kidney function, older adults with kidney disease are at increased risk of medication-related problems and related hospitalizations. One proa ctive approach to minimize this risk is deprescribing. Deprescribing refers to the systematic process of reducing or stopping a medication. Aside from preventing harm, deprescribing can potentially optimize patients’ quality of life by aligning medications with their goals of care. For some patients, deprescribing could involve less aggressive management of their diabetes and/or hypertension. In other instances, deprescribing targets may include potentially inappropriate medications that carry greater risk of harm than benefit in older adults, medications that have questionable efficacy, including medications that have varying efficacy by degree of kidney function, and that increase medication regimen complexity. We include a guide for clinicians to utilize in deprescribing, the List, Evaluate, Shared Decision-Making, Support (LESS) framework. The LESS framework provides key considerations at each step of the deprescribing process that can be tailored for the medications and context of individu al patients. Patient characteristics or clinical events that warrant consideration of deprescribing include limited life expectancy, cognitive impairment, and health status changes, such as dialysis initiation or recent hospitalization. We acknowledge patient-, clinician-, and system-level challenges to the depre scribing process. These include patient hesitancy and challenges to discussing goals of care, clinician time constraints and a lack of evidence-based guidelines, and system-level challenges of interoperable electronic health records and limited incentives for deprescribing. However, novel evidence-based tools designed to facilitate deprescribing and future evidence on effectiveness of deprescribing could help mitigate these barriers. This review provides foundational knowledge on deprescribing as an emerging component of clinical practice and research within nephrology.

Dialysis facilities voluntarily reported severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in vaccinated dialysis patients detected between January 1, 2021, and August 31, 2021, to the Centers for Disease Control and Prevention. Among 4087 patients reported, most were symptomatic, a third required hospitalization, and 9% died within 30 days of diagnosis. Monitoring SARS-CoV-2 infections and outcomes among vaccinated people on dialysis provides valuable insight into this population.

Given the increased morbidity and mortality from COVID-19 among patients undergoing maintenance dialysis, we examined the seroresponse to an additional dose of SARS-CoV-2 mRNA vaccine, using a hypothesized protective anti-spike protein IgG antibody threshold of 7 based on prior work. Among 395 patients, 384 (97%) had seroresponse ≥7 following administration of the third dose. Among those with suboptimal (peak

BackgroundSARS-CoV-2 vaccine effectiveness during the Delta period and immunogenicity threshold associated with protection against COVID-19 related hospitalization or death in the dialysis population is unknown.MethodsA retrospective, observational study assessed SARS-CoV-2 vaccine effectiveness and immunogenicity threshold in all adult maintenance dialysis patients without COVID-19 history treated between February 1 and October 2, 2021. All COVID-19 infections, composite of hospitalization or death following COVID-19 and available SARS-CoV-2 anti-spike immunoglobulin (Ig) G values were extracted from electronic medical record. COVID-19 cases per 10,000 days at risk and vaccine effectiveness during pre-Delta and Delta periods were determined.ResultsOf 15,718 patients receiving dialysis during the study period, 11,191 (71%) were fully vaccinated, 733 (5%) were partially vaccinated and 3,794 (24%) were unvaccinated. 967 COVID-19 were cases identified: 511 (53%) occurred in unvaccinated patients and 579 (60%) occurred during the Delta period. COVID-19 related hospitalization or death was less likely among vaccinated versus unvaccinated patients for all vaccines (adjusted HR 0.19 [0.12, 0.30]) and for BNT162b2/Pfizer, mRNA-1273/Moderna, and Ad26.COV2.S/Janssen (adjusted HR=0.25 [0.16, 0.40], 0.14 [0.08, 0.22], and 0.34 [0.17, 0.68] respectively). Among those with anti-spike IgG levels, those with IgG level ≥ 7 had significantly lower risk of a COVID-19 diagnosis (HR=0.25 [0.15, 0.42]) and none experienced a COVID-related hospitalization or death.ConclusionsAmong maintenance dialysis patients, SARS-CoV-2 vaccination was associated with a lower risk of COVID-19 diagnosis and associated hospitalization or death. Among vaccinated patients, low anti-spike IgG level is associated with worse COVID-19 related outcomes.Significance StatementSARS-CoV-2 vaccine effectiveness and association between antibody levels and clinical outcomes in maintenance dialysis patients is not known. Between February 1 and October 2, 2021, vaccine effectiveness was 85% against COVID-19 infection and 81% against composite of COVID-related hospitalization or death. COVID-19 case rates and severe outcomes were higher during the Delta dominant period (June 27-October 2, 2021). Increasing time (weeks) since full vaccination status was associated with increased risk for COVID-19 related hospitalization or death. Anti-spike IgG level ≥ 7 had lower risk of a COVID-19 diagnosis and no COVID-related hospitalization or death. Our findings supports utilization of SARS-CoV-2 vaccination and suggests that monitoring SARS-CoV-2 antibody levels and administering additional vaccine doses to maintain adequate immunity will be beneficial.

Rationale & ObjectivesHigh dose influenza vaccine provides better protection against influenza infection in older adults than standard dose vaccine. We compared vaccine seroresponse among hemodialysis patients over 4 months after high dose inactivated (HD-IIV3), standard dose inactivated (SD-IIV4) or recombinant (RIV4) influenza vaccine.Study DesignProspective observational study.Setting & ParticipantsPatients at four hemodialysis clinics who received influenza vaccination. Hemagglutination inhibition titers were measured at baseline and at 1, 2, 3 and 4 months following vaccination with HD-IIV3, SD-IIV4 or RIV4 influenza vaccine.OutcomeThe primary outcome was seroprotection rates at ≥1:40 and ≥1:160 (which correspond to antibody levels providing protection from infection in about 50% and 95% immunocompetent individuals, respectively) at 1, 3 and 4 months after vaccination.Analytical approachWe determined GMT and seroprotection and seroconversion rates. Chi-square or Fisher exact tests were used for categorical data; continuous values were analyzed using Wilcoxon rank-sum tests. Generalized estimating equation was used to determine association between GMT and age.Results254 HD patients received HD-IIV3 (n=141), SD-IIV4 (n=36) or RIV4 (n=77) vaccine. A robust initial seroresponse to influenza A strains was observed after all 3 vaccines, with no difference in seroprotection rates at either the ≥1:40 or ≥1:160 titer at 1 and 2 months. Seroresponses to RIV4 and SD-IIV4 waned thereafter, such that by month 3 and 4, seroprotection by HD-IIV3 was significantly higher. Seroprotection rates were lower to the B strains across all three vaccines. Results trended similarly across patients aged below 65 years.LimitationsDue to use of observational data, bias by unmeasured confounders may exist. Some of the subgroups by age were low in number.ConclusionsHemodialysis patients achieved high seroprotection rates after all 3 vaccines. The seroresponse waned more slowly with HD-IIV3 as compared to SD-IIV4 or RIV4 vaccine.

Background and ObjectivesWhile most maintenance dialysis patients exhibit initial seroresponse to vaccination, concerns remain regarding the durability of this antibody response. This study evaluated immunity over time.Design, setting, participants, and measurementsThis retrospective cohort study included maintenance dialysis patients from a midsize national dialysis provider who received a complete SARS-CoV-2 vaccine series and had at least one antibody titer checked after full vaccination. Immunoglobulin G spike antibodies (SAb-IgG) titers were assessed monthly with routine labs beginning after full vaccination and followed over time; the semiquantitative SAb-IgG titer reported a range between 0 and ≥ 20 U/L. Descriptive analyses compared trends over time by prior history of COVID-19 and type of vaccine received. Time-to-event analyses were conducted for the outcome of loss of seroresponse (SAb-IgG < 1 U/L or development of COVID-19). Cox proportional hazards regression was used to adjust for additional clinical characteristics of interest.ResultsAmong 1898 maintenance dialysis patients, 1567 (84%) had no prior history of COVID-19. Patients without a history of COVID-19 had declining titers over time. Among 441 BNT162b2/Pfizer recipients, median [IQR] SAb-IgG titer declined from 20 [5.99-20] U/L in month 1 to 1.30 [0.15-3.59] U/L by month 6. Among 779 mRNA-1273/Moderna recipients, median [IQR] SAb-IgG titer declined from 20 [20-20] in month 1 to 6.20 [1.74-20] by month 6. The 347 Ad26.COV2.S/Janssen recipients had a lower titer response than mRNA vaccine recipients over all time periods. In time-to-event analyses, Ad26.COV2.S/Janssen and mRNA-1273/Moderna recipients had the shortest and longest time to loss of seroresponse, respectively. The maximum titer reached in the first two months after full vaccination was predictive of the durability of the SAb-IgG seroresponse; patients with SAb-IgG titer 1-19.99 U/L were more likely to have loss of seroresponse compared to patients with SAb-IgG titer ≥ 20 U/L (HR 23.9 [95% CI: 16.1-35.5]).ConclusionsVaccine-induced seroresponse wanes over time among maintenance dialysis patients across vaccine types. Early titers after full vaccination predict the durability of seroresponse.

BACKGROUND AND OBJECTIVES: Although most patients receiving maintenance dialysis exhibit initial seroresponse to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination, concerns exist regarding the durability of this antibody response. This study evaluated seroresponse over time. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This retrospective cohort study included patients on maintenance dialysis, from a midsize national dialysis provider, who received a complete SARS-CoV-2 vaccine series and had at least one antibody titer checked after full vaccination. IgG spike antibodies (anti-spike IgG) titers were assessed monthly with routine laboratory tests after vaccination; the semiquantitative assay reported a range between zero and ≥20 Index. Descriptive analyses compared trends over time by history of coronavirus disease 2019 (COVID-19) and vaccine type. Time-to-event analyses examined the outcome of loss of seroresponse (anti-spike IgG

ImportanceVaccines against SARS-CoV-2 are highly effective in the general population; however, their efficacy may be diminished in maintenance dialysis patients, a population particularly vulnerable to COVID-19 infection and morbidity.ObjectiveWe assessed vaccine response in a national sample of maintenance dialysis patients and identified predictors of response.DesignRetrospective cohort studySetting130 Dialysis Clinic, Inc (DCI) facilitiesParticipantsMaintenance dialysis patients without known prior COVID-19 or a positive baseline antibody titerExposure(s)Vaccine type and clinical characteristicsMain Outcome(s)Using a semi-quantitative assay for antibodies against SARS-CoV-2 spike antigen, vaccine response was defined as at least one titer ≥1 U/L between 14 and 74 days after completion of a SARS-CoV-2 vaccine series. Regression analysis was used to identify characteristics associated with response.ResultsAmong 1528 patients, 437 received BNT162b2/Pfizer vaccine, 766 received mRNA-1273/Moderna, and 325 received Ad26.COV2.S/Janssen. Serologic response differed significantly by vaccine type: 381/437 (87%) among BNT162b2/Pfizer recipients, 736/766 (96%) among mRNA-1273/Moderna recipients, and 119/325 (37%) among Ad26.COV2.S/Janssen recipients. Vaccine type, older age, immune-modulating medication, history of transplantation, and lower serum albumin were associated with vaccine non-response.Conclusions and RelevanceSerologic response to mRNA vaccines is robust among maintenance dialysis patients. Future research should evaluate durability of this response, correlation between seroresponse and protection from COVID-19, and the role of the AD26.COV2.S/Janssen vaccine in this vulnerable population.

Medication-related problems are a leading cause of morbidity and mortality. Patients requiring dialysis are at a heightened risk of adverse drug reactions because of the prevalence of polypharmacy, multiple chronic conditions, and altered (but not well understood) medication pharmacokinetics and pharmacodynamics inherent to renal failure. To minimize preventable medication-related problems, healthcare providers need to prioritize medication safety for this population. The cornerstone of medication safety is medication reconciliation. Here, we present a case highlighting adverse outcomes when medication reconciliation is insufficient at care transitions. We review available literature on the prevalence of medication discrepancies worldwide. We also explain effective medication reconciliation and the practical considerations for implementation of effective medication reconciliation in dialysis units. In light of the addition of medication reconciliation requirements to the Centers for Medicare and Medicaid Services End-Stage Renal Disease (ESRD) Quality Incentive Program, this review also provides guidance to dialysis unit leadership for improving current medication reconciliation practices. Prioritization of medication reconciliation has the potential to positively impact rates of medication-related problems, as well as, medication adherence, healthcare costs, and quality of life.

Background and objectives High-dose influenza vaccine, which contains fourfold more antigen than standard dose, is associated with fewer cases of influenza and less influenza-related morbidity in the elderly general population. Whether the high-dose influenza vaccine benefits patients on dialysis, whose immune response to vaccination is less robust than that of healthy patients, is uncertain. Design, setting, participants, & measurements We compared hospitalizations and deaths during the 2015–2016 and 2016–2017 influenza seasons by vaccine type (standard trivalent, standard quadrivalent, and high-dose trivalent influenza vaccine) administered within a national dialysis organization. The association of vaccine type with outcomes was estimated using Cox proportional hazards regression with adjustment for patient factors and “center effect.” Analyses were stratified by age and dialysis modality. Results Between September 1 and December 31, 2015, standard dose trivalent, standard dose quadrivalent, and high-dose trivalent influenza vaccines were administered to 3057 (31%), 5981 (61%), and 805 (8%) patients, respectively. The adjusted rates of first hospitalizations by vaccine type during the influenza season were 8.43, 7.88, and 7.99 per 100 patient-months, respectively, and the adjusted rates of death were 1.00, 0.97, and 1.04, respectively. These differences were not significant. In 2016, 3614 (39%) received quadrivalent vaccine, and 5700 (61%) received high-dose trivalent vaccine. The adjusted rates of first hospitalization by vaccine type were 8.71 and 8.04 per 100 patient-months, respectively, and the adjusted rates of death were 0.98 and 1.02, respectively. Receipt of high dose was associated with a significant reduction in hospitalization (hazard ratio, 0.93; 95% confidence interval, 0.86 to 1.00; P=0.04); there was no significant association with death. There was no significant heterogeneity of either association by age group or dialysis modality. Conclusions Receipt of high-dose compared with standard dose influenza vaccine in 2016–2017 was associated with lower rates of hospitalization in patients on dialysis, although that was not seen in 2015–2016.

Rationale & objective During the COVID-19 pandemic, patients receiving maintenance dialysis are a highly vulnerable population due to their comorbidities and circumstances that limit physical distancing during treatment. This study sought to characterize the risk factors for and outcomes following COVID-19 infection in this population. Study design Retrospective cohort study. Setting & participants Maintenance dialysis patients in clinics with at least one patient with a positive test for SARS-CoV-2 from February to June 2020, treated by a mid-size national dialysis provider. Predictors Demographics, dialysis characteristics, residence in a congregate setting, comorbid conditions, measures of frailty, and use of selected medications. Outcomes COVID-19 defined as having a positive SARS-CoV-2 test and all-cause mortality among those with COVID-19. Analytical approach Logistic regression analyses to identify clinical characteristics associated with COVID-19and risk factors associated with mortality among patients following COVID-19. Results 438/7948 (5.5%) maintenance dialysis patients developed COVID-19. Male sex, Black race, in-center dialysis (vs. home dialysis), treatment at an urban clinic, residence in a congregate setting, and greater comorbidity were associated with contracting COVID-19. Odds of COVID-19 was 17-fold higher for those residing in a congregate setting [OR = 17.10 (95% CI 13.51, 21.54)]. Of the 438 maintenance dialysis patients with COVID-19, 109 (24.9%) died. Older age, heart disease, and markers of frailty were associated with mortality. Limitations No distinction between symptomatic and asymptomatic SARS-CoV-2 positivity, with asymptomatic screening limited by testing capacity during this initial COVID-19 surge period. Conclusions COVID-19 is common among patients receiving maintenance dialysis, particularly those residing in congregate settings. Among maintenance dialysis patients with COVID-19, mortality is high, exceeding 20%.

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.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 of400 in both the serum and the peritoneal cavity for a variety of iv vancomycin dosing schemes (1-2 g every 24-48 h).In the probability of target attainment (PTA) analyses, only 2 g of iv vancomycin every 24 h conferred90% probability of achieving an AUC/MIC ratio of400 for MIC values2 mg/L in the serum. However, this dosing regimen resulted in average trough concentrations20 mg/L. In the peritoneal cavity, no regimen yielded PTA ≥90% for MIC values ≥0.5 mg/L.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.

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.

Screening processes to identify patients who have chronic kidney disease (CKD) early in the disease allow time to manage its comorbidities and complications effectively and aggressively. The Kidney Early Evaluation Program (KEEP), sponsored by the National Kidney Foundation (NKF), is a free screening program that targets people who have diabetes, hypertension, and parents, grandparents, or siblings with diabetes, hypertension, or CKD.To (1) introduce KEEP and its objectives and (2) review population data and progress with goals to date.The KEEP goals are to raise awareness of CKD, especially in high-risk patients, provide free testing, and encourage dialogue between patients and their physicians, leading to a treatment plan. Of the 55,000 patients who have been screened through KEEP, approximately 13,000 (29%), or nearly 1 in 3 patients, have been identified as having CKD. Once a patient has been diagnosed with CKD, clinicians must address risk factors such as diabetes, hypertension, and kidney-specific diseases (e.g., glomerular diseases) that contribute to the process of renal decline. The NKF through the Kidney Disease Outcomes Quality Initiative has assembled a series of guidelines addressing dialysis adequacy, vascular access, anemia, nutrition, CKD, bone and mineral metabolism, dyslipidemia, hypertension, cardiovascular disease, and diabetes.CKD is quite common but often unrecognized and undertreated, even though rigorous guidelines for diagnosis and care have been developed. Ten areas have been identified as important for optimal care of the CKD patient. Each of these areas should be addressed and closely monitored in this population: hypertension, anemia, glucose control, lipid control, smoking cessation, aspirin prophylaxis and use of a beta-blocker post-myocardial infarction, use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, diet, exercise, and weight control.

Background. End-stage renal disease (ESRD) patients are prescribed numerous medications. The United States Renal Data System (USRDS) reported on medication prescribing patterns in 1998. Since then, several new medications, treatment guidelines and recommendations have been introduced. The objective was to analyse and compare haemodialysis (HD) patient medication prescribing patterns between the Dialysis Clinic, Inc. (DCI) database and the USRDS report. Methods. Point-prevalent (01/01/03) medication use data from the DCI national database was obtained. Data collected included patient demographics, reason for and duration of ESRD, and medication listed on profile. All medications were classified similar to the USRDS and by where taken (clinic vs home). Medication prescribing patterns were compared between DCI and USRDS databases. Comparisons between age groups (

Over the last 10 years, the main advances in RCN have come in our ability to predict outcomes for an individual patient. Treatment trials have been almost all uniformly disappointing. Recent positive trials with acetylcysteine and PGE1 will require confirmation in larger trials that are adequately powered for meaningful end points in the PCI population. In the meantime, adequate prehydration and maintenance of post-PCI urine flow rates of > 150 mL/min remain the most prudent measures. As the population ages, breakthroughs with respect to new contrast agents or effective prevention measures will be needed to offer PCI to the spectrum of patients at risk for renal injury.

There is increasing use of intermittent dosing of antibiotics to treat peritoneal dialysis (PD)-related peritonitis. The disposition of intravenous cefazolin and tobramycin was studied in automated PD (APD) patients. Ten patients were recruited and received a single intravenous dose of cefazolin (15 mg/kg) and tobramycin (0.6 mg/kg). Blood and dialysate samples were collected at the beginning, middle, and end of dwells 1 to 3 (on cycler), and at the end of dwells 4 to 5 (off cycler) for a 24-h period. Baseline and 24-h urine samples were collected. Pharmacokinetic parameters were calculated using a monoexponential model. Cefazolin and tobramycin half-lives were markedly different on cycler than off cycler (cefazolin on cycler : 10.67 +/- 4.66 h; cefazolin off cycler : 23.09 +/- 5.6 h; P = 0.001; tobramycin on cycler : 14.27 +/- 4.53 h; tobramycin off cycler : 68. 5 +/- 26.47 h; P < 0.001). Mean serum and dialysate concentrations were above minimum inhibitory concentrations of susceptible organisms throughout the 24-h period for both drugs with intravenous administration. A model was developed to examine serum and dialysate concentrations after intermittent intraperitoneal administration of 15 mg/kg cefazolin and 0.6 mg/kg tobramycin. Model-predicted intraperitoneal cefazolin provides adequate serum and dialysate concentrations for 24 h. Intermittent intraperitoneal tobramycin doses must be 1.5 mg/kg for one exchange during the first day and then given as 0.5 mg/kg thereafter. It is concluded that the current empiric dosing recommendations for PD-related peritonitis may be adequate for cefazolin (15 to 20 mg/kg); however, tobramycin doses must be changed to 1.5 mg/kg intraperitoneally on day 1, then to 0.5 mg/kg intraperitoneally thereafter in APD patients.

Background Hemodialysis (HD) patients are at risk for medication-related problems (MRP). The MRP number, type, and appearance rate over time in ambulatory HD patients has not been investigated. Methods Randomly selected HD patients were enrolled to receive monthly pharmaceutical care visits. At each visit, MRP were identified through review of the patient chart, electronic medical record, patient interview, and communications with other healthcare disciplines. All MRP were categorized by type and medication class. MRP appearance rate was determined as the number of MRP identified per month/number of months in study. The number of MRP per patient-drug exposures were determined using: {[(number of patients) × (mean number of medications)]/(number of months of study)} /number of MRP identified. Results were expressed as mean ± standard deviation or percentages. Results Patients were 62.6 ± 15.9 years old, had 6.4 ± 2.0 comorbid conditions, were taking 12.5 ± 4.2 medications, and 15.7 ± 7.2 doses per day at baseline. Medication-dosing problems (33.5%), adverse drug reactions (20.7%), and an indication that was not currently being treated (13.5%) were the most common MRP. 5,373 medication orders were reviewed and a MRP was identified every 15.2 medication exposures. Overall MRP appearance rate was 0.68 ± 0.46 per patient per month. Conclusion MRP continue to occur at a high rate in ambulatory HD patients. Healthcare providers taking care of HD patients should be aware of this problem and efforts to avoid or resolve MRP should be undertaken at all HD clinics.

Gentamicin pharmacokinetics during slow daily home hemodialysis.BackgroundGentamicin is commonly used in hemodialysis patients. Gentamicin pharmacokinetics during traditional hemodialysis have been described. Slow daily home (SDH) hemodialysis (7 to 9 hours a day/6 days a week) use is increasing due to benefits observed with increased hemodialysis. We determined gentamicin pharmacokinetics for SDH hemodialysis patients.MethodsEight patients (four male and four female) received a single intravenous dose of 0.6 mg/kg gentamicin post-hemodialysis. Blood samples were collected at 5, 10, 15, 30, and 60 minutes after dose. The next day patients underwent a typical SDH hemodialysis (high-flux F50NR dialyzer) session. Blood samples were taken at 0, 5, 15, 60, 120, 240, 360, 480 minutes during and 15, 30 and 60 minutes post-hemodialysis. Baseline and 24-hour urine samples were collected. Pharmacokinetic parameters were calculated assuming a one-compartment model.ResultsPatients were 42.5 ± 13.1 years old (mean ± SD). Inter-, intra-, and post-hemodialysis collection periods were 17.0 ± 2.1 hours, 8.1 ± 0.4 hours, and 1.1 ± 0.1 hours, respectively. Intra-, and interdialytic gentamicin half-lives were different (intradialytic, 3.7 ± 0.8 hours; interdialytic, 20.4 ± 4.7 hours; P < 0.0001). Hemodialysis clearance accounted for 70.5% gentamicin total clearance. Renal clearance correlated with glomerular filtration rate (GFR) (renal clearance = 1.2 GFR; r2 = 0.98; P < 0.001). Mean peak and trough of hemodialysis concentrations were 1.8 ± 0.6 μg/mL and 0.5 ± 0.2 μg/mL, respectively. Post-hemodialysis rebound was 3.1 ± 8.8% at 1 hour.ConclusionPharmacokinetic model predicts 2.0 to 2.5 mg/kg dose gentamicin post-hemodialysis would provide peak (1 hour post-dose) and trough (end of SDH hemodialysis session) concentrations of 6.0 to 7.5 μg/mL and 0.7 to 0.8 μg/mL, respectively. This would provide adequate coverage for most gram-negative organisms in SDH hemodialysis patients.

The paper reports the results of a digital computer simulation in which a sample of connected speech was analyzed and resynthesized in terms of a series of orthogonalized exponentially damped sinusoids. It was found to be possible to synthesize each pitch period from a function set having only 16 fixed frequencies with fixed damping at each frequency. The processing was done pitch‐synchronously on an IBM‐7090 digital computer, using 10‐bit accuracy speech which had been digitized at a rate of 12000 samples per second. Procedures for generating the sample values of the function set on a digital computer, manual pitch extraction, and data‐processing methods are described. Comparisons of the input and resynthesized speech samples are presented both visually and aurally by means of a tape recording. The results indicate that both the phonetic content and the quality of the speaker's voice are retained in the analysis‐synthesis process. This analysis‐synthesis process, simulated in this investigation, is amenable to real‐time analog realization. (This work was supported by the Rome Air Development Center under contract No. AF 30(602)‐2446.)

Time‐domain speech processors, that analyze the short‐time autocorrelation function in terms of a set of orthogonal functions, are shown to yield parameters that are the coefficients of a generalized Fourier cosine series representation of the speech power spectrum. Two examples are described, one using a Laguerre filter and one using a tapped delay line as in the autocorrelation Vocoder. In the case of the autocorrelation Vocoder, the derived power spectrum representation reduces to a simple Fourier cosine series in the frequency domain.

Background Intravenous iron is typically administered during the hemodialysis (HD) procedure. HD patients may be prescribed high-flux (HF) or high-efficiency (HE) dialysis membranes. The extent of iron sucrose and iron dextran removal by HD using HF or HE membranes and by ultrafiltration rate (UFR) is unknown. Methods Two in vitro HD systems were designed and constructed to determine the dialyzabiltiy of iron from a simulated blood system (SBS) containing 100 mg iron sucrose or iron dextran (system A) or 1000 mg iron sucrose (system B). Both in vitro systems utilized a 6-L closed-loop SBS system that was subject to 4 different HD conditions conducted over 4 hours: HE membrane + 0 ml/hr UFR; HE membrane + 500 ml/hr UFR; HF membrane + 0 ml/hr UFR; HF membrane + 500 ml/hr UFR. Blood flow and dialysate flow rates were 500 ml/min and 800 ml/min, respectively. The dialysate compartment was a 192-L open system for system A and a 6-L closed-loop system for system B. Samples from the SBS and dialysate compartments were taken at various time points and iron elimination rate and HD clearance was determined. Iron removal from the SBS > 15% was considered clinically significant. Results The greatest percentage removal from the SBS was 13.5% and -0.03% utilizing system A and B, respectively. Iron sucrose and iron dextran dialysate concentration was below the lower limits of assay (< 2 ppm) for system A. Dialysate recovery of iron was negligible: 0 – 5.4 mg system A and 5.47 – 23.59 mg for system B. Dialyzer type or UFR did not affect iron removal. Conclusion HF or HE dialysis membranes do not remove clinically significant amounts of iron sucrose or dextran formulations over a 4-hour HD session. This effect remained constant even controlling for UFR up to 500 ml/hour. Therefore, iron sucrose and iron dextran are not dialyzed by HE or HF dialysis membranes irrespective of UFR.

Disclosed is a system whereby in a transmit mode analog speech is sampled d converted digitally to 12 bits of accuracy and then fed into a fast Fourier transform (FFT) processor which analyzes the speech into spectral and pitch parameters. These parameters are then quantized into a data stream which acts as an input to a differential phase shift keying modulator. The modulator constructs a multi-tone modem output signal from a 25 tone stack which is converted to an analog signal which is fed into a communications channel. In the receive mode a modem input signal from the communications channel is fed through the same analog to digital converter which was used for input speech. A data stream is now provided which is coupled back into the same digital FFT processor which now operates to provide pitch spectral coefficients which are then separated and used by a synthesizer to reconstruct a speech waveform. The speech waveform is applied to a digital analog converter which is the same converter used to produce the line signal when the processor operates in the transmit mode. The FFT processor implements a single FFT algorithm which is used for both vocoder and modem processing in both the transmit and receive modes.

This paper describes a digital cepstrum‐pitch detector designed to work in real time on a 12‐bit binary machine. Spectrum and cepstrum analysis of raw speech data is accomplished through the use of a single complex Fast Fourier Transform (FFT) algorithm. Pitch detection is accomplished by a cepstrum‐peak scanning logic designed to locate the position of a peak corresponding to the pitch period. Since other peaks may exist in the data, logic is required to differentiate these peaks from the desired one. Because of the limited word size of the machine, special processing algorithms were developed to perform logging and to avoid the squaring of variables. Various logical operations performed on the spectrum and cepstrum functions in voicing detection and in the extraction of pitch are presented and discussed. A demonstration of the performance of this pitch detector when operated with a 2400‐bit/sec digital vocoder will be presented by means of a tape recording. [Work supported under contract.]

In this paper, an experiment is described in which articulation scores were measured as the number of transmitted spectral parameters was varied from 6 to 16 in a Laguerre autocorrelation vocoder. The transmitted spectral parameters were the expansion coefficients of the short‐time‐averaged speech autocorrelation function in terms of Laguerre functions. Thus, these parameters are the same as the expansion coefficients of the speech power spectrum in terms of the Fourier cosine transforms of the Laguerre functions. The analysis and synthesis filters in this vocoder were synthesized from a number of identical RC transistor circuits. The time constant of the Laguerre analysis and synthesis filters was 125×10−6 sec. The system was operated in an analog back‐to‐back mode for these tests. The results presented show that about 16 parameters are required to achieve performance comparable to contemporary filter‐bank vocoders. The intelligibility tests were performed by Bolt Beranek and Newman Inc., in early 1965.

Speech compression systems are described which make use of orthonormal function expansions of either the speech waveform itself or the short‐time autocorrelation function of the speech waveform. A system of this type theoretically can be optimized so that a minimum number of independent, slowly varying parameters are transmitted for a given level of desired performance. In both types of systems, the compression in data rate is obtained through the optimization of the expansion series, the truncation of the series, and by averaging the coefficients of the expansion over several pitch periods. In addition, the phase spectrum of the speech signal can be eliminated in a systematic manner in both the system wherein the waveform is analyzed and the systems where the autocorrelation function is analyzed.