Conversion from Intravenous Vitamin D Analogs to Oral Calcitriol in Patients Receiving Maintenance Hemodialysis.

BACKGROUND AND OBJECTIVES: In the United States, intravenous vitamin D analogs are the first-line therapy for management of secondary hyperparathyroidism in hemodialysis patients. Outside the United States, oral calcitriol (1,25-dihydroxyvitamin D3) is routinely used. We examined standard laboratory parameters of patients on in-center hemodialysis receiving intravenous vitamin D who switched to oral calcitriol. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a retrospective cohort study of adult patients treated within Fresenius Kidney Care clinics. During a 6-month period (December 2013 to May 2014), we identified patients on an intravenous vitamin D analog (doxercalciferol or paricalcitol) who switched to oral calcitriol and matched them to patients receiving an intravenous vitamin D analog. Mean serum calcium, phosphate, and intact parathyroid hormone (iPTH) concentrations were examined for up to 12 months of follow-up. We used Poisson and Cox proportional hazards regression models to examine hospitalization and survival rates. The primary analysis was conducted as intention-to-treat; secondary analyses included an as-treated evaluation. RESULTS: A total of 2280 patients who switched to oral calcitriol were matched to 2280 patients receiving intravenous vitamin D. Compared with patients on intravenous vitamin D, mean calcium and phosphate levels in the oral calcitriol group were lower after the change to oral calcitriol. In contrast, iPTH levels were higher in the oral calcitriol group. At 12 months, the percentage of patients with composite laboratories in target range (calcium <10 mg/dl, phosphate 3.0-5.5 mg/dl, and iPTH 150-600 pg/ml) were comparable between groups (45% versus 45%; P=0.96). Hospital admissions, length of hospital stay, and survival were comparable between groups. An as-treated analysis and excluding those receiving cinacalcet did not reveal significant between-group differences. CONCLUSIONS: Among patients receiving in-center hemodialysis who were switched to oral calcitriol versus those on an intravenous vitamin D analog, the aggregate of all mineral and bone laboratory parameters in range was largely similar between groups.

The positive effects of an antimicrobial stewardship program targeting outpatient hemodialysis facilities.

BACKGROUND: Antimicrobial stewardship programs are effective in optimizing antimicrobial prescribing patterns and decreasing the negative outcomes of antimicrobial exposure, including the emergence of multidrug-resistant organisms. In dialysis facilities, 30%-35% of antimicrobials are either not indicated or the type of antimicrobial is not optimal. Although antimicrobial stewardship programs are now implemented nationwide in hospital settings, programs specific to the maintenance dialysis facilities have not been developed. OBJECTIVE: To quantify the effect of an antimicrobial stewardship program in reducing antimicrobial prescribing.Study design and settingAn interrupted time-series study in 6 outpatient hemodialysis facilities was conducted in which mean monthly antimicrobial doses per 100 patient months during the 12 months prior to the program were compared to those in the 12-month intervention period. RESULTS: Implementation of the antimicrobial stewardship program was associated with a 6% monthly reduction in antimicrobial doses per 100 patient months during the intervention period (P=.02). The initial mean of 22.6 antimicrobial doses per 100 patient months decreased to a mean of 10.5 antimicrobial doses per 100 patient months at the end of the intervention. There were no significant changes in antimicrobial use by type, including vancomycin. Antimicrobial adjustments were recommended for 30 of 145 antimicrobial courses (20.6%) for which there were sufficient clinical data. The most frequent reasons for adjustment included de-escalation from vancomycin to cefazolin for methicillin-susceptible Staphylococcus aureus infections and discontinuation of antimicrobials when criteria for presumed infection were not met. CONCLUSIONS: Within 6 hemodialysis facilities, implementation of an antimicrobial stewardship was associated with a decline in antimicrobial prescribing with no negative effects.

Depressive affect in incident hemodialysis patients.

BACKGROUND: The prevalence of depressive affect is not well defined in the incident hemodialysis (HD) population. We investigated the prevalence of and associated risk factors and hospitalization rates for depressive affect in incident HD patients. METHODS: We performed a prospective investigation using the Patient Health Questionnaire 2 (PHQ2) depressive affect assessment. From January to July of 2013 at 108 in-center clinics randomly selected across tertiles of baseline quality measures, we contacted 577 and 543 patients by telephone for depressive affect screening. PHQ2 test scores range from 0 to 6 (scores ≥3 suggest the presence of depressive affect). The prevalence of depressive affect was measured at 1-30 and 121-150 days after initiating HD; depressive affect risk factors and hospitalization rates by depressive affect status at 1-30 days after starting HD were computed. RESULTS: Of 1120 contacted patients, 340 completed the PHQ2. In patients screened at 1-30 or 121-150 days after starting HD, depressive affect prevalence was 20.2% and 18.5%, respectively (unpaired t-test, P = 0.7). In 35 patients screened at both time points, there were trends for lower prevalence of depressive affect at the end of incident HD, with 20.0% and 5.7% of patients positive for depressive affect at 1-30 and 121-150 days, respectively (paired t-test, P = 0.1). Hospitalization rates were higher in patients with depressive affect during the first 30 days, exhibiting 1.5 more admissions (P < 0.001) and 10.5 additional hospital days (P = 0.008) per patient-year. Females were at higher risk for depressive affect at 1-30 days (P = 0.01). CONCLUSIONS: The prevalence of depressive affect in HD patients is high throughout the incident period. Rates of hospital admissions and hospital days are increased in incident HD patients with depressive affect.

Right TraC™ Post-Hospitalization Care Transitions Program to Reduce Readmissions for Hemodialysis Patients.

BACKGROUND: Hemodialysis (HD) patients have high hospitalization rates. This nonrandomized trial tested the effect of a bundle of renal-specific "Right TraC™" strategies on 30-day all-cause readmission rates and, secondarily, 90-day readmissions and overall admissions among HD patients. METHODS: Twenty-six Fresenius clinics in West Virginia, Ohio, and Kentucky participated in the interventions. Eighteen matched clinics served as controls; intervention clinics also served as their own controls. We deployed the intervention in 3 incremental phases focused on patient information exchange, post-hospital follow-up, and telephonic case management. Thirty-day hospital readmissions per patient year (ppy) were calculated by dividing the total number of readmissions within 30 days of index admission by the total number of patient-years in baseline (2012) and remeasurement (2014) periods. We also compared readmission rates from 2010 to 2015. We used repeated measures Poisson regression to compare outcomes between groups and time periods. RESULTS: From 2012 to 2014, 30-day all-cause readmissions ppy declined for Right TraC clinics (from 0.88 to 0.66 [p < 0.001]; for controls, from 0.73 to 0.61 [p = 0.16]). Difference in change between groups was nonsignificant (p = 0.26). Overall admissions ppy declined: for Right TraC clinics from 2.51 to 1.97 (p < 0.001); for controls from 2.14 to1.92 (p = 0.21); difference in change between groups was significant (p = 0.01). For 2010, 2011, and 2012, Right TraC clinic 30-day readmissions ppy were unchanged: 0.89, 1.00, 0.88 (p = 0.61 and p = 0.49); they declined to 0.66 (p < 0.001) in 2014 (intervention year); rose to 0.70 (p = 0.06) in 2015 (interventions discontinued). CONCLUSION: We conclude that Right TraC interventions may have been helpful in reducing hospital readmission rates.

Improvements in MBD lab outcomes associated with improved pharmaceutical care in hemodialysis patients.

End stage renal disease (ESRD) patients require a large number of medications and are known to have high rates of nonadherence. It is estimated that >50% of ESRD patients do not take their phosphate binders as prescribed. The renal pharmacy FreseniusRx provides coordinated ESRD medication delivery and adherence support for enrolled patients. We investigated whether coordinated pharmacy care of mineral and bone disorder (MBD) therapies is associated with improvements in laboratory. outcomes. We used data from hemodialysis patients treated at Fresenius Medical Care North America (FMCNA) clinics from February 2014 to January 2015. We included patients who were residing in a state with >100 patients in the FMCNA network, not in a nursing home, and prescribed a phosphate binder and/or calcimimetic. We found 15,287 pharmacy patients who met the study criteria. Concurrent control patients not in the pharmacy were matched to pharmacy patients on a monthly basis that was based off the first date of receipt of therapy from FreseniusRx using 1:1 nearest neighbor matching on the logit of the propensity score for an array of clinical and non-clinical parameters. Logistic regression was used to measure the association between pharmacy care and patients achieving their laboratory goals for phosphorus (PO4) and intact parathyroid hormone (iPTH), and combined goals for total calcium (Ca), PO4, and iPTH. We analyzed data from 30,574 patients (15,287 pharmacy and control). In unadjusted and adjusted analyses, we consistently observed that pharmacy patients were more likely to achieve their MBD laboratory goals as compared to controls. In an adjusted analysis, we found pharmacy patients were more likely to achieve their MBD laboratory targets at 3, 6, 9, and 12 months for PO4 (11.1%, 10.5%, 11.8% and 12.7% respectively), iPTH (8.9%, 17.5%, 23.4% and 27.9% respectively) and combined goals for Ca, PO4, and. iPTH (12.1%, 13.4%, 16.7% and 21.2% respectivelv) versus controls (n<0.01 for all comparisons). These findings indicate that coordinated pharmaceutical care may be associated with improvements in patients achieving their MBD laboratory goals.

Outcomes among patients receiving in-center, self-care hemodialysis.

Modalities of renal replacement therapy are categorized into incenter hemodialysis and home therapies. A subset of hemodialysis patients referred to as in-center self-care hemodialysis (ICSCHD) receive patient training as if they were going home but instead perform their dialysis in-center with minimal staff support. Preliminary data suggests ICSCHD is associated with better outcomes than traditional in-center hemodialysis. We looked at ICSCHD patients initiating maintenance dialysis from April 1, 2011 to March 30, 2014 and compared them at a 1:2 ratio to propensity-score matched controls from surrounding facilities within the same catchment area. The median follow-up was 14 months. Patients on ICSCHD had lower mortality rate (0.02 vs 0.07 per patient year; p <0.05), fewer hospitalization events (0.82 vs. 1.70 per patient year; p = 0.008) and fewer missed treatments (1.1% vs 3.8% of all treatments; p = 0.005) than matched controls. We concluded that patients on ICSCHD had lower mortality rates and fewer hospital days than well-matched controls and spent more time on dialysis and missed fewer treatments. Establishing a facility-wide.

Order-restricted inference for multivariate longitudinal data with applications to the natural history of hearing loss.

Multivariate outcomes are often measured longitudinally. For example, in hearing loss studies, hearing thresholds for each subject are measured repeatedly over time at several frequencies. Thus, each patient is associated with a multivariate longitudinal outcome. The multivariate mixed-effects model is a useful tool for the analysis of such data. There are situations in which the parameters of the model are subject to some restrictions or constraints. For example, it is known that hearing thresholds, at every frequency, increase with age. Moreover, this age-related threshold elevation is monotone in frequency, that is, the higher the frequency, the higher, on average, is the rate of threshold elevation. This means that there is a natural ordering among the different frequencies in the rate of hearing loss. In practice, this amounts to imposing a set of constraints on the different frequencies' regression coefficients modeling the mean effect of time and age at entry to the study on hearing thresholds. The aforementioned constraints should be accounted for in the analysis. The result is a multivariate longitudinal model with restricted parameters. We propose estimation and testing procedures for such models. We show that ignoring the constraints may lead to misleading inferences regarding the direction and the magnitude of various effects. Moreover, simulations show that incorporating the constraints substantially improves the mean squared error of the estimates and the power of the tests. We used this methodology to analyze a real hearing loss study.

Constrained inference in mixed-effects models for longitudinal data with application to hearing loss.

In medical studies, endpoints are often measured for each patient longitudinally. The mixed-effects model has been a useful tool for the analysis of such data. There are situations in which the parameters of the model are subject to some restrictions or constraints. For example, in hearing loss studies, we expect hearing to deteriorate with time. This means that hearing thresholds which reflect hearing acuity will, on average, increase over time. Therefore, the regression coefficients associated with the mean effect of time on hearing ability will be constrained. Such constraints should be accounted for in the analysis. We propose maximum likelihood estimation procedures, based on the expectation-conditional maximization either algorithm, to estimate the parameters of the model while accounting for the constraints on them. The proposed methods improve, in terms of mean square error, on the unconstrained estimators. In some settings, the improvement may be substantial. Hypotheses testing procedures that incorporate the constraints are developed. Specifically, likelihood ratio, Wald, and score tests are proposed and investigated. Their empirical significance levels and power are studied using simulations. It is shown that incorporating the constraints improves the mean squared error of the estimates and the power of the tests. These improvements may be substantial. The methodology is used to analyze a hearing loss study.