How to Apply Multiple Imputation in Propensity Score Matching with Partially Observed Confounders: A Simulation Study and Practical Recommendations

Propensity score matching (PSM) has been widely used to mitigate confounding in observational studies, although complications arise when the covariates used to estimate the PS are only partially observed. Multiple imputation (MI) is a potential solution for handling missing covariates in the estimation of the PS. However, it is not clear how to best apply MI strategies in the context of PSM. We conducted a simulation study to compare the performances of popular non-MI missing data methods and various MI-based strategies under different missing data mechanisms. We found that commonly applied missing data methods resulted in biased and inefficient estimates, and we observed large variation in performance across MI-based strategies. Based on our findings, we recommend 1) estimating the PS after applying MI to impute missing confounders; 2) conducting PSM within each imputed dataset followed by averaging the treatment effects to arrive at one summarized finding; 3) a bootstrapped-based variance to account for uncertainty of PS estimation, matching, and imputation; and 4) inclusion of key auxiliary variables in the imputation model

Performance of statistical models to predict mental health and substance abuse cost

BACKGROUND: Providers use risk-adjustment systems to help manage healthcare costs. Typically, ordinary least squares (OLS) models on either untransformed or log-transformed cost are used. We examine the predictive ability of several statistical models, demonstrate how model choice depends on the goal for the predictive model, and examine whether building models on samples of the data affects model choice. METHODS: Our sample consisted of 525,620 Veterans Health Administration patients with mental health (MH) or substance abuse (SA) diagnoses who incurred costs during fiscal year 1999. We tested two models on a transformation of cost: a Log Normal model and a Square-root Normal model, and three generalized linear models on untransformed cost, defined by distributional assumption and link function: Normal with identity link (OLS); Gamma with log link; and Gamma with square-root link. Risk-adjusters included age, sex, and 12 MH/SA categories. To determine the best model among the entire dataset, predictive ability was evaluated using root mean square error (RMSE), mean absolute prediction error (MAPE), and predictive ratios of predicted to observed cost (PR) among deciles of predicted cost, by comparing point estimates and 95% bias-corrected bootstrap confidence intervals. To study the effect of analyzing a random sample of the population on model choice, we re-computed these statistics using random samples beginning with 5,000 patients and ending with the entire sample. RESULTS: The Square-root Normal model had the lowest estimates of the RMSE and MAPE, with bootstrap confidence intervals that were always lower than those for the other models. The Gamma with square-root link was best as measured by the PRs. The choice of best model could vary if smaller samples were used and the Gamma with square-root link model had convergence problems with small samples. CONCLUSION: Models with square-root transformation or link fit the data best. This function (whether used as transformation or as a link) seems to help deal with the high comorbidity of this population by introducing a form of interaction. The Gamma distribution helps with the long tail of the distribution. However, the Normal distribution is suitable if the correct transformation of the outcome is used

Ultrafiltration rate and incident atrial fibrillation among older individuals initiating hemodialysis

BACKGROUND: Higher ultrafiltration (UF) rates are associated with numerous adverse cardiovascular outcomes among individuals receiving maintenance hemodialysis. We undertook this study to investigate the association of UF rate and incident atrial fibrillation in a large, nationally representative US cohort of incident, older hemodialysis patients. METHODS: We used the US Renal Data System linked to the records of a large dialysis provider to identify individuals ≥67years of age initiating hemodialysis between January 2006 and December 2011. We applied an extended Cox model as a function of a time-varying exposure to compute adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the association of delivered UF rate and incident atrial fibrillation. RESULTS: Among the 15 414 individuals included in the study, 3177 developed atrial fibrillation. In fully adjusted models, a UF rate >13mL/h/kg (versus ≤13mL/h/kg) was associated with a higher hazard of incident atrial fibrillation [adjusted HR 1.19 (95% CI 1.07-1.30)]. Analyses using lower UF rate thresholds (≤10 versus >10mL/h/kg and ≤8 versus >8mL/h/kg, separately) yielded similar results. Analyses specifying the UF rate as a cubic spline (per 1mL/h/kg) confirmed an approximately linear dose-response relationship between the UF rate and the risk of incident atrial fibrillation: risk began at UF rates of ~6mL/h/kg and the magnitude of this risk flattened, but remained elevated, at rates ≥9mL/h/kg. CONCLUSION: In this observational study of older individuals initiating hemodialysis, higher UF rates were associated with higher incidences of atrial fibrillation

The Association of Pre-Kidney Transplant Dialysis Modality with de novo Posttransplant Heart Failure

BACKGROUND: Heart failure (HF) after kidney transplantation is a significant but understudied problem. Pretransplant dialysis modality could influence incident HF risk through differing cardiac stressors. However, whether pretransplant dialysis modality is associated with the development of posttransplant HF is unknown. METHODS: We used the US Renal Data System to assemble a cohort of 27,701 patients who underwent their first kidney transplant in the USA between the years 2005 and 2012 and who had Medicare fee-for-service coverage for \u3e6 months preceding their transplant date. Patients with any HF diagnosis prior to transplant were excluded. Detailed baseline patient characteristics and comorbidities were abstracted. The outcome of interest was de novo posttransplant HF. Pretransplant dialysis modality was defined as the dialysis modality used at the time of transplant. We conducted time-to-event analyses using Cox regression. Death was treated as a competing risk in the study\u27s primary analysis. Graft failure was included as a time-varying covariate. RESULTS: Among eligible patients, 81% were treated with hemodialysis prior to transplant, and hemodialysis patients were more likely to be male, had a shorter dialysis vintage, and had more diabetes and vascular disease diagnoses. When adjusted for all available demographic and clinical data, pretransplant treatment with hemodialysis (vs. peritoneal dialysis) was associated with a 19% increased risk in de novo posttransplant HF, with sub-distribution HR 1.19 (95% CI: 1.09-1.29). CONCLUSIONS: Our results suggest that choice of pretransplant dialysis modality may impact the development of posttransplant HF

Glycemic Control and Infections Among US Hemodialysis Patients With Diabetes Mellitus

INTRODUCTION: Patients with diabetes mellitus (DM) on hemodialysis (HD) may be particularly vulnerable to infections. METHODS: We used merged data from the United States Renal Data System and electronic health records data from a large US dialysis provider to retrospectively examine the association between glycemic control and infections in these patients. Adult patients with DM aged ≥18 years who initiated in-center maintenance HD treatment from 2006 to 2011 and survived \u3e90 days were included. Quarterly mean time-averaged hemoglobin A1c (HbA1c) values were categorized into RESULTS: In a cohort of 33,753 eligible patients, those with higher HbA1c levels had higher rates of diabetic foot infections and skin and soft tissue infections, with patients with HbA1c ≥8.5% having 23% (95% CI, 5%, 45%) and 22% (95% CI, 5%, 42%) higher rates, respectively, compared with HbA1c 5.5 to CONCLUSION: This study highlights the need for greater attention to foot evaluation and skin and soft tissue infections among patients on HD with less than optimal diabetes control

Dialysis Modality, Transplant Characteristics, and Incident Atrial Fibrillation After Kidney Transplant: An Observational Study Using USRDS Data

RATIONALE & OBJECTIVE: Atrial fibrillation is the most common arrhythmia and is increasing in prevalence. The prevalence of atrial fibrillation is high among patients receiving dialysis, affecting ∼21.3% of the patients receiving hemodialysis and 15.5% of those receiving peritoneal dialysis. The association of previous dialysis modality with incident atrial fibrillation in patients after receiving their first kidney transplant has not been studied. STUDY DESIGN: We used the United States Renal Data System to retrospectively identify adult, Medicare-insured patients who received their first kidney transplant between January 1, 2005, and September 30, 2012 and who had not previously been diagnosed with atrial fibrillation. SETTING & PARTICIPANTS: The study included 43,621 patients who were aged 18 years older when receiving a first kidney transplant between January 1, 2005, and September 30, 2012 and whose primary payer was Medicare (parts A and B) at the time of transplantation and the 6 months preceding it. EXPOSURE: Dialysis modality used before transplant. OUTCOME: Time to incidence of atrial fibrillation up to 3 years posttransplant. ANALYTICAL APPROACH: Multivariable Cox regression was used to estimate HRs. RESULTS: Of 43,621 patients, 84.9% received hemodialysis and 15.1% received peritoneal dialysis before transplant. The mean ± SD age was 51 ± 13.6 years; 60.8% were male, 55.6% White, and 35.8% Black race. The mean dialysis vintage was 4.3 ± 2.8 years. Newly diagnosed atrial fibrillation after kidney transplant occurred in 286 patients (during 15,363 person-years) who had received peritoneal dialysis and in 2,315 patients (during 83,536 person-years) who had received hemodialysis. After multivariable adjustment, atrial fibrillation was 20% (95% CI, 4%-38%) more likely in those who had been receiving hemodialysis versus peritoneal dialysis, regardless of whether death was considered a competing risk or a censoring event. Each year of pretransplant dialysis vintage increased the risk of posttransplant atrial fibrillation by 6% (95% CI, 3%-9%). LIMITATIONS: Residual confounding; data from billing claims does not specify the duration of atrial fibrillation or whether it is valvular. CONCLUSIONS: Pretransplant hemodialysis, as compared with peritoneal dialysis, was associated with higher risk of newly diagnosed atrial fibrillation after a first kidney transplant. PLAIN-LANGUAGE SUMMARY: New-onset atrial fibrillation (AF) occurs in 7% of kidney transplant recipients in the first 3 years posttransplantation. We conducted this study to determine whether pretransplant dialysis modality was associated with posttransplant AF. We identified 43,621 patients; 84.9% used hemodialysis and 15.1% used peritoneal dialysis pretransplant. Multivariable Cox regression was used to estimate hazard ratios. We found that patients receiving hemodialysis pretransplant were at 20% increased risk of developing posttransplant AF as compared with patients receiving peritoneal dialysis. As our understanding of transplant-specific risk factors for AF increases, we may be able to better risk-stratify transplant patients and develop monitoring and management strategies that can improve outcomes

Associations of Serum and Dialysate Potassium Concentrations With Incident Atrial Fibrillation in a Cohort Study of Older US Persons Initiating Hemodialysis for Kidney Failure.

INTRODUCTION: Atrial fibrillation (AF) disproportionally affects persons on maintenance hemodialysis (HD). Associations of serum and dialysate potassium concentrations [K+] with AF incidence are poorly understood. METHODS: We conducted a cohort study using Medicare claims merged with clinical data from a dialysis provider to determine whether serum-[K+] and/or dialysate-[K+] independently associated with AF incidence. Persons insured by fee-for-service Medicare aged ≥67 years at dialysis initiation and free from diagnosed AF prior to day 120 of dialysis were eligible. Serum-[K+] and dialysate-[K+] were assessed in 30-day intervals and patients were followed-up with for AF incidence in subsequent 30-day intervals. RESULTS: During 2006 to 2011, 15,190 persons (mean age = 76.3 years) initiating HD had no prior AF diagnosis. Mean serum-[K+] was 4.5 mEq/l; dialysate-[K+] was 3 mEq/l in 34% and 2 mEq/l in 52% of patients. Followed-up over 21,907 person-years, 2869 persons had incident AF (incidence/100 person-years, 13.1 [95% confidence interval [CI], 12.6–13.6]). The multivariable-adjusted association of serum-[K+] with incident AF was J-shaped as follows: relative to a serum-[K+] of 4.5 mEq/l, lower serum-[K+] associated with increased AF risk, whereas confidence bands for higher serum-[K+] indicated no association. Dialysis against a dialysate-[K+] of 3 mEq/l versus 2 mEq/l independently associated with a 14% (95% CI, 5%–24%) lower incidence of AF. No effect modification between serum-[K+] and dialysate-[K+] was detected (P = 0.34). CONCLUSION: Lower serum-[K+] was independently associated with incident AF whereas elevated serum-[K+] was not. The findings support adoption of dialysate solutions with a dialysate-[K+] of 3 mEq/l, regardless of patients’ serum-[K+], and elimination of lower dialysate-[K+] solutions from practice. Clinical trials randomizing patients to different dialysate-[K+] are warranted to establish causality

Blood Pressure and Incident Atrial Fibrillation in Older Patients Initiating Hemodialysis

BACKGROUND AND OBJECTIVES: We examined the association of predialysis systolic and diastolic BP and intradialytic hypotension with incident atrial fibrillation in older patients initiating hemodialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We used the US Renal Data System linked to the records of a large dialysis provider to identify patients aged ≥67 years initiating hemodialysis between January 2006 and October 2011. We examined quarterly average predialysis systolic BP, diastolic BP, and proportion of sessions with intradialytic hypotension (i.e., nadir systolic BP <90 mm Hg). We applied an extended Cox model to compute adjusted hazard ratios (HRs) of each exposure with incident atrial fibrillation. RESULTS: Among 17,003 patients, 3785 developed atrial fibrillation. When comparing predialysis systolic BP to a fixed reference of 140 mm Hg, lower predialysis systolic BP was associated with a higher hazard of atrial fibrillation, whereas higher systolic BP was associated with a lower hazard of atrial fibrillation. When comparing across a range of systolic BP for two hypothetical patients with similar measured covariates, the association varied by mean systolic BP: at systolic BP 190 mm Hg, each 10 mm Hg lower systolic BP was associated with lower atrial fibrillation hazard (HR, 0.94; 95% confidence interval, 0.90 to 1.00), whereas at systolic BP 140 mm Hg, a 10 mm Hg lower systolic BP was associated with a higher atrial fibrillation hazard (HR, 1.12; 95% confidence interval, 1.10 to 1.14). Lower diastolic BP was associated with higher atrial fibrillation hazards. Intradialytic hypotension was weakly associated with atrial fibrillation. CONCLUSIONS: In this observational study of older patients initiating hemodialysis, lower predialysis systolic BP and diastolic BP were associated with higher incidence of atrial fibrillation