The Associations Between Opioid Use Disorder and Healthcare-Related Outcomes in Vaso-occlusive Crisis.

BACKGROUND: In patients who experience frequent vaso-occlusive crises (VOC), opioid dependence may be due to a need for pain control as opposed to addiction; the implications of opioid use disorder (OUD) in this population are unclear. OBJECTIVE: To compare outcomes in hospitalizations for VOC in those with a history of OUD to those without a history of OUD. DESIGN: A retrospective assessment of hospitalizations for adults in the USA with a primary discharge diagnosis of VOC using the National Inpatient Sample database from 2016 to 2019. We also compared VOC hospitalizations to hospitalizations for all other reasons to assess differences in OUD-associated clinical factors. PARTICIPANTS: In total, 273,460 hospitalizations for VOC; 23,120 (8.5%) of these hospital stays involved a secondary diagnosis of OUD. MAIN MEASURES: Primary outcomes were length of hospital stay and cost. Mortality was a secondary outcome. KEY RESULTS: Hospital length of stay was increased (mean 6.2 vs 4.9 days) in patients with OUD (adjusted rate ratio = 1.24, 95% CI 1.20-1.29, p < 0.001). Mean cost was also higher in those with OUD ($9076) than those without OUD ($8020, p < 0.001). Mortality was decreased in VOC hospitalizations in those with OUD, but the difference was not statistically significant (adjusted OR = 0.64, 95% CI 0.028-1.48, p = 0.30). CONCLUSIONS: OUD is associated with increased length of stay and costs in patients with VOC. While there are many possible explanations, providers should consider undertreatment of pain due to addiction concerns as a potential factor; individualized pain plans to mitigate this challenge could be explored.

Staging and clean room: Constructs designed to facilitate transparency and reduce bias in comparative analyses of real-world data.

PURPOSE: We describe constructs designed to protect the integrity of the results from comparative analyses using real-world data (RWD): staging and clean room. METHODS: Staging involves performing sequential preliminary analyses and evaluating the population size available and potential bias before conducting comparative analyses. A clean room involves restricted access to data and preliminary results, policies governing exploratory analyses and protocol deviations, and audit trail. These constructs are intended to allow decisions about protocol deviations, such as changes to design or model specification, to be made without knowledge of how they might affect subsequent analyses. We describe an example for implementing staging with a clean room. RESULTS: Stage 1 may involve selecting a data source, developing and registering a protocol, establishing a clean room, and applying inclusion/exclusion criteria. Stage 2 may involve attempting to achieve covariate balance, often through propensity score models. Stage 3 may involve evaluating the presence of residual confounding using negative control outcomes. After each stage, check points may be implemented when a team of statisticians, epidemiologists and clinicians masked to how their decisions may affect study outcomes, reviews the results. This review team may be tasked with making recommendations for protocol deviations to address study precision or bias. They may recommend proceeding to the next stage, conducting additional analyses to address bias, or terminating the study. Stage 4 may involve conducting the comparative analyses. CONCLUSIONS: The staging and clean room constructs are intended to protect the integrity and enhance confidence in the results of analyses of RWD.

Contemporary Practice of Anemia Treatment Among Dialysis Patients in the United States.

Introduction: The treatment of anemia is a major activity in the care of patients undergoing maintenance hemodialysis (HD). The comparative effectiveness of new pharmacologic treatments, relative to erythropoiesis-stimulating agents (ESAs), should be anticipated on the bases of controlled trials and current practice. We describe the contemporary practice of anemia treatment in a national cohort of patients undergoing maintenance HD. Methods: We analyzed the United States Renal Data System (USRDS) data to identify adult patients undergoing in-facility HD in 2016 to 2019. Using the Consolidated Renal Operations in a Web-Enabled Network (CROWNWeb) dataset, we identified hemoglobin and ESA utilization (agent and cumulative dose) during each patient-month, as well as intravenous (IV) iron utilization, ferritin, and transferrin saturation. We compared ESA dosing during the study era to dosing in the Normal Hematocrit Cardiac Trial (NHCT), conducted in the 1990s. We assessed ESA hyporesponsiveness by estimating the prevalence of the following: (i) high erythropoietin resistance index (ERI) and (ii) either 3 or 6 consecutive months with hemoglobin <10 g/dl. Results: Nearly two-thirds of patient-months had hemoglobin of 10.0 to 11.9 g/dl. Mean ESA utilization was 76.7% per month, with increasing use of pegylated epoetin beta. ESA dosing was stable; epoetin alfa dosing was slightly lower than in the low-target arm of the NHCT. The prevalence of ESA hyporesponsiveness was 22.2% if defined by high ERI, but only 2.1% to 6.0% if defined by 3 to 6 consecutive months with hemoglobin <10 g/dl. Median transferrin saturation was 22.3% with high ERI and persistently low hemoglobin. Conclusion: Hemoglobin and ESA dosing distributions are stable, with epoetin alfa dosing below the low-target arm of the NHCT. Persistently low hemoglobin occurs infrequently and may reflect iron depletion.

Symptom Trajectories in the Electronic Health Record during the Transition to Maintenance Dialysis.

How symptoms recorded in the electronic health record change during the transition to dialysis has not been fully explored. We used the Optum deidentified Integrated Claims-Clinical dataset to identify individuals with CKD stages 4 or 5 who transitioned to dialysis. We searched structured data elements from clinical notes, identified by natural language processing, for symptoms recorded across weekly intervals in the 6 months before and after dialysis initiation and estimated changes in the odds of a symptom being recorded with an interrupted time series analysis using segmented logistic regression. The cohort comprised 728 individuals (aged 68±13 years, 44% women, 56% White, 30% Black). Before dialysis initiation, 83% were recorded as having pain, 68% fatigue/weakness, 66% shortness of breath, 61% nausea/vomiting, and 37% difficulty concentrating. Before dialysis initiation, odds of pain being recorded increased (slope: odds ratio [OR] 1.02 per week, 95% confidence interval [CI], 1.01 to 1.03); initiation was associated with a decrease (intercept change: OR 0.70, 95% CI, 0.59 to 0.82). After initiation, odds of pain were unchanged (postdialysis slope: OR 1.00 per week, 95% CI, 0.99 to 1.01), although this represented an improved trajectory relative to the predialysis period (change in slope: OR 0.98 per week, 95% CI, 0.96 to 0.99). For fatigue/weakness, odds increased before initiation (OR 1.03 per week, 95% CI, 1.02 to 1.04) but decreased on initiation (OR 0.62, 95% CI, 0.51 to 0.75) and thereafter (OR 0.98 per week, 95% CI, 0.97 to 0.99), representing a reduction in slope (OR 0.95 per week, 95% CI, 0.94 to 0.97). Patterns for shortness of breath, nausea/vomiting, and difficulty concentrating were similar to those of pain. Thus, the odds of five key symptoms being recorded in the electronic health record increased over time in the 6 months before dialysis initiation, decreased immediately on initiation, and, generally, remained unchanged in the 6 months thereafter.

Increased Access, Persistent Disparities: Trends in Disparities in Peritoneal Dialysis (PD) Use, 2009-2019.

Peritoneal dialysis (PD) use has increased in the United States since 2009, but how this has affected disparities in PD use is unclear. We used data from the United States Renal Data System to identify a cohort of incident dialysis patients from 2009 to 2019. We used logistic regression models to examine how odds of PD use changed by demographic characteristics. The incident PD population increased by 203% from 2009 to 2019, and the odds of PD use increased in every subgroup. PD use increased more among older people because the odds for those aged 75 years or older increased 15% more per 5-year period compared with individuals aged 18-44 years (odds ratio [OR] 1.68, 95% confidence interval [CI], 1.64 to 1.73 versus OR 1.46, 95% CI, 1.42 to 1.50). The odds of PD use increased 5% more per 5-year period among Hispanic people compared with White people (OR 1.58, 95% CI, 1.53 to 1.63 versus OR 1.51, 95% CI, 1.48 to 1.53). There was no difference in odds of PD initiation among people who were Black, Asian, or of another race. The odds of PD use increased 5% more for people living in urban areas compared with people living in nonurban areas (5-year OR 1.54, 95% CI, 1.52 to 1.56 versus 5-year OR 1.46, 95% CI, 1.42 to 1.50). The odds of PD use increased 7% more for people living in socioeconomically advantaged areas compared with people living in more deprived areas (5-year OR 1.60, 95% CI, 1.56 to 1.63 for neighborhoods with lowest Social Deprivation Index versus 5-year OR 1.50, 95% CI, 1.48 to 1.53 in the most deprived areas). Expansion of PD use led to a reduction in disparities for older people and for Hispanic people. Although PD use increased across all strata of socioeconomic deprivation, the gap in PD use between people living in the least deprived areas and those living in the most deprived areas widened.

Association of the End-Stage Renal Disease Treatment Choices Payment Model With Home Dialysis Use at Kidney Failure Onset From 2016 to 2022.

Importance: The Centers for Medicare & Medicaid Services designed a mandatory payment model to incentivize home dialysis use: the End-Stage Renal Disease Treatment Choices (ETC). Outpatient dialysis facilities and health care professionals providing nephrology services were randomly assigned to ETC participation at the hospital referral region level. Objective: To assess the association between ETC and home dialysis use in the incident dialysis population in its first 18 months of implementation. Design, Setting, and Participants: A cohort study with controlled, interrupted time series analysis of the US End-Stage Renal Disease Quality Reporting System database was conducted, using generalized estimating equations. All adults initiating home-based dialysis in the US between January 1, 2016, and June 30, 2022, without a prior kidney transplant were included in the analysis. Exposures: Prior to vs after ETC onset in January 1, 2021, and random assignment to ETC participation of facilities and health care professionals involved in patient care. Main Outcomes and Measures: Percentage of patients started on incident home dialysis and yearly change in percentage initiating home dialysis. Results: A total of 817 177 adults initiated home dialysis during the study period, of whom 750 314 were included in the study cohort. The cohort included 41.4% women; 26.2% of the patients were Black, 17.4% were Hispanic, and 49.1% were White. Approximately half (49.6%) of the patients were aged at least 65 years. A total of 31.2% received care from health care professionals assigned to ETC participation, and 33.6% had Medicare fee-for-service coverage. Overall, home dialysis use increased from 10.0% in January 2016 to 17.4% in June 2022. Home dialysis use increased more in ETC markets than in non-ETC markets after January 2021 (by 1.07%; 95% CI, 0.16%-1.97%). The rate of increase in home dialysis use in the entire cohort nearly doubled after January 2021 to 1.66% per year (95% CI, 1.14%-2.19%) compared with before 2021, when the rate was 0.86% per year (95% CI, 0.75%-0.97%), but the difference in rate of increase in home dialysis use was not significant between ETC and non-ETC markets. Conclusions and Relevance: This study noted that, although the overall rate of dialysis use at home was greater after ETC implementation, the increase occurred more among patients in ETC markets than among those in non-ETC markets. These findings suggest that federal policy and financial incentives affected care for the entire incident dialysis population in the US.

A Collaborative Pilot to Support Patients With Diabetes Through Tailored Food Box Home Delivery.

We conducted a randomized, controlled prospective pilot study to determine feasibility and impact of food bank and health system collaboration to home-delivered food to adults with type 2 diabetes mellitus experiencing food insecurity. Treatment group received biweekly, ethnically tailored, home-delivered food for 24 weeks. Analysis included intervention feasibility and impact on healthcare utilization, HbA1c, and other health-related measures. Intervention was feasible and successful with high levels of participant satisfaction. At baseline, participants with highest HbA1c reported poorer health, lower medication adherence and self-care, and higher diabetes distress and medicine for food tradeoffs. At 24 weeks, treatment group reported improved food security and health status. There were no differences in HbA1c or healthcare utilization measures between the two groups. It is feasible for a community food bank and nearby hospital to successfully collaborate and provide supplemental food staples to food insecure adults with type 2 diabetes and improve food insecurity and health status. Public policy efforts should utilize and expand this strategy with the goal of improving health and reducing health disparities. Future work could include more comprehensive food support focused on those with poorest glycemic control, and expanded, coordinated interventions directed at other social determinants of health. Future programming and policies should be cocreated with community input to ensure greatest success.

Associations of COVID-19 Outcomes with Dialysis Modalities and Settings.

How maintenance dialysis modality, dialysis setting, and residence in a nursing facility have jointly associated with coronavirus disease 2019 (COVID-19)-related outcomes in the United States is relevant to future viral outbreaks. Using Medicare claims, we determined the incidence of COVID-19-related infection, hospitalization, and death between March 15, 2020 and June 5, 2021. The exposure was one of five combinations of dialysis modality and care setting: in-facility hemodialysis without a recent history of skilled nursing facility care, in-facility hemodialysis with a recent history of skilled nursing facility care, hemodialysis in a skilled nursing facility, home hemodialysis, and (home) peritoneal dialysis. Patient-weeks were pooled to estimate the adjusted associations of event incidence with each dialysis modality/setting during four intervals in 2020-2021. Relative to in-facility hemodialysis without a recent history of skilled nursing facility care, home dialysis was associated with 36%-60% lower odds of all events during weeks 12-23 of 2020; 24%-37% lower odds of all events during weeks 24-37 of 2020; 20%-33% lower odds of infection and hospitalization during the winter of 2020-2021; and similar odds of all events thereafter. In contrast, exposure to skilled nursing facilities was associated with 570%-1140% higher odds of all events during spring of 2020, although excess risk attenuated as the pandemic transpired, especially among patients who received hemodialysis in skilled nursing facilities. In conclusion, home dialysis was associated with lower risks of COVID-19 diagnosis, hospitalization, and death until vaccines were available, whereas care in skilled nursing facilities was associated with higher risks.

Kidney-Metabolic Factors Associated with Cognitive Impairment in Chronic Kidney Disease: A Pilot Study.

INTRODUCTION: The associations of kidney-metabolic biomarkers with cognitive impairment (CI) beyond the estimated glomerular filtration rate (eGFR, in mL/min/1.73 m2) and albuminuria levels are not well understood. In exploratory analysis, our objective was to determine the extent that three kidney-metabolic factors, previously proposed as mechanisms of CI and commonly abnormal in chronic kidney disease (CKD), were associated with prevalent CI in CKD participants, adjusted for kidney function measures. METHODS: The study cohort included community-dwelling individuals aged ≥45 years with CKD (eGFR <60), not requiring dialysis, recruited from four health systems. We examined the serum biomarkers bicarbonate (CO2), TNFαR1, and cholesterol as primary exposures. A structured neuropsychological battery conducted by trained staff measured global and domain-specific cognitive performance. Logistic regression analyses estimated the cross-sectional associations between kidney-metabolic measures and global and cognitive domain-specific moderate/severe (Mod/Sev) CI, adjusted for the eGFR, urinary albumin-creatinine ratio (UACR, mg/g), demographics, comorbid conditions, and other kidney-metabolic biomarkers commonly abnormal in CKD. RESULTS: Among 436 CKD participants with mean age 70 years, 16% were Black, the mean eGFR was 34, and the median [IQR] UACR was 49 [0.0, 378] mg/g. In adjusted models, increased TNFαR1 was associated with global Mod/Sev CI (odds ratio [95% confidence interval] = 1.40 [1.02, 1.93]; p = 0.04); low bicarbonate (CO2 <20 mEq/L) with Mod/Sev memory impairment (3.04 [1.09, 8.47]; p = 0.03), and each 10-mg/dL lower cholesterol was associated with Mod/Sev executive function/processing speed impairment (1.12 [1.02, 1.23]; p = 0.02). However, after adjustment for multiple comparisons, these associations were no longer significant nor were any other kidney-metabolic factors significant for any CI classification. CONCLUSION: In exploratory analyses in a CKD population, three kidney-metabolic factors were associated with CI, but after adjustment for multiple comparisons, were no longer significant. Future studies in larger CKD populations are needed to assess these potential risk factors for CI.

Catheter-Associated Bloodstream Infections among Patients on Hemodialysis: Progress before and during the COVID-19 Pandemic.

Measures implemented to prevent transmission of severe acute respiratory syndrome coronavirus 2 in outpatient dialysis facilities may also help to prevent catheter-associated bloodstream infections in patients receiving hemodialysis. We used United States Renal Data System data to examine rates of antibiotic administration within dialysis facilities and rates of hospital admission for catheter-associated bloodstream infection from March 2018 through November 2020, and rates of hospitalization for sepsis, to address overall changes in hospitalization during the coronavirus disease 2019 (COVID-19) pandemic. Using logistic regression, we estimated year-over-year adjusted odds ratios of these events in 3-month intervals. During the first 6 months of the pandemic, rates of antibiotic administration were between 20% and 21% lower, and rates of hospitalization for catheter-associated bloodstream infection were between 17% and 24% lower than during corresponding periods in 2019, without significant changes in rates of hospitalization for sepsis. However, rates of catheter-associated events also decreased between 2018 and 2019, driven by reductions in facilities operated by a large dialysis provider. These data suggest that significant reductions in catheter-associated infections occurred during the pandemic, superimposed on nonpandemic-related reductions in some facilities before the pandemic. Even after the pandemic, it may be prudent to continue some COVID-19 mitigation measures to prevent catheter-associated bloodstream infections.

Cinacalcet and gastrointestinal bleeding risk in patients receiving hemodialysis.

PURPOSE: Secondary hyperparathyroidism (SHPT) is common among dialysis patients, and calcimimetics are a mainstay of treatment. This study assessed whether cinacalcet use is associated with gastrointestinal bleeding in a large hemodialysis cohort. METHODS: A linked database of clinical records and medical claims for patients receiving hemodialysis in a large dialysis organization, 2007-2010, was used. A nested case-control study was performed among patients aged ≥18 years who had received hemodialysis for ≥90 days, had Medicare Parts A, B, and D coverage for ≥1 year, and had clinical evidence of SHPT (parathyroid hormone >300 pg/mL). Cases were those who experienced death or hospitalization caused by gastrointestinal bleeding. Each case was matched to up to four controls. Exposure was measured by any cinacalcet use, current use, past use, cumulative exposure days, and cumulative dosage. Conditional logistic models were used to assess the association. RESULTS: Of 48 437 patients included, 2570 experienced gastrointestinal bleeding events (2498 non-fatal, 72 fatal), and 2465 (2397 non-fatal, 68 fatal) were matched to 9500 controls; 17.2% of cases and 15.8% of controls had cinacalcet exposure and 11.1% of both cases and controls had current use. The adjusted odds ratios (95% CI) of gastrointestinal bleeding for any use, current use, and past use of cinacalcet were 1.04 (0.91-1.19), 0.97 (0.83-1.13), and 1.22 (0.99-1.50), respectively, with no use as the reference. CONCLUSION: The results do not suggest an elevated risk of gastrointestinal bleeding resulting in hospitalization or death for hemodialysis patients exposed to cinacalcet.

Changes in Treatment of Patients with Incident ESKD during the Novel Coronavirus Disease 2019 Pandemic.

BACKGROUND: The COVID-19 pandemic caused major disruptions to care for patients with advanced CKD. METHODS: We investigated the incidence of documented ESKD, ESKD treatment modalities, changes in eGFR at dialysis initiation, and use of incident central venous catheters (CVCs) by epidemiologic week during the first half of 2020 compared with 2017-2019 historical trends, using Centers for Medicare and Medicaid Services data. We used Poisson and logistic regression for analyses of incidence and binary outcomes, respectively. RESULTS: Incidence of documented ESKD dropped dramatically in 2020 compared with the expected incidence, particularly during epidemiologic weeks 15-18 (April, incidence rate ratio [IRR], 0.75; 95% CI, 0.73 to 0.78). The decrease was most pronounced for individuals aged ≥75 years (IRR, 0.69; 95% CI, 0.66 to 0.73). Pre-emptive kidney transplantation decreased markedly during weeks 15-18 (IRR, 0.56; 95% CI, 0.46 to 0.67). Mean eGFR at dialysis initiation decreased by 0.33 ml/min per 1.73 m2 in weeks 19-22; non-Hispanic Black patients exhibited the largest decrease, at 0.61 ml/min per 1.73 m2. The odds of initiating dialysis with eGFR <10 ml/min per 1.73 m2 were highest during weeks 19-22 (May, OR, 1.14; 95% CI, 1.05 to 1.17), corresponding to an absolute increase of 2.9%. The odds of initiating peritoneal dialysis (versus hemodialysis) were 24% higher (OR, 1.24; 95% CI, 1.14 to 1.34) in weeks 11-14, an absolute increase of 2.3%. Initiation with a CVC increased by 3.3% (OR, 1.30; 95% CI, 1.20 to 1.41). CONCLUSIONS: During the first wave of the COVID-19 pandemic, the number of patients starting treatment for ESKD fell to a level not observed since 2011. Changes in documented ESKD incidence and other aspects of ESKD-related care may reflect differential access to care early in the pandemic.

Development and outcomes of hyperkalemia in hospitalized patients: potential implications for care.

INTRODUCTION: While severe hyperkalemia is commonly encountered, its manifestation in hospitalized patients and related outcomes are unclear. We aimed to examine development of hyperkalemia in hospitalized patients and associated outcomes. METHODS: Data from a county hospital electronic health record were used to assess all inpatient admissions, 2012-2016, for non-dialysis-dependent patients with ≥1 K value for development of hyperkalemia. Unadjusted odds ratios (ORs) were calculated for associations of the maximum K value with in-hospital mortality and adjusted ORs were calculated for death associated with hyperkalemia. RESULTS: In 47,018 individual patient hospitalizations, 1.3% had a maximum K ≥6.0 mEq/L and 4.2% <3.5 mEq/L. Fifth and 95th percentiles for maximum K values were 3.5 and 5.3 mEq/L. For high-K patients with a prior K value, the mean (SD) of the immediate pre-maximum K value was 5.0 ± 1.0 mEq/L, and the mean difference in K values (immediate pre-maximum to maximum) was 1.5 ± 1.1 mEq/L; mean duration between these two K tests was 10.7 ± 14.9 hours. Compared with maximum K values 3.5 to 4.0 mEq/L, ORs for death were 37.1 (95% confidence intervals, 25.8-53.3) for K 6.0 to <6.5, 88.6 (56.8-138.2) for K ≥7.0, and 18.9 (4.3-82.2) for K <3.0 mEq/L. In adjusted models, the OR for death for K ≥6.0 mEq/L was 4.9 (3.7-6.4). DISCUSSION/CONCLUSIONS: Peak K values ≥6.0 mEq/L were associated with mortality. Values tended to increase rapidly, limiting opportunities for detection and treatment. Systems-based approaches to detect life-threatening hyperkalemia should be studied.

Testing Patterns for CKD-MBD Abnormalities in a Sample US Population.

INTRODUCTION: Patterns of testing, treatment, and retesting following treatment for disorders of chronic kidney disease mineral bone disorder (CKD-MBD) have not been explored using a large electronic database. METHODS: To determine concordance with CKD-MBD management guidelines, we used 2010 to 2019 data from an electronic health record (>50 million patients) to create cohorts of incident CKD stage 3, 4, and 5 patients using diagnosis codes and estimated glomerular filtration rates. The CKD-MBD test ordering and relevant drug prescribing were assessed during follow-up. We estimated cumulative incidence of posttreatment retesting (death as competing risk). We used multivariable Cox regression to examine baseline characteristics and pretreatment test results as predictors of retesting. RESULTS: For 215,553 stage 3, 43,576 stage 4, and 11,407 stage 5 CKD patients, the mean follow-up was 2.3, 1.7, and 0.6 years, respectively. Only 46% of stage 4 and 41% of stage 5 patients underwent parathyroid hormone (PTH) testing, 74% and 73% had phosphorus testing, and 38% and 25% had 25D testing. By 1 year after vitamin D sterol treatment, only 50%, 53%, and 60% of stage 3, 4, and 5 patients had been retested for PTH. By 1 year after treatment with ergocalciferol or cholecalciferol, only 46%, 49%, and 55% had 25D reassessed. Pretreatment levels of PTH and 25D were not associated in a graded fashion with likelihood of retesting after treatment. Rates of retesting were not highest for patients with the highest and lowest pre-treatment PTH and 25D levels, respectively. CONCLUSION: Frequency of testing for CKD-MBD abnormalities and posttreatment retesting appears to be suboptimal.