The Kidney Failure Risk Equation: Evaluation of Novel Input Variables including eGFR Estimated Using the CKD-EPI 2021 Equation in 59 Cohorts.

SIGNIFICANCE STATEMENT: The kidney failure risk equation (KFRE) uses age, sex, GFR, and urine albumin-to-creatinine ratio (ACR) to predict 2- and 5-year risk of kidney failure in populations with eGFR <60 ml/min per 1.73 m 2 . However, the CKD-EPI 2021 creatinine equation for eGFR is now recommended for use but has not been fully tested in the context of KFRE. In 59 cohorts comprising 312,424 patients with CKD, the authors assessed the predictive performance and calibration associated with the use of the CKD-EPI 2021 equation and whether additional variables and accounting for the competing risk of death improves the KFRE's performance. The KFRE generally performed well using the CKD-EPI 2021 eGFR in populations with eGFR <45 ml/min per 1.73 m 2 and was not improved by adding the 2-year prior eGFR slope and cardiovascular comorbidities. BACKGROUND: The kidney failure risk equation (KFRE) uses age, sex, GFR, and urine albumin-to-creatinine ratio (ACR) to predict kidney failure risk in people with GFR <60 ml/min per 1.73 m 2 . METHODS: Using 59 cohorts with 312,424 patients with CKD, we tested several modifications to the KFRE for their potential to improve the KFRE: using the CKD-EPI 2021 creatinine equation for eGFR, substituting 1-year average ACR for single-measure ACR and 1-year average eGFR in participants with high eGFR variability, and adding 2-year prior eGFR slope and cardiovascular comorbidities. We also assessed calibration of the KFRE in subgroups of eGFR and age before and after accounting for the competing risk of death. RESULTS: The KFRE remained accurate and well calibrated overall using the CKD-EPI 2021 eGFR equation. The other modifications did not improve KFRE performance. In subgroups of eGFR 45-59 ml/min per 1.73 m 2 and in older adults using the 5-year time horizon, the KFRE demonstrated systematic underprediction and overprediction, respectively. We developed and tested a new model with a spline term in eGFR and incorporating the competing risk of mortality, resulting in more accurate calibration in those specific subgroups but not overall. CONCLUSIONS: The original KFRE is generally accurate for eGFR <45 ml/min per 1.73 m 2 when using the CKD-EPI 2021 equation. Incorporating competing risk methodology and splines for eGFR may improve calibration in low-risk settings with longer time horizons. Including historical averages, eGFR slopes, or a competing risk design did not meaningfully alter KFRE performance in most circumstances.

Major cardiovascular events and subsequent risk of kidney failure with replacement therapy: a CKD Prognosis Consortium study.

AIMS: Chronic kidney disease (CKD) increases risk of cardiovascular disease (CVD). Less is known about how CVD associates with future risk of kidney failure with replacement therapy (KFRT). METHODS AND RESULTS: The study included 25 903 761 individuals from the CKD Prognosis Consortium with known baseline estimated glomerular filtration rate (eGFR) and evaluated the impact of prevalent and incident coronary heart disease (CHD), stroke, heart failure (HF), and atrial fibrillation (AF) events as time-varying exposures on KFRT outcomes. Mean age was 53 (standard deviation 17) years and mean eGFR was 89 mL/min/1.73 m2, 15% had diabetes and 8.4% had urinary albumin-to-creatinine ratio (ACR) available (median 13 mg/g); 9.5% had prevalent CHD, 3.2% prior stroke, 3.3% HF, and 4.4% prior AF. During follow-up, there were 269 142 CHD, 311 021 stroke, 712 556 HF, and 605 596 AF incident events and 101 044 (0.4%) patients experienced KFRT. Both prevalent and incident CVD were associated with subsequent KFRT with adjusted hazard ratios (HRs) of 3.1 [95% confidence interval (CI): 2.9-3.3], 2.0 (1.9-2.1), 4.5 (4.2-4.9), 2.8 (2.7-3.1) after incident CHD, stroke, HF and AF, respectively. HRs were highest in first 3 months post-CVD incidence declining to baseline after 3 years. Incident HF hospitalizations showed the strongest association with KFRT [HR 46 (95% CI: 43-50) within 3 months] after adjustment for other CVD subtype incidence. CONCLUSION: Incident CVD events strongly and independently associate with future KFRT risk, most notably after HF, then CHD, stroke, and AF. Optimal strategies for addressing the dramatic risk of KFRT following CVD events are needed.

Anemia Prevalence, Type, and Associated Risks in a Cohort of 5.0 Million Insured Patients in the United States by Level of Kidney Function.

RATIONALE & OBJECTIVE: Anemia is common in chronic kidney disease (CKD); although anemia is associated with adverse outcomes, the available treatments are not ideal. We characterized the burden, risk factors for, and risks associated with anemia by estimated glomerular filtration rate (eGFR) and hemoglobin level. STUDY DESIGN: Cross-sectional and prospective cohort study. SETTING & PARTICIPANTS: Outpatient data from 5,004,957 individuals across 57 health care centers in the United States from 2016 to 2019, extracted from the Optum Labs Data Warehouse. EXPOSURE: Severity of anemia, presence of low iron test results, eGFR. OUTCOME: Incident kidney failure with replacement therapy, cardiovascular disease, coronary heart disease, stroke, heart failure, death. ANALYTICAL APPROACH: The prevalences of anemia, low iron test results, vitamin B12 deficiency, and erythropoiesis-stimulating agent (ESA) use, stratified by sex and eGFR, were characterized. Polychotomous logistic regression was used to estimate the adjusted odds ratios of different hemoglobin levels across eGFR. Cox proportional hazards regression was used to calculate adjusted hazard ratios for adverse outcomes across hemoglobin level. RESULTS: The mean age was 54 years, and 42% were male. Lower eGFR was very strongly associated with increased prevalence of anemia, even after adjustment. Although iron studies were checked infrequently in patients with anemia, low iron test results were highly prevalent in those tested: 60.4% and 81.3% of men and women, respectively. ESA use was uncommon, with a prevalence of use of<4%. Lower hemoglobin was independently associated with increased risk of incident kidney failure with replacement therapy, cardiovascular disease, coronary heart disease, stroke, heart failure, and death. LIMITATIONS: Reliance on ICD codes for medical diagnoses, death information obtained from claims data, observational study. CONCLUSIONS: Severe anemia was common and strongly associated with lower eGFR and multiple adverse outcomes. Low-iron test results were highly prevalent in those tested despite iron studies being checked infrequently. ESA use in nondialysis CKD patients was uncommon.

Variation in Initiation, Engagement, and Retention on Medications for Opioid Use Disorder Based on Health Insurance Plan Design.

BACKGROUND: The association between cost-sharing and receipt of medication for opioid use disorder (MOUD) is unknown. METHODS: We constructed a cohort of 10,513 commercially insured individuals with a new diagnosis of opioid use disorder and information on insurance cost-sharing in a large national deidentified claims database. We examined 4 cost-sharing measures: (1) pharmacy deductible; (2) medical service deductible; (3) pharmacy medication copay; and (4) medical office copay. We measured MOUD (naltrexone, buprenorphine, or methadone) initiation (within 14 d of diagnosis), engagement (second receipt within 34 d of first), and 6-month retention (continuous receipt without 14-d gap). We used multivariable logistic regression to assess the association between cost-sharing and MOUD initiation, engagement, and retention. We calculated total out-of-pocket costs in the 30 days following MOUD initiation for each type of MOUD. RESULTS: Of 10,513 individuals with incident opioid use disorder, 1202 (11%) initiated MOUD, 742 (7%) engaged, and 253 (2%) were retained in MOUD at 6 months. A high ($1000+) medical deductible was associated with a lower odds of initiation compared with no deductible (odds ratio: 0.85, 95% confidence interval: 0.74-0.98). We found no significant associations between other cost-sharing measures for initiation, engagement, or retention. Median initial 30-day out-of-pocket costs ranged from $100 for methadone to $710 for extended-release naltrexone. CONCLUSIONS: Among insurance plan cost-sharing measures, only medical services deductible showed an association with decreased MOUD initiation. Policy and benefit design should consider ways to reduce cost barriers to initiation and retention in MOUD.

Conversion of Urine Protein-Creatinine Ratio or Urine Dipstick Protein to Urine Albumin-Creatinine Ratio for Use in Chronic Kidney Disease Screening and Prognosis : An Individual Participant-Based Meta-analysis.

BACKGROUND: Although measuring albuminuria is the preferred method for defining and staging chronic kidney disease (CKD), total urine protein or dipstick protein is often measured instead. OBJECTIVE: To develop equations for converting urine protein-creatinine ratio (PCR) and dipstick protein to urine albumin-creatinine ratio (ACR) and to test their diagnostic accuracy in CKD screening and staging. DESIGN: Individual participant-based meta-analysis. SETTING: 12 research and 21 clinical cohorts. PARTICIPANTS: 919 383 adults with same-day measures of ACR and PCR or dipstick protein. MEASUREMENTS: Equations to convert urine PCR and dipstick protein to ACR were developed and tested for purposes of CKD screening (ACR ≥30 mg/g) and staging (stage A2: ACR of 30 to 299 mg/g; stage A3: ACR ≥300 mg/g). RESULTS: Median ACR was 14 mg/g (25th to 75th percentile of cohorts, 5 to 25 mg/g). The association between PCR and ACR was inconsistent for PCR values less than 50 mg/g. For higher PCR values, the PCR conversion equations demonstrated moderate sensitivity (91%, 75%, and 87%) and specificity (87%, 89%, and 98%) for screening (ACR >30 mg/g) and classification into stages A2 and A3, respectively. Urine dipstick categories of trace or greater, trace to +, and ++ for screening for ACR values greater than 30 mg/g and classification into stages A2 and A3, respectively, had moderate sensitivity (62%, 36%, and 78%) and high specificity (88%, 88%, and 98%). For individual risk prediction, the estimated 2-year 4-variable kidney failure risk equation using predicted ACR from PCR had discrimination similar to that of using observed ACR. LIMITATION: Diverse methods of ACR and PCR quantification were used; measurements were not always performed in the same urine sample. CONCLUSION: Urine ACR is the preferred measure of albuminuria; however, if ACR is not available, predicted ACR from PCR or urine dipstick protein may help in CKD screening, staging, and prognosis. PRIMARY FUNDING SOURCE: National Institute of Diabetes and Digestive and Kidney Diseases and National Kidney Foundation.

Comparative adherence to diabetes drugs: An analysis of electronic health records and claims data.

Non-adherence to medications is a major challenge in diabetes care. The objective of this brief report is to compare adherence rates for 6 major classes of diabetes medications: metformin, sulfonylurea, thiazolidinedione, basal insulin, DPP-4 inhibitors, and GLP-1 receptor agonists. We used a data source that linked electronic prescriptions with insurance claims to assess whether new electronic prescriptions for diabetes medications were followed by dispensing claims consistent with that prescription. After one year of follow-up, the daily medication possession probability (MPP) - a measure of overall adherence - at one year for sulfonylurea was 0.49 and for metformin was 0.46. Thiazolidinediones and basal insulin had a similar final daily MPP at 0.36 and 0.39, respectively, which was significantly lower than that for sulfonylurea or metformin (P < .05). GLP-1 receptor agonists and DPP-4 inhibitors were also comparable to one another at a final daily MPP of .30 and .21, respectively (P < .05 compared to any of the aforementioned drug classes). In summary, the rates at which diabetes drugs are prescribed, and the rates at which patients actually take them, differ substantially. Physicians should be aware of potentially significant challenges concerning adherence to newer agents.

Agreement and validity of electronic health record prescribing data relative to pharmacy claims data: A validation study from a US electronic health record database.

BACKGROUND: Granular clinical and laboratory data available in electronic health record (EHR) databases provide researchers the opportunity to conduct investigations that would not be possible in insurance claims databases; however, for pharmacoepidemiology studies, accurate classification of medication exposure is critical. OBJECTIVE: The aim of this study was to evaluate the validity of classifying medication exposure using EHR prescribing (EHR-Rx) data. METHODS: We conducted a retrospective cohort study among patients with linked claims and EHR data in OptumLabs™ Data Warehouse. The agreement between EHR-Rx data and pharmacy claims (PC-Rx) data (for 40 medications) was determined using the positive predictive value (PPV) and medication possession ratio (MPR)-calculated in 1- and 12-month medication exposure periods (MEPs). Secondary analyses were restricted to incident vs prevalent EHR-Rxs, age ≥65 vs <65, white vs black race, males vs females, and number of EHR-Rxs. RESULTS: The validity metrics varied substantially among the 40 medications assessed. Across all medications, the period PPV and MPR were 62% and 63% in the 1-month MEP. They were 78% and 43% in the 12-month MEP. Overall, PPV and MPR were higher for patients with a prevalent EHR-Rx and age <65. CONCLUSIONS: Despite substantial variability among different medications, there was very good agreement between EHR-Rx data and PC-Rx data. To maximize the validity of classifying medication exposure with EHR prescribing data, researchers may consider using longer MEPs (eg, 12 months) and potentially require multiple EHR-Rxs to classify baseline medication exposure.

Stage 2 hypertension: predictors of failure to achieve blood pressure control and the impact of adding one additional antihypertensive class.

BACKGROUND AND OBJECTIVE: Controlling blood pressure (BP) for patients with stage 2 hypertension remains challenging. This research aimed to: (i) identify predictors of failure to achieve BP control, (ii) determine the association of adding one additional antihypertensive class with achieving BP control, and (iii) describe the prescribed antihypertensive regimens. METHODS: Electronic medical record data from 25 multi-specialty medical groups in the USA were used. The study cohort included patients with stage 2 hypertension in 2012. BP control rates were determined at 6 months from the date of the stage 2 BP. Using multivariable logistic regression and validation by Monte Carlo simulation, we determined independent baseline predictors of not achieving BP control (<140/90). RESULTS: Included were 107 903 patients. Baseline predictors of failure to achieve BP control included the following: a prior stage 2 BP, systolic BP ≥ 165, Black race, male sex, income ≤ $35 000, body mass index ≥ 30, age ≥ 65 years, and no office visits. Increasing from single-class to dual-class antihypertensive therapy was associated with a 42% increased odds of achieving BP control (odds ratio 1.42; 95% CI 1.22, 1.64); however, this effect was attenuated as the number of baseline antihypertensive classes increased. The 10 most frequently prescribed regimens accounted for only 40% of all antihypertensive regimens. CONCLUSIONS: Among patients with stage 2 hypertension, a prior stage 2 BP, a systolic BP ≥ 165, and fewer office visits were strong predictors of failure to achieve BP control. Increasing to dual-class antihypertensive therapy was significantly associated with achieving BP control. There is broad heterogeneity in the antihypertensive regimens prescribed.

Knowledge, Attitudes, and Practices Regarding Herpes Zoster Vaccination Among Specialists.

Recombinant zoster vaccine has been recommended by the US Advisory Committee on Immunization Practices (ACIP) for the prevention of herpes zoster (HZ) in immunocompetent adults aged at least 50 years since 2018. In January 2022, this was extended to immunodeficient/immunosuppressed adults aged at least 19 years. Key study objectives were to assess specialists' knowledge of the ACIP HZ vaccination recommendations, their attitudes toward HZ vaccination, and HZ vaccination practices/barriers. This cross-sectional, web-based survey (conducted in March 2022) included US dermatologists, gastroenterologists, infectious disease specialists, oncologists, and rheumatologists who treat patients with psoriasis, inflammatory bowel disease, human immunodeficiency syndrome, solid tumors/hematological malignancies, and rheumatoid arthritis, respectively. Although most of the 613 specialists correctly identified the ACIP HZ vaccination recommendations for adults aged at least 50 years (84%) and immunodeficient/immunosuppressed adults aged at least 19 years (67%), only 29% knew that recombinant zoster vaccine is recommended for individuals who have previously received zoster vaccine live, and only 18% knew all current ACIP recommendations. For patients with the diseases listed, 84% of specialists thought that HZ is a serious risk, 75% that HZ vaccination is extremely/very important, and 69% were extremely/very likely to recommend HZ vaccination. Only 36% administer vaccines themselves, mainly because patients receive vaccinations from others. Barriers to vaccination included more urgent/acute issues, insufficient time, and lack of patient motivation/willingness. Full knowledge of the ACIP HZ vaccination recommendations among the surveyed specialists was low. There may be a need to educate specialists to improve adherence to these recommendations. [Figure: see text].

Burden of Herpes Zoster Among Patients with Psoriatic Arthritis in the United States.

Purpose: Patients with psoriasis (PsO) and psoriatic arthritis (PsA) are at increased risk of herpes zoster (HZ), but healthcare resource use (HRU) and costs relating to HZ in adults with PsA are unknown. We aimed to estimate the incidence of HZ among adults with PsA vs without psoriatic disease and the additional HRU and costs among patients with PsA with vs without HZ. Patients and Methods: This retrospective, longitudinal, cohort study estimated HZ incidence in PsA+ vs PsO-/PsA- cohorts and HRU and medical/pharmacy costs among PsA+/HZ+ vs PsA+/HZ- cohorts comprised of adults from Optum's de-identified Clinformatics Data Mart Database during 2015-2020. For the HRU/cost analyses, index was the date of first HZ diagnosis (PsA+/HZ+ cohort) or was randomly assigned (PsA+/HZ- cohort). Generalized linear models were used for adjusted comparisons between cohorts. Results: HZ incidence was higher in the PsA+ (n = 57,126) vs PsO-/PsA- (n = 23,837,237) cohort (14.85 vs 7.67 per 1000 person-years; adjusted incidence rate ratio [aIRR]: 1.23; 95% confidence interval [CI]: 1.16-1.30). Numbers of outpatient visits, emergency department visits, and inpatient admissions were significantly higher in the PsA+/HZ+ (n = 1045) vs PsA+/HZ- (n = 36,091) cohorts during the first month after HZ diagnosis (outpatient: aIRR: 1.74; 95% CI: 1.63-1.86; emergency department: 3.14; 95% CI: 2.46-4.02; inpatient: aIRR: 2.61; 95% CI: 1.89-3.61). Mean all-cause per-patient costs were significantly higher in the PsA+/HZ+ vs PsA+/HZ- cohorts during the first month after index ($6493 vs $4521; adjusted cost difference: $2012; 95% CI: $1204-$3007). HRU and costs were numerically higher in the PsA+/HZ+ cohort during the first 3 and 12 months. Conclusion: These findings, which provide evidence on the increased incidence and HRU and economic burden associated with HZ among adults with PsA, could be used to inform clinical practice and decision-making.

Why was the study done? Psoriatic arthritis affects the joints of around 20% of patients with the skin condition, psoriasis.Patients with psoriatic arthritis are at increased risk of shingles, which can cause a painful skin rash and complications.This study aimed to provide information on how many patients with psoriatic arthritis get shingles and the healthcare use and costs of caring for patients with psoriatic arthritis and shingles. What did the researchers do and find? Using data from a large US health plan database, we estimated that for every 1000 patients with psoriatic arthritis observed for 1 year, 15 will develop shingles.Patients with psoriatic arthritis were 23% more likely to develop shingles than people without psoriatic disease.Patients with psoriatic arthritis and shingles had 2­3 times as many healthcare visits in the month after a shingles diagnosis as patients with psoriatic arthritis but no shingles.This resulted in an average additional cost of approximately $2000 per patient. What do these results mean? Psoriatic arthritis increases the risk of shingles.The costs associated with shingles in patients with psoriatic arthritis are substantial.Measures to prevent shingles in this population could be beneficial.

The potential impact of increased recombinant zoster vaccine coverage on the burden of herpes zoster among adults aged 50-59 years.

INTRODUCTION: Recombinant zoster vaccine (RZV) is recommended in the US for prevention of herpes zoster (HZ) in adults aged ≥50 years. Vaccination rates remain suboptimal for adults 50-59 years compared with adults ≥50 years overall. The objective of this study was to model changes in outcomes associated with improved RZV vaccination coverage in US adults 50-59 years. METHODS: A multicohort Markov model compared a scenario using real-world vaccination coverage for US adults 50-59 years in 2020 versus scenarios assuming higher coverage. Outcomes, based on a lifetime horizon, included HZ cases and complications avoided, quality-adjusted life-years (QALY), and costs. Model inputs included HZ epidemiology, RZV vaccine efficacy, coverage, adverse events, and costs, based on published literature and US sources. Some inputs were updated from previous models, including real-world estimates of RZV coverage, series completion, and reflecting longer-term data on waning of vaccine efficacy. The model utilized a cohort size of 42,756,488 individuals based on the 2020 US population census. RESULTS: The model projected that increasing RZV coverage in adults 50-59 years from 7.3 % to 14.6 % (to coverage for adults 60-64 years in 2020) would avoid an additional 504,468 HZ cases, 42,077 postherpetic neuralgia cases, and 56,247 cases of other HZ-associated complications. The increase in vaccine coverage would result in higher vaccination-related costs of $1,172,411,566, but the avoided HZ cases and complications would be expected to result in direct cost savings of $721,973,386 and indirect cost savings of $593,497,480 from avoided productivity loss. Overall, a gain of 5,230 discounted QALYs and cost savings of $143,059,299 from a societal perspective would be realized. CONCLUSION: Modestly higher RZV coverage in US adults 50-59 years could reduce the clinical burden associated with HZ and may result in societal cost savings. These findings demonstrate the potential value of increasing RZV vaccination in this population.

Predicting Chronic Opioid Use Among Patients With Osteoarthritis Using Electronic Health Record Data.

OBJECTIVE: To estimate the risk of a patient with osteoarthritis (OA) developing chronic opioid use (COU) within 1 year of a new opioid prescription by using electronic health record (EHR) data and predictive models. METHODS: We used EHR data from 13 health care organizations to identify patients with OA with an opioid prescription between March 1, 2017 and February 28, 2019 and no record of opioid use in the prior 6 months. We evaluated 4 machine learning models to estimate patients' risk of COU (≥3 prescriptions ≥84 days, maximum gap ≤60 days). We also estimated the transportability of models to organizations outside the training set. RESULTS: The cohort consisted of 33,894 patients with OA, of whom 2,925 (8.6%) developed COU within 1 year. All models demonstrated good discrimination, with the best-performing model (random forest) achieving an area under the receiver operating characteristic curve (AUC) of 0.728 (95% CI 0.711-0.745), but the simplest regression model performed nearly as well (AUC 0.717 [95% CI 0.699-0.734]). Predicted risk deciles spanned a range of 2% risk for the 10th percentile to 18% risk for the 90th percentile for well-calibrated models. Models showed highly variable discrimination across organizations (AUC 0.571-0.842). CONCLUSIONS: We found that EHR-based predictive models could estimate the risk of future COU among patients with OA to help inform care decisions. Black-box methods did not have significant advantages over more interpretable models. Care should be taken when extending all models into organizations not included in model training because of a high variability in performance across held-out organizations.

Burden of Herpes Zoster Among Patients with Psoriasis in the United States.

INTRODUCTION: Patients with psoriasis (PsO) are at increased risk of herpes zoster (HZ), but recent data on the incidence of HZ among patients with PsO and the impact of HZ on healthcare resource use (HRU) and costs for patients with PsO have not been described. METHODS: This retrospective, longitudinal, cohort study estimated HZ incidence in cohorts of adults with vs without PsO (PsO + vs PsO-) and HRU and costs among those with PsO, with vs without HZ (PsO + /HZ + vs PsO + /HZ-) using Optum's de-identified Clinformatics Data Mart Database during 2015-2020. Patients with psoriatic arthritis were excluded from all four cohorts. Comparisons between cohorts used generalized linear models to adjust outcomes based on various baseline characteristics. RESULTS: The incidence rate of HZ was significantly higher in the PsO + (n = 144,115) vs PsO- (n = 23,837,237) cohorts at 11.35 vs 7.67 per 1000 patient-years; adjusted incidence rate ratio (aIRR): 1.21, 95% confidence interval (CI): 1.16-1.25. HRU (outpatient, emergency department, and inpatient) was significantly higher in the PsO + /HZ + (n = 1859) vs PsO + /HZ- (n = 78,664) cohorts during 1 month and 3 months after HZ diagnosis (e.g., outpatient visits during month: 2.83 vs 1.30 per patient; aIRR: 1.96; 95% CI 1.86-2.06). Mean all-cause costs were also significantly higher in the PsO + /HZ + vs PsO + /HZ- cohort during both month ($5020 vs $2715 per patient; adjusted cost difference: $1390; 95% CI $842-$1964) and 3 months ($12,305 vs $8256; adjusted cost difference: $1422; 95% CI $280-$2889) after HZ diagnosis. CONCLUSION: These findings show the increased incidence of HZ among patients with PsO and the clinical and economic burdens of HZ in this population. Considering the high prevalence of PsO, insights into the impact of HZ in these patients provide valuable evidence to inform clinical decision-making.

Psoriasis is an inflammatory condition that causes flaky, scaly skin. Herpes zoster (shingles) causes a painful rash, usually on the abdomen. However, recent data on the proportion of patients with psoriasis who develop herpes zoster is lacking. Furthermore, little is known about the healthcare resources that are used or the costs of care for patients with psoriasis who develop herpes zoster. We found that patients with psoriasis were 21% more likely to have herpes zoster than patients without psoriasis. Among patients with psoriasis, those who developed herpes zoster had twice as many doctor's visits, 3 times as many emergency department visits, and twice as many inpatient hospital stays during the month after a herpes zoster diagnosis as patients without herpes zoster. This resulted in an additional cost of $1390 per patient with psoriasis and herpes zoster compared with those with psoriasis but without herpes zoster. Overall, patients with psoriasis are at increased risk of developing herpes zoster and the healthcare resource use and associated cost of treating herpes zoster in patients with psoriasis is substantial.

Fulfillment and Validity of the Kidney Health Evaluation Measure for People with Diabetes.

Objective: To evaluate the fulfillment and validity of the kidney health evaluation for people with diabetes (KED) Healthcare Effectiveness Data Information Set (HEDIS) measure. Patients and Methods: Optum Labs Data Warehouse (OLDW) was used to identify the nationally distributed US population aged 18 years and older, with diabetes, between January 1, 2017, and December 31, 2017. The OLDW includes deidentified medical, pharmacy, laboratory, and electronic health record (EHR) data. The KED fulfillment was defined in 2017 as both estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio testing within the measurement year. The KED validity was assessed using bivariate analyses of KED fulfillment with diabetes care measures in 2017 and chronic kidney disease (CKD) diagnosis and evidence-based kidney protective interventions in 2018. Results: Among eligible 5,635,619 Medicare fee-for-service beneficiaries, 736,875 Medicare advantage (MA) beneficiaries, and 660,987 commercial patients, KED fulfillment was 32.2%, 38.7%, and 37.7%, respectively. Albuminuria testing limited KED fulfillment with urinary albumin-creatinine ratio testing (<40%) and eGFR testing (>90%). The KED fulfillment was positively associated with receipt of diabetes care in 2017, CKD diagnosis in 2018, and evidence-based kidney protective interventions in 2018. The KED fulfillment trended lower for Black race, Medicare-Medicaid dual eligibility status, low neighborhood income, and low education status. Conclusion: Less than 40% of adults with diabetes received guideline-recommended testing for CKD in 2017. Routine KED was associated with diabetes care and evidence-based CKD interventions. Increasing guideline-recommended testing for CKD among people with diabetes should lead to timely and equitable CKD detection and treatment.

Including measures of chronic kidney disease to improve cardiovascular risk prediction by SCORE2 and SCORE2-OP.

AIMS: The 2021 European Society of Cardiology (ESC) guideline on cardiovascular disease (CVD) prevention categorizes moderate and severe chronic kidney disease (CKD) as high and very-high CVD risk status regardless of other factors like age and does not include estimated glomerular filtration rate (eGFR) and albuminuria in its algorithms, systemic coronary risk estimation 2 (SCORE2) and systemic coronary risk estimation 2 in older persons (SCORE2-OP), to predict CVD risk. We developed and validated an 'Add-on' to incorporate CKD measures into these algorithms, using a validated approach. METHODS: In 3,054 840 participants from 34 datasets, we developed three Add-ons [eGFR only, eGFR + urinary albumin-to-creatinine ratio (ACR) (the primary Add-on), and eGFR + dipstick proteinuria] for SCORE2 and SCORE2-OP. We validated C-statistics and net reclassification improvement (NRI), accounting for competing risk of non-CVD death, in 5,997 719 participants from 34 different datasets. RESULTS: In the target population of SCORE2 and SCORE2-OP without diabetes, the CKD Add-on (eGFR only) and CKD Add-on (eGFR + ACR) improved C-statistic by 0.006 (95%CI 0.004-0.008) and 0.016 (0.010-0.023), respectively, for SCORE2 and 0.012 (0.009-0.015) and 0.024 (0.014-0.035), respectively, for SCORE2-OP. Similar results were seen when we included individuals with diabetes and tested the CKD Add-on (eGFR + dipstick). In 57 485 European participants with CKD, SCORE2 or SCORE2-OP with a CKD Add-on showed a significant NRI [e.g. 0.100 (0.062-0.138) for SCORE2] compared to the qualitative approach in the ESC guideline. CONCLUSION: Our Add-ons with CKD measures improved CVD risk prediction beyond SCORE2 and SCORE2-OP. This approach will help clinicians and patients with CKD refine risk prediction and further personalize preventive therapies for CVD.

Potential barriers to filling buprenorphine and naltrexone prescriptions among a retrospective cohort of individuals with opioid use disorder.

INTRODUCTION: Medications for opioid use disorder (MOUD) are highly effective, but barriers along the cascade of care for opioid use disorder (OUD) from diagnosis to treatment limit their reach. For individuals desiring MOUD, the final step in the cascade is filling a written prescription, and fill rates have not been described. METHODS: We used data from a large de-identified database linking individuals' electronic medical records (EMR) and administrative claims data and employed a previously developed algorithm to identify individuals with a new diagnosis of OUD. We included individuals with a prescription for buprenorphine or naltrexone recorded in the EMR. The outcome was a prescription fill within 30 days as reported in claims data. We compared demographic and clinical characteristics between those who did and did not fill the prescription and used a Kaplan-Meier curve to assess whether fill rates differed based on patient copay. RESULTS: We identified 264 individuals with a new diagnosis of OUD who had a prescription written for buprenorphine or oral naltrexone. Of these, 70% (184) filled the prescription within 30 days, and more than half (57%) filled the prescription on the day it was written. Individuals with prescription copay at or below the mean had a 75% fill rate at 30 days compared with 63% for those with copay above the mean (p < 0.05) and this difference was consistent across fill times (log rank p-value <0.05). CONCLUSIONS: It is alarming that nearly 1 in 3 MOUD prescriptions go unfilled. More research is needed to understand and reduce barriers to this final step of the OUD cascade of care.

Development and Validation of Prediction Models of Adverse Kidney Outcomes in the Population With and Without Diabetes.

OBJECTIVE: To predict adverse kidney outcomes for use in optimizing medical management and clinical trial design. RESEARCH DESIGN AND METHODS: In this meta-analysis of individual participant data, 43 cohorts (N = 1,621,817) from research studies, electronic medical records, and clinical trials with global representation were separated into development and validation cohorts. Models were developed and validated within strata of diabetes mellitus (presence or absence) and estimated glomerular filtration rate (eGFR; ≥60 or <60 mL/min/1.73 m2) to predict a composite of ≥40% decline in eGFR or kidney failure (i.e., receipt of kidney replacement therapy) over 2-3 years. RESULTS: There were 17,399 and 24,591 events in development and validation cohorts, respectively. Models predicting ≥40% eGFR decline or kidney failure incorporated age, sex, eGFR, albuminuria, systolic blood pressure, antihypertensive medication use, history of heart failure, coronary heart disease, atrial fibrillation, smoking status, and BMI, and, in those with diabetes, hemoglobin A1c, insulin use, and oral diabetes medication use. The median C-statistic was 0.774 (interquartile range [IQR] = 0.753, 0.782) in the diabetes and higher-eGFR validation cohorts; 0.769 (IQR = 0.758, 0.808) in the diabetes and lower-eGFR validation cohorts; 0.740 (IQR = 0.717, 0.763) in the no diabetes and higher-eGFR validation cohorts; and 0.750 (IQR = 0.731, 0.785) in the no diabetes and lower-eGFR validation cohorts. Incorporating the previous 2-year eGFR slope minimally improved model performance, and then only in the higher-eGFR cohorts. CONCLUSIONS: Novel prediction equations for a decline of ≥40% in eGFR can be applied successfully for use in the general population in persons with and without diabetes with higher or lower eGFR.

A Retrospective Analysis of Therapeutic Inertia in Type 2 Diabetes Management Across a Diverse Population of Health Care Organizations in the USA.

INTRODUCTION: If their target glycated hemoglobin (HbA1c) is not achieved after 3 months, timely treatment intensification is recommended in people with type 2 diabetes to maintain glycemic control and minimize vascular complications. We retrospectively investigated potential therapeutic inertia in the management of type 2 diabetes in multiple health care organizations across the USA. METHODS: Electronic health records were analyzed from 22 American Medical Group Association (AMGA) health care organizations. Bolus insulin-naïve patients with type 2 diabetes and HbA1c ≥ 8.0% (≥ 64 mmol/mol) at baseline were followed for 24 months to identify the frequency and average duration of therapeutic inertia (no new class of glucose-lowering medication prescribed, or not achieving their target HbA1c [< 8.0%; < 64 mmol/mol]). RESULTS: The study cohort comprised almost 28,000 patients. Therapeutic inertia was observed in ≈ 50% of patients after 6 months, and in > 10% after 24 months. Less therapeutic inertia was observed in patients receiving one or no oral antidiabetic drugs (OADs) (36% or 28%, respectively, at 6 months), while more inertia was seen following multiple OADs or basal insulin (54% of those on baseline basal insulin at 6 months). Although an observable action was recorded for 90% of patients, many (44%) had still not achieved their target HbA1c after 24 months. CONCLUSION: The results corroborate the presence of therapeutic inertia in people with type 2 diabetes, suggesting that treatment intensification guidelines are not being followed. Extensive variability in the presence of therapeutic inertia was observed both across and within organizations; investigating this further and sharing best practices across providers might help improve the quality of patient care at organizational and national levels.

People with type 2 diabetes have their glycated hemoglobin (HbA_1c) level measured regularly by their care provider to check their blood sugar levels over the previous 2­3 months and the diabetes control achieved with their current treatment. To keep HbA_1c within an individually recommended range, changes to therapies or doses may be needed, which is known as 'treatment intensification.' Despite guidelines describing this best-practice approach, 'therapeutic inertia' (not intensifying treatment when needed) is common. This therapeutic inertia may be a result of complicated or confusing guidelines, a lack of time or awareness/understanding on the part of the health care provider, or patient-specific barriers such as treatment cost or fear of side effects. Due to therapeutic inertia, patients can have poorly controlled diabetes for a long time, increasing their risk of other diabetes-related health problems or complications. This study describes widespread therapeutic inertia in the management of type 2 diabetes across the USA, suggesting that treatment intensification in patients with poor diabetes control is not taking place when needed. Diabetes-related health complications caused by poorly controlled disease over a period of time can significantly reduce quality of life. Diabetes and its complications also increase costs for the health care system due to the resulting medical costs and diabetes-related reductions in productivity. It is important to encourage early diagnosis of diabetes and appropriate and timely treatment. Investigating the variations in therapeutic inertia seen within and between health care organizations and sharing the lessons learned by the top-performing organizations may help spread best practices and improve the quality of patient care.

Estimating Kidney Failure Risk Using Electronic Medical Records.

Background: The four-variable kidney failure risk equation (KFRE) is a well-validated tool for patients with GFR <60 ml/min per 1.73 m2 and incorporates age, sex, GFR, and urine albumin-creatinine ratio (ACR) to forecast individual risk of kidney failure. Implementing the KFRE in electronic medical records is challenging, however, due to low ACR testing in clinical practice. The aim of this study was to determine, when ACR is missing, whether to impute ACR from protein-to-creatinine ratio (PCR) or dipstick protein for use in the four-variable KFRE, or to use the three-variable KFRE, which does not require ACR. Methods: Using electronic health records from OptumLabs Data Warehouse, patients with eGFR <60 ml/min per 1.73 m2 were categorized on the basis of the availability of ACR testing within the previous 3 years. For patients missing ACR, we extracted urine PCR and dipstick protein results, comparing the discrimination of the three-variable KFRE (age, sex, GFR) with the four-variable KFRE estimated using imputed ACR from PCR and dipstick protein levels. Results: There were 976,299 patients in 39 health care organizations; 59% were women, the mean age was 72 years, and mean eGFR was 47 ml/min per 1.73 m2. The proportion with ACR testing was 19% within the previous 3 years. An additional 2% had an available PCR and 36% had a dipstick protein; the remaining 43% had no form of albuminuria testing. The four-variable KFRE had significantly better discrimination than the three-variable KFRE among patients with ACR testing, PCR testing, and urine dipstick protein levels, even with imputed ACR for the latter two groups. Calibration of the four-variable KFRE was acceptable in each group, but the three-variable equation showed systematic bias in the groups that lacked ACR or PCR testing. Conclusions: Implementation of the KFRE in electronic medical records should incorporate ACR, even if only imputed from PCR or urine dipstick protein levels.

Chronic Kidney Disease Testing Among Primary Care Patients With Type 2 Diabetes Across 24 U.S. Health Care Organizations.

OBJECTIVE: Clinical guidelines for people with diabetes recommend chronic kidney disease (CKD) testing at least annually using estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (uACR). We aimed to understand CKD testing among people with type 2 diabetes in the U.S. RESEARCH DESIGN AND METHODS: Electronic health record data were analyzed from 513,165 adults with type 2 diabetes receiving primary care from 24 health care organizations and 1,164 clinical practice sites. We assessed the percentage of patients with both one or more eGFRs and one or more uACRs and each test individually in the 1, 2, and 3 years ending September 2019 by health care organization and clinical practice site. Elevated albuminuria was defined as uACR ≥30 mg/g. RESULTS: The 1-year median testing rate across organizations was 51.6% for both uACR and eGFR, 89.5% for eGFR, and 52.9% for uACR. uACR testing varied (10th-90th percentile) from 44.7 to 63.3% across organizations and from 13.3 to 75.4% across sites. Over 3 years, the median testing rate for uACR across organizations was 73.7%. Overall, the prevalence of detected elevated albuminuria was 15%. The average prevalence of detected elevated albuminuria increased linearly with uACR testing rates at sites, with estimated prevalence of 6%, 15%, and 30% at uACR testing rates of 20%, 50%, and 100%, respectively. CONCLUSIONS: While eGFR testing rates are uniformly high among people with type 2 diabetes, testing rates for uACR are suboptimal and highly variable across and within the organizations examined. Guideline-recommended uACR testing should increase detection of CKD.