Publications

BACKGROUND Variability exists in acceptance of living kidney donor candidates across the US. This study sought to quantify the extent to which this variation is driven by donor candidate ancestry, transplant centers and providers.METHODS Using a retrospective cohort study of living donor candidates who completed donor evaluation across nine US transplant centers, we examined the Kidney Failure Risk Projection (KFRP) model (estimating donor risk of ESKD at 15 years) as a proxy of the threshold for donor acceptance. Mixed linear models clustered by transplant center and provider were used to relate donor ancestry to center decisions.RESULTS Among 1888 living donor candidates (median age 42 years, 62% women), 39% Black candidates were accepted to donate versus 45% Hispanic and 56% White candidates (p<0.001). KFRP scores were extremely low, with median risk of 0.13% (IQR 0.06-0.27). Accounting for the 15-year KFRP score in adjusted models, the odds of donor acceptance were higher for White candidates (OR 1.46; 95% CI 1.13-1.88) compared with Hispanic (referent) and Black candidates (OR 0.74; 95% CI 0.53-1.04). White donor candidates declined for donation had a higher KFRP score by 0.08% versus Hispanic and Black candidates (p<0.05). In mixed models, residual variability in donor acceptance was observed at the transplant center (SD 0.08% in the KFRP score) and provider levels (SD 0.04%) for those accepted as donors, without variability by donor ancestry.CONCLUSIONS In this cohort, although fewer Black donor candidates were accepted for donation versus White and Hispanic candidates, accepted candidates had extremely low risk of developing ESKD within 15 years, regardless of ancestry. Variability across providers and transplant centers was observed, but absolute differences in their threshold of acceptance (or non-acceptance) were small. Our findings suggest that disparities in living donor access by donor ancestry are not explained by differences in system-level variations in practice.

Background Slower chronic kidney disease (CKD) progression allows more time for transplant preparation. Whether differences in CKD progression by race/ethnicity associate with preemptive or living donor transplantation in youth has not been well studiedMethods We examined the association between time spent with low eGFR (between 10–30 mL/min/1.73 m 2 ) and odds of preemptive or living donor transplantation among youth with CKD. eGFR was estimated using the bedside Schwartz (if < 18 years) and CKD-EPI 2021 equations (if ≥ 18 years) and the CKiD U25 equation in sensitivity analysis. Time spent with low eGFR was compared by race/ethnicityResults Among 333 youth with CKD (median age 11 years [IQR 7,14]), median time spent with low eGFR was 28.8 months. 77% were preemptively waitlisted, and 45% received preemptive transplantation (56% of White and 24% of Black youth). Black (vs. White) youth had shorter time with low eGFR (–6.5 months; 95% CI –11.5, –1.4). Time with low eGFR did not differ across other groups. Findings were similar using the U25 equation. Every additional year spent with low eGFR was associated with higher odds of preemptive (OR 1.45; 95% CI 1.24–1.70) and living donor transplantation (OR 1.42; 95% CI 1.21–1.67), but not preemptive waitlisting (OR 0.96; 95% CI 0.83–1.11) in unadjusted analysesConclusions Longer time spent with low eGFR is associated with greater odds of preemptive and living donor transplantation. Earlier transplant referral for all children, especially Black youth, may help improve access to preemptive and living donor transplantation. Graphical abstract

Objective The aim of this study was to compare and rank the efficacy and safety of four final oocyte maturation trigger strategies—human chorionic gonadotropin (hCG), gonadotropin-releasing hormone agonist (GnRHa), dual, and double trigger—in predicted high responders undergoing in vitro fertilization (IVF) with GnRH antagonist protocols, using a network meta-analysis (NMA) approachMethods A systematic search of MEDLINE, EMBASE, CENTRAL, clinical trial registries, and the Cochrane Database of Systematic Reviews was conducted through December 2024. Eligible studies were randomized controlled trials (RCTs) including high responders, defined by elevated antral follicle count, anti-Müllerian hormone, or estradiol levels. Studies using GnRHa triggers followed by fresh embryo transfer were included only if intensive luteal phase support was provided. Oocyte donation cycles, quasi-randomized designs, and trials lacking outcome data were excluded. Data extraction and risk of bias assessment were independently conducted by two reviewers. Study integrity was evaluated using the TRACT checklist. NMA was performed in STATA (v16), and treatment ranking was based on Surface Under the Cumulative Ranking curve (SUCRA)Results Seven high-quality RCTs comprising 632 women were included. There were no significant differences in the number of oocytes retrieved between GnRHa and hCG triggers (mean difference [MD] 1.08, 95% CI –1.06 to 3.22), dual and hCG (MD 0.61, 95% CI –1.53 to 2.74), or GnRHa and dual (MD 1.08, 95% CI –1.06 to 3.22). Similarly, there were no significant differences in mature oocyte yield, clinical pregnancy rate (CPR), or miscarriage rate across comparisons. However, GnRHa trigger significantly reduced the risk of moderate to severe ovarian hyperstimulation syndrome (OHSS) compared with hCG (RR 0.23, 95% CI 0.07–0.82). There were no significant differences in OHSS risk between dual and hCG (RR 0.28, 95% CI 0.05–1.64) or between GnRHa and dual (RR 0.28, 95% CI 0.05–1.64)Conclusion GnRHa, hCG, and dual triggers demonstrate similar efficacy in terms of oocyte yield, maturity, and clinical pregnancy rates in predicted high responders. The GnRHa trigger, however, offers a superior safety profile by significantly lowering the risk of OHSS. Larger multicenter RCTs are required to evaluate live birth outcomes and the potential role of the double trigger in this population. Systematic review registration https://www.crd.york.ac.uk/prospero/ , identifier CRD42022351423.

Background Severe diabetes insipidus (DI) causes dynamic changes in creatinine before organ donation. It is unknown whether terminal or peak creatinine is the optimal measure of graft quality among donors with severe DIMethods Adult donors after brain death were identified from the United Network for Organ Sharing database, years 2015–2022. Kidney Donor Profile Index (KDPI) was computed using both terminal creatinine (KDPI-Terminal) and peak creatinine (KDPI-Peak). Model fit for the prediction of graft failure and reduced glomerular filtration rate (GFR) was compared. Logistic regression was used to determine the association between KDPI group reclassification and graft functionResults Of 28 718 kidney transplants, 29% of donors met criteria for severe DI. No differences in estimated GFR (eGFR) or all-cause graft failure were observed on the basis of the presence of DI. Among donors with severe DI, KDPI-Peak improved prediction of reduced eGFR at 1 y (eGFR <60 mL/min/1.73 m 2 , eGFR <30 mL/min/1.73 m 2 ). Additionally, patients who received organs from donors with severe DI whose KDPI group would be reclassified on the basis of the use of peak rather than terminal creatinine had 2-fold increased odds of reduced eGFR at 1 y (eGFR <30 mL/min/1.73 m 2 ; odds ratio, 1.92; 95% confidence interval, 1.37-2.69)Conclusions This national analysis confirms that while the presence of severe DI alone is not associated with graft outcomes, the use of peak creatinine significantly improves risk stratification of donor graft quality. Precise risk stratification is critical for efforts to improve appropriate kidney allocation and increase confidence in organ function after transplant.

RATIONALE & OBJECTIVE For transplant recipients with low estimated glomerular filtration rate (eGFR), early preparation is needed to optimize the transition back to dialysis or retransplantation. Our objective was to determine if the amount of time spent with low eGFR was associated with a higher likelihood of relisting or retransplantation within 1 year of graft failure.STUDY DESIGN Retrospective cohort study.SETTING & PARTICIPANTS We included adults who developed graft failure between 2010 and 2021 according to the US Renal Data System.EXPOSURE We modeled the time spent with eGFR between 20 and 5 mL/min/1.73 m2 using available serum creatinine values reported annually (henceforth referred to as time with low eGFR).OUTCOME Relisting or retransplantation within 1 year of graft failure.ANALYTICAL APPROACH We used Fine-Gray models accounting for the competing risk of death to determine the association between time spent with low eGFR (as a categorical variable) and outcomes of interest.RESULTS We included 14,680 patients; median age at graft failure was 53 years (IQR, 42-61). Within 1 year of graft failure, ∼18% (n = 2,690) of patients were relisted and 13% (n = 1,854) were retransplanted. In adjusted models, spending 2-4 years (SHR, 1.43; 95% confidence interval [CI], 1.16-1.75) or >4 years (SHR, 1.28; 95% CI, 1.04-1.57) with low eGFR was associated with a higher likelihood of relisting (vs spending <2 years with low eGFR). Similarly, spending 2-4 years (SHR, 1.37; 95% CI, 1.09-1.72) or >4 years (SHR, 1.73; 95% CI, 1.37-2.19) with low eGFR was also associated with a higher likelihood of retransplantation within 1 year of graft failure.LIMITATIONS Residual confounding; observational nature of study.CONCLUSIONS Timely preparation of patients with low eGFR for retransplantation could increase patients' likelihood of early relisting and retransplantation. For transplant recipients with low kidney function, the vast majority of patients will return to dialysis after graft failure, and many will not receive a second transplant. Our objective in this study was to determine if a longer time spent with low kidney function before the return to dialysis was associated with a higher likelihood of relisting or retransplantation in transplant recipients using national registry data. We found that spending more than 2 years with low eGFR was associated with a much higher likelihood of relisting and retransplantation than spending less than 2 years with low eGFR. Early preparation for retransplantation is needed to improve transplant patients’ likelihood of receiving a second transplant.

BACKGROUND AND HYPOTHESIS A decline in renal blood flow (RBF) precedes estimated glomerular filtration rate (eGFR) decline among patients with autosomal dominant polycystic kidney disease (ADPKD) and inversely associates with disease severity and progression. However, it is unknown whether RBF independently predicts progression to kidney failure in patients with ADPKD.METHODS 379 participants with early-stage ADPKD (age 36.6 ± 8.5 years [mean ± SD]; eGFR: 92.9 ± 17.1 mL/min/1.73m2) who participated in the HALT PKD Study A with baseline RBF (phase contrast MRI) data were included in the primary analysis. Kaplan Meier survival analysis and multivariate Cox proportional hazard models were used to determine the association of baseline RBF as a continuous and categorical variable with kidney failure risk (during HALT and subsequently linked to the US Renal Data System) over a median (IQR) follow-up period of 13.1 (7.5, 14.5) years (primary outcome). All-cause mortality was also considered as a competing risk (Fine and Gray method). The associations of RBF with eGFR slope and ∆ height-adjusted total kidney volume (htTKV) were evaluated with linear and logistic regression models.RESULTS The kidney failure incidence rate was the highest among those with the lowest RBF tertile (1.90 [1.31, 2.78] vs. 0.34 [0.14, 0.83] events/100 person-years in tertile 3). In the fully adjusted model, the lowest RBF tertile was associated with higher risk of progression to kidney failure (Hazard Ratio [HR (95% CI)] 3.19 [1.05, 9.67] vs. highest tertile). The association of RBF with kidney failure risk was slightly attenuated in adjusted models. All associations remained similar when considering death as a competing risk (HR: 0.82 [95% CI 0.67, 1.00] per 100 ml/min/1.73m2 higher RBF). Higher RBF was associated with slower eGFR decline and lower odds of rapid annual ∆htTKV.CONCLUSIONS Lower baseline RBF independently associates with greater risk of progression to kidney failure in early-stage patients with ADPKD.

Background/Objectives Embryo selection in IVF is traditionally based on morphology, yet many high-quality embryos fail to implant. Preimplantation genetic testing for aneuploidy (PGT-A) using next-generation sequencing (NGS) has been proposed to improve selection by identifying euploid embryos. However, its effectiveness in women of advanced maternal age remains unclear due to limited randomized data. This pilot trial assessed the feasibility of a full-scale RCT comparing PGT-A to morphology-based selection in women aged 35–42.Methods This single-centre, two-arm parallel RCT (NCT05009745) enrolled women aged 35–42 undergoing IVF/ICSI with ≥3 good-quality day-3 embryos. Participants were randomized (1:1) to either embryo selection by morphology with fresh transfer or PGT-A with frozen transfer of a single euploid embryo. Allocation concealment was achieved via a secure web-based randomization platform; patients and clinicians were unblinded, but the biostatistician remained blinded. The primary outcome was feasibility of recruitment, randomization, and adherence.Results Between June 2021 and January 2023, 138 women consented (recruitment rate: 55.8%, 95% CI: 49.7–62.0%) and 100 were randomized. Protocol adherence was 94%. Barriers to recruitment included preference for private PGT-A (19%) or fresh transfer (6%). Among biopsied embryos, 51.4% were euploid and 6.6% low-level mosaic. Intention-to-treat analysis showed no significant differences between PGT-A and control groups in clinical pregnancy rate (50% vs. 40%), live birth rate (50% vs. 38%), or miscarriage rate (12% vs. 8%). Cumulative live birth rate after up to three SETs was 72% vs. 52%, respectively (p > 0.05). No multiple pregnancies occurred.Conclusions RCTs of PGT-A in older women are feasible. A multicentre design with broader inclusion criteria could improve recruitment and allow better assessment of clinical benefit.

OBJECTIVE We evaluated the risk of persistent opioid use related to opioid pain management for hemodialysis access creation and identify patterns of opioid dosage and use.METHODS This retrospective cohort study included Medicare-enrolled opioid-naïve patients in the US Renal Data System who initiated hemodialysis for end-stage kidney disease between April 2015 and June 2019. Persistent opioid use was defined as an opioid prescription 90 to 180 days after surgery. The Cox proportional hazards model used censored patients at the time of hospitalization, subsequent hemodialysis access procedures, death, and end of Medicare enrollment. A mixed-effect logistic regression modeled opioid prescription, and a mixed-effect linear regression modeled opioid quantity in 5-mg hydrocodone equivalents.RESULTS A total of 28,404 patients (median age, 72 years; 25th, 75th percentile, 66, 79 years; 15,322 men [53.9%]) underwent index access creation, of whom 14,265 patients filled an opioid prescription at access creation (50.2%), with 3289 opioid prescriptions (23.1%) for ≥42 tablets of 5-mg hydrocodone equivalents (ie, ≥2 weeks prescription). Patients receiving ≥42 tablets of 5-mg hydrocodone equivalents (≥2 weeks) had 1.28 times the risk of persistent opioid use (95% confidence interval, 1.08-1.52) relative to those who did not fill an opioid prescription. In contrast, receipt of 20 or fewer tablets of 5-mg hydrocodone equivalents was not associated with an increased risk of persistent opioid use (hazard ratio 1.00; 95% confidence interval, 0.85-1.18).CONCLUSIONS Given the risk of persistent opioid use stemming from hemodialysis access procedures, the development of formal recommendations for conservative hemodialysis access pain management may be worth considering.

RATIONALE & OBJECTIVE Optimal blood pressure (BP) targets in advanced chronic kidney disease (CKD) are controversial. More intensive BP lowering in the setting of advanced CKD is thought to be associated with risk of acute kidney injury, hyperkalemia, and end-stage kidney disease. We conducted a pilot trial of intensive BP control to determine if lower home systolic BP (SBP) targets can be safely achieved for patients with CKD through titration of BP medications using in-home measured BP.STUDY DESIGN Nonblinded randomized controlled trial.SETTING & PARTICIPANTS 108 patients with advanced CKD (estimated glomerular filtration rate≤30mL/min/1.73m2) and hypertension.INTERVENTIONS Participants were randomized either to a target SBP goal of<120mm Hg (N=66) or a less intensive SBP goal (N=42). Antihypertensive medications were titrated to achieve the target home SBP range in the first 4 months of the study and maintained until the end of the study. Home BP was measured using a wireless Bluetooth-enabled monitor that transmitted readings to providers in real-time.OUTCOME The primary efficacy outcome was the difference in achieved clinic SBP between the 2 study arms from months 4-12. Safety outcomes included hyperkalemia, a composite outcome of falls or syncope, and onset of need for dialysis or kidney transplantation.RESULTS The mean clinic SBP at month 12 was 124.7mm Hg in the intensive SBP group versus 138.2mm Hg in the less intensive SBP group. Averaged over months 4-12, the achieved mean clinic SBP in the intensive SBP arm was 11.7mm Hg ([95% CI, 7.5-16], P<0.001), lower than the mean SBP achieved in the less intensive SBP arm. Primary safety outcomes were not statistically significantly different between the 2 arms (all P>0.05).LIMITATIONS Small sample size, which may have limited our ability to detect clinically significant differences in rates of adverse outcomes, and single-center design.CONCLUSIONS A clinic SBP goal of<120mm Hg is feasible to achieve with the help of real-time home BP monitoring and appears to be safe in this study population with advanced CKD. Larger trials to determine optimal BP targets in advanced CKD and the risks and benefits associated with more intensive BP control are warranted.FUNDING Grant from an educational institution (UCSF Research Allocation Program award).TRIAL REGISTRATION Registered at ClinicalTrials.gov with study number NCT02975505. PLAIN-LANGUAGESUMMARY We conducted a pilot trial to test the feasibility of lowering blood pressure (BP) intensively through the use of home BP monitoring in patients with low kidney function. We found that home BP monitoring used to guide antihypertensive medication dosing permitted better BP control for patients with chronic kidney disease and did not appear to be associated with major adverse events.

Autosomal dominant polycystic kidney disease (ADPKD) is a slowly progressive kidney disease, and the effect of interventions on hard outcomes such as onset of end-stage kidney disease (ESKD) may be challenging to ascertain given the short duration of most clinical trials, where the statistical power may be low.

BACKGROUND Prior research has linked higher body mass index (BMI) and greater visceral adiposity with more rapid progression of early-stage autosomal dominant polycystic kidney disease (ADPKD). We now evaluate the association between overweight and obesity in patients with early- and late-stage ADPKD with progression to ESKD.METHODS Participants with early-stage ADPKD (study A; N=556; eGFR: 91±17 ml/min per 1.73 m2) and late-stage ADPKD (study B; N=483; eGFR: 48±12 ml/min per 1.73 m2) who participated in the Halt Progression of Polycystic Kidney Disease (HALT) polycystic kidney disease trials were categorized by BMI as normal weight (18.5–24.9 kg/m2; ref; n=357), overweight (25.0–29.9 kg/m2; n=384), or obese (≥30 kg/m2; n=298). Kaplan–Meier survival analysis and multivariate Cox proportional hazard models were used to determine the association of baseline BMI as a continuous and categorical variable with risk of ESKD (according to the United States Renal Data System) over a median (interquartile range) follow-up period of 12.2 (7.5–13.3; study A) and 7.3 (5.1–11.7; study B) years (primary outcome). All-cause mortality (National Death Index) was also considered as a competing risk (Fine and Gray method).RESULTS The number of ESKD events was greater with overweight (n=24) and obesity (n=23) in HALT study A versus normal weight (n=12) but not in HALT study B (normal weight: n=89, overweight: n=102, obese: n=92). In fully adjusted models, higher BMI was associated with risk of progression to ESKD in study A (hazard ratio [HR (95% confidence interval)], 1.09 [1.03 to 1.15] per unit higher BMI) but not in study B (HR, 0.98 [0.96 to 1.00]). Obesity was associated with increased risk of ESKD (HR, 2.71 [1.22 to 6.02] versus normal weight) in study A only. Results were similar when considering death as a competing risk.CONCLUSIONS Higher BMI, particularly obesity, increased the risk of progression to ESKD in patients with early-stage ADPKD but not in those with late-stage ADPKD.

BACKGROUND There has been a recent trend toward starting dialysis at higher eGFRs in children, with no identified survival benefits. We aimed to determine whether there are similar trends in the timing of preemptive kidney transplant and whether higher eGFR (≥15 ml/min per 1.73 m2) at preemptive kidney transplant was associated with clinical outcomes among US children.METHODS We performed a retrospective cohort study of 1514 children in the United States Renal Data System who received a preemptive kidney transplant between 2006 and 2019. In primary analysis, we examined the association between calendar year and eGFR (ml/min per 1.73 m2) at the time of preemptive kidney transplant, categorized as higher (eGFR ≥15) versus lower (eGFR <15) using logistic regressions. The relationship between eGFR at preemptive kidney transplant and graft failure or death was assessed using Cox proportional hazards and Fine–Gray models.RESULTS We found a temporal trend in eGFR at preemptive kidney transplant in children; every 5-year increase in calendar period was associated with 55% higher odds (95% confidence interval, 1.35 to 1.79) of receiving a preemptive kidney transplant at higher eGFR. There was no association between preemptive kidney transplant at higher (versus lower) eGFR and risk of allograft failure or death (hazard ratio, 1.12; 95% confidence interval, 0.87 to 1.43) over a median follow-up of 5.7 years.CONCLUSIONS There has been a trend toward preemptive kidney transplant at higher eGFR over time in children. Receipt of a preemptive kidney transplant at higher eGFR was not associated with allograft or patient survival. Implications of these trends deserve further study.

Objective With the use of two-dimensional ultrasound (2D US) in embryo transfer (ET) procedures now a widely accepted practice, and preferred over clinical touch (CT), there is growing interest in whether three-dimensional (3D) and four-dimensional (4D) US provide better outcomes for ET compared with traditional 2D methods. We aim to perform a network meta-analysis (NMA) to compare the clinical efficacy and safety of CT, 2D transabdominal (TAUS), 2D transvaginal (TVUS), 3D, and 4D US-guided ET.Evidence Review Randomized controlled trials (RCTs) indexed in PubMed, MEDLINE, EMBASE, clinical trial registries, and Cochrane Database of Systematic Reviews were searched from inception to December 2023. Identified RCTs were assessed for trustworthiness using the Trustworthiness in RAndomized Controlled Trials. Statistical analysis for pairwise was performed using Review Manager version 5.3 and NMAs were performed using STATA version 16. Random-effects modeling was used for data-pooling. Key outcomes included clinical pregnancy (CPRs) and live birth rates (LBRs), miscarriage rates, and ectopic pregnancy rates.Results Twenty-five RCTs of high integrity assessing 8,884 ET outcomes comparing CT, 2D TAUS-, 2D TVUS-, 3D TAUS-, and 4D TVUS-guided ET were included. The NMA identified lower LBR with CT (risk ratio [RR]: 0.78, 95% confidence interval [CI]: 0.59–1.03) compared with 2D TAUS. There were no significant differences in LBR between other methods, including 2D TVUS vs. 2D TAUS (RR: 1.03, 95% CI: 0.61–1.74), and 3D TAUS vs. 2D TAUS (RR: 1.01, 95% CI: 0.78–1.32). Clinical touch-guided ET was associated with a lower CPR compared with 2D TAUS (RR: 0.83, 95% CI: 0.75–0.91). There was no significant CPR difference comparing 2D TVUS vs. 2D (RR: 0.98, 95% CI: 0.83–1.16), 3D TAUS vs. 2D TAUS (RR 0.98, 95% CI: 0.80–1.20). Four-dimensional TVUS did not show a significant difference in either LBR or CPR compared with 2D TAUS, 3D TAUS, or CT.Conclusion For CPR, our study reinforces that ET guided by CT alone is inferior to 2D TAUS-guided transfer. However, when comparing 2D TAUS-, 2D TVUS-, 3D TAUS-, and 4D TVUS-guided ET, we found no evidence of significant differences in LBR, CPR, miscarriage rates, or ectopic pregnancy rates. The certainty of evidence for our primary outcome of CPR was rated as moderate, reflecting confidence in the results, but with notable concerns regarding study limitations and paucity of trials assessing the use of 3D and 4D US.

Prior studies have shown that only 3.8% of children receiving outpatient dialysis had sufficient recovery of kidney function to discontinue dialysis within 1 year. However, little is known regarding the risk factors associated with the need for restarting kidney replacement therapy (KRT) after recovery from the need for chronic outpatient dialysis. This is particularly important in children, who are at risk of restarting KRT for a longer duration of time given their young age. Characterizing the factors that predict a high likelihood for restarting KRT after initial recovery of kidney function is important to better prepare children and families for this possible outcome and implement preventative therapies. The objective of this study was to identify the incidence and risk factors for needing KRT after recovery of kidney function in children using data from the US Renal Data System (USRDS).

OBJECTIVE To compare efficacy and safety of human chorionic gonadotropin (hCG), gonadotropin-releasing hormone (GnRH) agonist, dual, and double triggers in predicted healthy responders undergoing ovarian stimulation and in vitro fertilization.DESIGN A systematic review and network meta-analysis of randomized controlled trials (RCTs).DATA SOURCES Randomized controlled trials indexed in PubMed, MEDLINE, EMBASE, clinical trial registries, and Cochrane Database of Systematic Reviews up to December 2023.STUDY SELECTION AND SYNTHESIS Twelve high-integrity RCTs comprising 1,931 women were included, which compared hCG trigger with GnRH agonist trigger, dual trigger, and double trigger. Statistical analysis was performed using STATA version 16.MAIN OUTCOME MEASURES Key outcomes included clinical pregnancy rates (CPR), live birth rates (LBR), number of oocytes, number of mature oocytes, miscarriage rates, and rates of ovarian hyperstimulation syndrome.RESULTS The network meta-analysis for CPR were risk ratio (RR), 1.13; (95% confidence interval [CI], 0.80-1.60) for hCG vs. GnRH agonist trigger, RR, 1.23 (95% CI, 0.92-1.65) for hCG vs. dual trigger, RR, 0.38 (95% CI, 0.21-0.69) for hCG vs. double trigger, RR, 1.09 (95% CI, 0.70-1.70) for GnRH agonist vs. dual trigger and 0.34 (95% CI, 0.17-0.67) for GnRH agonist vs. double trigger, and RR, 0.31 (95% CI, 0.16-0.60) for double vs. dual trigger. Dual trigger demonstrated the highest Surface Under the Cumulative Ranking (85.1%), indicating superior efficacy for CPR. For LBR, although connectivity was limited, the RR was 1.31 (95% CI, 1.00-1.70) for dual vs. hCG trigger, and RR, 1.60 (95% CI, 1.05-2.43) for dual vs. GnRH agonist trigger. Ovarian hyperstimulation syndrome rates were significantly lower with the GnRH agonist compared with hCG trigger (RR, 0.56; 95% CI, 0.19-1.75). There were no RCTs reporting ovarian hyperstimulation syndrome rates with the use of dual or double trigger. No significant differences were observed in the number of oocytes retrieved, mature oocytes, or miscarriage rates among the trigger protocols.CONCLUSION AND RELEVANCE The findings indicate that there is no evidence to suggest that using GnRH agonist, dual, or double protocols is superior to hCG trigger in improving CPR. Although LBR may benefit from dual trigger, results are limited by available RCTs. Larger, multicenter trials are needed for further evaluation of LBR and understanding of long-term outcomes.

BACKGROUND Nephrology is one of the pediatric subspecialties with the largest workforce shortage in the United States. Waitlist registration is one of the first steps toward kidney transplantation and is facilitated by pediatric nephrologists. The objective of this study was to determine whether state-level density of pediatric nephrologists is associated with access to waitlisting (primary outcome) or kidney transplantation (secondary outcome) in children with kidney failure.METHODS Using Cox proportional hazards and logistic regression analyses, we studied children younger than 18 years who developed kidney failure between 2016 and 2020 according to the United States Renal Data System, the national kidney failure registry. The density of pediatric nephrologists (determined by the count of pediatric nephrologists per 100,000 children in each state) was estimated using workforce data from the American Board of Pediatrics and categorized into three groups: >1, 0.5–1, and <0.5.RESULTS We included 4497 children, of whom 3198 (71%) were waitlisted and 2691 (60%) received transplantation. Children residing in states with pediatric nephrologist density >1 had 33% (hazard ratio [HR], 1.33; 95% confidence interval [CI], 1.07 to 1.66) and 22% (HR, 1.22; 95% CI, 1.02 to 1.45) better access to waitlisting compared with those residing in states with <0.5 pediatric nephrologist density (reference group) in unadjusted and adjusted analysis, respectively. Pediatric nephrologist density was particularly important for the odds of preemptive waitlisting comparing the highest versus lowest workforce density (adjusted odds ratio, 1.56; 95% CI, 1.02 to 2.41). The adjusted HR was 1.25 (95% CI, 1.00 to 1.55; P = 0.046) for deceased donor transplantation and 1.24 (95% CI, 0.85 to 1.82) for living donor transplantation for children residing in states with pediatric nephrologist density >1 compared with the reference group.CONCLUSIONS Children residing in states with higher pediatric nephrologist density had better access to waitlist registration, especially preemptively, and deceased donor transplantation.

Objective To determine whether patient to nurse or patient to social worker staff ratios are associated with access to kidney transplant for adolescents and young adults.Design, Setting, and Participants Retrospective cohort study including patients aged 12 to 30 years who started dialysis between 2005 and 2019 at 8490 US facilities according to the US Renal Data System, the national end-stage kidney disease registry.Exposures Time-updated quartile of patient to nurse and patient to social worker ratios at dialysis facilities.Main Outcomes and Measures Fine-Gray models were used to relate the exposure to the incidence of waitlisting and kidney transplant, accounting for the competing risk of death. Subgroup analysis by age at dialysis initiation (<22 vs ≥22 years) was performed. Follow-up was censored in January 2020Results A total of 54 141 participants were included (median age, 25 years [IQR, 21-28]; 54.4% male; 4.3% of Asian race, 35.3% of non-Hispanic Black race). The median patient to staff ratios were 14.4 patients per nurse (IQR, 10.3-18.9) and 91.0 patients per social worker (IQR, 65.2-115.0). During a median follow-up of 2.6 years, 39.9% of patients (n = 21 598) received a transplant. In adjusted analysis, the highest (vs lowest) quartile of patient to nurse ratios was associated with 14% lower incidence of transplant (subhazard ratio [SHR], 0.86 [95% CI, 0.82-0.91]). The highest (vs lowest) quartile of patient to social worker ratios was associated with lower incidence of waitlisting (SHR, 0.95 [95% CI, 0.91-0.99]) and transplant (SHR, 0.85 [95% CI, 0.81-0.89]). For both staff ratios, there was an interaction with age at dialysis initiation, such that the association was more pronounced in patients starting dialysis at younger than 22 years (SHR, 0.71 [95% CI, 0.65-0.78] for the highest vs lowest quartile for nursing; SHR, 0.74 [95% CI, 0.68-0.80] for social work) compared with those 22 years and older (SHR, 1.00 [95% CI, 0.94-1.06] for nursing; SHR, 0.96 [95% CI, 0.91-1.02] for social work) for the outcome of transplantConclusions and Relevance Adolescents and young adults receiving care at dialysis facilities with higher patient to staff ratios had reduced access to waitlisting and transplant, particularly if they were younger than 22 years of age at dialysis initiation.

RATIONALE & OBJECTIVE Given the organ shortage in the United States, increasing living donation is vital to improving access to kidney transplantation, but many donor candidates do not complete the donor evaluation. Our objective was to understand potential living donors' perceived health and its association with the likelihood of completing the donor evaluation process.STUDY DESIGN Potential donors' self-reported health was ascertained using the Patient Reported Outcomes Measurement Information System (PROMIS) global physical and mental health and the Davies and Ware Health Perceptions surveys.SETTING & PARTICIPANTS Potential living donors who expressed interest in donation at a single medical center were recruited prospectively between 2017 and 2022.EXPOSURE Donors' self-reported health and health perceptions.OUTCOMES Completion of the donor evaluation.ANALYTICAL APPROACH Adjusted linear and logistic regression models were used to examine the association between self-reported health and health perceptions with outcomes.RESULTS A total of 1,347 individuals were included for study; 46% (N = 613) were < 40 years of age, 71% (n = 951) were female, 22% (n = 294) were of Hispanic ethnicity, and 16% (n = 215) completed the donor evaluation. The mean PROMIS global physical health (17.0 ± 1.9) and mental health (15.5 ± 2.7) raw scores were higher among donor candidates proceeding to completion of the donor evaluation when compared with those who withdrew early in the process (16.3 ± 2.2 for physical health and 14.9 ± 3.1 for mental health). Every z-score change in the PROMIS physical health score was associated with 1.48-fold higher odds of completing the donor evaluation (95% CI, 1.19-1.85). Fully adjusted models incorporating the PROMIS scores for predicting the completion of donor evaluations had a c-statistic of 0.70. Potential donors' Davies and Wares health perceptions did not predict the likelihood of completing the donor evaluation in fully adjusted models.LIMITATIONS Data are derived from a single center and may not generalize to the donor evaluation process at other transplant centers.CONCLUSIONS Donor candidates' self-reported physical health may serve as a predictor of the likelihood of completing the donor evaluation process and a potential avenue for future interventions. This study was designed to understand the health perceptions of living donor candidates. We found that donor candidates’ self-reported physical health strongly predicted their likelihood of completing the donor evaluation process. Further studies are needed to understand whether addressing donors’ self-perceptions of health may increase rates of completion of the donor evaluation.

Background Acute declines in estimated glomerular filtration rate (eGFR) occur commonly after starting angiotensin‐converting enzyme inhibitors. Whether declines in eGFR that occur after simultaneously starting angiotensin‐converting enzyme inhibitors with other antihypertensive agents modifies the benefits of these agents on cardiovascular outcomes is unclearMethods and Results We identified predictors of acute declines in eGFR (>15% over 3 months) during randomization to benazepril plus amlodipine versus benazepril plus hydrochlorothiazide in the ACCOMPLISH (Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension) trial. We then determined the relation between declines in eGFR (treated as a binary variable, ≤15% versus >15% and separately, as a restricted spline variable) and the composite risk of fatal and nonfatal cardiovascular events using Cox proportional hazards models. We included 10 714 participants (median age 68 years [Q1 63, Q3 73]), of whom 1024 reached the trial end point over median follow‐up of 2.8 years. Predictors of acute declines in eGFR>15% over 3 months included assignment to hydrochlorothiazide (versus amlodipine) and higher baseline albuminuria. Overall, declines in eGFR ≥15% (versus <15%) were associated with a 26% higher hazard of cardiovascular outcomes (95% CI, 1.07–1.48). In spline‐based analysis, risk for cardiovascular outcomes was higher in the hydrochlorothiazide arm at every level of decline in eGFR compared with the same magnitude of eGFR decline in the amlodipine armConclusion Combined use of benazepril and amlodipine remains superior to benazepril and hydrochlorothiazide for cardiovascular outcomes, regardless of the magnitude of the decline in eGFR that occurred with initiation of therapy.

In a cohort of 1817 children with type 1 diabetes (T1D), short-term hyperglycemia was associated with transient albuminuria (11 % during new-onset T1D without diabetic ketoacidosis (DKA), 12 % during/after DKA, 6 % during routine screening). Our findings have implications regarding future risk of diabetic kidney disease and further investigation is needed.

Objective We sought to evaluate the risk of preterm labor and hypertensive disorders in adolescent pregnancies with and without diabetes.Methods: We evaluated 1,843,139 adolescents (≤20 years old) with labor and delivery admissions in the national Kids’ Inpatient Database (KID) in years 2006, 2009, 2012, 2016, and 2019. International classification of disease codes was used to identify diabetes and medical factors affecting pregnancy. Weighted logistic regression was used to evaluate the association between diabetes and complications.Results: Among admissions, 0.2% had type 1 diabetes (T1D), 0.2% had type 2 diabetes (T2D), and 0.7% had gestational diabetes (GDM); 10.1% of admissions were complicated by hypertensive disorders and 5.8% by preterm labor. Compared to adolescents without diabetes, those with diabetes had a higher prevalence of hypertensive disorders (T1D: 35.4%, T2D: 37.8%, GDM: 24.9%, None: 9.9%; p < 0.001) and preterm labor (T1D: 21.5%, T2D: 16.8%, GDM: 6.8%, none: 5.7%; p < 0.001). In adjusted models, odds of hypertensive disorders were higher in later study years (2019 vs. 2006 OR 1.85, 95% CI 1.77–1.94), among those with T1D (OR 4.32, 95% CI 3.94–4.74), with T2D (OR 4.18, 95% CI 3.79–4.61), and with GDM (OR 1.99, 95% CI 1.89–2.10). Adjusted odds of preterm labor were higher among those with T1D (OR 4.53, 95% CI 4.09–5.02), with T2D (OR 3.35, 95% CI 2.96–3.78), and with GDM (OR 1.18, 95% CI 1.08–1.28); disparities were seen by race/ethnicity, insurance, and income.Conclusions: Diabetes, which is increasing among adolescents, is a significant risk factor for preterm labor and hypertensive disorders. Though the absolute number of adolescent pregnancies is decreasing, rates of hypertensive disorders have increased. Appropriate interventions are needed to ensure healthy outcomes for adolescents who are pregnant.

Background Use of eGFR to determine preemptive waitlisting eligibility may contribute to racial/ethnic disparities in access to waitlisting, which can only occur when the eGFR falls to ≤20 ml/min per 1.73 m2. Use of an alternative risk-based strategy for waitlisting may reduce these inequities (e.g., a kidney failure risk equation [KFRE] estimated 2-year risk of kidney failure) rather than the standard eGFR threshold for determining waitlist eligibility. Our objective was to model the amount of preemptive waittime that could be accrued by race and ethnicity, applying two different strategies to determine waitlist eligibilityMethods Using electronic health record data, linear mixed models were used to compare racial/ethnic differences in preemptive waittime that could be accrued using two strategies: estimating the time between an eGFR ≤20 and 5 ml/min per 1.73 m2 versus time between a 25% 2-year predicted risk of kidney failure (using the KFRE, which incorporates age, sex, albuminuria, and eGFR to provide kidney failure risk estimation) and eGFR of 5 ml/min per 1.73 m2Results Among 1290 adults with CKD stages 4–5, using the Chronic Kidney Disease Epidemiology Collaboration equation yielded shorter preemptive waittime between an eGFR of 20 and 5 ml/min per 1.73 m2 in Black (−6.8 months; 95% confidence interval [CI], −11.7 to −1.9), Hispanic (−10.2 months; −15.3 to −5.1), and Asian/Pacific Islander (−10.3 months; 95% CI, −15.3 to −5.4) patients compared with non-Hispanic White patients. Use of a KFRE threshold to determine waittime yielded smaller differences by race and ethnicity than observed when using a single eGFR threshold, with shorter time still noted for Black (−2.5 months; 95% CI, −7.8 to 2.7), Hispanic (−4.8 months; 95% CI, −10.3 to 0.6), and Asian/Pacific Islander (−5.4 months; −10.7 to −0.1) individuals compared with non-Hispanic White individuals, but findings only met statistical significance criteria in Asian/Pacific Islander individuals. When we compared potential waittime availability using a KFRE versus eGFR threshold, use of the KFRE yielded more equity in waittime for Black (P = 0.02), Hispanic (P = 0.002), and Asian/Pacific Islander (P = 0.002) patientsConclusions Use of a risk-based strategy was associated with greater racial equity in waittime accrual compared with use of a standard single eGFR threshold to determine eligibility for preemptive waitlisting.

Background Residence in rural areas is often a barrier to health care access. To date, differences in access to kidney transplantation among children who reside in rural and micropolitan areas of the US have not been exploredMethods A retrospective cohort study of children < 18 years who developed kidney failure between 2000 and 2019 according to the United States Renal Data System (USRDS). We examined the association between rurality of patient residence and time to living and/or deceased donor kidney transplantation (primary outcomes) and waitlist registration (secondary outcome) using Fine–Gray modelsResults We included 18,530 children, of whom 14,175 (76.5%) received a kidney transplant (39.8% from a living and 60.2% from a deceased donor). Residence in micropolitan (subhazard ratio (SHR) 1.16; 95% CI 1.06–1.27) and rural (SHR 1.18; 95% CI 1.06–1.3) areas was associated with better access to living donor transplantation compared with residence in metropolitan areas. There was no statistically significant association between residence in micropolitan (SHR, 0.95; 95%CI 0.88–1.03) and rural (SHR, 0.94; 95%CI 0.86–1.03) areas compared with metropolitan areas in the access of children to deceased donor transplantation. There was also no difference in the time to waitlist registration comparing micropolitan (SHR 1.04; 95%CI 0.98–1.10) and rural (SHR 1.05; 95% CI 0.98–1.13) versus metropolitan areasConclusions In children with kidney failure, residence in rural and micropolitan areas was associated with better access to living donor transplantation and similar access to deceased donor transplantation compared with residence in metropolitan areas. Graphical abstract

Significance Statement The Advancing American Kidney Health Initiative aims to increase rates of utilization of peritoneal dialysis (PD) in the United States. One of the first steps to PD is successful catheter placement, which can be performed by surgeons, interventional radiologists, or nephrologists. We examined the association between operator subspecialty and risk of needing a follow-up procedure in the first 90 days after initial PD catheter implantation. Overall, we found that 15.5% of catheters required revision, removal, or a second catheter placement within 90 days. The odds of requiring a follow-up procedure was 36% higher for interventional radiologists and 86% higher for interventional nephrologists compared with general surgeons. Further research is needed to understand how to optimize the function of catheters across different operator typesBackground The US government has implemented incentives to increase the use of PD. Successful placement of PD catheters is an important step to increasing PD utilization rates. Our objective was to compare initial outcomes after PD catheter placement by different types of operatorsMethods We included PD-naïve patients insured by Medicare who had a PD catheter inserted between 2010 and 2019. We examined the association between specialty of the operator (general surgeon, vascular surgeon, interventional radiologist, or interventional nephrologist) and odds of needing a follow-up procedure, which we defined as catheter removal, replacement, or revision within 90 days of the initial procedure. Mixed logistic regression models clustered by operator were used to examine the association between operator type and outcomesResults We included 46,973 patients treated by 5205 operators (71.1% general surgeons, 17.2% vascular surgeons, 9.7% interventional radiologists, 2.0% interventional nephrologists). 15.5% of patients required a follow-up procedure within 90 days of the initial insertion, of whom 2.9% had a second PD catheter implanted, 6.6% underwent PD catheter removal, and 5.9% had a PD catheter revision within 90 days of the initial insertion. In models adjusted for patient and operator characteristics, the odds of requiring a follow-up procedure within 90 days were highest for interventional nephrologists (HR, 1.86; 95% confidence interval [CI], 1.56 to 2.22) and interventional radiologists (odds ratio, 1.36; 95% CI, 1.17 to 1.58) followed by vascular surgeons (odds ratio, 1.06; 95% CI, 0.97 to 1.14) compared with general surgeonsConclusions The probability of needing a follow-up procedure after initial PD catheter placement varied by operator specialty and was higher for interventionalists and lowest for general surgeons.

Access to a second kidney transplant is a growing concern because approximately 13% of individuals added to the waitlist in 2020 had a failed allograft. Few studies have examined whether transplant center continuity is associated with differential access to a second transplant.

The ability to predict the likelihood of a live birth after single fresh embryo transfer is an important part of fertility treatment. While past studies have examined the likelihood of live birth based on the number of oocytes retrieved and cleavage-stage embryos available, the odds of a live birth based on the number of supernumerary blastocysts cryopreserved following a fresh embryo transfer has not been rigorously studied. We performed a retrospective analysis, stratified by age, on patients undergoing their first fresh autologous single day 5 blastocyst transfer to assess relationship between the likelihood of a live birth and number of supernumerary blastocysts cryopreserved. In patients aged <35 years and 35–39 years old, the likelihood of a live birth increased linearly between 1 and 6 supplementary blastocysts and non-linearly if 10 or more blastocysts were cryopreserved. When aged 40 years and above, the likelihood of a live birth increased linearly up to 4 cryopreserved blastocysts and then non-linearly if 10 or more blastocysts were cryopreserved. The present study demonstrated a non-linear relationship between the number of supernumerary blastocysts cryopreserved and the likelihood of a live birth after single blastocyst transfer in the first autologous fresh IVF/ICSI cycle across different age groups.

Background There is a paucity of data on the risk factors for the hyperosmolar hyperglycemic state (HHS) compared with diabetic ketoacidosis (DKA) in pediatric type 2 diabetes (T2D)Methods We used the national Kids’ Inpatient Database to identify pediatric admissions for DKA and HHS among those with T2D in the years 2006, 2009, 2012, and 2019. Admissions were identified using ICD codes. Those aged <9yo were excluded. We used descriptive statistics to summarize baseline characteristics and Chi-squared test and logistic regression to evaluate factors associated with admission for HHS compared with DKA in unadjusted and adjusted modelsResults We found 8,961 admissions for hyperglycemic emergencies in youth with T2D, of which 6% were due to HHS and 94% were for DKA. These admissions occurred mostly in youth 17–20 years old (64%) who were non-White (Black 31%, Hispanic 20%), with public insurance (49%) and from the lowest income quartile (42%). In adjusted models, there were increased odds for HHS compared to DKA in males (OR 1.77, 95% CI 1.42–2.21) and those of Black race compared to those of White race (OR 1.81, 95% CI 1.34–2.44). Admissions for HHS had 11.3-fold higher odds for major or extreme severity of illness and 5.0-fold higher odds for mortalityConclusion While DKA represents the most admissions for hyperglycemic emergencies among pediatric T2D, those admitted for HHS had higher severity of illness and mortality. Male gender and Black race were associated with HHS admission compared to DKA. Additional studies are needed to understand the drivers of these risk factors.

RATIONALE & OBJECTIVE Acute decreases in glomerular filtration rate (GFR) occur commonly during intensive blood pressure (BP) lowering. Our objective was to determine the relationship between acute decreases in estimated GFR and patient outcomes.STUDY DESIGN Retrospective observational study.SETTING & PARTICIPANTS Participants from 4 randomized controlled trials of intensive BP lowering in chronic kidney disease (Modification of Diet in Renal Disease study, African American Study of Kidney Disease and Hypertension, Systolic Blood Pressure Intervention Trial, and Action to Control Cardiovascular Risk in Diabetes trial).EXPOSURE A 4-category exposure defined by the level of acute decrease in estimated GFR (defined as>15% vs≤15% between baseline and month 4) and the randomization to intensive versus usual BP control.OUTCOMES Risk of kidney replacement therapy (primary outcome), defined as the need for dialysis or transplant except in the Action to Control Cardiovascular Risk in Diabetes trial, which defined its kidney outcome as a composite occurrence of serum creatinine concentration>3.3mg/dL, kidney failure, or kidney replacement therapy.ANALYTICAL APPROACH Multivariable Cox models.RESULTS We included 4,473 individuals randomly assigned to intensive versus usual BP control who had a total of 351 kidney outcomes and 304 deaths during median follow-up durations of 22 and 24 months, respectively. Approximately 14% of participants exhibited an acute decrease in eGFR, 11.0% in the usual BP treatment arm and 17.8% in the intensive BP treatment arm. In adjusted models, compared with a≤15% eGFR decrease in the usual BP arm, a≤15% eGFR decrease in the intensive BP control arm was associated with lower risk of the kidney outcome (HR, 0.75; 95% CI, 0.57-0.98). In contrast, a>15% decrease in eGFR was associated with a higher risk of the kidney outcome in the usual (HR, 2.47; 95% CI, 1.80-3.38) and intensive BP treatment arms (HR, 1.99; 95% CI, 1.45-2.73) compared with a≤15% decrease in the usual BP arm.LIMITATIONS Observational study, residual confounding.CONCLUSIONS Decreases in eGFR of>15% in the usual and intensive BP treatment arms were associated with a higher risk of kidney outcomes compared with a≤15% decrease in the usual BP arm and may be a harbinger of adverse outcomes.

The synergistic effects of RAAS inhibition and intensive blood pressure lowering in reducing proteinuria have not been well studied. We aimed to study this effect using data from the AASK Trial where our data suggest there is an additive and synergistic effect between RAAS inhibition and intensive blood pressure inhibition in reducing proteinuria.

Background As awareness around infertility is increasing among patients with chronic kidney disease (CKD), ever more of them are seeking Assisted Reproductive Technology (ART). Our aim was to perform a systematic review to describe obstetric and renal outcomes in women with CKD following ARTMethods The following databases were searched from 1946 to May 2021: (1) Cochrane Central Register of Controlled Trials (CENTRAL), (2) Cumulative Index to Nursing and Allied Health Literature (CINAHL), (3) Embase and (4) MEDLINEResults The database search identified 3520 records, of which 32 publications were suitable. A total of 84 fertility treatment cycles were analysed in 68 women. Median age at time of pregnancy was 32.5 years (IQR 30.0, 33.9 years). There were 60 clinical pregnancies resulting in 70 live births (including 16 multifetal births). Four women developed ovarian hyperstimulation syndrome which were associated with acute kidney injury. Hypertensive disorders complicated 26 pregnancies (38.3%), 24 (35.3%) pregnancies were preterm delivery, and low birth weight was present in 42.6% of pregnancies. Rates of live birth and miscarriage were similar for women with CKD requiring ART or having natural conception. However, more women with ART developed pre-eclampsia (p < 0.05) and had multifetal deliveries (p < 0.001), furthermore the babies were lower gestational ages (p < 0.001) and had lower birth weights (p < 0.001)Conclusion This systematic review represents the most comprehensive assessment of fertility outcomes in patients with CKD following ART. However, the high reported live birth rate is likely related to reporting bias. Patient selection remains crucial in order to maximise patient safety, screen for adverse events and optimise fertility outcomes.

Background and objectives Recovery of kidney function after the start of maintenance dialysis can occur, but data on the incidence and risk factors for restarting dialysis after recovery of kidney function in this population are limited. Design, setting, participants, & measurements We conducted a retrospective study of adult Medicare beneficiaries who started dialysis between 2005 and 2015 according to the United States Renal Data System but who had recovery of kidney function (defined as a ≥90-day dialysis-free interval). We identified risk factors that were associated with the risk for the reinitiation of dialysis within a 3-year time frame following the recovery of kidney function and at any time during follow-up using Cox proportional hazards modelsResults Of the 34,530 individuals previously on dialysis who had recovery of kidney function, 7217 (21%) restarted dialysis (absolute rate of 11.5 per 100 person-years) within 3 years of recovery of kidney function, and 9120 (26%) restarted dialysis during the entire follow-up period (absolute rate of 8.8 per 100 person-years). Among those with CKD stage 1 or 2 after recovery of kidney function, 10% of individuals restarted dialysis within 3 years of their recovery of kidney function, whereas among those with CKD stage 3, 4, or 5, 13%, 27%, and 36% of individuals restarted dialysis within 3 years of recovery of kidney function, respectively. Age at first dialysis, cause of kidney disease, history of CKD or nephrology care prior to starting dialysis, presence of heart failure, CKD stage following recovery of kidney function, and location of first dialysis initiation (inpatient versus outpatient) were some of the risk factors that were strongly associated with the risk of restarting dialysis after the recovery of kidney functionConclusions Over one in five patients with recovery of kidney function after kidney failure restarted dialysis within 3 years.

There are limited data on the degree of variability in practices surrounding prioritization of referrals for transplant evaluation and criteria for transplant candidacy and their association with transplantation rates. We surveyed transplant programs across the United States between January 2020 and May 2020 to determine current pre-transplantation practices. We examined the relation between these reported practices and the outcomes of waitlisted patients at responding programs between January 2015 and March 2021 using Scientific Registry of Transplant Recipients data. We used adjusted Cox models with random effects to accommodate clustering by program. Primary outcomes included living or deceased donor transplantation. Of 172 surveyed programs, 90 participated. Substantial variations were noted in when the candidacy evaluation began (13% reported when eGFR was <30 mL/min/1.73 m2 and 17% reported no set policy) and the approach to pre-transplantation cardiac workup (multi-modality [58%], stress echocardiogram [20%]). Using adjusted models, a program policy of using other measures of body habitus to determine transplant candidacy rather than requiring patients to meet a body mass index (BMI) threshold of ≤35 kg/m2 (reference group) for candidacy was associated with a higher hazard of living donor transplantation (HR 1.83 [95% CI 1.10-3.03]). Pre-transplant practices vary substantially across the United States, and select practices were associated with transplantation rates.

Background Hyponatremia before liver transplant (LT) increases risk of post-LT neurological complications in patients with decompensated cirrhosis, but it is unknown to what extent change in sodium from pre- to post-LT influences risk of central nervous system (CNS) sequelae. We assessed the relationship between pre- to post-LT delta sodium and prevalence of CNS complications during LT hospitalizationMethods We performed retrospective single-center chart review of 1265 adults with cirrhosis who underwent LT (2011–2020). Delta sodium is defined as the difference between maximum sodium within 48 h post-LT and lowest sodium within 7 d pre-LT. Primary outcomes are post-LT CNS events during same hospitalization—encephalopathy, delirium, seizure, coma, osmotic demyelination syndrome, or other altered mental status, determined by International Classification of Diseases codes. Secondary outcome is length of hospital stay post-LT (LOS). Logistic regression modeled association between delta sodium and post-LT CNS outcomes; negative binomial regression modeled LOSResults Median age was 59 y, 36% were female, and median Model for End-Stage Liver Disease score was 20. Median delta sodium was 8 mmol/L (interquartile range, 5–11). One hundred ninety-four (15%) experienced post-LT CNS complications. In multivariable analysis, controlling for confounders including pre-LT hyponatremia, every 5 mmol/L increase in delta sodium associated with 47% greater odds of CNS complication (95% confidence interval, 22%-77%). Delta sodium also associated with 7% increased LOS in adjusted regression (95% confidence interval, 3%-12%)Conclusions Adult LT recipients with higher perioperative delta sodium shifts displayed a higher risk of post-LT CNS complications, even after adjusting for pre-LT sodium. LT recipients, even those with pre-LT hyponatremia, may benefit from maintenance of stable serum sodium levels to minimize post-LT CNS complications.

Abstract Background Insulin pump use in type 1 diabetes management has significantly increased in recent years, but we have few data on its impact on inpatient admissions for acute diabetes complicationsMethods We used the 2006, 2009, 2012, and 2019 Kids’ Inpatient Database to identify all-cause type 1 diabetes hospital admissions in those with and without documented insulin pump use and insulin pump failure. We described differences in (1) prevalence of acute diabetes complications, (2) severity of illness during hospitalization and disposition after discharge, and (3) length of stay (LOS) and inpatient costsResults We identified 228 474 all-cause admissions. Insulin pump use was documented in 7% of admissions, of which 20% were due to pump failure. The prevalence of diabetic ketoacidosis (DKA) was 47% in pump nonusers, 39% in pump users, and 60% in those with pump failure. Admissions for hyperglycemia without DKA, hypoglycemia, sepsis, and soft tissue infections were rare and similar across all groups. Admissions with pump failure had a higher proportion of admissions classified as major severity of illness (14.7%) but had the lowest LOS (1.60 days, 95% CI 1.55-1.65) and healthcare costs ($13 078, 95% CI $12 549-$13 608)Conclusions Despite the increased prevalence of insulin pump in the United States, a minority of pediatric admissions documented insulin pump use, which may represent undercoding. DKA admission rates were lower among insulin pump users compared to pump nonusers. Improved accuracy in coding practices and other approaches to identify insulin pump users in administrative data are needed, as are interventions to mitigate risk for DKA.

African ancestry-specific variation in the apolipoprotein L1 gene (APOL1) is associated with faster progression of chronic kidney disease (CKD) in Black individuals. While there is preliminary evidence from the African American Study of Kidney Disease and Hypertension Study (AASK) trial that intensive blood pressure (BP) control may improve mortality in Black individuals with APOL1 high-risk (but not low-risk) genotypes, the AASK trial excluded individuals with diabetes. Whether intensive BP control confers additive kidney benefits in individuals with high-risk genotypes and type 2 diabetes is unknown. To test the hypothesis that intensive BP control confers less risk of adverse kidney outcomes by APOL1 risk status in patients with type 2 diabetes, we performed a retrospective analysis of the Action to Control Cardiovascular Risk in Diabetes-Blood Pressure (ACCORD-BP) trial.

OBJECTIVE To evaluate the evidence addressing the association between the use of ovarian stimulation drugs and the risk of breast cancer.DESIGN Systematic review and meta-analysis.SETTING Not applicable. PATIENT(S): Women without any previous history of breast cancer undergoing ovarian stimulation. INTERVENTION(S): Electronic databases were searched from 1990 until January 2020. All cohort studies reporting new incidences of breast cancer in infertile women using ovarian stimulating drugs were included. Treated (exposed) infertile women were compared with the unexposed general population with unexposed infertile women as controls. MAIN OUTCOME MEASURE(S): New diagnosis of breast cancer within an infertile and general population after exposure to ovarian stimulation drugs. RESULT(S): Overall, the quality of evidence was very low because of the serious risk of bias and indirectness (nonrandomized studies). There was no significant increase in the risk of breast cancer among women treated with any ovarian stimulation drug for infertility compared with that in unexposed controls from the general population and the infertile population (pooled odds ratio 1.03, 95% Confidence interval 0.86 to 1.23, 20 studies, I2 = 88.41%, very low quality of evidence). Furthermore, no significant increase in the risk of breast cancer was found with the use of clomiphene citrate or gonadotropins, alone or in combination. CONCLUSION(S): The current study found that the use of clomiphene citrate and gonadotropins in infertile women was not associated with an increased risk of breast cancer.

BACKGROUND AND OBJECTIVES Though patient factors are frequently linked to hemodialysis vascular access selection and outcomes, variability by surgeon and surgeon specialty may play a role as well. The objective of this study is to examine the extent to which individual surgeons influence selection of vascular access type, removal of tunneled hemodialysis catheter (THC), and repeat vascular access. DESIGN, SETTING, PARTICIPANTS, &MEASUREMENTS A national claims database was used to identify patients initiating hemodialysis via a THC between 2011 and 2017. Likelihood of repeat AVF/AVG was analyzed using mixed-effects logistic regression. Time from initial arteriovenous fistula (AVF)/graft (AVG) to THC removal and time to repeat AVF/AVG were analyzed using Weibull proportional hazard models. Individual surgeon identifier served as the random effect in all models.RESULTS 6,908 AVF/AVG met the inclusion criteria: 5366 (78%) AVF and 1,542 (22%) AVG. Surgeon specialty only had a significant influence on access type, with vascular surgeons having 26% greater odds of performing AVG compared to general surgeons (P = 0.006). Relative to the other independent variables, individual surgeon identifier had the greatest magnitude of effect on access type (median odds ratio, 2.36; 95% CI, 2.09-2.72). Individual surgeon identifier had the second greatest magnitude of effect likelihood of THC removal (median hazard ratio, 1.66; 95% CI, 1.58-1.77) and second access (median hazard ratio, 1.83; 95% CI, 1.66-2.05), in both cases second only to the effect of AVG, which was associated with greater likelihood of THC removal (hazard ratio 1.91; 95% CI, 1.77-2.07) and lower likelihood of second access (hazard ratio 0.44; 95% CI, 0.38-0.52).CONCLUSION Individual surgeons are associated with greater variation in vascular access type and likelihood of repeat access than surgeon specialty and measurable patient demographics/co-morbidities. Future research should focus on identifying which surgeon factors are associated with improved outcomes.

Background and Objectives Diabetic ketoacidosis (DKA) rates in the United States are rising. Prior studies suggest higher rates in younger populations, but no studies have evaluated national trends in pediatric populations and differences by subgroups. As such, we sought to examine national trends in pediatric DKAMethods We used the 2006, 2009, 2012, and 2016 Kids’ Inpatient Database to identify pediatric DKA admissions among a nationally representative sample of admissions of youth ≤20 years old. We estimate DKA admission per 10 000 admissions and per 10 000 population, charges, length of stay (LOS), and trends over time among all hospitalizations and by demographic subgroups. Regression models were used to evaluate differences in DKA rates within subgroups overtimeResults Between 2006 and 2016, there were 149 535 admissions for DKA. Unadjusted DKA rate per admission increased from 120.5 (95% CI, 115.9-125.2) in 2006 to 217.7 (95% CI, 208.3-227.5) in 2016. The mean charge per admission increased from $14 548 (95% CI, $13 971-$15 125) in 2006 to $20 997 (95% CI, $19 973-$22 022) in 2016, whereas mean LOS decreased from 2.51 (95% CI, 2.45-2.57) to 2.28 (95% CI, 2.23-2.33) days. Higher DKA rates occurred among 18- to 20-year-old females, Black youth, without private insurance, with lower incomes, and from nonurban areas. Young adults, men, those without private insurance, and from nonurban areas had greater increases in DKA rates across timeConclusions Pediatric DKA admissions have risen by 40% in the United States and vulnerable subgroups remain at highest risk. Further studies should characterize the challenges experienced by these groups to inform interventions to mitigate their DKA risk and to address the rising DKA rates nationally.

While the influenza vaccine is recommended for all pregnant women, influenza vaccine coverage among this high-risk population remains inadequate. Factors associated with vaccine coverage among pregnant women, including insurance status, are poorly understood. In a cross-sectional study of the National Health Interview Survey (NHIS) data from 2012 to 2018, we evaluated predictors of self-reported influenza vaccine coverage in pregnant women. Among 1,942 pregnant women surveyed, 39% reported receiving the influenza vaccine in accordance with national recommendations. Influenza vaccine coverage increased by 8 percentage points from 2012 to 2018. Only 15% of uninsured pregnant women received the influenza vaccine, compared to 41% of those with insurance (design-corrected F-test, p-value < 0.001). In the multivariate Poisson regression analysis, significant predictors of influenza vaccine coverage were health insurance (prevalence ratio [PR] 1.90, 95% confidence interval [CI] 1.23-2.93), ratio of household income to federal poverty level (FPL) threshold greater than 400% (PR 1.54, 95% CI 1.20-1.96), graduate school education (PR 1.52, 95% CI 1.04-2.23), and the 2015-2018 survey year period (PR 1.27, 95% CI 1.08-1.49). While previous literature focuses heavily on demographics, our research underscores the need to further explore modifiable factors that impact vaccine uptake during pregnancy, particularly the interplay between health insurance and access to care.

BACKGROUND Kidney replacement therapy is controversial for patients with hepatorenal syndrome who may not be liver transplant candidates. Data surrounding the likelihood of recovery of kidney function and mortality after outpatient dialysis initiation in patients with dialysis-requiring hepatorenal syndrome could inform discussions between patients and providers.METHODS We performed a retrospective cohort study of patients with hepatorenal syndrome who were registered in the United States Renal Data System between 1996 and 2015 (n=7830) as receiving maintenance dialysis. We characterized patients with hepatorenal syndrome by recovery of kidney function using Fine and Gray models. We also examined hazard of recovery of kidney function and death among those with hepatorenal syndrome versus those with acute tubular necrosis (n=48,861) using adjusted Fine-Gray and Cox models, respectively.RESULTS Of the patients with hepatorenal syndrome, 11% recovered kidney function. Those with higher likelihood of recovery were younger, non-Hispanic White, and had a history of alcohol use. Compared with patients with acute tubular necrosis, patients with hepatorenal syndrome as the attributed cause of kidney disease had a lower hazard of recovery (HR, 0.22; 95% CI, 0.21 to 0.24) and higher hazard of death within 1 year (HR, 3.10; 95% CI, 2.99 to 3.23) in fully adjusted models.CONCLUSIONS Patients with hepatorenal syndrome receiving chronic maintenance dialysis had a lower likelihood of recovery of kidney function and higher mortality risk compared with patients with acute tubular necrosis. Among patients with hepatorenal syndrome, those most likely to recover kidney function were younger, had a history of alcohol use, and lacked comorbid conditions. These data may inform prognosis and discussions surrounding treatment options when patients with hepatorenal syndrome need chronic maintenance dialysis therapy.

BACKGROUND Older adults undergoing surgery are at risk for geriatric events (GEs: delirium, dehydration, falls or fractures, failure to thrive, and pressure ulcers). The prevalence and association of GEs with clinical outcomes after elective surgery is unclear.MATERIALS AND METHODS Using the 2013-2014 National Inpatient Sample, we analyzed hospital admissions for the five most common elective procedures (total knee arthroplasty, right hemicolectomy, carotid endarterectomy, aortic valve replacement, and radical prostatectomy) in older adults (age ≥ 65). Our primary variable of interest was presence of any GE. Logistic regression estimated the association of GEs with (1) age group and (2) perioperative outcomes (mortality, postoperative complications, prolonged length of stay, and discharge to skilled nursing facility).RESULTS Of 1,255,120 admissions, 66.5% were aged ≥65. The overall rate of any GE was 2.4% and increased with age (55-64 y: 1.5%; 65-74: 2.2%; ≥75: 4.1%; P < 0.001). After adjustment, the probability of any GE increased with age (P < 0.001). Rates of GEs varied by procedure (P < 0.001). In comparison with admissions with no GEs, one or more GE was associated with higher probability of worse outcomes including mortality, postoperative complications, prolonged length of stay, and discharge to skilled nursing facility (all P < 0.001). In addition, there was a dose-dependent relationship between GEs and these poor perioperative outcomes.CONCLUSIONS GEs are strongly associated with poor perioperative outcomes. Efforts should focus on mutable factors responsible for GEs to optimize surgical care for older adults.

Elective discontinuation of dialysis is an increasingly common occurrence among patients with ESKD. Numerous studies have assessed predictors of the decision to stop dialysis in the inpatient setting and have consistently highlighted factors associated with a higher likelihood of this decision, including White race, female sex, and older age. In these settings, the decision to stop dialysis is often made in the context of acute medical complications or hospitalizations. Although these findings are important, there has been less focus on understanding the decision to discontinue dialysis outside of the acute hospitalized setting. The objective of this study was to determine factors associated with dialysis discontinuation in the absence of known acute medical complications, with particular focus on differences in discontinuation according to treatment modality.

BACKGROUND Black patients with end-stage renal disease (ESRD) represent 30.5% of the prevalent ESRD population in the United States, despite only accounting for 18% of the total population. Black patients are less likely to have pre-ESRD care compared with their white counterparts and are 3-4 times more likely to progress from chronic kidney disease to ESRD than whites, suggesting that black patients are particularly vulnerable to disparities in outcomes related to hemodialysis and ESRD. The objective of this study is to examine the association of race with outcomes of hemodialysis access and selection of arteriovenous fistula (AVF) versus arteriovenous graft (AVG).METHODS Patients with chronic kidney disease who initiated dialysis through a tunneled hemodialysis catheter (THC) were identified in the Optum's De-identified Clinformatics® Data Mart (OptumInsight, Eden Prairie, MN) claims database (2011-2017). The odds of AVF versus AVG creation and the odds of repeat vascular access creation were analyzed using logistic regression. Time from initial AVF/AVG to THC removal and time to repeat AVF/AVG were analyzed using Cox proportional hazards.RESULTS About 7,584 vascular access patients met the inclusion criteria: 5,852 (77%) AVF and 1,732 (23%) AVG. Median follow-up was 583 days overall (range, 1-2,543), 589 days among AVF patients (range, 1-2,543), and 260 days among AVG patients (range, 1-2,529). Between races, there was no clinically significant variation in characteristics or comorbidities, with the exception of a much lower rate of obesity among Asians. Black patients had 36% lower odds of AVF index versus AVG index (P < 0.001). Patients 70 years or older and patients with diabetes had lower odds of AVF index, whereas men and obese patients had greater odds of receiving AVF. Overall, graft patients were 73% more likely to have a shorter time to THC removal than fistula patients, but Hispanic graft patients were 25% more likely to have a shorter time to THC removal than whites. Patients with diabetes, patients with cardiac arrhythmia, and obesity were more likely to have a longer time to THC removal. About 1,589 (21%) patients underwent a repeat vascular access creation during the follow-up period: 19% of whites (n = 802), 26% of blacks (n = 483), 19% of Hispanics (n = 250), and 19% of Asians (n = 54) (P < 0.001). Multivariate analysis demonstrated that black patients had 58% greater odds of requiring a second access than white patients (P < 0.001). Graft patients, patients 70 years or older, and men had lower odds of repeat access. Black patients were 45% more likely to have a shorter time until second access creation. Graft patients, patients aged 70 years or older, and men were more likely to have a longer time until second access. Patients with obesity were more likely to have a shorter time until second access.CONCLUSIONS This study's findings suggest that after initial vascular access, compared with whites, blacks have no difference in time to index access success, but their access fails earlier and more frequently, independent of access type, age, and comorbidities. Given blacks constitute 30.5% of the hemodialysis population in the United States, it is imperative that future research investigate the root causes of these disparities.

BACKGROUND Our aim was to determine factors that influence time to removal of tunneled hemodialysis catheter (THC), probability of repeat vascular access creation, and time to repeat vascular access.METHODS The Optum Clinformatics Data Mart claims database was queried from 2011 to 2017 for patients who initiated hemodialysis with a THC. Time from initial arteriovenous fistula (AVF)/graft (AVG) to THC removal and time to repeat AVF/AVG were analyzed using Cox proportional hazards. The likelihood of repeat AVF/AVG was analyzed using logistic regression.RESULTS A total of 8941 vascular access met the inclusion criteria: 6913 (77%) AVF and 2028 (23%) AVG. Median follow-up was 595 days among AVF patients (range, 1-2543 days) and 579 days among AVG patients (range, 1-2529 days). Patients undergoing AVF were younger, more likely to be male, of white race, and obese. Patients undergoing AVF were also slightly less likely to have diabetes, cardiac arrhythmia, congestive heart failure, and peripheral vascular disease than patients undergoing AVG. At 90 days and at 180 days after index access creation, significantly more patients who underwent index AVG had their THC removed compared with patients who underwent index AVF. By day 365, 78% of patients in both AVF and AVG had their THC removed. A total of 2550 (28.5%) patients underwent a repeat vascular access creation during the follow-up period: 30% of index AVF and 24% of index AVG. At 90 days, 180 days, and 365 days, significantly more patients in the index AVF group underwent a repeat vascular access creation than those in the index AVG group. Multivariate analysis demonstrated a significant interaction between vascular access type and age ≥70 years (P < .001) for time to THC removal, likelihood of repeat vascular access, and time to repeat vascular access. In the age <70 group, patients who underwent AVG were 60% more likely to have a shorter time to THC, had a 50.4% lower odds of repeat vascular access, and were 47% more likely to have a longer time to repeat vascular access compared with patients who underwent index AVF. In the age ≥70 group, patients who underwent AVG were 98% more likely to have a shorter time to THC removal, had 69.7% lower odds of repeat vascular access, and were 66% more likely to have a longer time to repeat vascular access.CONCLUSIONS Creation of AVG vs AVF significantly decreases the time to THC removal in dialysis-dependent patients, with a larger difference in patients aged ≥70 vs <70. Initial AVG was associated with lower odds of repeat vascular access and longer time to repeat vascular access. These results suggest that the dictum of "fistula first" is not appropriate for all patient populations and supports judicious use of AVG in achieving the more recent shift toward "catheter last."

Older adults undergoing nonelective surgery are at risk for geriatric events (GEs: delirium, dehydration, falls/fractures, failure to thrive, and pressure ulcers), but the impact of GEs on postoperative outcomes is unclear. Using the 2013 to 2014 National Inpatient Sample, we analyzed nonelective hospital admissions for five common operations (laparoscopic cholecystectomy, colectomy, soft tissue debridement, small bowel resection, and laparoscopic appendectomy) in older adults (aged ≥65 years) and a younger referent group (aged 55–64 years). Nationally weighted descriptive statistics were generated for GEs. Logistic regression controlling for patient, procedure, and hospital characteristics estimated the association of 1) age with GEs and 2) GEs with outcomes. Of 471,325 overall admissions, 64.7 per cent were aged ≥65 years. The rate of any GE in older adults was 26.9 per cent; GEs varied by age and procedure ( P < 0.001). After adjustment, the probability of any GE increased with age category ( P < 0.001); having any GE was associated with higher probability of all outcomes ( P < 0.001): mortality (4.5% vs 0.8%), postoperative complications (61.7% vs 24.9%), prolonged length of stay (24.3% vs 7.9%), and skilled nursing facility discharge (46.6% vs 10.3%). In addition, there was a dose–response relationship between GEs and negative outcomes. GEs are prevalent in the nonelective surgery setting and associated with worse clinical outcomes. Quality improvement efforts should focus on addressing GEs.

Objective This observational study explores the association between palliative care (PC) involvement and high-cost imaging utilisation for patients with cancer patients during the last 3 months of lifeMethods Adult patients with cancer who died between 1 January 2012 and 31 May 2015 were identified. Referral to PC, intensity of PC service use, and non-emergent oncological imaging utilisation were determined. Associations between PC utilisation and proportion of patients imaged and mean number of studies per patient (mean imaging intensity (MII)) were assessed for the last 3 months and the last month of life. Similar analyses were performed for randomly matched case-control pairs (n = 197). Finally, the association between intensity of PC involvement and imaging utilisation was assessed.Results 3784 patients were included, with 3523 (93%) never referred to PC and 261 (7%) seen by PC, largely before the last month of life (61%). Similar proportions of patients with and without PC referral were imaged during the last 3 months, while a greater proportion of patients with PC referral were imaged in the last month of life. PC involvement was not associated with significantly different MII during either time frame. In the matched-pairs analysis, a greater proportion of patients previously referred to PC received imaging in the period between the first PC encounter and death, and in the last month of life. MII remained similar between PC and non-PC groups. Finally, intensity of PC services was similar for imaged and non-imaged patients in the final 3 months and 1 month of life. During these time periods, increased PC intensity was not associated with decreased MIIConclusions PC involvement in end-of-life oncological care was not associated with decreased use of non-emergent, high-cost imaging. The role of advanced imaging in the PC setting requires further investigation.

Purpose To develop and validate a deep learning algorithm that predicts the final diagnosis of Alzheimer disease (AD), mild cognitive impairment, or neither at fluorine 18 (18F) fluorodeoxyglucose (FDG) PET of the brain and compare its performance to that of radiologic readersMaterials and Methods Prospective 18F-FDG PET brain images from the Alzheimer's Disease Neuroimaging Initiative (ADNI) (2109 imaging studies from 2005 to 2017, 1002 patients) and retrospective independent test set (40 imaging studies from 2006 to 2016, 40 patients) were collected. Final clinical diagnosis at follow-up was recorded. Convolutional neural network of InceptionV3 architecture was trained on 90% of ADNI data set and tested on the remaining 10%, as well as the independent test set, with performance compared to radiologic readers. Model was analyzed with sensitivity, specificity, receiver operating characteristic (ROC), saliency map, and t-distributed stochastic neighbor embeddingResults The algorithm achieved area under the ROC curve of 0.98 (95% confidence interval: 0.94, 1.00) when evaluated on predicting the final clinical diagnosis of AD in the independent test set (82% specificity at 100% sensitivity), an average of 75.8 months prior to the final diagnosis, which in ROC space outperformed reader performance (57% [four of seven] sensitivity, 91% [30 of 33] specificity; P < .05). Saliency map demonstrated attention to known areas of interest but with focus on the entire brainConclusion By using fluorine 18 fluorodeoxyglucose PET of the brain, a deep learning algorithm developed for early prediction of Alzheimer disease achieved 82% specificity at 100% sensitivity, an average of 75.8 months prior to the final diagnosis. © RSNA, 2018 Online supplemental material is available for this article. See also the editorial by Larvie in this issue.

Abstract Radiomics is an emerging technology for imaging biomarker discovery and disease-specific personalized treatment management. This paper aims to determine the benefit of using multi-modality radiomics data from PET and MR images in the characterization breast cancer phenotype and prognosis. Eighty-four features were extracted from PET and MR images of 113 breast cancer patients. Unsupervised clustering based on PET and MRI radiomic features created three subgroups. These derived subgroups were statistically significantly associated with tumor grade (p = 2.0 × 10−6), tumor overall stage (p = 0.037), breast cancer subtypes (p = 0.0085), and disease recurrence status (p = 0.0053). The PET-derived first-order statistics and gray level co-occurrence matrix (GLCM) textural features were discriminative of breast cancer tumor grade, which was confirmed by the results of L2-regularization logistic regression (with repeated nested cross-validation) with an estimated area under the receiver operating characteristic curve (AUC) of 0.76 (95% confidence interval (CI) = [0.62, 0.83]). The results of ElasticNet logistic regression indicated that PET and MR radiomics distinguished recurrence-free survival, with a mean AUC of 0.75 (95% CI = [0.62, 0.88]) and 0.68 (95% CI = [0.58, 0.81]) for 1 and 2 years, respectively. The MRI-derived GLCM inverse difference moment normalized (IDMN) and the PET-derived GLCM cluster prominence were among the key features in the predictive models for recurrence-free survival. In conclusion, radiomic features from PET and MR images could be helpful in deciphering breast cancer phenotypes and may have potential as imaging biomarkers for prediction of breast cancer recurrence-free survival.

Background The objective of this study was to examine the presence and magnitude of US geographic variation in use rates of both recommended and high-cost imaging in young patients with early-stage breast cancer during the 18 month period after surgical treatment of their primary tumor.Methods Using the Truven Health MarketScan Commercial Database, a descriptive analysis was conducted of geographic variation in annual rates of dedicated breast imaging and high-cost body imaging of 36,045 women aged 18 to 64 years treated with surgery for invasive unilateral breast cancer between 2010 and 2012. Multivariate hierarchical analysis examined the relationship between likelihood of imaging and patient characteristics, with metropolitan statistical area (MSA) serving as a random effect. Patient characteristics included age group, BRCA1/2 carrier status, family history of breast cancer, combination of breast surgery type and radiation therapy, drug therapy, and payer type. All MSAs in the United States were included, with areas outside MSAs within a given state aggregated into a single area for analytic purposes.Results Descriptive analysis of rates of imaging use and intensity within MSA regions revealed wide geographic variation, irrespective of treatment cohort or age group. Increased probability of recommended postoperative dedicated breast imaging was primarily associated with age and treatment including both surgery and radiation therapy, followed by MSA region (odds ratio, 1.42). Increased probability of PET use-a high-cost imaging modality for which postoperative routine use is not recommended in the absence of specific clinical findings-was primarily associated with surgery type followed by MSA region (odds ratio, 1.82).Conclusions In patients with breast cancer treated for low-risk disease, geography has effects on the rates of posttreatment imaging, suggesting that some patients are not receiving beneficial dedicated breast imaging, and high-cost nonbreast imaging may not be targeted to those groups most likely to benefit.

Objectives To examine the association between geography and utilization rates of contralateral prophylactic mastectomy (CPM) relative to patient-level factors in patients with early stage breast cancer.Materials and Methods Using the Truven Health MarketScan Commercial Database, a descriptive analysis of geographic variation in genetic testing and CPM rates of 38,108 women ages 18 to 64 years treated with surgery for invasive unilateral breast cancer between 2010 and 2012 was conducted. Multivariate hierarchical analysis was used to examine the relationship between CPM likelihood and patient characteristics, with metropolitan statistical area (MSA) serving as a random effect. Patient characteristics included age group, BRCA1/2 carrier status, family history of breast cancer, breast surgery type, radiation therapy, drug therapy, and payer type. All MSAs in the United States were included, with areas outside MSAs within a given state aggregated into a single area for analytical purposes.Results Descriptive analysis demonstrated significant geographic variation in rates of CPM irrespective of risk inferred from primary malignancy treatment course (P<0.01 to <0.001). Odds of CPM were higher among BRCA1/2 carriers (odds ratio [OR], 1.76; 95% confidence interval [CI], 1.52-2.06), followed by MSA (median OR among all MSAs was 1.61; 95% CI, 1.51-1.73) and family history of breast cancer (OR, 1.49; 95% CI, 1.28-1.53), respectively. Patients who were not tested for BRCA1/2 were less likely (OR, 0.66; 95% CI, 0.61-0.71) to undergo CPM than patients with a negative BRCA test.Conclusions The large geographic variation we observed in CPM indicate a need to understand and optimize clinical decision-making.

PURPOSE The aim of this study was to assess the effect of spending patterns during the final year of life on high-cost imaging utilization in the final 3 months of life.METHODS An academic comprehensive cancer center's radiology, cancer registry, and claims records were matched to identify decedents with dates of death from April 2013 through June 2014. Spending patterns in the final year of life were identified using group-based trajectory modeling. Descriptive analysis of CT, MRI, and PET utilization across trajectories was conducted. Multivariate logistic regressions modeled the likelihood of imaging utilization in the final 3 months of life, and a sensitivity analysis assessed the impact of spending trajectories on model fit.RESULTS Six spending trajectories were identified. Membership in the late rising trajectory was the strongest predictor of high-cost imaging in the final 3 months of life (odds ratio, 11.61; P = .000), followed by diagnosis 12 to 6 months premortem (odds ratio, 7.49; P = .000). The likelihood of imaging the final 3 months of life was no different between high persistent and low persistent trajectory patients, despite the heterogeneity between the two patient groups. Sensitivity analysis indicated that spending trajectory improved the prediction of imaging in the final 3 months of life to a greater extent than temporal proximity to death at the time of diagnosis, which may serve as a proxy for severity and/or complexity.CONCLUSIONS Clinical measures of severity and patients' utilization histories should be considered by hospital administrators in estimations of aggregate and individual oncologic imaging utilization. This analytic approach may aid in evaluating participation in advanced payment models.

Objectives To retrospectively evaluate utilization of high-cost cancer imaging to clarify the extent to which variations in provider preferences drive imaging utilization.Study design At a United States academic cancer center, 4,605 patients were identified with 29,740 oncologist ordered tomographic imaging studies. Patients' dates of death ranged from January 2000 through December 2014. Imaging was restricted to CT, MR, and PET/PET-CT. Outcome variables were total imaging per patient and total imaging per patient by a single oncologist. The number of ordering oncologists per patient, patients receiving imaging in the final year of life, and patients receiving imaging ordered by a high-ordering oncologist were the predictors of interest.Methods Zero-truncated negative binomial regressions were used to model collective and individual oncologist per patient imaging counts, with the exposure period defined as the number of days from diagnosis to death.Results Patients with imaging ordered by one of the high-ordering medical oncologists predicted nearly a two-fold increase in total images from diagnosis to death (IRR, 1.93; 95% CI, 1.67–2.23). Increasing numbers of providers (2, 3, 4+ ordering oncologists) were associated with greater collective per patient imaging (IRRs 1.65, 2.19, 2.33). Mean imaging intensity increased in a linear manner as temporal proximity to death decreased, from 12 months pre-mortem to death, and imaging in the final year of life was associated with greater per patient imaging (IRR, 0.25; 95% CI, 0.23–0.27).Conclusion These findings suggest heterogeneous provider ordering preferences and lapses in care coordination are drivers of high-cost cancer imaging utilization.

Background In the present study, we retrospectively evaluated the use of tomographic imaging in adult cancer patients to clarify how recent growth plateaus in the use of tomographic imaging in the United States might have affected oncologic imaging during the same period.Methods At a U.S. academic cancer centre, 12,059 patients with dates of death from January 2000 through December 2014 were identified. Imaging was restricted to brain and body computed tomography (ct), brain and body magnetic resonance (mr), and body positron-emission tomography (pet) with and without superimposed ct. Trends during the staging (1 year after diagnosis), monitoring (18–6 months before death), and end-of-life (final 6 months before death) phases were analyzed.Results Comparing the 2005–2009 with the 2010–2014 period, mean intensity of pet imaging increased 21% during staging (p = 0.0000) and 27% during end of life (p = 0.0019). In the monitoring phase, mean intensity for ct brain, ct body, and mr body imaging decreased by 26% (p = 0.0133), 11% (p = 0.0118), and 26% (p = 0.0008), respectively. Aggregate mean intensity of imaging increased in the 13%–27% range every 3 months from 18 months before death to death, reaching 1.43 images in the final 3 months of life. Patients diagnosed in the final 18 months of life had an average of 1 additional image during both the 3 months after diagnosis (p = 0.0000) and the final 3 months before death (p = 0.0000).Conclusions Imaging increased as temporal proximity to death decreased, and patients diagnosed near death received more staging imaging, suggesting that imaging guidelines should consider imaging intensity within the context of treatment phase. Despite the development, by multiple organizations, of appropriateness criteria to reduce imaging utilization, aggregate per-patient imaging showed insignificant changes. Simultaneous fluctuations in the intensity of imaging by modality suggest recent changes in the modalities preferred by providers.