Transient albuminuria in the setting of short-term severe hyperglycemia in type 1 diabetes.

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.

Peritoneal Dialysis Catheter Complications after Insertion by Surgeons, Radiologists, or Nephrologists.

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 types. BACKGROUND: 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 operators. METHODS: 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 outcomes. RESULTS: 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 surgeons. CONCLUSIONS: 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.

Rurality of patient residence and access to transplantation among children with kidney failure in the United States.

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 explored. METHODS: 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 models. RESULTS: 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 areas. CONCLUSIONS: 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.

Strategies to Guide Preemptive Waitlisting and Equity in Waittime Accrual by Race/Ethnicity.

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 m 2 . 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 eligibility. METHODS: 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 m 2 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 m 2 . RESULTS: 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 m 2 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) patients. CONCLUSIONS: 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.

Risk Factors for Hyperosmolar Hyperglycemic State in Pediatric Type 2 Diabetes.

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 models. Results: 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 mortality. Conclusion: 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.

The Relationship between Number of Supernumerary Blastocysts Cryopreserved and Probability of a Live Birth Outcome after Single Fresh Blastocyst Transfer: Analysis of over 10 Thousand Cycles.

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.

Acute Declines in Estimated GFR in Blood Pressure Target Trials and Risk of Adverse Outcomes.

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.

Incidence and Risk Factors for Dialysis Reinitiation among Patients with a History of Dialysis Dependency.

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 models. RESULTS: 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 function. CONCLUSIONS: Over one in five patients with recovery of kidney function after kidney failure restarted dialysis within 3 years.

Kidney transplant candidacy evaluation and waitlisting practices in the United States and their association with access to transplantation.

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.

Perioperative Delta Sodium and Post-Liver Transplant Neurological Complications in Liver Transplant Recipients.

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 hospitalization. METHODS: 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 LOS. RESULTS: 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.

Insulin Pump-related Inpatient Admissions in a National Sample of Youth With Type 1 Diabetes.

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 complications. METHODS: 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 costs. RESULTS: 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.

Palliative care and imaging utilisation for patients with cancer.

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 life. METHODS: 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 MII. CONCLUSIONS: 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.

Risk of breast cancer in women treated with ovarian stimulation drugs for infertility: a systematic review and meta-analysis.

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.

National Trends in Pediatric Admissions for Diabetic Ketoacidosis, 2006-2016.

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 DKA. METHODS: 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 overtime. RESULTS: 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 time. CONCLUSIONS: 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.

Surgeon Factors Have a Larger Effect on Vascular Access Type and Outcomes than Patient Factors.

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.