Racial and Ethnic Disparity in Approach for Pediatric Intensive Care Unit Research Participation.

Importance: While disparities in consent rates for research have been reported in multiple adult and pediatric settings, limited data informing enrollment in pediatric intensive care unit (PICU) research are available. Acute care settings such as the PICU present unique challenges for study enrollment, given the highly stressful and emotional environment for caregivers and the time-sensitive nature of the studies. Objective: To determine whether race and ethnicity, language, religion, and Social Deprivation Index (SDI) were associated with disparate approach and consent rates in PICU research. Design, Setting, and Participants: This retrospective cohort study was performed at the Children's Hospital of Philadelphia PICU between July 1, 2011, and December 31, 2021. Participants included patients eligible for studies requiring prospective consent. Data were analyzed from February 2 to July 26, 2022. Exposure: Exposures included race and ethnicity (Black, Hispanic, White, and other), language (Arabic, English, Spanish, and other), religion (Christian, Jewish, Muslim, none, and other), and SDI (composite of multiple socioeconomic indicators). Main Outcomes and Measures: Multivariable regressions separately tested associations between the 4 exposures (race and ethnicity, language, religion, and SDI) and 3 outcomes (rates of approach among eligible patients, consent among eligible patients, and consent among those approached). The degree to which reduced rates of approach mediated the association between lower consent in Black children was also assessed. Results: Of 3154 children included in the study (median age, 6 [IQR, 1.9-12.5] years; 1691 [53.6%] male), rates of approach and consent were lower for Black and Hispanic families and those of other races, speakers of Arabic and other languages, Muslim families, and those with worse SDI. Among children approached for research, lower consent odds persisted for those of Black race (unadjusted odds ratio [OR], 0.73 [95% CI, 0.55-0.97]; adjusted OR, 0.68 [95% CI, 0.49-0.93]) relative to White race. Mediation analysis revealed that 51.0% (95% CI, 11.8%-90.2%) of the reduced odds of consent for Black individuals was mediated by lower probability of approach. Conclusions and Relevance: In this cohort study of consent rates for PICU research, multiple sociodemographic factors were associated with lower rates of consent, partly attributable to disparate rates of approach. These findings suggest opportunities for reducing disparities in PICU research participation.

The design and baseline characteristics for the HOPE Consortium Trial to reduce pain and opioid use in hemodialysis.

The HOPE Consortium Trial to Reduce Pain and Opioid Use in Hemodialysis (HOPE Trial) is a multicenter randomized trial addressing chronic pain among patients receiving maintenance hemodialysis for end-stage kidney disease. The trial uses a sequential, multiple assignment design with a randomized component for all participants (Phase 1) and a non-randomized component for a subset of participants (Phase 2). During Phase 1, participants are randomized to Pain Coping Skills Training (PCST), an intervention designed to increase self-efficacy for managing pain, or Usual Care. PCST consists of weekly, live, coach-led cognitive behavioral therapy sessions delivered by video- or tele-conferencing for 12 weeks followed by daily interactive voice response sessions delivered by telephone for an additional 12 weeks. At 24 weeks (Phase 2), participants in both the PCST and Usual Care groups taking prescription opioid medications at an average dose of ≥20 morphine milligram equivalents per day are offered buprenorphine, a partial opioid agonist with a more favorable safety profile than full-agonist opioids. All participants are followed for 36 weeks. The primary outcome is pain interference ascertained, for the primary analysis, at 12 weeks. Secondary outcomes include additional patient-reported measures and clinical outcomes including falls, hospitalizations, and death. Exploratory outcomes include acceptability, tolerability, and efficacy of buprenorphine. The enrollment target of 640 participants was met 27 months after trial initiation. The findings of the trial will inform the management of chronic pain, a common and challenging issue for patients treated with maintenance hemodialysis. NCT04571619.

Association of Racial Residential Segregation With Long-Term Outcomes and Readmissions After Out-of-Hospital Cardiac Arrest Among Medicare Beneficiaries.

Background The national impact of racial residential segregation on out-of-hospital cardiac arrest outcomes after initial resuscitation remains poorly understood. We sought to characterize the association between measures of racial and economic residential segregation at the ZIP code level and long-term survival and readmissions after out-of-hospital cardiac arrest among Medicare beneficiaries. Methods and Results In this retrospective cohort study, using Medicare claims data, our primary predictor was the index of concentration at the extremes, a measure of racial and economic segregation. The primary outcomes were death up to 3 years and readmissions. We estimated hazard ratios (HRs) across all 3 types of index of concentration at the extremes measures for each outcome while adjusting for beneficiary demographics, treating hospital characteristics, and index hospital procedures. In fully adjusted models for long-term survival, we found a decreased hazard of death and risk of readmission for beneficiaries residing in the more segregated White communities  and higher-income ZIP codes compared with the more segregated Black communities and lower-income ZIP codes across all 3 indices of concentration at the extremes measures (race: HR, 0.87 [95% CI, 0.81-0.93]; income: HR, 0.75 [95% CI, 0.69-0.78]; and race+income: HR, 0.77 [95% CI, 0.72-0.82]). Conclusions We found a decreased hazard of death and risk for readmission for those residing in the more segregated White communities  and higher-income ZIP codes compared with the more segregated Black communities and lower-income ZIP codes when using validated measures of racial and economic segregation. Although causal pathways and mechanisms remain unclear, disparities in outcomes after out-of-hospital cardiac arrest are associated with the structural components of race and wealth and persist up to 3 years after discharge.

Readmission Rates After Acute Respiratory Distress Syndrome in Children.

Importance: An increasing number of children survive after acute respiratory distress syndrome (ARDS). The long-term morbidity affecting these survivors, including the burden of hospital readmission and key factors associated with readmission, is unknown. Objective: To determine 1-year readmission rates among survivors of pediatric ARDS and to investigate the associations of 3 key index hospitalization factors (presence or development of a complex chronic condition, receipt of a tracheostomy, and hospital length of stay [LOS]) with readmission. Design, Setting, and Participants: This retrospective cohort study used data from the commercial or Medicaid IBM MarketScan databases between 2013 and 2017, with follow-up data through 2018. Participants included hospitalized children (aged ≥28 days to <18 years) who received mechanical ventilation and had algorithm-identified ARDS. Data analysis was completed from March 2022 to March 2023. Exposures: Complex chronic conditions (none, nonrespiratory, and respiratory), receipt of tracheostomy, and index hospital LOS. Main Outcomes and Measures: The primary outcome was 1-year, all-cause hospital readmission. Univariable and multivariable Cox proportional hazard models were created to test the association of key hospitalization factors with readmission. Results: One-year readmission occurred in 3748 of 13 505 children (median [IQR] age, 4 [0-14] years; 7869 boys [58.3%]) with mechanically ventilated ARDS who survived to hospital discharge. In survival analysis, the probability of 1-year readmission was 30.0% (95% CI, 29.0%-30.8%). One-half of readmissions occurred within 61 days of discharge (95% CI, 56-67 days). Both respiratory (adjusted hazard ratio [aHR], 2.69; 95% CI, 2.42-2.98) and nonrespiratory (aHR, 1.86; 95% CI, 1.71-2.03) complex chronic conditions were associated with 1-year readmission. Placement of a new tracheostomy (aHR, 1.98; 95% CI, 1.69-2.33) and LOS 14 days or longer (aHR, 1.87; 95% CI, 1.62-2.16) were associated with readmission. After exclusion of children with chronic conditions, LOS 14 days or longer continued to be associated with readmission (aHR, 1.92; 95% CI, 1.49-2.47). Conclusions and Relevance: In this retrospective cohort study of children with ARDS who survived to discharge, important factors associated with readmission included the presence or development of chronic medical conditions during the index admission, tracheostomy placement during index admission, and index hospitalization of 14 days or longer. Future studies should evaluate whether postdischarge interventions (eg, telephonic contact, follow-up clinics, and home health care) may help reduce the readmission burden.

Risk for Chronic Kidney Disease Progression After Acute Kidney Injury: Findings From the Chronic Renal Insufficiency Cohort Study.

BACKGROUND: Prior studies associating acute kidney injury (AKI) with more rapid subsequent loss of kidney function had methodological limitations, including inadequate control for differences between patients who had AKI and those who did not. OBJECTIVE: To determine whether AKI is independently associated with subsequent kidney function trajectory among patients with chronic kidney disease (CKD). DESIGN: Multicenter prospective cohort study. SETTING: United States. PARTICIPANTS: Patients with CKD (n = 3150). MEASUREMENTS: Hospitalized AKI was defined by a 50% or greater increase in inpatient serum creatinine (SCr) level from nadir to peak. Kidney function trajectory was assessed using estimated glomerular filtration rate (eGFR) based on SCr level (eGFRcr) or cystatin C level (eGFRcys) measured at annual study visits. RESULTS: During a median follow-up of 3.9 years, 433 participants had at least 1 AKI episode. Most episodes (92%) had stage 1 or 2 severity. There were decreases in eGFRcr (-2.30 [95% CI, -3.70 to -0.86] mL/min/1.73 m2) and eGFRcys (-3.61 [CI, -6.39 to -0.82] mL/min/1.73 m2) after AKI. However, in fully adjusted models, the decreases were attenuated to -0.38 (CI, -1.35 to 0.59) mL/min/1.73 m2 for eGFRcr and -0.15 (CI, -2.16 to 1.86) mL/min/1.73 m2 for eGFRcys, and the CI bounds included the possibility of no effect. Estimates of changes in eGFR slope after AKI determined by either SCr level (0.04 [CI, -0.30 to 0.38] mL/min/1.73 m2 per year) or cystatin C level (-0.56 [CI, -1.28 to 0.17] mL/min/1.73 m2 per year) also had CI bounds that included the possibility of no effect. LIMITATIONS: Few cases of severe AKI, no adjudication of AKI cause, and lack of information about nephrotoxic exposures after hospital discharge. CONCLUSION: After pre-AKI eGFR, proteinuria, and other covariables were accounted for, the association between mild to moderate AKI and worsening subsequent kidney function in patients with CKD was small. PRIMARY FUNDING SOURCE: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health.

Lowering PCO2 With Noninvasive Ventilation Is Associated With Improved Survival in Chronic Hypercapnic Respiratory Failure.

BACKGROUND: Chronic hypercapnic respiratory failure is associated with high mortality. Although previous work has demonstrated a mortality improvement with high-intensity noninvasive ventilation in COPD, it is unclear whether a PCO2 reduction strategy is associated with improved outcomes in other populations of chronic hypercapnia. METHODS: The objective of this study was to investigate the association between PCO2 reduction (by using transcutaneous PCO2 as an estimate for PaCO2 and survival in a broad population of individuals treated with noninvasive ventilation for chronic hypercapnia. We hypothesized that reductions in PCO2 would be associated with improved survival. Therefore, we performed a cohort study of all the subjects evaluated from February 2012 to January 2021 for noninvasive ventilation initiation and/or optimization due to chronic hypercapnia at a home ventilation clinic in an academic center. We used multivariable Cox proportional hazard models with time-varying coefficients and PCO2 as a time-varying covariate to test the association between PCO2 and all-cause mortality and when adjusting for known cofounders. RESULTS: The mean ± SD age of 337 subjects was 57 ± 16 years, 37% women, and 85% white. In a univariate analysis, survival probability increased with reductions in PCO2 to < 50 mm Hg after 90 d, and these remained significant after adjusting for age, sex, race, body mass index, diagnosis, Charlson comorbidity index, and baseline PCO2 . In the multivariable analysis, the subjects who had a PaCO2 < 50 mm Hg had a reduced mortality risk of 94% between 90 and 179 d (hazard ratio [HR] 0.06, 95% CI 0.01-0.50), 69% between 180 and 364 d (HR 0.31, 95% CI 0.12-0.79), and 73% for 365-730 d (HR 0.27, 95% CI 0.13-0.56). CONCLUSIONS: Reduction in PCO2 from baseline for subjects with chronic hypercapnia treated with noninvasive ventilation was associated with improved survival. Management strategies should target the greatest attainable reductions in PCO2 .

Validity of self-reported migraine in adolescents and children.

OBJECTIVE: To assess agreement for migraine day between self-report and diagnostic guidelines for children and adolescents using a headache diary. BACKGROUND: Trial guidelines recommend prospective collection of headache features and adoption of migraine day as an outcome measure, but there is no clear consensus on the definition of migraine day. METHODS: This is a secondary analysis of data from two projects-a prospective cohort study validating a pediatric scale of treatment expectancy and a clinical trial of occipital nerve blocks to treat status migrainosus. Participants completed a text message-based diary for 4 or 12 weeks (depending on treatment), and a detailed headache assessment on a random 20% of headache days. Using this assessment, we determined whether a headache day qualified for migraine or probable migraine, based on the International Classification of Headache Disorders, 3rd edition (ICHD-3). RESULTS: Of 122 enrolled children and adolescents, 106 (86.9%) completed ≥1 detailed headache assessment (438 entries). We found moderate agreement between self-reported and ICHD-derived migraine day, with a Cohen's Kappa of 0.50 (positive predictive value [PPV]: 0.66; negative predictive value [NPV]: 0.85; correlation: 0.51). Allowing for ICHD-derived probable migraine significantly increased PPV (0.66 vs. 0.94; 95% CI: 0.57-0.74 vs. 0.90-0.97), but decreased NPV (0.85 vs. 0.293; CI: 0.77-0.90 vs. 0.199-0.40), Cohen's Kappa (0.50 vs. 0.237; CI: 0. 389-0.60 vs. 0.139-0.352), and correlation (r = 0.51 vs. 0.302; CI: 0.41-0.61 vs. 0.192-0.41). Pain severity (OR: 5.7; CI: 2.39-13.8), photophobia (OR: 4.1; CI: 1.02-16.6), and phonophobia (OR: 7.5; CI: 1.95-29.3) were significantly associated with participants' perception of migraine. CONCLUSION: We found only moderate agreement between self-reported and ICHD-derived migraine day, suggesting both measures are not equal but may represent overlapping aspects of migraine as a disease. This highlights the difficulty of applying ICHD criteria to individual attacks. We recommend greater methodological transparency in future research to avoid readers conflating both measures.

Acute respiratory failure-related excess mortality in pediatric sepsis.

Excess mortality risk imparted by acute respiratory failure in children is unknown. We determined excess mortality risk associated with mechanically ventilated acute respiratory failure in pediatric sepsis. Novel ICD10-based algorithms were derived and validated to identify a surrogate for acute respiratory distress syndrome to calculate excess mortality risk. Algorithm-identified ARDS was identified with specificity of 96.7% (CI 93.0 - 98.9) and sensitivity of 70.5% (CI 44.0 - 89.7). Excess risk of mortality for ARDS was 24.4% (CI 22.9 - 26.2). Development of ARDS requiring mechanical ventilation imparts modest excess risk of mortality in septic children.

Probing the Association between Acute Kidney Injury and Cardiovascular Outcomes.

BACKGROUND: Patients hospitalized with AKI have higher subsequent risks of heart failure, atherosclerotic cardiovascular events, and mortality than their counterparts without AKI, but these higher risks may be due to differences in prehospitalization patient characteristics, including the baseline level of estimated glomerular filtration rate (eGFR), the rate of prior eGFR decline, and the proteinuria level, rather than AKI itself. METHODS: Among 2177 adult participants in the Chronic Renal Insufficiency Cohort study who were hospitalized in 2013-2019, we compared subsequent risks of heart failure, atherosclerotic cardiovascular events, and mortality between those with serum creatinine-based AKI (495 patients) and those without AKI (1682 patients). We report both crude associations and associations sequentially adjusted for prehospitalization characteristics including eGFR, eGFR slope, and urine protein-creatinine ratio (UPCR). RESULTS: Compared with patients hospitalized without AKI, those with hospitalized AKI had lower eGFR prehospitalization (42 versus 49 ml/min per 1.73 m 2 ), faster chronic loss of eGFR prehospitalization (-0.84 versus -0.51 ml/min per 1.73 m 2 per year), and more proteinuria prehospitalization (UPCR 0.28 versus 0.16 g/g); they also had higher prehospitalization systolic BP (130 versus 127 mm Hg; P < 0.01 for all comparisons). Adjustment for prehospitalization patient characteristics attenuated associations between AKI and all three outcomes, but AKI remained an independent risk factor. Attenuation of risk was similar after adjustment for absolute eGFR, eGFR slope, or proteinuria, individually or in combination. CONCLUSIONS: Prehospitalization variables including eGFR, eGFR slope, and proteinuria confounded associations between AKI and adverse cardiovascular outcomes, but these associations remained significant after adjusting for prehospitalization variables.

Novel Genetic Variants Associated with Chronic Kidney Disease Progression.

SIGNIFICANCE STATEMENT: eGFR slope has been used as a surrogate outcome for progression of CKD. However, genetic markers associated with eGFR slope among patients with CKD were unknown. We aimed to identify genetic susceptibility loci associated with eGFR slope. A two-phase genome-wide association study identified single nucleotide polymorphisms (SNPs) in TPPP and FAT1-LINC02374 , and 22 of them were used to derive polygenic risk scores that mark the decline of eGFR by disrupting binding of nearby transcription factors. This work is the first to identify the impact of TPPP and FAT1-LINC02374 on CKD progression, providing predictive markers for the decline of eGFR in patients with CKD. BACKGROUND: The incidence of CKD is associated with genetic factors. However, genetic markers associated with the progression of CKD have not been fully elucidated. METHODS: We conducted a genome-wide association study among 1738 patients with CKD, mainly from the KoreaN cohort study for Outcomes in patients With CKD. The outcome was eGFR slope. We performed a replication study for discovered single nucleotide polymorphisms (SNPs) with P <10 -6 in 2498 patients with CKD from the Chronic Renal Insufficiency Cohort study. Several expression quantitative trait loci (eQTL) studies, pathway enrichment analyses, exploration of epigenetic architecture, and predicting disruption of transcription factor (TF) binding sites explored potential biological implications of the loci. We developed and evaluated the effect of polygenic risk scores (PRS) on incident CKD outcomes. RESULTS: SNPs in two novel loci, TPPP and FAT1-LINC02374 , were replicated (rs59402340 in TPPP , Pdiscovery =7.11×10 -7 , PCRIC =8.13×10 -4 , Pmeta =7.23×10 -8 ; rs28629773 in FAT1-LINC02374 , Pdiscovery =6.08×10 -7 , PCRIC =4.33×10 -2 , Pmeta =1.87×10 -7 ). The eQTL studies revealed that the replicated SNPs regulated the expression level of nearby genes associated with kidney function. Furthermore, these SNPs were near gene enhancer regions and predicted to disrupt the binding of TFs. PRS based on the independently significant top 22 SNPs were significantly associated with CKD outcomes. CONCLUSIONS: This study demonstrates that SNP markers in the TPPP and FAT1-LINC02374 loci could be predictive markers for the decline of eGFR in patients with CKD.

Functional Impairment in Individuals With Prodromal or Unrecognized Parkinson Disease.

Importance: Daily functioning in individuals with prodromal Parkinson disease requires more detailed description. Objective: To evaluate whether functional limitations exist in individuals with Parkinson disease prior to diagnosis compared with the general population. Design, Setting, and Participants: This case-control study used Medicare-linked data from the National Health and Aging Trends Study (NHATS), a longitudinal survey in the US, for a random subsample of Medicare beneficiaries aged 65 years or older, with Black and older individuals oversampled by design. Patients with incident Parkinson disease were defined as having 2 or more Medicare diagnoses from January 2011 to December 2017, with Medicare eligibility 2 or more consecutive years prior to the first diagnosis. Controls were defined as individuals with Medicare eligibility at a baseline year and 2 or more years prior, with no Parkinson disease diagnosis. Analyses were conducted from November 2021 to June 2022. Exposures: Responses to survey questions addressing dexterity, eating, mobility, mood, pain, sleep, speech, strength, and vision. Main Outcome and Measures: Associations between survey responses and Parkinson disease diagnosis in the first year of diagnosis (baseline) and up to 3 years prior to diagnosis (ie, during the prodromal phase) were examined using logistic regression. Results: A total of 6674 participants were included. The participant numbers and case prevalence each year varied from 3492 to 5049 and from 700 to 1180 per 100 000 population, respectively. The median age groups were 75 to 79 years and 80 to 84 years, and the percentage of females varied from 48.21% (27 of 56 cases) to 59.98% (2079 of 3466 controls) across all years, with similar proportions among cases and controls. Individuals with prodromal Parkinson disease were less likely to report being able to walk 6 blocks (odds ratio [OR], 0.34; 95% CI, 0.15-0.82), stand independently from a kneeling position (OR, 0.30; 95% CI, 0.11-0.85), or lift a heavy object above one's head (OR, 0.36; 95% CI, 0.15-0.87) and were more likely to report imbalance (OR, 2.77; 95% CI, 1.24-6.20) 3 years prior to diagnosis. Conclusions and Relevance: The findings suggest that individuals with prodromal or unrecognized Parkinson disease may have greater impairment in activities involving mobility and strength up to 3 years prior to diagnosis compared with the general population. Identification of prodromal disease may facilitate earlier intervention to improve function.

Prospective associations of health literacy with clinical outcomes in adults with CKD: findings from the CRIC study.

BACKGROUND: Limited health literacy is associated with significant morbidity and mortality in the general population but the relation of health literacy with long-term clinical outcomes among adults with chronic kidney disease (CKD) is less clear. METHODS: Prospective data from the Chronic Renal Insufficiency Cohort (CRIC) Study (n = 3715) were used. Health literacy was assessed with the Short Test of Functional Health Literacy in Adults (dichotomized as limited/adequate). Cox proportional hazards models were used to separately examine the relations of health literacy with CKD progression, cardiovascular event (any of the following: myocardial infarction, congestive heart failure, stroke or peripheral artery disease), and all-cause, cardiovascular and non-cardiovascular mortality. Poisson regression was used to assess the health literacy-hospitalization association. Models were sequentially adjusted: Model 1 adjusted for potential confounders (sociodemographic factors), while Model 2 additionally adjusted for potential mediators (clinical and lifestyle factors) of the associations of interest. RESULTS: In confounder-adjusted models, participants with limited (vs adequate) health literacy [555 (15%)] had an increased risk of CKD progression [hazard ratio (HR) 1.34; 95% confidence interval (CI) 1.06-1.71], cardiovascular event (HR 1.67; 95% CI 1.39-2.00), hospitalization (rate ratio 1.33; 95% CI 1.26-1.40), and all-cause (HR 1.54; 95% CI 1.27-1.86), cardiovascular (HR 2.39; 95% CI 1.69-3.38) and non-cardiovascular (HR 1.27; 95% CI 1.01-1.60) mortality. Additional adjustments for potential mediators (Model 2) showed similar results except that the relations of health literacy with CKD progression and non-cardiovascular mortality were no longer statistically significant. CONCLUSIONS: In the CRIC Study, adults with limited (vs adequate) health literacy had a higher risk for CKD progression, cardiovascular event, hospitalization and mortality-regardless of adjustment for potential confounders.

Survival After Out-of-Hospital Cardiac Arrest: The Role of Racial Residential Segregation.

Racial and racialized economic residential segregation has been empirically associated with outcomes across multiple health conditions but not yet explored in relation to out-of-hospital cardiac arrest (OHCA). We sought to examine if measures of racial and economic residential segregation are associated with differences in survival to discharge after OHCA for Black and White Medicare beneficiaries. Utilizing age-eligible Medicare fee-for-service claims data from 2013 to 2015, we identified OHCA claims and determined survival to discharge. The primary predictor, residential segregation, was calculated using the index of concentration at the extremes (ICE) for the beneficiary residential ZIP code. Multilevel modified Poisson regression models were used to determine the association of OHCA outcomes and ZIP code level ICE measures. In total, 194,263 OHCA cases were identified among beneficiaries residing in 75% of US ZIP codes. Black beneficiaries exhibited 12.1% survival to discharge, compared with 12.5% of White beneficiaries. In fully adjusted models of the three ICE measures accounting for differences in treating hospital characteristics, there was as high as a 28% (RR 1.28, CI 1.23-1.26) higher relative likelihood of survival to discharge in the most segregated White ZIP codes (Q5) as compared to the most segregated Black ZIP codes (Q1). Racial residential segregation is independently associated with disparities in OHCA outcomes; among Medicare beneficiaries who generated a claim after suffering an OHCA, ICE measures of racial segregation are associated with a lower likelihood of survival to discharge for those living in the most segregated Black and lower income quintiles compared to higher quintiles.

Selected autonomic signs and symptoms as risk markers for phenoconversion and functional dependence in prodromal Parkinson's disease.

PURPOSE: To determine whether dysautonomia can stratify individuals with other prodromal markers of Parkinson's disease (PD) for risk of phenoconversion and functional decline, which may help identify subpopulations appropriate for experimental studies. METHODS: Data were obtained from Parkinson's Progression Markers Initiative. Cohorts without PD but with at-risk features were included (hyposmia and/or rapid-eye-movement-sleep behavior disorder, LRRK2 gene mutation, GBA gene mutation). Dysautonomia measures included Scales-for-Outcomes-in-Parkinson's-Disease Autonomic (SCOPA-AUT), seven SCOPA-AUT subscales, and cardiovascular dysfunction (supine hypertension, low pulse pressure, neurogenic orthostatic hypotension). Outcome measures were phenoconversion and Schwab-and-England Activities-of-Daily-Living (SE-ADL) ≤ 70, which indicates functional dependence. Cox proportional-hazards regression was used to evaluate survival to phenoconversion/SE-ADL ≤ 70 for each dysautonomia measure. If a significant association was identified, a likelihood-ratio test was employed to evaluate whether a significant interaction existed between the measure and cohort. If so, regression analysis was repeated stratified by cohort. RESULTS: Median follow-up was 30 months. On multivariable analysis, gastrointestinal and female sexual dysfunction subscales were associated with increased risk of phenoconversion, while the cardiovascular subscale and neurogenic orthostatic hypotension were associated with increased risk of SE-ADL ≤ 70; respective hazard ratios (95% confidence intervals) were 1.13 (1.01-1.27), 3.26 (1.39-7.61), 1.87 (1.16-2.99), 5.45 (1.40-21.25). Only the association between the cardiovascular subscale and SE-ADL ≤ 70 was modified by cohort. CONCLUSIONS: Symptoms of gastrointestinal and female sexual dysfunction predict phenoconversion in individuals with other risk markers for PD, while signs and symptoms of cardiovascular dysfunction may be associated with functional decline.

Absence of long-term changes in urine biomarkers after AKI: findings from the CRIC study.

BACKGROUND: Mechanisms by which AKI leads to CKD progression remain unclear. Several urine biomarkers have been identified as independent predictors of progressive CKD. It is unknown whether AKI may result in long-term changes in these urine biomarkers, which may mediate the effect of AKI on CKD progression. METHODS: We selected 198 episodes of hospitalized AKI (defined as peak/nadir inpatient serum creatinine values ≥ 1.5) among adult participants in the Chronic Renal Insufficiency Cohort (CRIC) Study. We matched the best non-AKI hospitalization (unique patients) for each AKI hospitalization using pre-hospitalization characteristics including eGFR and urine protein/creatinine ratio. Biomarkers were measured in banked urine samples collected at annual CRIC study visits. RESULTS: Urine biomarker measurements occurred a median of 7 months before and 5 months after hospitalization. There were no significant differences in the change in urine biomarker-to-creatinine ratio between the AKI and non-AKI groups: KIM-1/Cr + 9% vs + 7%, MCP-1/Cr + 4% vs + 1%, YKL-40/Cr + 7% vs -20%, EGF/Cr -11% vs -8%, UMOD/Cr -2% vs -7% and albumin/Cr + 17% vs + 13% (all p > 0.05). CONCLUSION: In this cohort of adults with CKD, AKI did not associate with long-term changes in urine biomarkers.

Reoperation Through a Prosthetic-Reinforced Abdominal Wall and Its Association With Postoperative Outcomes and Longitudinal Health Care Utilization.

Importance: Prosthetic reinforcement of critically sized incisional hernias is necessary to decrease hernia recurrence, but long-term prosthetic-mesh footprint may increase complication risk during subsequent abdominal operations. Objective: To investigate the association of prior incisional hernia repair with mesh (IHRWM) with postoperative outcomes and health care utilization after common abdominal operations. Design, Setting, and Participants: This was a population-based, retrospective cohort study of patients undergoing inpatient abdominal surgical procedures during the period of January 2009 to December 2016, with at least 1 year of follow-up within 5 geographically diverse statewide inpatient/ambulatory databases (Florida, Iowa, Nebraska, New York, Utah). History of an abdominal operation was ascertained within the 3-year period preceding the index operation. Patients admitted to the hospital with a history of an abdominal operation (ie, bariatric, cholecystectomy, small- or large-bowel resection, prostatectomy, gynecologic) were identified using the International Classification of Diseases, Ninth Revision and Tenth Revision, Clinical Modification procedure codes. Patients with prior IHRWM were propensity score matched (1:1) to controls both with and without a history of an abdominal surgical procedure based on clinical and operative characteristics. Data analysis was conducted from March 1 to November 27, 2021. Main Outcomes and Measures: The primary outcome was a composite of adverse postoperative outcomes (surgical and nonsurgical). Secondary outcomes included health care utilization determined by length of hospital stay, hospital charges, and 1-year readmissions. Logistic and Cox regression determined the association of prior IHRWM with the outcomes of interest. Additional subanalyses matched and compared patients with prior IHR without mesh (IHRWOM) to those with a history of an abdominal operation. Results: Of the 914 105 patients undergoing common abdominal surgical procedures (81 123 bariatric [8.9%], 284 450 small- or large-bowel resection [31.1%], 223 768 cholecystectomy [24.5%], 33 183 prostatectomy [3.6%], and 291 581 gynecologic [31.9%]), all 3517 patients (age group: 46-55 years, 1547 [44.0%]; 2396 majority sex [68.1%]) with prior IHRWM were matched to patients without a history of abdominal surgical procedures. After matching, prior IHRWM was associated with increased overall complications (odds ratio [OR], 1.43; 95% CI, 1.27-1.60), surgical complications (OR, 1.51; 95% CI, 1.34-1.70), length of hospital stay (mean increase of 1.03 days; 95% CI, 0.56-1.49 days; P < .001), index admission charges (predicted mean difference of $11 896.10; 95% CI, $6096.80-$17 695.40; P < .001), and 1-year unplanned readmissions (hazard ratio, 1.14; 95% CI, 1.05-1.25; P = .002). This trend persisted even when comparing matched patients with prior IHRWM to patients with a history of abdominal surgical procedures, and the treatment outcome disappeared when comparing patients with prior IHRWOM to those without a previous abdominal operation. Conclusions and Relevance: Reoperation through a previously prosthetic-reinforced abdominal wall was associated with increased surgical complications and health care utilization. This risk appeared to be independent of a history of abdominal surgical procedures and was magnified by the presence of a prosthetic-mesh footprint in the abdominal wall.