Physician and informal care use explained by the Pediatric Quality of Life Inventory (PedsQL) in children with suspected genetic disorders.

PURPOSE: To examine associations between Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core Scales and PedsQL Infant Scales with formal health care resource utilization (HCRU) and informal caregiver burden. METHODS: We studied a pediatric cohort of 837 patients (median age: 8.4 years) with suspected genetic disorders enrolled January 2019 through July 2021 in the NYCKidSeq program for diagnostic sequencing. Using linked ~ nine-month longitudinal survey and physician claims data collected through May 2022, we modeled the association between baseline PedsQL scores and post-baseline HCRU (median follow-up: 21.1 months) and informal care. We also assessed the longitudinal change in PedsQL scores with physician services using linear mixed-effects models. RESULTS: Lower PedsQL total and physical health scores were independently associated with increases in 18-month physician services, encounters, and weekly informal care. Comparing low vs. median total scores, increases were 10.6 services (95% CI: 1.0-24.6), 3.3 encounters (95% CI: 0.5-6.8), and $668 (95% CI: $350-965), respectively. For the psychosocial domain, higher scores were associated with decreased informal care. Based on adjusted linear mixed-effects modeling, every additional ten physician services was associated with diminished improvement in longitudinal PedsQL total score trajectories by 1.1 point (95% confidence interval: 0.6-1.6) on average. Similar trends were observed in the physical and psychosocial domains. CONCLUSION: PedsQL scores were independently associated with higher utilization of physician services and informal care. Moreover, longitudinal trajectories of PedsQL scores became less favorable with increased physician services. Adding PedsQL survey instruments to conventional measures for improved risk stratification should be evaluated in further research.

The Pediatric Quality of Life Inventory (PedsQL) is widely used to measure health-related quality of life in pediatric patients; however, few studies have examined whether the PedsQL is indicative of longitudinal outcomes of morbidity and health care needs. This study captures associations between PedsQL scores with utilization of physician and informal care in children with suspected genetic disorders. We demonstrate that lower PedsQL total and physical health scores are independently associated with greater utilization of physician services and informal care. Moreover, longitudinal trajectories of PedsQL scores become less favorable with increased physician services. Results can inform future applications of PedsQL instruments.

Power calculation for detecting interaction effect in cross-sectional stepped-wedge cluster randomized trials: an important tool for disparity research.

BACKGROUND: The stepped-wedge cluster randomized trial (SW-CRT) design has become popular in healthcare research. It is an appealing alternative to traditional cluster randomized trials (CRTs) since the burden of logistical issues and ethical problems can be reduced. Several approaches for sample size determination for the overall treatment effect in the SW-CRT have been proposed. However, in certain situations we are interested in examining the heterogeneity in treatment effect (HTE) between groups instead. This is equivalent to testing the interaction effect. An important example includes the aim to reduce racial disparities through healthcare delivery interventions, where the focus is the interaction between the intervention and race. Sample size determination and power calculation for detecting an interaction effect between the intervention status variable and a key covariate in the SW-CRT study has not been proposed yet for binary outcomes. METHODS: We utilize the generalized estimating equation (GEE) method for detecting the heterogeneity in treatment effect (HTE). The variance of the estimated interaction effect is approximated based on the GEE method for the marginal models. The power is calculated based on the two-sided Wald test. The Kauermann and Carroll (KC) and the Mancl and DeRouen (MD) methods along with GEE (GEE-KC and GEE-MD) are considered as bias-correction methods. RESULTS: Among three approaches, GEE has the largest simulated power and GEE-MD has the smallest simulated power. Given cluster size of 120, GEE has over 80% statistical power. When we have a balanced binary covariate (50%), simulated power increases compared to an unbalanced binary covariate (30%). With intermediate effect size of HTE, only cluster sizes of 100 and 120 have more than 80% power using GEE for both correlation structures. With large effect size of HTE, when cluster size is at least 60, all three approaches have more than 80% power. When we compare an increase in cluster size and increase in the number of clusters based on simulated power, the latter has a slight gain in power. When the cluster size changes from 20 to 40 with 20 clusters, power increases from 53.1% to 82.1% for GEE; 50.6% to 79.7% for GEE-KC; and 48.1% to 77.1% for GEE-MD. When the number of clusters changes from 20 to 40 with cluster size of 20, power increases from 53.1% to 82.1% for GEE; 50.6% to 81% for GEE-KC; and 48.1% to 79.8% for GEE-MD. CONCLUSIONS: We propose three approaches for cluster size determination given the number of clusters for detecting the interaction effect in SW-CRT. GEE and GEE-KC have reasonable operating characteristics for both intermediate and large effect size of HTE.

Potential Mediators for Treatment Effects of Novel Diabetes Medications on Cardiovascular and Renal Outcomes: A Meta-Regression Analysis.

BACKGROUND: Prior research suggests clinical effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) are mediated by changes in glycated hemoglobin, body weight, systolic blood pressure, hematocrit, and urine albumin-creatinine ratio. We aimed to confirm these findings using a meta-analytic approach. METHODS AND RESULTS: We updated a systematic review of 9 GLP-1RA and 13 SGLT2i trials and summarized longitudinal mediator data. We obtained hazard ratios (HRs) for cardiovascular, renal, and mortality outcomes. We performed linear mixed-effects modeling of LogHRs versus changes in potential mediators and investigated differences in meta-regression associations among drug classes using interaction terms. HRs generally became more protective with greater glycated hemoglobin reduction among GLP-1RA trials, with average HR improvements of 20% to 30%, reaching statistical significance for major adverse cardiovascular events (ΔHR, 23%; P=0.02). Among SGLT2i trials, associations with HRs were not significant and differed from GLP1-RA trials for major adverse cardiovascular events (Pinteraction=0.04). HRs for major adverse cardiovascular events, myocardial infarction, and stroke became less efficacious (ΔHR, -15% to -34%), with more weight loss for SGLT2i but not for GLP-1RA trials (ΔHR, 4%-7%; Pinteraction<0.05). Among 5 SGLT2i trials with available data, HRs for stroke became less efficacious with larger increases in hematocrit (ΔHR, 123%; P=0.09). No changes in HRs by systolic blood pressure (ΔHR, -11% to 9%) and urine albumin-creatinine ratio (ΔHR, -1% to 4%) were found for any outcome. CONCLUSIONS: We confirmed increased efficacy findings for major adverse cardiovascular events with reduction in glycated hemoglobin for GLP1-RAs. Further research is needed on the potential loss of cardiovascular benefits with increased weight loss and hematocrit for SGLT2i.

Physician services and costs after disclosure of diagnostic sequencing results in the NYCKidSeq program.

PURPOSE: To better understand the effects of returning diagnostic sequencing results on clinical actions and economic outcomes for pediatric patients with suspected genetic disorders. METHODS: Longitudinal physician claims data after diagnostic sequencing were obtained for patients aged 0 to 21 years with neurologic, cardiac, and immunologic disorders with suspected genetic etiology. We assessed specialist consultation rates prompted by primary diagnostic results, as well as marginal effects on overall 18-month physician services and costs. RESULTS: We included data on 857 patients (median age: 9.6 years) with a median follow-up of 17.3 months after disclosure of diagnostic sequencing results. The likelihood of having ≥1 recommendation for specialist consultation in 155 patients with positive findings was high (72%) vs 23% in 443 patients with uncertain findings and 21% in 259 patients with negative findings (P < .001). Follow-through consultation occurred in 30%. Increases in 18-month physician services and costs following a positive finding diminished after multivariable adjustment. Also, no significant differences between those with uncertain and negative findings were demonstrated. CONCLUSION: Our study did not provide evidence for significant increases in downstream physician services and costs after returning positive or uncertain diagnostic sequencing findings. More large-scale longitudinal studies are needed to confirm these findings.

Cardiovascular and Renal Benefits of Novel Diabetes Drugs by Baseline Cardiovascular Risk: A Systematic Review, Meta-analysis, and Meta-regression.

BACKGROUND: Eligibility for glucagon-like peptide 1 receptor agonists (GLP-1RA) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) has been expanded to patients with diabetes at lower cardiovascular risk, but whether treatment benefits differ by risk levels is not clear. PURPOSE: To investigate whether patients with varying risks differ in cardiovascular and renal benefits from GLP-1RA and SGLT2i with use of meta-analysis and meta-regression. DATA SOURCES: We performed a systematic review using PubMed through 7 November 2022. STUDY SELECTION: We included reports of GLP-1RA and SGLT2i confirmatory randomized trials in adult patients with safety or efficacy end point data. DATA EXTRACTION: Hazard ratio (HR) and event rate data were extracted for mortality, cardiovascular, and renal outcomes. DATA SYNTHESIS: We analyzed 9 GLP-1RA and 13 SGLT2i trials comprising 154,649 patients. Summary HRs were significant for cardiovascular mortality (GLP-1RA 0.87 and SGLT2i 0.86), major adverse cardiovascular events (0.87 and 0.88), heart failure (0.89 and 0.70), and renal (0.84 and 0.65) outcomes. For stroke, efficacy was significant for GLP-1RA (0.84) but not for SGLT2i (0.92). Associations between control arm cardiovascular mortality rates and HRs were nonsignificant. Five-year absolute risk reductions (0.80-4.25%) increased to 11.6% for heart failure in SGLT2i trials in patients with high risk (Pslope < 0.001). For GLP1-RAs, associations were nonsignificant. LIMITATIONS: Analyses were limited by lack of patient-level data, consistency in end point definitions, and variation in cardiovascular mortality rates for GLP-1RA trials. CONCLUSIONS: Relative effects of novel diabetes drugs are preserved across baseline cardiovascular risk, whereas absolute benefits increase at higher risks, particularly regarding heart failure. Our findings suggest a need for baseline risk assessment tools to identify variation in absolute treatment benefits and improve decision-making.

Benefits of an Early Mobility Program for Hospitalized Patients With Cancer.

PURPOSE: Patients with cancer are often hospitalized with complications from cancer and cancer treatment. Many experience a decline in physical functioning, including loss of mobility, which likely contributes to increased length of stay (LOS) and increased readmissions. We aimed to determine whether a mobility program would improve quality of care and decrease health care utilization. METHODS: We implemented a mobility aide program on an oncology unit in a large academic medical center for all patients without bedrest orders between October 1, 2018, and February 28, 2021. The program consisted of nursing evaluation using the Activity Measure for Post-Acute Care (AMPAC), an ordinal scale ranging from bed rest to ambulating ≥ 250 feet, to quantify mobility. Plan of care was determined in a multidisciplinary manner with physical therapy (PT), nursing, and a mobility aide, who is a medical assistant with enhanced rehabilitation training. Patients were then mobilized two times per day 7 days a week. Using descriptive statistics and mixed effects logistic regression, we evaluated the programs impact on LOS, readmissions, and changes in mobility during this time period compared with the 6-month interval before implementation. RESULTS: A total of 1,496 hospitalized patients were identified. The odds of hospital readmission within 30 days of discharge was significantly less for those who received the intervention (OR, 0.53; 95% CI, 0.37 to 0.78; P = .001). The odds ratio (OR) of having a final AMPAC score at or above the median was significantly higher for those who received the intervention (OR, 1.60; 95% CI, 1.04 to 2.45; P < .05). There was no significant difference in LOS. CONCLUSION: Use of this mobility program resulted in a significant decrease in readmissions and maintained or improved patients' mobility. This demonstrates that non-PT professionals can effectively mobilize hospitalized patients with cancer, thereby decreasing the burden on PT and nursing resources. Future work will evaluate the sustainability of the program and evaluate association with health care costs.

Night-to-night reliability and agreement of obstructive sleep apnea pathophysiologic mechanisms estimated with phenotyping using polysomnography in cognitively normal elderly participants.

STUDY OBJECTIVES: Phenotyping using polysomnography (PUP) is an algorithmic method to quantify physiologic mechanisms underlying obstructive sleep apnea (OSA): loop gain (LG1), arousal threshold (ArTH), and upper airway collapsibility (Vpassive) and muscular compensation (Vcomp). The consecutive-night test-retest reliability and agreement of PUP-derived estimates are unknown. From a cohort of elderly (age ≥55 years), largely non-sleepy, community-dwelling volunteers who underwent in-lab polysomnography (PSG) on 2 consecutive nights, we determined the test-retest reliability and agreement of PUP-estimated physiologic factors. METHODS: Participants who had an apnea-hypopnea index (AHI3A) of at least 15 events per hour on the first night were included. PUP analyses were performed on each of the two PSGs from each participant. Physiologic factor estimates were derived from NREM sleep and compared across nights using intraclass correlation coefficients for reliability and smallest real differences (SRD) for agreement. RESULTS: Two PSGs from each of 43 participants (86 total) were analyzed. A first-night effect was evident with increased sleep time and stability and decreased OSA severity on the second night. LG1, ArTH, and Vpassive demonstrated good reliability (ICC > 0.80). Vcomp had modest reliability (ICC = 0.67). For all physiologic factors, SRD values were approximately 20% or more of the observed ranges, suggesting limited agreement of longitudinal measurements for a given individual. CONCLUSIONS: For NREM sleep in cognitively normal elderly individuals with OSA, PUP-estimated LG1, ArTH, and Vpassive demonstrated consistent relative ranking of individuals (good reliability) on short-term repeat measurement. For all physiologic factors, longitudinal measurements demonstrated substantial intraindividual variability across nights (limited agreement).

Racial and Ethnical Diversity Within the Neurosurgery Resident and Faculty Workforce in the United States.

BACKGROUND: Promoting workplace diversity leads to a variety of benefits related to a broader range of perspectives and insights. Underrepresented in medicine (URiM), including African Americans, Latinx, and Natives (Americans/Alaskan/Hawaiians/Pacific Islanders), are currently accounting for approximately 40% of the US population. OBJECTIVE: To establish a snapshot of current URiM representation within academic neurosurgery (NS) programs and trends within NS residency. METHODS: All 115 NS residencies and academic programs accredited by the Accreditation Council for Graduate Medical Education in 2020 were included in this study. The National Residency Matching Program database was reviewed from 2011 to 2020 to analyze URiM representation trends over time within the NS resident workforce. The academic rank, academic and clinical title(s), subspecialty, sex, and race of URiM NS faculty (NSF) were obtained from publicly available data. RESULTS: The Black and Latinx NS resident workforce currently accounts for 4.8% and 5.8% of the total workforce, respectively. URiM NSF are present in 71% of the Accreditation Council for Graduate Medical Education-accredited NS programs and account for 8% (148 of 1776) of the workforce. Black and Latinx women comprise 10% of URiM NSF. Latinx NSFs are the majority within the URiM cohort for both men and women. URiM comprise 5% of all department chairs. All are men. Spine (26%), tumor (26%), and trauma (17%) were the top 3 subspecialties among URiM NSF. CONCLUSION: NS has evolved, expanded, and diversified in numerous directions, including race and gender representation. Our data show that ample opportunities remain to improve URiM representation within NS.

Telemedicine Utilization in the Ambulatory Palliative Care Setting: Are There Disparities?

CONTEXT: Given a shortage of specialty palliative care clinicians and geographic variation in availability, telemedicine has been proposed as one way to improve access to palliative care services for patients with cancer. However, the enduring digital divide raises questions about whether unequal access will exacerbate healthcare disparities. OBJECTIVES: To examine factors associated with utilization of telemedicine as compared to in-person visits by patients with cancer in the ambulatory palliative care setting. METHODS: We collected data on patients seen in Supportive Oncology clinic by palliative care clinicians with an in-person or telemedicine visit from March 1 to December 30, 2020. A logistic regression with generalized estimating equation was fit to assess the association between visit type and patient characteristics. RESULTS: A total of 491 patients and 1783 visits were identified, including 1061 (60%) in-person visits and 722 (40%) telemedicine visits. Female patients were significantly more likely to utilize telemedicine than male patients (OR 1.46; 95% CI 1.11-1.90). Spanish-speaking patients (OR 0.32, 95% CI 0.17-0.61), those without insurance (OR 0.28, 95% CI 0.15-0.52), and those without an activated patient portal (Inactivated: OR 0.46, 95% CI 0.26-0.82; Pending Activation: OR 0.29, 95% CI 0.18-0.48) were less likely to utilize telemedicine. CONCLUSION: Our study reveals disparities in telemedicine utilization in the ambulatory palliative care setting for patients with cancer who are male, Spanish-speaking, uninsured, or do not have an activated patient portal. In the wake of the COVID-19 pandemic, we can better meet the palliative care needs of patients with cancer through telemedicine only if equity is kept at the forefront of our discussions.

Altered K-complex morphology during sustained inspiratory airflow limitation is associated with next-day lapses in vigilance in obstructive sleep apnea.

STUDY OBJECTIVES: Determine if changes in K-complexes associated with sustained inspiratory airflow limitation (SIFL) during N2 sleep are associated with next-day vigilance and objective sleepiness. METHODS: Data from thirty subjects with moderate-to-severe obstructive sleep apnea who completed three in-lab polysomnograms: diagnostic, on therapeutic continuous positive airway pressure (CPAP), and on suboptimal CPAP (4 cmH2O below optimal titrated CPAP level) were analyzed. Four 20-min psychomotor vigilance tests (PVT) were performed after each PSG, every 2 h. Changes in the proportion of spontaneous K-complexes and spectral characteristics surrounding K-complexes were evaluated for K-complexes associated with both delta (∆SWAK), alpha (∆αK) frequencies. RESULTS: Suboptimal CPAP induced SIFL (14.7 (20.9) vs 2.9 (9.2); %total sleep time, p < 0.001) with a small increase in apnea-hypopnea index (AHI3A: 6.5 (7.7) vs 1.9 (2.3); p < 0.01) versus optimal CPAP. K-complex density (num./min of stage N2) was higher on suboptimal CPAP (0.97 ± 0.7 vs 0.65±0.5, #/min, mean ± SD, p < 0.01) above and beyond the effect of age, sex, AHI3A, and duration of SIFL. A decrease in ∆SWAK with suboptimal CPAP was associated with increased PVT lapses and explained 17% of additional variance in PVT lapses. Within-night during suboptimal CPAP K-complexes appeared to alternate between promoting sleep and as arousal surrogates. Electroencephalographic changes were not associated with objective sleepiness. CONCLUSIONS: Sustained inspiratory airflow limitation is associated with altered K-complex morphology including the increased occurrence of K-complexes with bursts of alpha as arousal surrogates. These findings suggest that sustained inspiratory flow limitation may be associated with nonvisible sleep fragmentation and contribute to increased lapses in vigilance.