Heart Rate Variability and Cardiac Autonomic Dysfunction: Prevalence, Risk Factors and Relationship to Arterial Stiffness in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) Study.

2019

2019 Sep 09

1935-5548

<p><strong>OBJECTIVE: </strong>To determine whether prior type 2 diabetes (T2D) treatment or glycemic control over time are independently associated with heart rate variability (HRV) and whether the presence of cardiac autonomic dysfunction is associated with arterial stiffness in young adults with youth-onset T2D enrolled in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study.</p>

<p><strong>RESEARCH DESIGN AND METHODS: </strong>Heartbeats over 10 min were measured to derive the normal R-Rs (NN intervals). Outcomes included the standard deviation of the NN intervals (SDNN), the root mean square differences of successive NN intervals (RMSSD), percent of NN beats that differ by more than 50 ms (PNN50), and the low-frequency (LF) power domain, high-frequency (HF) power domain, and their ratio (LF:HF). Autonomic dysfunction was defined as ≥3 of 5 abnormal HRV indices compared with obese controls from a separate study.</p>

<p><strong>RESULTS: </strong>A total of 397 TODAY participants were evaluated 7 years after randomization. TODAY participants had reduced HRV (SDNN; 57.9 ± 29.6 ms vs. controls 67.1 ± 25.4 ms; &lt; 0.0001) with parasympathetic loss (RMSSD; 53.0 ± 36.6 ms vs. controls 67.9 ± 35.2 ms; &lt; 0.0001) with sympathetic overdrive (LF:HF ratio; 1.4 ± 1.7 vs. controls 1.0 ± 1.1; &lt; 0.0001). Cardiac autonomic dysfunction was present in 8% of TODAY participants, and these participants had greater pulse wave velocity compared with those without dysfunction ( = 0.0001). HRV did not differ by randomized treatment, but higher hemoglobin A1c (HbA) over time was independently associated with lower SDNN and RMSSD and higher LF:HF ratio after adjustment for age, race-ethnicity, sex, and body mass index.</p>

<p><strong>CONCLUSIONS: </strong>Young adults with youth-onset T2D show evidence of cardiac autonomic dysfunction with both parasympathetic and sympathetic impairments that are associated with higher HbA.</p>

10.2337/dc19-0993

Diabetes Care

31501226

Patient and hospital factors associated with induction mortality in acute lymphoblastic leukemia.

2014

846-52

2014 May

1545-5017

<p><strong>BACKGROUND: </strong>Deaths during induction chemotherapy for pediatric acute lymphoblastic leukemia (ALL) account for one-tenth of ALL-associated mortality and half of ALL treatment-related mortality. We sought to ascertain patient- and hospital-level factors associated with induction mortality.</p>

<p><strong>PROCEDURE: </strong>We performed a retrospective cohort analysis of 8,516 children ages 0 to &lt;19 years with newly diagnosed ALL admitted to freestanding US children's hospitals from 1999 to 2009 using the Pediatric Health Information System database. Induction mortality risk was modeled accounting for demographics, intensive care unit-level interventions, and socioeconomic status (SES) using Cox regression. The association of ALL induction mortality with hospital-level factors including volume, hospital-wide mortality and payer mix was analyzed with multiple linear regression.</p>

<p><strong>RESULTS: </strong>ALL induction mortality was 1.12%. Race and patient-level SES factors were not associated with induction mortality. Patients receiving both mechanical ventilation and vasoactive infusions experienced nearly 50% mortality (hazard ratio 122.30, 95% CI 66.56-224.80). Institutions in the highest induction mortality quartile contributed 27% of all patients but nearly half of all deaths (47 of 95). Hospital payer mix was associated with ALL induction mortality after adjustment for other hospital-level factors (P = 0.046).</p>

<p><strong>CONCLUSIONS: </strong>The overall risk of induction death is low but substantially increased in patients with cardio-respiratory and other organ failures. Induction mortality varies up to three-fold across hospitals and is correlated with hospital payer mix. Further work is needed to improve induction outcomes in hospitals with higher mortality. These data suggest an induction mortality rate of less than 1% may be an attainable national benchmark.</p>

10.1002/pbc.24855

Pediatr Blood Cancer

24249480

Establishment of an 11-year cohort of 8733 pediatric patients hospitalized at United States free-standing children's hospitals with de novo acute lymphoblastic leukemia from health care administrative data.

2014

e1-6

2014 Jan

1537-1948

<p><strong>BACKGROUND: </strong>Acute lymphoblastic leukemia (ALL) accounts for almost one quarter of pediatric cancer in the United States. Despite cooperative group therapeutic trials, there remains a paucity of large cohort data on which to conduct epidemiology and comparative effectiveness research studies.</p>

<p><strong>RESEARCH DESIGN: </strong>We designed a 3-step process utilizing International Classification of Diseases-9 Clinical Modification (ICD-9) discharge diagnoses codes and chemotherapy exposure data contained in the Pediatric Health Information System administrative database to establish a cohort of children with de novo ALL. This process was validated by chart review at 1 of the pediatric centers.</p>

<p><strong>RESULTS: </strong>An ALL cohort of 8733 patients was identified with a sensitivity of 88% [95% confidence interval (CI), 83%-92%] and a positive predictive value of 93% (95% CI, 89%-96%). The 30-day all cause inpatient case fatality rate using this 3-step process was 0.80% (95% CI, 0.63%-1.01%), which was significantly different than the case fatality rate of 1.40% (95% CI, 1.23%-1.60%) when ICD-9 codes alone were used.</p>

<p><strong>CONCLUSIONS: </strong>This is the first report of assembly and validation of a cohort of de novo ALL patients from a database representative of free-standing children's hospitals across the United States. Our data demonstrate that the use of ICD-9 codes alone to establish cohorts will lead to substantial patient misclassification and result in biased outcome estimates. Systematic methods beyond the use of just ICD-9 codes must be used before analysis to establish accurate cohorts of patients with malignancy. A similar approach should be followed when establishing future cohorts from administrative data.</p>

10.1097/MLR.0b013e31824deff9

Med Care

22410405

Variation in hospital antibiotic prescribing practices for children with acute lymphoblastic leukemia.

2013

1633-9

2013 Aug

1029-2403

<p>Antibiotic variation among pediatric oncology patients has not been well-described. Identification of significant variability in antibiotic use within this population would warrant evaluation of its clinical impact. We conducted a retrospective cohort study of newly diagnosed patients with pediatric acute lymophoblastic leukemia (ALL) hospitalized from 1999 to 2009 in 39 freestanding US children's hospitals within the Pediatric Health Information System. Medication use data were obtained for the first 30 days from each patient's index ALL admission date. Antibiotic exposure rates were reported as antibiotic days/1000 hospital days. Unadjusted composite broad-spectrum antibiotic exposure rates varied from 577 to 1628 antibiotic days/1000 hospital days. This wide range of antibiotic exposure was unaffected by adjustment for age, gender, race and days of severe illness (adjusted range: 532-1635 days of antibiotic therapy/1000 hospital days). Antibiotic use for children with newly diagnosed ALL varies widely across children's hospitals and is not explained by demographics or illness severity.</p>

10.3109/10428194.2012.750722

Leuk. Lymphoma

23163631