Background The normal rate of subclinical vascular aging from adolescence to young adulthood has not been well-characterized. We conducted a 5-year longitudinal study among adolescents with ...normal-weight, obesity, and/or type 2 diabetes mellitus to examine trajectories of early vascular aging. Methods and Results Adolescents (mean SD age 17.6 3.5; 35.3% male) had either normal weight (n=141), obesity (n=156), or type 2 diabetes mellitus (n=151) at baseline. Primary metrics used for early vascular aging included measures of vascular structure (carotid intima-media thickness cIMT; common, internal, and bulb) and arterial stiffness (carotid-femoral pulse wave velocity, and augmentation index). Longitudinal (5-year) outcomes were examined using generalized estimating equations adjusting for baseline value, sex, race, and age. Compared with participants with normal weight, those with obesity had greater positive change in common cIMT (0.05 mm 0.03, 0.06;
<0.001), bulb cIMT (0.02 mm 0.00, 0.05;
=0.033), internal cIMT (0.03 mm 0.01, 0.05;
<0.001), and pulse wave velocity carotid-femoral (0.38 m/sec 0.14, 0.61;
=0.001), and those with type 2 diabetes mellitus had greater positive change in common cIMT (0.05 mm 0.04, 0.07;
<0.001), bulb cIMT (0.06 mm 0.04, 0.09;
<0.001), internal cIMT (0.04 mm 0.02, 0.07;
<0.001), augmentation index (4.67% 2.20, 7.13;
<0.001), and pulse wave velocity carotid-femoral (0.74 m/sec 0.46, 1.02;
<0.001). Higher baseline systolic blood pressure was associated with greater positive change in common cIMT (0.007 mm 0.003, 0.011;
<0.001), bulb cIMT (0.009 mm 0.002, 0.016;
=0.01), internal cIMT (0.008 mm 0.003, 0.013;
=0.001), and pulse wave velocity carotid-femoral (0.066 m/sec 0.002, 0.130;
=0.042). Conclusions These longitudinal data support the hypothesis that the presence of obesity, type 2 diabetes mellitus, and elevated baseline systolic blood pressure in early life accelerates the progression of risk factors key in the development of early vascular aging.
We hypothesize that the time, number of attempts, and physiologic stability of placement of an LMA would be superior compared to ETT.
Videotape and physiologic parameters of LMA (n = 36) and ETT (n = ...31) placement procedures for infants 28-36 weeks gestation were reviewed.
Duration of attempts (32 vs 66 s, p < 0.001) and mean total airway insertion time (88 vs 153 s, p = 0.06) was shorter for LMA compared to ETT. Mean number of attempts for successful placement was fewer for LMA (1.5 vs 1.9, p = 0.11). Physiologic parameters remained near baseline in both groups despite very different degrees of premedication.
Placement of an LMA required less time and fewer number of attempts compared to ETT. Physiologic stability of an LMA was maintained without the use of an analgesic and muscle relaxant. Use of an LMA is a favorable alternative to ETT placement for surfactant delivery in neonates.
NCT01116921.
Parenteral vitamin D is associated with improved survival among long-term hemodialysis patients. Among nondialyzed patients with chronic kidney disease (CKD), oral activated vitamin D reduces ...parathyroid hormone levels, but the impact on clinical outcomes is unknown. We evaluated associations of oral calcitriol use with mortality and dialysis dependence in 1418 nondialysis patients with CKD and hyperparathyroidism in the Veterans' Affairs Consumer Health Information and Performance Sets database. Incident calcitriol users and nonusers were selected on the basis of stages 3 to 4 CKD, hyperparathyroidism, and the absence of hypercalcemia before calcitriol use and then were matched by age and estimated kidney function. During a median follow-up of 1.9 yr, 408 (29%) patients died and 217 (16%) initiated long-term dialysis. After adjustment for demographics; comorbidities; estimated kidney function; medications; and baseline levels of parathyroid hormone, calcium, and phosphorous, oral calcitriol use was associated with a 26% lower risk for death (95% confidence interval 5 to 42% lower; P = 0.016) and a 20% lower risk for death or dialysis (95% confidence interval 1 to 35% lower; P = 0.038). The association of calcitriol with improved survival was not statistically different across baseline parathyroid hormone levels. Calcitriol use was associated with a greater risk for hypercalcemia. In conclusion, oral calcitriol use is associated with lower mortality in nondialysis patients with CKD.
Elevated serum phosphate levels have been linked with vascular calcification and mortality among dialysis patients. The relationship between phosphate and mortality has not been explored among ...patients with chronic kidney disease (CKD). A retrospective cohort study was conducted from eight Veterans Affairs' Medical Centers located in the Pacific Northwest. CKD was defined by two continuously abnormal outpatient serum creatinine measurements at least 6 mo apart between 1999 and 2002. Patients who received chronic dialysis, those with a present or previous renal transplant, and those without a recent phosphate measurement were excluded. The primary end point was all-cause mortality. Secondary end points were acute myocardial infarction and the combined end point of myocardial infarction plus death. A total of 95,619 veterans with at least one primary care or internal medicine clinic contact from a Northwest VA facility and two or more outpatient measurements of serum creatinine, at least 6 mo apart, between January 1, 1999, and December 31, 2002, were identified. From this eligible population, 7021 patients met our definition of CKD. After exclusions, 6730 CKD patients were available for analysis, and 3490 had a serum phosphate measurement during the previous 18 mo. After adjustment, serum phosphate levels >3.5 mg/dl were associated with a significantly increased risk for death. Mortality risk increased linearly with each subsequent 0.5-mg/dl increase in serum phosphate levels. Elevated serum phosphate levels were independently associated with increased mortality risk among this population of patients with CKD.
The lack of reliable biomarkers is a significant challenge impeding progress in orphan drug development. For appropriate interpretation of intervention-based results or for evaluating candidate ...biomarkers, other things being equal, lower variability in biomarker measurement would be helpful. However, variability in rare disease biomarkers is often poorly understood. Type 1 Gaucher disease (GD1) is one such rare lysosomal storage disorder. Oxidative stress and inflammation have been linked to the pathophysiology of GD1 and validated measures of these processes can provide predictive value for treatment success or disease progression. This study was undertaken to investigate and compare the extent of longitudinal biological variation over a three-month period for various blood-based oxidative stress and inflammation markers in participants with GD1 on stable standard-of-care therapy (N = 13), treatment-naïve participants with GD1 (N = 5), and in age- and gender-matched healthy volunteers (N = 18). We utilized Bland–Altman plots for visual comparison of the biological variability among the three measurements. We also report group-wise means and the percentage of coefficient of variation (%CV) for 15 biomarkers. Qualitatively, we show specific markers (IL-1Ra, IL-8, and MIP-1b) to be consistently altered in GD1, irrespective of therapy status, highlighting the need for adjunctive therapies that can target and modulate these biomarkers. This information can help guide the selection of candidate biomarkers for future intervention-based studies in GD1 patients.
To determine if preterm infants with moderate respiratory distress syndrome on continuous positive airway pressure (CPAP) who received surfactant via a laryngeal mask airway (LMA) would have a ...decreased rate of intubation and mechanical ventilation compared with those on CPAP who did not receive surfactant.
In this prospective, multicenter, randomized controlled trial, 103 premature infants 280/7-356/7 weeks gestation, ≥1250 g and ≤36 hours old on CPAP requiring fraction of inspired oxygen 0.30-0.40 were assigned to receive surfactant administered through an LMA then placed back on CPAP (LMA group) or maintained on CPAP with no surfactant administered (control group). The primary outcome was treatment failure necessitating intubation and mechanical ventilation in the first 7 days of life.
Surfactant administration through an LMA (n = 50) significantly decreased the rate of intubation and mechanical ventilation compared with controls (n = 53): 38% vs 64%, respectively, OR 0.30 (95% CI 0.13, 0.70), P = .006, number needed to treat: 4). There were no serious adverse events associated with placement of the LMA or surfactant administration.
In premature neonates with moderate respiratory distress syndrome, surfactant administered through an LMA decreased the rate of intubation and mechanical ventilation. This intervention may have significant impact on clinical care in both high and low resource settings.
ClinicalTrials.gov: NCT01116921.
The impact of parathyroidectomy (PTX) on the long-term risks for hip and other fractures is unknown. Uncontrolled case series have reported an increase in bone mineral density after PTX. However, ...very low serum parathyroid hormone levels have been associated with decreased bone mineral density, adynamic bone disease, and fractures. This study compared long-term fracture rates among hemodialysis patients who underwent PTX with a matched control group. Data were obtained from the US Renal Data System. Patients who underwent a first PTX while receiving hemodialysis were matched with up to three control patients by age, race, gender, year of dialysis initiation, primary cause of renal failure, and the dosage of intravenous vitamin D used before PTX. Patients with a history of fracture or renal transplantation were excluded. Study outcomes were incident hip, vertebral, and distal radius-wrist fractures identified using hospitalization codes. Incident hip fracture rates in the PTX and matched control groups were 6.0 and 9.3 fractures per 1000 person-years, respectively. After adjustment, PTX was associated with a significant 32% lower risk for hip fracture (95% confidence interval 0.54 to 0.86; P = 0.001) and a 31% lower risk for any analyzed fracture (95% confidence interval 0.57 to 0.83; P < 0.001) compared with matched control subjects. Fracture risks were lower among hemodialysis patients who underwent PTX compared with matched control subjects. Surgical amelioration of secondary hyperparathyroidism may outweigh the risk of parathyroid hormone oversuppression in terms of bone health.
The purposes of this study were to characterize the impact of depression and anxiety on the severity of obesity among youth seeking weight management treatment and to determine the extent to which ...emotional eating mediates the relationship between depression and/or anxiety and degree of obesity. This cross-sectional, retrospective chart review of 102 adolescent patients from a weight management clinic analyzed demographics, body mass index, depression (Patient Health Questionnaire-9), and anxiety (Generalized Anxiety Disorder Scale-7) screens and the Child Eating Behavior Questionnaire, Emotional Over-Eating subscale. After adjusting for demographics and emotional eating, the odds of having severe obesity versus obesity were 3.5 times higher for patients with depression compared with those without (odds ratio OR = 3.5; 95% CI = 1.1, 11.3; P = .038) and nearly 5 times higher for those with anxiety (OR = 4.9; CI = 1.2, 20.9; P = .030). Emotional eating, however, was not a mediator between depression/anxiety and degree of adiposity.
The laryngeal mask airway (LMA) has been used in adult and pediatric populations for decades. While the familiarity of its use in the neonatal population is increasing, there are few data ...investigating this.
The objective of this study was to determine the feasibility of LMA placement in neonates by investigating the time and number of attempts required for successful placement and physiologic stability during the placement of the device.
This study is one component of a national, multicenter, randomized controlled trial investigating surfactant administration through an LMA in neonates. Videotape of LMA placement was reviewed to determine the total procedure time and the number of attempts required to successfully place the device. Heart rate and oxygen saturation (SaO2) were analyzed as change from baseline, in order to examine physiologic stability during device placement.
Videotape and physiologic data were analyzed for 36 infants. Gestational age ranged from 293/7 to 354/7 weeks (mean 33 ± 1.7) with the birth weight ranging from 1,290 to 3,180 g (mean 2,006 ± 482). Average total procedure time was 88 s (±136) with 64% of the procedures successfully completed in <35 s. Successful placement was achieved on the first attempt in 69% of the cases. Compared to baseline, heart rate increased by an average of 1 bpm (±4.5) and SaO2 decreased an average of 6% (±7).
Successful placement was achieved in the majority of patients in <35 s and required only one attempt. Physiologic parameters were maintained close to baseline, measured by minimal fluctuation in heart rate and SaO2 during the procedure. Placement of the LMA is feasible in neonates.
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