Catch-Up growth in former preterm neonates: no time to waste

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Catch-up growth in former preterm neonates: No time to waste

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QTc intervals are not prolonged in former ELBW infants at pre-adolescent age

Background: Whether preterm birth is associated with cardiac conduction or repolarization abnormalities in later life is still poorly explored, with conflicting data on QTc prolongation in former extreme low birth weight (ELBW, &lt;1000 g) infants. Methods: Twelve lead electrocardiograms (ECG) at rest, collected in the PREMATurity as predictor of children’s Cardiovascular-renal Health (PREMATCH) study in former ELBW cases and term controls during pre-adolescence (8–14 years) were analyzed on corrected QT time (QTc, Bazett) and QT dispersion (QTd). ECG findings were compared between groups (Mann−Whitney), and associations with clinical and biochemical findings were explored (Spearman). In ELBW cases, associations between QTc and perinatal characteristics (at birth, neonatal stay) were explored (Mann−Whitney, Spearman). Results: QTc and QTd were similar between 93 ELBW cases and 87 controls [409 (range 360–465) versus 409 (337–460); 40 (0–100) versus 39 (0–110)] ms. Age, height, weight, or body mass index were not associated with the QTc interval, while female sex (median difference 11.4 ms) and lower potassium (r = −0.26) were associated with longer QTc interval. We could not observe any significant association between QTc interval and perinatal characteristics. Conclusions: There were no differences in QTc or QTd between ELBW and term controls in ECGs at rest in pre-adolescents. Impact: This study aimed to assess the differences in QTc and QTd intervals between extreme low birth weight infants (ELBW) and term controls in electrocardiographic measurements at rest during pre-adolescence.This analysis confirmed the absence of significant differences in QTc or QTd findings between ELBW cases and term controls, while female sex and lower potassium were associated with a prolonged QTc interval.These data suggest that QTc screening strategies—including for pharmacovigilance—should not differentiate between former ELBW cases and term controls. Clinical trial registration: ClinicalTrials.gov Identifier NCT02147457.</p

The impact of structural uncertainty on cost-effectiveness models for adjuvant endocrine breast cancer treatments: The need for disease-specific model standardization and improved guidance

__Abstract__ Introduction: Structural uncertainty relates to differences in model structure and parameterization. For many published health economic analyses in oncology, substantial differences in model structure exist, leading to differences in analysis outcomes and potentially impacting decision-making processes. The objectives of this analysis were (1) to identify differences in model structure and parameterization for cost-effectiveness analyses (CEAs) comparing tamoxifen and anastrazole for adjuvant breast cancer (ABC) treatment; and (2) to quantify the impact of these differences on analysis outcome metrics. Methods: The analysis consisted of four steps: (1) review of the literature for identification of eligible CEAs; (2) definition and implementation of a base model structure, which included the core structural components for all identified CEAs; (3) definition and implementation of changes or additions in the base model structure or parameterization; and (4) quantification of the impact of changes in model structure or parameterizations on the analysis outcome metrics life-years gained (LYG), incremental costs (IC) and the incremental cost-effectiveness ratio (ICER). Results: Eleven CEA analyses comparing anastrazole and tamoxifen as ABC treatment were identified. The base model consisted of the following health states: (1) on treatment; (2) off treatment; (3) local recurrence; (4) metastatic disease; (5) death due to breast cancer; and (6) death due to other causes. The base model estimates of anastrazole versus tamoxifen for the LYG, IC and ICER were 0.263 years, €3,647 and €13,868/LYG, respectively. In the published models that were evaluated, differences in model structure included the addition of different recurrence health states, and associated transition rates were identified. Differences in parameterization were related to the incidences of recurrence, local recurrence to metastatic disease, and metastatic disease to death. The separate impact of these model components on the LYG ranged from 0.207 to 0.356 years, while incremental costs ranged from €3,490 to €3,714 and ICERs ranged from €9,804/LYG to €17,966/LYG. When we re-analyzed the published CEAs in our framework by including their respective model properties, the LYG ranged from 0.207 to 0.383 years, IC ranged from €3,556 to €3,731 and ICERs ranged from €9,683/LYG to €17,570/LYG. Conclusion:

Catch-up growth in the first two years of life in Extremely Low Birth Weight (ELBW) infants is associated with lower body fat in young adolescence

Aim To investigate growth patterns and anthropometrics in former extremely low birth weight (ELBW, <1000 g) children and link these outcomes to neurocognition and body

Retinal and Renal Microvasculature in Relation to Central Hemodynamics in 11‐Year‐Old Children Born Preterm or At Term

Background Prematurity disrupts the perinatal maturation of the microvasculature and macrovasculature and confers high risk of vascular dysfunction later in life. No previous studies have investigated the crosstalk between the microvasculature and macrovasculature in childhood. Methods and Results In a case‐control study, we enrolled 55 children aged 11 years weighing \u3c1000 g at birth and 71 matched controls (October 2014–November 2015). We derived central blood pressure (BP) wave by applanation tonometry and calculated the forward/backward pulse waves by an automated pressure–based wave separation algorithm. We measured the renal resistive index by pulsed wave Doppler and the central retinal arteriolar equivalent by computer‐assisted program software. Compared with controls, patients had higher central systolic BP (101.5 versus 95.2 mm Hg, P\u3c0.001) and backward wave amplitude (15.5 versus 14.2 mm Hg, P=0.029), and smaller central retinal arteriolar equivalent (163.2 versus 175.4 µm, P\u3c0.001). In multivariable analyses, central retinal arteriolar equivalent was smaller with higher values (+1 SD) of central systolic BP (−2.94 µm; 95% CI, −5.18 to −0.70 µm [P=0.011]) and forward (−2.57 µm; CI, −4.81 to −0.32 µm [P=0.026]) and backward (−3.20 µm; CI, −5.47 to −0.94 µm [P=0.006]) wave amplitudes. Greater renal resistive index was associated with higher backward wave amplitude (0.92 mm Hg, P=0.036). Conclusions In childhood, prematurity compared with term birth is associated with higher central systolic BP and forward/backward wave amplitudes. Higher renal resistive index likely moves reflection points closer to the heart, thereby explaining the inverse association of central retinal arteriolar equivalent with central systolic BP and backward wave amplitude. These observations highlight the crosstalk between the microcirculation and macrocirculation in children. Registration URL: http://www.clinicaltrials.gov. Unique Identifier: NCT02147457

The QT_c-Bazett Interval in Former Very Preterm Infants in Adolescence and Young Adulthood is Not Different from Term-Born Controls

Introduction: Although relevant for precision pharmacovigilance, there are conflicting data on whether former preterm birth is associated with QTc-Bazett prolongation in later life. Methods: To explore QTc-Bazett interval differences between former preterm and/or extremely low birth weight (ELBW) cases and term-born controls in adolescence and young adulthood, we analyzed pooled individual data after a structured search on published cohorts. To test the absence of a QTc-Bazett difference, a non-inferiority approach was applied (one-sided, upper limit of the 95% confidence interval [CI] mean QTc-Bazett difference, 5 and 10 ms). We also investigated the impact of characteristics, either perinatal or at assessment, on QTc-Bazett in the full dataset (cases and controls). Data were reported as median and range. Results: The pooled dataset contained 164 former preterm and/or ELBW (cases) and 140 controls born full-term from three studies. The median QTc-Bazett intervals were 409 (335–490) and 410 (318–480) ms in cases and controls. The mean QTc-Bazett difference was 1 ms, with an upper 95% CI of 6 ms (p &gt; 0.05 and p &lt; 0.01 for 5 and 10 ms, respectively). In the full dataset, females had a significantly longer QTc-Bazett than males (415 vs. 401 ms; p &lt; 0.0001). Conclusions: QTc-Bazett intervals are not significantly different between former preterm and/or ELBW cases and term-born controls, and we rejected a potential prolongation &gt; 10 ms in cases. When prescribing QTc-prolonging drugs, pharmacovigilance practices in this subpopulation should be similar to the general public (NCT05243537).</p

Association between cognition and the retinal microvasculature in 11-year old children born preterm or at term

Background: Retinal microvessels can be visualized non-invasively and mirror the status of the cerebral microvasculature. Aims: To investigate whether in young children born prematurely or at term cognitive performance is related to retinal microvascular traits. Study design, subjects: In 93 prematurely born infants (birth weight < 1000 g) and 87 controls born at term, we measured head circumference (HC) and determined intelligence quotient (IQ) by combining matrix reasoning and spatial span (Wechsler Non-Verbal test, Dutch version) and post-processed retinal photographs using Singapore I Vessel Assessment software (version 3.6). Outcome measures, results: Compared with controls, cases had smaller HC (51.7 vs 53.4 cm; p < 0.001), lower IQ (93.9 vs 109.2; p < 0.001), smaller retinal arteriolar (CRAE; 162.7 vs 174.0 μm; p < 0.001) and venular (CRVE; 234.9 vs 242.8 μm; p = 0.003) diameters and CRAE/CRVE ratio (0.69 vs 0.72; p = 0.001). A 1-SD decrease in CRAE was associated with smaller HC (−0.53 cm; p < 0.001) and lower total IQ (−3.74; p < 0.001), matrix reasoning (−1.77; p = 0.004) and spatial span (−2.03; p = 0.002). These associations persisted after adjustment for sex and age and risk factors for cognitive impairment, including blood pressure, body mass index and parental educational attainment. Conclusions: HC, total IQ, matrix reasoning and spatial span decrease with smaller retinal arteriolar diameter. Our findings suggest that maldevelopment of the cerebral microcirculation, as mirrored by the retinal microvasculature, has lasting effects on the growth of the brain and cognitive performance of prematurely born children

Reproducibility of Retinal Microvascular Traits Decoded by the Singapore i Vessel Assessment Software Across the Human Age Range

Retinal microvascular traits predict adverse health outcomes. The Singapore I Vessel Assessment (SIVA) software improved automated postprocessing of retinal photographs. In addition to microvessel caliber, it generates measure