How best to capture the respiratory consequences of prematurity?

Chronic respiratory morbidity is a common complication of premature birth, generally defined by the presence of bronchopulmonary dysplasia, both clinically and in trials of respiratory therapies. However, recent data have highlighted that bronchopulmonary dysplasia does not correlate with chronic respiratory morbidity in older children born preterm. Longitudinally evaluating pulmonary morbidity from early life through to childhood provides a more rational method of defining the continuum of chronic respiratory morbidity of prematurity, and offers new insights into the efficacy of neonatal respiratory interventions. The changing nature of preterm lung disease suggests that a multimodal approach using dynamic lung function assessment will be needed to assess the efficacy of a neonatal respiratory therapy and predict the long-term respiratory consequences of premature birth. Our aim is to review the literature regarding the long-term respiratory outcomes of neonatal respiratory strategies, the difficulties of assessing dynamic lung function in infants, and potential new solutions

[Assessment of pulmonary function in a follow-up of premature infants: our experience].

Respiratory diseases are a major cause of morbidity in neonates, especially preterm infants; a long term complication of prematurity such as bronchopulmonary dysplasia (BPD) is particularly relevant today. The exact role of the Pulmonary Function Test (PFT) in this area is not yet well defined; the PFT in newborns and infants - in contrast to what happens in uncooperative children and adults - are routinely used only in a few centers. The assessment of pulmonary function in newborns and infants, however, is nowadays possible with the same reliability that in cooperative patients with the possibility to extend the assessment of polmonary function from bench to bed. The assessment of pulmonary function must be carried out with non invasive and safe methods, at the bedside, with the possibility of continuous monitoring and providing adequate calculation and management of data. The ability to assess lung function helps to define the mechanisms of respiratory failure, improving the treatment and its effects and is therefore a useful tool in the follow-up of newborn and infant with pulmonary disease

Mitigating Increased Driving after the COVID-19 Pandemic: An Analysis on Mode Share, Travel Demand, and Public Transport Capacity

Reduced transit capacity to accommodate social distancing during the COVID-19 pandemic was a sudden constraint that along with a large reduction in total travel volume and a shift in activity patterns contributed to abrupt changes in transportation mode shares across cities worldwide. There are major concerns that as the total travel demand rises back toward prepandemic levels, the overall transport system capacity with transit constraints will be insufficient for the increasing demand. This paper uses city-level scenario analysis to examine the potential increase in post-COVID-19 car use and the feasibility of shifting to active transportation, based on prepandemic mode shares and varying levels of reduction in transit capacity. An application of the analysis to a sample of cities in Europe and North America is presented. Mitigating an increase in driving requires a substantial increase in active transportation mode share, particularly in cities with high pre-COVID-19 transit ridership; however, such a shift may be possible based on the high percentage of short-distance motorized trips. The results highlight the importance of making active transportation attractive and reinforce the value of multimodal transportation systems as a strategy for urban resilience. This paper provides a strategic planning tool for policy makers facing challenging transportation system decisions in the aftermath of the COVID-19 pandemic

Tidal Breathing Measurements in Former Preterm Infants: A Retrospective Longitudinal Study

To investigate in preterm infants with or without bronchopulmonary dysplasia (BPD the trajectory of tidal breathing flow-volume (TBFV) parameters in the first two years of life; the association between TBFV parameters and perinatal risk factors; and the predictive value of TBFV parameters for re-hospitalizations due to respiratory infections and wheeze,

HIPK2 Controls Cytokinesis and Prevents Tetraploidization by Phosphorylating Histone H2B at the Midbody

Failure in cytokinesis, the final step in cell division, by generating tetra- and polyploidization promotes chromosomal instability, a hallmark of cancer. Here we show that HIPK2, a kinase involved in cell fate decisions in development and response to stress, controls cytokinesis and prevents tetraploidization through its effects on histone H2B. HIPK2 binds and phosphorylates histone H2B at S14 (H2B-S14 P), and the two proteins colocalize at the midbody. HIPK2 depletion by targeted gene disruption or RNA interference results in loss of H2B-S14 P at the midbody, prevention of cell cleavage, and tetra- and polyploidization. In HIPK2 null cells, restoration of wild-type HIPK2 activity or expression of a phosphomimetic H2B-S14D derivative abolishes cytokinesis defects and rescues cell proliferation, showing that H2B-S14 P is required for a faithful cytokinesis. Overall, our data uncover mechanisms of a critical HIPK2 function in cytokinesis and in the prevention of tetraploidization. © 2012 Elsevier Inc

Brivaracetam as add‐on treatment in focal epilepsy: A real‐world time‐based analysis

The study assessed the clinical response to add-on brivaracetam (BRV) in real-world practice by means of time-to-baseline seizure count methodology. Patients with focal epilepsy who were prescribed add-on BRV were identified. Primary endpoint was the time-to-baseline seizure count defined as the number of days until each patient experienced the number of focal seizures that occurred in the 90 days before BRV initiation. Subgroup analysis was performed according to levetiracetam (LEV) status (naive vs prior use). Three-hundred eighty-seven patients were included. The overall median time-to-baseline seizure count was 150 (95% confidence interval [CI] = 130-175) days. The median time-to-baseline seizure count was 198 (lower limit of 95% CI = 168) days for LEV-naive patients, 126 (95% CI = 105-150) days for patients with prior LEV use and withdrawal due to insufficient efficacy, and 170 (95% CI = 128-291) days for patients who discontinued LEV due to adverse events (P = .002). The number of prior antiseizure medications (adjusted hazard ratio [adjHR] = 1.07, 95% CI = 1.02-1.13, P = .009) and baseline monthly seizure frequency (adjHR = 1.004, 95% CI = 1.001-1.008, P = .028) were independently associated with the primary endpoint. Add-on BRV improved seizure control in LEV-naive and LEV-prior patients. The time-to-baseline seizure count represents an informative endpoint alongside traditional study outcomes and designs

Brivaracetam as add-on treatment in patients with post-stroke epilepsy: real-world data from the BRIVAracetam add-on First Italian netwoRk Study (BRIVAFIRST)

Objective: Post-stroke epilepsy (PSE) is one of the most common causes of acquired epilepsy and accounts for about 10-15% of all newly diagnosed epilepsy cases. However, evidence about the clinical profile of antiseizure medications in the PSE setting is currently limited. Brivaracetam (BRV) is a rationally developed compound characterized by high-affinity binding to synaptic vesicle protein 2A. The aim of this study was to assess the 12-month effectiveness and tolerability of adjunctive BRV in patients with PSE treated in a real-world setting. Methods: This was a subgroup analysis of patients with PSE included in the BRIVAracetam add-on First Italian netwoRk Study (BRIVAFIRST). The BRIVAFIRST was a 12-month retrospective, multicentre study including adult patients prescribed adjunctive BRV. Effectiveness outcomes included the rates of seizure response (≥50% reduction in baseline seizure frequency), seizure-freedom, and treatment discontinuation. Safety and tolerability outcomes included the rate of treatment discontinuation due to adverse events (AEs) and the incidence of AEs. Results: Patients with PSE included in the BRIVAFIRST were 75 and had a median age of 57 (interquartile range, 42-66) years. The median daily doses of BRV at 3, 6, and 12 months from starting treatment were 100 (100-150) mg, 125 (100-200) mg and 100 (100-200) mg, respectively. At 12 months, 32 (42.7%) patients had a reduction in their baseline seizure frequency by at least 50%, and the seizure freedom rates was 26/75 (34.7%). During the 1-year study period, 10 (13.3%) patients discontinued BRV. The reasons of treatment withdrawal were insufficient efficacy in 6 (8.0%) patients and poor tolerability in 4 (5.3%) patients. Adverse events were reported by 13 (20.3%) patients and were rated as mild in 84.6% and moderate in 15.4% of cases. Significance: Adjunctive BRV was efficacious and generally well-tolerated when used in patients with PSE in clinical practice. Adjunctive BRV can be a suitable therapeutic option for patients with PSE