2,3-Dihydrobellendine

Association Between Early Low-Dose Hydrocortisone Therapy in Extremely Preterm Neonates and Neurodevelopmental Outcomes at 2 Years of Age.[Pubmed:28384828]

JAMA. 2017 Apr 4;317(13):1329-1337.

Importance: Dexamethasone to prevent bronchopulmonary dysplasia in very preterm neonates was associated with adverse neurodevelopmental events. Early low-dose hydrocortisone treatment has been reported to improve survival without bronchopulmonary dysplasia but its safety with regard to neurodevelopment remains to be assessed. Objective: To assess whether early hydrocortisone therapy in extremely preterm infants is associated with neurodevelopmental impairment at 2 years of age. Design, Setting, and Participants: An exploratory secondary analysis of the PREMILOC (Early Low-Dose Hydrocortisone to Improve Survival without Bronchopulmonary Dysplasia in Extremely Preterm Infants) randomized clinical trial conducted between 2008 and 2014 in 21 French neonatal intensive care units. Randomization was stratified by gestational age groups. Neurodevelopmental assessments were completed from 2010 to 2016. Interventions: After birth, patients were randomly assigned to receive placebo or hydrocortisone (0.5 mg/kg twice per day for 7 days, followed by 0.5 mg/kg per day for 3 days). Main Outcomes and Measures: The prespecified exploratory secondary outcome of neurodevelopmental impairment was based on a standardized neurological examination and the revised Brunet-Lezine scale (global developmental quotient score and subscores; mean norm, 100 [SD, 15]). The minimal clinically important difference on the global developmental quotient was 5 points. Results: Of 1072 neonates screened, 523 were assigned to hydrocortisone (n = 256) or placebo (n = 267) and 406 survived to 2 years of age. A total of 379 patients (93%; 46% female) were evaluated (194 in the hydrocortisone group and 185 in the placebo group) at a median corrected age of 22 months (interquartile range, 21-23 months). The distribution of patients without neurodevelopmental impairment (73% in the hydrocortisone group vs 70% in the placebo group), with mild neurodevelopmental impairment (20% in the hydrocortisone group vs 18% in the placebo group), or with moderate to severe neurodevelopmental impairment (7% in the hydrocortisone group vs 11% in the placebo group) was not statistically significantly different between groups (P = .33). The mean global developmental quotient score was not statistically significantly different between groups (91.7 in the hydrocortisone group vs 91.4 in the placebo group; between-group difference, 0.3 [95% CI, -2.7 to 3.4]; P = .83). The incidence of cerebral palsy or other major neurological impairments was not significantly different between groups. Conclusions and Relevance: In this exploratory analysis of secondary outcomes of a randomized clinical trial of extremely preterm infants, early low-dose hydrocortisone was not associated with a statistically significant difference in neurodevelopment at 2 years of age. Further randomized studies are needed to provide definitive assessment of the neurodevelopmental safety of hydrocortisone in extremely preterm infants. Trial Registration: clinicaltrials.gov Identifier: NCT00623740.

Determining the 2-Dimensional Threshold for Perception of Artificial-Appearing Lips.[Pubmed:28384792]

JAMA Facial Plast Surg. 2017 Sep 1;19(5):392-398.

Importance: Recognizing the perceptual threshold for artificial-appearing lips is important to avoid an undesirable outcome of treatment. Objective: To characterize the quantitative measurements for the perceptual threshold of artificial- and unnatural-appearing lips. Design, Setting, and Participants: Photographs of a female model's lips were digitally altered incrementally in 5 sets of features (the upper lip, lower lip, upper and lower lips, and shape of the Cupid's bow). From December 1, 2013, to January 30, 2014, participants viewed the photographs in random sequence using an online survey and responded to 2 questionnaires after each photograph. The participants were prompted to respond whether each altered photograph of the lips appeared to have received any cosmetic treatment, and whether the lips looked attractive and natural or artificial and unnatural. The measurement of each lip at which 50% of the observers perceived the lips as being treated and 50% of the observers perceived the lips as being artificial was determined. The difference in these 2 measurements was defined as dTA50, which represents the threshold differential between the perception of treated lips and artificial lips for 50% of the observers. Main Outcomes and Measures: Survey responses of the participants to the appearance of the lips in the photographs. Results: A total of 98 participants (76 females and 22 males; mean age, 42 years) provided usable responses to the survey. Each area of the lips had a unique quantitative measurement at which the observers perceived the lips as being treated and artificial. Enhancement of the upper lip alone had a narrower margin for artificial appearance (dTA50, 0.9 mm) compared with enhancement of both the upper and lower lips (dTA50, 1.5 mm). Any alteration to the Cupid's bow resulted in the narrowest margin for artificial appearance (dTA50, 0.3 mm). The difference in the perceptual threshold between the age of the observers was the most significant for the upper lip. Conclusions and Relevance: The perceptual threshold for treated and/or artificial appearance is unique for each area of the lips. Level of Evidence: NA.