Current guidelines, initially published in 1995, recommend antenatal corticosteroids for mothers with preterm labor from 24 to 34 weeks' gestational age, but not before 24 weeks due to lack of data. ...However, many infants born before 24 weeks' gestation are provided intensive care.
To determine if use of antenatal corticosteroids is associated with improvement in major outcomes for infants born at 22 and 23 weeks' gestation.
Cohort study of data collected prospectively on inborn infants with a birth weight between 401 g and 1000 g (N = 10,541) born at 22 to 25 weeks' gestation between January 1, 1993, and December 31, 2009, at 23 academic perinatal centers in the United States. Certified examiners unaware of exposure to antenatal corticosteroids performed follow-up examinations on 4924 (86.5%) of the infants born between 1993 and 2008 who survived to 18 to 22 months. Logistic regression models generated adjusted odds ratios (AORs), controlling for maternal and neonatal variables.
Mortality and neurodevelopmental impairment at 18 to 22 months' corrected age.
Death or neurodevelopmental impairment at 18 to 22 months was significantly lower for infants who had been exposed to antenatal corticosteroids and were born at 23 weeks' gestation (83.4% with exposure to antenatal corticosteroids vs 90.5% without exposure; AOR, 0.58 95% CI, 0.42-0.80), at 24 weeks' gestation (68.4% with exposure to antenatal corticosteroids vs 80.3% without exposure; AOR, 0.62 95% CI, 0.49-0.78), and at 25 weeks' gestation (52.7% with exposure to antenatal corticosteroids vs 67.9% without exposure; AOR, 0.61 95% CI, 0.50-0.74) but not in those infants born at 22 weeks' gestation (90.2% with exposure to antenatal corticosteroids vs 93.1% without exposure; AOR, 0.80 95% CI, 0.29-2.21). If the mothers had received antenatal corticosteroids, the following events occurred significantly less in infants born at 23, 24, and 25 weeks' gestation: death by 18 to 22 months; hospital death; death, intraventricular hemorrhage, or periventricular leukomalacia; and death or necrotizing enterocolitis. For infants born at 22 weeks' gestation, the only outcome that occurred significantly less was death or necrotizing enterocolitis (73.5% with exposure to antenatal corticosteroids vs 84.5% without exposure; AOR, 0.54 95% CI, 0.30-0.97).
Among infants born at 23 to 25 weeks' gestation, antenatal exposure to corticosteroids compared with nonexposure was associated with a lower rate of death or neurodevelopmental impairment at 18 to 22 months.
Physical activity during menopause can be effective in reducing the physiological changes associated with reproductive aging that increase risks for noncommunicable diseases, yet many women do not ...meet the recommendations for physical activity.
This study aimed to synthesize factors influencing physical activity for women across menopausal transition phases using a socioecological approach.
The Preferred Reporting Items for Systematic Reviews and Meta-Analysis was used to systematically search 10 databases between 2001 and 2021. A comprehensive search strategy was used to identify studies on physical activity of women in various stages of menopause. A socioecological model was used to categorize the reported barriers and enablers.
Twenty studies met the inclusion criteria. The findings highlight several intrapersonal barriers such as existing health complaints versus enablers such as awareness of the health benefits of physical activity during menopause. Ensuring women's safety, preventing injury, and enhancing exercise self-efficacy were important components of programs. Social support was also an important enabler of women's engagement in activities.
Several barriers and enablers were identified and can inform practitioners and future interventions to encourage physical activity among women in various stages of menopause. For instance, when encouraging physical activity during menopause, practitioners should consider other health complaints, safety, and injury prevention while discussing the benefits of physical activity related to managing menopausal symptoms. There was a lack of theoretically informed studies exploring the barriers and enablers to physical activity for women in various stages of menopause; thus, research designs may not have fully accounted for influences. Future research that combines socioecological and individual theories of behavior is needed to comprehensively understand the complexity of physical activity among women across the menopausal transition.
Objective To determine whether anti-reflux medications reduce bradycardia episodes attributed to clinically suspected gastroesophageal reflux (GER). Study design We conducted a masked trial comparing ...metoclopramide, 0.2 mg/kg/dose q 6 hours, and ranitidine, 2 mg/kg/dose q 8 hours, with saline placebo. Each infant served as his own control. Preterm infants having >3 bradycardia episodes per 2 days were eligible if the clinician intended to begin anti-reflux medications for bradycardia attributed to GER. Results The mean (SD) birth weight was 1238 (394) g and gestational age was 29 (3) weeks. Eighteen infants were enrolled at 35 (22) days of age. There were 4.6 (3.1) and 3.6 (2.7) bradycardia episodes per day in the drug and placebo periods, respectively. The mean difference (drug minus placebo) was 0.94 (95% CI, 0.04 to 1.95) ( P = .04 by t test). There was a decrease in bradycardia episodes over time ( P < .001 by nonparametric repeated-measures analysis of variance). Conclusions Anti-reflux medications did not reduce, and may have increased, bradycardia episodes in preterm infants with GER. Because there was an improvement of bradycardia episodes over time, unrelated to treatment, unmasked therapeutic trials of medications are likely to lead to misleading conclusions.
To compare the effects of stress dose hydrocortisone therapy with placebo on survival without neurodevelopmental impairments in high-risk preterm infants.
We recruited 64 extremely low birth weight ...(birth weight ≤1000 g) infants between the ages of 10 and 21 postnatal days who were ventilator-dependent and at high-risk for bronchopulmonary dysplasia. Infants were randomized to a tapering 7-day course of stress dose hydrocortisone or saline placebo. The primary outcome at follow-up was a composite of death, cognitive or language delay, cerebral palsy, severe hearing loss, or bilateral blindness at a corrected age of 18-22 months. Secondary outcomes included continued use of respiratory therapies and somatic growth.
Fifty-seven infants had adequate data for the primary outcome. Of the 28 infants randomized to hydrocortisone, 19 (68%) died or survived with impairment compared with 22 of the 29 infants (76%) assigned to placebo (relative risk: 0.83; 95% CI, 0.61 to 1.14). The rates of death for those in the hydrocortisone and placebo groups were 31% and 41%, respectively (P = 0.42). Randomization to hydrocortisone also did not significantly affect the frequency of supplemental oxygen use, positive airway pressure support, or need for respiratory medications.
In high-risk extremely low birth weight infants, stress dose hydrocortisone therapy after 10 days of age had no statistically significant effect on the incidence of death or neurodevelopmental impairment at 18-22 months. These results may inform the design and conduct of future clinical trials.
ClinicalTrials.gov NCT00167544.
Opioid continuous infusions are commonly used for end-of-life (EOL) symptoms in hospital settings. However, prescribing practices vary, and even the recent literature contains conflicting protocols ...and guidelines for best practice.
To determine the prevalence of potentially inappropriate opioid infusion use for EOL comfort care at an academic medical center, and determine if inappropriate use is associated with distress.
Through literature review and iterative interdisciplinary discussion, we defined three criteria for “potentially inappropriate” infusion use. We conducted a retrospective, observational study of inpatients who died over six months, abstracting demographics, opioid use patterns, survival time, palliative care (PC) involvement, and evidence of patient/caregiver/staff distress from the electronic medical record.
We identified 193 decedents who received opioid infusions for EOL comfort care. Forty-four percent received opioid infusions that were classified as “potentially inappropriate.” Insufficient use of as-needed intravenous opioid boluses and use of opioid infusions in opioid-naïve patients were the most common problems observed. Potentially inappropriate infusions were associated with more frequent patient (24% vs. 2%; P < 0.001) and staff distress (10% vs. 2%; P = 0.02) and were less common when PC provided medication recommendations (20% vs. 50%; P < 0.001).
Potentially inappropriate opioid infusions are prevalent at our hospital, an academic medical center with an active PC team and existing contracts for in-hospital hospice care. Furthermore, potentially inappropriate opioid infusions are associated with increased patient and staff distress. We are developing an interdisciplinary intervention to address this safety issue.
The International Knockout Mouse Consortium was formed in 2007 to inactivate ("knockout") all protein-coding genes in the mouse genome in embryonic stem cells. Production and characterization of ...these mice, now underway, has generated and phenotyped 3,100 strains with knockout alleles. Skin and adnexa diseases are best defined at the gross clinical level and by histopathology. Representative retired breeders had skin collected from the back, abdomen, eyelids, muzzle, ears, tail, and lower limbs including the nails. To date, 169 novel mutant lines were reviewed and of these, only one was found to have a relatively minor sebaceous gland abnormality associated with follicular dystrophy. The B6N(Cg)-Far2tm2b(KOMP)Wtsi/2J strain, had lesions affecting sebaceous glands with what appeared to be a secondary follicular dystrophy. A second line, B6N(Cg)-Ppp1r9btm1.1(KOMP)Vlcg/J, had follicular dystrophy limited to many but not all mystacial vibrissae in heterozygous but not homozygous mutant mice, suggesting that this was a nonspecific background lesion. We discuss potential reasons for the low frequency of skin and adnexal phenotypes in mice from this project in comparison to those seen in human Mendelian diseases, and suggest alternative approaches to identification of human disease-relevant models.
The innate immune response to pathogenic challenge is a complex, multi-staged process involving thousands of genes. While numerous transcription factors that act as master regulators of this response ...have been identified, the temporal complexity of gene expression changes in response to pathogen-associated molecular pattern receptor stimulation strongly suggest that additional layers of regulation remain to be uncovered. The evolved pathogen response program in mammalian innate immune cells is understood to reflect a compromise between the probability of clearing the infection and the extent of tissue damage and inflammatory sequelae it causes. Because of that, a key challenge to delineating the regulators that control the temporal inflammatory response is that an innate immune regulator that may confer a selective advantage in the wild may be dispensable in the lab setting. In order to better understand the complete transcriptional response of primary macrophages to the bacterial endotoxin lipopolysaccharide (LPS), we designed a method that integrates temporally resolved gene expression and chromatin-accessibility measurements from mouse macrophages. By correlating changes in transcription factor binding site motif enrichment scores, calculated within regions of accessible chromatin, with the average temporal expression profile of a gene cluster, we screened for transcriptional factors that regulate the cluster. We have validated our predictions of LPS-stimulated transcriptional regulators using ChIP-seq data for three transcription factors with experimentally confirmed functions in innate immunity. In addition, we predict a role in the macrophage LPS response for several novel transcription factors that have not previously been implicated in immune responses. This method is applicable to any experimental situation where temporal gene expression and chromatin-accessibility data are available.
Extremely low birth weight (ELBW) infants are at risk for end-organ hypoxia and ischemia. Regional tissue oxygenation of the brain and gut as monitored with near-infrared spectroscopy (NIRS) may ...change with postnatal age, but normal ranges are not well defined.
A prospective study of ELBW preterm infants utilized NIRS monitoring to assess changes in cerebral and mesenteric saturation (Csat and Msat) over the first week after birth. This secondary study of a multicenter trial comparing hemoglobin transfusion thresholds assessed cerebral and mesenteric fractional tissue oxygen extraction (cFTOE and mFTOE) and relationships with perinatal variables.
In 124 infants, both Csat and Msat declined over the first week, with a corresponding increase in oxygen extraction. With lower gestational age, lower birth weight, and 5-min Apgar score ≤5, there was a greater increase in oxygen extraction in the brain compared to the gut. Infants managed with a lower hemoglobin transfusion threshold receiving ≥2 transfusions in the first week had the lowest Csat and highest cFTOE (p < 0.001).
Brain oxygen extraction preferentially increased in more immature and anemic preterm infants. NIRS monitoring may enhance understanding of cerebral and mesenteric oxygenation patterns and inform future protective strategies in the preterm ELBW population.
Simultaneous monitoring of cerebral and mesenteric tissue saturation demonstrates the balance of oxygenation between preterm brain and gut and may inform protective strategies. Over the first week, oxygen saturation of the brain and gut declines as oxygen extraction increases. A low hemoglobin transfusion threshold is associated with lower cerebral saturation and higher cerebral oxygen extraction compared to a high hemoglobin transfusion threshold, although this did not translate into clinically relevant differences in the TOP trial primary outcome. Greater oxygen extraction by the brain compared to the gut occurs with lower gestational age, lower birth weight, and 5-min Apgar score ≤5.
Abstract Purpose Previous research has indicated that patients with anorexia nervosa (AN) or atypical AN with premorbid history of overweight/obesity have greater weight loss and longer illness ...duration than patients with no such history. However, little is known about the association of premorbid overweight/obesity and receiving inpatient medical care during treatment for an eating disorder. Methods Using logistic regression, we sought to determine if history of overweight/obesity was associated with receiving inpatient medical care in a sample of 522 patients (mean age 15.5 years, 88% female) with AN/atypical AN. Results Binary results demonstrated greater percent weight loss (27.4% vs. 16.2%) and higher percent median body mass index (%mBMI, 99.8% vs. 85.2%) at presentation in those with a history of overweight/obesity ( p < .001) but no difference in duration of illness ( p = .09). In models adjusted for demographics and percent weight loss, history of overweight/obesity was associated with lower odds of receiving inpatient medical care (odds ratio .60 95% confidence interval: .45–.80) at 1-year follow-up. However, these associations were no longer significant after adjusting for %mBMI. Mediation results suggest that %mBMI fully mediates the relationship between history of overweight/obesity and inpatient medical care, in that those with a history of overweight/obesity are less likely to receive care due to presenting at a higher weight. Conclusions Our findings suggest that, despite greater degree of weight loss and no difference in duration of illness, participants with a history of overweight/obesity are less likely to receive inpatient medical care.
To determine if iron supplementation of 2 mg/kg per day, in addition to routine iron-fortified formula or mother's milk, increased the hematocrit (Hct) at 36 weeks' postmenstrual age (PMA).
: Infants ...with a birth weight <1500 g who reached 120 mL/kg per day of feedings before 32 weeks' PMA were randomly assigned to iron (multivitamin with iron) or control (multivitamin) from enrollment until 36 weeks' PMA (or discharge, if sooner). Investigators and caregivers were masked. Transfusion guidelines were used. The primary outcome was Hct at 36 weeks' PMA. A nonparametric rank sum analysis was performed so that infants who died before 36 weeks and infants who were transfused could be included in an intention-to-treat analysis. Infants were ranked by death (lowest rank) then by number of transfusions (next lowest ranks). For infants who survived and were not transfused, the 36-week PMA Hct was used for the rank.
One hundred fifty infants were enrolled (76 iron, 74 controls). There were 2 deaths (1 in each group). One hundred other infants (47 iron, 53 controls) received transfusion(s). There was no significant difference in the primary outcome ranking (P = .59), in the number of transfusions per subject (P = .64), or in 36-week Hct (iron mean ± SD, 29.2% ± 4.0%; control, 28.3% ± 4.5%; mean difference and 95% confidence interval 0.9 -0.5 to 2.3; P = .21) or reticulocyte count among survivors. No short-term adverse effects of iron supplementation were observed.
Among infants <1500 g birth weight, iron supplementation, in addition to routine iron intake, did not significantly increase the 36-week Hct or the decrease number of transfusions.
PDF
