Physical Activity and Systemic Biomarkers in Persons With COPD: Insights from a Web-Based Pedometer-Mediated Intervention.

Background: The relationships between physical activity (PA) and exercise performance and systemic biomarkers in persons with COPD have not been well characterized. The impact of PA promotion on biomarkers reflecting myocardial stress, systemic inflammation, and muscle injury is unclear. Methods: This secondary analysis used three previously published studies in persons with COPD, two examined a PA intervention that promoted community-based walking for 3 months, to explore these relationships. PA (daily step counts) and exercise performance (6-minute walk test; 6MWT) were assessed. Serum N-terminal pro-ß-type natriuretic peptide (NT-proBNP), the soluble receptor for advanced glycation end products (sRAGE), and muscle-type creatine kinase (CKMM) were assayed at baseline and three months. General linear models examined associations between PA/exercise performance and systemic biomarkers at baseline and the effect of the PA intervention on change in biomarkers. Results: Participants included 366 US Veterans - 98% male, mean age 70±8 years, and FEV1 % predicted 59±21%. Lower baseline NT-proBNP, but not sRAGE or CKMM, was associated with higher daily step count (-0.95 pg/ml per 1,000 steps/day, p=.060) and higher 6MWT distance (-0.80 pg/ml per 100 meters, p=.001). Change in daily step count, but not 6MWT, was significantly greater in the intervention (789±1,864) compared to the control group (-174±1,448; p=.002). The PA intervention had no significant impact on change in the systemic biomarkers. Interpretation: Exercise performance is associated with NT-proBNP in persons with COPD. A 3-month community-based walking intervention is not associated with myocardial stress or muscle injury as assessed by NT-proBNP and CKMM, respectively.

Effectiveness of Fludrocortisone Plus Hydrocortisone versus Hydrocortisone Alone in Septic Shock: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

Rationale: The use of hydrocortisone in adult patients with septic shock is controversial, and the effectiveness of adding fludrocortisone to hydrocortisone remains uncertain. Objectives: To assess the comparative effectiveness and safety of fludrocortisone plus hydrocortisone, hydrocortisone alone, and placebo or usual care in adults with septic shock. Methods: A systematic review and a Bayesian network meta-analysis of peer-reviewed randomized trials were conducted. The primary outcome was all-cause mortality at last follow-up. Treatment effects are presented as relative risks (RRs) with 95% credible intervals (CrIs). Placebo or usual care was the reference treatment. Measurements and Main Results: Among 7,553 references, we included 17 trials (7,688 patients). All-cause mortality at last follow-up was lowest with fludrocortisone plus hydrocortisone (RR, 0.85; 95% CrI, 0.72-0.99; 98.3% probability of superiority, moderate-certainty evidence), followed by hydrocortisone alone (RR, 0.97; 95% CrI, 0.87-1.07; 73.1% probability of superiority, low-certainty evidence). The comparison of fludrocortisone plus hydrocortisone versus hydrocortisone alone was based primarily on indirect evidence (only two trials with direct evidence). Fludrocortisone plus hydrocortisone was associated with a 12% lower risk of all-cause mortality compared with hydrocortisone alone (RR, 0.88; 95% CrI, 0.74-1.03; 94.2% probability of superiority, moderate-certainty evidence). Conclusions: In adult patients with septic shock, fludrocortisone plus hydrocortisone was associated with lower risk of all-cause mortality at last follow-up than placebo and hydrocortisone alone. The scarcity of head-to-head trials comparing fludrocortisone plus hydrocortisone versus hydrocortisone alone led our network meta-analysis to rely primarily on indirect evidence for this comparison. Although we undertook several sensitivity analyses and assessments, these findings should be considered while also acknowledging the heterogeneity of included trials.

Emerging therapies and management for neonatal encephalopathy-controversies and current approaches.

Neonatal encephalopathy (NE) continues to have a major impact on newborn survival and neurodevelopmental outcomes worldwide. In high-income settings, therapeutic hypothermia is the only established standard treatment for neonates with moderate-to-severe NE, with compelling evidence that cooling reduces mortality and major neurodevelopmental impairment in survivors. Despite therapeutic hypothermia, a significant proportion of cooled infants continue to suffer long-term disability from brain injury. Innovative therapies offer the possibility of further improving neurodevelopmental outcomes by working synergistically with therapeutic hypothermia to decrease hypoxia-ischemia-induced excitotoxicity, prevent progression to secondary energy failure, and in some cases, promote neuroregeneration in the developing neonatal brain. This review discusses emerging NE therapies currently under investigation, offers insight into controversies surrounding various approaches to clinical care during therapeutic hypothermia, and identifies ongoing knowledge deficits that hinder attainment of optimal outcomes for neonates with NE.

Opioid and benzodiazepine use during therapeutic hypothermia in encephalopathic neonates.

OBJECTIVES: To evaluate the use of sedatives and analgesics during therapeutic hypothermia in encephalopathic neonates and assess associations between medication exposure and hospital outcomes. STUDY DESIGN: We identified neonates ≥35 weeks gestational age treated with therapeutic hypothermia at 125 neonatal intensive care units between 2007 and 2015. We compared characteristics and hospital outcomes between unexposed neonates and neonates exposed to opioids and/or benzodiazepines. RESULTS: Opioids were administered to 1 677/2 621 (64%) neonates, and exposure increased from 38% in 2008 to 68% in 2015. Sedation/analgesia varied widely between centers. Opioid-exposed neonates experienced greater durations of respiratory support and were more likely to receive inotropes and inhaled nitric oxide. Mortality during postnatal days 0-3 was lower among opioid-exposed neonates (31/625 [5%]) than unexposed neonates (64/714 [9%]). CONCLUSIONS: Sedation/analgesia during therapeutic hypothermia is prevalent but not uniform across centers. Prospective studies are needed to assess if exposure independently predicts intensity and duration of physiologic support.

Historic condition in a modern child with autism.

CASE: Haven is an 11-year-old primary care patient who you have followed since her birth. She was the 9 lb 6 oz product of a 38-week gestation complicated by maternal hypertension and seizure disorder treated with tegretol. Her delivery and neonatal course were uneventful. She was diagnosed with austistic disorder at age 2 years, at which time she used no functional language or gestures, had repetitive motor mannerisms, and limited eye contact. She had strong tactile sensory aversions. Her diet was very restricted including only banana yogurt and drinking milk and apple juice for the first several years of life. She was followed by a developmental-behavioral pediatrician approximately annually through age 8 years and then more frequently. She was healthy other than lead exposure (maximum serum level 18 at age 3 years) and multiple febrile seizures with other possible absence episodes. Her development remained very delayed with use of single words and short phrases. She developed multiple repetitive, anxious, obsessive behaviors (picking up lint, organizing, cleaning, and freezing in certain postures) that were treated with a selective serotonin reuptake inhibitors fluvoxamine. Sensory issues were ongoing, with restrictive eating (primarily peanut butter and jelly sandwiches, cereal bars, milk, and a kiwi-strawberry drink). She took a liquid multivitamin until age 8.At age 11 years, 3 weeks prior to admission, Haven developed acute loss of ambulation over the course of 1 day, initially dragging her right leg, and then refusing to walk and her parents brought her in to see you. She had fever, vomiting, and general weakness. She developed extensive bruising over her legs, especially in the popliteal fossae. She was also noted to have friability and dark discoloration of her gums. Initially, you suspected a post-viral syndrome and close monitoring. She was seen twice in the next 2 weeks in a local emergency room where her erythrocyte sedimentation rate was reported to be elevated and juvenile rheumatoid arthritis or a reaction to fluvoxamine were suspected. Antibiotics were also prescribed for gingivitis. She was seen by an orthopedist who felt it was not an orthopedic issue and leg films were unremarkable. With her second emergency room visit, she was transferred to a tertiary medical center and admitted for further evaluation. Where would you go from here?