Regulation of iron homeostasis through the erythroferrone-hepcidin axis in sickle cell disease

Sickle cell disease (SCD) has a distinct pattern of transfusional iron overload (IO) when compared to transfusion-dependent β-thalassaemia major (TDT). We conducted a single institution prospective study to evaluate plasma biomarkers of iron regulation and inflammation in patients with SCD with IO (SCD IO cases, n = 22) and without IO (SCD non-IO cases, n = 11), and non-SCD controls (n = 13). Hepcidin was found to be inappropriately low, as evidenced by a significantly higher median hepcidin/ferritin ratio in non-SCD controls compared to SCD IO cases (0·3 vs. 0·02, P < 0·0001) and SCD non-IO cases (0·3 vs. 0·02, P < 0·0001), suggesting that certain inhibitory mechanism (s) work to suppress hepcidin in SCD. As opposed to the SCD non-IO state, where hepcidin shows a strong significant positive correlation with ferritin (Spearman ρ = 0·7, P = 0·02), this correlation was lost when IO occurs (Spearman ρ = −0·2, P = 0·4). Although a direct non-linear correlation between erythroferrone (ERFE) and hepcidin did not reach statistical significance both in the IO (Spearman ρ = −0·4, P = 0·08) and non-IO state (Spearman ρ = −0·6, P = 0·07), patients with highest ERFE had low hepcidin levels, suggesting that ERFE contributes to hepcidin regulation in some patients. Our results suggest a multifactorial mechanism of hepcidin regulation in SCD.     

Protocols,practices, and needs for investigating sudden unexpected infant deaths

Understanding case identification practices, protocols, and training needs of medical examiners and coroners (MEC) may inform efforts to improve cause-of-death certification. We surveyed a U.S.-representative sample of MECs and described investigation practices and protocols used in certifying sudden unexpected infant deaths (SUID). We also identified MEC training and resource needs. Of the 377 respondents, use of the SUID Investigation Reporting Form or an equivalent was 89% for large, 87% for medium, and 52% for small jurisdictions. Routine completion of infant medical history, witness interviews, autopsy, photos or videos, and family social history for infant death investigations was ≥80%, but routine scene re-creation with a doll was 30% in small, 64% in medium, and 59% in large offices. Seventy percent of MECs reported infant death investigation training needs. Increased training and use of standardized practices may improve SUID cause-of-death certification, allowing us to better understand SUID.     

Pediatric Healthcare Professionals’ Views on Autism Spectrum Disorder Screening at 12–18 Months

This study explored North Carolina pediatric healthcare professional’s (PHP) perceptions of screening 12–18 month old infants for Autism Spectrum Disorder (ASD). Eight focus groups (66 PHPs) were conducted across practice settings. The purpose was to explore PHP’s perspectives to: inform development of ASD screening tools and ultimately impact their use in PHP settings. PHPs reported concerns, barriers, and the need for research to support early ASD screening. Additionally, they expressed the need for: (a) clear “red flags” of ASD for 12–18 month olds; (b) socioculturally sensitive and effective screening tools; (c) effective early interventions; (d) systems to handle potential increases in referrals; and (e) continuing education. PHPs also demonstrated preferences about screening tool characteristics and processes for enhancing screening efforts.     

PEER umbrella systematic review of systematic reviews: Management of osteoarthritis in primary care

ObjectiveTo determine how many patients with chronic osteoarthritis pain respond to various non-surgical treatments.Data sourcesPubMed and the Cochrane Library.Study selection Published systematic reviews of randomized controlled trials (RCTs) that included meta-analysis of responder outcomes for at least 1 of the following interventions were included: acetaminophen, oral nonsteroidal anti-inflammatory drugs (NSAIDs), topical NSAIDs, serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants, cannabinoids, counseling, exercise, platelet-rich plasma, viscosupplementation, glucosamine, chondroitin, intra-articular corticosteroids, rubefacients, or opioids.Synthesis In total, 235 systematic reviews were included. Owing to limited reporting of responder meta-analyses, a post hoc decision was made to evaluate individual RCTs with responder analysis within the included systematic reviews. New meta-analyses were performed where possible. A total of 155 RCTs were included. Interventions that led to more patients attaining meaningful pain relief compared with control included exercise (risk ratio [RR] of 2.36; 95% CI 1.79 to 3.12), intra-articular corticosteroids (RR = 1.74; 95% CI 1.15 to 2.62), SNRIs (RR = 1.53; 95% CI 1.25 to 1.87), oral NSAIDs (RR = 1.44; 95% CI 1.36 to 1.52), glucosamine (RR = 1.33; 95% CI 1.02 to 1.74), topical NSAIDs (RR = 1.27; 95% CI 1.16 to 1.38), chondroitin (RR = 1.26; 95% CI 1.13 to 1.41), viscosupplementation (RR = 1.22; 95% CI 1.12 to 1.33), and opioids (RR = 1.16; 95% CI 1.02 to 1.32). Preplanned subgroup analysis demonstrated no effect with glucosamine, chondroitin, or viscosupplementation in studies that were only publicly funded. When trials longer than 4 weeks were analyzed, the benefits of opioids were not statistically significant.ConclusionInterventions that provide meaningful relief for chronic osteoarthritis pain might include exercise, intra-articular corticosteroids, SNRIs, oral and topical NSAIDs, glucosamine, chondroitin, viscosupplementation, and opioids. However, funding of studies and length of treatment are important considerations in interpreting these data.     

Photoaging

Given the many ways our culture promotes deeply tanned skin as a symbol of beauty, health, and even happiness, physicians face an uphill battle in promoting the healthy aspects of a pale complexion. Not only can excessive solar exposure accelerate and intensify aging in skin, it can also lead to serious health risks. Drs Browder and Beers tell why photoaging happens and how to prevent it.