Citations

Objectives To address concerns related to the safety profile of both Food and Drug Administration (FDA)–approved and non‐FDA‐approved intranasal corticosteroid (INCS) use in the pediatric population. Data Source Systematic review of MEDLINE, PubMed, and EMBASE databases using comprehensive search strategy, including all INCS formulations and adverse events. The study design was developed using Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines. Additional sources were identified from study references of relevant articles. Review Methods A structured literature search was conducted. Extracted data included age, population size, study design, drug (dosage, route, and frequency), presence of hypothalamic‐pituitary‐adrenal (HPA) axis suppression, ocular symptoms, and growth velocity adverse events. Results A total of 33 studies met inclusion criteria. The studies included use of INCS as nasal sprays and drops. There were no persistent abnormalities noted in cortisol level or intraocular pressure change. Growth velocity reduction was reported in 3 of 10 randomized trials. Meta‐analysis of epistaxis and headache showed no significant difference in the incidence of headache or epistaxis when FDA‐approved INCSs were compared to placebo, with a relative risk of 1.12 (95% CI, 0.77‐1.63; P =. 56) and 0.84 (95% CI, 0.60‐1.18; P =. 32), respectively. Meta‐analysis was not performed for growth velocity, HPA axis suppression, and ocular change. Conclusions INCSs in FDA‐approved routes of administration are generally safe to use in the pediatric population. Use of non‐FDA‐approved INCS drops may increase risk of iatrogenic Cushing’s syndrome. Growth velocity reduction, HPA axis suppression, and visual changes due to INCS are uncommon.

ObjectivesTo address concerns related to the safety profile of both Food and Drug Administration (FDA)–approved and non–FDA‐approved intranasal corticosteroid (INCS) use in the adult population.Data SourceSystematic review of MEDLINE, PubMed, and EMBASE databases using a comprehensive search strategy including all INCS formulations and adverse events. The study design was developed using Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines. Additional sources were identified from study references of relevant articles.Review MethodsA structured literature search was conducted. Each study was graded for level of evidence using the Oxford Centre for Evidence‐Based Medicine. Extracted data included population size, study design, drug (dosage, route, and frequency), presence of hypothalamus pituitary axis suppression, ocular symptoms, and treatment‐related adverse events.ResultsA total of 60 studies met inclusion criteria. The studies included use of INCS as metered nasal sprays, drops, injections, aerosols, and irrigations. There were no persistent abnormalities in cortisol level or intraocular pressure change. Meta‐analysis of epistaxis showed a significantly increased risk in the FDA‐approved treatment group in comparison with control (risk ratio 1.56; 95% confidence interval, 1.13‐2.14; P =. 007).ConclusionsOverall, it appears that the use of both FDA and published non‐FDA application of INCS are safe in the adult population. Meta‐analysis demonstrated an increased risk of epistaxis in patients using INCS compared with placebo. Otherwise, there was no significant difference between in adults in the treatment group and placebo group. As an important caveat, the interpretation of safety of nonstandard INCS is restricted to delivery methods and dosages published in the literature.

Background Past research in population health trends has shown that injuries form a substantial burden of population health loss. Regular updates to injury burden assessments are critical. We report Global Burden of Disease (GBD) 2017 Study estimates on morbidity and mortality for all injuries. Methods We reviewed results for injuries from the GBD 2017 study. GBD 2017 measured injury-specific mortality and years of life lost (YLLs) using the Cause of Death Ensemble model. To measure non-fatal injuries, GBD 2017 modelled injury-specific incidence and converted this to prevalence and years lived with disability (YLDs). YLLs and YLDs were summed to calculate disability-adjusted life years (DALYs). Findings In 1990, there were 4 260 493 (4 085 700 to 4 396 138) injury deaths, which increased to 4 484 722 (4 332 010 to 4 585 554) deaths in 2017, while age-standardised mortality decreased from 1079 (1073 to 1086) to 738 (730 to 745) per 100 000. In 1990, there were 354 064 302 (95% uncertainty interval: 338 174 876 to 371 610 802) new cases of injury globally, which increased to 520 710 288 (493 430 247 to 547 988 635) new cases in 2017. During this time, age-standardised incidence decreased non-significantly from 6824 (6534 to 7147) to 6763 (6412 to 7118) per 100 000. Between 1990 and 2017, age-standardised DALYs decreased from 4947 (4655 to 5233) per 100 000 to 3267 (3058 to 3505). Interpretation Injuries are an important cause of health loss globally, though mortality has declined between 1990 and 2017. Future research in injury burden should focus on prevention in high-burden populations, improving data collection and ensuring access to medical care.

Background The epidemiological transition of non-communicable diseases replacing infectious diseases as the main contributors to disease burden has been well documented in global health literature. Less focus, however, has been given to the relationship between sociodemographic changes and injury. The aim of this study was to examine the association between disability-adjusted life years (DALYs) from injury for 195 countries and territories at different levels along the development spectrum between 1990 and 2017 based on the Global Burden of Disease (GBD) 2017 estimates. Methods Injury mortality was estimated using the GBD mortality database, corrections for garbage coding and CODEm—the cause of death ensemble modelling tool. Morbidity estimation was based on surveys and inpatient and outpatient data sets for 30 cause-of-injury with 47 nature-of-injury categories each. The Socio-demographic Index (SDI) is a composite indicator that includes lagged income per capita, average educational attainment over age 15 years and total fertility rate. Results For many causes of injury, age-standardised DALY rates declined with increasing SDI, although road injury, interpersonal violence and self-harm did not follow this pattern. Particularly for self-harm opposing patterns were observed in regions with similar SDI levels. For road injuries, this effect was less pronounced. Conclusions The overall global pattern is that of declining injury burden with increasing SDI. However, not all injuries follow this pattern, which suggests multiple underlying mechanisms influencing injury DALYs. There is a need for a detailed understanding of these patterns to help to inform national and global efforts to address injury-related health outcomes across the development spectrum.

AbstractIntroductionA recent study reported that diffuse left ventricular (LV) fibrosis is a predictor of atrial fibrillation (AF) recurrence following catheter ablation, by measuring postcontrast cardiac T1 (an error prone metric as per the 2017 Society for Cardiovascular Magnetic Resonance consensus statement) using an inversion‐recovery pulse sequence (an error prone method in arrhythmia) in AF ablation candidates. The purpose of this study was to verify the prior study, by measuring extracellular volume (ECV) fraction (an accurate metric) using a saturation‐recovery pulse sequence (accurate method in arrhythmia).Methods and ResultsThis study examined 100 AF patients (mean age = 62 ± 11 years, 69 males and 31 females, 67 paroxysmal [pAF] and 33 persistent [peAF]) who underwent a preablation cardiovascular magnetic resonance (CMR) exam. LV ECV and left atrial (LA) and LV functional parameters were quantified using standard analysis methods. During an average follow‐up period of 457 ± 261 days with 4 ± 3 rhythm checks per patient, 72 patients maintained sinus rhythm. Between those who maintained sinus rhythm (n = 72) and those who reverted to AF (n = 28), the only clinical characteristic that was significantly different was age (60 ± 12 years vs 66 ± 9 years); for CMR metrics, neither mean LV ECV (25.1 ± 3.3% vs 24.7 ± 3.7%), native LV T1 (1093.8 ± 73.5 ms vs 1070.2 ± 115.9 ms), left ventricular ejection fraction (54.1 ± 11.2% vs 55.7 ± 7.1%), nor LA end diastolic volume/body surface area (42.4 ± 14.8 mL/m2 vs 43.4 ± 19.6 mL/m2) were significantly different (P ≥ .23). According to Cox regression tests, none of the clinical and imaging variables predict AF recurrence.ConclusionNeither LV ECV nor other CMR metrics predict recurrence of AF following catheter ablation.

Background and ObjectivesSurgical resection of retroperitoneal sarcomas (RPS) often involves removal of the ipsilateral kidney. We evaluated the long‐term post‐operative renal function in patients who underwent a nephrectomy as part of their en‐bloc resection of RPS.MethodsRetrospective review of an institutional database identified RPS patients who underwent nephrectomy for curative intent from 1990 to 2014. The primary outcome measured was chronic kidney disease (CKD) calculated by the glomerular filtration rate (GFR).ResultsOf the 47 patients in our study, 19 (40%), 18 (38%), and 10 (21%) patients had a preoperative CKD stage 1, 2, and 3, respectively. The GFR decreased by an average of 33.4 mL/min/1.73 m2 with 66% of patients demonstrating mild progression of their renal impairment. Only three (6%) patients progressed to CKD stage 4 or 5, one of which required life‐long dialysis.ConclusionNephrectomy as part of an en‐bloc resection is associated with a decrease in GFR that is not clinically significant. Fear of kidney failure should not prevent a surgeon from performing a nephrectomy in the treatment of RPS.

Purpose This trial assessed the efficacy and safety of docetaxel monotherapy or docetaxel in combination with ramucirumab (vascular endothelial growth factor receptor 2 antibody) or icrucumab (vascular endothelial growth factor receptor 1 antibody) after progression during or within 12 months of platinum-based regimens for patients with locally advanced or metastatic urothelial carcinoma. Patients and Methods Patients were randomly assigned (1:1:1) to receive docetaxel 75 mg/m2 intravenously (IV) on day 1 of a 3-week cycle (arm A), docetaxel 75 mg/m2 IV plus ramucirumab 10 mg/kg IV on day 1 of a 3-week cycle (arm B), or docetaxel 75 mg/m2 IV on day 1 plus icrucumab 12 mg/kg IV on days 1 and 8 of a 3-week cycle (arm C). Treatment continued until disease progression or unacceptable toxicity. The primary end point was investigator-assessed progression-free survival (PFS). Results A total of 140 patients were randomly assigned and treated in arms A (n = 45), B (n = 46), or C (n = 49). PFS was significantly longer in arm B compared with arm A (median, 5.4 months; 95% CI, 3.1 to 6.9 months v 2.8 months; 95% CI, 1.9 to 3.6 months; stratified hazard ratio, 0.389; 95% CI, 0.235 to 0.643; P = .0002). Arm C did not experience improved PFS compared with arm A (1.6 months; 95% CI, 1.4 to 2.9; stratified hazard ratio, 0.863; 95% CI, 0.550 to 1.357; P = .5053). The most common grade 3 or worse adverse events (arms A, B, and C) were neutropenia (36%, 33%, and 39%), fatigue (13%, 30%, and 20%), febrile neutropenia (13%, 17%, and 6.1%), and anemia (6.7%, 13%, and 14%, respectively). Conclusion The addition of ramucirumab to docetaxel met the prespecified efficacy end point for prolonging PFS in patients with locally advanced or metastatic urothelial carcinoma receiving second-line treatment and warrants further investigation in the phase III setting.