War on the Wards: The collapse of health care infrastructure resulting from violent conflict

Introduction: While utilizing satellite images to verify reports of hospital damage resulting from armed conflict allows for remote assessment, the use of private satellites to gain access to images prohibits widespread use. The questions this study sought to answer were: Is it possible to replicate the findings of previous reports of hospital damage that used the services of private satellite imagery using open source software, such as Google Earth? What variations exist among the different sites where damage to hospitals is visible, and what gradation is possible? Is this methodology applicable to other examples of armed conflict? Methods: Using the map of bombed Syrian hospitals published and maintained by Physicians for Human Rights, hospitals were selected according to their location and the time period of the attack. These coordinates were entered into Google maps and once the attack was verified, a grade of damage was assigned. This methodology was then applied to reports of similar attacks in Iraq. Results: While much information can be gleaned from open source data such as Google Earth, the level of detail in satellite images is lower and coordinates data is less specific. [Further results pending.] Conclusion: There is room for the use of open source satellite technology to track and grade the damage done to health care infrastructure during armed conflict. [More conclusions pending.

Current state of antimicrobial stewardship in children’s hospital emergency departments

BACKGROUND Antimicrobial stewardship programs (ASPs) effectively optimize antibiotic use for inpatients; however, the extent of emergency department (ED) involvement in ASPs has not been described. OBJECTIVE To determine current ED involvement in children's hospital ASPs and to assess beliefs and preferred methods of implementation for ED-based ASPs. METHODS A cross-sectional survey of 37 children's hospitals participating in the Sharing Antimicrobial Resistance Practices collaboration was conducted. Surveys were distributed to ASP leaders and ED medical directors at each institution. Items assessed included beliefs regarding ED antibiotic prescribing, ED prescribing resources, ASP methods used in the ED such as clinical decision support and clinical care guidelines, ED participation in ASP activities, and preferred methods for ED-based ASP implementation. RESULTS A total of 36 ASP leaders (97.3%) and 32 ED directors (86.5%) responded; the overall response rate was 91.9%. Most ASP leaders (97.8%) and ED directors (93.7%) agreed that creation of ED-based ASPs was necessary. ED resources for antibiotic prescribing were obtained via the Internet or electronic health records (EHRs) for 29 hospitals (81.3%). The main ASP activities for the ED included production of antibiograms (77.8%) and creation of clinical care guidelines for pneumonia (83.3%). The ED was represented on 3 hospital ASP committees (8.3%). No hospital ASPs actively monitored outpatient ED prescribing. Most ASP leaders (77.8%) and ED directors (81.3%) preferred implementation of ED-based ASPs using clinical decision support integrated into the EHR. CONCLUSIONS Although ED involvement in ASPs is limited, both ASP and ED leaders believe that ED-based ASPs are necessary. Many children's hospitals have the capability to implement ED-based ASPs via the preferred method: EHR clinical decision support. Infect Control Hosp Epidemiol 2017;38:469-475

Early experience with targeted therapy as a first-line adjuvant treatment for pediatric low-grade glioma.

OBJECTIVE: Pediatric low-grade gliomas (pLGGs) frequently exhibit dysregulation of the mitogen-activated protein kinase (MAPK) pathway. Targeted therapies, including mutant BRAF inhibitors (dabrafenib) and MEK inhibitors (trametinib), have shown promise in patients in whom conventional chemotherapy has failed. However, few studies have investigated the use of targeted therapy as a first-line treatment for pLGG. Here, the authors reviewed their institutional experience with using a personalized medicine approach to patients with newly diagnosed pLGGs. METHODS: All pediatric patients at the authors\u27 institution who had been treated with dabrafenib or trametinib for pLGG without first receiving conventional chemotherapy or radiation were retrospectively reviewed. Demographic, clinical, and radiological data were collected. RESULTS: Eight patients underwent targeted therapy as a first-line treatment for pLGG. Five patients had a BRAF alteration (1 with a BRAFV600E mutation, 4 with a KIAA1549:BRAF fusion), and 3 patients had an NF1 mutation. One of the 8 patients was initially treated with dabrafenib, and trametinib was added later. Seven patients were initially treated with trametinib; of these, 2 later transitioned to dual therapy, whereas 5 continued with trametinib monotherapy. Six patients (75%) demonstrated a partial response to therapy during their treatment course, whereas stable disease was identified in the remaining 2 patients (25%). One patient experienced mild disease progression after completing a course of trametinib monotherapy, but ultimately stabilized after a period of close observation. Another patient experienced tumor progression while on dabrafenib, but subsequently responded to dual therapy with dabrafenib and trametinib. The most common adverse reactions to targeted therapy were cutaneous toxicity (100%) and diarrhea (50%). CONCLUSIONS: Targeted therapies have the potential to become a standard treatment option for pLGG due to their favorable toxicity profile and oral route of administration. This case series provides preliminary evidence that targeted therapies can induce an early disease response as a first-line adjuvant treatment; however, large-scale studies are required to assess long-term durability and safety

Unacceptably High Mortality Related to Measles Epidemics in Niger, Nigeria, and Chad

BACKGROUND: Despite the comprehensive World Health Organization (WHO)/United Nations Children's Fund (UNICEF) measles mortality–reduction strategy and the Measles Initiative, a partnership of international organizations supporting measles mortality reduction in Africa, certain high-burden countries continue to face recurrent epidemics. To our knowledge, few recent studies have documented measles mortality in sub-Saharan Africa. The objective of our study was to investigate measles mortality in three recent epidemics in Niamey (Niger), N'Djamena (Chad), and Adamawa State (Nigeria). METHODS AND FINDINGS: We conducted three exhaustive household retrospective mortality surveys in one neighbourhood of each of the three affected areas: Boukoki, Niamey, Niger (April 2004, n = 26,795); Moursal, N'Djamena, Chad (June 2005, n = 21,812); and Dong District, Adamawa State, Nigeria (April 2005, n = 16,249), where n is the total surveyed population in each of the respective areas. Study populations included all persons resident for at least 2 wk prior to the study, a duration encompassing the measles incubation period. Heads of households provided information on measles cases, clinical outcomes up to 30 d after rash onset, and health-seeking behaviour during the epidemic. Measles cases and deaths were ascertained using standard WHO surveillance-case definitions. Our main outcome measures were measles attack rates (ARs) and case fatality ratios (CFRs) by age group, and descriptions of measles complications and health-seeking behaviour. Measles ARs were the highest in children under 5 y old (under 5 y): 17.1% in Boukoki, 17.2% in Moursal, and 24.3% in Dong District. CFRs in under 5-y-olds were 4.6%, 4.0%, and 10.8% in Boukoki, Moursal, and Dong District, respectively. In all sites, more than half of measles cases in children aged under 5 y experienced acute respiratory infection and/or diarrhoea in the 30 d following rash onset. Of measles cases, it was reported that 85.7% (979/1,142) of patients visited a health-care facility within 30 d after rash onset in Boukoki, 73.5% (519/706) in Moursal, and 52.8% (603/1,142) in Dong District. CONCLUSIONS: Children in these countries still face unacceptably high mortality from a completely preventable disease. While the successes of measles mortality–reduction strategies and progress observed in measles control in other countries of the region are laudable and evident, they should not overshadow the need for intensive efforts in countries that have just begun implementation of the WHO/UNICEF comprehensive strategy

Estradiol Regulates Expression of Estrogen Receptor ERα46 in Human Macrophages

BACKGROUND:Monocytes and macrophages are key innate immune effector cells that produce cytokines and chemokines upon activation. We and others have shown that 17beta-estradiol (E2) has a direct role in the modulation of monocyte and macrophage immune function. However, relatively little is known about the ability of E2 to regulate isoform expression of estrogen receptors (ERs) in these cells. METHODOLOGY/PRINCIPAL FINDINGS:In this study, we quantify expression of ERalpha and ERbeta in human monocytes and macrophages. We also show for the first time that the N-terminal truncated ERalpha variant, ERalpha46, is expressed in both cell types. Promoter utilization studies reveal that transcription of ERalpha in both cell types occurs from upstream promoters E and F. Treatment with E2 induces ERalpha expression in macrophages but has no effect on ERbeta levels in either cell type. During monocyte-to-macrophage differentiation, ERalpha is upregulated in a time-dependent manner. Previous studies by our group demonstrated that E2 treatment attenuates production of the chemokine CXCL8 in an ER-dependent manner. We now show that ERalpha expression levels parallel the ability of E2 to suppress CXCL8 production. CONCLUSIONS/SIGNIFICANCE:This work demonstrates for the first time that human macrophages predominantly express the truncated ER variant ERalphap46, which is estradiol-inducible. This is mediated through usage of the ERalpha F promoter. Alternative promoter usage may account for tissue and cell type-specific differences in estradiol-induced effects on gene expression. These studies signify the importance of ERalpha expression and regulation in the ability of E2 to modulate innate immune responses