Institutionalizing health technology assessment in Ethiopia: Seizing the window of opportunity

Ethiopia’s commitment to achieving universal health coverage (UHC) requires an efficient and equitable health priority-setting practice. The Ministry of Health aims to institutionalize health technology assessment (HTA) to support evidence-based decision making. This commentary highlights key considerations for successful formulation, adoption, and implementation of HTA policies and practices in Ethiopia, based on a review of international evidence and published normative principles and guidelines. Stakeholder engagement, transparent policymaking, sustainable financing, workforce education, and political economy analysis and power dynamics are critical factors that need to be considered when developing a national HTA roadmap and implementation strategy. To ensure ownership and sustainability of HTA, effective stakeholder engagement and transparency are crucial. Regulatory embedding and sustainable financing ensure legitimacy and continuity of HTA production, and workforce education and training are essential for conducting and interpreting HTA. Political economy analysis helps identify opportunities and constraints for effective HTA implementation. By addressing these considerations, Ethiopia can establish a well-designed HTA system to inform evidence-based and equitable resource allocation toward achieving UHC and improving health outcomes.publishedVersio

A multifaceted quality improvement project improves intraoperative redosing of surgical antimicrobial prophylaxis during pediatric surgery

BackgroundAccurate intraoperative antibiotic redosing contributes to prevention of surgical site infections in pediatric patients. Ensuring compliance with evolving national guidelines of weight‐based, intraoperative redosing of antibiotics is challenging to pediatric anesthesiologists.AimsOur primary aim was to increase compliance of antibiotic redoses at the appropriate time and appropriate weight‐based dose to 70%. Secondary aims included a subset analysis of time compliance and dose compliance individually, and compliance based on order entry method of the first dose (verbal or electronic).MethodsAt a freestanding, academic pediatric hospital, we reviewed surgical cases between May 1, 2014, and October 31, 2017 requiring antibiotic redoses. After an institutional change in cefazolin dosing in May 2015, phased interventions to improve compliance included electronic countermeasures to display previous and next dose timing, an alert 5 minutes prior to next dose, and weight‐based dose recommendation (September 2015). Physical countermeasures include badge cards, posting of guidelines, and updates to housestaff manual (September 2015). Statistical process control charts were used to assess overall antibiotic redose compliance, time compliance, and dose compliance. The chi‐square test was used to analyze group differences.ResultsA total of 3015 antibiotic redoses were administered during 2341 operative cases between May 1, 2014, and October 31, 2017. Mean monthly compliance with redosing was 4.3% (May 2014‐April 2015) and 73% (November 2015‐October 2017) (P < 0.001). Dose‐only compliance increased from 76% to 89% (P < 0.001), and time‐only compliance increased from 4.9% to 82% (P < 0.001). After implementation of countermeasures, electronic order entry compared with verbal order was associated with higher dose compliance, 90% vs 86% (P = 0.015).ConclusionThis quality improvement project, utilizing electronic and physical interventions, was effective in improving overall prophylactic antibiotic redosing compliance in accordance with institutional redosing guidelines.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/150557/1/pan13651_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150557/2/pan13651.pd

Impact of microRNAs in Resistance to Chemotherapy and Novel Targeted Agents in Non-Small Cell Lung Cancer

Despite recent advances in understanding the cancer signaling pathways and in developing new therapeutic strategies, non-small cell lung cancer (NSCLC) shows grim prognosis and high incidence of recurrence. Insufficient dis- ruption of oncogenic signaling and drug resistance are the most common causes of tumor recurrence. Drug resistance, in- trinsic or acquired, represents a main obstacle in NSCLC therapeutics by limiting the efficacy both of conventional che- motherapeutic compounds and new targeted agents. Therefore, novel and more innovative approaches are required for treatment of this tumor. MicroRNAs (miRNAs) are a family of small non-coding RNAs that regulate gene expression by sequence-specific targeting of mRNAs causing mRNA degradation or translational repression. Accumulating evidence suggests that impairment of candidate miRNAs may be involved in the acquisition of tumor cell resistance to conventional chemotherapy and novel biological agents by affecting the drug sensitivity of cancer cells. The modulation of these miR- NAs, using antagomiRs or miRNA mimics, can restore key gene networks and signaling pathways, and optimize anti- cancer therapies by inhibition of tumor cell proliferation and increasing the drug sensitivity. Therefore, miRNA-based therapeutics provides an attractive anti-tumor approach for developing new and more effective individualized therapeutic strategies, improving drug efficiency, and for predicting the response to different anticancer drugs. In this review, we pre- sent an overview on the role of miRNAs in resistance mechanisms of NSCLC, discussing the main studies on the aberra- tions in apoptosis, cell cycle and DNA damage repair pathways, as well as in novel drug targets

Transcript analysis reveals a specific HOX signature associated with positional identity of human endothelial cells.

The endothelial cell has a remarkable ability for sub-specialisation, adapted to the needs of a variety of vascular beds. The role of developmental programming versus the tissue contextual environment for this specialization is not well understood. Here we describe a hierarchy of expression of HOX genes associated with endothelial cell origin and location. In initial microarray studies, differential gene expression was examined in two endothelial cell lines: blood derived outgrowth endothelial cells (BOECs) and pulmonary artery endothelial cells. This suggested shared and differential patterns of HOX gene expression between the two endothelial lines. For example, this included a cluster on chromosome 2 of HOXD1, HOXD3, HOXD4, HOXD8 and HOXD9 that was expressed at a higher level in BOECs. Quantative PCR confirmed the higher expression of these HOXs in BOECs, a pattern that was shared by a variety of microvascular endothelial cell lines. Subsequently, we analysed publically available microarrays from a variety of adult cell and tissue types using the whole "HOX transcriptome" of all 39 HOX genes. Using hierarchical clustering analysis the HOX transcriptome was able to discriminate endothelial cells from 61 diverse human cell lines of various origins. In a separate publically available microarray dataset of 53 human endothelial cell lines, the HOX transcriptome additionally organized endothelial cells related to their organ or tissue of origin. Human tissue staining for HOXD8 and HOXD9 confirmed endothelial expression and also supported increased microvascular expression of these HOXs. Together these observations suggest a significant involvement of HOX genes in endothelial cell positional identity

Detection of atomic spin labels in a lipid bi-layer using a single-spin nanodiamond probe

Magnetic field fluctuations arising from fundamental spins are ubiquitous in nanoscale biology, and are a rich source of information about the processes that generate them. However, the ability to detect the few spins involved without averaging over large ensembles has remained elusive. Here we demonstrate the detection of gadolinium spin labels in an artificial cell membrane under ambient conditions using a single-spin nanodiamond sensor. Changes in the spin relaxation time of the sensor located in the lipid bilayer were optically detected and found to be sensitive to near-individual proximal gadolinium atomic labels. The detection of such small numbers of spins in a model biological setting, with projected detection times of one second, opens a new pathway for in-situ nanoscale detection of dynamical processes in biology.Comment: 16 pages, 4 figure

CSF1R mosaicism in a family with hereditary diffuse leukoencephalopathy with spheroids

Mutations in the colony stimulating factor 1 receptor

Circulating BMP9 Protects the Pulmonary Endothelium during Inflammation-induced Lung Injury in Mice.

Rationale: Pulmonary endothelial permeability contributes to the high-permeability pulmonary edema that characterizes acute respiratory distress syndrome. Circulating BMP9 (bone morphogenetic protein 9) is emerging as an important regulator of pulmonary vascular homeostasis. Objectives:To determine whether endogenous BMP9 plays a role in preserving pulmonary endothelial integrity and whether loss of endogenous BMP9 occurs during LPS challenge. Methods: A BMP9-neutralizing antibody was administrated to healthy adult mice, and lung vasculature was examined. Potential mechanisms were delineated by transcript analysis in human lung endothelial cells. The impact of BMP9 administration was evaluated in a murine acute lung injury model induced by inhaled LPS. Levels of BMP9 were measured in plasma from patients with sepsis and from endotoxemic mice. Measurements and Main Results: Subacute neutralization of endogenous BMP9 in mice (N = 12) resulted in increased lung vascular permeability (P = 0.022), interstitial edema (P = 0.0047), and neutrophil extravasation (P = 0.029) compared with IgG control treatment (N = 6). In pulmonary endothelial cells, BMP9 regulated transcriptome pathways implicated in vascular permeability and cell-membrane integrity. Augmentation of BMP9 signaling in mice (N = 8) prevented inhaled LPS-induced lung injury (P = 0.0027) and edema (P < 0.0001). In endotoxemic mice (N = 12), endogenous circulating BMP9 concentrations were markedly reduced, the causes of which include a transient reduction in hepatic BMP9 mRNA expression and increased elastase activity in plasma. In human patients with sepsis (N = 10), circulating concentratons of BMP9 were also markedly reduced (P < 0.0001). Conclusions: Endogenous circulating BMP9 is a pulmonary endothelial-protective factor, downregulated during inflammation. Exogenous BMP9 offers a potential therapy to prevent increased pulmonary endothelial permeability in lung injury

Inspiring STEM undergraduates to tackle the AMR crisis

To address the growing problem of antimicrobial resistance (AMR), it is necessary to invest in, inspire and attract future generations of scientists to this research area. Undergraduate education should be a focus for attention and efforts should be made to ensure that students are afforded opportunities to actively engage with AMR. We illustrate how as a topic AMR provides opportunities to deliver effective research-led teaching in addition to traditional teaching methods. We have used a selection of case studies to illustrate how students can be engaged with AMR using a variety of research-led approaches to develop the required skills for biology-centric students. In addition, we indicate how these skills map to the UK Quality Assurance Framework and the Vision and Change report developed by the American Association for the Advancement of Science