Introduction Sepsis is a major health problem with a high incidence and mortality. ADM, a free-circulating peptide mainly expressed and secreted by vascular endothelial cells, shows vasodilatory properties and causes hypotension when present in higher concentrations during sepsis. Areas covered Adrecizumab (ADZ) (HAM 8101) is a humanized targeted therapy directed against the N-terminus of adrenomedullin (ADM). ADZ inhibits excessive circulating sepsis-induced ADM and stimulates protective effects on the endothelial barrier, and decreases interstitial vasodilatory effects. ADZ demonstrated a promising safety profile in healthy subjects in phase I studies. According to these results, a phase II proof of concept study enrolling 300 septic patients is currently in course (NCT03085758). Expert opinion ADZ is the first humanized antibody directed against ADM. The main interest of ADZ is its potential use as a 'biomarker-guided therapy' in septic patients with high circulating ADM. ADZ is increasingly seen as a potential adjunct therapy to restore endothelial function in septic shock. A positive pivotal phase III trial is indeed needed to convince the intensive care community to prescribe ADZ in septic shock patients. Further, it would be of interest to see whether ADZ might also benefit other critical diseases such as cardiogenic shock where endothelial dysfunction has also been described.β-thalassemia is one of the most prevalent genetic diseases worldwide. The current treatment for β-thalassemia is allogeneic hematopoietic stem cell transplantation (HSCT), which is limited due to lack of matched donors. Gene therapy has been developed as an alternative therapeutic option for transfusion-dependent β-thalassemia (TDT). However, successful gene therapy for β-thalassemia patients in China has not been reported. Here we present the results of preclinical studies of an optimally designed LV named LentiHBBT87Q in hematopoietic stem and progenitor cells (HSPCs) derived from Chinese TDT patients. LentiHBBT87Q was selected from a series of LVs with optimized backbone and de novo cloning strategy. It contains an exogenous T87Q β-globin gene (HBBT87Q) driven by a specific reconstituted locus control region (rLCR) and efficiently express HBB mRNA and HBB protein in erythroblasts derived from cord blood (CB) HSPCs. To facilitate clinical transformation, we manufactured clinical grade LentiHBBT87Q (cLentiHBBT87Q) and optimized its transduction procedure. Importantly, transduction of cLentiHBBT87Q restored expression of HBB monomer and adult hemoglobin (HbA) tetramer to relatively normal level in erythroblasts from bone marrow (BM) HSPCs of Chinese TDT patients, that carry the most common mutation types and cover various genotypes, including β0/β0. Furthermore, viral integration sites (VIS) of cLentiHBBT87Q were similar to other LVs safely used in previous clinical trials and gene-ontology (GO term) analysis of VIS targeted genes suggest no tumor-associated pathways were enriched in treated samples. Taken together, we have engineered the cLentiHBBT87Q that can restore β-globin expression in the HSPCs-derived erythroblasts of Chinese TDT patients with minimal risk on tumorigenesis, providing a favorable starting point for future clinical application.
Value-Based Health Care (VBHC) is an evolving model of healthcare delivery aimed at achieving better patient outcomes at lower costs to the healthcare provider. The practise of VBHC requires efficient information systems with good reporting capability and subsequent outcome measuring
Information systems within the National Health Service (NHS) are often multiple and not necessarily integrated to one another. We therefore developed a systematic approach to collecting, validating and analysing data from multiple sources and information systems, with the aim of designing and endorsing an automatic system to capture health outcomes data in heart failure to support future VBHC models.

A retrospective cohort of heart failure patients with reduced ejection fraction undergoing Implantable Cardioverter Defibrillator (ICD) or Cardiac Resynchronization Therapy (CRT) procedures within a limited geographical area in South London were evaluated. A purpose built database was created to integrate, transform and validate health care data from multiple information systems.

Validation analysis shows that our implemented methodology has produced a robust dataset. https://www.selleckchem.com/products/cl-82198.html Our limited cohort of 134 patients does not allow for any complex statistical analysis however has identified some important themes related to outcomes and costs.

We have created a validated database specific to our Trust that can be upscaled locally with ease and transferred to other health diseases. Due to variations in local procedure from one Trust to another, this methodology now requires implementation across multiple sites to understand differences in transformation of data and outcome measuring.
We have created a validated database specific to our Trust that can be upscaled locally with ease and transferred to other health diseases. Due to variations in local procedure from one Trust to another, this methodology now requires implementation across multiple sites to understand differences in transformation of data and outcome measuring.
Research is an important tool for sustainable development and the advancement of health. In Bhutan, the need for strengthening the national health research effort has been recognized only in recent years. As a part of research capacity building, this study was conducted to assess the knowledge, attitude and practices of the country's health care professionals towards research.

This was a nationwide cross-sectional study. Simple random sampling was used to obtain a proportionate composition of health professionals. A self-administered questionnaire was developed to assess knowledge through 10 multiple-choice questions, attitude through rating statements, and practices through assessing experiences with research. Knowledge was scored out of 10. Besides analysing proportions, correlation and simple linear regression coefficients were calculated to assess the association of knowledge score with age, work experience, qualification, and the number of research projects undertaken.

A total of 420 valid questionnaires were collected (response rate = 95.