Towards sustainable healthcare system performance in the 21st century in high-income countries: a protocol for a systematic review of the grey literature.

INTRODUCTION: There is wide recognition that, if healthcare systems continue along current trajectories, they will become harder to sustain. Ageing populations, accelerating rates of chronic disease, increasing costs, inefficiencies, wasteful spending and low-value care pose significant challenges to healthcare system durability. Sustainable healthcare systems are important to patients, society, policy-makers, public and private funders, the healthcare workforce and researchers. To capture current thinking about improving healthcare system sustainability, we present a protocol for the systematic review of grey literature to capture the current state-of-knowledge and to compliment a review of peer-reviewed literature. METHODS AND ANALYSIS: The proposed search strategy, based on the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines, includes Google Advanced Search, snowballing techniques and targeted hand searching of websites of lead organisations such as WHO, Organisation for Economic Cooperation and Development, governments, public policy institutes, universities and non-government organisations. Documents will be selected after reviewing document summaries. Included documents will undergo full-text review. The following criteria will be used: grey literature document; English language; published January 2013-March 2018; relevant to the healthcare delivery system; the content has international or national scope in high-income countries. Documents will be assessed for quality, credibility and objectivity using validated checklists. Descriptive data elements will be extracted: identified sustainability threats, definitions of sustainability, attributes of sustainable healthcare systems, solutions for improvement and outcome measures of sustainability. Data will be analysed using novel text-mining methods to identify common concept themes and meanings. This will be triangulated with the more traditional analysis and concept theming by the researchers. ETHICS AND DISSEMINATION: No primary data will be collected, therefore ethical approval will not be sought. The results will be disseminated in peer-reviewed literature, as conference presentations and as condensed summaries for policy-makers and health system partners. PROSPERO REGISTRATION NUMBER: CRD42018103076.

Built to last? The sustainability of health system improvements, interventions and change strategies: a study protocol for a systematic review.

INTRODUCTION: The sustainability of healthcare interventions and change programmes is of increasing importance to researchers and healthcare stakeholders interested in creating sustainable health systems to cope with mounting stressors. The aim of this protocol is to extend earlier work and describe a systematic review to identify, synthesise and draw meaning from studies published within the last 5 years that measure the sustainability of interventions, improvement efforts and change strategies in the health system. METHODS AND ANALYSIS: The protocol outlines a method by which to execute a rigorous systematic review. The design includes applying primary and secondary data collection techniques, consisting of a comprehensive database search complemented by contact with experts, and searching secondary databases and reference lists, using snowballing techniques. The review and analysis process will occur via an abstract review followed by a full-text screening process. The inclusion criteria include English-language, peer-reviewed, primary, empirical research articles published after 2011 in scholarly journals, for which the full text is available. No restrictions on location will be applied. The review that results from this protocol will synthesise and compare characteristics of the included studies. Ultimately, it is intended that this will help make it easier to identify and design sustainable interventions, improvement efforts and change strategies. ETHICS AND DISSEMINATION: As no primary data were collected, ethical approval was not required. Results will be disseminated in conference presentations, peer-reviewed publications and among policymaker bodies interested in creating sustainable health systems.

Utilization of site-specific recombination for generating therapeutic protein producing cell lines.

The AttSite Recombinase Technology from Intrexon, Blacksburg, VA, utilizes specific DNA sequences and proprietary recombinase enzymes to catalyze the insertion of a gene of interest at a specific location in the host cell genome. Using this technology, we have developed Chinese Hamster Ovary (CHO) cell lines that have incorporated attB recombination sites at highly transcriptionally active loci or 'hot spots' within the cell genome. Subsequently, these attB site containing host cell lines could then be used for the expression of future Centocor products. Candidate production cell lines would be generated by a simple recombination event. Since the therapeutic gene of interest would preferentially integrate into the pre-selected high-expressing attB site, candidate cell lines would consistently express high levels of the gene of interest. We have been able to demonstrate that the AttSite Recombinase Technology could be a valid approach for the development of high-expressing production cell lines.

The maternal-effect, selfish genetic element Medea is associated with a composite Tc1 transposon.

Maternal-Effect Dominant Embryonic Arrest ("Medea") factors are selfish nuclear elements that combine maternal-lethal and zygotic-rescue activities to gain a postzygotic survival advantage. We show that Medea(1) activity in Tribolium castaneum is associated with a composite Tc1 transposon inserted just downstream of the neurotransmitter reuptake symporter bloated tubules (blot), whose Drosophila ortholog has both maternal and zygotic functions. The 21.5-kb insertion contains defective copies of elongation initiation factor-3, ATP synthase subunit C, and an RNaseD-related gene, as well as a potentially intact copy of a prokaryotic DUF1703 gene. Sequence comparisons suggest that the current distribution of Medea(1) reflects global emanation after a single transpositional event in recent evolutionary time. The Medea system in Tribolium represents an unusual type of intragenomic conflict and could provide a useful vehicle for driving desirable genes into populations.

Development of a clinical pathway for near-term and convalescing premature infants in a Level II nursery.

A subcategory of premature infants, those born near term at 34 to 36 and 6/7 weeks gestation, may represent a previously unrecognized at-risk neonatal population. Evidence-based practice guidelines, crafted specifically for this population, are needed to effectively manage their care. In an effort to meet the needs of the near-term infant (NTI) population, and concurrently address the needs of the convalescing premature infants reverse transported to a Level II nursery setting, a multidisciplinary team of clinicians designed tools to provide a more consistent approach to care for and discharge these infants. This article describes the design, implementation, and evaluation of an evidence-based multidisciplinary clinical pathway specific to the needs of the NTI, including care plans, a standardized physician admission and discharge order set, evidence-based interventions, parent education, and recommendations for follow-up after hospital discharge that were developed for use in a Level II nursery. The use of the premature and near-term infant pathway has now been expanded to NTIs cared for in the newborn nursery, thereby ensuring safe, consistent, quality care for this population, regardless of their setting.