A bibliometric analysis of systematic reviews on vaccines and immunisation.

INTRODUCTION: SYSVAC is an online bibliographic database of systematic reviews and systematic review protocols on vaccines and immunisation compiled by the London School of Hygiene & Tropical Medicine and hosted by the World Health Organization (WHO) through their National Immunization Technical Advisory Groups (NITAG) resource centre (www.nitag-resource.org). Here the development of the database and a bibliometric review of its content is presented, describing trends in the publication of policy-relevant systematic reviews on vaccines and immunisation from 2008 to 2016. MATERIALS AND METHODS: Searches were conducted in seven scientific databases according to a standardized search protocol, initially in 2014 with the most recent update in January 2017. Abstracts and titles were screened according to specific inclusion criteria. All included publications were coded into relevant categories based on a standardized protocol and subsequently analysed to look at trends in time, topic, area of focus, population and geographic location. RESULTS: After screening for inclusion criteria, 1285 systematic reviews were included in the database. While in 2008 there were only 34 systematic reviews on a vaccine-related topic, this increased to 322 in 2016. The most frequent pathogens/diseases studied were influenza, human papillomavirus and pneumococcus. There were several areas of duplication and overlap. DISCUSSION: As more systematic reviews are published it becomes increasingly time-consuming for decision-makers to identify relevant information among the ever-increasing volume available. The risk of duplication also increases, particularly given the current lack of coordination of systematic reviews on vaccine-related questions, both in terms of their commissioning and their execution. The SYSVAC database offers an accessible catalogue of vaccine-relevant systematic reviews with, where possible access or a link to the full-text. CONCLUSIONS: SYSVAC provides a freely searchable platform to identify existing vaccine-policy-relevant systematic reviews. Systematic reviews will need to be assessed adequately for each specific question and quality

Sexual health promotion and contraceptive services in local authorities: a systematic review of economic evaluations 2010-2015

Background Since 2013, health commissioners in England’s local authorities have been responsible for sexual health services, including contraception, HIV testing, STI testing and treatment, health education and specialist sexual health services. Effective commissioning requires information to indicate which interventions may, or may not, be cost-effective. However, current UK guidance and recent research on the cost-effectiveness of sexual health services provides patchy and fragmented evidence. This study aims systematically to review the evidence available on the cost-effectiveness of OECD-based interventions relevant to UK local authority-commissioned sexual health services. Methods Key informants, bibliographic database searches and reference lists of guidance documents and included studies were searched for potentially relevant research. Guided by key stakeholders, we sought economic evaluations of sexual health interventions within the responsibility of local authorities, and focused in the UK, on contraception and on health promotion, published between 2010 and 2015 in English. Eligible studies were full economic evaluations based in an OECD country. Studies were classified using a specifically developed tool and assessed for methodological risk of bias using one of three design-specific assessment tools. Descriptive frequencies of codes were analysed to provide a ‘map’ of research that informed stakeholder discussions to focus the subsequent synthesis. The characteristics of studies, quality ratings and cost outcomes from each included study were extracted into tables and findings summarised narratively. Studies were assessed for their relative cost-saving or cost-effectiveness according to NICE guidance. Results In total, 17,705 references were screened; of these, 29 met our inclusion criteria and were included in the synthesis. Nine studies were undertaken in the UK; the remainder were US based. Fifteen studies examined the economics of contraception and 14 evaluated health promotion. Overall, studies were of medium methodological quality. In general, economic evaluations of contraception reported cost-effectiveness or cost savings for ulipristal acetate (UPA) as emergency contraception, long-acting reversible contraceptives (LARCs) for regular, post-natal and post-abortion contraception, and targeting to high risk groups; none, however, reported costs per quality-adjusted life year (QALY) within NICE thresholds. Economic evaluations of sexual health promotion interventions indicated more mixed results. Only three interventions were found to be cost-effective according to the NICE thresholds for HIV or sexually transmitted infection (STI) outcomes: nurse-led rapid testing and tailored counselling; condom negotiations skills training for female sex workers; and a teacher-led STI prevention and skills training intervention. UK studies focused on health promotion and contraception, and supported the above findings. In general, there has been a reasonable amount of economic research into sexual health interventions since 2010, and these support current NICE sexual health guidance. Abstract Sexual health promotion and contraceptive services in local authorities: a systematic review of economic evaluations 2010-2015 vi Conclusions The broad nature of the research question posed in this systematic review resulted in the inclusion of a dataset very diverse in terms of populations, interventions, outcomes and types of economic evaluation designs. In considering the cost-effectiveness of these strategies in relation to their own commissioning climate, policy and decision makers should consider carefully the fit between their context and that of individual studies. Use of longer-term outcomes in trials used in economic evaluations would strengthen estimates of effects such as QALYs, as would the routine use of longitudinal cohort data

Identification of Novel Pheromone-response Regulators through Systematic Overexpression of 120 Protein Kinases in Yeast

Protein kinases are well known to transmit and regulate signaling pathways. To identify additional regulators of the pheromone signaling apparatus in yeast, we evaluated an array of 120 likely protein kinases encoded by the yeast genome. Each kinase was fused to glutathione S-transferase, overexpressed, and tested for changes in pheromone responsiveness in vivo. As expected, several known components of the pathway (YCK1, STE7, STE11, FUS3, and KSS1) impaired the growth arrest response. Seven other kinases also interfered with pheromone-induced growth arrest; in rank order they are as follows: YKL116c (renamed PRR1) = YDL214c (renamed PRR2) > YJL141c (YAK1, SRA1) > YNR047w = YCR091w (KIN82) = YIL095w (PRK1) > YCL024w (KCC4). Inhibition of pheromone signaling by PRR1, but not PRR2, required the glutathione S-transferase moiety. Both kinases inhibited gene transcription after stimulation with pheromone, a constitutively active kinase mutant STE11-4, or overexpression of the transcription factor STE12. Neither protein altered the ability of the mitogen-activated protein kinase (MAPK) Fus3 to feedback phosphorylate a known substrate, the MAPK kinase Ste7. These results reveal two new components of the pheromone-signaling cascade in yeast, each acting at a point downstream of the MAPK

Single-Cell Analysis of Aneurysmal Aortic Tissue in Patients with Marfan Syndrome Reveals Dysfunctional TGF-β Signaling

The molecular and cellular processes leading to aortic aneurysm development in Marfan syndrome (MFS) remain poorly understood. In this study, we examined the changes of aortic cell populations and gene expression in MFS by performing single-cell RNA sequencing (scRNA seq) on ascending aortic aneurysm tissues from patients with MFS (n = 3) and age-matched non-aneurysmal control tissues from cardiac donors and recipients (n = 4). The expression of key molecules was confirmed by immunostaining. We detected diverse populations of smooth muscle cells (SMCs), fibroblasts, and endothelial cells (ECs) in the aortic wall. Aortic tissues from MFS showed alterations of cell populations with increased de-differentiated proliferative SMCs compared to controls. Furthermore, there was a downregulation of MYOCD and MYH11 in SMCs, and an upregulation of COL1A1/2 in fibroblasts in MFS samples compared to controls. We also examined TGF-β signaling, an important pathway in aortic homeostasis. We found that TGFB1 was significantly upregulated in two fibroblast clusters in MFS tissues. However, TGF-β receptor genes (predominantly TGFBR2) and SMAD genes were downregulated in SMCs, fibroblasts, and ECs in MFS, indicating impairment in TGF-β signaling. In conclusion, despite upregulation of TGFB1, the rest of the canonical TGF-β pathway and mature SMCs were consistently downregulated in MFS, indicating a potential compromise of TGF-β signaling and lack of stimulus for SMC differentiation