Use and value of systematic reviews in English local authority public health: a qualitative study

Background Responsibility for public health in England transferred from the National Health Service to local authorities in 2013, representing a different decision-making environment. Systematic reviews are considered the gold standard of evidence for clinical decisionmaking but little is known about their use in local government public health. This study aimed to explore the extent to which public health decision-makers in local authorities engage with systematic reviews and how they do so. Methods Semi-structured interviews were conducted with senior public health practitioners (n=14) in Yorkshire and the Humber local authorities. Sampling was purposive and involved contacting Directors of Public Health directly and snowballing through key contacts. Face-to-face or telephone interviews were digitally recorded, transcribed verbatim and analysed using the Framework Method. Results Public health practitioners described using systematic reviews directly in decision-making and engaging with them more widely in a range of ways, often through a personal commitment to professional development. They saw themselves as having a role to advocate for the use of rigorous evidence, including systematic reviews, in the wider local authority. Systematic reviews were highly valued in principle and public health practitioners had relevant skills to find and appraise them. However, the extent of use varied by individual and local authority and was limited by the complexity of decision-making and various barriers. Barriers included that there were a limited number of systematic reviews available on certain public health topics, such as the wider determinants of health, and that the narrow focus of reviews was not reflective of complex public health decisions facing local authorities. Reviews were used alongside a range of other evidence types, including grey literature. The source of evidence was often considered an indicator of quality, with specific organisations, such as Public Health England, NICE and Cochrane, particularly trusted. Conclusions Research use varies and should be considered within the specific decision-making and political context. There is a need for systematic reviews to be more reflective of the decisions facing local authority public health teams

Fermentation of lignocellulosic material by the alternative industrial ethanol yeast Dekkera bruxellensis

Bioethanol is one alternative energy fuel that can be produced from different types of biomass. Second generation bioethanol comes from fermentation of lignocellulosic material and can be seen as a more environmental friendly alternative as e.g. forest residues and agricultural by-products are used. To be able to use lignocellulosic biomass in ethanol production, it has to be subjected to different treatments first. In this study, aspen sawdust was used as lignocellulosic material. After pretreatment with steam explosion and hydrolysis, using enzymes, a hydrolysate was obtained containing dissolved sugars, e.g. glucose. Fermentation of glucose into ethanol was done using two different yeasts to compare the differences: the traditional baker’s yeast Saccharomyces cerevisiae J672 and the yeast Dekkera bruxellensis CBS 11269, most known as a spoilage yeast but recently found to be the producing organism of ethanol in an ethanol production plant. In the study, the addition of (NH4)2SO4 at 2 g/L did not affect the growth negatively. Yeast extract was observed to be an essential media component for growth of D. bruxellensis CBS 11269 and improved the growth for S. cerevisiae J672. Due to the high amounts of toxic compounds acting inhibitory to the yeast, the hydrolysate produced needed to be diluted in order to achieve yeast growth. Unadapted S. cerevisiae J672 grew in 1:5 and 1:10 diluted hydrolysate while D. bruxellensis CBS 11269 only grew in the 1:10 dilution. Adapted yeast cells, of both yeasts, in a continuous experiment with recirculation, grew well in both 1:10 and 1:5 diluted hydrolysate resulting in an ethanol yield between 0.21-0.26 g ethanol/g glucose. No clear difference between the yeasts was seen. When applying the same procedure in fermenters, the same dilution rate as in the smaller scale experiment was not achieved properly and neither did the dilution rate become the same for both yeasts. No comparison between the yeasts could therefore be made for the fermenter part. The ethanol yield for S. cerevisiae J672 was between 0.35-0.36 g ethanol/g glucose for the media compositions that occurred during the experiments and for D. bruxellensis CBS 11269 it varied between 0.31-0.37 g ethanol/g glucose

Strategies for recruitment and retention of teen mothers in a program to prevent repeat pregnancy

Background: We describe challenges to recruitment and retention of teen mothers in a study to prevent repeat teen pregnancies, and strategies used to overcome them. Methods: We documented recruitment efforts, the teens who were retained at each stage of the intervention and changes to strategies. Results: Challenges to recruitment and retention were related to lifestyles, immaturity, and competing demands, among others. Successful strategies included bus advertisements, early pairing of teens with mentors, using electronic media, convenient meeting times with a meal, providing child care, transportation vouchers and immediate incentives. Conclusions: This study highlights impediments to teen mother research recruitment and retention, and the value of emerging technologies and strong bonding relationships early in the intervention to maximize recruitment and retention

A systematic review of mental health measurement scales for evaluating the effects of mental health prevention interventions

Background: Consistent and appropriate measurement is needed in order to improve understanding and evaluation of preventative interventions. This review aims to identify individual-level measurement tools used to evaluate mental health prevention interventions to inform harmonisation of outcome measurement in this area. Methods: Searches were conducted in PubMed, PsychInfo, CINAHL, Cochrane and OpenGrey for studies published between 2008 and 2018. that aimed to evaluate prevention interventions for common mental health problems in adults and used at least one measurement scale (PROSPERO CRD42018095519). For each study, mental health measurement tools were identified and reviewed for reliability, validity, ease-of-use, and cultural sensitivity. Results: 127 studies were identified that used 65 mental health measurement tools. Most were used by a single study (57%, N = 37) and measured depression (N = 20) or overall mental health (N = 18). The most commonly used questionnaire (15%) was the Centre for Epidemiological Studies Depression Scale (CES-D). A further 125 tools were identified which measured non- mental health specific outcomes. Conclusions: There was little agreement in measurement tools used across mental health prevention studies, which may hinder comparison across studies. Future research on measurement properties and acceptability of measurements in applied and scientific settings could be explored. Further work on supporting researchers to decide on appropriate outcome measurement for prevention would be beneficial for the field

Antidepressant treatment for postnatal depression

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:. To assess the effectiveness and safety of antidepressant drugs in comparison with any other treatment (psychological, psychosocial, or pharmacological), placebo, or treatment as usual for PND

Global population divergence and admixture of the brown rat (Rattus norvegicus)

Native to China and Mongolia, the brown rat (Rattus norvegicus) now enjoys a worldwide distribution. While black rats and the house mouse tracked the regional development of human agricultural settlements, brown rats did not appear in Europe until the 1500s, suggesting their range expansion was a response to relatively recent increases in global trade. We inferred the global phylogeography of brown rats using 32 k SNPs, and detected 13 evolutionary clusters within five expansion routes. One cluster arose following a southward expansion into Southeast Asia. Three additional clusters arose from two independent eastward expansions: one expansion from Russia to the Aleutian Archipelago, and a second to western North America. Westward expansion resulted in the colonization of Europe from which subsequent rapid colonization of Africa, the Americas and Australasia occurred, and multiple evolutionary clusters were detected. An astonishing degree of fine-grained clustering between and within sampling sites underscored the extent to which urban heterogeneity shaped genetic structure of commensal rodents. Surprisingly, few individuals were recent migrants, suggesting that recruitment into established populations is limited. Understanding the global population structure of R. norvegicus offers novel perspectives on the forces driving the spread of zoonotic disease, and aids in development of rat eradication programmes

The effectiveness of ablative and non-surgical therapies for early hepatocellular carcinoma: systematic review and network meta-analysis of randomised controlled trials

Background & Aims Non-surgical therapies are frequently used for patients with early or very early hepatocellular carcinoma (HCC). The aim of this systematic review and network meta-analysis (NMA) was to evaluate and compare the effectiveness of ablative and non-surgical therapies for patients with small HCC. Methods Nine databases were searched (March 2021) along with clinical trial registries. Randomised controlled trials (RCTs) of any ablative or non-surgical therapy versus any comparator in patients with HCC ≤ 3cm were eligible. Risk of bias (RoB) was assessed using the Cochrane RoB 2 tool. The effectiveness of therapies was compared using NMA. Threshold analysis was undertaken to identify which NMA results had less robust evidence. Results Thirty-seven eligible RCTs were included (including over 3700 patients). Most were from China (n=17) or Japan (n=7). Sample sizes ranged from 30 to 308 patients. The majority had a high RoB or some RoB concerns. No RCTs were identified for some therapies and no RCTs reported quality of life outcomes. The results of the NMA and treatment effectiveness rankings were very uncertain. However, the evidence demonstrated that percutaneous ethanol injection was worse than radiofrequency ablation for overall survival (hazard ratio [HR]: 1.45, 95% credible interval [CrI]: 1.16-1.82), progression-free survival (HR: 1.36, 95% CrI: 1.11-1.67), overall recurrence (relative risk [RR]: 1.19, 95% CrI: 1.02-1.39) and local recurrence (RR: 1.80, 95% CrI: 1.19-2.71). The threshold analysis suggested that robust evidence was lacking for some comparisons. Conclusions It is unclear which treatment is most effective for patients with small HCC because of limitations in the evidence base. It is also not known how these treatments would impact on quality of life. Further high quality RCTs are needed to provide robust evidence but may be difficult to undertake. Funding: National Institute for Health and Care Research (UK). Registration: PROSPERO CRD42020221357

Multinational characterization of neurological phenotypes in patients hospitalized with COVID-19

Neurological complications worsen outcomes in COVID-19. To define the prevalence of neurological conditions among hospitalized patients with a positive SARS-CoV-2 reverse transcription polymerase chain reaction test in geographically diverse multinational populations during early pandemic, we used electronic health records (EHR) from 338 participating hospitals across 6 countries and 3 continents (January–September 2020) for a cross-sectional analysis. We assessed the frequency of International Classification of Disease code of neurological conditions by countries, healthcare systems, time before and after admission for COVID-19 and COVID-19 severity. Among 35,177 hospitalized patients with SARS-CoV-2 infection, there was an increase in the proportion with disorders of consciousness (5.8%, 95% confidence interval [CI] 3.7–7.8%, pFDR < 0.001) and unspecified disorders of the brain (8.1%, 5.7–10.5%, pFDR < 0.001) when compared to the pre-admission proportion. During hospitalization, the relative risk of disorders of consciousness (22%, 19–25%), cerebrovascular diseases (24%, 13–35%), nontraumatic intracranial hemorrhage (34%, 20–50%), encephalitis and/or myelitis (37%, 17–60%) and myopathy (72%, 67–77%) were higher for patients with severe COVID-19 when compared to those who never experienced severe COVID-19. Leveraging a multinational network to capture standardized EHR data, we highlighted the increased prevalence of central and peripheral neurological phenotypes in patients hospitalized with COVID-19, particularly among those with severe disease

Gauging NOTCH1 Activation in Cancer Using Immunohistochemistry

Fixed, paraffin-embedded (FPE) tissues are a potentially rich resource for studying the role of NOTCH1 in cancer and other pathologies, but tests that reliably detect activated NOTCH1 (NICD1) in FPE samples have been lacking. Here, we bridge this gap by developing an immunohistochemical (IHC) stain that detects a neoepitope created by the proteolytic cleavage event that activates NOTCH1. Following validation using xenografted cancers and normal tissues with known patterns of NOTCH1 activation, we applied this test to tumors linked to dysregulated Notch signaling by mutational studies. As expected, frequent NICD1 staining was observed in T lymphoblastic leukemia/lymphoma, a tumor in which activating NOTCH1 mutations are common. However, when IHC was used to gauge NOTCH1 activation in other human cancers, several unexpected findings emerged. Among B cell tumors, NICD1 staining was much more frequent in chronic lymphocytic leukemia than would be predicted based on the frequency of NOTCH1 mutations, while mantle cell lymphoma and diffuse large B cell lymphoma showed no evidence of NOTCH1 activation. NICD1 was also detected in 38% of peripheral T cell lymphomas. Of interest, NICD1 staining in chronic lymphocytic leukemia cells and in angioimmunoblastic lymphoma was consistently more pronounced in lymph nodes than in surrounding soft tissues, implicating factors in the nodal microenvironment in NOTCH1 activation in these diseases. Among carcinomas, diffuse strong NICD1 staining was observed in 3.8% of cases of triple negative breast cancer (3 of 78 tumors), but was absent from 151 non-small cell lung carcinomas and 147 ovarian carcinomas. Frequent staining of normal endothelium was also observed; in line with this observation, strong NICD1 staining was also seen in 77% of angiosarcomas. These findings complement insights from genomic sequencing studies and suggest that IHC staining is a valuable experimental tool that may be useful in selection of patients for clinical trials