How Do Patients with Life-Limiting Illness and Caregivers Want End-Of-Life Prognostic Information Delivered? A Pilot Study

We aimed to identify the level of prognostic disclosure, type of prognostic information and delivery format of prognostic communication that older adults diagnosed with a life-limiting illness or caregivers prefer to receive. We developed and pilot tested an open-ended survey to 15 older patients and caregivers who had experience in health services for life-limiting illness either for a relative, friend or themselves. Five hypothetical clinical scenarios of prognostic options were presented to ascertain preferences. The preferred format to receive prognostic information was verbal delivery by the clinician with a written summary. Photos and videos were less favoured, and a table with numbers/percentages was least preferred. Distress levels to the prognostic scenarios were low, with the exception of a photo. We conclude that older patients/caregivers want end-of-life prognostic information delivered the traditional way, verbally by clinicians. Options to deliver prognostic information may vary across patient groups but empower clinicians in introducing end-of-life discussions with patients/caregivers. Our study illustrates the feasibility of involving terminal patients and caregivers in research that contributes to eliciting prognostic preferences. Further research is needed to understand whether the prognostic preferences of hospitalized patients with life-limiting illness differ

The end-of-life needs of Aboriginal and immigrant communities: a challenge to conventional medical models

IntroductionConcerns have been raised internationally about the palliative care needs of migrants and First Nations people. This article presents insights from research investigating the end-of-life needs of Aboriginal and culturally and linguistically diverse people living in Western Sydney, Australia. This region has a large rapidly growing, and highly diverse population and on average low socioeconomic status. The research was guided by an advisory panel made up of representatives of supportive and palliative medicine, bereavement support, Aboriginal health, and multicultural health facilities. It aimed to generate findings to support the delivery of culturally sensitive services in the public health system.MethodThe multi-method design and the conduct of the research were informed by the literature on researching with marginalized groups which highlights the ethical considerations needed to avoid replicating past injustices. Qualitative data was generated from key informants and community focus groups.ResultsThe analysis revealed seven themes and some suggested solutions which were relevant across several themes. The seven themes were: the Need for trusted relationships; Talking about death and dying; Knowledge of key services; Decision-making and obtaining consent from the patient; Appropriate physical spaces; Cultural practices around EOL; and Language barriers.DiscussionWithin each theme a variety of cultural beliefs and practices were revealed that conflicted with mainstream medical systems, indicating the need for changes in such systems. ‘Compassionate Communities' was identified as a model to support the necessary changes

Interventions to Improve Vaccination Uptake and Cost Effectiveness of Vaccination Strategies in Newly Arrived Migrants in the EU/EEA: A Systematic Review

Newly arrived migrants to the EU/EEA (arrival within the past five years), as well as other migrant groups in the region, might be under-immunised and lack documentation of previous vaccinations, putting them at increased risk of vaccine-preventable diseases circulating in Europe. We therefore performed a systematic review conforming to PRISMA guidelines (PROSPERO CRD42016045798) to explore: (i) interventions that improve vaccine uptake among migrants; and (ii) cost-effectiveness of vaccination strategies among this population. We searched MEDLINE, Embase, CINAHL, and Cochrane Database of Systematic Reviews (CDSR) between 1 January 2006 to 18 June 2018. We included three primary intervention studies performed in the EU/EEA or high-income countries and one cost effectiveness study relevant to vaccinations in migrants. Intervention studies showed small but promising impact only on vaccine uptake with social mobilization/community outreach, planned vaccination programs and education campaigns. Targeting migrants for catch-up vaccination is cost effective for presumptive vaccination for diphtheria, tetanus, and polio, and there was no evidence of benefit of carrying out pre-vaccination serological testing. The cost-effectiveness is sensitive to the seroprevalence and adherence to vaccinations of the migrant. We conclude that scarce but direct EU/EEA data suggest social mobilization, vaccine programs, and education campaigns are promising strategies for migrants, but more research is needed. Research should also study cost effectiveness of strategies. Vaccination of migrants should continue to be a public heath priority in EU/EEA

Initiation and completion of treatment for latent tuberculosis infection in migrants globally:a systematic review and meta-analysis

BACKGROUND: Latent tuberculosis infection (LTBI) is one of the most prevalent infections globally and can lead to the development of active tuberculosis disease. In many low-burden countries, LTBI is concentrated within migrant populations often because of a higher disease burden in the migrant's country of origin. National programmes consequently focus on screening and treating LTBI in migrants to prevent future tuberculosis cases; however, how effective these programmes are is unclear. We aimed to assess LTBI treatment initiation and outcomes among migrants, and the factors that influence both. METHODS: For this systematic review and meta-analysis, we searched Embase, MEDLINE, and Global Health, and manually searched grey literature from Jan 1, 2000, to April 21, 2020. We included primary research articles reporting on LTBI treatment initiation or completion, or both, in migrants and excluded articles in which data were not stratified by migrant status, or in which the data were related to outcomes before 2000. There were no geographical or language restrictions. All included studies were quality appraised using recognised tools depending on their design, and we assessed the heterogeneity of analyses using I2. We extracted data on the numbers of migrants initiating and completing treatment. Our primary outcomes were LTBI treatment initiation and completion in migrants (defined as foreign-born). We used random-effects meta-regression to examine the influence of factors related to these outcomes. The study is registered with PROSPERO (CRD42019140338). FINDINGS: 2199 publications were retrieved screened, after which 39 publications from 13 mostly high-income, low-burden countries were included in our analyses, with treatment initiation and completion data reported for 31 598 migrants positive for LTBI, with not all articles reporting the full pathway from initiation to completion. The pooled estimate for the true proportion of migrants testing positive who initiated treatment was 69% (95% CI 51-84; I2= 99·62%; 4409 of 8764). The pooled estimate for the true proportion of migrants on treatment in datasets, who subsequently completed it was 74% (95% CI = 66-81; I2= 99·19%; 15 516 of 25 629). Where data were provided for the entire treatment pathway, the pooled estimate for the true proportion of migrants who initiated and completed treatment after a positive test was only 52% (95% CI 40-64; I2= 98·90%; 3289 of 6652). Meta-regression showed that LTBI programmes are improving, with more recent reported data (2010-20) associated with better rates of treatment initiation and completion, with multiple complex factors affecting treatment outcomes in migrants. INTERPRETATION: Although our analysis highlights that LTBI treatment initiation and completion in migrants has improved considerably from 2010-20, there is still room for improvement, with drop out reported along the entire treatment pathway. The delivery of these screening and treatment programmes will require further strengthening if the targets to eradicate tuberculosis in low-incidence countries are to be met, with greater focus needed on engaging migrants more effectively in the clinic and understanding the diverse and unique barriers and facilitators to migrants initiating and completing treatment. FUNDING: European Society of Clinical Microbiology and Infectious Diseases, the Rosetrees Trust, the National Institute for Health Research, and the Academy of Medical Sciences

What must be done to tackle vaccine hesitancy and barriers to COVID-19 vaccination in migrants?

Migrants have been disproportionately impacted by COVID-19 and emerging evidence suggests they may face barriers to COVID-19 vaccination. Participatory approaches and engagement strategies are urgently needed to strengthen uptake, alongside innovative delivery mechanisms and sharing of best practice, to ensure migrants are better consider within countries’ existing vaccine priority structures

Strengthening screening for infectious diseases and vaccination among migrants in Europe: What is needed to close the implementation gaps?

Migration to the European Union (EU)/European Economic Area (EEA) affects the epidemiology of infectious diseases, including tuberculosis (TB), HIV, hepatitis B/C, and parasitic diseases. Some sub-populations of migrants are also considered to be an under-immunised group and thus at risk of vaccine-preventable diseases. Providing high-risk migrants access to timely and efficacious screening and vaccination, and understanding how best to implement more integrated screening and vaccination programmes into European health systems ensuring linkage to care and treatment, is key to improving the health of migrants and their communities, alongside meeting national and regional targets for infection surveillance, control, and elimination. The European Centre for Disease Prevention and Control (ECDC) has responded to calls to action to improve migrant health and strengthen universal health coverage by developing evidence-based guidance for policy makers, public health experts, and front-line healthcare professionals on how to approach screening and vaccination in newly arrived migrants within the EU/EEA. In this Commentary, we provide a perspective towards developing efficacious screening and vaccination of newly arrived migrants, with a focus on defining implementation challenges and evidence gaps in high-migrant receiving EU/EEA countries. There is a need now to leverage the increasing momentum around migrant health to both strengthen the evidence-base and to advocate for universal access to health care for all migrants in the EU/EEA, including undocumented migrants. This should include voluntary, confidential, and non-stigmatising screening and vaccination that should be free of charge and facilitate linkage to appropriate care and treatment

Novel gene function revealed by mouse mutagenesis screens for models of age-related disease

Determining the genetic bases of age-related disease remains a major challenge requiring a spectrum of approaches from human and clinical genetics to the utilization of model organism studies. Here we report a large-scale genetic screen in mice employing a phenotype-driven discovery platform to identify mutations resulting in age-related disease, both late-onset and progressive. We have utilized N-ethyl-N-nitrosourea mutagenesis to generate pedigrees of mutagenized mice that were subject to recurrent screens for mutant phenotypes as the mice aged. In total, we identify 105 distinct mutant lines from 157 pedigrees analysed, out of which 27 are late-onset phenotypes across a range of physiological systems. Using whole-genome sequencing we uncover the underlying genes for 44 of these mutant phenotypes, including 12 late-onset phenotypes. These genes reveal a number of novel pathways involved with age-related disease. We illustrate our findings by the recovery and characterization of a novel mouse model of age-related hearing loss

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial

Background: Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. Methods: We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124. Findings: Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82–1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98). Interpretation: We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial

Genomic epidemiology of SARS-CoV-2 in a UK university identifies dynamics of transmission

AbstractUnderstanding SARS-CoV-2 transmission in higher education settings is important to limit spread between students, and into at-risk populations. In this study, we sequenced 482 SARS-CoV-2 isolates from the University of Cambridge from 5 October to 6 December 2020. We perform a detailed phylogenetic comparison with 972 isolates from the surrounding community, complemented with epidemiological and contact tracing data, to determine transmission dynamics. We observe limited viral introductions into the university; the majority of student cases were linked to a single genetic cluster, likely following social gatherings at a venue outside the university. We identify considerable onward transmission associated with student accommodation and courses; this was effectively contained using local infection control measures and following a national lockdown. Transmission clusters were largely segregated within the university or the community. Our study highlights key determinants of SARS-CoV-2 transmission and effective interventions in a higher education setting that will inform public health policy during pandemics.</jats:p