Drink wise, age well; reducing alcohol related harm among people over 50: a study protocol

Background: Evidence suggests that the use of alcohol among older adults (defined as those aged 50+) has increased in recent years, with people aged 55-64 now more likely to exceed the recommended weekly guidelines than any other age group. Methods/ design: This is a quasi-experimental study with a before-after design. A postal questionnaire will be sent to 76,000 people aged 50 and over registered with a general practice in five different 'demonstration' (intervention) and control areas in the UK. Multiple interventions will then be delivered in demonstration areas across the UK. At the end of the programme, a postal questionnaire will be sent to the same individuals who completed it pre-programme to establish if there has been a reduction in alcohol use, at-risk drinking and alcohol related problems. Qualitative interviews with clients and staff will explore how the interventions were experienced; how they may work to bring about change and to identify areas for practice improvements. Discussion: This study protocol describes a multi-level, multi-intervention prevention-to-treatment programme which aims to reduce alcohol-related harm in people aged 50 and over

Accessibility and suitability of residential alcohol treatment for older adults: a mixed method study

Background Whilst alcohol misuse is decreasing amongst younger adults in many countries, it is increasing in older adults. Residential rehabilitation (rehab) is a vital component of the alcohol treatment system, particularly for those with relatively complex needs and entrenched alcohol problems. In this study, we sought to find out to what extent rehabs in England have upper age limits that exclude older adults, whether rehabs are responsive to older adults’ age-related needs and how older adults experience these services. Method This is a mixed method study. A search was carried out of Public Health England’s online directory of rehabs to identify upper age thresholds. Semi-structured qualitative interviews were carried out with 16 individuals who had attended one of five residential rehabs in England and Wales since their 50th birthday. A researcher with experience of a later life alcohol problem conducted the interviews. Results Of the 118 services listed on Public Health England’s online directory of rehabs, 75% stated that they had an upper age limit that would exclude older adults. Perceived differences in values, attitudes and behaviour between younger and older residents had an impact on older residents’ experience of rehab. Activities organised by the rehabs were often based on physical activity that some older adults found it difficult to take part in and this could create a sense of isolation. Some older adults felt unsafe in rehab and were bullied, intimidated and subjected to ageist language and attitudes. Conclusion This study identified direct and indirect age discrimination in rehabs contrary to the law. Further research is required to find out if age discrimination exists in rehabs in other countries. Rehabs should remove arbitrary age limits and ensure that they are responsive to the needs of older adults

Alcohol, other drugs and sight loss: a scoping study.

The research team and Thomas Pocklington Trust have produced a guide for professionals working in substance use and sight loss

Alcohol service provision for older people in an area experiencing high alcohol use and health inequalities

UK society is ageing. Older people who drink alcohol, drink more than those from previous generations, drink more frequently than other age groups and are more likely to drink at home and alone. Alcohol problems in later life however are often under-detected and under-reported meaning older people experiencing alcohol problems have high levels of unmet need

Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity

The combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, common and rare variants from whole-exome sequencing data of about 4000 SARS-CoV-2-positive individuals were used to define an interpretable machine-learning model for predicting COVID-19 severity. First, variants were converted into separate sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. The Boolean features selected by these logistic models were combined into an Integrated PolyGenic Score that offers a synthetic and interpretable index for describing the contribution of host genetics in COVID-19 severity, as demonstrated through testing in several independent cohorts. Selected features belong to ultra-rare, rare, low-frequency, and common variants, including those in linkage disequilibrium with known GWAS loci. Noteworthily, around one quarter of the selected genes are sex-specific. Pathway analysis of the selected genes associated with COVID-19 severity reflected the multi-organ nature of the disease. The proposed model might provide useful information for developing diagnostics and therapeutics, while also being able to guide bedside disease management. © 2021, The Author(s)

Genetic mechanisms of critical illness in Covid-19.

Host-mediated lung inflammation is present,1 and drives mortality,2 in critical illness caused by Covid-19. Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development.3 Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study(GWAS) in 2244 critically ill Covid-19 patients from 208 UK intensive care units (ICUs). We identify and replicate novel genome-wide significant associations, on chr12q24.13 (rs10735079, p=1.65 [Formula: see text] 10-8) in a gene cluster encoding antiviral restriction enzyme activators (OAS1, OAS2, OAS3), on chr19p13.2 (rs2109069, p=2.3 [Formula: see text] 10-12) near the gene encoding tyrosine kinase 2 (TYK2), on chr19p13.3 (rs2109069, p=3.98 [Formula: see text] 10-12) within the gene encoding dipeptidyl peptidase 9 (DPP9), and on chr21q22.1 (rs2236757, p=4.99 [Formula: see text] 10-8) in the interferon receptor gene IFNAR2. We identify potential targets for repurposing of licensed medications: using Mendelian randomisation we found evidence in support of a causal link from low expression of IFNAR2, and high expression of TYK2, to life-threatening disease; transcriptome-wide association in lung tissue revealed that high expression of the monocyte/macrophage chemotactic receptor CCR2 is associated with severe Covid-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms, and mediators of inflammatory organ damage in Covid-19. Both mechanisms may be amenable to targeted treatment with existing drugs. Large-scale randomised clinical trials will be essential before any change to clinical practice

Perception of health-related quality of life in children with chronic kidney disease by the patients and their caregivers: Multicentre national study results

OBJECTIVE: The aim of the study was to analyse the health-related quality of life (HRQoL) in Polish children with chronic kidney disease (CKD) dependant on the CKD stage, treatment modality and selected social life elements in families of the patients. Furthermore, potential differences between self-report and parent/proxy reports and the factors influencing them were assessed. METHODS: A total of 203 CKD children (on haemodialysis (HD), peritoneal dialysis (PD) and conservative treatment (CT)) and their 388 parent/proxies were enrolled into a cross-sectional national study. The demographic and social data were evaluated. We used the Paediatric Quality of Life Inventory 4.0 Generic Core Scales to assess the HRQoL in children. RESULTS: Health-related quality of life scores for all CKD groups were significantly lower in all domains compared with population norms, the lowest one being in the HD group. In CT children, HRQoL did not depend on the CKD stage. Both parents assessed the HRQoL of their children differently depending on their involvement in the care. There are differences between the HRQoL scores of the children and their parents. CONCLUSION: The HRQoL in children with CKD is lower than in healthy children. This is already observed in the early stages of the disease. The disease itself influences the child’s mental state. Children on HD require special support on account of the lowest demonstrated overall HRQoL. Children’s lower rating of the quality of life observed by their parents may render the patients unmotivated and adversely affect their adjustment to life in later years. It may also create conflicts between the parents and the children

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

Background: Many patients with COVID-19 have been treated with plasma containing anti-SARS-CoV-2 antibodies. We aimed to evaluate the safety and efficacy of convalescent plasma therapy in patients admitted to hospital with COVID-19. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. The trial is underway at 177 NHS hospitals from across the UK. Eligible and consenting patients were randomly assigned (1:1) to receive either usual care alone (usual care group) or usual care plus high-titre convalescent plasma (convalescent plasma group). The primary outcome was 28-day mortality, analysed on an intention-to-treat basis. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. Findings: Between May 28, 2020, and Jan 15, 2021, 11558 (71%) of 16287 patients enrolled in RECOVERY were eligible to receive convalescent plasma and were assigned to either the convalescent plasma group or the usual care group. There was no significant difference in 28-day mortality between the two groups: 1399 (24%) of 5795 patients in the convalescent plasma group and 1408 (24%) of 5763 patients in the usual care group died within 28 days (rate ratio 1·00, 95% CI 0·93–1·07; p=0·95). The 28-day mortality rate ratio was similar in all prespecified subgroups of patients, including in those patients without detectable SARS-CoV-2 antibodies at randomisation. Allocation to convalescent plasma had no significant effect on the proportion of patients discharged from hospital within 28 days (3832 [66%] patients in the convalescent plasma group vs 3822 [66%] patients in the usual care group; rate ratio 0·99, 95% CI 0·94–1·03; p=0·57). Among those not on invasive mechanical ventilation at randomisation, there was no significant difference in the proportion of patients meeting the composite endpoint of progression to invasive mechanical ventilation or death (1568 [29%] of 5493 patients in the convalescent plasma group vs 1568 [29%] of 5448 patients in the usual care group; rate ratio 0·99, 95% CI 0·93–1·05; p=0·79). Interpretation: In patients hospitalised with COVID-19, high-titre convalescent plasma did not improve survival or other prespecified clinical outcomes. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research