Report 14: Online community involvement in COVID-19 research & outbreak response: early insights from a UK perspective

The Patient Experience Research Centre (PERC) at Imperial College London is developing research to explore and understand people’s views about, experiences of and behavioural responses to the outbreak in the UK and elsewhere. To guide that effort and to help inform COVID-19 research and responses more broadly - for example in mathematical modelling and policy - PERC launched an online community involvement initiative that sought rapid, early insight from members of the public and aimed to establish a network for ongoing community engagement. Priority areas for COVID-19 research Vaccine development was considered the most urgent research priority for many respondents. Social studies exploring the public’s experiences, risk perceptions and behaviours during this outbreak were necessary and important according to 95% of the respondents. Such research could: Improve the way the current outbreak response is planned and implemented; Improve the way information and guidance is provided to and understood by the public; Optimise the support provided to communities and vulnerable groups; and Improve future outbreak preparedness. Other recommended areas of research included: Understanding the role of the media in influencing how people react and respond; Furthering our basic understanding of the virus – how it spreads, who it affects the most and why, and whether people achieve and maintain immunity after being infected; Critiquing the UK’s response to the pandemic against that of other countries; and Ensuring lessons can be learnt from this outbreak to better equip us for future outbreaks, and public health emergencies in general. Key unmet needs amongst communities The main challenges described by respondents were ineffective communication, including access to information and information overload; and conflicting guidance and misinformation. Respondents’ described feelings of concern, confusion and, in some cases, panic as a result of these communication and information challenges. Others shared their frustration that there was nowhere to post their concerns or questions. In addition, respondents expressed a need for more detailed and bespoke practical guidance about their risk and how best to prepare and protect themselves and their loved ones. Almost half (47%) wanted to hear about the latest research on the virus, and 45% wanted a dedicated internet portal where they could access the latest information and trusted guidance. Making information more accessible to different communities, including those who are not online and those who have English as a second language was also highlighted as a priority

Infection-related and -unrelated malignancies, HIV and the aging population

Funding Information: Conflicts of interest: JR reports personal fees from Abbvie, Bionor, BMS, Boehringer, Gilead, Merck, Janssen, Tobira, Tibotec and ViiV, outside the submitted work. OK has received honoraria, consultancy and/or lecture fees from Abbott, Gilead, GSK, Janssen, Merck, Tibotec and Viiv outside the submitted work. All other authors state no commercial or other associations that may pose a conflict of interest. Funding: Primary support for EuroSIDA is provided by the European Commission BIOMED 1 (CT94-1637), BIOMED 2 (CT97-2713), 5th Framework (QLK2-2000-00773), 6th Framework (LSHP-CT-2006-018632) and 7th Framework (FP7/2007?2013; EuroCoord n? 260694) programmes. Current support also includes unrestricted grants from Janssen R&D, Merck and Co. Inc., Pfizer Inc. and GlaxoSmithKline LLC. The participation of centres in Switzerland was supported by The Swiss National Science Foundation (Grant 108787). The authors have no financial disclosures to make. Author contributions: LS developed the project, analysed the data, and was responsible for writing the manuscript. ?HB and OK contributed to the study design and analysis, interpretation of the data and writing of the manuscript. JL proposed the project and contributed to the study design, ideas for analysis, interpretation of the data and writing of the manuscript. BL, PD, AC, JR, BK, JT and IK contributed to national coordination, study design and writing of the manuscript. AM supervised the project and contributed to the study design and analysis, interpretation of the data and writing of the manuscript. Publisher Copyright: © 2016 British HIV AssociationObjectives: HIV-positive people have increased risk of infection-related malignancies (IRMs) and infection-unrelated malignancies (IURMs). The aim of the study was to determine the impact of aging on future IRM and IURM incidence. Methods: People enrolled in EuroSIDA and followed from the latest of the first visit or 1 January 2001 until the last visit or death were included in the study. Poisson regression was used to investigate the impact of aging on the incidence of IRMs and IURMs, adjusting for demographic, clinical and laboratory confounders. Linear exponential smoothing models forecasted future incidence. Results: A total of 15 648 people contributed 95 033 person-years of follow-up, of whom 610 developed 643 malignancies [IRMs: 388 (60%); IURMs: 255 (40%)]. After adjustment, a higher IRM incidence was associated with a lower CD4 count [adjusted incidence rate ratio (aIRR) CD4 count < 200 cells/μL: 3.77; 95% confidence interval (CI) 2.59, 5.51; compared with ≥ 500 cells/μL], independent of age, while a CD4 count < 200 cells/μL was associated with IURMs in people aged < 50 years only (aIRR: 2.51; 95% CI 1.40–4.54). Smoking was associated with IURMs (aIRR: 1.75; 95% CI 1.23, 2.49) compared with never smokers in people aged ≥ 50 years only, and not with IRMs. The incidences of both IURMs and IRMs increased with older age. It was projected that the incidence of IRMs would decrease by 29% over a 5-year period from 3.1 (95% CI 1.5–5.9) per 1000 person-years in 2011, whereas the IURM incidence would increase by 44% from 4.1 (95% CI 2.2–7.2) per 1000 person-years over the same period. Conclusions: Demographic and HIV-related risk factors for IURMs (aging and smoking) and IRMs (immunodeficiency and ongoing viral replication) differ markedly and the contribution from IURMs relative to IRMs will continue to increase as a result of aging of the HIV-infected population, high smoking and lung cancer prevalence and a low prevalence of untreated HIV infection. These findings suggest the need for targeted preventive measures and evaluation of the cost−benefit of screening for IURMs in HIV-infected populations.publishersversionPeer reviewe

Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe

Non-AIDS defining cancers in the D:A:D Study-time trends and predictors of survival : a cohort study

BACKGROUND:Non-AIDS defining cancers (NADC) are an important cause of morbidity and mortality in HIV-positive individuals. Using data from a large international cohort of HIV-positive individuals, we described the incidence of NADC from 2004-2010, and described subsequent mortality and predictors of these.METHODS:Individuals were followed from 1st January 2004/enrolment in study, until the earliest of a new NADC, 1st February 2010, death or six months after the patient's last visit. Incidence rates were estimated for each year of follow-up, overall and stratified by gender, age and mode of HIV acquisition. Cumulative risk of mortality following NADC diagnosis was summarised using Kaplan-Meier methods, with follow-up for these analyses from the date of NADC diagnosis until the patient's death, 1st February 2010 or 6 months after the patient's last visit. Factors associated with mortality following NADC diagnosis were identified using multivariable Cox proportional hazards regression.RESULTS:Over 176,775 person-years (PY), 880 (2.1%) patients developed a new NADC (incidence: 4.98/1000PY [95% confidence interval 4.65, 5.31]). Over a third of these patients (327, 37.2%) had died by 1st February 2010. Time trends for lung cancer, anal cancer and Hodgkin's lymphoma were broadly consistent. Kaplan-Meier cumulative mortality estimates at 1, 3 and 5 years after NADC diagnosis were 28.2% [95% CI 25.1-31.2], 42.0% [38.2-45.8] and 47.3% [42.4-52.2], respectively. Significant predictors of poorer survival after diagnosis of NADC were lung cancer (compared to other cancer types), male gender, non-white ethnicity, and smoking status. Later year of diagnosis and higher CD4 count at NADC diagnosis were associated with improved survival. The incidence of NADC remained stable over the period 2004-2010 in this large observational cohort.CONCLUSIONS:The prognosis after diagnosis of NADC, in particular lung cancer and disseminated cancer, is poor but has improved somewhat over time. Modifiable risk factors, such as smoking and low CD4 counts, were associated with mortality following a diagnosis of NADC

Report 10: Public response to UK Government recommendations on COVID-19: population survey, 17-18 March 2020

On Monday 16th March 2020 the UK government announced new actions to control COVID-19. These recommendations directly affected the entire UK population, and included the following: stop non-essential contact with others; stop all unnecessary travel; start working from home where possible; avoid pubs, clubs, theatres and other such social venues; and to isolate at home for 14 days if anyone in the household has a high temperature or a new and continuous cough. To capture public sentiment towards these recommendations, a YouGov survey was commissioned by the Patient Experience Research Centre (PERC), Imperial College London. The survey was completed by 2,108 UK adults between the dates of 17th – 18th March 2020. The survey results show the following: • 77% reported being worried about the COVID-19 outbreak in the UK. • 48% of adults who have not tested positive for COVID-19 believe it is likely they will be infected at some point in the future. • 93% of adults reported personally taking at least one measure to protect themselves from COVID-19 infection, including: o 83% washed their hands more frequently; o 52% avoided crowded areas; o 50% avoided social events; o 36% avoided public transport; o 31% avoided going out; o 11% avoided going to work; o 28% avoided travel to areas outside the UK. • There is high reported ability and willingness to self-isolate for 7 days* if advised to do so by a health professional (88%). • However only 44% reported being able to work from home. This was higher among managerial and professional workers (60%) than manual, semi-skilled, and casual workers (19%)^, reflecting less flexible job roles for manual and lower grade workers. • 71% reported changing behaviour in response to government guidance. The figure (53%) was lower for young adults (18-24 year-olds). • Hand washing (63%), avoiding persons with symptoms (61%), and covering your sneeze (53%) were more likely to be perceived as ‘very effective’ measures to prevent COVID-19 spread than common social distancing measures (avoiding going out (31%), to work (23%), to shops (16%) or to schools (19%))

Kappa-light chain predominance in serum and cerebrospinal-fluid from human-immunodeficiency-virus type-1 (HIV-1)-infected patients

We measured kappa/lambda light chain ratios of Ig and IgG in 41 serum and 34 cerebrospinal fluid (CSF) samples from 47 patients at different chemical stages of human immunodeficiency virus type 1 (HIV-1) infection and in serum and CSF samples from control subjects. Both ratios were more elevated in HIV-1 seropositive subjects than controls. The elevation was more evident in samples from asymptomatic seropositive patients (ASP) than those from patients with acquired immunodeficiency syndrome (AIDS). In addition, there was a statistically significant elevation of Ig kappa/lambda ratios in ASP CSF compared to serum. We also delineated the light chain composition of oligoclonal IgG bands (OCB) by isoelectric focusing followed by immunofixation in CSF and serum samples from selected ASP and patients with AIDS who had neurological involvement. Five of six AIDS and all seven ASP samples had IgG OCB exclusively or predominantly of the kappa type. Four IgG OCB of the lambda type and one free lambda chain band were seen in CSF from a pediatric AIDS patient. The presence of an abnormally elevated kappa/lambda ratio correlated with the presence of IgG kappa OCB (p &lt; 0.02). We conclude that HIV-1 infection is associated with a kappa light chain predominance and with OCB mainly composed of kappa light chains

Perceptions and behavioural responses of the general public during the COVID-19 pandemic: A cross-sectional survey of UK Adults

Objective: To examine risk perceptions and behavioural responses of the UK adult population during the early phase of the COVID-19 epidemic in the UK. Design: A cross-sectional survey Setting: Conducted with a nationally representative sample of UK adults within 48 hours of the UK Government advising the public to stop non-essential contact with others and all unnecessary travel. Participants: 2,108 adults living in the UK aged 18 years and over. Data were collected between March 17 and 18 2020. Main outcome measures: Descriptive statistics for all survey questions, including the number of respondents and the weighted percentages. Logistic regression was used to identify sociodemographic variation in: (1) adoption of social-distancing measures, (2) ability to work from home, and (3) willingness and (4) ability to self-isolate. Results Overall, 1,992 (94.2%) respondents reported taking at least one preventive measure: 85.8% washed their hands with soap more frequently; 56.5% avoided crowded areas and 54.5% avoided social events. Adoption of social-distancing measures was higher in those aged over 70 compared to younger adults aged 18 to 34 years (aOR:1.9; 95% CI:1.1 to 3.4). Those with the lowest household income were six times less likely to be able to work from home (aOR:0.16; 95% CI:0.09 to 0.26) and three times less likely to be able to self-isolate (aOR:0.31; 95% CI:0.16 to 0.58). Ability to self-isolate was also lower in black and minority ethnic groups (aOR:0.47; 95% CI:0.27 to 0.82). Willingness to self-isolate was high across all respondents. Conclusions The ability to adopt and comply with certain NPIs is lower in the most economically disadvantaged in society. Governments must implement appropriate social and economic policies to mitigate this. By incorporating these differences in NPIs among socio-economic subpopulations into mathematical models of COVID-19 transmission dynamics, our modelling of epidemic outcomes and response to COVID-19 can be improved