Background There remains uncertainty about the epidemiology of SARS-CoV-2 among school students and staff and the extent to which non-pharmaceutical-interventions reduce the risk of school settings. Methods We conducted an open cohort study in a sample of 59 primary and 97 secondary schools in 15 English local authority areas that were implementing government guidance to schools open during the pandemic. We estimated SARS-CoV-2 infection prevalence among those attending school, antibody prevalence, and antibody negative to positive conversion rates in staff and students over the school year (November 2020–July 2021). Findings 22,585 staff and students participated. SARS-CoV-2 infection prevalence among those attending school was highest during the first two rounds of testing in the autumn term, ranging from 0.7% (95% CI 0.2, 1.2) among primary staff in November 2020 to 1.6% (95% CI 0.9, 2.3) among secondary staff in December 2020. Antibody conversion rates were highest in the autumn term. Infection patterns were similar between staff and students, and between primary and secondary schools. The prevalence of nucleoprotein antibodies increased over the year and was lower among students than staff. SARS-CoV-2 infection prevalence in the North-West region was lower among secondary students attending school on normal school days than the regional estimate for secondary school-age children. Interpretation SARS-CoV-2 infection prevalence in staff and students attending school varied with local community infection rates. Non-pharmaceutical interventions intended to prevent infected individuals attending school may have partially reduced the prevalence of infection among those on the school site. Funding UK Department of Health and Social Care.
Background: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces a prothrombotic state, but long-term effects of COVID-19 on incidence of vascular diseases are unclear. Methods: We studied vascular diseases after COVID-19 diagnosis in population-wide anonymized linked English and Welsh electronic health records from January 1 to December 7, 2020. We estimated adjusted hazard ratios comparing the incidence of arterial thromboses and venous thromboembolic events (VTEs) after diagnosis of COVID-19 with the incidence in people without a COVID-19 diagnosis. We conducted subgroup analyses by COVID-19 severity, demographic characteristics, and previous history. Results: Among 48 million adults, 125 985 were hospitalized and 1 319 789 were not hospitalized within 28 days of COVID-19 diagnosis. In England, there were 260 279 first arterial thromboses and 59 421 first VTEs during 41.6 million person-years of follow-up. Adjusted hazard ratios for first arterial thrombosis after COVID-19 diagnosis compared with no COVID-19 diagnosis declined from 21.7 (95% CI, 21.0–22.4) in week 1 after COVID-19 diagnosis to 1.34 (95% CI, 1.21–1.48) during weeks 27 to 49. Adjusted hazard ratios for first VTE after COVID-19 diagnosis declined from 33.2 (95% CI, 31.3–35.2) in week 1 to 1.80 (95% CI, 1.50–2.17) during weeks 27 to 49. Adjusted hazard ratios were higher, for longer after diagnosis, after hospitalized versus nonhospitalized COVID-19, among Black or Asian versus White people, and among people without versus with a previous event. The estimated whole-population increases in risk of arterial thromboses and VTEs 49 weeks after COVID-19 diagnosis were 0.5% and 0.25%, respectively, corresponding to 7200 and 3500 additional events, respectively, after 1.4 million COVID-19 diagnoses. Conclusions: High relative incidence of vascular events soon after COVID-19 diagnosis declines more rapidly for arterial thromboses than VTEs. However, incidence remains elevated up to 49 weeks after COVID-19 diagnosis. These results support policies to prevent severe COVID-19 by means of COVID-19 vaccines, early review after discharge, risk factor control, and use of secondary preventive agents in high-risk patients.
5q- Spinal muscular atrophy (SMA) is a progressive inherited disorder of the motor neurons due to bi allelic mutations in SMN1 gene responsible for a high mortality in infancy, and significant morbidity in childhood, adolescence and into adult life. Advent of SMN1 gene splice modifiers have revolutionised the therapeutic landscape in SMA. Nusinersen is the first such treatment in SMA and is delivered intrathecally via lumbar puncture (LP). Nusinersen is currently accessible to the UK SMA patients via a managed access agreement. LPs are difficult in some patients due to previous spinal fusion surgery (especially in Type 2 SMA), obesity, and other anatomical challenges. Some patients and families find repeat LPs intolerable. A proportion of SMA patients therefore have not been able to access nusinersen for the above reasons, although they would otherwise choose nusinersen as the treatment of first-choice. Nusinersen delivery via a lumbar port and catheter system is not licensed. However it has been successfully attempted in other European and US centres before. Here we report the details and protocols of the first UK adult and paediatric SMA patients who underwent lumbar port and catheter insertion to successfully deliver nusinersen treatment, thereby maintaining the choice of a therapeutic option for a proportion of SMA patients.
Objectives Across diverse ethnic groups in the UK, explore attitudes and intentions towards COVID-19 vaccination and sources of COVID-19 information. Design Remote qualitative interviews and focus groups (FGs) conducted June–October 2020 before UK COVID-19 vaccine approval. Data were transcribed and analysed through inductive thematic analysis and mapped to the Theoretical Domains Framework. Setting England and Wales. Participants 100 participants from 19 self-identified ethnic groups. Results Mistrust and doubt were reported across ethnic groups. Many participants shared concerns about perceived lack of information about COVID-19 vaccine safety and efficacy. There were differences within each ethnic group, with factors such as occupation and perceived health status influencing intention to accept a vaccine once made available. Across ethnic groups, participants believed that public contact occupations, older adults and vulnerable groups should be prioritised for vaccination. Perceived risk, social influences, occupation, age, comorbidities and engagement with healthcare influenced participants’ intentions to accept vaccination once available. All Jewish FG participants intended to accept, while all Traveller FG participants indicated they probably would not. Facilitators to COVID-19 vaccine uptake across ethnic groups included: desire to return to normality and protect health and well-being; perceived higher risk of infection; evidence of vaccine safety and efficacy; vaccine availability and accessibility. COVID-19 information sources were influenced by social factors and included: friends and family; media and news outlets; research literature; and culture and religion. Participants across most different ethnic groups were concerned about misinformation or had negative attitudes towards the media. Conclusions During vaccination rollout, including boosters, commissioners and providers should provide accurate information, authentic community outreach and use appropriate channels to disseminate information and counter misinformation. Adopting a context-specific approach to vaccine resources, interventions and policies and empowering communities has potential to increase trust in the programme.
Background Poor sexual and reproductive health (SRH) outcomes amongst adolescent girls in India have been associated with inadequate knowledge of SRH. Evidence suggests that social media can promote health-seeking behaviors. Our objective in this study was to determine the association between exposure to social media and SRH knowledge among adolescent girls in Bihar and Uttar Pradesh, India. Methods A cross-sectional study was conducted with 10,425 adolescent girls from the UDAYA survey (wave-2, 2018–19). Girls’ exposure to social media was the key predictor, and SRH knowledge of sexual intercourse and pregnancy, contraceptive methods, and HIV/AIDS were outcomes of interest. Multivariable logistic regression models were performed to assess the association between exposure to social media and knowledge of SRH among adolescent girls. Results Of the study participants (n = 10,425), 28.0% (n = 3,160) had exposure to social media. Overall, 8.7%, 11.4%, and 6.6% of respondents had sufficient knowledge of sexual intercourse and pregnancy, contraceptive methods, and HIV/AIDS, respectively. Exposure to social media was associated with increased odds of knowledge of sexual intercourse and pregnancy (Odds ratio [OR]: 1.38; 95% confidence interval [CI]: 1.18, 1.61), contraceptive methods (OR: 1.46; 95% CI: 1.27, 1.67), and HIV/AIDS (OR: 2.18; 95% CI: 1.84, 2.58). Conclusions Our study shows the potency of exposure to social media in influencing SRH knowledge, which exclusively benefits female adolescents who are educated, residing in urban areas, and from wealthier families. Digital media-focused interventions inclusive of socio-cultural contexts (e.g., strategic investment in education and creating economic opportunities) are crucial to optimize social media's impact on SRH knowledge enhancements.
Introduction: The Radiography Research Ethics Standards for Europe (RRESFE) project aims to provide a cross-sectional snapshot of current research ethics systems, processes, and awareness of such, across Europe together with identifying the associated challenges, education, and training needs. Methods: A cross-sectional online survey targeting radiography researchers in Europe was conducted. Data collection took place between April 26 and July 12, 2021, using a snowball sampling approach. Descriptive and analytical statistics were used to identify trends in research ethics frameworks across Europe. Results: 285 responses were received across 33 European and 23 non-European countries. Most (n = 221; 95%) European respondents stated ethics approval is required before commencing research in their country. Requirements around research ethics approval and awareness of such requirements varied by European region (X2 (2, n = 129) = 7.234, p = 0.013) and were found to differ depending on the type of research participant and study design. Additionally, European respondents reported ethics approval is a national requirement more often than their non-European counterparts (X2 (1, n = 282) = 4.316, p = 0.049). Requirements for ethics approval were also associated with the undergraduate programme duration (2-year vs. 3-year vs. 3.5 year vs. 4-year vs. multiple programme durations; X2 (4, n = 231) = 10.075, p = 0.016) and availability of postgraduate training (postgraduate training available vs. postgraduate training not available; X2 (1, n = 231) = 15.448, p = <0.001) within respondents' country. Conclusion: Respondents from countries with longer programme durations/availability of multiple programme lengths, availability of postgraduate training, and establishment of European Qualifications Framework Level 6 were generally associated with less uncertainty and more comprehensive research ethics requirements. Implications for practice: Results are informative of the current status of research ethics within evidence-based radiography.
Introduction: The Radiography Research Ethics Standards for Europe (RRESFE) project aimed to provide a cross-sectional view of the current state of radiography research ethics across Europe. This included investigating education and training in research ethics, and identifying the key challenges and potential improvements associated with using existing research ethics frameworks. Methods: This cross-sectional online survey targeting radiography researchers in Europe was conducted between April 26 and July 12, 2021. Descriptive and analytical statistics were used to identify research ethics education and training trends. Content analysis of qualitative responses was employed to identify significant challenges and proposed improvements in research ethics frameworks of practice. Results: There were 232 responses received across 33 European countries. Most (n ¼ 132; 57%) respondents had received some research ethics training; however, fewer participants had received training on safeguarding vulnerable patients (n ¼ 72; 38%), diversity and inclusivity (n ¼ 62; 33%), or research with healthy volunteers (n ¼ 60; 32%). Training was associated with a greater perceived importance of the need for research ethics review (p ¼ 0.031) and with the establishment of EQF Level 6 training (p ¼ 0.038). The proportion of formally trained researchers also varied by region (p ¼ <0.001). Time-toethics-approval was noted as the biggest challenge for professionals making research ethics applications. Conclusion: Early and universal integration of research-oriented teaching within the radiography education framework which emphasises research ethics is recommended. Additionally, study findings suggest research ethics committee application and approval processes could be further simplified and streamlined. Implications for practice: The survey contributes to a growing body of knowledge surrounding the importance of education and training in research ethics for assuring a high standard of research outputs
Objectives To explore public reactions to the COVID-19 pandemic across diverse ethnic groups. Design Remote qualitative interviews and focus groups in English or Punjabi. Data were transcribed and analysed through inductive thematic analysis. Setting England and Wales, June to October 2020. Participants 100 participants from 19 diverse ‘self-identified’ ethnic groups. Results Dismay, frustration and altruism were reported across all ethnic groups during the first 6–9 months of the COVID-19 pandemic. Dismay was caused by participants’ reported individual, family and community risks, and loss of support networks. Frustration was caused by reported lack of recognition of the efforts of ethnic minority groups (EMGs), inaction by government to address COVID-19 and inequalities, rule breaking by government advisors, changing government rules around: border controls, personal protective equipment, social distancing, eating out, and perceived poor communication around COVID-19 and the Public Health England COVID-19 disparities report (leading to reported increased racism and social isolation). Altruism was felt by all, in the resilience of National Health Service (NHS) staff and their communities and families pulling together. Data, participants’ suggested actions and the behaviour change wheel informed suggested interventions and policies to help control COVID-19. Conclusion To improve trust and compliance future reports or guidance should clearly explain any stated differences in health outcomes by ethnicity or other risk group, including specific messages for these groups and concrete actions to minimise any risks. Messaging should reflect the uncertainty in data or advice and how guidance may change going forward as new evidence becomes available. A contingency plan is needed to mitigate the impact of COVID-19 across all communities including EMGs, the vulnerable and socially disadvantaged individuals, in preparation for any rise in cases and for future pandemics. Equality across ethnicities for healthcare is essential, and the NHS and local communities will need to be supported to attain this.
Background Knowledge of the window of SARS-CoV-2 infectiousness is crucial in developing policies to curb transmission. Mathematical modelling based on scarce empirical evidence and key assumptions has driven isolation and testing policy, but real-world data are needed. We aimed to characterise infectiousness across the full course of infection in a real-world community setting. Methods The Assessment of Transmission and Contagiousness of COVID-19 in Contacts (ATACCC) study was a UK prospective, longitudinal, community cohort of contacts of newly diagnosed, PCR-confirmed SARS-CoV-2 index cases. Household and non-household exposed contacts aged 5 years or older were eligible for recruitment if they could provide informed consent and agree to self-swabbing of the upper respiratory tract. The primary objective was to define the window of SARS-CoV-2 infectiousness and its temporal correlation with symptom onset. We quantified viral RNA load by RT-PCR and infectious viral shedding by enumerating cultivable virus daily across the course of infection. Participants completed a daily diary to track the emergence of symptoms. Outcomes were assessed with empirical data and a phenomenological Bayesian hierarchical model. Findings Between Sept 13, 2020, and March 31, 2021, we enrolled 393 contacts from 327 households (the SARS-CoV-2 pre-alpha and alpha variant waves); and between May 24, 2021, and Oct 28, 2021, we enrolled 345 contacts from 215 households (the delta variant wave). 173 of these 738 contacts were PCR positive for more than one timepoint, 57 of which were at the start of infection and comprised the final study population. The onset and end of infectious viral shedding were captured in 42 cases and the median duration of infectiousness was 5 (IQR 3–7) days. Although 24 (63%) of 38 cases had PCR-detectable virus before symptom onset, only seven (20%) of 35 shed infectious virus presymptomatically. Symptom onset was a median of 3 days before both peak viral RNA and peak infectious viral load (viral RNA IQR 3–5 days, n=38; plaque-forming units IQR 3–6 days, n=35). Notably, 22 (65%) of 34 cases and eight (24%) of 34 cases continued to shed infectious virus 5 days and 7 days post-symptom onset, respectively (survival probabilities 67% and 35%). Correlation of lateral flow device (LFD) results with infectious viral shedding was poor during the viral growth phase (sensitivity 67% [95% CI 59–75]), but high during the decline phase (92% [86–96]). Infectious virus kinetic modelling suggested that the initial rate of viral replication determines the course of infection and infectiousness. Interpretation Less than a quarter of COVID-19 cases shed infectious virus before symptom onset; under a crude 5-day self-isolation period from symptom onset, two-thirds of cases released into the community would still be infectious, but with reduced infectious viral shedding. Our findings support a role for LFDs to safely accelerate deisolation but not for early diagnosis, unless used daily. These high-resolution, community-based data provide evidence to inform infection control guidance. Funding National Institute for Health and Care Research.
As robotic assisted surgery (RAS) expands to smaller centres, platforms are shared between specialities. Healthcare providers must consider case volume and mix required to maintain quality and cost-effectiveness. This can be informed, in-part, by the volume-outcome relationship. We perform a systematic review to describe the volume-outcome relationship in intra-abdominal robotic assisted surgery to report on suggested minimum volumes standards. A literature search of Medline, NICE Evidence Search, Health Technology Assessment Database and Cochrane Library using the terms: “robot*”, “surgery”, “volume” and “outcome” was performed. The included procedures were gynaecological: hysterectomy, urological: partial and radical nephrectomy, cystectomy, prostatectomy, and general surgical: colectomy, oesophagectomy. Hospital and surgeon volume measures and all reported outcomes were analysed. 41 studies, including 983149 procedures, met the inclusion criteria. Study quality was assessed using the Newcastle-Ottawa Quality Assessment Scale and the retrieved data was synthesised in a narrative review. Significant volume-outcome relationships were described in relation to key outcome measures, including operative time, complications, positive margins, lymph node yield and cost. Annual surgeon and hospital volume thresholds were described. We concluded that in centres with an annual volume of fewer than 10 cases of a given procedure, having multiple surgeons performing these procedures led to worse outcomes and, therefore, opportunities should be sought to perform other complimentary robotic procedures or undertake joint cases.
Recently England and Netherlands have changed their consent system from Opt In to Opt Out. The reflections shared in this paper give insight and may be helpful for other nation considering likewise. Strong support in England for the change in legislation led to Opt Out being introduced without requiring a vote in parliament in 2019. In Netherlands the bill passed by the smallest possible majority in 2018. Both countries implemented a public campaign to raise awareness. In England registration on the Donor Register is voluntary. Registration was required in Netherlands for all residents 18 years and older. For those not already on the register, letters were sent by the Dutch Government to ask individuals to register. If people did not respond they would be legally registered as having “no objection.” After implementation of Opt Out in England 42.3% is registered Opt In, 3.6% Opt Out, and 54.1% has no registration. In contrast in Netherlands the whole population is registered with 45% Opt In, 31% Opt Out and 24% “No Objection.” It is too soon to draw conclusions about the impact on the consent rate and number of resulting organ donors. However, the first signs are positive.
Background People with kidney failure have high risk of postoperative morbidity and mortality. Although the Revised Cardiac Risk Index (RCRI) is used to estimate the risk of major postoperative events, it has not been validated in this population. We aimed to externally validate the RCRI and determine whether updating the model improved predictions for people with kidney failure. Methods We derived a retrospective, population-based cohort of adults with kidney failure (maintenance dialysis or sustained estimated glomerular filtration rate [eGFR] <15 mL/min/1.73 m²) who had surgery in Alberta, Canada between 2005 and 2019. We categorized participants based on RCRI variables and assigned risk estimates of death or major cardiac events, and then estimated predictive performance. We re-estimated the coefficients for each RCRI variable and internally validated the updated model. Net benefit was estimated with decision curve analysis. Results After 38,541 surgeries, 1,204 (3.1%) events occurred. The estimated C-statistic for the original RCRI was 0.64 (95% confidence interval [CI]: 0.62, 0.65). Examination of calibration revealed significant risk overestimation. In the re-estimated RCRI model, discrimination was marginally different (C-statistic 0.67 [95%CI 0.66, 0.69]), though calibration was improved. There was net benefit when examined with decision curve analysis, while the original RCRI was associated with harm. Conclusions The RCRI performed poorly in a Canadian kidney failure cohort and significantly overestimated risk, suggesting RCRI use in similar kidney failure populations should be limited. A re-estimated kidney failure specific RCRI may be promising, though needs external validation. Novel perioperative models for this population are urgently needed.
Background X-linked lymphoproliferative disease (XLP) is a primary immunodeficiency arising from SH2D1A mutations leading to loss of SLAM-associated protein (SAP). SAP is an intracellular adaptor protein that binds to SLAM family receptors (SFR) and is expressed in specific lymphoid lineages. In T-cells, SAP relays activatory signals from the T-cell receptor but in its absence SHP1, SHP2 and SHIP proteins induce T-cell inhibitory signals leading to abnormal T-cell responses. This results severe clinical manifestations including immune dysregulation, dysgammaglobulinaemia, lymphoma and haemophagocytic lymphohistiocytosis (HLH). Current treatment relies on supportive therapies including immunoglobulin replacement and symptom directed therapy, with haematopoietic stem cell transplant (HSCT) offering the only curative option. Objectives As most XLP symptoms are due to defective T-cell function, we investigated whether inhibition of SHP2 can restore cellular function in the absence of SAP. Methods Healthy donor and XLP patient T-cells were activated with anti-CD3/CD28 in T-cell media supplemented with a SHP2 inhibitor (RMC-4550 in vitro for 24h) and functional assays performed to assess T follicular helper cells (TFH) function, CD8 cytotoxicity and sensitivity to restimulation induced cell death (RICD). Additionally, SAP deficient (SAPy/-) mice were treated with RMC-4550 before T-cell mediated challenge with NP-CGG and subsequent assessment of humoral immunity analysing TFH cell population, germinal centre formation and antigen dependent immunoglobulin secretion. Results We show that the use of RMC-4550 restores T-cell function in XLP patient cells and a SAPy/- model, demonstrating restoration of TFH cell function through immunoglobulin and cytokine secretion analysis alongside rescue of cytotoxicity and RICD. Conclusions These data suggest that SHP2 inhibitors could offer a novel and effective targeted treatment approach for XLP patients.
Introduction: Understanding the effectiveness and durability of protection against SARS-CoV-2 infection conferred by previous infection and COVID-19 is essential to inform ongoing management of the pandemic. This study aims to determine whether prior SARS-CoV-2 infection or COVID-19 vaccination in healthcare workers protects against future infection. Methods and analysis: This is a prospective cohort study design in staff members working in hospitals in the UK. At enrolment, participants are allocated into cohorts, positive or naïve, dependent on their prior SARS-CoV-2 infection status, as measured by standardised SARS-CoV-2 antibody testing on all baseline serum samples and previous SARS-CoV-2 test results. Participants undergo monthly antibody testing and fortnightly viral RNA testing during follow-up and based on these results may move between cohorts. Any results from testing undertaken for other reasons (eg, symptoms, contact tracing) or prior to study entry will also be captured. Individuals complete enrolment and fortnightly questionnaires on exposures, symptoms and vaccination. Follow-up is 12 months from study entry, with an option to extend follow-up to 24 months.The primary outcome of interest is infection with SARS-CoV-2 after previous SARS-CoV-2 infection or COVID-19 vaccination during the study period. Secondary outcomes include incidence and prevalence (both RNA and antibody) of SARS-CoV-2, viral genomics, viral culture, symptom history and antibody/neutralising antibody titres. Ethics and dissemination: The study was approved by the Berkshire Research Ethics Committee, Health Research Authority (IRAS ID 284460, REC reference 20/SC/0230) on 22 May 2020; the vaccine amendment was approved on 12 January 2021. Participants gave informed consent before taking part in the study.Regular reports to national and international expert advisory groups and peer-reviewed publications ensure timely dissemination of findings to inform decision making. Trial registration number: ISRCTN11041050.
Environmental carcinogenic exposures are major contributors to global disease burden yet how they promote cancer is unclear. Over 70 years ago, the concept of tumour promoting agents driving latent clones to expand was first proposed. In support of this model, recent evidence suggests that human tissue contains a patchwork of mutant clones, some of which harbour oncogenic mutations, and many environmental carcinogens lack a clear mutational signature. We hypothesised that the environmental carcinogen, <2.5μm particulate matter (PM2.5), might promote lung cancer promotion through non-mutagenic mechanisms by acting on pre-existing mutant clones within normal tissues in patients with lung cancer who have never smoked, a disease with a high frequency of EGFR activating mutations. We analysed PM2.5 levels and cancer incidence reported by UK Biobank, Public Health England, Taiwan Chang Gung Memorial Hospital (CGMH) and Korean Samsung Medical Centre (SMC) from a total of 463,679 individuals between 2006-2018. We report associations between PM2.5 levels and the incidence of several cancers, including EGFR mutant lung cancer. We find that pollution on a background of EGFR mutant lung epithelium promotes a progenitor-like cell state and demonstrate that PM accelerates lung cancer progression in EGFR and Kras mutant mouse lung cancer models. Through parallel exposure studies in mouse and human participants, we find evidence that inflammatory mediators, such as interleukin-1ꞵ, may act upon EGFR mutant clones to drive expansion of progenitor cells. Ultradeep mutational profiling of histologically normal lung tissue from 247 individuals across 3 clinical cohorts revealed oncogenic EGFR and KRAS driver mutations in 18% and 33% of normal tissue samples, respectively. These results support a tumour-promoting role for PM acting on latent mutant clones in normal lung tissue and add to evidence providing an urgent mandate to address air pollution in urban areas.
The main objective of this guideline is to assist practitioners in managing individuals diagnosed with Trichomonas vaginalis (TV). It offers recommendations on the diagnostic tests, treatment regimens and health promotion principles needed for the effective management of TV. It covers the management of the initial presentation, as well as how to prevent transmission and future re-infection. It is aimed primarily at people aged 16 years or older presenting to health care professionals, working in departments offering specialist care in sexually transmitted infection (STI) management within the United Kingdom. However, the principles of the recommendations are applicable across all levels of STI care providers (N.B. non-specialist services may need to develop, where appropriate, local care pathways).
Background: Impaired kidney function is associated with an increased risk of vascular events in acute stroke patients, when assessed by single measurements of estimated glomerular filtration rate (eGFR). It is unknown whether repeated measurements provide additional information for risk prediction. Methods: The Systematic Monitoring for Detection of Atrial Fibrillation in Patients with Acute Ischemic Stroke (MonDAFIS) study randomly assigned 3,465 acute ischemic-stroke patients to either standard procedures or an additive Holter-ECG. Baseline eGFR (CKD-epi formula) were dichotomized into values <vs.≥60ml/min/1.73m2 . eGFR dynamics were classified based on two in-hospital values: "stable normal" (≥60ml/min/1.73m2 ), "increasing" (by at least 15% from baseline, 2nd value ≥60ml/min/1.73m2 ), "decreasing" (by at least 15% from baseline ≥60ml/min/1.73m2 ), and "stable decreased" (<60ml/min/1.73m2 ). The composite endpoint (stroke, major-bleeding, myocardial-infarction, all-cause death) was assessed after 24 months. We estimated hazard ratios in confounder adjusted models. Results: eGFR at baseline was available in 2,947 and a 2nd value in 1,623 patients. After adjusting for age, stroke severity, cardiovascular risk factors, and randomization, eGFR <60ml/min/1.73m2 at baseline (HR 2.2; 95%CI 1.40-3.54) as well as "decreasing" (HR 1.79; 95%CI: 1.07-2.99) and "stable decreased" eGFR (HR 1.64; 95%CI: 1.20-2.24) were independently associated with the composite endpoint. In addition, eGFR<60ml/min/1.732 at baseline (HR 3.02; 95%CI: 1.51-6.10) and "decreasing" eGFR were associated with all-cause death (HR 3.12; 95%CI: 1.63-5.98). Conclusions: In addition to patients with low eGFR levels at baseline also those with decreasing eGFR have an increased risk for vascular events and death, hence, repeated estimates of eGFR might add relevant information to risk prediction. Trial registration number Clinicaltrials.gov NCT02204267.
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