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The Centre for Evidence-Based Medicine (CEBM) at Oxford University develops, promotes and disseminates better evidence for health care.
Perceptions on undertaking regular asymptomatic self-testing for COVID-19 using lateral flow tests: A qualitative study of university students and staff
Background There has been an increased interest from governments in implementing mass testing for COVID-19 of asymptomatic individuals using Lateral Flow Tests (LFTs). Successful implementation of such programmes depends on several factors, including feasibility, acceptability and how people act on test results. There is a paucity of studies examining these issues. Objective We aimed to examine experiences of university students and staff with experience of regular asymptomatic self-testing using LFTs, and their subsequent behaviours. Methods We invited people who were participating in a ‘weekly testing’ feasibility study. We conducted semi-structured remote interviews between December 2020 and January 2021. Additional qualitative data from a survey were also analysed. Data were analysed thematically. Results We interviewed 18 and surveyed 214 participants. Participants were motivated to regularly self-test as they wanted to know whether or not they were infected with SARS-CoV-2. Most reported that a negative test result did not change their behaviour but it did provide them with reassurance to engage with permitted activities. In contrast, some participants reported making decisions about visiting other people when they would not have done so otherwise, because they felt reassured by a negative test result. Participants valued the test training but some participants still doubted their ability to carry out the test. Participants were concerned about safety of attending test sites with lots of people and reported home testing was most convenient. Conclusions If governments want to increase uptake of LFT use, clear messages highlighting the benefits of regular testing for family, friends and society in identifying asymptomatic cases are needed. This should be coupled with transparent communication about accuracy of LFTs and how to act on either a positive or negative result. Concerns about safety, convenience of testing, and ability to do tests need to be addressed to ensure successful scaling up asymptomatic testing.
Long-term monitoring in primary care for chronic kidney disease and chronic heart failure: a multi-method research programme
Background Long-term monitoring is important in chronic condition management. Despite considerable costs of monitoring, there is no or poor evidence on how, what and when to monitor. The aim of this study was to improve understanding, methods, evidence base and practice of clinical monitoring in primary care, focusing on two areas: chronic kidney disease and chronic heart failure. Objectives The research questions were as follows: does the choice of test affect better care while being affordable to the NHS? Can the number of tests used to manage individuals with early-stage kidney disease, and hence the costs, be reduced? Is it possible to monitor heart failure using a simple blood test? Can this be done using a rapid test in a general practitioner consultation? Would changes in the management of these conditions be acceptable to patients and carers? Design Various study designs were employed, including cohort, feasibility study, Clinical Practice Research Datalink analysis, seven systematic reviews, two qualitative studies, one cost-effectiveness analysis and one cost recommendation. Setting This study was set in UK primary care. Data sources Data were collected from study participants and sourced from UK general practice and hospital electronic health records, and worldwide literature. Participants The participants were NHS patients (Clinical Practice Research Datalink: 4.5 million patients), chronic kidney disease and chronic heart failure patients managed in primary care (including 750 participants in the cohort study) and primary care health professionals. Interventions The interventions were monitoring with blood and urine tests (for chronic kidney disease) and monitoring with blood tests and weight measurement (for chronic heart failure). Main outcome measures The main outcomes were the frequency, accuracy, utility, acceptability, costs and cost-effectiveness of monitoring. Results Chronic kidney disease: serum creatinine testing has increased steadily since 1997, with most results being normal (83% in 2013). Increases in tests of creatinine and proteinuria correspond to their introduction as indicators in the Quality and Outcomes Framework. The Chronic Kidney Disease Epidemiology Collaboration equation had 2.7% greater accuracy (95% confidence interval 1.6% to 3.8%) than the Modification of Diet in Renal Disease equation for estimating glomerular filtration rate. Estimated annual transition rates to the next chronic kidney disease stage are ≈ 2% for people with normal urine albumin, 3–5% for people with microalbuminuria (3–30 mg/mmol) and 3–12% for people with macroalbuminuria (> 30 mg/mmol). Variability in estimated glomerular filtration rate-creatinine leads to misclassification of chronic kidney disease stage in 12–15% of tests in primary care. Glycaemic-control and lipid-modifying drugs are associated with a 6% (95% confidence interval 2% to 10%) and 4% (95% confidence interval 0% to 8%) improvement in renal function, respectively. Neither estimated glomerular filtration rate-creatinine nor estimated glomerular filtration rate-Cystatin C have utility in predicting rate of kidney function change. Patients viewed phrases such as ‘kidney damage’ or ‘kidney failure’ as frightening, and the term ‘chronic’ was misinterpreted as serious. Diagnosis of asymptomatic conditions (chronic kidney disease) was difficult to understand, and primary care professionals often did not use ‘chronic kidney disease’ when managing patients at early stages. General practitioners relied on Clinical Commissioning Group or Quality and Outcomes Framework alerts rather than National Institute for Health and Care Excellence guidance for information. Cost-effectiveness modelling did not demonstrate a tangible benefit of monitoring kidney function to guide preventative treatments, except for individuals with an estimated glomerular filtration rate of 60–90 ml/minute/1.73 m2, aged < 70 years and without cardiovascular disease, where monitoring every 3–4 years to guide cardiovascular prevention may be cost-effective. Chronic heart failure: natriuretic peptide-guided treatment could reduce all-cause mortality by 13% and heart failure admission by 20%. Implementing natriuretic peptide-guided treatment is likely to require predefined protocols, stringent natriuretic peptide targets, relative targets and being located in a specialist heart failure setting. Remote monitoring can reduce all-cause mortality and heart failure hospitalisation, and could improve quality of life. Diagnostic accuracy of point-of-care N-terminal prohormone of B-type natriuretic peptide (sensitivity, 0.99; specificity, 0.60) was better than point-of-care B-type natriuretic peptide (sensitivity, 0.95; specificity, 0.57). Within-person variation estimates for B-type natriuretic peptide and weight were as follows: coefficient of variation, 46% and coefficient of variation, 1.2%, respectively. Point-of-care N-terminal prohormone of B-type natriuretic peptide within-person variability over 12 months was 881 pg/ml (95% confidence interval 380 to 1382 pg/ml), whereas between-person variability was 1972 pg/ml (95% confidence interval 1525 to 2791 pg/ml). For individuals, monitoring provided reassurance; future changes, such as increased testing, would be acceptable. Point-of-care testing in general practice surgeries was perceived positively, reducing waiting time and anxiety. Community heart failure nurses had greater knowledge of National Institute for Health and Care Excellence guidance than general practitioners and practice nurses. Health-care professionals believed that the cost of natriuretic peptide tests in routine monitoring would outweigh potential benefits. The review of cost-effectiveness studies suggests that natriuretic peptide-guided treatment is cost-effective in specialist settings, but with no evidence for its value in primary care settings. Limitations No randomised controlled trial evidence was generated. The pathways to the benefit of monitoring chronic kidney disease were unclear. Conclusions It is difficult to ascribe quantifiable benefits to monitoring chronic kidney disease, because monitoring is unlikely to change treatment, especially in chronic kidney disease stages G3 and G4. New approaches to monitoring chronic heart failure, such as point-of-care natriuretic peptide tests in general practice, show promise if high within-test variability can be overcome. Future work The following future work is recommended: improve general practitioner–patient communication of early-stage renal function decline, and identify strategies to reduce the variability of natriuretic peptide. Study registration This study is registered as PROSPERO CRD42015017501, CRD42019134922 and CRD42016046902. Funding This project was funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research programme and will be published in full in Programme Grants for Applied Research; Vol. 9, No. 10. See the NIHR Journals Library website for further project information.
Understanding the facilitators and barriers of stroke survivors' adherence to recovery-oriented self-practice: a thematic synthesis.
PURPOSE: Stroke survivors receive considerable rehabilitation efforts as inpatients, but one-on-one therapy decreases after discharge. The gap between the amount of required therapy and the lack of its availability in this phase of care may be partly overcome by self-practice. However, patient's adherence to prescribed programs is often low. While single studies have examined factors affecting adherence in this specific case, they have not been reviewed and synthesised previously. METHODS: A thematic synthesis of qualitative studies explored factors affecting stroke survivors' adherence to prescribed, recovery-oriented self-practice. Five databases were systematically searched for references: Medline, Psycinfo, CINAHL, Embase, and ASSIA. Quality assessment was undertaken using the CASP tool. RESULTS: From 1308 references, 68 potential papers were read in full, and 12 were included in the review. An overarching theme was identified as: "Tailoring and personalization rather than standardization." It was informed by the following three analytical themes: "The meaning of 'self' in self-practice," "Identifying self-practice as a team effort," and "Self-practice that is grounded in one's reality." CONCLUSION: To have a positive effect on adherence to self-practice, clinicians are advised to spend time learning about each individual's life circumstances, so they can tailor proposed exercise programs to patients' personal situations, preferences, and needs.IMPLICATIONS FOR REHABILITATIONThe topic of patient's adherence to self-practice of prescribed exercise is a common concern, often voiced by frustrated rehabilitation health professionals. Bridging the gap between the patient's needs for post-discharge intensive therapy and the inability of healthcare systems to provide it could be filled partly by self-practice.Adherence to self-practice has become even more essential since the COVID 19 pandemic and the decrease in face-to-face delivery of rehabilitation due to social distancing requirements.Adherence to exercise is a broad topic. Reasons for poor adherence differ between patient populations and the exercises they are prescribed. This study focuses on post-discharge stroke survivors' adherence to recovery targeted exercise that could be described as repetitive and less physically demanding movements and functions.Reviewed studies were qualitative and usually included a relatively small number of participants within a specific context. Using thematic synthesis, we combined these small pieces of the puzzle into a larger picture, to produce recommendations that could be drawn on by clinicians to improve self-practice adherence.
Benefits and harms of Risperidone and Paliperidone for treatment of patients with schizophrenia or bipolar disorder: a meta-analysis involving individual participant data and clinical study reports
Background: Schizophrenia and bipolar disorder are severe mental illnesses which are highly prevalent worldwide. Risperidone and Paliperidone are treatments for either illnesses, but their efficacy compared to other antipsychotics and growing reports of hormonal imbalances continue to raise concerns. As existing evidence on both antipsychotics are solely based on aggregate data, we aimed to assess the benefits and harms of Risperidone and Paliperidone in the treatment of patients with schizophrenia or bipolar disorder, using individual participant data (IPD), clinical study reports (CSRs) and publicly available sources (journal publications and trial registries). Methods: We searched MEDLINE, Central, EMBASE and PsycINFO until December 2020 for randomised placebo-controlled trials of Risperidone, Paliperidone or Paliperidone palmitate in patients with schizophrenia or bipolar disorder. We obtained IPD and CSRs from the Yale University Open Data Access project. The primary outcome Positive and Negative Syndrome Scale (PANSS) score was analysed using one-stage IPD meta-analysis. Random-effect meta-analysis of harm outcomes involved methods for coping with rare events. Effect-sizes were compared across all available data sources using the ratio of means or relative risk. We registered our review on PROSPERO, CRD42019140556. Results: Of the 35 studies, IPD meta-analysis involving 22 (63%) studies showed a significant clinical reduction in the PANSS in patients receiving Risperidone (mean difference − 5.83, 95% CI − 10.79 to − 0.87, I2 = 8.5%, n = 4 studies, 1131 participants), Paliperidone (− 6.01, 95% CI − 8.7 to − 3.32, I2 = 4.3%, n = 13, 3821) and Paliperidone palmitate (− 7.89, 95% CI − 12.1 to − 3.69, I2 = 2.9%, n = 5, 2209). CSRs reported nearly two times more adverse events (4434 vs. 2296 publication, relative difference (RD) = 1.93, 95% CI 1.86 to 2.00) and almost 8 times more serious adverse events (650 vs. 82; RD = 7.93, 95% CI 6.32 to 9.95) than the journal publications. Meta-analyses of individual harms from CSRs revealed a significant increased risk among several outcomes including extrapyramidal disorder, tardive dyskinesia and increased weight. But the ratio of relative risk between the different data sources was not significant. Three treatment-related gynecomastia events occurred, and these were considered mild to moderate in severity. Conclusion: IPD meta-analysis conclude that Risperidone and Paliperidone antipsychotics had a small beneficial effect on reducing PANSS score over 9 weeks, which is more conservative than estimates from reviews based on journal publications. CSRs also contained significantly more data on harms that were unavailable in journal publications or trial registries. Sharing of IPD and CSRs are necessary when performing meta-analysis on the efficacy and safety of antipsychotics.
Cycling in the UK has surged during the Covid-19 pandemic, and cycling is being encouraged by the Government as a healthier and more sustainable means of transport. However, deaths involving pedal cyclists also increased by 40% during the pandemic. In this report, we analyse coronial Prevention of Future Deaths (PFD) reports involving cyclists in England and Wales between July 2013 and April 2021. We identified 33 preventable deaths involving cyclists, summarised in 32 reports. All deaths involved pedal cycles, except for one that involved a motorised electric bicycle. Reports were sent to 53 addressees, most (43%; n=23) sent to local councils. However, compliance with regulation 29 of The Coroners (Investigations) Regulation 2013, which mandates a response within 56 days, was poor; 26 reports (49%) sent by coroners had responses posted on the Courts and Tribunals Judiciary website at the time of analysis (July 2021). Across England and Wales, there was substantial geographical variation in the writing of reports; coroners in London (21%; n=7) and Dorset (9%; n=3) reported the most deaths, and many areas reported none. In 10 cases (30%), coroners raised concerns regarding cycle lanes—either that there was an absence of cycle lanes or that such lanes were in an inadequate condition or had confusing information. In several cases, coroners raised concerns that the location of the accident was structurally dangerous (18%; n=6) and that inspection and classification of defects on carriageways were inappropriate (12%; n=4). In three cases, the coroners had concerns about poor practices at cycling events, and in two cases, the coroners highlighted a lack of education on cycling safely. In one case, regulations for electric bicycles were highlighted. PFDs highlight important lessons, and addressees comply poorly with their duty to respond to coroners’ concerns. We created a publicly available tool, https://preventabledeathstracker.net/, displaying coroners’ reports in England and Wales to streamline access and identify important lessons to prevent future deaths. Local councils, which received most cycling-related reports, are responsible for implementing policies set out in national guidelines or dependent on funding from the Government. To prevent future cycling-related deaths, PFDs ought to be addressed both locally and nationally to improve the safety of roads and their design so that cycling can be encouraged as a healthy, sustainable, and safe mode of transport.
Background: SARS-CoV-2 RNA has been detected in fomites which suggests the virus could be transmitted via inanimate objects. However, there is uncertainty about the mechanistic pathway for such transmissions. Our objective was to identify, appraise and summarise the evidence from primary studies and systematic reviews assessing the role of fomites in transmission. Methods: This review is part of an Open Evidence Review on Transmission Dynamics of SARS-CoV-2. We conduct ongoing searches using WHO Covid-19 Database, LitCovid, medRxiv, and Google Scholar; assess study quality based on five criteria and report important findings on an ongoing basis. Results: We found 64 studies: 63 primary studies and one systematic review (n=35). The settings for primary studies were predominantly in hospitals (69.8%) including general wards, ICU and SARS-CoV-2 isolation wards. There were variations in the study designs including timing of sample collection, hygiene procedures, ventilation settings and cycle threshold. The overall quality of reporting was low to moderate. The frequency of positive SARS-CoV-2 tests across 51 studies (using RT-PCR) ranged from 0.5% to 75%. Cycle threshold values ranged from 20.8 to 44.1. Viral concentrations were reported in 17 studies; however, discrepancies in the methods for estimation prevented comparison. Eleven studies (17.5%) attempted viral culture, but none found a cytopathic effect. Results of the systematic review showed that healthcare settings were most frequently tested (25/35, 71.4%), but laboratories reported the highest frequency of contaminated surfaces (20.5%, 17/83). Conclusions: The majority of studies report identification of SARS-CoV-2 RNA on inanimate surfaces; however, there is a lack of evidence demonstrating the recovery of viable virus. Lack of positive viral cultures suggests that the risk of transmission of SARS-CoV-2 through fomites is low. Heterogeneity in study designs and methodology prevents comparisons of findings across studies. Standardized guidelines for conducting and reporting research on fomite transmission is warranted.
Background: SARS-CoV-2 has been detected in fomites which suggests the virus could be transmitted via inanimate objects. However, there is uncertainty about the mechanistic pathway for such transmissions. Our objective was to identify, appraise and summarise the evidence from primary studies and systematic reviews assessing the role of fomites in transmission. Methods: This review is part of an Open Evidence Review on Transmission Dynamics of SARS-CoV-2. We conduct ongoing searches using WHO Covid-19 Database, LitCovid, medRxiv, and Google Scholar; assess study quality based on five criteria and report important findings on an ongoing basis. Results: We found 64 studies: 63 primary studies and one systematic review (n=35). The settings for primary studies were predominantly in hospitals (69.8%) including general wards, ICU and SARS-CoV-2 isolation wards. There were variations in the study designs including timing of sample collection, hygiene procedures, ventilation settings and cycle threshold. The overall quality of reporting was low to moderate. The frequency of positive SARS-CoV-2 tests across 51 studies (using RT-PCR) ranged from 0.5% to 75%. Cycle threshold values ranged from 20.8 to 44.1. Viral concentrations were reported in 17 studies; however, discrepancies in the methods for estimation prevented comparison. Eleven studies (17.5%) attempted viral culture, but none found a cytopathic effect. Results of the systematic review showed that healthcare settings were most frequently tested (25/35, 71.4%), but laboratories reported the highest frequency of contaminated surfaces (20.5%, 17/83). Conclusions: The majority of studies report identification of SARS-CoV-2 RNA on inanimate surfaces; however, there is a lack of evidence demonstrating the recovery of viable virus. Lack of positive viral cultures and variation in cycle thresholds create uncertainty about fomites as a mode of transmission. Heterogeneity in study designs and methodology prevents comparisons of findings across studies. Standardized guidelines for conducting and reporting research on fomite transmission is warranted.
Background: Mode of transmission of SARS-CoV-2 is of key public health importance. SARS-CoV-2 has been detected in the feces of some COVID-19 patients, suggesting the possibility that the virus could, in addition to droplet and fomite transmission, be transmitted via the orofecal route. Methods: This review is part of an Open Evidence Review on Transmission Dynamics of COVID-19. We conduct ongoing searches using WHO COVID-19 Database, LitCovid, medRxiv, and Google Scholar; assess study quality based on five criteria and report important findings on an ongoing basis. Where necessary, authors are contacted for further details on the content of their articles. Results: We include searches up until 20 December 2020. We included 110 relevant studies: 76 primary observational studies or reports, and 35 reviews (one cohort study also included a review) examining the potential role of orofecal transmission of SARS-CoV-2. Of the observational studies, 37 were done in China. A total of 48 studies (n=9,081 patients) reported single cases, case series or cohort data on individuals with COVID-19 diagnosis or their contacts and 46 (96%) detected binary RT-PCR with 535 out of 1358 samples positive for SARs-CoV-2 (average 39.4%). The results suggest a long duration of fecal shedding, often recorded after respiratory samples tested negative, and symptoms of gastrointestinal disease were reported in several studies. Twenty-nine studies reported finding SARS-CoV-2 RNA in wastewater, river water or toilet areas. Six studies attempted viral culture from COVID-19 patients’ fecal samples: culture was successful in 3 of 6 studies, and one study demonstrated invasion of the virus into the intestinal epithelial cells. Conclusions: Varied observational and mechanistic evidence suggests SARS-CoV-2 can infect and be shed from the gastrointestinal tract, including some data demonstrating viral culture in fecal samples. Future studies should test this hypothesis rigorously to allow the development of appropriate public health measures.
Simple and adaptable R implementation of WHO/ISH cardiovascular risk charts for all epidemiological subregions of the world
The World Health Organisation and International Society of Hypertension (WHO/ISH) cardiovascular disease (CVD) risk assessment charts have been implemented in many low- and middle-income countries as part of the WHO Package of Essential Non-Communicable Disease (PEN) Interventions for Primary Health Care in Low-Resource settings. Evaluation of the WHO/ISH cardiovascular risk charts and their use is a key priority and since they only exist in paper or PDF formats, we developed a simple R implementation of the charts for all epidemiological subregions of the world. The main strengths of this implementation are that it is built in a free, open-source, coding language with simple syntax, can be modified by the user, and can be used with a standard computer.
Background: SARS-CoV-2 transmission has been reported to be associated with close contact with infected individuals. However, the mechanistic pathway for transmission in close contact settings is unclear. Our objective was to identify, appraise and summarise the evidence from studies assessing the role of close contact in SARS-CoV-2 transmission. Methods: This review is part of an Open Evidence Review on Transmission Dynamics of SARS-CoV-2. We conduct ongoing searches using WHO Covid-19 Database, LitCovid, medRxiv, PubMed and Google Scholar; assess study quality based on the QUADAS-2 criteria and report important findings on an ongoing basis. Results: We included 181 studies: 171 primary studies and 10 systematic reviews. The settings for primary studies were predominantly in home/quarantine facilities (31.6%) and acute care hospitals (15.2%). The overall reporting quality of the studies was low to moderate. There was significant heterogeneity in design and methodology. The frequency of attack rates (PCR testing) was 3.5-75%; attack rates were highest in prison and wedding venues, and in households. The frequency of secondary attack rates was 0.3-100% with rates highest in home/quarantine settings. Three studies showed no transmission if index cases had recurrent infection. Viral culture was performed in three studies of which two found viable virus; culture results were negative where index cases had recurrent infections. Ten studies performed genomic sequencing with phylogenetic analysis – the completeness of genomic similarity ranged from 81-100%. Findings from systematic reviews showed that children were significantly less likely to transmit SARS-CoV-2 and household contact was associated with a significantly increased risk of infection. Conclusions: The evidence from published studies demonstrates that SARS-CoV-2 can be transmitted via close contact settings. The risk of transmission is greater in household contacts. There was wide variation in methodology. Standardized guidelines for reporting transmission in close contact settings should be developed to improve the quality reporting.
Given the rapidly changing nature of COVID-19, clinicians and policy makers require urgent review and summary of the literature, and synthesis of evidence-based guidelines to inform practice. The WHO advocates for rapid reviews in these circumstances. The purpose of this rapid guideline is to provide recommendations on the organizational management of intensive care units caring for patients with COVID-19 including: planning a crisis surge response; crisis surge response strategies; triage, supporting families, and staff.
Association of Major Depression With Risk of Ischemic Heart Disease in a Mega-Cohort of Chinese Adults: The China Kadoorie Biobank Study
© 2016 The Authors. Background-Increasing evidence has suggested that major depression (MD) is associated with an increased risk of ischemic heart disease (IHD). We examined this association in Chinese adults using data from the China Kadoorie Biobank study. Methods and Results-Over 0.5 million adults aged 30 to 79 years were followed from baseline interview (2004-2008) until December 31, 2013. Past year MD was measured with the modified Chinese version of Composite International Diagnostic Interview-Short Form at baseline. Incident IHD cases were identified through linkage to related medical databases, and defined as having International Statistical Classification of Diseases and Related Health Problems 10th Revision codes of I20 to I25. Cox proportional hazards regression models were used to estimate hazard ratios and 95% CIs for the MD-IHD association with adjustment for sociodemographic variables and established cardiovascular risk factors. During 3 423 542 person-years of followup, 24 705 incident IHD cases were documented. Higher IHD incidence was observed in participants with MD compared with those without (8.76 versus 7.21 per 1000 person-years), and the multivariable-adjusted hazard ratio was 1.32 (95% CI 1.15-1.53). Geographic location modified the association (P for interaction=0.005), and a positive association was observed in urban residents (hazard ratio 1.72; 95% CI 1.39-2.14) but not rural residents (1.13; 0.93-1.37). Compared with participants without depressive symptoms, the hazard ratio (95% CI) of IHD was 1.13 (1.04-1.23) for those with depressive symptoms only and 1.33 (1.15-1.53) for those with MD. Conclusions-Past year major depression was associated with an increased risk of IHD in Chinese adults, independent of other major cardiovascular risk factors.
Changes in GFR and Albuminuria in Routine Clinical Practice and the Risk of Kidney Disease Progression
Rationale & Objective: Changes in urinary albumin-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) have been used separately as alternative kidney disease outcomes in randomized trials. We tested the hypothesis that combined changes in UACR and eGFR predict advanced kidney disease better than either alone. Study Design: Observational cohort study. Setting & Participants: 91,319 primary care patients assembled from the Clinical Practice Research Datalink in the United Kingdom between 2000 and 2015. Exposures: Changes in UACR and eGFR (categorized as ≥30% increase, stable, or ≥30% decrease), alone and in combination, over a 3-year period. Outcomes: The primary outcome was advanced CKD (sustained eGFR <30 mL/min/1.73 m2); secondary outcomes included kidney failure, cardiovascular disease, and all-cause mortality. Analytical Approach: Multivariable Cox regression with bias from missing values assessed using multiple imputation; discrimination statistics compared across exposure groups. Results: 91,319 individuals were studied, with a mean eGFR of 72.6 mL/min/1.73 m2 and median UACR of 9.7 mg/g; 70,957 (77.7%) had diabetes. During a median follow-up of 2.9 years, 2,541 people progressed to advanced CKD. Compared with stable values, hazard ratios for a ≥30% increase in UACR and ≥30% decrease in eGFR were 1.78 (95% CI, 1.59-1.98) and 7.53 (95% CI, 6.70-8.45), respectively, for the outcome of advanced CKD. Compared with stable values of both, the hazard ratio for the combination of an increase in UACR and a decrease in eGFR was 15.15 (95% CI, 12.43-18.46) for the outcome of advanced CKD. The combination of changes in UACR and eGFR predicted kidney outcomes better than either alone. Limitations: Selection bias, relatively small proportion of individuals without diabetes, and very few kidney failure events. Conclusions: In a large-scale general population, the combination of an increase in UACR and a decrease in eGFR was strongly associated with the risk of advanced CKD. Further assessment of combined changes in UACR and eGFR as an alternative outcome for kidney failure in trials of CKD progression is warranted.