Quality of life in older adults with chronic kidney disease and transient changes in renal function: Findings from the Oxford Renal cohort.

BACKGROUND: Quality of life (QoL) is an important measure of disease burden and general health perception. The relationship between early chronic kidney disease (CKD) and QoL remains poorly understood. The Oxford Renal Study (OxRen) cohort comprises 1063 adults aged ≥60 years from UK primary care practices screened for early CKD, grouped according to existing or screen-detected CKD diagnoses, or biochemistry results indicative of reduced renal function (referred to as transient estimated glomerular filtration rate (eGFR) reduction). OBJECTIVES: This study aimed to compare QoL in participants known to have CKD at recruitment to those identified as having CKD through a screening programme. METHODS: Health profile data and multi-attribute utility scores were reported for two generic questionnaires: 5-level EuroQol-5 Dimension (EQ-5D-5L) and ICEpop CAPability measure for Adults (ICECAP-A). QoL was compared between patients with existing and screen-detected CKD; those with transient eGFR reduction served as the reference group in univariable and multivariable linear regression. RESULTS: Mean and standard deviation utility scores were not significantly different between the subgroups for EQ-5D-5L (screen-detected:0.785±0.156, n = 480, transient:0.779±0.157, n = 261, existing CKD:0.763±0.171, n = 322, p = 0.216) or ICECAP-A (screen-detected:0.909±0.094, transient:0.904±0.110, existing CKD:0.894±0.115, p = 0.200). Age, smoking status, and number of comorbidities were identified as independent predictors of QoL in this cohort. CONCLUSION: QoL of participants with existing CKD diagnoses was not significantly different from those with screen-detected CKD or transient eGFR reduction and was similar to UK mean scores for the same age, suggesting that patient burden of early CKD is minor. Moreover, CKD-related comorbidities contribute more significantly to disease burden in earlier stages of CKD than renal function per se. Larger prospective studies are required to define the relationship between QoL and CKD progression more precisely. These data also confirm the essentially asymptomatic nature of CKD, implying that routine screening or case finding are required to diagnose it.

Change in glomerular filtration rate over time in the Oxford Renal Cohort Study: observational study.

BACKGROUND: Decline in kidney function can result in adverse health outcomes. The Oxford Renal Cohort Study has detailed baseline assessments from 884 participants ≥60 years of age. AIM: To determine the proportion of participants with a decline in estimated glomerular filtration rate (eGFR), identify determinants of decline, and determine proportions with chronic kidney disease (CKD) remission. DESIGN AND SETTING: Observational cohort study in UK primary care. METHOD: Data were used from baseline and annual follow-up assessments to monitor change in kidney function. Rapid eGFR decline was defined as eGFR decrease >5 ml/min/1.73 m2/year, improvement as eGFR increase >5 ml/min/1.73 m2/year, and remission in those with CKD at baseline and eGFR >60 ml/min/1.73 m2 during follow-up. Cox proportional hazard models were used to identify factors associated with eGFR decline. RESULTS: There was a net decline in eGFR in the 884 participants over 5 years of follow-up. In 686 participants with >2 eGFR tests with a median follow-up of 2.1 years, 164 (24%) evidenced rapid GFR decline, 185 (27%) experienced eGFR improvement, and 82 of 394 (21%) meeting CKD stage 1-4 at baseline experienced remission. In the multivariable analysis, smoking status, higher systolic blood pressure, and being known to have CKD at cohort entry were associated with rapid GFR decline. Those with CKD stage 3 at baseline were less likely to exhibit GFR decline compared with normal kidney function. CONCLUSION: This study established that 24% of people evidenced rapid GFR decline whereas 21% evidenced remission of CKD. People at risk of rapid GFR decline may benefit from closer monitoring and appropriate treatment to minimise risks of adverse outcomes, although only a small proportion meet the National Institute for Health and Care Excellence criteria for referral to secondary care.

Feasibility and Acceptability of Community Coronavirus Disease 2019 Testing Strategies (FACTS) in a University Setting.

BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic in 2020, the UK government began a mass severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing program. This study aimed to determine the feasibility and acceptability of organized regular self-testing for SARS-CoV-2. METHODS: This was a mixed-methods observational cohort study in asymptomatic students and staff at University of Oxford, who performed SARS-CoV-2 antigen lateral flow self-testing. Data on uptake and adherence, acceptability, and test interpretation were collected via a smartphone app, an online survey, and qualitative interviews. RESULTS: Across 3 main sites, 551 participants (25% of those invited) performed 2728 tests during a follow-up of 5.6 weeks; 447 participants (81%) completed at least 2 tests, and 340 (62%) completed at least 4. The survey, completed by 214 participants (39%), found that 98% of people were confident to self-test and believed self-testing to be beneficial. Acceptability of self-testing was high, with 91% of ratings being acceptable or very acceptable. A total of 2711 (99.4%) test results were negative, 9 were positive, and 8 were inconclusive. Results from 18 qualitative interviews with students and staff revealed that participants valued regular testing, but there were concerns about test accuracy that impacted uptake and adherence. CONCLUSIONS: This is the first study to assess feasibility and acceptability of regular SARS-CoV-2 self-testing. It provides evidence to inform recruitment for, adherence to, and acceptability of regular SARS-CoV-2 self-testing programs for asymptomatic individuals using lateral flow tests. We found that self-testing is acceptable and people were able to interpret results accurately.

Perceptions on undertaking regular asymptomatic self-testing for COVID-19 using lateral flow tests: a qualitative study of university students and staff.

OBJECTIVES: Successful implementation of asymptomatic testing programmes using lateral flow tests (LFTs) depends on several factors, including feasibility, acceptability and how people act on test results. We aimed to examine experiences of university students and staff of regular asymptomatic self-testing using LFTs, and their subsequent behaviours. DESIGN AND SETTING: A qualitative study using semistructured remote interviews and qualitative survey responses, which were analysed thematically. PARTICIPANTS: People who were participating in weekly testing feasibility study, between October 2020 and January 2021, at the University of Oxford. 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 because they felt reassured by a negative test result. Participants valued the training but some 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: 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 the 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 of asymptomatic testing.

Point-of-care HbA1c testing in an urban primary care diabetes clinic in South Africa: a mixed methods feasibility study.

INTRODUCTION: Monitoring and treatment of type 2 diabetes in South Africa usually takes place in primary care using random blood glucose testing to guide treatment decisions. This study explored the feasibility of using point-of-care haemoglobin A1c (HbA1c) testing in addition to glucose testing in a busy primary care clinic in Cape Town, South Africa. SUBJECTS: 185 adults aged 19-88 years with type 2 diabetes. MATERIALS AND METHODS: Participants recruited to this mixed methods cohort study received a point-of-care HbA1c test. Doctors were asked to use the point-of-care HbA1c result for clinical decision-making. Qualitative interviews were held with clinical staff. RESULTS: Point-of-care HbA1c test results were obtained for 165 participants of whom 109 (65%) had poor glycaemic control (>8% HbA1c, 64 mmol/mol). Medical officers reported using a combination of HbA1c and blood glucose 77% of the time for clinical decision-making. Nurses found the analyser easy to use and doctors valued having the HbA1c result to help with decision-making. DISCUSSION: Our results suggest that 30% of patients may have received inappropriate medication or not received necessary additional medication if random blood glucose alone had been used in routine appointments. Clinicians valued having access to the HbA1c test result to help them make treatment decisions.

Prevalence and factors associated with multimorbidity among primary care patients with decreased renal function.

OBJECTIVES: To establish the prevalence of multimorbidity in people with chronic kidney disease (CKD) stages 1-5 and transiently impaired renal function and identify factors associated with multimorbidity. DESIGN AND SETTING: Prospective cohort study in UK primary care. PARTICIPANTS: 861 participants aged 60 and older with decreased renal function of whom, 584 (65.8%) had CKD and 277 (32.2%) did not have CKD. INTERVENTIONS: Participants underwent medical history and clinical assessment, and blood and urine sampling. PRIMARY AND SECONDARY OUTCOME MEASURES: Multimorbidity was defined as presence of ≥2 chronic conditions including CKD. Prevalence of each condition, co-existing conditions and multimorbidity were described and logistic regression was used to identify predictors of multimorbidity. RESULTS: The mean (±SD) age of participants was 74±7 years, 54% were women and 98% were white. After CKD, the next most prevalent condition was hypertension (n = 511, 59.3%), followed by obesity (n = 265, 30.8%) ischemic heart disease (n = 145, 16.8%) and diabetes (n = 133, 15.4%). Having two co-existing conditions was most common (27%), the most common combination of which was hypertension and obesity (29%). One or three conditions was the next most prevalent combination (20% and 21% respectively). The prevalence of multimorbidity was 73.9% (95%CI 70.9-76.8) in all participants and 86.6% (95%CI 83.9-89.3) in those with any-stage CKD. Logistic regression found a significant association between increasing age (OR 1.07, 95%CI 1.04-0.10), increasing BMI (OR 1.15, 95%CI 1.10-1.20) and decreasing eGFR (OR 0.99, 95%CI 0.98-1.00) with multimorbidity. CONCLUSIONS: This analysis is the first to provide an accurate estimate of the prevalence of multimorbidity in a screened older primary care population living with or at risk of CKD across all stages. Hypertension and obesity were the most common combination of conditions other than CKD that people were living with, suggesting that there may be multiple reasons for closely monitoring health status in individuals with CKD.

Prevalence of chronic kidney disease in the community using data from OxRen: a UK population-based cohort study.

BACKGROUND: Chronic kidney disease (CKD) is a largely asymptomatic condition of diminished renal function, which may not be detected until advanced stages without screening. AIM: To establish undiagnosed and overall CKD prevalence using a cross-sectional analysis. DESIGN AND SETTING: Longitudinal cohort study in UK primary care. METHOD: Participants aged ≥60 years were invited to attend CKD screening visits to determine whether they had reduced renal function (estimated glomerular filtration rate [eGFR] <60 ml/min/1.73 m2 or albumin:creatinine ratio ≥3 mg/mmol). Those with existing CKD, low eGFR, evidence of albuminuria, or two positive screening tests attended a baseline assessment (CKD cohort). RESULTS: A total of 3207 participants were recruited and 861 attended the baseline assessment. The CKD cohort consisted of 327 people with existing CKD, 257 people with CKD diagnosed through screening (CKD prevalence of 18.2%, 95% confidence interval [CI] = 16.9 to 19.6), and 277 with borderline/transient decreased renal function. In the CKD cohort, 54.4% were female, mean standard deviation (SD) age was 74.0 (SD 6.9) years, and mean eGFR was 58.0 (SD 18.4) ml/min/1.73 m2. Of the 584 with confirmed CKD, 44.0% were diagnosed through screening. Over half of the CKD cohort (51.9%, 447/861) fell into CKD stages 3-5 at their baseline assessment, giving an overall prevalence of CKD stages 3-5 of 13.9% (95% CI = 12.8 to 15.1). More people had reduced eGFR using the Modification of Diet in Renal Disease (MDRD) equation than with CKD Epidemiology Collaboration (CKD-EPI) equation in the 60-75-year age group and more had reduced eGFR using CKD-EPI in the ≥80-year age group. CONCLUSION: This study found that around 44.0% of people living with CKD are undiagnosed without screening, and prevalence of CKD stages 1-5 was 18.2% in participants aged >60 years. Follow-up will provide data on annual incidence, rate of CKD progression, determinants of rapid progression, and predictors of cardiovascular events.

Impact of patient and public involvement on enrolment and retention in clinical trials: systematic review and meta-analysis.

OBJECTIVE: To investigate the impact of patient and public involvement (PPI) on rates of enrolment and retention in clinical trials and explore how this varies with the context and nature of PPI. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Ten electronic databases, including Medline, INVOLVE Evidence Library, and clinical trial registries. ELIGIBILITY CRITERIA: Experimental and observational studies quantitatively evaluating the impact of a PPI intervention, compared with no intervention or non-PPI intervention(s), on participant enrolment and/or retention rates in a clinical trial or trials. PPI interventions could include additional non-PPI components inseparable from the PPI (for example, other stakeholder involvement). DATA EXTRACTION AND ANALYSIS: Two independent reviewers extracted data on enrolment and retention rates, as well as on the context and characteristics of PPI intervention, and assessed risk of bias. Random effects meta-analyses were used to determine the average effect of PPI interventions on enrolment and retention in clinical trials: main analysis including randomised studies only, secondary analysis adding non-randomised studies, and several exploratory subgroup and sensitivity analyses. RESULTS: 26 studies were included in the review; 19 were eligible for enrolment meta-analysis and five for retention meta-analysis. Various PPI interventions were identified with different degrees of involvement, different numbers and types of people involved, and input at different stages of the trial process. On average, PPI interventions modestly but significantly increased the odds of participant enrolment in the main analysis (odds ratio 1.16, 95% confidence interval and prediction interval 1.01 to 1.34). Non-PPI components of interventions may have contributed to this effect. In exploratory subgroup analyses, the involvement of people with lived experience of the condition under study was significantly associated with improved enrolment (odds ratio 3.14 v 1.07; P=0.02). The findings for retention were inconclusive owing to the paucity of eligible studies (odds ratio 1.16, 95% confidence interval 0.33 to 4.14), for main analysis). CONCLUSIONS: These findings add weight to the case for PPI in clinical trials by indicating that it is likely to improve enrolment of participants, especially if it includes people with lived experience of the health condition under study. Further research is needed to assess which types of PPI work best in particular contexts, the cost effectiveness of PPI, the impact of PPI at earlier stages of trial design, and the impact of PPI interventions specifically targeting retention. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016043808.

Impact of a single eGFR and eGFR-estimating equation on chronic kidney disease reclassification: a cohort study in primary care.

BACKGROUND: Chronic kidney disease (CKD) is diagnosed using the estimated glomerular filtration rate (eGFR) and the urinary albumin:creatinine ratio (ACR). The eGFR is calculated from serum creatinine levels using the Modification of Diet in Renal Disease (MDRD) or Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations. AIM: To compare the performance of one versus two eGFR/ACR measurements, and the impact of equation choice, on CKD diagnosis and classification. DESIGN AND SETTING: Cohort study in primary care in the Thames Valley region of the UK. METHOD: Data were from 485 participants aged >60 years in the Oxford Renal Cohort Study with at least two eGFR tests. The proportion of study participants diagnosed and classified into different CKD stages using one and two positive tests were compared. Prevalence of CKD diagnosis and classification by CKD stage were compared when eGFR was calculated using MDRD and CKD-EPI equations. RESULTS: Participants included in the analysis had a mean age of 72.1 (±6.8) years and 57.0% were female. Use of a single screening test overestimated the proportion of people with CKD by around 25% no matter which equation was used, compared with the use of two tests. The mean eGFR was 1.4 ml/min/1.73 m2 (95% CI = 1.1 to 1.6) higher using the CKD-EPI equation compared with the MDRD equation. More patients were diagnosed with CKD when using the MDRD equation, compared with the CKD-EPI equation, once (64% versus 63%, respectively) and twice (39% versus 38%, respectively), and 16 individuals, all of who had CKD stages 2 or 3A with MDRD, were reclassified as having a normal urinary ACR when using the CKD-EPI equation. CONCLUSION: Current guidance to use two eGFR measures to diagnose CKD remains appropriate in an older primary care population to avoid overdiagnosis. A change from MDRD to CKD-EPI equation could result in one in 12 patients with a CKD diagnosis with MDRD no longer having a diagnosis of CKD.

Systematic Review and Metaanalysis Comparing the Bias and Accuracy of the Modification of Diet in Renal Disease and Chronic Kidney Disease Epidemiology Collaboration Equations in Community-Based Populations.

BACKGROUND: The majority of patients with chronic kidney disease are diagnosed and monitored in primary care. Glomerular filtration rate (GFR) is a key marker of renal function, but direct measurement is invasive; in routine practice, equations are used for estimated GFR (eGFR) from serum creatinine. We systematically assessed bias and accuracy of commonly used eGFR equations in populations relevant to primary care. CONTENT: MEDLINE, EMBASE, and the Cochrane Library were searched for studies comparing measured GFR (mGFR) with eGFR in adult populations comparable to primary care and reporting both the Modification of Diet in Renal Disease (MDRD) and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations based on standardized creatinine measurements. We pooled data on mean bias (difference between eGFR and mGFR) and on mean accuracy (proportion of eGFR within 30% of mGFR) using a random-effects inverse-variance weighted metaanalysis. We included 48 studies of 26875 patients that reported data on bias and/or accuracy. Metaanalysis of within-study comparisons in which both formulae were tested on the same patient cohorts using isotope dilution-mass spectrometry-traceable creatinine showed a lower mean bias in eGFR using CKD-EPI of 2.2 mL/min/1.73 m2 (95% CI, 1.1-3.2; 30 studies; I2 = 74.4%) and a higher mean accuracy of CKD-EPI of 2.7% (1.6-3.8; 47 studies; I2 = 55.5%). Metaregression showed that in both equations bias and accuracy favored the CKD-EPI equation at higher mGFR values. SUMMARY: Both equations underestimated mGFR, but CKD-EPI gave more accurate estimates of GFR.

Performance of point-of-care HbA1c test devices: implications for use in clinical practice - a systematic review and meta-analysis.

BACKGROUND: Point-of-care (POC) devices could be used to measure hemoglobin A1c (HbA1c) in the doctors' office, allowing immediate feedback of results to patients. Reports have raised concerns about the analytical performance of some of these devices. We carried out a systematic review and meta-analysis using a novel approach to compare the accuracy and precision of POC HbA1c devices. METHODS: Medline, Embase and Web of Science databases were searched in June 2015 for published reports comparing POC HbA1c devices with laboratory methods. Two reviewers screened articles and extracted data on bias, precision and diagnostic accuracy. Mean bias and variability between the POC and laboratory test were combined in a meta-analysis. Study quality was assessed using the QUADAS2 tool. RESULTS: Two researchers independently reviewed 1739 records for eligibility. Sixty-one studies were included in the meta-analysis of mean bias. Devices evaluated were A1cgear, A1cNow, Afinion, B-analyst, Clover, Cobas b101, DCA 2000/Vantage, HemoCue, Innovastar, Nycocard, Quo-Lab, Quo-Test and SDA1cCare. Nine devices had a negative mean bias which was significant for three devices. There was substantial variability in bias within devices. There was no difference in bias between clinical or laboratory operators in two devices. CONCLUSIONS: This is the first meta-analysis to directly compare performance of POC HbA1c devices. Use of a device with a mean negative bias compared to a laboratory method may lead to higher levels of glycemia and a lower risk of hypoglycaemia. The implications of this on clinical decision-making and patient outcomes now need to be tested in a randomized trial.

Global Prevalence of Chronic Kidney Disease - A Systematic Review and Meta-Analysis.

Chronic kidney disease (CKD) is a global health burden with a high economic cost to health systems and is an independent risk factor for cardiovascular disease (CVD). All stages of CKD are associated with increased risks of cardiovascular morbidity, premature mortality, and/or decreased quality of life. CKD is usually asymptomatic until later stages and accurate prevalence data are lacking. Thus we sought to determine the prevalence of CKD globally, by stage, geographical location, gender and age. A systematic review and meta-analysis of observational studies estimating CKD prevalence in general populations was conducted through literature searches in 8 databases. We assessed pooled data using a random effects model. Of 5,842 potential articles, 100 studies of diverse quality were included, comprising 6,908,440 patients. Global mean(95%CI) CKD prevalence of 5 stages 13·4%(11·7-15·1%), and stages 3-5 was 10·6%(9·2-12·2%). Weighting by study quality did not affect prevalence estimates. CKD prevalence by stage was Stage-1 (eGFR>90+ACR>30): 3·5% (2·8-4·2%); Stage-2 (eGFR 60-89+ACR>30): 3·9% (2·7-5·3%); Stage-3 (eGFR 30-59): 7·6% (6·4-8·9%); Stage-4 = (eGFR 29-15): 0·4% (0·3-0·5%); and Stage-5 (eGFR<15): 0·1% (0·1-0·1%). CKD has a high global prevalence with a consistent estimated global CKD prevalence of between 11 to 13% with the majority stage 3. Future research should evaluate intervention strategies deliverable at scale to delay the progression of CKD and improve CVD outcomes.

Quantifying the effects of diuretics and ß-adrenoceptor blockers on glycaemic control in diabetes mellitus - a systematic review and meta-analysis.

AIMS: Although there are reports that ß-adrenoceptor antagonists (beta-blockers) and diuretics can affect glycaemic control in people with diabetes mellitus, there is no clear information on how blood glucose concentrations may change and by how much. We report results from a systematic review to quantify the effects of these antihypertensive drugs on glycaemic control in adults with established diabetes. METHODS: We systematically reviewed the literature to identify randomized controlled trials in which glycaemic control was studied in adults with diabetes taking either beta-blockers or diuretics. We combined data on HbA1c and fasting blood glucose using fixed effects meta-analysis. RESULTS: From 3864 papers retrieved, we found 10 studies of beta-blockers and 12 studies of diuretics to include in the meta-analysis. One study included both comparisons, totalling 21 included reports. Beta-blockers increased fasting blood glucose concentrations by 0.64 mmol l(-1) (95% CI 0.24, 1.03) and diuretics by 0.77 mmol l(-1) (95% CI 0.14, 1.39) compared with placebo. Effect sizes were largest in trials of non-selective beta-blockers (1.33, 95% CI 0.72, 1.95) and thiazide diuretics (1.69, 95% CI 0.60, 2.69). Beta-blockers increased HbA1c concentrations by 0.75% (95% CI 0.30, 1.20) and diuretics by 0.24% (95% CI -0.17, 0.65) compared with placebo. There was no significant difference in the number of hypoglycaemic events between beta-blockers and placebo in three trials. CONCLUSIONS: Randomized trials suggest that thiazide diuretics and non-selective beta-blockers increase fasting blood glucose and HbA1c concentrations in patients with diabetes by moderate amounts. These data will inform prescribing and monitoring of beta-blockers and diuretics in patients with diabetes.

The need for randomization in animal trials: an overview of systematic reviews.

BACKGROUND AND OBJECTIVES: Randomization, allocation concealment, and blind outcome assessment have been shown to reduce bias in human studies. Authors from the Collaborative Approach to Meta Analysis and Review of Animal Data from Experimental Studies (CAMARADES) collaboration recently found that these features protect against bias in animal stroke studies. We extended the scope the work from CAMARADES to include investigations of treatments for any condition. METHODS: We conducted an overview of systematic reviews. We searched Medline and Embase for systematic reviews of animal studies testing any intervention (against any control) and we included any disease area and outcome. We included reviews comparing randomized versus not randomized (but otherwise controlled), concealed versus unconcealed treatment allocation, or blinded versus unblinded outcome assessment. RESULTS: Thirty-one systematic reviews met our inclusion criteria: 20 investigated treatments for experimental stroke, 4 reviews investigated treatments for spinal cord diseases, while 1 review each investigated treatments for bone cancer, intracerebral hemorrhage, glioma, multiple sclerosis, Parkinson's disease, and treatments used in emergency medicine. In our sample 29% of studies reported randomization, 15% of studies reported allocation concealment, and 35% of studies reported blinded outcome assessment. We pooled the results in a meta-analysis, and in our primary analysis found that failure to randomize significantly increased effect sizes, whereas allocation concealment and blinding did not. In our secondary analyses we found that randomization, allocation concealment, and blinding reduced effect sizes, especially where outcomes were subjective. CONCLUSIONS: Our study demonstrates the need for randomization, allocation concealment, and blind outcome assessment in animal research across a wide range of outcomes and disease areas. Since human studies are often justified based on results from animal studies, our results suggest that unduly biased animal studies should not be allowed to constitute part of the rationale for human trials.

Diagnostic accuracy of point-of-care tests for detecting albuminuria: a systematic review and meta-analysis.

BACKGROUND: Experts recommend screening for albuminuria in patients at risk for kidney disease. PURPOSE: To systematically review evidence about the diagnostic accuracy of point-of-care (POC) tests for detecting albuminuria in individuals for whom guidelines recommend such detection. DATA SOURCES: Cochrane Library, EMBASE, Medion database, MEDLINE, and Science Citation Index from 1963 through 5 December 2013; hand searches of other relevant journals; and reference lists. STUDY SELECTION: Cross-sectional studies, published in any language, that compared the accuracy of machine-read POC tests of urinary albumin-creatinine ratio with that of laboratory measurement. DATA EXTRACTION: Two independent reviewers extracted study data and assessed study quality using the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2) tool. DATA SYNTHESIS: Sixteen studies (n = 3356 patients) that evaluated semiquantitative or quantitative POC tests and used random urine samples collected in primary or secondary ambulatory care settings met inclusion criteria. Pooling results from a bivariate random-effects model gave sensitivity and specificity estimates of 76% (95% CI, 63% to 86%) and 93% (CI, 84% to 97%), respectively, for the semiquantitative test. Sensitivity and specificity estimates for the quantitative test were 96% (CI, 78% to 99%) and 98% (CI, 93% to 99%), respectively. The negative likelihood ratios for the semiquantitative and quantitative tests were 0.26 (CI, 0.16 to 0.40) and 0.04 (CI, 0.01 to 0.25), respectively. LIMITATION: Accuracy estimates were based on data from single-sample urine measurement, but guidelines require that diagnosis of albuminuria be based on at least 2 of 3 samples collected in a 6-month period. CONCLUSION: A negative semiquantitative POC test result does not rule out albuminuria, whereas quantitative POC testing meets required performance standards and can be used to rule out albuminuria. PRIMARY FUNDING SOURCE: None.

Changes in HbA1c level over a 12-week follow-up in patients with type 2 diabetes following a medication change.

BACKGROUND: Current guidance about the interval needed before retesting HbA1c when monitoring for glycaemic control is based on expert opinion rather than well-powered studies. The aim of our work was to explore how fast HbA1c changes after a change in glucose-lowering medication. This has implications for whether routine HbA1c testing intervals before 12 weeks could inform diabetes medication adjustments. METHODS: This 12-week cohort study recruited patients from 18 general practices in the United Kingdom with non-insulin treated diabetes who were initiating or changing dose of oral glucose-lowering medication. HbA1c was measured at baseline and 2, 4, 8 and 12 weeks after recruitment. HbA1c levels at earlier time intervals were correlated with 12-week HbA1c. A ROC curve analysis was used to identify the 8-week threshold above which medication adjustment may be clinically appropriate. RESULTS: Ninety-three patients were recruited to the study. Seventy-nine patients with no change in medication and full 12-week follow-up had the following baseline characteristics: mean ± standard deviation age of 61.3 ± 10.8 years, 34% were female and diabetes duration of 6.0 ± 4.3 years. Mean HbA1c at baseline, 2, 4, 8 and 12 weeks was 8.7 ± 1.5%, (72.0 ± 16.8 mmol/mol) 8.6 ± 1.6% (70.7 ± 17.0 mmol/mol), 8.4 ± 1.5% (68.7 ± 15.9 mmol/mol), 8.2 ± 1.4% (66.3 ± 15.8 mmol/mol) and 8.1 ± 1.4% (64.8 ± 15.7 mmol/mol) respectively. At the end of the study 61% of patients had sub-optimal glycaemic control (HbA1c>7.5% or 59 mmol/mol). The 8-week change correlated significantly with the 12-week change in HbA1c and an HbA1c above 8.2% (66 mmol/mol) at 8 weeks correctly classified all 28 patients who had not achieved glycaemic control by 12 weeks. CONCLUSIONS/INTERPRETATION: This is the first study designed with sufficient power to examine short-term changes in HbA1c. The 12-week change in HbA1c can be predicted 8 weeks after a medication change. Many participants who had not achieved glycaemic control after 12 weeks may have benefitted from an earlier review of their HbA1c and medication.

Quantifying the effect of metformin treatment and dose on glycemic control.

OBJECTIVE: Metformin is the first-line oral medication recommended for glycemic control in patients with type 2 diabetes. We reviewed the literature to quantify the effect of metformin treatment on glycated hemoglobin (HbA(1c)) levels in all types of diabetes and examine the impact of differing doses on glycemic control. RESEARCH DESIGN AND METHODS: MEDLINE, EMBASE, and the Cochrane Library were searched from 1950 to June 2010 for trials of at least 12 weeks' duration in which diabetic patients were treated with either metformin monotherapy or as an add-on therapy. Data on change in HbA(1c) were pooled in a meta-analysis. Data from dose-comparison trials were separately pooled. RESULTS: A total of 35 trials were identified for the main analysis and 7 for the dose-comparison analysis. Metformin monotherapy lowered HbA(1c) by 1.12% (95% CI 0.92-1.32; I(2) = 80%) versus placebo, metformin added to oral therapy lowered HbA(1c) by 0.95% (0.77-1.13; I(2) = 77%) versus placebo added to oral therapy, and metformin added to insulin therapy lowered HbA(1c) by 0.60% (0.30-0.91; I(2) = 79.8%) versus insulin only. There was a significantly greater reduction in HbA(1c) using higher doses of metformin compared with lower doses of metformin with no significant increase in side effects. CONCLUSIONS: Evidence supports the effectiveness of metformin therapy in a clinically important lowering of HbA(1c) used as monotherapy and in combination with other therapeutic agents. There is potential for using higher doses of metformin to maximize glycemic control in diabetic patients without increasing gastrointestinal effects.

The impact of renin-angiotensin-aldosterone system inhibitors on Type 1 and Type 2 diabetic patients with and without early diabetic nephropathy.

Renin-angiotensin-aldosterone system inhibitors prevent the progression of kidney disease in patients with diabetic nephropathy, and we studied how that benefit varies by the type of diabetes and baseline urinary albumin. We pooled data from 49 randomized controlled trials in a meta-analysis using the ratio of endpoint urinary albumin levels in those treated compared to those untreated with renin-angiotensin-aldosterone system inhibitors in both fixed- and random-effects models. The urinary albumin excretion for treated microalbuminuric patients with Type 1 diabetes was on average 60% lower at the end of the trial compared with patients not treated with renin-angiotensin-aldosterone system inhibitors using the fixed-effects model and 67% lower using the random-effects model. There was no significant effect of treatment in patients with normal albumin excretion. For normoalbuminuric patients with Type 2 diabetes, urinary albumin excretion was on average 12% lower after treatment using the fixed-effects model compared to 21% lower using the random-effects model. For microalbuminuric patients, urinary albumin excretion was on average 23% lower using the fixed-effects model and 27% lower using the random-effects model. Thus, renin-angiotensin-aldosterone system inhibition reduced urinary albumin excretion for Type 1 diabetic patients with micro-, but not those with normoalbuminuria. Treatment reduced urinary albumin excretion for Type 2 diabetic patients with and without microalbuminuria.