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.
IMPORTANCE: Self-monitoring of blood pressure with self-titration of antihypertensives (self-management) results in lower blood pressure in patients with hypertension, but there are no data about ...patients in high-risk groups. OBJECTIVE: To determine the effect of self-monitoring with self-titration of antihypertensive medication compared with usual care on systolic blood pressure among patients with cardiovascular disease, diabetes, or chronic kidney disease. DESIGN, SETTING, AND PATIENTS: A primary care, unblinded, randomized clinical trial involving 552 patients who were aged at least 35 years with a history of stroke, coronary heart disease, diabetes, or chronic kidney disease and with baseline blood pressure of at least 130/80 mm Hg being treated at 59 UK primary care practices was conducted between March 2011 and January 2013. INTERVENTIONS: Self-monitoring of blood pressure combined with an individualized self-titration algorithm. During the study period, the office visit blood pressure measurement target was 130/80 mm Hg and the home measurement target was 120/75 mm Hg. Control patients received usual care consisting of seeing their health care clinician for routine blood pressure measurement and adjustment of medication if necessary. MAIN OUTCOMES AND MEASURES: The primary outcome was the difference in systolic blood pressure between intervention and control groups at the 12-month office visit. RESULTS: Primary outcome data were available from 450 patients (81%). The mean baseline blood pressure was 143.1/80.5 mm Hg in the intervention group and 143.6/79.5 mm Hg in the control group. After 12 months, the mean blood pressure had decreased to 128.2/73.8 mm Hg in the intervention group and to 137.8/76.3 mm Hg in the control group, a difference of 9.2 mm Hg (95% CI, 5.7-12.7) in systolic and 3.4 mm Hg (95% CI, 1.8-5.0) in diastolic blood pressure following correction for baseline blood pressure. Multiple imputation for missing values gave similar results: the mean baseline was 143.5/80.2 mm Hg in the intervention group vs 144.2/79.9 mm Hg in the control group, and at 12 months, the mean was 128.6/73.6 mm Hg in the intervention group vs 138.2/76.4 mm Hg in the control group, with a difference of 8.8 mm Hg (95% CI, 4.9-12.7) for systolic and 3.1 mm Hg (95% CI, 0.7-5.5) for diastolic blood pressure between groups. These results were comparable in all subgroups, without excessive adverse events. CONCLUSIONS AND RELEVANCE: Among patients with hypertension at high risk of cardiovascular disease, self-monitoring with self-titration of antihypertensive medication compared with usual care resulted in lower systolic blood pressure at 12 months. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN87171227
Purpose Venous thromboembolism (VTE) is common in patients with cancer. Long-term daily subcutaneous low molecular weight heparin has been standard treatment for such patients. The purpose of this ...study was to assess if an oral factor Xa inhibitor, rivaroxaban, would offer an alternative treatment for VTE in patients with cancer. Patient and Methods In this multicenter, randomized, open-label, pilot trial in the United Kingdom, patients with active cancer who had symptomatic pulmonary embolism (PE), incidental PE, or symptomatic lower-extremity proximal deep vein thrombosis (DVT) were recruited. Allocation was to dalteparin (200 IU/kg daily during month 1, then 150 IU/kg daily for months 2-6) or rivaroxaban (15 mg twice daily for 3 weeks, then 20 mg once daily for a total of 6 months). The primary outcome was VTE recurrence over 6 months. Safety was assessed by major bleeding and clinically relevant nonmajor bleeding (CRNMB). A sample size of 400 patients would provide estimates of VTE recurrence to within ± 4.5%, assuming a VTE recurrence rate at 6 months of 10%. Results A total of 203 patients were randomly assigned to each group, 58% of whom had metastases. Twenty-six patients experienced recurrent VTE (dalteparin, n = 18; rivaroxaban, n = 8). The 6-month cumulative VTE recurrence rate was 11% (95% CI, 7% to 16%) with dalteparin and 4% (95% CI, 2% to 9%) with rivaroxaban (hazard ratio HR, 0.43; 95% CI, 0.19 to 0.99). The 6-month cumulative rate of major bleeding was 4% (95% CI, 2% to 8%) for dalteparin and 6% (95% CI, 3% to 11%) for rivaroxaban (HR, 1.83; 95% CI, 0.68 to 4.96). Corresponding rates of CRNMB were 4% (95% CI, 2% to 9%) and 13% (95% CI, 9% to 19%), respectively (HR, 3.76; 95% CI, 1.63 to 8.69). Conclusion Rivaroxaban was associated with relatively low VTE recurrence but higher CRNMB compared with dalteparin.
Aim
To provide reliable survival estimates for people with chronic heart failure and explain variation in survival by key factors including age at diagnosis, left ventricular ejection fraction, ...decade of diagnosis, and study setting.
Methods and results
We searched in relevant databases from inception to August 2018 for non‐interventional studies reporting survival rates for patients with chronic or stable heart failure in any ambulatory setting. Across the 60 included studies, there was survival data for 1.5 million people with heart failure. In our random effects meta‐analyses the pooled survival rates at 1 month, 1, 2, 5 and 10 years were 95.7% (95% confidence interval 94.3–96.9), 86.5% (85.4–87.6), 72.6% (67.0–76.6), 56.7% (54.0–59.4) and 34.9% (24.0–46.8), respectively. The 5‐year survival rates improved between 1970–1979 and 2000–2009 across healthcare settings, from 29.1% (25.5–32.7) to 59.7% (54.7–64.6). Increasing age at diagnosis was significantly associated with a reduced survival time. Mortality was lowest in studies conducted in secondary care, where there were higher reported prescribing rates of key heart failure medications. There was significant heterogeneity among the included studies in terms of heart failure diagnostic criteria, participant co‐morbidities, and treatment rates.
Conclusion
These results can inform health policy and individual patient advanced care planning. Mortality associated with chronic heart failure remains high despite steady improvements in survival. There remains significant scope to improve prognosis through greater implementation of evidence‐based treatments. Further research exploring the barriers and facilitators to treatment is recommended.
Summary Background Primary care is the main source of health care in many health systems, including the UK National Health Service (NHS), but few objective data exist for the volume and nature of ...primary care activity. With rising concerns that NHS primary care workload has increased substantially, we aimed to assess the direct clinical workload of general practitioners (GPs) and practice nurses in primary care in the UK. Methods We did a retrospective analysis of GP and nurse consultations of non-temporary patients registered at 398 English general practices between April, 2007, and March, 2014. We used data from electronic health records routinely entered in the Clinical Practice Research Datalink, and linked CPRD data to national datasets. Trends in age-standardised and sex-standardised consultation rates were modelled with joinpoint regression analysis. Findings The dataset comprised 101 818 352 consultations and 20 626 297 person-years of observation. The crude annual consultation rate per person increased by 10·51%, from 4·67 in 2007–08, to 5·16 in 2013–14. Consultation rates were highest in infants (age 0–4 years) and elderly people (≥85 years), and were higher for female patients than for male patients of all ages. The greatest increases in age-standardised and sex-standardised rates were in GPs, with a rise of 12·36% per 10 000 person-years, compared with 0·9% for practice nurses. GP telephone consultation rates doubled, compared with a 5·20% rise in surgery consultations, which accounted for 90% of all consultations. The mean duration of GP surgery consultations increased by 6·7%, from 8·65 min (95% CI 8·64–8·65) to 9·22 min (9·22–9·23), and overall workload increased by 16%. Interpretation Our findings show a substantial increase in practice consultation rates, average consultation duration, and total patient-facing clinical workload in English general practice. These results suggest that English primary care as currently delivered could be reaching saturation point. Notably, our data only explore direct clinical workload and not indirect activities and professional duties, which have probably also increased. This and additional research questions, including the outcomes of workload changes on other sectors of health care, need urgent answers for primary care provision internationally. Funding Department of Health Policy Research Programme.
AbstractObjectivesTo report reliable estimates of short term and long term survival rates for people with a diagnosis of heart failure and to assess trends over time by year of diagnosis, hospital ...admission, and socioeconomic group.DesignPopulation based cohort study.SettingPrimary care, United Kingdom.ParticipantsPrimary care data for 55 959 patients aged 45 and overwith a new diagnosis of heart failure and 278 679 age and sex matched controls in the Clinical Practice Research Datalink from 1 January 2000 to 31 December 2017 and linked to inpatient Hospital Episode Statistics and Office for National Statistics mortality data.Main outcome measuresSurvival rates at one, five, and 10 years and cause of death for people with and without heart failure; and temporal trends in survival by year of diagnosis, hospital admission, and socioeconomic group.ResultsOverall, one, five, and 10 year survival rates increased by 6.6% (from 74.2% in 2000 to 80.8% in 2016), 7.2% (from 41.0% in 2000 to 48.2% in 2012), and 6.4% (from 19.8% in 2000 to 26.2% in 2007), respectively. There were 30 906 deaths in the heart failure group over the study period. Heart failure was listed on the death certificate in 13 093 (42.4%) of these patients, and in 2237 (7.2%) it was the primary cause of death. Improvement in survival was greater for patients not requiring admission to hospital around the time of diagnosis (median difference 2.4 years; 5.3 v 2.9 years, P<0.001). There was a deprivation gap in median survival of 0.5 years between people who were least deprived and those who were most deprived (4.6 v 4.1 years, P<0.001).ConclusionsSurvival after a diagnosis of heart failure has shown only modest improvement in the 21st century and lags behind other serious conditions, such as cancer. New strategies to achieve timely diagnosis and treatment initiation in primary care for all socioeconomic groups should be a priority for future research and policy.
A previous efficacy trial found benefit from inhaled budesonide for COVID-19 in patients not admitted to hospital, but effectiveness in high-risk individuals is unknown. We aimed to establish whether ...inhaled budesonide reduces time to recovery and COVID-19-related hospital admissions or deaths among people at high risk of complications in the community.
PRINCIPLE is a multicentre, open-label, multi-arm, randomised, controlled, adaptive platform trial done remotely from a central trial site and at primary care centres in the UK. Eligible participants were aged 65 years or older or 50 years or older with comorbidities, and unwell for up to 14 days with suspected COVID-19 but not admitted to hospital. Participants were randomly assigned to usual care, usual care plus inhaled budesonide (800 μg twice daily for 14 days), or usual care plus other interventions, and followed up for 28 days. Participants were aware of group assignment. The coprimary endpoints are time to first self-reported recovery and hospital admission or death related to COVID-19, within 28 days, analysed using Bayesian models. The primary analysis population included all eligible SARS-CoV-2-positive participants randomly assigned to budesonide, usual care, and other interventions, from the start of the platform trial until the budesonide group was closed. This trial is registered at the ISRCTN registry (ISRCTN86534580) and is ongoing.
The trial began enrolment on April 2, 2020, with randomisation to budesonide from Nov 27, 2020, until March 31, 2021, when the prespecified time to recovery superiority criterion was met. 4700 participants were randomly assigned to budesonide (n=1073), usual care alone (n=1988), or other treatments (n=1639). The primary analysis model includes 2530 SARS-CoV-2-positive participants, with 787 in the budesonide group, 1069 in the usual care group, and 974 receiving other treatments. There was a benefit in time to first self-reported recovery of an estimated 2·94 days (95% Bayesian credible interval BCI 1·19 to 5·12) in the budesonide group versus the usual care group (11·8 days 95% BCI 10·0 to 14·1 vs 14·7 days 12·3 to 18·0; hazard ratio 1·21 95% BCI 1·08 to 1·36), with a probability of superiority greater than 0·999, meeting the prespecified superiority threshold of 0·99. For the hospital admission or death outcome, the estimated rate was 6·8% (95% BCI 4·1 to 10·2) in the budesonide group versus 8·8% (5·5 to 12·7) in the usual care group (estimated absolute difference 2·0% 95% BCI –0·2 to 4·5; odds ratio 0·75 95% BCI 0·55 to 1·03), with a probability of superiority 0·963, below the prespecified superiority threshold of 0·975. Two participants in the budesonide group and four in the usual care group had serious adverse events (hospital admissions unrelated to COVID-19).
Inhaled budesonide improves time to recovery, with a chance of also reducing hospital admissions or deaths (although our results did not meet the superiority threshold), in people with COVID-19 in the community who are at higher risk of complications.
National Institute of Health Research and United Kingdom Research Innovation.
Summary Background Control of blood pressure is a key component of cardiovascular disease prevention, but is difficult to achieve and until recently has been the sole preserve of health ...professionals. This study assessed whether self-management by people with poorly controlled hypertension resulted in better blood pressure control compared with usual care. Methods This randomised controlled trial was undertaken in 24 general practices in the UK. Patients aged 35–85 years were eligible for enrolment if they had blood pressure more than 140/90 mm Hg despite antihypertensive treatment and were willing to self-manage their hypertension. Participants were randomly assigned in a 1:1 ratio to self-management, consisting of self-monitoring of blood pressure and self-titration of antihypertensive drugs, combined with telemonitoring of home blood pressure measurements or to usual care. Randomisation was done by use of a central web-based system and was stratified by general practice with minimisation for sex, baseline systolic blood pressure, and presence or absence of diabetes or chronic kidney disease. Neither participants nor investigators were masked to group assignment. The primary endpoint was change in mean systolic blood pressure between baseline and each follow-up point (6 months and 12 months). All randomised patients who attended follow-up visits at 6 months and 12 months and had complete data for the primary outcome were included in the analysis, without imputation for missing data. This study is registered as an International Standard Randomised Controlled Trial , number ISRCTN17585681. Findings 527 participants were randomly assigned to self-management (n=263) or control (n=264), of whom 480 (91%; self-management, n=234; control, n=246) were included in the primary analysis. Mean systolic blood pressure decreased by 12·9 mm Hg (95% CI 10·4–15·5) from baseline to 6 months in the self-management group and by 9·2 mm Hg (6·7–11·8) in the control group (difference between groups 3·7 mm Hg, 0·8–6·6; p=0·013). From baseline to 12 months, systolic blood pressure decreased by 17·6 mm Hg (14·9–20·3) in the self-management group and by 12·2 mm Hg (9·5–14·9) in the control group (difference between groups 5·4 mm Hg, 2·4–8·5; p=0·0004). Frequency of most side-effects did not differ between groups, apart from leg swelling (self-management, 74 patients 32%; control, 55 patients 22%; p=0·022). Interpretation Self-management of hypertension in combination with telemonitoring of blood pressure measurements represents an important new addition to control of hypertension in primary care. Funding Department of Health Policy Research Programme, National Coordinating Centre for Research Capacity Development, and Midlands Research Practices Consortium.
It is uncertain whether being overweight, but not obese, is associated with advanced chronic kidney disease (CKD) and how the size and shape of associations between body-mass index (BMI) and advanced ...CKD differs among different types of people.
We used Clinical Practice Research Datalink records (2000-2014) with linkage to English secondary care and mortality data to identify a prospective cohort with at least one BMI measure. Cox models adjusted for age, sex, smoking and social deprivation and subgroup analyses by diabetes, hypertension and prior cardiovascular disease assessed relationships between BMI and CKD stages 4-5 and end-stage renal disease (ESRD).
1,405,016 adults aged 20-79 with mean BMI 27.4kg/m2 (SD 5.6) were followed for 7.5 years. Compared to a BMI of 20 to <25kg/m2, higher BMI was associated with a progressively increased risk of CKD stages 4-5 (hazard ratio 1.34, 95% CI 1.30-1.38 for BMI 25 to <30kg/m2; 1.94, 1.87-2.01 for BMI 30 to <35kg/m2; and 3.10, 2.95-3.25 for BMI ≥35kg/m2). The association between BMI and ESRD was shallower and reversed at low BMI. Current smoking, prior diabetes, hypertension or cardiovascular disease all increased risk of CKD, but the relative strength and shape of BMI-CKD associations, which were generally log-linear above a BMI of 25kg/m2, were similar among those with and without these risk factors. There was direct evidence that being overweight was associated with increased risk of CKD stages 4-5 in these subgroups. Assuming causality, since 2000 an estimated 39% (36-42%) of advanced CKD in women and 26% (22-30%) in men aged 40-79 resulted from being overweight or obese.
This study provides direct evidence that being overweight increases risk of advanced CKD, that being obese substantially increases such risk, and that this remains true for those with and without diabetes, hypertension or cardiovascular disease. Strategies to reduce weight among those who are overweight, as well as those who are obese may reduce CKD risk, with each unit reduction in BMI yielding similar relative reductions in risk.
Antihypertensives are effective at reducing the risk of cardiovascular disease, but limited data exist quantifying their association with serious adverse events, particularly in older people with ...frailty. This study aimed to examine this association using nationally representative electronic health record data.
This was a retrospective cohort study utilising linked data from 1,256 general practices across England held within the Clinical Practice Research Datalink between 1998 and 2018. Included patients were aged 40+ years, with a systolic blood pressure reading between 130 and 179 mm Hg, and not previously prescribed antihypertensive treatment. The main exposure was defined as a first prescription of antihypertensive treatment. The primary outcome was hospitalisation or death within 10 years from falls. Secondary outcomes were hypotension, syncope, fractures, acute kidney injury, electrolyte abnormalities, and primary care attendance with gout. The association between treatment and these serious adverse events was examined by Cox regression adjusted for propensity score. This propensity score was generated from a multivariable logistic regression model with patient characteristics, medical history and medication prescriptions as covariates, and new antihypertensive treatment as the outcome. Subgroup analyses were undertaken by age and frailty. Of 3,834,056 patients followed for a median of 7.1 years, 484,187 (12.6%) were prescribed new antihypertensive treatment in the 12 months before the index date (baseline). Antihypertensives were associated with an increased risk of hospitalisation or death from falls (adjusted hazard ratio aHR 1.23, 95% confidence interval (CI) 1.21 to 1.26), hypotension (aHR 1.32, 95% CI 1.29 to 1.35), syncope (aHR 1.20, 95% CI 1.17 to 1.22), acute kidney injury (aHR 1.44, 95% CI 1.41 to 1.47), electrolyte abnormalities (aHR 1.45, 95% CI 1.43 to 1.48), and primary care attendance with gout (aHR 1.35, 95% CI 1.32 to 1.37). The absolute risk of serious adverse events with treatment was very low, with 6 fall events per 10,000 patients treated per year. In older patients (80 to 89 years) and those with severe frailty, this absolute risk was increased, with 61 and 84 fall events per 10,000 patients treated per year (respectively). Findings were consistent in sensitivity analyses using different approaches to address confounding and taking into account the competing risk of death. A strength of this analysis is that it provides evidence regarding the association between antihypertensive treatment and serious adverse events, in a population of patients more representative than those enrolled in previous randomised controlled trials. Although treatment effect estimates fell within the 95% CIs of those from such trials, these analyses were observational in nature and so bias from unmeasured confounding cannot be ruled out.
Antihypertensive treatment was associated with serious adverse events. Overall, the absolute risk of this harm was low, with the exception of older patients and those with moderate to severe frailty, where the risks were similar to the likelihood of benefit from treatment. In these populations, physicians may want to consider alternative approaches to management of blood pressure and refrain from prescribing new treatment.