BMJ medicine最新文献

Objective: To develop new risk prediction equations for kidney failure in patients with chronic kidney disease who do not require data for the urine albumin to creatinine ratio.

Design: Retrospective cohort study.

Setting: Stockholm Creatinine Measurements (SCREAM) database of routinely collected electronic healthcare records in primary and outpatient care from the region of Stockholm, Sweden.

Participants: 116 158 adults with chronic kidney disease stages 3-4, defined by two estimated glomerular filtration rate (eGFR) results of <60 to ≥15 mL/min/1.73 m², at least 90 days apart, with no intermediate eGFR value ≥60 mL/min/1.73 m², between 1 January 2010 to 31 December 2018.

Main outcome measure: Kidney failure, defined as starting kidney replacement therapy, recorded within five years of the index date.

Results: Based on temporal split sample validation, development and validation cohorts included 85 012 patients (736 kidney replacement therapy events) and 28 338 patients (114 kidney replacement therapy events), respectively. After Cox regression with automated backwards selection, the final model included 10 predictors (in order of significance): eGFR, age, diabetes, sex, atrial fibrillation, antihypertensive drugs, peripheral artery disease, reduction in eGFR slope, acute kidney injury, and hypertension. Model discrimination was excellent in both the development cohort (C statistic 0.941, 95% confidence interval (CI) 0.932 to 0.951) and validation cohort (C statistic 0.944, 0.923 to 0.965). In 26 229 patients with data for the urine albumin to creatinine ratio, the four variable kidney failure risk equation (KFRE) showed marginal improvement in discrimination over our new equation (C statistic 0.950, 95% CI 0.942 to 0.958 for KFRE v 0.926, 0.915 to 0.936, for the new equation). KFRE under-estimated the risk in the study cohort, however, with an observed-expected event probability ratio of 2.11, suggesting that recalibration is required.

Conclusions: The findings of the study indicate that predicting the risk of kidney failure with high accuracy in a general population of patients with chronic kidney disease is possible based on data that are routinely available, without requiring data for the urine albumin to creatinine ratio.

Objective: To directly compare the efficacy and safety of different intensive systolic blood pressure targets (<120 or <130 mm Hg) versus usual care on cardiovascular and renal outcomes.

Design: Meta-analysis of randomised controlled trials.

Data sources: Web of Science and Medline, from inception to 20 May 2025.

Eligibility criteria for selecting studies: Randomised controlled trials comparing intensive versus usual systolic blood pressure targets. Studies reported cardiovascular disease or kidney outcomes, or both.

Results: The study included 18 randomised controlled trials of 60 629 participants. Intensive control of systolic blood pressure significantly reduced the risk of major adverse cardiovascular events (relative risk 0.82, 95% confidence interval (CI) 0.78 to 0.87, P<0.001), including myocardial infarction, stroke, heart failure, and death from cardiovascular disease. Systolic blood pressure targets of <120 mm Hg and <130 mm Hg provided comparable cardiovascular protection. Intensive control of systolic blood pressure increased the risk of the composite chronic kidney disease outcome (relative risk 1.40, 95% CI 1.01 to 1.94, P=0.046), but with a likely higher risk for the target of <120 mm Hg. A systolic blood pressure target of <120 mm Hg also reduced the risk of albuminuria, but increased the risk of bradycardia and hypotension.

Conclusions: Intensive control of systolic blood pressure provided substantial cardiovascular benefits but increased the risk of renal adverse events. A systolic blood pressure target of <130 mm Hg had a similar degree of cardiovascular protection as <120 mm Hg with a more favourable renal safety profile, supporting a personalised risk based approach to treatment intensification.

Trial registration: PROSPERO CRD42025629962.

Objectives: To evaluate the effect of overall time restricted eating on metabolic health outcomes, and to identify the optimal types of time restricted eating in terms of timing and duration of eating.

Design: Systematic review and network meta-analysis.

Data sources: PubMed, Embase, and the Cochrane databases, from inception to 3 January 2023.

Eligibility criteria for selecting studies: Randomised controlled trials investigating the relation between time restricted eating (intervention period >one month) and metabolic health outcomes in humans.

Results: 41 randomised controlled trials of 2287 participants were included. Time restricted eating was categorised according to time of eating (early, mid-, late, and self-selected; last meal eaten before 1700, between 1700 and 1900, after 1900, or chosen by participant, respectively) and specific duration or window of eating each day (<8 hours, eight hours, and >8 hours). Compared with usual diets, overall time restricted eating significantly improved body weight, body mass index, fat mass, waist circumference, systolic blood pressure, and levels of fasting blood glucose, fasting insulin, and triglycerides. For different time restricted eating subtypes, early time restricted eating consistently showed higher P score rankings for anthropometric measurements (P score range 0.62-0.86, except for fat free mass-lean mass; a score closer to one indicating more favourable subtype) and glycaemic parameters (P score range 0.66-0.99). Compared with late time restricted eating, early time restricted eating significantly reduced body weight (mean difference -1.15 kg, 95% confidence interval -1.86 to -0.45) and fasting insulin concentrations (-3.32 μIU/ml, -5.36 to -1.28; 1 μIU/mL=6.95 pmol/L) and the certainty of the evidence was high. P value rankings for eating duration were inconsistent. Assessment of risk of bias, based on the risk of bias 2 tool, found that most of the included studies (90%) were rated as low risk of bias. In the confidence in network meta-analysis (CINeMA) assessment, about 60.2% of the network evidence showed moderate to high certainty. Inconsistency was generally low (I²<75% for 87% of associations).

Conclusions: Time restricted eating overall improved metabolic health outcomes compared with usual diets, and early time restricted eating was superior to late time restricted eating. The association between duration of eating and metabolic health outcomes was inconsistent.

Systematic review registration: PROSPERO CRD42022302737.

Objective: To study the performance of two contemporary sets of estimating equations for glomerular filtration rate, published by CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) and EKFC (European Kidney Function Consortium) that include one (creatinine or cystatin C only) and combined (creatinine and cystatin C) biomarkers, to assess their accuracy in a population with moderate chronic kidney disease.

Design: Prospective cohort study.

Setting: Primary, secondary, and tertiary care in six centres in England. Participants were recruited from April 2014 to January 2017.

Participants: 1167 adults, aged ≥18 years, with moderate chronic kidney disease (estimated glomerular filtration rate 30-59 mL/min/1.73 m² sustained over at least three months before recruitment).

Main outcome measures: Accuracy of estimating equations CKD-EPI_creatinine, CKD-EPI_cystatin, CKD-EPI_{creatinine-cystatin}, EKFC_creatinine, EKFC_cystatin, and EKFC_{creatinine-cystatin} compared with measured glomerular filtration rate (iohexol clearance). Remodelled 2021 versions of the CKD-EPI equations were also studied. Accuracy was expressed as P30 (percentage of estimates within 30% of measured glomerular filtration rate).

Results: Median age was 67.5 years, 58.3% of patients were men, 86.9% were white participants, and 27.8% had diabetes. Median measured glomerular filtration rate was 47.0 mL/min/1.73 m²; 57.0% of participants had albuminuria. Test calibration critically affected measurement of cystatin C. After recalibration of cystatin C, P30 values were 90.2% (CKD-EPI_creatinine), 89.5% (CKD-EPI_cystatin), 94.9% (CKD-EPI_{creatinine-cystatin}), 88.0% (CKD-EPI(2021)_creatinine), 94.9% (CKD-EPI(2021)_{creatinine-cystatin}), 89.4% (EKFC_creatinine), 91.0% (EKFC_cystatin), and 94.9% (EKFC_{creatinine-cystatin}). Creatinine based equations showed varying bias depending on the glomerular filtration rate level; inclusion of cystatin C in the equations improved this effect. Differences in accuracy in age, sex, and glomerular filtration rate level subgroups varied by equation. Equations combining creatinine and cystatin performed equally across age, sex, diabetes status, albuminuria status, and body mass index categories.

Conclusions: The CKD-EPI_creatinine equation had acceptable accuracy in a white population in England with moderate chronic kidney disease. Combined dual biomarker equations showed higher accuracy than the CKD-EPI_creatinine equation and their equivalent creatinine only equations. Further research is needed to determine the most accurate equation to use in people of black and South Asian origin living in England.

Objective: To examine the associations of long term engagement in individual physical activities and physical activity variety with the risk of death.

Design: Prospective cohort studies.

Setting: Nurses' Health Study (1986-2018) and Health Professionals Follow-Up Study (1986-2020).

Participants: 70 725 women and 40 742 men who were free of diabetes, cardiovascular disease, cancer, respiratory disease, or neurological disease and had complete physical activity information at baseline (leisure time physical activity was biennially updated using validated questionnaires during follow-up; the variety of physical activity was measured as the total number of individual physical activities in which participants consistently engaged).

Main outcome measures: All cause and cause specific mortality.

Results: During 2 431 318 person years of follow-up, 38 847 deaths were recorded, with 9901 from cardiovascular disease, 10 719 from cancer, and 3159 from respiratory disease. Total physical activity and most individual physical activities, except for swimming, were associated with lower mortality with non-linear dose-response relations. The pooled multivariable adjusted hazard ratios for all cause mortality in the highest categories of physical activity levels, compared with the lowest, were 0.83 (95% confidence interval 0.80 to 0.85) for walking, 0.89 (0.85 to 0.94) for jogging, 0.87 (0.80 to 0.93) for running, 0.96 (0.93 to 0.99) for bicycling, 1.01 (0.97 to 1.05) for swimming, 0.85 (0.80 to 0.89) for tennis or squash, 0.90 (0.87 to 0.93) for climbing stairs, 0.86 (0.84 to 0.89) for rowing or callisthenics, and 0.87 (0.82 to 0.91) for weight training or resistance exercises. Higher physical activity variety was associated with lower mortality. After adjustment for total physical activity levels, participants in the group with the highest physical activity variety score (group 5), compared with those in the lowest group (group 1), had a 19% lower all cause mortality and 13-41% lower mortality from cardiovascular disease, cancer, respiratory disease, and other causes (all P for trend <0.001).

Conclusions: Habitual engagement in most types of physical activity was associated with lower mortality. The variety of physical activity was inversely associated with mortality, independent of total physical activity levels. Overall, these data support the notion that long term engagement in multiple types of physical activity may help extend the lifespan.

Objective: To quantify the changes in opioid prescribing over time to a population with high rates of opioid use to understand the impact of longer elective wait times during the covid-19 pandemic.

Design: With the approval of NHS England, a retrospective cohort study using linked electronic health record data in OpenSAFELY-TPP.

Setting: Primary and secondary care electronic health records of people registered at general practices in England that use TPP SystmOne software, covering about 43% of the total registered population in England, linked to data from the Waiting List Minimum Dataset (WLMDS) within the OpenSAFELY-TPP platform, which is part of the NHS England OpenSAFELY covid-19 service.

Participants: 63 850 eligible patients on the waiting list for elective trauma procedures or orthopaedic procedures whose wait ended in admission between May 2021 and April 2022.

Main outcome measures: Opioid prescribing to eligible patients before referral to the waiting list, while waiting for treatment, and after discharge from treatment. Opioids were classified based on their strength (weak, moderate, or strong opioids) and duration of action (immediate release v modified release opioids).

Results: Of 63 850 people on elective trauma or orthopaedic waiting lists whose wait ended during the study period (median age 61 years, 54.6% female), 20.5% waited for more than 52 weeks to be admitted. In the three months before their waiting list referral date, 9890 (15.5%) participants had three or more opioid prescriptions, and 3790 (5.9%) were prescribed a strong opioid. Weekly opioid prescribing rates per 100 people on the waiting list were stable over time, with prescription rates peaking immediately after treatment and plateauing about three months after treatment. Comparing the three month period before the waiting list referral date to the period four to six months after the waiting list end date, changes in the proportion of people with three or more prescriptions for an opioid during that period were -1.6% (95% confidence interval -2.2% to -1.0%) for people on the waiting list for 18 weeks or less, -1.1% (-1.7% to -0.5%) for people waiting for 19-52 weeks, and -0.5% (-1.4% to 0.4%) for people waiting for more than 52 weeks.

Conclusions: In this study, one in five people who received treatment for an elective orthopaedic procedure between May 2021 and April 2022 waited for more than one year. Nearly one in seven people were prescribed opioids long term before their referral date to the waiting list, and only small reductions in long term opioid prescribing were observed after a patient's procedure, regardless of length of time spent on the waiting list.