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Several studies have suggested that patients with kidney failure may benefit from high-dose hemodiafiltration as compared with standard hemodialysis. However, given the limitations of the various published studies, additional data are needed. We conducted a pragmatic, multinational, randomized, controlled trial involving patients with kidney failure who had received high-flux hemodialysis for at least 3 months. All the patients were deemed to be candidates for a convection volume of at least 23 liters per session (as required for high-dose hemodiafiltration) and were able to complete patient-reported outcome assessments. The patients were assigned to receive high-dose hemodiafiltration or continuation of conventional high-flux hemodialysis. The primary outcome was death from any cause. Key secondary outcomes were cause-specific death, a composite of fatal or nonfatal cardiovascular events, kidney transplantation, and recurrent all-cause or infection-related hospitalizations. A total of 1360 patients underwent randomization: 683 to receive high-dose hemodiafiltration and 677 to receive high-flux hemodialysis. The median follow-up was 30 months (interquartile range, 27 to 38). The mean convection volume during the trial in the hemodiafiltration group was 25.3 liters per session. Death from any cause occurred in 118 patients (17.3%) in the hemodiafiltration group and in 148 patients (21.9%) in the hemodialysis group (hazard ratio, 0.77; 95% confidence interval, 0.65 to 0.93). In patients with kidney failure resulting in kidney-replacement therapy, the use of high-dose hemodiafiltration resulted in a lower risk of death from any cause than conventional high-flux hemodialysis. (Funded by the European Commission Research and Innovation; CONVINCE Dutch Trial Register number, NTR7138.).

Carotid intima-media thickness (cIMT) is related to the risk of cardiovascular events in the general population. An association between changes in cIMT and cardiovascular risk is frequently assumed but has rarely been reported. Our aim was to test this association. We identified general population studies that assessed cIMT at least twice and followed up participants for myocardial infarction, stroke, or death. The study teams collaborated in an individual participant data meta-analysis. Excluding individuals with previous myocardial infarction or stroke, we assessed the association between cIMT progression and the risk of cardiovascular events (myocardial infarction, stroke, vascular death, or a combination of these) for each study with Cox regression. The log hazard ratios (HRs) per SD difference were pooled by random effects meta-analysis. Of 21 eligible studies, 16 with 36 984 participants were included. During a mean follow-up of 7·0 years, 1519 myocardial infarctions, 1339 strokes, and 2028 combined endpoints (myocardial infarction, stroke, vascular death) occurred. Yearly cIMT progression was derived from two ultrasound visits 2–7 years (median 4 years) apart. For mean common carotid artery intima-media thickness progression, the overall HR of the combined endpoint was 0·97 (95% CI 0·94–1·00) when adjusted for age, sex, and mean common carotid artery intima-media thickness, and 0·98 (0·95–1·01) when also adjusted for vascular risk factors. Although we detected no associations with cIMT progression in sensitivity analyses, the mean cIMT of the two ultrasound scans was positively and robustly associated with cardiovascular risk (HR for the combined endpoint 1·16, 95% CI 1·10–1·22, adjusted for age, sex, mean common carotid artery intima-media thickness progression, and vascular risk factors). In three studies including 3439 participants who had four ultrasound scans, cIMT progression did not correlate between occassions (reproducibility correlations between r=−0·06 and r=−0·02). The association between cIMT progression assessed from two ultrasound scans and cardiovascular risk in the general population remains unproven. No conclusion can be derived for the use of cIMT progression as a surrogate in clinical trials. Deutsche Forschungsgemeinschaft.

Cardiovascular disease （CVD） is the leading cause of death worldwide and contributes considerably to morbidity The underlying cause is atherosclerosisThe development of new preventive therapies is one of the steps to control the CVD epidemic. It is increasingly demanded that promising therapies be evaluated in trials using cardiovascular （CV） morbidity and mortality （M and M） as a primary outcome.

Diabetes is a strong risk factor for vascular disease. There is compelling evidence that the relative risk of vascular disease associated with diabetes is substantially higher in women than men. The mechanisms that explain the sex difference have not been identified. However, this excess risk could be due to certain underlying biological differences between women and men. In addition to other cardiometabolic pathways, sex differences in body anthropometry and patterns of storage of adipose tissue may be of particular importance in explaining the sex differences in the relative risk of diabetes-associated vascular diseases. Besides biological factors, differences in the uptake and provision of health care could also play a role in women’s greater excess risk of diabetic vascular complications. In this review, we will discuss the current knowledge regarding sex differences in both biological factors, with a specific focus on sex differences adipose tissue, and in health care provided for the prevention, management, and treatment of diabetes and its vascular complications. While progress has been made towards understanding the underlying mechanisms of women’s higher relative risk of diabetic vascular complications, many uncertainties remain. Future research to understanding these mechanisms could contribute to more awareness of the sex-specific risk factors and could eventually lead to more personalized diabetes care. This will ensure that women are not affected by diabetes to a greater extent and will help to diminish the burden in both women and men.

[This corrects the article DOI: 10.1371/journal.pone.0309773.].

Most evidence on the relationship between sodium and potassium intake and cardiovascular disease originated from general population studies. This study aimed to evaluate the relation between estimated 24-hour sodium and potassium urinary excretion and the risk of recurrent vascular events and mortality in patients with vascular disease. 7561 patients with vascular disease enrolled in the UCC-SMART cohort (1996-2015) were included. Twenty-four hour sodium and potassium urinary excretion were estimated (Kawasaki formulae) from morning urine samples. Cox proportional hazard models with restricted cubic splines were used to evaluate the relation between estimated urinary salt excretion and major adverse cardiovascular events (MACE; including myocardial infarction, stroke, cardiovascular mortality) and all-cause mortality. After a median follow-up of 7.4 years (interquartile range: 4.1-11.0), the relations between estimated 24-hour sodium urinary excretion and outcomes were J-shaped with nadirs of 4.59 gram/day for recurrent MACE and 4.97 gram/day for all-cause mortality. The relation between sodium-to-potassium excretion ratio and outcomes were also J-shaped with nadirs of 2.71 for recurrent MACE and 2.60 for all-cause mortality. Higher potassium urinary excretion was related to an increased risk of both recurrent MACE (HR 1.25 per gram potassium excretion per day; 95%CI 1.13-1.39) and all cause-mortality (HR 1.13 per gram potassium excretion per day; 95%CI 1.03-1.25). In patients with established vascular disease, lower and higher sodium intake were associated with higher risk of recurrent MACE and all-cause mortality. Higher estimated 24-hour potassium urinary excretion was associated with a higher risk of recurrent MACE and all-cause mortality.

Risk of readmissions is an important quality indicator for stroke care. Such information is limited among low- and middle-income countries. We assessed the trends for 28-day readmissions after a stroke in Malaysia from 2008 to 2015 and evaluated the causes and factors associated with readmissions in 2015. Using the national hospital admission records database, we included all stroke patients who were discharged alive between 2008 and 2015 for this secondary data analysis. The risk of readmissions was described in proportion and trends. Reasons were coded according to the International Classification of Diseases, 10th Edition. Multivariable logistic regression was performed to identify factors associated with readmissions. Among 151729 patients, 11 to 13% were readmitted within 28 days post-discharge from their stroke events each year. The trend was constant for ischemic stroke but decreasing for hemorrhagic stroke. The leading causes for readmissions were recurrent stroke (32.1%), pneumonia (13.0%) and sepsis (4.8%). The risk of 28-day readmission was higher among those with stroke of hemorrhagic (adjusted odds ratio (AOR): 1.52) and subarachnoid hemorrhage (AOR: 2.56) subtypes, and length of index admission >3 days (AOR: 1.48), but lower among younger age groups of 35-64 (AORs: 0.61-0.75), p values <0.001. The risk of 28-day readmission remained constant from 2008 to 2015, where one in eight stroke patients required readmission, mainly attributable to preventable causes. Age, ethnicity, stroke subtypes and duration of the index admission influenced the risk of readmission. Efforts should focus on minimizing potentially preventable admissions, especially among those at higher risk.

Clinical decision support systems (CDSSs) based on routine care data, using artificial intelligence (AI), are increasingly being developed. Previous studies focused largely on the technical aspects of using AI, but the acceptability of these technologies by patients remains unclear. We aimed to investigate whether patient-physician trust is affected when medical decision-making is supported by a CDSS. We conducted a vignette study among the patient panel (N=860) of the University Medical Center Utrecht, the Netherlands. Patients were randomly assigned into 4 groups-either the intervention or control groups of the high-risk or low-risk cases. In both the high-risk and low-risk case groups, a physician made a treatment decision with (intervention groups) or without (control groups) the support of a CDSS. Using a questionnaire with a 7-point Likert scale, with 1 indicating \"strongly disagree\" and 7 indicating \"strongly agree,\" we collected data on patient-physician trust in 3 dimensions: competence, integrity, and benevolence. We assessed differences in patient-physician trust between the control and intervention groups per case using Mann-Whitney U tests and potential effect modification by the participant's sex, age, education level, general trust in health care, and general trust in technology using multivariate analyses of (co)variance. In total, 398 patients participated. In the high-risk case, median perceived competence and integrity were lower in the intervention group compared to the control group but not statistically significant (5.8 vs 5.6; P=.16 and 6.3 vs 6.0; P=.06, respectively). However, the effect of a CDSS application on the perceived competence of the physician depended on the participant's sex (P=.03). Although no between-group differences were found in men, in women, the perception of the physician's competence and integrity was significantly lower in the intervention compared to the control group (P=.009 and P=.01, respectively). In the low-risk case, no differences in trust between the groups were found. However, increased trust in technology positively influenced the perceived benevolence and integrity in the low-risk case (P=.009 and P=.04, respectively). We found that, in general, patient-physician trust was high. However, our findings indicate a potentially negative effect of AI applications on the patient-physician relationship, especially among women and in high-risk situations. Trust in technology, in general, might increase the likelihood of embracing the use of CDSSs by treating professionals.

Frequent hemodialysis provided more than three times per week may lower mortality and improve health-related quality of life. Yet, the evidence is inconclusive. We evaluated the benefits and harms of frequent hemodialysis in people with kidney failure compared with standard hemodialysis. We performed a systematic review of randomized controlled trials including adults on hemodialysis with highly sensitive searching in MEDLINE, Embase, CENTRAL, and Google Scholar on 3 January 2024. Data were pooled using random-effects meta-analysis. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool. We adjudicated evidence certainty using GRADE. From 11,142 unique citations, only seven studies involving 518 participants proved eligible. The effects of frequent hemodialysis on physical and mental health were imprecise due to few data. Frequent hemodialysis probably had uncertain effect on death from all cause compared with standard hemodialysis (relative risk 0.79, 95% confidence interval 0.33-1.91, low certainty evidence). Data were not reported for death from cardiovascular causes, major cardiovascular events, fatigue or vascular access. The evidentiary basis for frequent hemodialysis is incomplete due to clinical trials with few or no events reported for mortality and cardiovascular outcome measures and few participants in which patient-reported outcomes including health-related quality of life and symptoms were reported.