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In this cluster-randomized, multiple-crossover trial conducted in 5 ICUs, intravenous administration of balanced crystalloids resulted in a lower rate of the composite outcome — death from any cause, new renal-replacement therapy, or persistent renal dysfunction — than saline.

Patients with type 2 diabetes at high risk for cardiovascular disease who were already taking a renin–angiotensin system blocker were randomly assigned to the direct renin inhibitor aliskiren or placebo. The study was discontinued early for no benefit, or even possible harm. Mortality associated with type 2 diabetes remains nearly twice that when diabetes is absent. 1 Complications of diabetes, particularly renal and cardiovascular disease, substantially increase the risk of subsequent severe illness and death. When a patient has both renal and cardiovascular disease, the risk is magnified further. 2 , 3 Blood-pressure lowering is beneficial in slowing renal-disease progression, reducing cardiovascular disease events, and preventing premature death. 4 Renin–angiotensin–aldosterone system (RAAS) blockers are highly effective, with apparent benefits extending beyond simple blood-pressure lowering 5 – 8 ; such agents have become the preferred first-line interventions in high-risk persons with diabetes. Theoretically, dual RAAS blockade should be more . . .

Objective To examine the risk of serious infection conveyed by tumour necrosis factor α (TNFα) inhibitors in the treatment of rheumatoid arthritis (RA). Methods Data from patients with RA enrolled in the German biologics register RABBIT were used for analysis. Baseline patient characteristics, time-varying risk factors (treatment changes, functional capacity) and selection processes caused by dropout, death or switching to non-anti-TNF treatment were taken into account to estimate the adjusted incidence rate ratios (IRRadj) of serious infection during treatment with TNF inhibitors compared with non-biological disease-modifying antirheumatic drug treatment. Results Data were available on 5044 patients, in whom 392 serious infections occurred. The crude rates of serious infections in patients treated with TNF inhibitors declined over the first 3 years of observation (from 4.8 to 2.2/100 patient-years). This decline was driven by (1) treatment termination or loss to follow-up in patients at increased risk and (2) a risk reduction through decreasing glucocorticoid doses and improvement in function. Adjusted for selection processes and time-varying risk factors, the following parameters assessed at baseline (age, chronic diseases) or at follow-up prior to the infection were significantly associated with an increased risk: age >60 years, chronic lung or renal disease, low functional capacity, history of serious infections, treatment with glucocorticoids (7.5–14 mg/day, IRRadj 2.1 (95% CI 1.4 to 3.2); ≥15 mg/day, IRRadj 4.7 (95% CI 2.4 to 9.4)) and treatment with TNFα inhibitors (IRRadj 1.8 (95% CI 1.2 to 2.7)). Conclusion Reasons for the decline in infection rates observed at the group level were identified. The results enable expected infection rates to be calculated in individual patients based on their risk profiles.

Long-term antiretroviral therapy for the treatment of human immunodeficiency virus infection is associated with a substantial rate of complications. Structured interruption of antiretroviral therapy, in the setting of a preserved CD4+ count, has been considered in order to minimize these side effects. In this randomized study of 5472 patients, CD4+ count–guided intermittent use of antiretroviral drugs was found to be associated with increased rates of opportunistic disease, death from any cause, and severe adverse events, as compared with the continuous use of antiretroviral therapy. CD4+ count–guided intermittent use of antiretroviral drugs was found to be associated with increased rates of opportunistic disease, death from any cause, and severe adverse events, as compared with the continuous use of antiretroviral therapy. With the advent of potent combination antiretroviral therapy came the hope that such therapy might lead to the eradication of infection with the human immunodeficiency virus (HIV). 1 It was soon recognized, however, that this goal was unlikely to be achieved owing to the existence of latent reservoirs; people infected with HIV would need to receive antiretroviral therapy for many years, if not for life. 2 , 3 Potent antiretroviral therapy is associated with substantial benefits with regard to morbidity and mortality. 4 – 6 However, the therapy is also associated with both short-term and long-term adverse events. 7 , 8 Major metabolic and cardiovascular complications have . . .

Gender-based clinical differences are increasingly being identified as having significant influence on the outcomes of patients with cardiovascular disease (CVD), including atrial fibrillation (AF). To perform detailed clinical phenotyping on a cohort of hospitalised patients with chronic forms of AF to understand if gender-based differences exist in the clinical presentation, thrombo-embolic risk and therapeutic management of high risk patients hospitalised with chronic AF. We are undertaking the Standard versus Atrial Fibrillation spEcific managemenT studY (SAFETY) - a multi-centre, randomised controlled trial of an AF-specific management intervention versus usual care. Extensive baseline profiling of recruited patients was undertaken to identify gender-specific differences for risk delineation. We screened 2,438 patients with AF and recruited 335 into SAFETY. Of these, 48.1% were women who were, on average, 5 years older than their male counterparts. Women and men displayed divergent antecedent profiles, with women having a higher thrombo-embolic risk but being prescribed similar treatment regimens. More women than men presented to hospital with co-morbid thyroid dysfunction, depression, renal impairment and obesity. In contrast, more men presented with coronary artery disease (CAD) and/or chronic obstructive pulmonary disease (COPD). Even when data was age-adjusted, women were more likely to live alone (odds ratio [OR] 2.33; 95% confidence interval [CI] 1.47 to 3.69), have non-tertiary education (OR 2.69; 95% CI 1.61 to 4.48) and be symptomatic (OR 1.93; 95% CI 1.06 to 3.52). Health care providers should be cognisant of gender-specific differences in an attempt to individualise and, hence, optimise the management of patients with chronic AF and reduce potential morbidity and mortality.

Tailored hydration strategies appear to provide an effective solution for preventing contrast-induced nephropathy (CIN) after percutaneous coronary intervention (PCI). The Vigileo/FloTrac system could predict the patients’ fluid responsiveness and tolerance to hydration. This prospective multicenter, randomized controlled, open-label study evaluated the efficacy of aggressive hydration guided by the Vigileo/FloTrac system for CIN prevention in patients with acute myocardial infarction (AMI). This trial enrolled patients with AMI undergoing urgent PCI, and these patients were randomized (1:1) to receive either aggressive hydration guided by Vigileo/FloTrac system (intervention group) or general hydration (control group). Patients with AMI in the intervention group received a loading dose of saline, and the hydration speed was adjusted according to the change of Vigileo/FloTrac index. The primary end point is CIN, which was defined as a >25% or >0.5 mg/100 ml increase in serum creatinine compared with baseline during the first 72 hours after urgent PCI. This trial was registered in ClinicalTrials.gov (NCT04382313). A total of 344 patients with AMI were enrolled and randomized in our trial, and the baseline characteristics, including risk factors of CIN, of the Vigileo/FloTrac-guided hydration group (n = 173) and control group (n = 171) were well balanced (all p >0.05). The total hydration volume in Vigileo/FloTrac-guided hydration group was significantly much more than control group (1,910 ± 600 vs 440 ± 90 ml, p <0.001). The incidence of CIN in the Vigileo/FloTrac-guided hydration group was significantly decreased than that in the control group (12.1% [21/173] vs 22.2% [38/171], p = 0.013). There was not significantly different in the incidence of acute heart failure after PCI (9.2% [16/173] vs 7.6% [13/171], p = 0.583). The incidence of main adverse cardiovascular events in the Vigileo/FloTrac-guided hydration group was lower than that in the control group but without statistically difference (30 events [17.3%] vs 38 events [22.2%], p = 0.256). In conclusion, Vigileo/FloTrac system-guided aggressive hydration could effectively decrease the risk of CIN for patients with AMI undergoing urgent PCI and avoid attack of acute heart failure at the same time.

The predictive value of serum adiponectin for hypertensive cardiovascular outcomes is unknown. This study was performed to investigate the association of adiponectin with incident cardiovascular and renal events (CV events) in hypertensive patients. We performed post-hoc analysis on 1,228 hypertensive patients enrolled in the ATTEMPT-CVD study, a prospective randomized study comparing the effects of two antihypertensive therapies. The participants were divided into quartiles of baseline serum total adiponectin or high molecular weight (HMW) adiponectin. Multivariable Cox proportional hazards analysis was performed to determine the prognostic factors associated with CV events. Kaplan-Meier analysis for CV events by quartiles of baseline total adiponectin showed that patients in the highest total adiponectin quartile (Q4) had more CV events (P = 0.0135). On the other hand, no significant difference was noted regarding the incidence of CV events among patients stratified by HMW adiponectin quartile (P = 0.2551). Even after adjustment for potential confounders, the highest total adiponectin quartile (Q4) remained independently associated with incident CV events in hypertensive patients (HR = 1.949: 95%CI 1.051–3.612; P = 0.0341). These results showed that total adiponectin, but not HMW adiponectin, was independently associated with the incidence of CV events in treated hypertensive patients, thereby highlighting total adiponectin as a valuable predictor for hypertensive cardiovascular outcomes.

Comorbidities are associated with increased mortality among patients receiving long-term kidney replacement therapy (KRT). However, it is not known whether primary kidney disease modifies the effect of comorbidities on KRT patients' survival. An incident cohort of all patients (n = 8696) entering chronic KRT in Finland in 2000-2017 was followed until death or end of 2017. All data were obtained from the Finnish Registry for Kidney Diseases. Information on comorbidities (coronary artery disease, peripheral vascular disease, left ventricular hypertrophy, heart failure, cerebrovascular disease, malignancy, obesity, underweight, and hypertension) was collected at the start of KRT. The main outcome measure was relative risk of death according to comorbidities analyzed in six groups of primary kidney disease: type 2 diabetes, type 1 diabetes, glomerulonephritis (GN), polycystic kidney disease (PKD), nephrosclerosis, and other or unknown diagnoses. Kaplan-Meier estimates and Cox regression were used for survival analyses. In the multivariable model, heart failure increased the risk of death threefold among PKD and GN patients, whereas in patients with other kidney diagnoses the increased risk was less than twofold. Obesity was associated with worse survival only among GN patients. Presence of three or more comorbidities increased the age- and sex-adjusted relative risk of death 4.5-fold in GN and PKD patients, but the increase was only 2.5-fold in patients in other diagnosis groups. Primary kidney disease should be considered when assessing the effect of comorbidities on survival of KRT patients as it varies significantly according to type of primary kidney disease.

Background Cytomegalovirus (CMV) prophylaxis may prevent CMV indirect effects in renal transplant recipients. This study aimed to compare the efficacy of valganciclovir and valacyclovir prophylaxis for CMV after renal transplantation with the focus on chronic histologic damage within the graft. Methods From November 2007 through April 2012, adult renal transplant recipients were randomized, in an open-label, single-center study, at a 1:1 ratio to 3-month prophylaxis with valganciclovir ( n  = 60) or valacyclovir ( n  = 59). The primary endpoint was moderate-to-severe interstitial fibrosis and tubular atrophy assessed by protocol biopsy at 3 years evaluated by a single pathologist blinded to the study group. The analysis was conducted in an intention-to-treat population. Results Among the 101 patients who had a protocol biopsy specimen available, the risk of moderate-to-severe interstitial fibrosis and tubular atrophy was significantly lower in those treated with valganciclovir (22% versus 34%; adjusted odds ratio, 0.31; 95% confidence interval, 0.11–0.90; P  = 0.032 by multivariate logistic regression). The incidence of CMV disease (9% versus 2%; P  = 0.115) and CMV DNAemia (36% versus 42%; P  = 0.361) were not different at 3 years. Conclusions Valganciclovir prophylaxis, as compared with valacyclovir, was associated with a reduced risk of moderate-to-severe interstitial fibrosis and tubular atrophy in patients after renal transplantation. Trial registration Australian New Zealand Clinical Trials Registry ( ACTRN12610000016033 ). Registered on September 26, 2007

Background The long-term prognosis of Henoch-Schönlein Purpura (HSP) is predominantly determined by the extent of renal involvement. There is no consensus as to whether treatment with prednisolone at presentation can prevent or ameliorate the progression of nephropathy in HSP. Methods Children under 18 years of age with new-onset HSP were randomly assigned to receive prednisolone or placebo for 14 days. The primary outcomes were (a) the presence of proteinuria at 12 months (defined as urine protein : creatinine ratio (UP : UC) >20 mg/mmol) and (b) the need for additional treatment (defined as the presence of hypertension requiring treatment or renal biopsy anomalies or the need for treatment of renal disease) during the 12 month study period. Results 352 children were randomised. Of those patients with laboratory UP : UC results available at 12 months, 18/123 (15%) patients on prednisolone and 13/124 (10%) patients on placebo had UP : UC >20 mg/mmol. There was no significant difference in the proportion of patients with UP : UC >20 mg/mmol at 12 months between the treatment groups (OR (prednisolone/placebo)=1.46, 95% CI 0.68 to 3.14, n=247), even after adjusting for baseline proteinuria and medications known to affect proteinuria (adjusted OR=1.29, 95% CI 0.58 to 2.82, n=247). Similarly, there was no significant difference in the time needed for additional treatment between the two groups (hazard ratio (HR) (prednisolone/placebo)=0.53, 95% CI 0.18 to 1.59, n=323). Conclusions This is the largest trial of the role of steroids in children with HSP. We found no evidence to suggest that early treatment with prednisolone reduces the prevalence of proteinuria 12 months after disease onset in children with HSP. Trial registration Number ISRCTN71445600