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In this trial, patients with stage 4 chronic kidney disease and poorly controlled hypertension, as confirmed by 24-hour ambulatory blood-pressure monitoring, were randomly assigned to receive chlorthalidone (12.5 mg per day, with increases every 4 weeks if needed to a maximum dose of 50 mg per day) or placebo. Chlorthalidone therapy improved blood-pressure control at 12 weeks as compared with placebo.

In a trial involving patients with recurrent kidney stones who received once-daily 12.5-mg, 25-mg, or 50-mg doses of hydrochlorothiazide or placebo, the incidence of stone recurrence was similar in all groups.

Spironolactone is effective at reducing blood pressure in patients with uncontrolled resistant hypertension. However, the use of spironolactone in patients with chronic kidney disease can be restricted by hyperkalaemia. We evaluated use of the potassium binder patiromer to allow more persistent use of spironolactone in patients with chronic kidney disease and resistant hypertension. In this phase 2 multicentre, randomised, double-blind, placebo-controlled study, we enrolled participants aged 18 years and older with chronic kidney disease (estimated glomerular filtration rate 25 to ≤45 mL/min per 1·73 m2) and uncontrolled resistant hypertension from 62 outpatient centres in ten countries (Bulgaria, Croatia, Georgia, Hungary, Ukraine, France, Germany, South Africa, the UK, and the USA). Patients meeting all eligibility criteria at the final screening visit were stratified by local serum potassium measurement (4·3 to <4·7 mmol/L vs 4·7 to 5·1 mmol/L) and history of diabetes. Participants were randomly assigned (1:1) with an interactive web response system to receive either placebo or patiromer (8·4 g once daily), in addition to open-label spironolactone (starting at 25 mg once daily) and their baseline blood pressure medications. Participants, the study team that administered treatments and measured blood pressure, and the investigators were masked to assigned treatment groups. Dose titrations were permitted after 1 week (patiromer) and 3 weeks (spironolactone). The primary endpoint was the between-group difference at week 12 in the proportion of patients on spironolactone. Efficacy endpoints and safety were assessed in all randomised patients (intention to treat). The study was registered with Clinicaltrials.gov, NCT03071263. Between Feb 13, 2017, and Aug 20, 2018, we screened 574 patients. 295 (51%) of 574 patients met all inclusion criteria and were randomly assigned to spironolactone in addition to double-blind treatment with either placebo (n=148) or patiromer (n=147). At week 12, 98 (66%) of 148 patients in the placebo group and 126 (86%) of 147 patients in the patiromer group remained on spironolactone (between-group difference 19·5%, 95% CI 10·0–29·0; p<0·0001). Adverse events were mostly mild or moderate in severity and occurred in 79 (53%) of 148 patients in the placebo group and 82 (56%) of 147 patients in the patiromer group. In patients with resistant hypertension and chronic kidney disease, patiromer enabled more patients to continue treatment with spironolactone with less hyperkalaemia. Persistent spironolactone enablement in this population of patients has clinical relevance for the treatment of resistant hypertension. Relypsa, a Vifor Pharma Group Company.

Evidence is scarce on the efficacy of long-term human albumin (HA) administration in patients with decompensated cirrhosis. The human Albumin for the treatmeNt of aScites in patients With hEpatic ciRrhosis (ANSWER) study was designed to clarify this issue. We did an investigator-initiated multicentre randomised, parallel, open-label, pragmatic trial in 33 academic and non-academic Italian hospitals. We randomly assigned patients with cirrhosis and uncomplicated ascites who were treated with anti-aldosteronic drugs (≥200 mg/day) and furosemide (≥25 mg/day) to receive either standard medical treatment (SMT) or SMT plus HA (40 g twice weekly for 2 weeks, and then 40 g weekly) for up to 18 months. The primary endpoint was 18-month mortality, evaluated as difference of events and analysis of survival time in patients included in the modified intention-to-treat and per-protocol populations. This study is registered with EudraCT, number 2008–000625–19, and ClinicalTrials.gov, number NCT01288794. From April 2, 2011, to May 27, 2015, 440 patients were randomly assigned and 431 were included in the modified intention-to-treat analysis. 38 of 218 patients died in the SMT plus HA group and 46 of 213 in the SMT group. Overall 18-month survival was significantly higher in the SMT plus HA than in the SMT group (Kaplan-Meier estimates 77% vs 66%; p=0·028), resulting in a 38% reduction in the mortality hazard ratio (0·62 [95% CI 0·40–0·95]). 46 (22%) patients in the SMT group and 49 (22%) in the SMT plus HA group had grade 3–4 non-liver related adverse events. In this trial, long-term HA administration prolongs overall survival and might act as a disease modifying treatment in patients with decompensated cirrhosis. Italian Medicine Agency.

Patients with acute decompensated heart failure received intravenous furosemide at either a low or a high dose and either boluses every 12 hours or continuous infusion. At 72 hours, there was no significant difference in symptoms or in the change in creatinine level from baseline for either comparison. Acute decompensated heart failure is the most common cause of hospital admissions among patients older than 65 years of age and is responsible for more than 1 million hospitalizations annually in the United States. 1 Intravenous loop diuretics are an essential component of current treatment and are administered to approximately 90% of patients who are hospitalized with heart failure. 2 Despite decades of clinical experience with these agents, prospective data to guide the use of loop diuretics are sparse, and current guidelines are based primarily on expert opinion. 3 , 4 As a result, clinical practice varies widely with regard to both the mode . . .

Key PointsQuestionDoes an intervention aimed at improving guideline adherence for the management of acute heart failure, including intensive intravenous nitrate therapy and management of precipitating factors, improve hospital discharge and survival at 30 days?FindingsIn this stepped-wedge cluster randomized trial that included 503 patients 75 years and older who presented to the emergency department with acute heart failure, implementation of an early and comprehensive care bundle compared with usual care improved guideline adherence, but had no significant effect on number of days alive and out of hospital at 30 days (median of 19 d in both groups).MeaningsThis emergency department care bundle did not improve 30-day outcomes among older patients with acute heart failure. AbstractImportanceClinical guidelines for the early management of acute heart failure in the emergency department (ED) setting are based on only moderate levels of evidence, with subsequent low adherence to these guidelines.ObjectiveTo test the effect of an early guideline-recommended care bundle on short-term prognosis in older patients with acute heart failure in the ED.Design, Setting, and ParticipantsStepped-wedge cluster randomized trial in 15 EDs in France of 503 patients 75 years and older with a diagnosis of acute heart failure in the ED from December 2018 to September 2019 and followed up for 30 days until October 2019.InterventionsA care bundle that included early intravenous nitrate boluses; management of precipitating factors, such as acute coronary syndrome, infection, or atrial fibrillation; and moderate dose of intravenous diuretics (n = 200). In the control group, patient care was left to the discretion of the treating emergency physician (n = 303). Each center was randomized to the order in which they switched to the “intervention period.” After the initial 4-week control period for all centers, 1 center entered in the intervention period every 2 weeks.Main Outcomes and MeasuresThe primary end point was the number of days alive and out of hospital at 30 days. Secondary outcomes included 30-day all-cause mortality, 30-day cardiovascular mortality, unscheduled readmission, length of hospital stay, and kidney impairment.ResultsAmong 503 patients who were randomized (median age, 87 years; 298 [59%] women), 502 were analyzed. In the intervention group, patients received a median (interquartile range) of 27.0 (9-54) mg of intravenous nitrates in the first 4 hours vs 4.0 (2.0-6.0) mg in the control group (adjusted difference, 23.8 [95% CI, 13.5-34.1]). There was a significantly higher percentage of patients in the intervention group treated for their precipitating factors than in the control group (58.8% vs 31.9%; adjusted difference, 31.1% [95% CI, 14.3%-47.9%]). There was no statistically significant difference in the primary end point of the number of days alive and out of hospital at 30 days (median [interquartile range], 19 [0- 24] d in both groups; adjusted difference, −1.9 [95% CI, −6.6 to 2.8]; adjusted ratio, 0.88 [95% CI, 0.64-1.21]). At 30 days, there was no significant difference between the intervention and control groups in mortality (8.0% vs 9.7%; adjusted difference, 4.1% [95% CI, −17.2% to 25.3%]), cardiovascular mortality (5.0% vs 7.4%; adjusted difference, 2.1% [95% CI, −15.5% to 19.8%]), unscheduled readmission (14.3% vs 15.7%; adjusted difference, −1.3% [95% CI, −26.3% to 23.7%]), median length of hospital stay (8 d in both groups; adjusted difference, 2.5 [95% CI, −0.9 to 5.8]), and kidney impairment (1% in both groups).Conclusions and RelevanceAmong older patients with acute heart failure, use of a guideline-based comprehensive care bundle in the ED compared with usual care did not result in a statistically significant difference in the number of days alive and out of the hospital at 30 days. Further research is needed to identify effective treatments for acute heart failure in older patients.Trial Registration ClinicalTrials.gov Identifier: NCT03683212

The Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial showed that initial antihypertensive therapy with benazepril plus amlodipine was superior to benazepril plus hydrochlorothiazide in reducing cardiovascular morbidity and mortality. We assessed the effects of these drug combinations on progression of chronic kidney disease. ACCOMPLISH was a double-blind, randomised trial undertaken in five countries (USA, Sweden, Norway, Denmark, and Finland). 11 506 patients with hypertension who were at high risk for cardiovascular events were randomly assigned via a central, telephone-based interactive voice response system in a 1:1 ratio to receive benazepril (20 mg) plus amlodipine (5 mg; n=5744) or benazepril (20 mg) plus hydrochlorothiazide (12·5 mg; n=5762), orally once daily. Drug doses were force-titrated for patients to attain recommended blood pressure goals. Progression of chronic kidney disease, a prespecified endpoint, was defined as doubling of serum creatinine concentration or end-stage renal disease (estimated glomerular filtration rate <15 mL/min/1·73 m 2 or need for dialysis). Analysis was by intention to treat (ITT). This trial is registered with ClinicalTrials.gov, number NCT00170950. The trial was terminated early (mean follow-up 2·9 years [SD 0·4]) because of superior efficacy of benazepril plus amlodipine compared with benazepril plus hydrochlorothiazide. At trial completion, vital status was not known for 143 (1%) patients who were lost to follow-up (benazepril plus amlodipine, n=70; benazepril plus hydrochlorothiazide, n=73). All randomised patients were included in the ITT analysis. There were 113 (2·0%) events of chronic kidney disease progression in the benazepril plus amlodipine group compared with 215 (3·7%) in the benazepril plus hydrochlorothiazide group (HR 0·52, 0·41–0·65, p<0·0001). The most frequent adverse event in patients with chronic kidney disease was peripheral oedema (benazepril plus amlodipine, 189 of 561, 33·7%; benazepril plus hydrochlorothiazide, 85 of 532, 16·0%). In patients with chronic kidney disease, angio-oedema was more frequent in the benazepril plus amlodipine group than in the benazepril plus hydrochlorothiazide group. In patients without chronic kidney disease, dizziness, hypokalaemia, and hypotension were more frequent in the benazepril plus hydrochlorothiazide group than in the benazepril plus amlodipine group. Initial antihypertensive treatment with benazepril plus amlodipine should be considered in preference to benazepril plus hydrochlorothiazide since it slows progression of nephropathy to a greater extent. Novartis.

Furosemide is the most commonly used diuretic in intensive care units (ICU). We aimed to evaluate the physiological effects of adjunctive acetazolamide with furosemide on diuresis and the prevention of potential furosemide-induced metabolic alkalosis. We performed a two-center, pilot, open-label, randomized trial. Where the treating physicians planned intravenous diuretic therapy, we randomized ICU patients to a bolus of furosemide (40 mg) plus acetazolamide (500 mg) (n = 15) or furosemide alone (40 mg) (n = 15). Urine output, additional furosemide use, acid-base parameters, and electrolytes were compared following a Bayesian framework. Adjunctive acetazolamide didn't increase urine output in the first six hours (mean difference: −112 ml, credible interval: [−742, 514]). However, compared with furosemide alone, it maintained a greater urine output response to furosemide over 24 h, with 100 % probability. Acetazolamide also acidified plasma (pH difference: −0.045, [−0.081, −0.008]) while alkalinizing urine (1.10, [0.04, 2.11]) at six hours, compared to furosemide alone with >95 % probability. Finally, we didn't observe severe acidosis or electrolyte disturbances over 24 h. Adjunctive acetazolamide may increase diuretic efficacy and counterbalance furosemide-induced metabolic alkalosis without safety concerns. Larger trials are warranted to verify these findings and assess their impacts on clinical outcomes. ACTRN12623000624684. A pilot trial of single versus dual diuretic therapy in the intensive care unit. •Pathophysiologic effects of adjunctive acetazolamide were assessed in this pilot RCT.•Acetazolamide may have preserved urine output response to furosemide.•Acetazolamide may have counterbalanced furosemide-induced metabolic alkalosis.•Adjunctive acetazolamide may not result in severe acidosis or electrolyte disturbance.•Larger trials to evaluate the effect of adjunctive acetazolamide appear justified.

•Peripheral venous pressure (PVP) measurement provides a noninvasive, bedside assessment of vascular congestion that could enhance fluid management without the risks of invasive monitoring.•This study investigates whether PVP-guided diuretic therapy is superior to standard care in managing heart failure (HF) patients, specifically in improving decongestion outcomes.•The primary endpoint is a composite of all-cause mortality, hospitalizations, and emergency department visits. Secondary outcomes include cardiovascular mortality, HF-related hospitalizations, and emergency department visits.•If successful, this study could significantly improve HF management by enabling more precise, individualized diuretic therapy, reducing rehospitalizations, and improving long-term outcomes related to vascular congestion and renal function. Congestive symptoms are the primary cause of hospitalizations in heart failure (HF), and diuretics remain the cornerstone of their management. However, clinical practice varies widely due to a lack of a reliable measure of congestion guiding diuretic use. Consequently, many HF patients are discharged prematurely without adequate decongestion, leading to increased readmissions and mortality. Peripheral venous pressure (PVP) has emerged as a promising noninvasive measure of vascular congestion. This study will enroll 650 patients aged 18-99 years admitted with de novo or acutely decompensated chronic HF. In the standard care arm, diuretic dosing and discharge decisions will be at the physician's discretion. In the PVP-guided arm, the goal is to maintain a PVP of <9 mmHg, with diuretic dosing adjusted based on daily PVP changes and urine output. The primary outcome is a composite of all-cause mortality, hospitalizations, and emergency department visits, with secondary outcomes including cardiovascular mortality and HF-related readmissions. We hypothesize that PVP-guided diuretic therapy will provide more precise and effective decongestion than standard care, reducing rehospitalizations and mortality. In conclusion, this study will offer valuable insights into the relationship between diuretic therapy, vascular congestion, and cardiac and renal outcomes. Trial registration: ClinicalTrials.gov Identifier: NCT06495892

The act of filling the bladder prior to obtaining an ultrasound is often the rate limiting factor in the diagnosis of ovarian torsion in pediatric females. The objective of this study was to evaluate if low dose furosemide plus IV fluid administration results in faster bladder filling time in comparison to IV fluid administration alone in females age 8–18 with suspected ovarian torsion. This was a randomized, placebo controlled, single blinded pilot study using convenience sampling to target females ages 8 to 18 years seen in the pediatric emergency department and undergoing a trans-abdominal pelvic US to assess for ovarian torsion. Enrolled patients were assigned to the experimental group, receiving 0.1 mg/kg (max 5 mg) of furosemide, or the control group, receiving a 5 mL normal saline (NS) flush. Point of Care Ultrasound (POCUS) evaluation of the bladder was performed every 30 min until the bladder was determined to be of adequate size and morphology to perform the trans-abdominal pelvic US. Bladder filling as confirmed by POCUS occurred a median of 90 min sooner in the furosemide group compared with the control group (p ≤0.001). Compared with the control group, radiology-performed US occurred 92 min sooner (p ≤0.001) and US interpretation by a radiologist occurred 94 min sooner (p ≤0.001) for individuals receiving furosemide. Furosemide administration leads to a statistically and clinically significant difference in the time to fill the bladder of pediatric females awaiting pelvic US and leads to more rapid ultrasonography and interpretation by a radiologist in our setting. •Bladder filling is time consuming for pediatric females awaiting pelvic ultrasound.•Evaluation of furosemide versus intravenous fluids for bladder filling.•Bladder shape, size, and volume evaluated with point-of-care ultrasound.•Furosemide lead to a 90 min faster bladder filling time.