Efficacy and safety of a four-drug, quarter-dose treatment for hypertension: the QUARTET USA randomized trial.

New approaches are needed to lower blood pressure (BP) given persistently low control rates. QUARTET USA sought to evaluate the effect of four-drug, quarter-dose BP lowering combination in patients with hypertension. QUARTET USA was a randomized (1:1), double-blinded trial conducted in federally qualified health centers among adults with hypertension. Participants received either a quadpill of candesartan 2 mg, amlodipine 1.25 mg, indapamide 0.625 mg, and bisoprolol 2.5 mg or candesartan 8 mg for 12 weeks. If BP was >130/>80 mm Hg at 6 weeks in either arm, then participants received open label add-on amlodipine 5 mg. The primary outcome was mean change in systolic blood pressure (SBP) at 12 weeks, controlling for baseline BP. Secondary outcomes included mean change in diastolic blood pressure (DBP), and safety included serious adverse events, relevant adverse drug effects, and electrolyte abnormalities. Among 62 participants randomized between August 2019-May 2022 (n = 32 intervention, n = 30 control), mean (SD) age was 52 (11.5) years, 45% were female, 73% identified as Hispanic, and 18% identified as Black. Baseline mean (SD) SBP was 138.1 (11.2) mmHg, and baseline mean (SD) DBP was 84.3 (10.5) mmHg. In a modified intention-to-treat analysis, there was no significant difference in SBP (-4.8 mm Hg [95% CI: -10.8, 1.3, p = 0.123] and a -4.9 mmHg (95% CI: -8.6, -1.3, p = 0.009) greater mean DBP change in the intervention arm compared with the control arm at 12 weeks. Adverse events did not differ significantly between arms. The quadpill had a similar SBP and greater DBP lowering effect compared with candesartan 8 mg. Trial registration number: NCT03640312.

Efficacy and safety of a quadruple ultra-low-dose treatment for hypertension (QUARTET USA): Rationale and design for a randomized controlled trial.

BACKGROUND: Over half of patients with elevated blood pressure require multi-drug treatment to achieve blood pressure control. However, multi-drug treatment may lead to lower adherence and more adverse drug effects compared with monotherapy. OBJECTIVE: The Quadruple Ultra-low-dose Treatment for Hypertension (QUARTET) USA trial was designed to evaluate whether initiating treatment with ultra-low-dose quadruple-combination therapy will lower office blood pressure more effectively, and with fewer side effects, compared with initiating standard dose monotherapy in treatment naive patients with SBP < 180 and DBP < 110 mm Hg and patients on monotherapy with SBP < 160 and DBP < 100 mm Hg. METHODS/DESIGN: QUARTET USA was a prospective, randomized, double-blind trial (ClinicalTrials.gov NCT03640312) conducted in federally qualified health centers in a large city in the US. Patients were randomly assigned (1:1) to either ultra-low-dose quadruple combination therapy or standard dose monotherapy. The primary outcome was mean change from baseline in office systolic blood pressure at 12-weeks, adjusted for baseline values. Secondary outcomes included measures of blood pressure change and variability, medication adherence, and health related quality of life. Safety outcomes included occurrence of serious adverse events, relevant adverse drug effects, and electrolyte abnormalities. A process evaluation aimed to understand provider experiences of implementation and participant experiences around side effects, adherence, and trust with clinical care. DISCUSSION: QUARTET USA was designed to evaluate whether a novel approach to blood pressure control would lower office blood pressure more effectively, and with fewer side effects, compared with standard dose monotherapy. QUARTET USA was conducted within a network of federally qualified healthcare centers with the aim of generating information on the safety and efficacy of ultra-low-dose quadruple-combination therapy in diverse groups that experience a high burden of hypertension.

Osmotic Shifts, Cerebral Edema, and Neurologic Deterioration in Severe Hepatic Encephalopathy.

OBJECTIVES: We sought to determine the effect of acute electrolyte and osmolar shifts on brain volume and neurologic function in patients with liver failure and severe hepatic encephalopathy. DESIGN: Retrospective analysis of brain CT scans and clinical data. SETTING: Tertiary care hospital ICUs. PATIENTS: Patients with acute or acute-on-chronic liver failure and severe hepatic encephalopathy. INTERVENTIONS: Clinically indicated CT scans and serum laboratory studies. MEASUREMENTS AND MAIN RESULTS: Change in intracranial cerebrospinal fluid volume between sequential CT scans was measured as a biomarker of acute brain volume change. Corresponding changes in serum osmolality, chemistry measurements, and Glasgow Coma Scale were determined. Associations with cerebrospinal fluid volume change and Glasgow Coma Scale change for initial volume change assessments were identified by Spearman's correlations (rs) and regression models. Consistency of associations with repeated assessments was evaluated using generalized estimating equations. Forty patients were included. Median baseline osmolality was elevated (310 mOsm/Kg [296-321 mOsm/Kg]) whereas sodium was normal (137 mEq/L [134-142 mEq/L]). Median initial osmolality change was 9 mOsm/kg (5-17 mOsm/kg). Neuroimaging consistent with increased brain volume occurred in 27 initial assessments (68%). Cerebrospinal fluid volume change was more strongly correlated with osmolality (r = 0.70; p = 4 × 10) than sodium (r = 0.28; p = 0.08) change. Osmolality change was independently associated with Glasgow Coma Scale change (p = 1 × 10) and cerebrospinal fluid volume change (p = 2.7 × 10) in initial assessments and in generalized estimating equations using all 103 available assessments. CONCLUSIONS: Acute decline in osmolality was associated with brain swelling and neurologic deterioration in severe hepatic encephalopathy. Minimizing osmolality decline may avoid neurologic deterioration.

Performance of Temporary Hemodialysis Catheter Insertion by Nephrology Fellows and Attending Nephrologists.

BACKGROUND AND OBJECTIVES: Concerns have been raised about nephrology fellows' skills in inserting temporary hemodialysis catheters. Less is known about temporary hemodialysis catheter insertion skills of attending nephrologists supervising these procedures. The aim of this study was to compare baseline temporary hemodialysis catheter insertion skills of attending nephrologists with the skills of nephrology fellows before and after a simulation-based mastery learning (SBML) intervention. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This pre- post-intervention study with a pretest-only comparison group was conducted at the University of Toronto in September of 2014. Participants were nephrology fellows and attending nephrologists from three university-affiliated academic hospitals who underwent baseline assessment of internal jugular temporary hemodialysis catheter insertion skills using a central venous catheter simulator. Fellows subsequently completed an SBML intervention, including deliberate practice with the central venous catheter simulator. Fellows were expected to meet or exceed a minimum passing score at post-test. Fellows who did not meet the minimum passing score completed additional deliberate practice. Attending nephrologist and fellow baseline performance on the temporary hemodialysis catheter skills assessment was compared. Fellows' pre- and post-test temporary hemodialysis catheter insertion performance was compared to assess the effectiveness of SBML. The skills assessment was scored using a previously published 28-item checklist. The minimum passing score was set at 79% of checklist items correct. RESULTS: In total, 19 attending nephrologists and 20 nephrology fellows participated in the study. Mean attending nephrologist checklist scores (46.1%; SD=29.5%) were similar to baseline scores of fellows (41.1% items correct; SD=21.4%; P=0.55). Only two of 19 attending nephrologists (11%) met the minimum passing score at baseline. After SBML, fellows' mean post-test score improved to 91.3% (SD=6.9%; P<0.001). Median time between pre- and post-test was 24 hours. CONCLUSIONS: Attending nephrologists' baseline temporary hemodialysis catheter insertion skills were highly variable and similar to nephrology fellows' skills, with only a small minority able to competently insert a temporary hemodialysis catheter. SBML was extremely effective for training fellows and should be considered for attending nephrologists who supervise temporary hemodialysis catheter insertions.

Preoperative nuclear renal scan underestimates renal function after radical nephrectomy.

OBJECTIVE: To compare expected and actual renal function after nephrectomy. Nuclear renal scan estimates differential kidney function and is commonly used to calculate expected postoperative renal function after radical nephrectomy. However, the observed postoperative renal function is often different from the expected. METHODS: A retrospective review was performed on 136 patients who underwent radical nephrectomy or nephroureterectomy and had a preoperative renal scan with calculated differential function. RESULTS: Glomerular filtration rate (GFR) values, preoperative and postoperative, were calculated with the Modification of Diet in Renal Disease (MDRD) equation. The expected postoperative GFR based on renal scan was compared with the actual postoperative GFR. The average age of patients undergoing surgery was 58.6 years, and the indication for surgery was for benign causes in 59 (44%) patients and cancer in 76 (56%) patients. The average preoperative creatinine and estimated GFR were 1.0 mg/dL and 69.9 mL/min/1.73 m(2). At a median follow-up of 3.3 months, the actual postoperative GFR exceeded the expected GFR by an average of 12.1% (interquartile range, 2.6%-25.2%). When stratified by preoperative GFR >90, 60-90, and <60 mL/min/1.73 m(2), respectively, the observed GFR exceeded the expected GFR by 4.3%, 12.6%, and 14.9%, respectively (P = .16). This trend was maintained when GFR was plotted over time. CONCLUSION: After nephrectomy, the remaining kidney exceeded the expected postoperative GFR by 12% in this cohort of patients with preoperative renal scans. Patients with existing renal insufficiency had the greatest compensatory response, and this was durable over time.

Use of a national continuing medical education meeting to provide simulation-based training in temporary hemodialysis catheter insertion skills: a pre-test post-test study.

BACKGROUND: Simulation-based-mastery-learning (SBML) is an effective method to train nephrology fellows to competently insert temporary, non-tunneled hemodialysis catheters (NTHCs). Previous studies of SBML for NTHC-insertion have been conducted at a local level. OBJECTIVES: Determine if SBML for NTHC-insertion can be effective when provided at a national continuing medical education (CME) meeting. Describe the correlation of demographic factors, prior experience with NTHC-insertion and procedural self-confidence with simulated performance of the procedure. DESIGN: Pre-test - post-test study. SETTING: 2014 Canadian Society of Nephrology annual meeting. PARTICIPANTS: Nephrology fellows, internal medicine residents and medical students. MEASUREMENTS: Participants were surveyed regarding demographics, prior NTHC-insertion experience, procedural self-confidence and attitudes regarding the training they received. NTHC-insertion skills were assessed using a 28-item checklist. METHODS: Participants underwent a pre-test of their NTHC-insertion skills at the internal jugular site using a realistic patient simulator and ultrasound machine. Participants then had a training session that included a didactic presentation and 2 hours of deliberate practice using the simulator. On the following day, trainees completed a post-test of their NTHC-insertion skills. All participants were required to meet or exceed a minimum passing score (MPS) previously set at 79%. Trainees who did not reach the MPS were required to perform more deliberate practice until the MPS was achieved. RESULTS: Twenty-two individuals participated in SBML training. None met or exceeded the MPS at baseline with a median checklist score of 20 (IQR, 7.25 to 21). Seventeen of 22 participants (77%) completed post-testing and improved their scores to a median of 27 (IQR, 26 to 28; p < 0.001). All met or exceeded the MPS on their first attempt. There were no significant correlations between demographics, prior experience or procedural self-confidence with pre-test performance. LIMITATIONS: Small sample-size and self-selection of participants. Costs could limit the long-term feasibility of providing this type of training at a CME conference. CONCLUSIONS: Despite most participants reporting having previously inserted NTHCs in clinical practice, none met the MPS at baseline; this suggests their prior training may have been inadequate.

CONTEXTE: L'apprentissage assuré par la simulation est une méthode efficace pour former les résidents en néphrologie à insérer un cathéter d'hémodialyse non tunnellisé. Des études précédentes sur l'apprentissage assuré par la simulation pour l'insertion de cathéters non tunnellisés ont été effectuées à l'échelon local. OBJECTIFS: Déterminer si l'apprentissage assuré par la simulation pour l'insertion de cathéters non tunnellisés peut être efficace lorsque les possibilités sont offertes lors d'une conférence nationale de formation médicale continue (FMC). Décrire la corrélation entre les facteurs démographiques, les expériences antérieures d'insertion de cathéters non tunnellisés, de même que l'assurance personnelle en matière de simulation de la procédure. Évaluer la perception des apprenants face à l'apprentissage assuré par la simulation dans le cadre d'une conférence nationale de FMC. TYPE D'ÉTUDE: Prétest/post-test. CONTEXTE: Réunion annuelle 2014 de la Société canadienne de néphrologie. PARTICIPANTS: Les résidents en néphrologie et en médecine interne et les étudiants en médecine. MESURES: On a effectué un sondage auprès des participants au sujet des caractéristiques démographiques, de leurs expériences antérieures d'insertion de cathéters non tunnellisés, de leur assurance personnelle et leur attitude par rapport à la formation reçue. Les compétences en matière d'insertion de cathéters non tunnellisés ont été évaluées selon une liste de contrôle en 28 points. MÉTHODES: Les participants ont subi un prétest de leurs compétences en matière d'insertion de cathéters non tunnellisés dans la veine jugulaire interne, à l'aide d'un simulateur de patient et d'une machine à échographie. Les participants ont ensuite suivi une séance de formation qui comprenait une présentation didactique et deux heures d'exercices sur le simulateur. Le jour suivant, ils ont subi un post-test de leurs compétences. Tous les participants devaient atteindre ou dépasser la note minimale de passage précédemment fixée à 79%. Ceux qui n'ont pas atteint cette note ont dû effectuer des exercices supplémentaires jusqu'à l'atteindre. RÉSULTATS: Vingt-deux personnes ont participé à la formation sur l'insertion de cathéters d'hémodialyse non tunnellisés. Aucun d'entre eux n'a atteint ou dépassé la note minimale de passage en premier lieu, pour une médiane de 20 (ÉI = écart interquartile, entre 7,25 et 21). Dix-sept des 22 participants (77%) ont terminé le post-test en améliorant leur note, pour une médiane de 27 (ÉI, entre 26 et 28; p < 0,0001). Tous ont atteint ou excédé la note de passage lors de leur premier essai. Il n'existe aucune corrélation significative entre les facteurs démographiques, l'expérience antérieure et l'assurance personnelle, d'une part, et les résultats du prétest, d'autre part. Les participants ont confirmé l'apport de la formation, et qu'elle devrait être intégrée à la formation postdoctorale en néphrologie. LIMITES DE L'ÉTUDE: Échantillonnage restreint et autosélection des participants. Le rapport coût-efficacité n'a pas été évalué. Les coûts pourraient limiter la faisabilité à long terme de la prestation de ce type de formation au cours de conférences de FMC. CONCLUSIONS: Bien que plusieurs participants aient rapporté posséder de l'expérience antérieure dans l'insertion de cathéters non tunnellisés en pratique clinique, aucun d'entre eux n'a atteint la note minimale de passage en premier lieu; ceci suggère que leur formation antérieure ait été inadéquate. Il est possible d'offrir des possibilités d'apprentissage assuré par la simulation pour l'insertion de cathéters d'hémodialyse non tunnellisés qui soit efficace dans le contexte d'une conférence nationale de formation médicale continue.

Association of C-reactive protein and microalbuminuria (from the National Health and Nutrition Examination Surveys, 1999 to 2004).

Chronic kidney disease and cardiovascular disease share many risk factors. Injury to the vascular endothelium, measured by elevated levels of serum C-reactive protein (CRP), may play a role in kidney and cardiovascular disease. We therefore examined the association of CRP with microalbuminuria, a marker of early kidney injury. We conducted a cross-sectional analysis of a nationally representative, population-based survey. Weighted multiple logistic regression was used to study the association between CRP and microalbuminuria, adjusting for well-known risk factors. CRP was analyzed by a continuous variable and two categorized variables using quartiles and clinically recommended cutpoints. CRP concentration was positively associated with microalbuminuria. In the multivariate model, a one unit (in milligrams per liter) increase in CRP concentration was associated with a 2% increased odds of microalbuminuria (odds ratio 1.02, 95% confidence interval [CI] 1.01 to 1.02, p=0.0003). When CRP concentrations were stratified by clinically recommended cutpoints, compared with persons with CRP concentrations<1 mg/dl, persons with CRP concentrations between 1 and 3 mg/L and >3 mg/L were 1.15 times (95% CI 0.94 to 1.42) and 1.33 times (95% CI 1.08 to 1.65) more likely to have microalbuminuria, respectively. In subgroup analyses, the strength of association was comparable or stronger. In conclusion, elevated CRP levels were associated with microalbuminuria in a large, nationally representative data set. Vascular inflammation, as measured by CRP, may be a common contributor to early heart and kidney disease.