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To evaluate the effects of a low-sodium and high-potassium salt-substitute on lowering blood pressure (BP) among Tibetans living at high altitude (4300 meters). The study was a patient-blinded randomized controlled trial conducted between February and May 2009 in Dangxiong County, Tibetan Autonomous Region, China. A total of 282 Tibetans aged 40 or older with known hypertension (systolic BP≥140 mmHg) were recruited and randomized to intervention (salt-substitute, 65% sodium chloride, 25% potassium chloride and 10% magnesium sulfate) or control (100% sodium chloride) in a 1: 1 allocation ratio with three months' supply. Primary outcome was defined as the change in BP levels measured from baseline to followed-up with an automated sphygmomanometer. Per protocol (PP) and intention to treat (ITT) analyses were conducted. After the three months' intervention period, the net reduction in SBP/DBP in the intervention group in comparison to the control group was -8.2/-3.4 mmHg (all p<0.05) in PP analysis, after adjusting for baseline BP and other variables. ITT analysis showed the net reduction in SBP/DBP at -7.6/-3.5 mmHg with multiple imputations (all p<0.05). Furthermore, the whole distribution of blood pressure showed an overall decline in SBP/DBP and the proportion of patients with BP under control (SBP/DBP<140 mmHg) was significantly higher in salt-substitute group in comparison to the regular salt group (19.2% vs. 8.8%, p = 0.027). Low sodium high potassium salt-substitute is effective in lowering both systolic and diastolic blood pressure and offers a simple, low-cost approach for hypertension control among Tibetans in China. ClinicalTrials.gov NCT01429246.

Background Isotonic saline (IS) is widely used to secure perioperative cardiovascular stability. However, the high amount of chloride in IS can induce hyperchloremic acidosis. Therefore, IS is suspected to increase the risk of acute kidney injury (AKI). Biomarkers may have potential as indicators. Methods In a double-blinded, placebo-controlled study, 38 patients undergoing primary uncemented hip replacement were randomized to IS or PlasmaLyte (PL). Infusion was given during surgery as 15 ml/kg the first hour and 5 ml/kg the following two hours. Urinary samples were collected upon admission and the day after surgery. As surgery was initiated, urine was collected over the course of 4 h. Hereafter, another urine collection proceeded until the morning. Urine was analyzed for markers of AKI neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1). Arterious and venous blood samples for measurements of pH and plasma electrolytes including chloride (p-Cl) were collected as surgery was initiated, at the end of surgery and the following morning. Results IS induced an increase in p-Cl (111 ± 2 mmol/L after IS and 108 ± 3 after PL, p  = 0.004) and a decrease in pH (7.39 ± 0.02 after IS and 7.43 ± 0.03 after PL, p  = 0.001). Urinary NGAL excretion increased in both groups (ΔNGAL: 5.5 [4.1; 11.7] μg/mmol creatinine p  = 0.004 after IS vs. 5.5 [2.1;9.4] μg/mmol creatinine after PL, p  < 0.001). No difference was found between the groups ( p  = 0.839). Similarly, urinary KIM-1 excretion increased in both groups (ΔKIM-1: IS 115.8 [74.1; 156.2] ng/mmol creatinine, p  < 0.001 vs. PL 152.4 [120.1; 307.9] ng/mmol creatinine, p < 0.001). No difference between the groups ( p  = 0.064). FE Na increased (1.08 ± 0.52% after IS and 1.66 ± 1.15% after PL, p  = 0.032). ENaC excretion was different within groups ( p  = 0.019). Conclusion A significantly higher plasma chloride and a lower pH was present in the group receiving isotonic saline. However, u-NGAL and u-KIM-1 increased significantly in both groups after surgery despite absence of changes in creatinine. These results indicate that surgery induced subclinical kidney injury. Also, the IS group had a delayed sodium excretion as compared to the PL group which may indicate that IS affects renal sodium excretion differently from PL. Trial registration ClinicalTrials.gov Identifier:  NCT02528448 , 19/08/2015

Diabetic ketoacidosis in children may cause brain injury. In this randomized, controlled trial, neither the rate of administration nor the sodium chloride content of intravenous fluids significantly influenced neurologic outcomes in children with diabetic ketoacidosis.

•In TOPCAT-Americas, baseline loop diuretic and combined loop and thiazide diuretic therapy was associated with elevated crude risk of CV death and total HHFs compared to no diuretic use.•Higher baseline doses of loop diuretics were associated with higher risk of CV death and total HHFs.•Thiazide monotherapy was not associated with an increased risk of any CV or HF endpoints, but when thiazide was added to loop diuretic therapy, it further increased the risk of CV death. Trials in heart failure with preserved ejection fraction (HFpEF) frequently apply baseline diuretic use as enrichment criterion. However, the role of thiazides and loop diuretic dose for enrichment is unclear. We aimed to assess baseline loop and thiazide diuretic use, loop diuretic dose, and associations with cardiovascular (CV) outcomes in HFpEF. We performed a post-hoc analysis of TOPCAT-Americas. The primary outcome was CV death and total hospitalizations for heart failure (HHF). 1765 patients were followed for a median of 2.9 years. At baseline, loop diuretic monotherapy was used in 67%, thiazide monotherapy in 10% and the combination in 12%. Loop diuretic monotherapy and combined loop+thiazide diuretic treatment were associated with higher risk of the primary outcome (HR 1.59, 95% CI 1.23-2.07, P < .001; and HR 2.07, 95% CI 1.55-2.76, P < .001 respectively), as well as first HHF, total HHFs and the composite of first HHF or CV death. Only combined loop+thiazide diuretic therapy was associated with CV death alone (HR 1.85, 95% CI 1.13-3.04, P = .015). For all above endpoints, the combined diuretic therapy was associated with greater risk than loop diuretics alone. Thiazide monotherapy was not associated with any endpoints. Higher baseline loop diuretic doses were associated with higher risk of all outcomes. In HFpEF, baseline use and higher doses of loop diuretics were associated with higher risk of CV death and total HHFs. Thiazide alone was not associated with any endpoints, but when added to loop diuretics it was associated with additional risk for all outcomes.

Purpose The purpose of this study was to compare the incidence of hypotension during sedation in adults presenting for elective colonoscopy and randomized to intravenous Plasma-Lyte 148 ® at either 2 mL·kg −1 (low volume) or 20 mL·kg −1 (high volume). Methods Patients aged ≥ 18 yr presenting for elective colonoscopy, with or without gastroscopy, after oral bowel preparation were randomized to receive the intervention immediately before the start of the procedure. Hypotension was defined as a ≥ 25% decrease in systolic blood pressure (SBP) from baseline during the procedure. Secondary outcomes included SBP < 90 mmHg, lowest SBP during sedation, duration of hypotension, use of vasopressors, postoperative outcomes, and cost. Results Seventy-five patients were randomly allocated to either the low-volume or high-volume group, respectively (total n = 150). The incidence of hypotension was similar in the two groups (59% vs 56%, respectively; odds ratio, 0.90; 95% confidence interval, 0.47 to 1.71; P = 0.74). The incidence of SBP < 90 mmHg, the lowest SBP during sedation, the duration of hypotension, the use of vasopressors, and postoperative outcomes were also similar in the two groups. Conclusions This study does not support the routine use of 20 mL·kg −1 of intravenous Plasma-Lyte 148 to prevent hypotension and other complications during sedation for elective colonoscopy in adult patients. Clinical Trials Registry (ANZCTR 12615001288516).

In this study from sub-Saharan Africa, children with severe febrile illness and impaired perfusion were randomly assigned to fluid-bolus therapy or no bolus. Albumin or saline boluses significantly increased 48-hour mortality in critically ill children with impaired perfusion. Rapid, early fluid resuscitation in patients with shock, a therapy that is aimed at the correction of hemodynamic abnormalities, is one component of goal-driven emergency care guidelines. This approach is widely endorsed by pediatric life-support training programs, which recommend the administration of up to 60 ml of isotonic fluid per kilogram of body weight within 15 minutes after the diagnosis of shock. 1 Children who do not have an adequate response to fluid resuscitation require intensive care for inotropic and ventilatory support. 1 Substantial improvements in the outcomes of pediatric septic shock have been attributed to this approach. 2 , 3 Nevertheless, evidence regarding . . .

Saline and Plasma-Lyte have different physiochemical contents; consequently, they may differently affect patients' renal function. We compared the effects of fluid therapy with 0.9% saline and with Plasma-Lyte 148 on renal function as assessed by creatinine concentration among patients undergoing major surgery. We conducted a prospective, double-blinded cluster crossover trial comparing the effects of the two fluids on major surgery patients. The primary aim was to establish the pilot feasibility, safety and preliminary efficacy evidence base for a large interventional trial to establish whether saline or Plasma-Lyte is the preferred crystalloid fluid for managing major surgery patients. The primary efficacy outcome was the proportion of patients with changes in renal function as assessed by creatinine concentration during their index hospital admission. We used changes in creatinine to define acute kidney injury (AKI) according to the RIFLE criteria. The study was feasible with 100% patient and clinician acceptance. There were no deviations from the trial protocol. After screening, we allocated 602 patients to saline and 458 to Plasma-Lyte. The median (IQR) volume of intraoperative fluid received was 2000 mL (1000:2000) in both groups. Forty-nine saline patients (8.1%) and 49 Plasma-Lyte patients (10.7%) developed a postoperative AKI (adjusted incidence rate ratio [aIRR]: 1.34; 95% CI: 0.93-1.95; p = 0.120). No differences were observed in the development of postoperative complications (aIRR: 0.98; 95% CI: 0.89-1.08) or the severity of the worst complication (aIRR: 1.00; 95% CI: 0.78-1.30). The median (IQR) length of hospital stay was six days (3:11) for the saline group and five days (3:10) for the Plasma-Lyte group (aIRR: 0.85; 95% CI: 0.73-0.98). There were no serious adverse events relating to the trial fluids, nor were there fluid crossover or contamination events. The study design was feasible to support a future follow-up larger clinical trial. Patients treated with saline did not demonstrate an increased incidence of postoperative AKI (defined as changes in creatinine) compared to those treated with Plasma-Lyte. Our findings imply that clinicians can reasonably use either solution intraoperatively for adult patients undergoing major surgery. Registry: Australian New Zealand Clinical Trials Registry; ACTRN12613001042730; URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=364988.

Use of hypotonic intravenous fluid to maintain hydration in children in hospital has been associated with hyponatraemia, leading to neurological morbidity and mortality. We aimed to assess whether use of fluid solutions with a higher sodium concentration reduced the risk of hyponatraemia compared with use of hypotonic solutions. We did a randomised controlled double-blind trial of children admitted to The Royal Children's Hospital (Melbourne, VIC, Australia) who needed intravenous maintenance hydration for 6 h or longer. With an online randomisation system that used unequal block sizes, we randomly assigned patients (1:1) to receive either isotonic intravenous fluid containing 140 mmol/L of sodium (Na140) or hypotonic fluid containing 77 mmol/L of sodium (Na77) for 72 h or until their intravenous fluid rate decreased to lower than 50% of the standard maintenance rate. We stratified assignment by baseline sodium concentrations. Study investigators, treating clinicians, nurses, and patients were masked to treatment assignment. The primary outcome was occurrence of hyponatraemia (serum sodium concentration <135 mmol/L with a decrease of at least 3 mmol/L from baseline) during the treatment period, analysed by intention to treat. The trial was registered with the Australian New Zealand Clinical Trials Registry, number ACTRN1260900924257. Between Feb 2, 2010, and Jan 29, 2013, we randomly assigned 690 patients. Of these patients, primary outcome data were available for 319 who received Na140 and 322 who received Na77. Fewer patients given Na140 than those given Na77 developed hyponatraemia (12 patients [4%] vs 35 [11%]; odds ratio [OR] 0·31, 95% CI 0·16–0·61; p=0·001). No clinically apparent cerebral oedema occurred in either group. Eight patients in the Na140 group (two potentially related to intravenous fluid) and four in the Na77 group (none related to intravenous fluid) developed serious adverse events during the treatment period. One patient in the Na140 had seizures during the treatment period compared with seven who received Na77. Use of isotonic intravenous fluid with a sodium concentration of 140 mmol/L had a lower risk of hyponatraemia without an increase in adverse effects than did fluid containing 77 mmol/L of sodium. An isotonic fluid should be used as intravenous fluid for maintenance hydration in children. National Health and Medical Research Council, Murdoch Childrens Research Institute, The Royal Children's Hospital, and the Australian and New Zealand College of Anaesthetists.

We optically measured effects of orally available ivacaftor (Kalydeco®) on sweat rates of identified glands in 3 R117H subjects, each having a unique set of additional mutations, and compared them with 5 healthy control subjects tested contemporaneously. We injected β-adrenergic agonists intradermally to stimulate CFTR-dependent 'C-sweat' and methacholine to stimulate 'M-sweat', which persists in CF subjects. We focused on an R117H-7T/F508del subject who produced quantifiable C-sweat off ivacaftor and was available for 1 blinded, 3 off ivacaftor, and 3 on ivacaftor tests, allowing us to estimate in vivo fold-increase in sweat rates produced by ivacaftor's effect on the open probability (PO) of R117H-CFTR. Measured sweat rates must be corrected for sweat losses. With estimated sweat losses of 0.023 to 0.08 nl·gland-1·min-1, ivacaftor increased the average C-sweat rates 3-7 fold, and estimated function as % of WT were 4.1-12% off ivacaftor and 21.9-32% on ivacaftor (larger values reflect increased loss estimates). Based on single tests, an R117H-7T/ R117H-7T subject showed 6-9% WT function off ivacaftor and 28-43% on ivacaftor. Repeat testing of an R117H-5T/F508del subject detected only trace responding to ivacaftor. We conclude that in vivo, R117H PO is strongly increased by ivacaftor, but channel number, mainly determined by variable deletion of exon 10, has a marked influence on outcomes.

This study evaluated the efficacy of intravenous (IV) calcium pretreatment for preventing diltiazem-induced hypotension and assessed its safety in adult patients with atrial fibrillation (AF)/atrial flutter (AFL) with rapid ventricular response (RVR). This randomized, double-blind, placebo-controlled trial included 217 adults with AF/AFL and a ventricular rate > 120 beats per minute, who were randomized into three groups: those who received an IV NaCl 0.9 % placebo pretreatment prior to IV diltiazem (PD; 73 patients) and those who received 90 mg (C90D; 71 patients) and 180 mg (C180D; 73 patients) IV calcium chloride pretreatment before IV diltiazem. We compared participants' systolic blood pressure (SBP) and heart rate (HR) at baseline and at 5, 10, and 15 min post-treatment, as well as the incidence of adverse events (e.g., hypotension, urticaria, nausea) among the groups. The PD and C90D pretreatment groups had significantly lower HR measurements at 10 and 15 min compared to the C180D group. In addition, at 5 min, the mean SBP in the PD group was significantly lower compared to the C90D and C180D groups. At 10 min, the mean SBP was significantly higher in the C180D group than in the other groups. Furthermore, at 15 min, the mean SBP was significantly higher in both the C90D and C180D groups than in the PD group. There were no significant differences between the calcium pretreatment and placebo groups in terms of the need for additional diltiazem doses or the incidence of adverse events. IV calcium pretreatment effectively prevents diltiazem-induced hypotension in patients with AF/AFL with RVR without compromising the efficacy of diltiazem in achieving and maintaining ventricular rate control. Trial registry: National Library of Medicine Clinical Trial Registry; No.: NCT06494007; URL: https://clinicaltrials.gov/study/NCT06494007