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Reductions in salt intake have the potential to markedly improve population health at low cost. Real life interventions that explore the feasibility and health effects of a gradual salt reduction lasting at least four weeks are required. The randomized controlled SalT Reduction InterVEntion (STRIVE) trial was developed to investigate the metabolic, behavioral and health effects of four months of consuming gradually salt reduced bread alone or in combination with dietary counselling. This paper describes the rationale and methods of STRIVE. Aiming at 120 healthy families, participants were recruited in February 2018 from the Danish Capital Region and randomly allocated into: (A) Salt reduced bread; (B) Salt reduced bread and dietary counseling; (C) Standard bread. Participants were examined before the intervention and at four months follow-up. Primary outcome is change in salt intake measured by 24 h urine. Secondary outcomes are change in urine measures of potassium and sodium/ potassium ratio, blood pressure, plasma lipids, the renin-angiotensin system, the sympathetic nervous response, dietary intake as well as salt taste sensitivity and preferences. The results will qualify mechanisms affected during a gradual reduction in salt intake in compliance with the current public health recommendations.

•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.

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.

The decisions made by food companies are a potent factor shaping the nutritional quality of the food supply. A number of non-governmental organizations (NGOs) advocate for corporate action to reduce salt levels in foods, but few data define the effectiveness of advocacy. This present report describes the process evaluation of an advocacy intervention delivered by one Australian NGO directly to food companies to reduce the salt content of processed foods. Food companies were randomly assigned to intervention (n = 22) or control (n = 23) groups. Intervention group companies were exposed to pre-planned and opportunistic communications, and control companies to background activities. Seven pre-defined interim outcome measures provided an indication of the effect of the intervention and were assessed using intention-to-treat analysis. These were supplemented by qualitative data from nine semi-structured interviews. The mean number of public communications supporting healthy food made by intervention companies was 1.5 versus 1.8 for control companies (p = 0.63). Other outcomes, including the mean number of news articles, comments and reports (1.2 vs. 1.4; p = 0.72), a published nutrition policy (23% vs. 44%; p = 0.21), public commitment to the Australian government’s Food and Health Dialogue (FHD) (41% vs. 61%; p = 0.24), evidence of a salt reduction plan (23% vs. 30%; p = 0.56), and mean number of communications with the NGO (15 vs. 11; p = 0.28) were also not significantly different. Qualitative data indicated the advocacy trial had little effect. The absence of detectable effects of the advocacy intervention on the interim markers indicates there may be no impact of the NGO advocacy trial on the primary outcome of salt reduction in processed foods.

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 . . .

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.

Abstract Rationale Bronchiectasis is a chronic debilitating disease with few evidence-based long-term treatments. Objectives A randomized controlled trial assessing the efficacy of nebulized gentamicin therapy over 1 year in patients with non–cystic fibrosis bronchiectasis. Methods Sixty-five patients were randomized to either twice-daily nebulized gentamicin, 80 mg, or nebulized 0.9% saline, for 12 months. All were reviewed at three-monthly intervals during treatment and at 3 months' follow-up. Measurements and Main Results At each review the following were assessed: quantitative and qualitative sputum bacteriology; sputum purulence and 24-hour volume; FEV1, FVC, and forced expiratory flow, midexpiratory phase; exercise capacity; Leicester Cough Questionnaire and St. George's Respiratory Questionnaire; and exacerbation frequency. Fifty-seven patients completed the study. At the end of 12 months' treatment, compared with the saline group, in the gentamicin group there was reduced sputum bacterial density with 30.8% eradication in those infected with Pseudomonas aeruginosa and 92.8% eradication in those infected with other pathogens; less sputum purulence (8.7% vs. 38.5%; P < 0.0001); greater exercise capacity (510 [350–690] m vs. 415 [267.5–530] m; P = 0.03); and fewer exacerbations (0 [0–1] vs. 1.5 [1–2]; P < 0.0001) with increased time to first exacerbation (120 [87–161.5] d vs. 61.5 [20.7–122.7] d; P = 0.02). The gentamicin group had greater improvements in Leicester Cough Questionnaire (81.4% vs. 20%; P < 0.01) and St. George's Respiratory Questionnaire (87.5% vs. 19.2%; P < 0.004) score. No differences were seen in 24-hour sputum volume, FEV1, FVC, or forced expiratory flow, midexpiratory phase. No P. aeruginosa isolates developed resistance to gentamicin. At follow-up, all outcome measures were similar to baseline. Conclusions Regular, long-term nebulized gentamicin is of significant benefit in non–cystic fibrosis bronchiectasis but treatment needs to be continuous for its ongoing efficacy. Clinical trial registered with www.clinicaltrials.gov (NCT00749866).

Background and aimsSensitive outcome measures to assess the efficacy of therapeutic interventions in patients with cystic fibrosis (CF) with mild lung disease are currently lacking. Our objective was to study the ability of the lung clearance index (LCI), a measure of ventilation inhomogeneity, to detect a treatment response to hypertonic saline inhalation in paediatric patients with CF with normal spirometry.MethodsIn a crossover trial, 20 patients with CF received 4 weeks of hypertonic saline (HS) and isotonic saline (IS) in a randomised sequence separated by a 4 week washout period. The primary end point was the change in the LCI due to HS versus IS.ResultsBaseline characteristics including the LCI were not significantly different between both study periods. Four weeks of twice-daily HS inhalation significantly improved the LCI compared with IS (1.16, 95% CI 0.26 to 2.05; p=0.016), whereas other outcome measures such as spirometry and quality of life failed to reach statistical significance. Randomisation order had no significant impact on the treatment effect.ConclusionsThe LCI, but not spirometry was able to detect a treatment effect from HS inhalation in patients with CF with mild disease and may be a suitable tool to assess early intervention strategies in this patient population.Clinical trial numberNCT00635141.

Purpose To evaluate the clinical effect of the warming step for subcutaneous (SC) injection on injection site pain (ISP). Methods A single center, randomized, partially blinded, crossover study in 44 healthy participants was conducted. Participants self-injected with autoinjectors (1 mL) with either high pain (citrate/sodium chloride (NaCl)) or low pain (mannitol) formulations at refrigerated temperature or warmed to room temperature (RT) according to the instructions for use (IFU). The ISP was recorded using visual analog scale (VAS) and injection site reactions (ISRs) were captured using severity scores. Results The average VAS scores were clinically different between high pain and low pain formulation but not affected by the warming step. While the average VAS was not affected by injectate temperature, some individual participants reported bidirectional VAS responses to injectate temperature. A post injection questionnaire showed that most participants were not bothered by the cold sensation of the injected solution. The clinical results are consistent with modeling that indicates rapid temperature equilibration of subcutaneously injected solutions. Conclusion Formulation composition was the dominating factor contributing to ISP as compared to solution temperature due to transient thermal equilibrium of the injected solution in SC tissue. While injection temperature may be a lever for improving the injection experience for some patients, the warming step is unlikely to reduce ISP for most patients. Although this study was conducted with 1 mL injection of two representative formulations, this finding of lack of correlation between ISP and solution temperature is likely extrapolatable to most small volume (e.g., ≤ 2 mL) injections of subcutaneous formulations.

In this study of infants with bronchiolitis, there was no difference in the length of hospital stay between those treated with inhaled adrenaline and those treated with inhaled saline. Infants treated on demand had a shorter length of stay than those treated on a fixed schedule. Acute bronchiolitis in infants, which frequently leads to hospitalization 1 , 2 and sometimes requires ventilatory support, is occasionally fatal 3 ; it is usually viral in origin, with respiratory syncytial virus 4 being the most common cause. The clinical disease is characterized by nasal flaring, tachypnea, dyspnea, chest retractions, crepitations, and wheezing. 5 Bronchodilators are not recommended 6 , 7 but are often used in the treatment of bronchiolitis, 8 – 10 as are saline inhalations. Adrenaline reduces mucosal swelling, 11 giving it an edge over the β 2 -adrenergic agonists, 12 and has led to the frequent use of inhaled adrenaline, 13 which has improved symptoms 12 , 14 – 20 and reduced . . .