Erratum:The behavioral and psychological symptoms of dementia in down syndrome scale (BPSD-DS II): Optimization and further validation

BACKGROUND: People with Down syndrome (DS) are at high risk to develop Alzheimer's disease dementia (AD). Behavioral and psychological symptoms of dementia (BPSD) are common and may also serve as early signals for dementia. However, comprehensive evaluation scales for BPSD, adapted to DS, are lacking. Therefore, we previously developed the BPSD-DS scale to identify behavioral changes between the last six months and pre-existing life-long characteristic behavior. OBJECTIVE: To optimize and further study the scale (discriminative ability and reliability) in a large representative DS study population. METHODS: Optimization was based on item irrelevance and clinical experiences obtained in the initial study. Using the shortened and refined BPSD-DS II, informant interviews were conducted to evaluate 524 DS individuals, grouped according to dementia status: no dementia (DS, N = 292), questionable dementia (DS + Q, N = 119), and clinically diagnosed dementia (DS + AD, N = 113). RESULTS: Comparing item change scores between groups revealed prominent changes in frequency and severity for anxious, sleep-related, irritable, restless/stereotypic, apathetic, depressive, and eating/drinking behavior. For most items, the proportion of individuals displaying an increased frequency was highest in DS + AD, intermediate in DS + Q, and lowest in DS. For various items within sections about anxious, sleep-related, irritable, apathetic, and depressive behaviors, the proportion of individuals showing an increased frequency was already substantial in DS + Q, suggesting that these changes may serve as early signals of AD in DS. Reliability data were promising. CONCLUSION: The optimized scale yields largely similar results as obtained with the initial version. Systematically evaluating BPSD in DS may increase understanding of changes among caregivers and (timely) adaptation of care/treatment

Peri-operative red blood cell transfusion in neonates and infants: NEonate and Children audiT of Anaesthesia pRactice IN Europe: A prospective European multicentre observational study

BACKGROUND: Little is known about current clinical practice concerning peri-operative red blood cell transfusion in neonates and small infants. Guidelines suggest transfusions based on haemoglobin thresholds ranging from 8.5 to 12 g dl-1, distinguishing between children from birth to day 7 (week 1), from day 8 to day 14 (week 2) or from day 15 (≥week 3) onwards. OBJECTIVE: To observe peri-operative red blood cell transfusion practice according to guidelines in relation to patient outcome. DESIGN: A multicentre observational study. SETTING: The NEonate-Children sTudy of Anaesthesia pRactice IN Europe (NECTARINE) trial recruited patients up to 60 weeks' postmenstrual age undergoing anaesthesia for surgical or diagnostic procedures from 165 centres in 31 European countries between March 2016 and January 2017. PATIENTS: The data included 5609 patients undergoing 6542 procedures. Inclusion criteria was a peri-operative red blood cell transfusion. MAIN OUTCOME MEASURES: The primary endpoint was the haemoglobin level triggering a transfusion for neonates in week 1, week 2 and week 3. Secondary endpoints were transfusion volumes, 'delta haemoglobin' (preprocedure - transfusion-triggering) and 30-day and 90-day morbidity and mortality. RESULTS: Peri-operative red blood cell transfusions were recorded during 447 procedures (6.9%). The median haemoglobin levels triggering a transfusion were 9.6 [IQR 8.7 to 10.9] g dl-1 for neonates in week 1, 9.6 [7.7 to 10.4] g dl-1 in week 2 and 8.0 [7.3 to 9.0] g dl-1 in week 3. The median transfusion volume was 17.1 [11.1 to 26.4] ml kg-1 with a median delta haemoglobin of 1.8 [0.0 to 3.6] g dl-1. Thirty-day morbidity was 47.8% with an overall mortality of 11.3%. CONCLUSIONS: Results indicate lower transfusion-triggering haemoglobin thresholds in clinical practice than suggested by current guidelines. The high morbidity and mortality of this NECTARINE sub-cohort calls for investigative action and evidence-based guidelines addressing peri-operative red blood cell transfusions strategies. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02350348

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Sweat rate and sweat composition following active or passive heat re-acclimation: A pilot study

The purpose of this study was to investigate local sweat rate (LSR) and sweat composition before and after active or passive heat re-acclimation (HRA). Fifteen participants completed four standardized heat stress tests (HST): before and after ten days of controlled hyperthermia (CH) heat acclimation (HA), and before and after five days of HRA. Each HST consisted of 35 min of cycling at 1.5W·kg−1 body mass (33°C and 65% relative humidity), followed by a graded exercise test. For HRA, participants were re-exposed to either CH (CH-CH, n = 6), hot water immersion (water temperature ~40°C for 40 min; CH-HWI, n = 5) or control (CH-CON, n = 4). LSR, sweat sodium, chloride, lactate and potassium concentrations were determined on the arm and back. LSR increased following HA (arm +18%; back +41%, P ≤  0.03) and HRA (CH-CH: arm +31%; back +45%; CH-HWI: arm +65%; back +49%; CH-CON arm +11%; back +11%, P ≤ 0.021). Sweat sodium, chloride and lactate decreased following HA (arm 25–34; back 21–27%, P < 0.001) and HRA (CH-CH: arm 26–54%; back 20–43%; CH-HWI: arm 9–49%; back 13–29%; CH-CON: arm 1–3%, back 2–5%, P < 0.001). LSR increases on both skin sites were larger in CH-CH and CH-HWI than CH-CON (P ≤ 0.010), but CH-CH and CH-HWI were not different (P ≥ 0.148). Sweat sodium and chloride conservation was larger in CH-CH than CH-HWI and CH-CON on the arm and back, whilst CH-HWI and CH-CON were not different (P ≥ 0.265). These results suggest that active HRA leads to similar increases in LSR, but more conservation of sweat sodium and chloride than passive HRA. Abbreviations: ANOVA: Analysis of variance; ATP: Adenosine triphosphate; BSA (m2): Body surface area; CH: Controlled hyperthermia; CH-CH: Heat re-acclimation by controlled hyperthermia; CH-CON: Control group (no heat re-acclimation); CH-HWI: Heat re-acclimation by hot water immersion; CV (%): Coefficient of variation; dt (min): Duration of a stimulus; F: Female; GEE: Generalized estimating equations; HA: Heat acclimation; HRA : Heat re-acclimation; HST: Heat stress test; LSR (mg·cm−2·min−1) : Local sweat rate; LOD (mmol·L−1): Limit of detection; M: Male; (Formula presented.) (mg): Mass of x; RH (%): Relative humidity; RT: Recreationally trained; SA (cm2): Surface area; t (min): Time; T: Trained; Tsk (°C): Skin temperature; Tre (°C): Rectal temperature; USG : Urine specific gravity; VO2peak (mL·kg−1·min−1): Peak oxygen uptake; WBSL (L): Whole-body sweat loss; WBSR (L·h−1): Whole-body sweat rate

The (in)dependency of blood and sweat sodium, chloride, potassium, ammonia, lactate and glucose concentrations during submaximal exercise

Purpose To reduce the need for invasive and expensive measures of human biomarkers, sweat is becoming increasingly popular in use as an alternative to blood. Therefore, the (in)dependency of blood and sweat composition has to be explored. Methods In an environmental chamber (33 °C, 65% relative humidity; RH), 12 participants completed three subsequent 20-min cycling stages to elicit three different local sweat rates (LSR) while aiming to limit changes in blood composition: at 60% of their maximum heart rate (HRmax), 70% HRmax and 80% HRmax, with 5 min of seated-rest in between. Sweat was collected from the arm and back during each stage and post-exercise. Blood was drawn from a superficial antecubital vein in the middle of each stage. Concentrations of sodium, chloride, potassium, ammonia, lactate and glucose were determined in blood plasma and sweat. Results With increasing exercise intensity, LSR, sweat sodium, chloride and glucose concentrations increased (P ≤ 0.026), while simultaneously limited changes in blood composition were elicited for these components (P ≥ 0.093). Sweat potassium, lactate and ammonia concentrations decreased (P ≤ 0.006), while blood potassium decreased (P = 0.003), and blood ammonia and lactate concentrations increased with higher exercise intensities (P = 0.005; P = 0.007, respectively). The vast majority of correlations between blood and sweat parameters were non-significant (P > 0.05), with few exceptions. Conclusion The data suggest that sweat composition is at least partly independent of blood composition. This has important consequences when targeting sweat as non-invasive alternative for blood measurements.ISSN:1439-6319ISSN:0301-5548ISSN:1439-632