The effect of walnut intake on factors related to prostate and vascular health in older men

<p>Abstract</p> <p>Background</p> <p>Tocopherols may protect against prostate cancer and cardiovascular disease (CVD).</p> <p>Methods</p> <p>We assessed the effect of walnuts, which are rich in tocopherols, on markers of prostate and vascular health in men at risk for prostate cancer. We conducted an 8-week walnut supplement study to examine effects of walnuts on serum tocopherols and prostate specific antigen (PSA). Subjects (<it>n </it>= 21) consumed (in random order) their usual diet +/- a walnut supplement (75 g/d) that was isocalorically incorporated in their habitual diets. Prior to the supplement study, 5 fasted subjects participated in an acute timecourse experiment and had blood taken at baseline and 1, 2, 4, and 8 h after consuming walnuts (75 g).</p> <p>Results</p> <p>During the timecourse experiment, triglycerides peaked at 4 h, and gamma-tocopherol (γ-T) increased from 4 to 8 h. Triglyceride – normalized γ-T was two-fold higher (<it>P </it>= 0.01) after 8 versus 4 h. In the supplement study, change from baseline was +0.83 ± 0.52 μmol/L for γ-T, -2.65 ± 1.30 μmol/L for alpha-tocopherol (α-T) and -3.49 ± 1.99 for the tocopherol ratio (α-T: γ-T). A linear mixed model showed that, although PSA did not change, the ratio of free PSA:total PSA increased and approached significance (P = 0.07). The α-T: γ-T ratio decreased significantly (<it>P </it>= 0.01), partly reflecting an increase in serum γ-T, which approached significance (<it>P </it>= 0.08).</p> <p>Conclusion</p> <p>The significant decrease in the α-T: γ-T ratio with an increase in serum γ-T and a trend towards an increase in the ratio of free PSA:total PSA following the 8-week supplement study suggest that walnuts may improve biomarkers of prostate and vascular status.</p

Multicountry survey of emergency and critical care medicine physicians' fluid resuscitation practices for adult patients with early septic shock

Evidence to guide fluid resuscitation evidence in sepsis continues to evolve. We conducted a multicountry survey of emergency and critical care physicians to describe current stated practice and practice variation related to the quantity, rapidity and type of resuscitation fluid administered in early septic shock to inform the design of future septic shock fluid resuscitation trials.Using a web-based survey tool, we invited critical care and emergency physicians in Canada, the UK, Scandinavia and Saudi Arabia to complete a self-administered electronic survey.A total of 1097 physicians responses were included. 1 L was the most frequent quantity of resuscitation fluid physicians indicated they would administer at a time (46.9%, n=499). Most (63.0%, n=671) stated that they would administer the fluid challenges as quickly as possible. Overall, normal saline and Ringers solutions were the preferred crystalloid fluids used often or always in 53.1% (n=556) and 60.5% (n=632) of instances, respectively. However, emergency physicians indicated that they would use normal saline often or always in 83.9% (n=376) of instances, while critical care physicians said that they would use saline often or always in 27.9% (n=150) of instances. Only 1.0% (n=10) of respondents indicated that they would use hydroxyethyl starch often or always; use of 5% (5.6% (n=59)) or 20-25% albumin (1.3% (n=14)) was also infrequent. The majority (88.4%, n=896) of respondents indicated that a large randomised controlled trial comparing 5% albumin to a crystalloid fluid in early septic shock was important to conduct.Critical care and emergency physicians stated that they rapidly infuse volumes of 500-1000 mL of resuscitation fluid in early septic shock. Colloid use, specifically the use of albumin, was infrequently reported. Our survey identifies the need to conduct a trial on the efficacy of albumin and crystalloids on 90-day mortality in patients with early septic shock

Overnight staffing in Canadian neonatal and pediatric intensive care units

AimInfants and children who require specialized medical attention are admitted to neonatal and pediatric intensive care units (ICUs) for continuous and closely supervised care. Overnight in-house physician coverage is frequently considered the ideal staffing model. It remains unclear how often this is achieved in both pediatric and neonatal ICUs in Canada. The aim of this study is to describe overnight in-house physician staffing in Canadian pediatric and level-3 neonatal ICUs (NICUs) in the pre-COVID-19 era.MethodsA national cross-sectional survey was conducted in 34 NICUs and 19 pediatric ICUs (PICUs). ICU directors or their delegates completed a 29-question survey describing overnight staffing by resident physicians, fellow physicians, nurse practitioners, and attending physicians. A comparative analysis was conducted between ICUs with and without in-house physicians.ResultsWe obtained responses from all 34 NICUs and 19 PICUs included in this study. A total of 44 ICUs (83%) with in-house overnight physician coverage provided advanced technologies, such as extracorporeal life support, and included all ICUs that catered to patients with cardiac, transplant, or trauma conditions. Residents provided the majority of overnight coverage, followed by the Critical Care Medicine fellows. An attending physician was in-house overnight in eight (15%) out of the 53 ICUs, seven of which were NICUs. Residents participating in rotations in the ICU would often have rotation durations of less than 6 weeks and were often responsible for providing care during shifts lasting 20–24 h.ConclusionMost PICUs and level-3 NICUs in Canada have a dedicated in-house physician overnight. These physicians are mainly residents or fellows, but a notable variation exists in this arrangement. The potential effects on patient outcomes, resident learning, and physician satisfaction remain unclear and warrant further investigation

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

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