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Writing Committee for the REMAP-CAP Investigators IMPORTANCE The evidence for benefit of convalescent plasma for critically ill patients with COVID-19 is inconclusive.OBJECTIVE To determine whether convalescent plasma would improve outcomes for critically ill adults with COVID-19. DESIGN, SETTING, AND PARTICIPANTSThe ongoing Randomized, Embedded, Multifactorial, Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP) enrolled and randomized 4763 adults with suspected or confirmed COVID-19 between March 9, 2020, and January 18, 2021, within at least 1 domain; 2011 critically ill adults were randomized to open-label interventions in the immunoglobulin domain at 129 sites in 4 countries. Follow-up ended on April 19, 2021. INTERVENTIONSThe immunoglobulin domain randomized participants to receive 2 units of high-titer, ABO-compatible convalescent plasma (total volume of 550 mL ± 150 mL) within 48 hours of randomization (n = 1084) or no convalescent plasma (n = 916). MAIN OUTCOMES AND MEASURESThe primary ordinal end point was organ support-free days (days alive and free of intensive care unit-based organ support) up to day 21 (range, −1 to 21 days; patients who died were assigned -1 day). The primary analysis was an adjusted bayesian cumulative logistic model. Superiority was defined as the posterior probability of an odds ratio (OR) greater than 1 (threshold for trial conclusion of superiority >99%). Futility was defined as the posterior probability of an OR less than 1.2 (threshold for trial conclusion of futility >95%). An OR greater than 1 represented improved survival, more organ support-free days, or both. The prespecified secondary outcomes included in-hospital survival; 28-day survival; 90-day survival; respiratory support-free days; cardiovascular support-free days; progression to invasive mechanical ventilation, extracorporeal mechanical oxygenation, or death; intensive care unit length of stay; hospital length of stay; World Health Organization ordinal scale score at day 14; venous thromboembolic events at 90 days; and serious adverse events. RESULTS Among the 2011 participants who were randomized (median age, 61 [IQR, 52 to 70] years and 645/1998 [32.3%] women), 1990 (99%) completed the trial. The convalescent plasma intervention was stopped after the prespecified criterion for futility was met. The median number of organ support-free days was 0 (IQR, -1 to 16) in the convalescent plasma group and 3 (IQR, -1 to 16) in the no convalescent plasma group. The in-hospital mortality rate was 37.3% (401/1075) for the convalescent plasma group and 38.4% (347/904) for the no convalescent plasma group and the median number of days alive and free of organ support was 14 (IQR, 3 to 18) and 14 (IQR, 7 to 18), respectively. The median-adjusted OR was 0.97 (95% credible interval, 0.83 to 1.15) and the posterior probability of futility (OR <1.2) was 99.4% for the convalescent plasma group compared with the no convalescent plasma group. The treatment effects were consistent across the primary outcome and the 11...

Adrenal crises are life-threatening complications of adrenal insufficiency. These events have an estimated incidence of between 5 and 10  adrenal crises/100 patient years and are responsible for some of the increased morbidity and excess mortality experienced by patients with adrenal insufficiency. Treatment involves urgent administration of IV/IM hydrocortisone and IV fluids. Patient education regarding preventive measures, such as increasing the dose of replacement therapy ("stress dosing") when sick, using parenteral hydrocortisone as necessary and accessing medical assistance promptly, is still considered the best approach to averting the onset of an adrenal crisis at times of physiological stress, most commonly an infection. However, recent evidence has demonstrated that patient education does not prevent many adrenal crisis events and the reasons for this are not fully understood. Furthermore, there is no widely accepted definition of an adrenal crisis. Without a validated adrenal crisis definition it is difficult to interpret variations in the incidence of adrenal crises and determine the effectiveness of preventive measures. This article aims to review the clinical aspects of adrenal crisis events, to explore the epidemiology, and to offer a definition of an adrenal crisis and to offer a perspective on future directions for research into adrenal crisis prevention.

Adrenal crises (AC) are life-threatening physiological disturbances that occur at a rate of 5–10/100 patient years in patients with adrenal insufficiency (AI). Despite their seriousness, there is a paucity of information on the epidemiology of AC events in the paediatric population specifically, as most investigations have focused on AI and ACs in adults. Improved surveillance of AC-related morbidity and mortality should improve the delineation of AC risk overall and among different subgroups of paediatric patients with AI. Valid incidence measures are essential for this purpose and also for the evaluation of interventions aimed at reducing adverse health outcomes from ACs. However, the absence of an agreed AC definition limits the potential benefit of research and surveillance in this area. While approaches to the treatment and prevention of ACs have much in common across the lifespan, there are important differences between children and adults with regards to the physiological, psychological, and social milieu in which these events occur. Education is considered to be an essential element of AC prevention but studies have shown that ACs occur even among well-educated patients, suggesting that new strategies may be needed. In this review, we examine the current knowledge regarding AC events in children with AI; assess the existing definitions of an AC and offer a new definition for use in research and the clinic; and suggest areas for further investigation that are aimed at reducing the incidence and health impact of ACs in the paediatric age group.

BackgroundAn adrenal crisis (AC) is a major cause of morbidity in hypoadrenal patients. However, there is little information available on the incidence and underlying causes of AC.MethodsThe aim of the present study was to describe the incidence of AC in New South Wales (NSW), Australia. Using a health department database, we selected de-identified data on all adults aged 20 years and over who were treated in any hospital in NSW between July1, 2000-June 30, 2011, with either a principal or secondary diagnosis of an AC. AC admission rates were calculated overall and within age categories. Frequencies of co-morbid diagnoses were analysed by age and sex groups. Poisson regression was used to assess the significance of the observed change in AC related admissions with age, while controlling for any secular trends by including year in the model. Chi sq tests were used to assess the differences in frequencies of categorical variables between groups.Results824 patients received treatment for an AC in hospital, corresponding to 74.9 admissions/year. The majority (62.5%) of the patients were women and 52.8% were aged 60 years and over. Admission rates were significantly associated with increasing age (p < 0.0001). Patients in the 60–69, 70–79 and 80+ age groups had the highest average admission rates (24.3, 35.2 and 45.8 per million/year). A principal or secondary diagnosis of an infection was reported in 317 (38.5%) patients and infection was significantly associated with age (p < 0.0001) with older patients having the highest proportion of cases. The most frequent infections were pneumonia/lower respiratory tract infection in 85 (10.3%) cases and urinary tract infection (UTI) in 82 (10.0%) patients. Women experienced 78.0% of the reported UTIs. There were 125 patients (15.2%) with an AC and a record of gastroenteritis. Twenty-six (3.2%) patients died in hospital but, of these, only 4 deaths (0.9%) were recorded among the 467 patients with a principal diagnosis of an AC.ConclusionsThe incidence of AC increases with age. Infections, especially bacterial infections, are associated with the incidence of ACs and this increases with age.

Context There are growing reports of dopamine agonist (DA)-induced impulse control disorders (ICDs) in hyperprolactinemic patients. However, the magnitude of this risk and predictive factors remain uncertain. Objective To determine ICD prevalence and risk factors in DA-treated hyperprolactinemic patients compared to community controls. Design, Setting and Participants Multicenter cross-sectional analysis of 113 patients and 99 healthy controls. Main Outcome Measures Participants completed a neuropsychological questionnaire consisting of the Depression Anxiety Stress Scale (DASS21), Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s Disease (QUIP-S), Hypersexual Behavior Inventory (HBI), Hypersexual Behavior Consequences Scale and Social Desirability Response Set Scale. Demographic and clinical data were collated to determine ICD risk factors. Patients testing positive for an ICD were offered a semistructured psychological interview. Results Patients were more likely than controls to test positive by QUIP-S for any ICD (61.1 vs 42.4%, P = .01), hypersexuality (22.1 vs 8.1%, P = .009), compulsive buying (15.9 vs 6.1%, P = .041) and punding (18.6 vs 6.1%, P = 0.012), and by HBI for hypersexuality (8.0 vs 0.0%, P = 0.004). Independent risk factors were male sex (odds ratio [OR] 13.85), eugonadism (OR 7.85), Hardy’s tumor score and psychiatric comorbidity (OR 6.86) for hypersexuality, and age (OR 0.95) for compulsive buying. DASS21 subset scores were higher in patients vs controls and in patients with vs without different ICDs. Only 19/51 (37.3%) interviewed patients were aware of the relationship between DAs and ICDs before the study. Conclusions DA therapy poses a high, previously underestimated risk of ICDs, especially in the form of hypersexuality in eugonadal men.

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Prehospital and in-hospital management of children with CAH can vary between health services. Children under 12 months have lower levels of stress dosing prior to hospital than other age groups. Experience with acute episodes improves self-management of CAH in the context of acute illness in educated patient populations.