Circulating adrenomedullin estimates survival and reversibility of organ failure in sepsis: the prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock-1 (AdrenOSS-1) study

Background: Adrenomedullin (ADM) regulates vascular tone and endothelial permeability during sepsis. Levels of circulating biologically active ADM (bio-ADM) show an inverse relationship with blood pressure and a direct relationship with vasopressor requirement. In the present prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock 1 (, AdrenOSS-1) study, we assessed relationships between circulating bio-ADM during the initial intensive care unit (ICU) stay and short-term outcome in order to eventually design a biomarker-guided randomized controlled trial. Methods: AdrenOSS-1 was a prospective observational multinational study. The primary outcome was 28-day mortality. Secondary outcomes included organ failure as defined by Sequential Organ Failure Assessment (SOFA) score, organ support with focus on vasopressor/inotropic use, and need for renal replacement therapy. AdrenOSS-1 included 583 patients admitted to the ICU with sepsis or septic shock. Results: Circulating bio-ADM levels were measured upon admission and at day 2. Median bio-ADM concentration upon admission was 80.5 pg/ml [IQR 41.5-148.1 pg/ml]. Initial SOFA score was 7 [IQR 5-10], and 28-day mortality was 22%. We found marked associations between bio-ADM upon admission and 28-day mortality (unadjusted standardized HR 2.3 [CI 1.9-2.9]; adjusted HR 1.6 [CI 1.1-2.5]) and between bio-ADM levels and SOFA score (p < 0.0001). Need of vasopressor/inotrope, renal replacement therapy, and positive fluid balance were more prevalent in patients with a bio-ADM > 70 pg/ml upon admission than in those with bio-ADM ≤ 70 pg/ml. In patients with bio-ADM > 70 pg/ml upon admission, decrease in bio-ADM below 70 pg/ml at day 2 was associated with recovery of organ function at day 7 and better 28-day outcome (9.5% mortality). By contrast, persistently elevated bio-ADM at day 2 was associated with prolonged organ dysfunction and high 28-day mortality (38.1% mortality, HR 4.9, 95% CI 2.5-9.8). Conclusions: AdrenOSS-1 shows that early levels and rapid changes in bio-ADM estimate short-term outcome in sepsis and septic shock. These data are the backbone of the design of the biomarker-guided AdrenOSS-2 trial. Trial registration: ClinicalTrials.gov, NCT02393781. Registered on March 19, 2015

Parenting Culture(s): Ideal-Parent Beliefs Across 37 Countries

What is it to be “an ideal parent”? Does the answer differ across countries and social classes? To answer these questions in a way that minimizes bias and ethnocentrism, we used open-ended questions to explore ideal-parent beliefs among 8,357 mothers and 3,517 fathers from 37 countries. Leximancer Semantic Network Analysis was utilized to first determine parenting culture zones (i.e., countries with shared ideal-parent beliefs) and then extract the predominant themes and concepts in each culture zone. The results yielded specific types of ideal-parent beliefs in five parenting culture zones: being “responsible and children/family-focused” for Asian parents, being “responsible and proper demeanor-focused” for African parents, and being “loving and responsible” for Hispanic-Italian parents. Although the most important themes and concepts were the same in the final two zones—being “loving and patient,” there were subtle differences: English-speaking, European Union, and Russian parents emphasized “being caring,” while French-speaking parents valued “listening” or being “present.” Ideal-parent beliefs also differed by education levels within culture zones, but no general pattern was discerned across culture zones. These findings suggest that the country in which parents were born cannot fully explain their differences in ideal-parent beliefs and that differences arising from social class or education level cannot be dismissed. Future research should consider how these differences affect the validity of the measurements in question and how they can be incorporated into parenting intervention research within and across cultures

Parenting Culture(s): Ideal-Parent Beliefs Across 37 Countries

What is it to be “an ideal parent”? Does the answer differ across countries and social classes? To answer these questions in a way that minimizes bias and ethnocentrism, we used open-ended questions to explore ideal-parent beliefs among 8,357 mothers and 3,517 fathers from 37 countries. Leximancer Semantic Network Analysis was utilized to first determine parenting culture zones (i.e., countries with shared ideal-parent beliefs) and then extract the predominant themes and concepts in each culture zone. The results yielded specific types of ideal-parent beliefs in five parenting culture zones: being “responsible and children/family-focused” for Asian parents, being “responsible and proper demeanor-focused” for African parents, and being “loving and responsible” for Hispanic-Italian parents. Although the most important themes and concepts were the same in the final two zones—being “loving and patient,” there were subtle differences: English-speaking, European Union, and Russian parents emphasized “being caring,” while French-speaking parents valued “listening” or being “present.” Ideal-parent beliefs also differed by education levels within culture zones, but no general pattern was discerned across culture zones. These findings suggest that the country in which parents were born cannot fully explain their differences in ideal-parent beliefs and that differences arising from social class or education level cannot be dismissed. Future research should consider how these differences affect the validity of the measurements in question and how they can be incorporated into parenting intervention research within and across cultures

Parental Burnout Around the Globe: a 42-Country Study

High levels of stress in the parenting domain can lead to parental burnout, a condition that has severe consequences for both parents and children. It is not yet clear, however, whether parental burnout varies by culture, and if so, why it might do so. In this study, we examined the prevalence of parental burnout in 42 countries (17,409 parents; 71% mothers; M_{age} = 39.20) and showed that the prevalence of parental burnout varies dramatically across countries. Analyses of cultural values revealed that individualistic cultures, in particular, displayed a noticeably higher prevalence and mean level of parental burnout. Indeed, individualism plays a larger role in parental burnout than either economic inequalities across countries, or any other individual and family characteristic examined so far, including the number and age of children and the number of hours spent with them. These results suggest that cultural values in Western countries may put parents under heightened levels of stress

Regional Practice Variation and Outcomes in the Standard Versus Accelerated Initiation of Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) Trial: A Post Hoc Secondary Analysis

OBJECTIVES: Among patients with severe acute kidney injury (AKI) admitted to the ICU in high-income countries, regional practice variations for fluid balance (FB) management, timing, and choice of renal replacement therapy (RRT) modality may be significant. DESIGN: Secondary post hoc analysis of the STandard vs. Accelerated initiation of Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial (ClinicalTrials.gov number NCT02568722). SETTING: One hundred-fifty-three ICUs in 13 countries. PATIENTS: Altogether 2693 critically ill patients with AKI, of whom 994 were North American, 1143 European, and 556 from Australia and New Zealand (ANZ). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Total mean FB to a maximum of 14 days was +7199 mL in North America, +5641 mL in Europe, and +2211 mL in ANZ (p < 0.001). The median time to RRT initiation among patients allocated to the standard strategy was longest in Europe compared with North America and ANZ (p < 0.001; p < 0.001). Continuous RRT was the initial RRT modality in 60.8% of patients in North America and 56.8% of patients in Europe, compared with 96.4% of patients in ANZ (p < 0.001). After adjustment for predefined baseline characteristics, compared with North American and European patients, those in ANZ were more likely to survive to ICU (p < 0.001) and hospital discharge (p < 0.001) and to 90 days (for ANZ vs. Europe: risk difference [RD], -11.3%; 95% CI, -17.7% to -4.8%; p < 0.001 and for ANZ vs. North America: RD, -10.3%; 95% CI, -17.5% to -3.1%; p = 0.007). CONCLUSIONS: Among STARRT-AKI trial centers, significant regional practice variation exists regarding FB, timing of initiation of RRT, and initial use of continuous RRT. After adjustment, such practice variation was associated with lower ICU and hospital stay and 90-day mortality among ANZ patients compared with other regions