Six studies explored the overlap between racial and gender stereotypes, and the consequences of this overlap for interracial dating, leadership selection, and athletic participation. Two initial ...studies captured the explicit and implicit gender content of racial stereotypes: Compared with the White stereotype, the Asian stereotype was more feminine, whereas the Black stereotype was more masculine. Study 3 found that heterosexual White men had a romantic preference for Asians over Blacks and that heterosexual White women had a romantic preference for Blacks over Asians; preferences for masculinity versus femininity mediated participants' attraction to Blacks relative to Asians. The pattern of romantic preferences observed in Study 3 was replicated in Study 4, an analysis of the data on interracial marriages from the 2000 U.S. Census. Study 5 showed that Blacks were more likely and Asians less likely than Whites to be selected for a masculine leadership position. In Study 6, an analysis of college athletics showed that Blacks were more heavily represented in more masculine sports, relative to Asians. These studies demonstrate that the gender content of racial stereotypes has important real-world consequences.
The American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) collects detailed clinical data from participating hospitals using standardized data definitions, analyzes ...these data, and provides participating hospitals with reports that permit risk-adjusted comparisons with a surgical quality standard. Since its inception, the ACS NSQIP has worked to refine surgical outcomes measurements and enhance statistical methods to improve the reliability and validity of this hospital profiling. From an original focus on controlling for between-hospital differences in patient risk factors with logistic regression, ACS NSQIP has added a variable to better adjust for the complexity and risk profile of surgical procedures (procedure mix adjustment) and stabilized estimates derived from small samples by using a hierarchical model with shrinkage adjustment. New models have been developed focusing on specific surgical procedures (eg, “Procedure Targeted” models), which provide opportunities to incorporate indication and other procedure-specific variables and outcomes to improve risk adjustment. In addition, comparative benchmark reports given to participating hospitals have been expanded considerably to allow more detailed evaluations of performance. Finally, procedures have been developed to estimate surgical risk for individual patients. This article describes the development of, and justification for, these new statistical methods and reporting strategies in ACS NSQIP.
Summary Background Long-term complications of critical illness include intensive care unit (ICU)-acquired weakness and neuropsychiatric disease. Immobilisation secondary to sedation might potentiate ...these problems. We assessed the efficacy of combining daily interruption of sedation with physical and occupational therapy on functional outcomes in patients receiving mechanical ventilation in intensive care. Methods Sedated adults (≥18 years of age) in the ICU who had been on mechanical ventilation for less than 72 h, were expected to continue for at least 24 h, and who met criteria for baseline functional independence were eligible for enrolment in this randomised controlled trial at two university hospitals. We randomly assigned 104 patients by computer-generated, permuted block randomisation to early exercise and mobilisation (physical and occupational therapy) during periods of daily interruption of sedation (intervention; n=49) or to daily interruption of sedation with therapy as ordered by the primary care team (control; n=55). The primary endpoint—the number of patients returning to independent functional status at hospital discharge—was defined as the ability to perform six activities of daily living and the ability to walk independently. Therapists who undertook patient assessments were blinded to treatment assignment. Secondary endpoints included duration of delirium and ventilator-free days during the first 28 days of hospital stay. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov , number NCT00322010. Findings All 104 patients were included in the analysis. Return to independent functional status at hospital discharge occurred in 29 (59%) patients in the intervention group compared with 19 (35%) patients in the control group (p=0·02; odds ratio 2·7 95% CI 1·2–6·1). Patients in the intervention group had shorter duration of delirium (median 2·0 days, IQR 0·0–6·0 vs 4·0 days, 2·0–8·0; p=0·02), and more ventilator-free days (23·5 days, 7·4–25·6 vs 21·1 days, 0·0–23·8; p=0·05) during the 28-day follow-up period than did controls. There was one serious adverse event in 498 therapy sessions (desaturation less than 80%). Discontinuation of therapy as a result of patient instability occurred in 19 (4%) of all sessions, most commonly for perceived patient-ventilator asynchrony. Interpretation A strategy for whole-body rehabilitation—consisting of interruption of sedation and physical and occupational therapy in the earliest days of critical illness—was safe and well tolerated, and resulted in better functional outcomes at hospital discharge, a shorter duration of delirium, and more ventilator-free days compared with standard care. Funding None.
Physical and occupational therapy are possible immediately after intubation in mechanically ventilated medical intensive care unit patients. The objective of this study was to describe a protocol of ...daily sedative interruption and early physical and occupational therapy and to specify details of intensive care unit-based therapy, including neurocognitive state, potential barriers, and adverse events related to this intervention.
Detailed descriptive study of the intervention arm of a trial of mechanically ventilated patients receiving early physical and occupational therapy.
Two tertiary care academic medical centers participating in a randomized controlled trial.
Patients underwent daily sedative interruption followed by physical and occupational therapy every hospital day until achieving independent functional status. Therapy began with active range of motion and progressed to activities of daily living, sitting, standing, and walking as tolerated.
Forty-nine mechanically ventilated patients received early physical and occupational therapy occurring a median of 1.5 days (range, 1.0-2.1 days) after intubation. Therapy was provided on 90% of MICU days during mechanical ventilation. While endotracheally intubated, subjects sat at the edge of the bed in 69% of all physical and occupational therapy sessions, transferred from bed to chair in 33%, stood in 33%, and ambulated during 15% (n = 26 of 168) of all physical and occupational therapy sessions (median distance of 15 feet; range, 15-20 feet). At least one potential barrier to mobilization during mechanical ventilation (acute lung injury, vasoactive medication administration, delirium, renal replacement therapy, or body mass index ≥ 30 kg/m) was present in 89% of patient encounters. Therapy was interrupted prematurely in 4% of all sessions, most commonly for patient-ventilator asynchrony and agitation.
Early physical and occupational therapy is feasible from the onset of mechanical ventilation despite high illness acuity and presence of life support devices. Adverse events are uncommon, even in this high-risk group.
Hosts are likely to respond to parasitic infections by a combination of resistance (expulsion of pathogens) and tolerance (active mitigation of pathology). Of these strategies, the basis of tolerance ...in animal hosts is relatively poorly understood, with especially little known about how tolerance is manifested in natural populations. We monitored a natural population of field voles using longitudinal and cross-sectional sampling modes and taking measurements on body condition, infection, immune gene expression, and survival. Using analyses stratified by life history stage, we demonstrate a pattern of tolerance to macroparasites in mature compared to immature males. In comparison to immature males, mature males resisted infection less and instead increased investment in body condition in response to accumulating burdens, but at the expense of reduced reproductive effort. We identified expression of the transcription factor Gata3 (a mediator of Th2 immunity) as an immunological biomarker of this tolerance response. Time series data for individual animals suggested that macroparasite infections gave rise to increased expression of Gata3, which gave rise to improved body condition and enhanced survival as hosts aged. These findings provide a clear and unexpected insight into tolerance responses (and their life history sequelae) in a natural vertebrate population. The demonstration that such responses (potentially promoting parasite transmission) can move from resistance to tolerance through the course of an individual's lifetime emphasises the need to incorporate them into our understanding of the dynamics and risk of infection in the natural environment. Moreover, the identification of Gata3 as a marker of tolerance to macroparasites raises important new questions regarding the role of Th2 immunity and the mechanistic nature of the tolerance response itself. A more manipulative, experimental approach is likely to be valuable in elaborating this further.
Context:
Insulin resistance can be compensated by increased functional pancreatic β-cell mass; otherwise, diabetes ensues. Such compensation depends not only on environmental and genetic factors but ...also on the baseline β-cell mass from which the expansion originates.
Objective:
Little is known about assembly of a baseline β-cell mass in humans. Here, we examined formation of β-cell populations relative to other pancreatic islet cell types and associated neurons throughout the normal human lifespan.
Design and Methods:
Human pancreatic sections derived from normal cadavers aged 24 wk premature to 72 yr were examined by immunofluorescence. Insulin, glucagon, and somatostatin were used as markers for β-, α-, and δ-cells, respectively. Cytokeratin-19 marked ductal cells, Ki67 cell proliferation, and Tuj1 (neuronal class III β-tubulin) marked neurons.
Results:
Most β-cell neogenesis was observed preterm with a burst of β-cell proliferation peaking within the first 2 yr of life. Thereafter, little indication of β-cell growth was observed. Postnatal proliferation of α- and δ-cells was rarely seen, but a wave of ductal cell proliferation was found mostly associated with exocrine cell expansion. The β-cell to α-cell ratio doubled neonatally, reflecting increased growth of β-cells, but during childhood, there was a 7-fold change in the β-cell to δ-cell ratio, reflecting an additional loss of δ-cells. A close association of neurons to pancreatic islets was noted developmentally and retained throughout adulthood. Negligible neuronal association to exocrine pancreas was observed.
Conclusion:
Human baseline β-cell population and appropriate association with other islet cell types is established before 5 yr of age.
More children are surviving critical illness but are at risk of residual or new health conditions. An evidence-informed and stakeholder-recommended core outcome set is lacking for pediatric critical ...care outcomes. Our objective was to create a multinational, multistakeholder-recommended pediatric critical care core outcome set for inclusion in clinical and research programs.
A two-round modified Delphi electronic survey was conducted with 333 invited research, clinical, and family/advocate stakeholders. Stakeholders completing the first round were invited to participate in the second. Outcomes scoring greater than 69% "critical" and less than 15% "not important" advanced to round 2 with write-in outcomes considered. The Steering Committee held a virtual consensus conference to determine the final components.
Multinational survey.
Stakeholder participants from six continents representing clinicians, researchers, and family/advocates.
Overall response rates were 75% and 82% for each round. Participants voted on seven Global Domains and 45 Specific Outcomes in round 1, and six Global Domains and 30 Specific Outcomes in round 2. Using overall (three stakeholder groups combined) results, consensus was defined as outcomes scoring greater than 90% "critical" and less than 15% "not important" and were included in the final PICU core outcome set: four Global Domains (Cognitive, Emotional, Physical, and Overall Health) and four Specific Outcomes (Child Health-Related Quality of Life, Pain, Survival, and Communication). Families (n = 21) suggested additional critically important outcomes that did not meet consensus, which were included in the PICU core outcome set-extended.
The PICU core outcome set and PICU core outcome set-extended are multistakeholder-recommended resources for clinical and research programs that seek to improve outcomes for children with critical illness and their families.
1. Rates of whole-system metabolism (production and respiration) are fundamental indicators of ecosystem structure and function. Although first-order, proximal controls are well understood, ...assessments of the interactions between proximal controls and distal controls, such as land use and geographic region, are lacking. Thus, the influence of land use on stream metabolism across geographic regions is unknown. Further, there is limited understanding of how land use may alter variability in ecosystem metabolism across regions. 2. Stream metabolism was measured in nine streams in each of eight regions (n = 72) across the United States and Puerto Rico. In each region, three streams were selected from a range of three land uses: agriculturally influenced, urban-influenced, and reference streams. Stream metabolism was estimated from diel changes in dissolved oxygen concentrations in each stream reach with correction for reaeration and groundwater input. 3. Gross primary production (GPP) was highest in regions with little riparian vegetation (sagebrush steppe in Wyoming, desert shrub in Arizona/New Mexico) and lowest in forested regions (North Carolina, Oregon). In contrast, ecosystem respiration (ER) varied both within and among regions. Reference streams had significantly lower rates of GPP than urban or agriculturally influenced streams. 4. GPP was positively correlated with photosynthetically active radiation and autotrophic biomass. Multiple regression models compared using Akaike's information criterion (AIC) indicated GPP increased with water column ammonium and the fraction of the catchment in urban and reference land-use categories. Multiple regression models also identified velocity, temperature, nitrate, ammonium, dissolved organic carbon, GPP, coarse benthic organic matter, fine benthic organic matter and the fraction of all land-use categories in the catchment as regulators of ER. 5. Structural equation modelling indicated significant distal as well as proximal control pathways including a direct effect of land-use on GPP as well as SRP, DIN, and PAR effects on GPP; GPP effects on autotrophic biomass, organic matter, and ER; and organic matter effects on ER. 6. Overall, consideration of the data separated by land-use categories showed reduced inter-regional variability in rates of metabolism, indicating that the influence of agricultural and urban land use can obscure regional differences in stream metabolism.
Ibrutinib represents a therapeutic advance in chronic lymphocytic leukemia (CLL) but as monotherapy produces few complete remissions in previously treated patients. Anti-CD20 antibodies have improved ...response and progression-free survival (PFS) when combined with chemotherapy. We evaluated the safety and activity of adding ofatumumab to ibrutinib in 3 different administration sequences. Patients with CLL/small lymphocytic lymphoma (SLL), prolymphocytic leukemia, or Richter's transformation who failed ≥2 prior therapies were enrolled. Patients received ibrutinib 420 mg daily and 12 doses of ofatumumab 300/2000 mg in 3 schedules: ibrutinib lead-in (group 1; n = 27), concurrent start (group 2; n = 20), or ofatumumab lead-in (group 3; n = 24). Seventy-one patients were treated; most had high-risk disease including del(17)(p13.1) (44%) or del(11)(q22.3) (31%). The most frequent adverse events (any grade) were diarrhea (70%), infusion-related reaction (45%), and peripheral sensory neuropathy (44%). Overall response rates in CLL/SLL patients (n = 66) were 100%, 79%, and 71% in groups 1, 2, and 3, respectively. Estimated 12-month PFSs for all patients were 89%, 85%, and 75%, respectively. Four patients in group 3 progressed prior to receiving ibrutinib. This study demonstrates the tolerability and clinical activity of this combination with quicker time to best response than single-agent ibrutinib and with durable responses. This trial was registered at www.clinicaltrials.gov as #NCT01217749.
•Ibrutinib combined with ofatumumab in relapsed CLL had had an ORR of 83% with median time to response of <3 months in all groups.•All 3 sequences of administration were acceptably tolerated and active; responses were durable, and median PFS was not yet reached.
Patients who have received mechanical ventilation can have prolonged cognitive impairment for which there is no known treatment. We aimed to establish whether early mobilisation could reduce the ...rates of cognitive impairment and other aspects of disability 1 year after critical illness.
In this single-centre, parallel, randomised controlled trial, patients admitted to the adult medical-surgical intensive-care unit (ICU), at the University of Chicago (IL, USA), were recruited. Inclusion criteria were adult patients (aged ≥18 years) who were functionally independent and mechanically ventilated at baseline and within the first 96 h of mechanical ventilation, and expected to continue for at least 24 h. Patients were randomly assigned (1:1) via computer-generated permuted balanced block randomisation to early physical and occupational therapy (early mobilisation) or usual care. An investigator designated each assignment in consecutively numbered, sealed, opaque envelopes; they had no further involvement in the trial. Only the assessors were masked to group assignment. The primary outcome was cognitive impairment 1 year after hospital discharge, measured with a Montreal Cognitive Assessment. Patients were assessed for cognitive impairment, neuromuscular weakness, institution-free days, functional independence, and quality of life at hospital discharge and 1 year. Analysis was by intention to treat. This trial was registered with ClinicalTrials.gov, number NCT01777035, and is now completed.
Between Aug 11, 2011, and Oct 24, 2019, 1222 patients were screened, 200 were enrolled (usual care n=100, intervention n=100), and one patient withdrew from the study in each group; thus 99 patients in each group were included in the intention-to-treat analysis (113 57% men and 85 43% women). 65 (88%) of 74 in the usual care group and 62 (89%) of 70 in the intervention group underwent testing for cognitive impairment at 1 year. The rate of cognitive impairment at 1 year with early mobilisation was 24% (24 of 99 patients) compared with 43% (43 of 99) with usual care (absolute difference -19·2%, 95% CI -32·1 to -6·3%; p=0·0043). Cognitive impairment was lower at hospital discharge in the intervention group (53 54% 99 patients vs 68 69% 99 patients; -15·2%, -28·6 to -1·7; p=0·029). At 1 year, the intervention group had fewer ICU-acquired weaknesses (none 0% of 99 patients vs 14 14% of 99 patients; -14·1%; -21·0 to -7·3; p=0·0001) and higher physical component scores on quality-of-life testing than did the usual care group (median 52·4 IQR 45·3-56·8 vs median 41·1 31·8-49·4; p<0·0001). There was no difference in the rates of functional independence (64 65% of 99 patients vs 61 62% of 99 patients; 3%, -10·4 to 16·5%; p=0·66) or mental component scores (median 55·9 50·2-58·9 vs median 55·2 49·5-59·7; p=0·98) between the intervention and usual care groups at 1 year. Seven adverse events (haemodynamic changes n=3, arterial catheter removal n=1, rectal tube dislodgement n=1, and respiratory distress n=2) were reported in six (6%) of 99 patients in the intervention group and in none of the patients in the usual care group (p=0·029).
Early mobilisation might be the first known intervention to improve long-term cognitive impairment in ICU survivors after mechanical ventilation. These findings clearly emphasise the importance of avoiding delays in initiating mobilisation. However, the increased adverse events in the intervention group warrants further investigation to replicate these findings.
None.
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