Variation in Sedative and Analgesic Use During the COVID-19 Pandemic and Associated Outcomes.

BACKGROUND: Providing analgesia and sedation is an essential component of caring for many mechanically ventilated patients. The selection of analgesic and sedative medications during the COVID-19 pandemic, and the impact of these sedation practices on patient outcomes, remain incompletely characterized. RESEARCH QUESTION: What were the hospital patterns of analgesic and sedative use for patients with COVID-19 who received mechanical ventilation (MV), and what differences in clinical patient outcomes were observed across prevailing sedation practices? STUDY DESIGN AND METHODS: We conducted an observational cohort study of hospitalized adults who received MV for COVID-19 from February 2020 through April 2021 within the Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS) COVID-19 Registry. To describe common sedation practices, we used hierarchical clustering to group hospitals based on the percentage of patients who received various analgesic and sedative medications. We then used multivariable regression models to evaluate the association between hospital analgesia and sedation cluster and duration of MV (with a placement of death [POD] approach to account for competing risks). RESULTS: We identified 1,313 adults across 35 hospitals admitted with COVID-19 who received MV. Two clusters of analgesia and sedation practices were identified. Cluster 1 hospitals generally administered opioids and propofol with occasional use of additional sedatives (eg, benzodiazepines, alpha-agonists, and ketamine); cluster 2 hospitals predominantly used opioids and benzodiazepines without other sedatives. As compared with patients in cluster 2, patients admitted to cluster 1 hospitals underwent a shorter adjusted median duration of MV with POD (ß-estimate, -5.9; 95% CI, -11.2 to -0.6; P = .03). INTERPRETATION: Patients who received MV for COVID-19 in hospitals that prioritized opioids and propofol for analgesia and sedation experienced shorter adjusted median duration of MV with POD as compared with patients who received MV in hospitals that primarily used opioids and benzodiazepines.

The Association of Anticoagulation Intensity with Outcomes in Hospitalized COVID-19 Patients.

Venous thromboembolism (VTE) risk is increased in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A key question was whether increased intensity of anticoagulation would help prevent VTE and improve patient outcomes, including transfer to the intensive care unit (ICU) and mortality. At the start of the coronavirus disease-19 (COVID-19) pandemic, our institution, Boston Medical Center, instituted a VTE risk stratification protocol based on patients' initial D-dimer levels, medical history, and presence of thrombosis to determine whether they should receive standard-dose prophylaxis, high-dose prophylaxis, or therapeutic anticoagulation. We performed a retrospective observational cohort study examining the association of degree of anticoagulation with outcomes in 915 hospitalized COVID-19 patients hospitalized initially on the general inpatient wards between March 1,, 2020, and June 1, 2020. Patients directly hospitalized in the ICU were excluded. Most, 813 patients (89%), in our cohort were on standard-dose prophylaxis; 32 patients (3.5%) received high-dose prophylaxis; 70 patients (7.7%), were treated with therapeutic anticoagulation. VTE occurred in 45 patients (4.9%), and the overall in-hospital mortality rate was 5.4% (49 deaths). On multivariable analysis of clinical outcomes in relation to type of anticoagulation, in the high-dose prophylaxis group, there was a trend towards increased in-hospital mortality (odds ratio 2.4 (0.8-7.5, 95% CI)) and increased ICU transfer (odds ratio 2.2 (0.9-5.7, 95% CI)). Our results suggest that patients receiving high-dose prophylaxis had more severe disease that was not mitigated by intermediate-dose anticoagulation.

The role of GammaTile in the treatment of brain tumors: a technical and clinical overview.

Malignant and benign brain tumors with a propensity to recur continue to be a clinical challenge despite decades-long efforts to develop systemic and more advanced local therapies. GammaTile (GT Medical Technologies Inc., Tempe AZ) has emerged as a novel brain brachytherapy device placed during surgery, which starts adjuvant radiotherapy immediately after resection. GammaTile received FDA clearance in 2018 for any recurrent brain tumor and expanded clearance in 2020 to include upfront use in any malignant brain tumor. More than 1,000 patients have been treated with GammaTile to date, and several publications have described technical aspects of the device, workflow, and clinical outcome data. Herein, we review the technical aspects of this brachytherapy treatment, including practical physics principles, discuss the available literature with an emphasis on clinical outcome data in the setting of brain metastases, glioblastoma, and meningioma, and provide an overview of the open and pending clinical trials that are further defining the efficacy and safety of GammaTile.

Exposure to Family Member Deaths Across the Life Course for Hispanic Individuals.

The present study documents differences in exposure to family member deaths among foreign-born and U.S.-born Hispanic individuals compared with non-Hispanic Black and non-Hispanic White individuals. We use data from the Health and Retirement Study (HRS; 1992-2016, ages 51+; N = 23,228) and the National Longitudinal Study of Adolescent to Adult Health (Add Health; Waves I-V, ages 12-43; N = 11,088) to estimate the risk of exposure to the death of a mother, father, spouse, sibling, and child across the life course. HRS results show more inequities in exposure to family deaths compared with Add Health results, suggesting differences by age or birth cohort. Compared with non-Hispanic Whites, U.S.-born Hispanic individuals in the HRS have a higher risk of experiencing a child's death throughout adulthood and a sibling's death in later life; the latter is explained by larger sibship size, indicating a greater lifetime risk of bereavement experiences. The higher risk of parental death during childhood for U.S.-born and foreign-born Hispanic individuals is explained by covariates (e.g., lower levels of educational attainment). Hispanic individuals generally have a lower risk of family deaths than non-Hispanic Black individuals, but at times a higher risk of exposure relative to non-Hispanic White individuals.

Variation in Troponin I Measurement and the Cardiovascular Management Approach Following Elevated Troponin I Among Critically Ill Patients With Sepsis.

Troponin I is frequently elevated in sepsis, but optimal clinical approaches to diagnosis and management of troponin I during sepsis are unclear. OBJECTIVES: We aimed to describe the variation in troponin I measurement and the cardiovascular diagnostic and therapeutic approach to elevated troponin I among critically ill adults with sepsis. DESIGN SETTING AND PARTICIPANTS: Observational cohort study of the hospital-level variation in serial troponin I measurement, trending troponin I to peak, echocardiography, cardiac stress test, cardiac catheterization, antiplatelet agents, therapeutic anticoagulation, beta-blockers, and statins quantified using hospital median odds ratios-the median odds of receiving an intervention at randomly selected higher versus lower rate hospitals-derived from multivariable-adjusted random-effects logistic regression models with hospital site as the random effect. The Premier Healthcare Database was used. Patients were adults aged greater than 18 years admitted to the ICU with sepsis from 2016 to 2020. MAIN OUTCOMES AND MEASURES: The hospital-level median odds ratios of troponin I measurement as well as cardiovascular diagnostics and therapeutics. RESULTS: Among 85,830 adults with sepsis, 53,058 (61.8%) had a troponin I measured, with a median odds ratio of troponin measurement across hospitals of 5.30 (95% CI, 4.98-5.67). Among 27,665 adults (32.2%) with sepsis and an elevated troponin I level, 84.8% had serial troponin I measurements, 66.0% had troponin trended to peak level, 66.7% had an echocardiogram, 4.1% had a cardiac stress test, 6.6% underwent cardiac catheterization, 48.3% received antiplatelet agents, 8.3% received therapeutic anticoagulation, 50.5% received beta-blockers, and 38.1% received statins. The median odds ratios between hospitals for cardiovascular diagnostics and therapeutics ranged from 1.28 (95% CI, 1.24-1.32) for use of beta-blockers to 7.58 (95% CI, 6.43-8.77) for use of therapeutic anticoagulation. CONCLUSIONS AND RELEVANCE: Both troponin I measurement and the approach to an elevated troponin I among critically ill adults with sepsis varied widely across hospitals consistent with disparate practice and care efficiency. Prospective studies are needed to guide an informed approach to troponin I measurement and cardiovascular evaluation in sepsis.

Variation in Use of High-Flow Nasal Cannula and Noninvasive Ventilation Among Patients With COVID-19.

BACKGROUND: The use of high-flow nasal cannula (HFNC) and noninvasive ventilation (NIV) for hypoxemic respiratory failure secondary to COVID-19 are recommended by critical-care guidelines; however, apprehension about viral particle aerosolization and patient self-inflicted lung injury may have limited use. We aimed to describe hospital variation in the use and clinical outcomes of HFNC and NIV for the management of COVID-19. METHODS: This was a retrospective observational study of adults hospitalized with COVID-19 who received supplemental oxygen between February 15, 2020, and April 12, 2021, across 102 international and United States hospitals by using the COVID-19 Registry. Associations of HFNC and NIV use with clinical outcomes were evaluated by using multivariable adjusted hierarchical random-effects logistic regression models. Hospital variation was characterized by using intraclass correlation and the median odds ratio. RESULTS: Among 13,454 adults with COVID-19 who received supplemental oxygen, 8,143 (60%) received nasal cannula/face mask only, 2,859 (21%) received HFNC, 878 (7%) received NIV, 1,574 (12%) received both HFNC and NIV, with 3,640 subjects (27%) progressing to invasive ventilation. The hospital of admission contributed to 24% of the risk-adjusted variation in HFNC and 30% of the risk-adjusted variation in NIV. The median odds ratio for hospital variation of HFNC was 2.6 (95% CI 1.4-4.9) and of NIV was 3.1 (95% CI 1.2-8.1). Among 5,311 subjects who received HFNC and/or NIV, 2,772 (52%) did not receive invasive ventilation and survived to hospital discharge. Hospital-level use of HFNC or NIV were not associated with the rates of invasive ventilation or mortality. CONCLUSIONS: Hospital variation in the use of HFNC and NIV for acute respiratory failure secondary to COVID-19 was great but was not associated with intubation or mortality. The wide variation and relatively low use of HFNC/NIV observed within our study signaled that implementation of increased HFNC/NIV use in patients with COVID-19 will require changes to current care delivery practices. (ClinicalTrials.gov registration NCT04323787.).

Smartphone-Guided Self-prone Positioning vs Usual Care in Nonintubated Hospital Ward Patients With COVID-19: A Pragmatic Randomized Clinical Trial.

BACKGROUND: Safe, effective, and easily implementable treatments that reduce the progression of respiratory failure in COVID-19 are urgently needed. Despite the increased adoption of prone positioning during the pandemic, the effectiveness of this technique on progression of respiratory failure among nonintubated patients is unclear. RESEARCH QUESTION: What is the effectiveness of smartphone-guided self-prone positioning recommendations and instructions compared with usual care in reducing progression of respiratory failure among nonintubated patients with COVID-19? STUDY DESIGN AND METHODS: Awake Prone Position for Early Hypoxemia in COVID-19 (APPEX-19) is a multicenter randomized clinical trial that randomized nonintubated adults with COVID-19 on < 6 L/min of supplemental oxygen to receive a smartphone-guided self-prone positioning intervention or usual care. The primary outcome was the composite of respiratory deterioration (an increase in supplemental oxygen requirement) or ICU transfer. Using a Bayesian statistical approach, the posterior probability of superiority within each treatment arm (superiority threshold 95%) was calculated. RESULTS: The trial was stopped early for slow enrollment. A total of 293 participants were included in the modified intention-to-treat analysis (159 self-prone positioning intervention and 134 usual care). Among participants who self-reported body positioning (n = 139 [70 intervention, 69 usual care]), 71.4% in the intervention arm and 59.4% in the usual care arm attempted prone positioning. Thirty-one participants (posterior mean, 24.7%; 95% credible interval, 18.6-31.4) receiving usual care and 32 participants (posterior mean, 22.1%; 95% credible interval, 16.6-28.1) receiving the self-prone positioning intervention experienced the primary outcome; the posterior probability of superiority for the self-prone positioning intervention was 72.1%, less than the 95% threshold for superiority. Adverse events occurred in 26.9% of participants in the usual care arm and in 11.9% of participants in the intervention arm. INTERPRETATION: Among nonintubated patients with COVID-19, smartphone-guided self-prone positioning recommendations and instructions did not promote strong adherence to prone positioning. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT04344587; URL: www. CLINICALTRIALS: gov.

Hospital Variation in Management and Outcomes of Acute Respiratory Distress Syndrome Due to COVID-19.

OBJECTIVES: To describe hospital variation in use of "guideline-based care" for acute respiratory distress syndrome (ARDS) due to COVID-19. DESIGN: Retrospective, observational study. SETTING: The Society of Critical Care Medicine's Discovery Viral Infection and RESPIRATORY ILLNESS UNIVERSAL STUDY COVID-19 REGISTRY. PATIENTS: Adult patients with ARDS due to COVID-19 between February 15, 2020, and April 12, 2021. INTERVENTIONS: Hospital-level use of "guideline-based care" for ARDS including low-tidal-volume ventilation, plateau pressure less than 30 cm H2O, and prone ventilation for a Pao2/Fio2 ratio less than 100. MEASUREMENTS AND MAIN RESULTS: Among 1,495 adults with COVID-19 ARDS receiving care across 42 hospitals, 50.4% ever received care consistent with ARDS clinical practice guidelines. After adjusting for patient demographics and severity of illness, hospital characteristics, and pandemic timing, hospital of admission contributed to 14% of the risk-adjusted variation in "guideline-based care." A patient treated at a randomly selected hospital with higher use of guideline-based care had a median odds ratio of 2.0 (95% CI, 1.1-3.4) for receipt of "guideline-based care" compared with a patient receiving treatment at a randomly selected hospital with low use of recommended therapies. Median-adjusted inhospital mortality was 53% (interquartile range, 47-62%), with a nonsignificantly decreased risk of mortality for patients admitted to hospitals in the highest use "guideline-based care" quartile (49%) compared with the lowest use quartile (60%) (odds ratio, 0.7; 95% CI, 0.3-1.9; p = 0.49). CONCLUSIONS: During the first year of the COVID-19 pandemic, only half of patients received "guideline-based care" for ARDS management, with wide practice variation across hospitals. Strategies that improve adherence to recommended ARDS management strategies are needed.

Severe Acute Respiratory Syndrome Coronavirus 2 and Respiratory Virus Sentinel Surveillance, California, USA, May 10, 2020-June 12, 2021.

State and local health departments established the California Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and Respiratory Virus Sentinel Surveillance System to conduct enhanced surveillance for SARS-CoV-2 and other respiratory pathogens at sentinel outpatient testing sites in 10 counties throughout California, USA. We describe results obtained during May 10, 2020‒June 12, 2021, and compare persons with positive and negative SARS-CoV-2 PCR results by using Poisson regression. We detected SARS-CoV-2 in 1,696 (19.6%) of 8,662 specimens. Among 7,851 specimens tested by respiratory panel, rhinovirus/enterovirus was detected in 906 (11.5%) specimens and other respiratory pathogens in 136 (1.7%) specimens. We also detected 23 co-infections with SARS-CoV-2 and another pathogen. SARS-CoV-2 positivity was associated with male participants, an age of 35-49 years, Latino race/ethnicity, obesity, and work in transportation occupations. Sentinel surveillance can provide useful virologic and epidemiologic data to supplement other disease monitoring activities and might become increasingly useful as routine testing decreases.

Variation in Use of Repurposed Medications Among Patients With Coronavirus Disease 2019. From The Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study: Coronavirus Disease 2019 Registry Investigator Group.

IMPORTANCE: At the start of the coronavirus disease 2019 pandemic, medications repurposed for management of coronavirus disease 2019 were used in the absence of clinical trial evidence. OBJECTIVES: To describe the variation and evolution in use of repurposed medications for coronavirus disease 2019. DESIGN SETTING AND PARTICIPANTS: Observational cohort study of adults hospitalized with coronavirus disease 2019 between February 15, 2020, and April 12, 2021, across 76 United States and international hospitals within the Society of Critical Care Medicine's Discovery Viral Infection and Respiratory Illness Universal Study coronavirus disease 2019 registry. MAIN OUTCOMES AND MEASURES: Hospital variation was quantified using multivariable adjusted random effects logistic regression models and unsupervised clustering. Repurposed medications included antivirals, corticosteroids, hydroxychloroquine, immunomodulators, and therapeutic dose anticoagulants. RESULTS: Among 7,069 adults hospitalized with coronavirus disease 2019, 1,979 (28%) received antivirals, 2,876 (41%) received corticosteroids, 1,779 (25%) received hydroxychloroquine, 620 (9%) received immunomodulators, and 2,154 (31%) received therapeutic dose anticoagulants. Contribution of hospital site to risk-adjusted variation was 46% for antivirals, 30% for corticosteroids, 48% for hydroxychloroquine, 46% for immunomodulators, and 52% for therapeutic dose anticoagulants. Compared with the early pandemic, the later pandemic practice phenotypes converged with increased use of antivirals (odds ratio, 3.14; 95% CI, 2.40-4.10) and corticosteroids (odds ratio, 5.43; 95% CI, 4.23-6.97), with decreased use of hydroxychloroquine (odds ratio, 0.02; 95% CI, 0.01-0.04) and immunomodulators (odds ratio, 0.49; 95% CI, 0.34-0.70). There was no clinically significant change in the use of therapeutic dose anticoagulants (odds ratio, 1.01; 95% CI, 1.01-1.02). There were no differences in risk-adjusted mortality between hospitals with high rates of repurposed medication use compared with hospitals with low rates of use. CONCLUSIONS AND RELEVANCE: Hospital variation in the use of repurposed medications varied widely across hospitals early in the pandemic and later converged with the emergence of randomized clinical trials. Platforms developed for rapid activation and enrollment in clinical trials of repurposed medications are needed prior to the next pandemic to expedite effective, evidence-based practice.

Work-Family Reconciliation and Children's Well-Being Disparities across OECD Countries.

Socioeconomic inequalities in health and well-being are large, beginning early in childhood and accumulating over the life course, but they also vary widely across rich developed nations. Despite this well-known cross-national variation, research has yet to examine why children's health disparities might be larger or smaller based on national policy contexts and macroeconomic conditions. Parental health and well-being suffer under high work-family or economic strain, which may directly impact children's health inequalities by family social class. These childhood health disadvantages, if not substantially improved, compound to even larger adult inequalities. To examine the role of national work-family reconciliation in children's health, we merge country-level policy data with 2006 and 2010 World Health Organization child-level data on mental and physical well-being and family economic disadvantage. Based on adjusted estimates, we find greatly narrowed disparities in children's self-rated health as work flexibility and vacation-sick leave mandates become more generous. However, cash transfer policies including family benefits spending and childcare costs were not associated with the size of children's health disparities. Taken together, our results suggest the distinctive value of better work-family accommodations, rather than any generic cash allowances, for lessening family-based inequalities in children's health and human capital development.

Predictors to forgo resuscitative effort during Covid-19 critical illness at the height of the pandemic : A retrospective cohort study.

BACKGROUND: Early in the Covid-19 pandemic, there was uncertainty regarding critical illness prognosis and challenges to traditional face-to-face family meetings. Ethnic minority populations have suffered disproportionately worse outcomes during the pandemic, which may in part relate to differences in end-of-life decision-making. AIM: Characterize patterns of and factors associated with decisions to forgo resuscitative efforts, as measured by do-not-resuscitate orders, during critical illness with Covid-19. DESIGN: Retrospective cohort with medical record abstraction. SETTING/PARTICIPANTS: Adult patients diagnosed with SARS-Cov-2 virus via polymerase chain reaction and admitted to the intensive care unit at an academic hospital, which cares for the city's underserved communities, between March 1 and June 7, 2020 who underwent invasive mechanical ventilation for at least 48 hours. RESULTS: In this cohort (n = 155), 45% were black people, and 51% spoke English as their primary language. Median time to first goals-of-care conversation was 3.9 days (IQR 1.9-7.6) after intensive care unit admission. Overall 61/155 patients (39%) transitioned to do-not-resuscitate status, and 50/62 (82%) patients who died had do-not-resuscitate orders. Multivariate analysis shows age and palliative care involvement as the strongest predictors of decision to instate do-not-resuscitate order. There was no association between race, ethnicity, or language and decisions to forego resuscitation. CONCLUSIONS: During this time of crisis and uncertainty with limited resources and strained communication, time to first goals of care conversation was shorter than in pre-pandemic studies, but rates of foregoing resuscitation remained similar, with no differences observed by race, ethnicity, or language. This study suggests that early palliative care involvement and non-traditional communications, including videoconferencing, to facilitate goals of care conversations could have mitigated potential disparities in end-of-life decision making patterns during the pandemic.

Association between Troponin I Levels during Sepsis and Postsepsis Cardiovascular Complications.

Rationale: Sepsis commonly results in elevated serum troponin levels and increased risk for postsepsis cardiovascular complications; however, the association between troponin levels during sepsis and cardiovascular complications after sepsis is unclear.Objectives: To evaluate the association between serum troponin levels during sepsis and 1 year after sepsis cardiovascular events.Methods: We analyzed adults aged ⩾40 years without preexisting cardiovascular disease within 5 years, admitted with sepsis across 21 hospitals from 2011 to 2017. Peak serum troponin I levels during sepsis were grouped as normal (⩽0.04 ng/ml) or tertiles of abnormal (>0.04 to ⩽0.09 ng/ml, >0.09 to ⩽0.42 ng/ml, or >0.42 ng/ml). Multivariable adjusted cause-specific Cox proportional hazards models with death as a competing risk were used to assess associations between peak troponin I levels and a composite cardiovascular outcome (atherosclerotic cardiovascular disease, atrial fibrillation, and heart failure) in the year following sepsis. Models were adjusted for presepsis and intrasepsis factors considered potential confounders.Measurements and Main Results: Among 14,046 eligible adults with troponin I measured, 2,012 (14.3%) experienced the composite cardiovascular outcome, including 832 (10.9%) patients with normal troponin levels, as compared with 370 (17.3%), 376 (17.6%), and 434 (20.3%) patients within each sequential abnormal troponin tertile, respectively (P < 0.001). Patients within the elevated troponin tertiles had increased risks of adverse cardiovascular events (adjusted hazard ratio [aHR]troponin0.04-0.09 = 1.37; 95% confidence interval [CI], 1.20-1.55; aHRtroponin0.09-0.42 = 1.44; 95% CI, 1.27-1.63; and aHRtroponin>0.42 = 1.77; 95% CI, 1.56-2.00).Conclusions: Among patients without preexisting cardiovascular disease, troponin elevation during sepsis identified patients at increased risk for postsepsis cardiovascular complications. Strategies to mitigate cardiovascular complications among this high-risk subset of patients are warranted.

Rationale and Design of the Awake Prone Position for Early Hypoxemia in COVID-19 Study Protocol: A Clinical Trial.

The unprecedented public health burdens of coronavirus disease (COVID-19) have intensified the urgency of identifying effective, low-cost treatments that limit the need for advanced life support measures and improve clinical outcomes. However, personal protective equipment and staffing shortages, disease virulence, and infectivity have created significant barriers to traditional clinical trial practices. We present the novel design of a pragmatic, adaptive, multicenter, international, prospective randomized controlled clinical trial evaluating the safety and effectiveness of awake prone positioning in spontaneously breathing patients with COVID-19 (APPEX-19 [Awake Prone Position for Early Hypoxemia in COVID-19]). Key innovations of this trial include 1) a novel smartphone-based communication process that facilitates rapid enrollment and intervention delivery while allowing social distancing and conservation of personal protective equipment, 2) Bayesian response-adaptive randomization to allow preferential assignment to the most effective intervention and expedite trial completion compared with frequentist designs, 3) remote electronic collection of patient-reported outcomes and electronic medical record data, and 4) pragmatic prospective use of patient-reported data and data collected as part of routine clinical care. Clinical trial registered with www.clinicaltrials.gov (NCT04344587).

Outcomes of Patients With Coronavirus Disease 2019 Receiving Organ Support Therapies: The International Viral Infection and Respiratory Illness Universal Study Registry.

OBJECTIVES: To describe the outcomes of hospitalized patients in a multicenter, international coronavirus disease 2019 registry. DESIGN: Cross-sectional observational study including coronavirus disease 2019 patients hospitalized with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 infection between February 15, 2020, and November 30, 2020, according to age and type of organ support therapies. SETTING: About 168 hospitals in 16 countries within the Society of Critical Care Medicine's Discovery Viral Infection and Respiratory Illness University Study coronavirus disease 2019 registry. PATIENTS: Adult hospitalized coronavirus disease 2019 patients who did and did not require various types and combinations of organ support (mechanical ventilation, renal replacement therapy, vasopressors, and extracorporeal membrane oxygenation). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Primary outcome was hospital mortality. Secondary outcomes were discharge home with or without assistance and hospital length of stay. Risk-adjusted variation in hospital mortality for patients receiving invasive mechanical ventilation was assessed by using multilevel models with hospitals as a random effect, adjusted for age, race/ethnicity, sex, and comorbidities. Among 20,608 patients with coronavirus disease 2019, the mean (± sd) age was 60.5 (±17), 11,1887 (54.3%) were men, 8,745 (42.4%) were admitted to the ICU, and 3,906 (19%) died in the hospital. Hospital mortality was 8.2% for patients receiving no organ support (n = 15,001). The most common organ support therapy was invasive mechanical ventilation (n = 5,005; 24.3%), with a hospital mortality of 49.8%. Mortality ranged from 40.8% among patients receiving only invasive mechanical ventilation (n =1,749) to 71.6% for patients receiving invasive mechanical ventilation, vasoactive drugs, and new renal replacement therapy (n = 655). Mortality was 39% for patients receiving extracorporeal membrane oxygenation (n = 389). Rates of discharge home ranged from 73.5% for patients who did not require organ support therapies to 29.8% for patients who only received invasive mechanical ventilation, and 8.8% for invasive mechanical ventilation, vasoactive drugs, and renal replacement; 10.8% of patients older than 74 years who received invasive mechanical ventilation were discharged home. Median hospital length of stay for patients on mechanical ventilation was 17.1 days (9.7-28 d). Adjusted interhospital variation in mortality among patients receiving invasive mechanical ventilation was large (median odds ratio 1.69). CONCLUSIONS: Coronavirus disease 2019 prognosis varies by age and level of organ support. Interhospital variation in mortality of mechanically ventilated patients was not explained by patient characteristics and requires further evaluation.

ICU outcomes in Covid-19 patients with obesity.

The reviews of this paper are available via the supplemental material section.

Race, death of a child, and mortality risk among aging parents in the United States.

The death of a child is a stressful and traumatic life event that has been linked to increased mortality risk among parents. Tragically, black parents are significantly more likely than white parents to lose a child in the United States; however, prior research has not addressed this racial disadvantage in relation to parents' mortality risk. In this study, we focus on the racial context of the United States to suggest that black parents already face higher mortality rates compared to white parents, and the unequal burden of child death adds to their mortality risk. Using discrete-time event history models, we consider whether the death of a child by midlife is associated with increased mortality risk for black parents and for white parents in mid- to later-life using longitudinal data from the Health and Retirement Study (HRS; 1996-2016). Descriptive results show that by midlife, black parents, especially black mothers, experience substantially higher child mortality compared with white parents. At the same time, we find that losing a child prior to midlife is associated with heightened mortality risk for aging black mothers and white mothers. Controlling for educational attainment explains the association between child death and parental mortality risk among white mothers, whereas heightened biopsychosocial and behavioral risk factors explain the association for black mothers. Overall, the death of a child is associated with increased mortality risk for black mothers and for white mothers, but the processes linking child death to parental mortality seem to differ for black and white parents. These findings have implications for policies and interventions that address increased mortality risk for parents following the death of a child.

Stereotactic Radiosurgery to More Than 10 Brain Metastases: Evidence to Support the Role of Radiosurgery for Ideal Hippocampal Sparing in the Treatment of Multiple Brain Metastases.

BACKGROUND: Brain metastases are a common occurrence, with literature supporting the treatment of a limited number of brain metastases with stereotactic radiosurgery (SRS), as opposed to whole brain radiotherapy (WBRT). Less well understood is the role of SRS in patients with ≥10 brain metastases. METHODS: Patients treated with SRS to ≥10 brain metastases without concurrent WBRT between March 1999 and December 2016 were reviewed. Analysis was performed for overall survival, treated lesion freedom from progression (FFP), freedom from new metastases (FFNMs), and adverse radiation effect. Hippocampal volumes were retrospectively generated in patients treated with up-front SRS for evaluation of dose volume metrics. RESULTS: A total of 143 patients were identified with 75 patients having up-front SRS and 68 patients being treated as salvage therapy after prior WBRT. The median number of lesions per patient was 13 (interquartile range [IQR], 11-17). Median total volume of treatment was 4.1 cm3 (IQR, 2.0-9.9 cm3). The median 12-month FFP for up-front and salvage treatment was 96.8% (95% confidence interval [CI], 95.5-98.1) and 83.6% (95% CI, 79.9-87.5), respectively (P < 0.001). Twelve-month FFNMs for up-front and salvage SRS was 18.8% (95% CI, 10.9-32.3) versus 19.2% (95% CI, 9.7-37.8), respectively (P = 0.90). The mean hippocampal dose was 150 cGy (IQR, 100-202 cGy). CONCLUSIONS: Excellent rates of local control can be achieved when treating patients with >10 intracranial metastases either in the up-front or salvage setting. Hippocampal sparing is readily achievable with expected high rates of new metastatic lesions in treated patients.

Death of a Child Prior to Midlife, Dementia Risk, and Racial Disparities.

OBJECTIVES: This study considers whether experiencing the death of a child prior to midlife (by parental age 40) is associated with subsequent dementia risk, and how such losses, which are more common for black than for white parents, may add to racial disparities in dementia risk. METHODS: We use discrete-time event history models to predict dementia incidence among 9,276 non-Hispanic white and 2,182 non-Hispanic black respondents from the Health and Retirement Study, 2000-2014. RESULTS: Losing a child prior to midlife is associated with increased risk for later dementia, and adds to disparities in dementia risk associated with race. The death of a child is associated with a number of biosocial variables that contribute to subsequent dementia risk, helping to explain how the death of child may increase risk over time. DISCUSSION: The death of a child prior to midlife is a traumatic life course stressor with consequences that appear to increase dementia risk for both black and white parents, and this increased risk is explained by biosocial processes likely activated by bereavement. However, black parents are further disadvantaged in that they are more likely than white parents to experience the death of a child, and such losses add to the already substantial racial disadvantage in dementia risk.

MARITAL STRAIN AND PSYCHOLOGICAL DISTRESS IN SAME-SEX AND DIFFERENT-SEX COUPLES.

OBJECTIVE: This study examines the association of marital strain - as reported by each spouse - with psychological distress and considers whether the associations vary for men and women in gay, lesbian, and heterosexual marriages. BACKGROUND: Prior studies show that marital strain is associated with psychological distress. However, most studies rely on only one spouse's perspective and do not consider how appraisals of strain from both spouses may contribute to distress. Moreover, possible gender differences in these associations have been considered only for heterosexual couples. METHOD: Analyses are based on 10 days of dyadic diary data from 756 midlife U.S. men and women in 378 gay, lesbian, and heterosexual marriages. Multilevel modeling is used to examine the association of self- and spouse-reported marital strain with psychological distress; actor-partner interdependence models (APIM) explore possible gender differences in these associations. RESULTS: Both self- and spousal-reports of marital strain are associated with psychological distress, with notable gender differences. The associations of self- and spouse-reported marital strain with distress are stronger for women in different-sex marriages when compared to men in same-sex and different-sex marriages. The association is also stronger for women in different-sex marriages compared to women in same-sex marriages, but for self-reported strain only. CONCLUSION: Marital appraisals by both spouses are important for psychological well-being and may be especially important for the well-being of women in different-sex marriages.