Effectiveness of preoxygenation strategies: a systematic review and network meta-analysis.

BACKGROUND: Preoxygenation is universally recommended before induction of general anaesthesia to prolong safe apnoea time. The optimal technique for preoxygenation is unclear. We conducted a systematic review to determine the preoxygenation technique associated with the greatest effectiveness in adult patients having general anaesthesia. METHODS: We searched six databases for randomised controlled trials of patients aged ≥16 yr, receiving general anaesthesia in any setting and comparing different preoxygenation techniques and methods. Our primary effectiveness outcome was safe apnoea time, and secondary outcomes included incidence of arterial oxygen desaturation; lowest SpO2 during airway management; time to end-tidal oxygen concentration of 90%; and [Formula: see text] and [Formula: see text] at the end of preoxygenation. We assessed the quality of evidence according to Grading of Recommendations, Assessment, Development and Evaluation (GRADE) recommendations. RESULTS: We included 52 studies of 3914 patients. High-flow nasal oxygen with patients in a head-up position was most likely to be associated with a prolonged safe apnoea time when compared with other strategies, with a mean difference (95% credible interval) of 291 (138-456) s and 203 (79-343) s compared with preoxygenation with a facemask in the supine and head-up positions, respectively. Subgroup analysis of studies without apnoeic oxygenation also showed high-flow nasal oxygen in the head-up position as the highest ranked technique, with a statistically significantly delayed mean difference (95% credible interval) safe apnoea time compared with facemask in supine and head-up positions of 222 (63-378) s and 139 (15-262) s, respectively. High-flow nasal oxygen was also the highest ranked technique for increased [Formula: see text] at the end of preoxygenation. However, the incidence of arterial desaturation was less likely to occur when a facemask with pressure support was used compared with other techniques, and [Formula: see text] was most likely to be lowest when preoxygenation took place with patients deep breathing in a supine position. CONCLUSIONS: Preoxygenation of adults before induction of general anaesthesia was most effective in terms of safe apnoea time when performed with high-flow nasal oxygen with patients in the head-up position in comparison with facemask alone. Also, high-flow nasal oxygen in the head-up position is likely to be the most effective technique to prolong safe apnoea time among those evaluated. Clinicians should consider this technique and patient position in routine practice. SYSTEMATIC REVIEW PROTOCOL: PROSPERO CRD42022326046.

Poor haemorrhagic stroke outcomes during the COVID-19 pandemic are driven by socioeconomic disparities: analysis of nationally representative data.

Background: Nationally representative studies evaluating the impact of the COVID-19 pandemic on haemorrhagic stroke outcomes are lacking. Methods: In this pooled cross-sectional analysis, we identified adults (≥18 years) with primary intracerebral haemorrhage (ICH) or subarachnoid haemorrhage (SAH) from the National Inpatient Sample (2016-2020). We evaluated differences in rates of in-hospital outcomes between the prepandemic (January 2016-February 2020) and pandemic (March-December 2020) periods using segmented logistic regression models. We used multivariable logistic regression to evaluate differences in mortality between patients admitted from April to December 2020, with and without COVID-19, and those admitted from April to December 2019. Stratified analyses were conducted among patients residing in low-income and high-income zip codes, as well as among patients with extreme loss of function (E-LoF) and those with minor to major loss of function (MM-LoF). Results: Overall, 309 965 patients with ICH (47% female, 56% low income) and 112 210 patients with SAH (62% female, 55% low income) were analysed. Prepandemic, ICH mortality decreased by ~1% per month (adjusted OR, 95% CI: 0.99 (0.99 to 1.00); p<0.001). However, during the pandemic, the overall ICH mortality rate increased, relative to prepandemic, by ~2% per month (1.02 (1.00 to 1.04), p<0.05) and ~4% per month (1.04 (1.01 to 1.07), p<0.001) among low-income patients. There was no significant change in trend among high-income patients with ICH (1.00 (0.97 to 1.03)). Patients with comorbid COVID-19 in 2020 had higher odds of mortality (versus 2019 cohort) only among patients with MM-LoF (ICH, 2.15 (1.12 to 4.16), and SAH, 5.77 (1.57 to 21.17)), but not among patients with E-LoF. Conclusion: Sustained efforts are needed to address socioeconomic disparities in healthcare access, quality and outcomes during public health emergencies.

Minimally Invasive Surgery With Thrombolysis for Intracerebral Hemorrhage Evacuation: Bayesian Reanalysis of a Randomized Controlled Trial.

BACKGROUND AND OBJECTIVES: Bayesian analysis of randomized controlled trials (RCTs) can extend the value of trial data beyond interpretations based on conventional p value-based binary cutoffs. We conducted an exploratory post hoc Bayesian reanalysis of the minimally invasive surgery with thrombolysis for intracerebral hemorrhage (ICH) evacuation (MISTIE-3) trial and derived probabilities of potential intervention effect on functional and survival outcomes. METHODS: MISTIE-3 was a multicenter phase 3 RCT designed to evaluate the efficacy and safety of the MISTIE intervention. Five hundred and six adults (18 years or older) with spontaneous, nontraumatic, supratentorial ICH of ≥30 mL were randomized to receive either the MISTIE intervention (n = 255) or standard medical care (n = 251). We provide Bayesian-derived estimates of the effect of the MISTIE intervention on achieving a good 365-day modified Rankin Scale score (mRS score 0-3) as relative risk (RR) and absolute risk difference (ARD), and the probabilities that these treatment effects are greater than prespecified thresholds. We used 2 sets of prior distributions: (1) reference priors, including minimally informative, enthusiastic, and skeptical priors, and (2) data-derived prior distribution, using a hierarchical random effects model. We additionally evaluated the potential effects of the MISTIE intervention on 180-day and 30-day mRS and 365-, 180-, and 30-day mortality using data-derived priors. RESULTS: The Bayesian-derived probability that MISTIE intervention has any beneficial effect (RR >1) on achieving a good 365-day mRS score was 70% using minimally informative prior, 87% with enthusiastic prior, 68% with skeptical prior, and 73% with data-derived prior. However, these probabilities were ≤55% for RR >1.10 and 0% for RR >1.52 across a range of priors. The probabilities of achieving RR >1 for 180- and 30-day mRS scores are 65% and 80%, respectively. Furthermore, the probabilities of achieving RR <1 for 365-, 180-, and 30-day mortality are 93%, 98%, and 99%, respectively. DISCUSSION: Our exploratory analyses indicate that across a range of priors, the Bayesian-derived probability of MISTIE intervention having any beneficial effect on 365-day mRS for patients with ICH is between 68% and 87%. These analyses do not change the frequentist-based interpretation of the trial. However, unlike the frequentist p values, which indirectly evaluate treatment effects and only provide an arbitrary binary cutoff (such as 0.05), the Bayesian framework directly estimates the probabilities of potential treatment effects. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov/ct2/show/NCT01827046. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that minimally invasive surgery (MIS) + recombinant tissue plasminogen activator (rt-PA) does not significantly improve functional outcome in patients with ICH. However, this study lacks the precision to exclude a potential benefit of MIS + rt-PA.

Seasonal variation in the incidence of primary intracerebral hemorrhage: a 16-year nationwide analysis.

Introduction: Data on nationwide trends and seasonal variations in the incidence of Intracerebral Hemorrhage (ICH) in the United States (US) are lacking. Methods: We used the Nationwide Inpatient Sample (2004-2019) and Census Bureau data to calculate the quarterly (Q1:January-March; Q2:April-June; Q3:July-September; Q4:October-December) incidence rates (IR) of adult (≥18 years) ICH hospitalizations, aggregated across Q1-Q4 and Q2-Q3. We report adjusted incidence rate ratios (aIRR) and 95% confidence intervals (CI) for differences in the quarterly incidence of ICH, as compared to acute ischemic stroke (AIS), between Q1Q4 and Q2Q3 using a multivariable Poisson regression model. We additionally performed stratified analyses across the four US regions. Results: Among 822,143 (49.0% female) ICH and 6,266,234 (51.9% female) AIS hospitalizations, the average quarterly crude IR of ICH was consistently higher in Q1Q4 compared to Q2Q3 (5.6 vs. 5.2 per 100,000) (aIRR, CI: 1.09, 1.08-1.11)-this pattern was similar across all four US regions. However, a similar variation pattern was not observed for AIS incidence. The incidence (aIRR, CI) of both ICH (1.01, 1.00-1.02) and AIS (1.03, 1.02-1.03) is rising. Conclusion: Unlike AIS, ICH incidence is consistently higher in colder quarters, underscoring the need for evaluation and prevention of factors driving seasonal variations in ICH incidence.

Lifelong cerebrovascular disease burden among CADASIL patients: analysis from a global health research network.

Introduction: Data reporting on patients with Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) within the United States population is limited. We sought to evaluate the overt cerebrovascular disease burden among patients with CADASIL. Methods: Harmonized electronic medical records were extracted from the TriNetX global health research network. CADASIL patients were identified using diagnostic codes and those with/without history of documented stroke sub-types (ischemic stroke [IS], intracerebral hemorrhage [ICH], subarachnoid hemorrhage [SAH] and transient ischemic attack [TIA]) were compared. Adjusted odds ratios (OR) and 95% confidence intervals (CI) of stroke incidence and mortality associated with sex were computed. Results: Between September 2018 and April 2020, 914 CADASIL patients were identified (median [IQR] age: 60 [50-69], 61.3% females); of whom 596 (65.2%) had documented cerebrovascular events (i.e., CADASIL-Stroke patients). Among CADASIL-Stroke patients, 89.4% experienced an IS, co-existing with TIAs in 27.7% and hemorrhagic strokes in 6.2%; initial stroke events occurred ≤65 years of age in 71% of patients. CADASIL-Stroke patients (vs. CADASIL-non-Stroke) had higher cardiovascular and neurological (migraines, cognitive impairment, epilepsy/seizures, mood disorders) burden. In age- and comorbidity-adjusted models, males had higher associated risk of stroke onset (OR: 1.37, CI: 1.01-1.86). Mortality risk was higher for males (OR: 2.72, CI: 1.53-4.84). Discussion: Early screening and targeted treatment strategies are warranted to help CADASIL patients with symptom management and risk mitigation.

A Neuro-Informatics Pipeline for Cerebrovascular Disease: Research Registry Development.

BACKGROUND: Although stroke is well recognized as a critical disease, treatment options are often limited. Inpatient stroke encounters carry critical information regarding the mechanisms of stroke and patient outcomes; however, these data are typically formatted to support administrative functions instead of research. To support improvements in the care of patients with stroke, a substantive research data platform is needed. OBJECTIVE: To advance a stroke-oriented learning health care system, we sought to establish a comprehensive research repository of stroke data using the Houston Methodist electronic health record (EHR) system. METHODS: Dedicated processes were developed to import EHR data of patients with primary acute ischemic stroke, intracerebral hemorrhage (ICH), transient ischemic attack, and subarachnoid hemorrhage under a review board-approved protocol. Relevant patients were identified from discharge diagnosis codes and assigned registry patient identification numbers. For identified patients, extract, transform, and load processes imported EHR data of primary cerebrovascular disease admissions and available data from any previous or subsequent admissions. Data were loaded into patient-focused SQL objects to enable cross-sectional and longitudinal analyses. Primary data domains (admission details, comorbidities, laboratory data, medications, imaging data, and discharge characteristics) were loaded into separate relational tables unified by patient and encounter identification numbers. Computed tomography, magnetic resonance, and angiography images were retrieved. Imaging data from patients with ICH were assessed for hemorrhage characteristics and cerebral small vessel disease markers. Patient information needed to interface with other local and national databases was retained. Prospective patient outreach was established, with patients contacted via telephone to assess functional outcomes 30, 90, 180, and 365 days after discharge. Dashboards were constructed to provide investigators with data summaries to support access. RESULTS: The Registry of Neurological Endpoint Assessments among Patients with Ischemic and Hemorrhagic Stroke (REINAH) database was constructed as a series of relational category-specific SQL objects. Encounter summaries and dashboards were constructed to draw from these objects, providing visual data summaries for investigators seeking to build studies based on REINAH data. As of June 2022, the database contains 18,061 total patients, including 1809 (10.02%) with ICH, 13,444 (74.43%) with acute ischemic stroke, 1221 (6.76%) with subarachnoid hemorrhage, and 3165 (17.52%) with transient ischemic attack. Depending on the cohort, imaging data from computed tomography are available for 85.83% (1048/1221) to 98.4% (1780/1809) of patients, with magnetic resonance imaging available for 27.85% (340/1221) to 85.54% (11,500/13,444) of patients. Outcome assessment has successfully contacted 56.1% (240/428) of patients after ICH, with 71.3% (171/240) of responders providing consent for assessment. Responders reported a median modified Rankin Scale score of 3 at 90 days after discharge. CONCLUSIONS: A highly curated and clinically focused research platform for stroke data will establish a foundation for future research that may fundamentally improve poststroke patient care and outcomes.

Stroke severity mediates the effect of socioeconomic disadvantage on poor outcomes among patients with intracerebral hemorrhage.

Background: Socioeconomic deprivation drives poor functional outcomes after intracerebral hemorrhage (ICH). Stroke severity and background cerebral small vessel disease (CSVD) burden have each been linked to socioeconomic status and independently contribute to worse outcomes after ICH, providing distinct, plausible pathways for the effects of deprivation. We investigate whether admission stroke severity or cerebral small vessel disease (CSVD) mediates the effect of socioeconomic deprivation on 90-day functional outcomes. Methods: Electronic medical record data, including demographics, treatments, comorbidities, and physiological data, were analyzed. CSVD burden was graded from 0 to 4, with severe CSVD categorized as ≥3. High deprivation was assessed for patients in the top 30% of state-level area deprivation index scores. Severe disability or death was defined as a 90-day modified Rankin Scale score of 4-6. Stroke severity (NIH stroke scale (NIHSS)) was classified as: none (0), minor (1-4), moderate (5-15), moderate-severe (16-20), and severe (21+). Univariate and multivariate associations with severe disability or death were determined, with mediation evaluated through structural equation modelling. Results: A total of 677 patients were included (46.8% female; 43.9% White, 27.0% Black, 20.7% Hispanic, 6.1% Asian, 2.4% Other). In univariable modelling, high deprivation (odds ratio: 1.54; 95% confidence interval: [1.06-2.23]; p = 0.024), severe CSVD (2.14 [1.42-3.21]; p < 0.001), moderate (8.03 [2.76-17.15]; p < 0.001), moderate-severe (32.79 [11.52-93.29]; p < 0.001), and severe stroke (104.19 [37.66-288.12]; p < 0.001) were associated with severe disability or death. In multivariable modelling, severe CSVD (3.42 [1.75-6.69]; p < 0.001) and moderate (5.84 [2.27-15.01], p < 0.001), moderate-severe (27.59 [7.34-103.69], p < 0.001), and severe stroke (36.41 [9.90-133.85]; p < 0.001) independently increased odds of severe disability or death; high deprivation did not. Stroke severity mediated 94.1% of deprivation's effect on severe disability or death (p = 0.005), while CSVD accounted for 4.9% (p = 0.524). Conclusion: CSVD contributed to poor functional outcome independent of socioeconomic deprivation, while stroke severity mediated the effects of deprivation. Improving awareness and trust among disadvantaged communities may reduce admission stroke severity and improve outcomes.

Geographic Disparities in Case Fatality and Discharge Disposition Among Patients With Primary Intracerebral Hemorrhage.

Background We evaluate nationwide trends and urban-rural disparities in case fatality (in-hospital mortality) and discharge dispositions among patients with primary intracerebral hemorrhage (ICH). Methods and Results In this repeated cross-sectional study, we identified adult patients (≥18 years of age) with primary ICH from the National Inpatient Sample (2004-2018). Using a series of survey design Poisson regression models, with hospital location-time interaction, we report the adjusted risk ratio (aRR), 95% CI, and average marginal effect (AME) for factors associated with ICH case fatality and discharge dispositions. We performed a stratified analysis of each model among patients with extreme loss of function and minor to major loss of function. We identified 908 557 primary ICH hospitalizations (overall mean age [SD], 69.0 [15.0] years; 445 301 [49.0%] women; 49 884 [5.5%] rural ICH hospitalizations). The crude ICH case fatality rate was 25.3% (urban hospitals: 24.9%, rural hospitals:32.5%). Urban (versus rural) hospital patients had a lower likelihood of ICH case fatality (aRR, 0.86 [95% CI, 0.83-0.89]). ICH case fatality is declining over time; however, it is declining faster in urban hospitals (AME, -0.049 [95% CI, -0.051 to -0.047]) compared with rural hospitals (AME, -0.034 [95% CI, -0.040 to -0.027]). Conversely, home discharge is increasing significantly among urban hospitals (AME, 0.011 [95% CI, 0.008-0.014]) but not significantly changing in rural hospitals (AME, -0.001 [95% CI, -0.010 to 0.007]). Among patients with extreme loss of function, hospital location was not significantly associated with ICH case fatality or home discharge. Conclusions Improving access to neurocritical care resources, particularly in resource-limited communities, may reduce the ICH outcomes disparity gap.

Partitioning into phosphatidylcholine-cholesterol membranes: liposome measurements, coarse-grained simulations, and implications for bioaccumulation.

Membrane-water partitioning is an important physical property for the assessment of bioaccumulation and environmental impact. Here, we advance simulation methodology for predicting the partitioning of small molecules into lipid membranes and compare the computational predictions to experimental measurements in liposomes. As a step towards high-throughput screening, we present an automated mapping and parametrization procedure to produce coarse-grained models compatible with the Martini 3 force field. The methodology is general and can also be used for other applications where coarse-grained simulations are appropriate. This article addresses the effect on membrane-water partitioning of adding cholesterol to POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) membranes. Nine contrasting neutral, zwitterionic and charged solutes are tested. Agreement between experiment and simulation is generally good, with the most challenging cases being permanently charged solutes. For all solutes, partitioning is found to be insensitive to membrane cholesterol concentration up to 25% mole fraction. Hence, for assessment of bioaccumulation into a range of membranes (such as those found in fish), partitioning data measured in pure lipid membranes are still informative.

Real-world effectiveness of COVID-19 vaccines and anti-SARS-CoV-2 monoclonal antibodies against postacute sequelae of SARS-CoV-2: analysis of a COVID-19 observational registry for a diverse US metropolitan population.

OBJECTIVES: We evaluated the effectiveness of COVID-19 vaccines and monoclonal antibodies (mAbs) against postacute sequelae of SARS-CoV-2 infection (PASC). DESIGN AND SETTING: A retrospective cohort study using a COVID-19 specific, electronic medical record-based surveillance and outcomes registry from an eight-hospital tertiary hospital system in the Houston metropolitan area. Analyses were replicated across a global research network database. PARTICIPANTS: We identified adult (≥18) patients with PASC. PASC was defined as experiencing constitutional (palpitations, malaise/fatigue, headache) or systemic (sleep disorder, shortness of breath, mood/anxiety disorders, cough and cognitive impairment) symptoms beyond the 28-day postinfection period. STATISTICAL ANALYSIS: We fit multivariable logistic regression models and report estimated likelihood of PASC associated with vaccination or mAb treatment as adjusted ORs with 95% CIs. RESULTS: Primary analyses included 53 239 subjects (54.9% female), of whom 5929, 11.1% (95% CI 10.9% to 11.4%), experienced PASC. Both vaccinated breakthrough cases (vs unvaccinated) and mAb-treated patients (vs untreated) had lower likelihoods for developing PASC, aOR (95% CI): 0.58 (0.52-0.66), and 0.77 (0.69-0.86), respectively. Vaccination was associated with decreased odds of developing all constitutional and systemic symptoms except for taste and smell changes. For all symptoms, vaccination was associated with lower likelihood of experiencing PASC compared with mAb treatment. Replication analysis found identical frequency of PASC (11.2%, 95% CI 11.1 to 11.3) and similar protective effects against PASC for the COVID-19 vaccine: 0.25 (0.21-0.30) and mAb treatment: 0.62 (0.59-0.66). CONCLUSION: Although both COVID-19 vaccines and mAbs decreased the likelihood of PASC, vaccination remains the most effective tool for the prevention of long-term consequences of COVID-19.

A Contemporary Review of Epidemiology, Risk Factors, Etiology, and Outcomes of Premature Stroke.

PURPOSE OF REVIEW: Recent data identifies increases in young ischemic and hemorrhagic strokes. We provide a contemporary overview of current literature on stroke among young patients or premature stroke along with directions for future investigation. RECENT FINDINGS: Strokes in the young are highly heterogenous and often cryptogenic. Sex distribution and risk factors shift from women among the youngest age groups (< 35) to men over the age of 45, with a coinciding rise in traditional vascular risk factors. Incidence is higher in minority and socioeconomically disadvantaged populations, and the impact of stroke among these communities may be exaggerated by disparities in symptom recognition and access to care. Special diagnostic work-up may be needed, and a lower threshold for diagnosis is warranted as potential misdiagnosis is a concern and may preclude necessary triage and management. Although "premature strokes" form a relatively small proportion of total incidence, they vary greatly across subgroups and present an outsized impact on quality of life and productivity.

COVID-19 associated disruptions in routine health care of people with mild cognitive impairment or dementia.

Introduction: We report the COVID-19 pandemic's impact on health-care use disruption among people with mild cognitive impairment or Alzheimer's disease and related dementia (MCI/ADRD). Methods: We compared the pandemic-period health-care use between MCI/ADRD and matched non-MCI/ADRD patients. Using 4-year pre-pandemic data, we modeled three health-care use types (inpatient, outpatient, emergency encounters) to predict pandemic-period use, disaggregated for lockdown and post-lockdown periods. Observed health-care use was compared to the predicted. Proportional differences (confidence intervals) are reported. Results: Both MCI/ADRD and non-MCI/ADRD patients (n = 5479 each) experienced pandemic-related health-care use disruptions, which were significantly larger for the MCI/ADRD group for outpatient, -13.2% (-16.2%, -10.2%), and inpatient encounters, -12.8% (-18.4%, -7.3%). Large health-care disruptions during lockdown were similar for both groups. However, post-lockdown outpatient, -14.4% (-17.3%, -11.5%), and inpatient, -15.2% (-21.0%, -9.5%), disruptions were significantly greater for MCI/ADRD patients. Conclusion: MCI/ADRD patients experienced greater and sustained pandemic-related health-care use disruptions, highlighting the need for robust strategies to sustain their essential health care during pandemic-like catastrophes.

Sex differences in post-stroke cognitive decline: A population-based longitudinal study of nationally representative data.

BACKGROUND: Sex differences in post-stroke cognitive decline have not been systematically evaluated in a nationally representative cohort. We use a quasi-experimental design to investigate sex differences in rate of post-stroke cognitive decline. METHODS: Utilizing the event study design, we use the Health and Retirement Study (HRS) data (1996-2016) to evaluate the differences (percentage points [95% Confidence interval]) in the rate of change in cognitive function, measured using the modified version of the Telephone Interview for Cognitive Status (TICS-m) score, before and after incident stroke, and among patients with and without incident stroke. We estimated this event study model for the overall study population and separately fit the same model for male and female participants. RESULTS: Of 25,872 HRS participants included in our study, 14,459 (55.9%) were females with an overall mean age (SD) of 61.2 (9.3) years. Overall, 2,911 (11.3%) participants reported experiencing incident stroke. Participants with incident stroke (vs. no stroke) had lower baseline TICS-m score (15.6 vs. 16.1). Among participants with incident stroke, the mean pre-stroke TICS-m score was higher than the mean post-stroke TICS-m score (14.9 vs. 12.7). Event study revealed a significant short-term acceleration of cognitive decline for the overall population (4.2 [1.7-6.6] percentage points, p value = 0.001) and among female participants (5.0 [1.7-8.3] percentage points, p value = 0.003). We, however, found no evidence of long-term acceleration of cognitive decline after stroke. Moreover, among males, incident stroke was not associated with significant changes in rate of post-stroke cognitive decline. CONCLUSION: Females, in contrast to males, experience post-stroke cognitive deficits, particularly during early post-stroke period. Identifying the sex-specific stroke characteristics contributing to differences in post stroke cognitive decline may inform future strategies for reducing the burden of post-stroke cognitive impairment and dementia.

Contemporary Trends in the Nationwide Incidence of Primary Intracerebral Hemorrhage.

BACKGROUND: We report contemporary trends in nationwide incidence of intracerebral hemorrhage (ICH) across demographic and regional strata over a 15-year period. METHODS: Utilizing the Nationwide Inpatient Sample (2004-2018) and US Census Bureau data, we calculated ICH incidence rates for age, race/ethnicity, sex, and hospital region sub-cohorts across 5 consecutive 3-year periods (2004-2006 to 2016-2018). We fit Poisson and log binomial regression models to evaluate demographic and regional differences in ICH incidence and trends in prevalence of hypertension and past/current anticoagulant use among hospitalized ICH patients. RESULTS: Overall, the annual incidence rate (95% CI) of ICH per 100 000 was 23.15 (23.10-23.20). The 3-year incidence of ICH (per 100 000) increased from 62.79 in 2004 to 2006 to 78.86 in 2016 to 2018 (adjusted incidence rate ratio, CI: 1.11 [1.02-1.20]), coinciding with increased 3-year prevalence of hypertension and anticoagulant use among hospitalized ICH patients (adjusted risk ratio, CI: hypertension-1.16 [1.15-1.17]; anticoagulant use-2.30 [2.14-2.47]). We found a significant age-time interaction, whereby ICH incidence increased significantly faster among those aged 18 to 44 years (adjusted incidence rate ratio, CI: 1.10 [1.05-1.14]) and 45 to 64 years (adjusted incidence rate ratio, CI: 1.08 [1.03-1.13]), relative to those aged ≥75 years. CONCLUSIONS: Rising ICH incidence among young and middle-aged Americans warrants ICH prevention strategies targeting these economically productive age groups.

Cognitive Impairment After Intracerebral Hemorrhage: A Systematic Review of Current Evidence and Knowledge Gaps.

Background: Cognitive impairment (CI) is commonly observed after intracerebral hemorrhage (ICH). While a growing number of studies have explored this association, several evidence gaps persist. This review seeks to investigate the relationship between CI and ICH. Methods: A two-stage systematic review of research articles, clinical trials, and case series was performed. Initial search used the keywords ["Intracerebral hemorrhage" OR "ICH"] AND ["Cognitive Impairment" OR "Dementia OR "Cognitive Decline"] within the PubMed (last accessed November 3rd, 2020) and ScienceDirect (last accessed October 27th, 2020) databases, without publication date limits. Articles that addressed CI and spontaneous ICH were accepted if CI was assessed after ICH. Articles were rejected if they did not independently address an adult human population or spontaneous ICH, didn't link CI to ICH, were an unrelated document type, or were not written in English. A secondary snowball literature search was performed using reviews identified by the initial search. The Agency for Healthcare research and Quality's assessment tool was used to evaluate bias within studies. Rates of CI and contributory factors were investigated. Results: Search yielded 32 articles that collectively included 22,631 patients. Present evidence indicates a high rate of post-ICH CI (65-84%) in the acute phase (<4 weeks) which is relatively lower at 3 (17.3-40.2%) and 6 months (19-63.3%). Longer term follow-up (≥1 year) demonstrates a gradual increase in CI. Advanced age, female sex, and prior stroke were associated with higher rates of CI. Associations between post-ICH CI and cerebral microbleeds, superficial siderosis, and ICH volume also exist. Pre-ICH cognitive assessment was missing in 28% of included studies. The Mini Mental State Evaluation (44%) and Montreal Cognitive Assessment (16%) were the most common cognitive assessments, albeit with variable thresholds and definitions. Studies rarely (<10%) addressed racial and ethnic disparities. Discussion: Current findings suggest a dynamic course of post-ICH cognitive impairment that may depend on genetic, sociodemographic and clinical factors. Methodological heterogeneity prevented meta-analysis, limiting results. There is a need for the methodologies and time points of post-ICH cognitive assessments to be harmonized across diverse clinical and demographic populations.

Pilot-administered anaesthesia and the Royal Flying Doctor Service of Australia: An interview with Captain Keith Galloway.

The lack of radio navigational aids in early Royal Flying Doctor Service aircraft in Australia occasionally resulted in aircraft being stranded at a remote site with a critically injured patient due to weather and other conditions. For a brief period in the 1950s, at least one Royal Flying Doctor Service pilot was trained to administer anaesthesia to critically ill patients who could not be immediately evacuated. The aim of this paper is to describe the circumstances in which this arose and how it worked in practice. This is based largely on the recollections of pilot anaesthetist Captain Keith Galloway, who shared his recollections during interviews with the authors.

National Trends in Transfer of Patients with Primary Intracerebral Hemorrhage: An Analysis of 12-Year Nationwide Data.

OBJECTIVES: The guidelines of the American Hospital Association encourage transferring intracerebral hemorrhage patients from community hospitals to centers with stroke expertise. However, research on the differences in outcomes between transferred intracerebral hemorrhage hospitalizations and directly admitted hospitalizations have been largely limited to small single-center studies. In this study, we explored the national trends in transferred intracerebral hemorrhage hospitalizations, as well as evaluated the differences, in terms of demographic characteristics, co-morbidity, resource utilization, and outcomes, between transferred intracerebral hemorrhage hospitalizations and directly admitted hospitalizations. MATERIALS AND METHODS: From the National Inpatient Sample (2004 - 2016), we assessed the linear trends in the proportion of interhospital transfers for intracerebral hemorrhage hospitalizations. We constructed a series of multivariate logistic regression models to explore the association of transfer status with inpatient mortality and discharge disposition, controlling for demographic, clinical, and hospital characteristics. We used survey design variables to report nationally weighted estimates. RESULTS: Among 786,999 hospitalizations, 137,340 (17.5%, 95% CI: 16.4-18.6) were transferred. Overall, interhospital transfers for intracerebral hemorrhage has been increasing over the 12-year period of this study. Patients in transferred hospitalizations were younger, more likely to be white, and more likely to have private insurance. Transferred hospitalizations were associated with significantly lower adjusted odds of inpatient mortality, compared to directly admitted hospitalizations. CONCLUSIONS: As the US healthcare system continues shifting towards value-based care, evidence on the short- and long-term outcomes of transfer of intracerebral hemorrhage patients will inform optimal management of intracerebral hemorrhage patients.

Automated Coarse-Grained Mapping Algorithm for the Martini Force Field and Benchmarks for Membrane-Water Partitioning.

With a view to high-throughput simulations, we present an automated system for mapping and parameterizing organic molecules for use with the coarse-grained Martini force field. The method scales to larger molecules and a broader chemical space than existing schemes. The core of the mapping process is a graph-based analysis of the molecule's bonding network, which has the advantages of being fast, general, and preserving symmetry. The parameterization process pays special attention to coarse-grained beads in aromatic rings. It also includes a method for building efficient and stable frameworks of constraints for molecules with structural rigidity. The performance of the method is tested on a diverse set of 87 neutral organic molecules and the ability of the resulting models to capture octanol-water and membrane-water partition coefficients. In the latter case, we introduce an adaptive method for extracting partition coefficients from free-energy profiles to take into account the interfacial region of the membrane. We also use the models to probe the response of membrane-water partitioning to the cholesterol content of the membrane.

SARS-CoV-2 Susceptibility and COVID-19 Mortality Among Older Adults With Cognitive Impairment: Cross-Sectional Analysis From Hospital Records in a Diverse US Metropolitan Area.

Introduction: Persistent knowledge gaps exist as to the extent that preexisting cognitive impairment is a risk factor for susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and mortality from the coronavirus disease 2019 (COVID-19). Methods: We conducted a cross-sectional analysis of adults tested for SARS-CoV-2 at a tertiary healthcare system. Cognitive impairment was identified utilizing diagnosis codes (mild cognitive impairment, Alzheimer's disease, vascular, and other dementias) or cognitive impairment-specific medication use. Propensity score (PS) matched analyses were utilized to report odds ratios (OR) and 95% confidence intervals (CI) for association of cognitive impairment with SARS-CoV-2 susceptibility and COVID-19 mortality. Results: Between March-3rd and December-11th, 2020, 179,979 adults were tested, of whom 21,607 (12.0%) tested positive. We identified 6,364 individuals with preexisting cognitive impairment (mean age: 78.5 years, 56.8% females), among whom 843 (13.2%) tested positive and 139 (19.5%) of those hospitalized died. In the pre-PS matched cohort, cognitive impairment was significantly associated with increased SARS-CoV-2 susceptibility (OR, CI: 1.12, 1.04-1.21) and COVID-19 mortality (OR, CI: 2.54, 2.07-3.12). One-to-one matches were identified for 6,192 of 6,364 (97.3%) individuals with prior cognitive impairment and 687 of 712 (96.5%) hospitalized patients with prior cognitive impairment. In the fully balanced post-matched cohort, preexisting cognitive impairment was significantly associated with higher likelihood of SARS-CoV-2 infection (OR, CI: 1.51, 1.35-1.70); however, cognitive impairment did not confer higher risk of COVID-19 mortality (OR, CI: 0.96, 0.73-1.25). Discussion: To mitigate the effects of healthcare catastrophes such as the COVID-19 pandemic, strategies for targeted prevention and risk-stratified comorbidity management are warranted among the vulnerable sub-population living with cognitive impairment.