Victim of a Revolution: Nicholas Cresswell\u27s American Odyssey, 1774-1777

The diary of Nicholas Cresswell, a young Englishman who traveled in America from 1774-1777, has long been an important primary source on the American Revolution. Cresswell\u27s travels took him from the eastern seaboard (and Barbados) to Kentucky and Ohio, and from Williamsburg, Virginia to New York City. The people he met encompassed almost the entire political spectrum of the day, ranging from William Howe and Loyalist operatives such as John Connolly to grassroots patriot activists on the Committees of Public Safety and founding luminaries such as George Rogers Clark, Thomas Jefferson, and Patrick Henry. He rubbed shoulders with people from radically different social, ethnic, and cultural groups: prosperous merchants in Alexandria and Philadelphia; plantation elites and their slaves in Barbados, Maryland, and Virginia; struggling Scots-Irish pioneers on the frontier; peaceful Delaware Indians and Moravian converts; poor tenant farmers in Loudoun County, Virginia; and the wildly diverse inhabitants of British-occupied New York City, including naval captains and crews, redcoats and Hessians, Loyalist refugees, and the beggars and prostitutes that constituted the social dregs of a city under siege. Above all, he had adventures, described in vivid detail and with a wry humor. Despite the diary\u27s popularity as a cornucopia of useful quotations, historians have written almost nothing about Cresswell himself, nor have they examined his diary simply for its own sake. In order to make Cresswell\u27s fascinating record of his American journey more accessible, this work will take advantage of a new edition of the diary text to provide a detailed narrative retelling and restore chronological order to the story while also including necessary historical context and analysis. Cresswell did not remain politically neutral but instead acted decisively to support the British cause during the early years of the Revolutionary War, which he viewed as a grassroots insurrection sparked by the Intolerable Acts of 1774 and goaded on by the zealous Committees of Public Safety, without any broader philosophical or ideological justification. His experiences among the Delaware Indians on the western frontier caused a remarkable transformation in his attitude towards American Indians, and his descriptions of relationships with American women reveal important facts about eighteenth-century views of women, marriage, and sexuality. The diary of Nicholas Cresswell, often quoted but seldom read, can open a valuable window on the life of a remarkable individual and the remarkably ordinary people around him during the crucial early years of the American Revolution

Utilization of Hyperbaric Oxygen Therapy and Induced Hypothermia After Hydrogen Sulfide Exposure

Hydrogen sulfide is a toxic gas produced as a byproduct of organic waste and many industrial processes. Hydrogen sulfide exposure symptoms may vary from mild (dizziness, headaches, nausea) to severe lactic acidosis via its inhibition of oxidative phosphorylation, leading to cardiac arrhythmias and death. Treatment is generally supportive. We report the case of a patient presenting with cardiac arrest secondary to hydrogen sulfide exposure treated with both hyperbaric oxygen therapy and therapeutic hypothermia with great improvement in neurologic function

Beyond the bundle - journey of a tertiary care medical intensive care unit to zero central line-associated bloodstream infections

INTRODUCTION: We set a goal to reduce the incidence rate of catheter-related bloodstream infections to rate of <1 per 1,000 central line days in a two-year period. METHODS: This is an observational cohort study with historical controls in a 25-bed intensive care unit at a tertiary academic hospital. All patients admitted to the unit from January 2008 to December 2011 (31,931 patient days) were included. A multidisciplinary team consisting of hospital epidemiologist/infectious diseases physician, infection preventionist, unit physician and nursing leadership was convened. Interventions included: central line insertion checklist, demonstration of competencies for line maintenance and access, daily line necessity checklist, and quality rounds by nursing leadership, heightened staff accountability, follow-up surveillance by epidemiology with timely unit feedback and case reviews, and identification of noncompliance with evidence-based guidelines. Molecular epidemiologic investigation of a cluster of vancomycin-resistant Enterococcus faecium (VRE) was undertaken resulting in staff education for proper acquisition of blood cultures, environmental decontamination and daily chlorhexidine gluconate (CHG) bathing for patients. RESULTS: Center for Disease Control/National Health Safety Network (CDC/NHSN) definition was used to measure central line-associated bloodstream infection (CLA-BSI) rates during the following time periods: baseline (January 2008 to December 2009), intervention year (IY) 1 (January to December 2010), and IY 2 (January to December 2011). Infection rates were as follows: baseline: 2.65 infections per 1,000 catheter days; IY1: 1.97 per 1,000 catheter days; the incidence rate ratio (IRR) was 0.74 (95% CI = 0.37 to 1.65, P = 0.398); residual seven CLA-BSIs during IY1 were VRE faecium blood cultures positive from central line alone in the setting of findings explicable by noninfectious conditions. Following staff education, environmental decontamination and CHG bathing (IY2): 0.53 per 1,000 catheter days; the IRR was 0.20 (95% CI = 0.06 to 0.65, P = 0.008) with 80% reduction compared to the baseline. Over the two-year intervention period, the overall rate decreased by 53% to 1.24 per 1,000 catheter-days (IRR of 0.47 (95% CI = 0.25 to 0.88, P = 0.019) with zero CLA-BSI for a total of 15 months. CONCLUSIONS: Residual CLA-BSIs, despite strict adherence to central line bundle, may be related to blood culture contamination categorized as CLA-BSIs per CDC/NHSN definition. Efforts to reduce residual CLA-BSIs require a strategic multidisciplinary team approach focused on epidemiologic investigations of practitioner- or unit-specific etiologies

Early Restrictive or Liberal Fluid Management for Sepsis-Induced Hypotension

BACKGROUND: Intravenous fluids and vasopressor agents are commonly used in early resuscitation of patients with sepsis, but comparative data for prioritizing their delivery are limited. METHODS: In an unblinded superiority trial conducted at 60 U.S. centers, we randomly assigned patients to either a restrictive fluid strategy (prioritizing vasopressors and lower intravenous fluid volumes) or a liberal fluid strategy (prioritizing higher volumes of intravenous fluids before vasopressor use) for a 24-hour period. Randomization occurred within 4 hours after a patient met the criteria for sepsis-induced hypotension refractory to initial treatment with 1 to 3 liters of intravenous fluid. We hypothesized that all-cause mortality before discharge home by day 90 (primary outcome) would be lower with a restrictive fluid strategy than with a liberal fluid strategy. Safety was also assessed. RESULTS: A total of 1563 patients were enrolled, with 782 assigned to the restrictive fluid group and 781 to the liberal fluid group. Resuscitation therapies that were administered during the 24-hour protocol period differed between the two groups; less intravenous fluid was administered in the restrictive fluid group than in the liberal fluid group (difference of medians, -2134 ml; 95% confidence interval [CI], -2318 to -1949), whereas the restrictive fluid group had earlier, more prevalent, and longer duration of vasopressor use. Death from any cause before discharge home by day 90 occurred in 109 patients (14.0%) in the restrictive fluid group and in 116 patients (14.9%) in the liberal fluid group (estimated difference, -0.9 percentage points; 95% CI, -4.4 to 2.6; P = 0.61); 5 patients in the restrictive fluid group and 4 patients in the liberal fluid group had their data censored (lost to follow-up). The number of reported serious adverse events was similar in the two groups. CONCLUSIONS: Among patients with sepsis-induced hypotension, the restrictive fluid strategy that was used in this trial did not result in significantly lower (or higher) mortality before discharge home by day 90 than the liberal fluid strategy. (Funded by the National Heart, Lung, and Blood Institute; CLOVERS ClinicalTrials.gov number, NCT03434028)

An Assessment of H1N1 Influenza-Associated Acute Respiratory Distress Syndrome Severity after Adjustment for Treatment Characteristics

Pandemic influenza caused significant increases in healthcare utilization across several continents including the use of high-intensity rescue therapies like extracorporeal membrane oxygenation (ECMO) or high-frequency oscillatory ventilation (HFOV). The severity of illness observed with pandemic influenza in 2009 strained healthcare resources. Because lung injury in ARDS can be influenced by daily management and multiple organ failure, we performed a retrospective cohort study to understand the severity of H1N1 associated ARDS after adjustment for treatment. Sixty subjects were identified in our hospital with ARDS from “direct injury” within 24 hours of ICU admission over a three month period. Twenty-three subjects (38.3%) were positive for H1N1 within 72 hours of hospitalization. These cases of H1N1-associated ARDS were compared to non-H1N1 associated ARDS patients. Subjects with H1N1-associated ARDS were younger and more likely to have a higher body mass index (BMI), present more rapidly and have worse oxygenation. Severity of illness (SOFA score) was directly related to worse oxygenation. Management was similar between the two groups on the day of admission and subsequent five days with respect to tidal volumes used, fluid balance and transfusion practices. There was, however, more frequent use of “rescue” therapy like prone ventilation, HFOV or ECMO in H1N1 patients. First morning set tidal volumes and BMI were significantly associated with increased severity of lung injury (Lung injury score, LIS) at presentation and over time while prior prescription of statins was protective. After assessment of the effect of these co-interventions LIS was significantly higher in H1N1 patients. Patients with pandemic influenza-associated ARDS had higher LIS both at presentation and over the course of the first six days of treatment when compared to non-H1N1 associated ARDS controls. The difference in LIS persisted over the duration of observation in patients with H1N1 possibly explaining the increased duration of mechanical ventilation

Association Between Neuromuscular Blocking Agents and Outcomes of Emergency Tracheal Intubation: A Secondary Analysis of Randomized Trials

Study objective: To examine the association between the neuromuscular blocking agent received (succinylcholine versus rocuronium) and the incidences of successful intubation on the first attempt and severe complications during tracheal intubation of critically ill adults in an emergency department (ED) or ICU. Methods: We performed a secondary analysis of data from 2 multicenter randomized trials in critically ill adults undergoing tracheal intubation in an ED or ICU. Using a generalized linear mixed-effects model with prespecified baseline covariates, we examined the association between the neuromuscular blocking agent received (succinylcholine versus rocuronium) and the incidences of successful intubation on the first attempt (primary outcome) and severe complications during tracheal intubation (secondary outcome). Results: Among the 2,440 patients in the trial data sets, 2,339 (95.9%) were included in the current analysis; 475 patients (20.3%) received succinylcholine and 1,864 patients (79.7%) received rocuronium. Successful intubation on the first attempt occurred in 375 patients (78.9%) who received succinylcholine and 1,510 patients (81.0%) who received rocuronium (an adjusted odds ratio of 0.87; 95% CI 0.65 to 1.15). Severe complications occurred in 67 patients (14.1%) who received succinylcholine and 456 patients (24.5%) who received rocuronium (adjusted odds ratio, 0.88; 95% CI 0.62 to 1.26). Conclusion: Among critically ill adults undergoing tracheal intubation, the incidences of successful intubation on the first attempt and severe complications were not significantly different between patients who received succinylcholine and patients who received rocuronium

Comparison of test-negative and syndrome-negative controls in SARS-CoV-2 vaccine effectiveness evaluations for preventing COVID-19 hospitalizations in the United States

BackgroundTest-negative design (TND) studies have produced validated estimates of vaccine effectiveness (VE) for influenza vaccine studies. However, syndrome-negative controls have been proposed for differentiating bias and true estimates in VE evaluations for COVID-19. To understand the use of alternative control groups, we compared characteristics and VE estimates of syndrome-negative and test-negative VE controls.MethodsAdults hospitalized at 21 medical centers in 18 states March 11-August 31, 2021 were eligible for analysis. Case patients had symptomatic acute respiratory infection (ARI) and tested positive for SARS-CoV-2. Control groups were test-negative patients with ARI but negative SARS-CoV-2 testing, and syndrome-negative controls were without ARI and negative SARS-CoV-2 testing. Chi square and Wilcoxon rank sum tests were used to detect differences in baseline characteristics. VE against COVID-19 hospitalization was calculated using logistic regression comparing adjusted odds of prior mRNA vaccination between cases hospitalized with COVID-19 and each control group.Results5811 adults (2726 cases, 1696 test-negative controls, and 1389 syndrome-negative controls) were included. Control groups differed across characteristics including age, race/ethnicity, employment, previous hospitalizations, medical conditions, and immunosuppression. However, control-group-specific VE estimates were very similar. Among immunocompetent patients aged 18-64&nbsp;years, VE was 93&nbsp;% (95&nbsp;% CI: 90-94) using syndrome-negative controls and 91&nbsp;% (95&nbsp;% CI: 88-93) using test-negative controls.ConclusionsDespite demographic and clinical differences between control groups, the use of either control group produced similar VE estimates across age groups and immunosuppression status. These findings support the use of test-negative controls and increase confidence in COVID-19 VE estimates produced by test-negative design studies

Thrombospondin-1 Contributes to Mortality in Murine Sepsis through Effects on Innate Immunity

BACKGROUND:Thrombospondin-1 (TSP-1) is involved in many biological processes, including immune and tissue injury response, but its role in sepsis is unknown. Cell surface expression of TSP-1 on platelets is increased in sepsis and could activate the anti-inflammatory cytokine transforming growth factor beta (TGFβ1) affecting outcome. Because of these observations we sought to determine the importance of TSP-1 in sepsis. METHODOLOGY/PRINCIPAL FINDINGS:We performed studies on TSP-1 null and wild type (WT) C57BL/6J mice to determine the importance of TSP-1 in sepsis. We utilized the cecal ligation puncture (CLP) and intraperitoneal E. coli injection (i.p. E. coli) models of peritoneal sepsis. Additionally, bone-marrow-derived macrophages (BMMs) were used to determine phagocytic activity. TSP-1-/- animals experienced lower mortality than WT mice after CLP. Tissue and peritoneal lavage TGFβ1 levels were unchanged between animals of each genotype. In addition, there is no difference between the levels of major innate cytokines between the two groups of animals. PLF from WT mice contained a greater bacterial load than TSP-1-/- mice after CLP. The survival advantage for TSP-1-/- animals persisted when i.p. E. coli injections were performed. TSP-1-/- BMMs had increased phagocytic capacity compared to WT. CONCLUSIONS:TSP-1 deficiency was protective in two murine models of peritoneal sepsis, independent of TGFβ1 activation. Our studies suggest TSP-1 expression is associated with decreased phagocytosis and possibly bacterial clearance, leading to increased peritoneal inflammation and mortality in WT mice. These data support the contention that TSP-1 should be more fully explored in the human condition

Interim Estimates of 2024-2025 Seasonal Influenza Vaccine Effectiveness - Four Vaccine Effectiveness Networks, United States, October 2024-February 2025

Annual influenza vaccination is recommended for all persons aged ≥6 months in the United States. Interim influenza vaccine effectiveness (VE) was calculated among patients with acute respiratory illness–associated outpatient visits and hospitalizations from four VE networks during the 2024–25 influenza season (October 2024–February 2025). Among children and adolescents aged \u3c18 years, VE against any influenza was 32%, 59%, and 60% in the outpatient setting in three networks, and against influenza-associated hospitalization was 63% and 78% in two networks. Among adults aged ≥18 years, VE in the outpatient setting was 36% and 54% in two networks and was 41% and 55% against hospitalization in two networks. Preliminary estimates indicate that receipt of the 2024–2025 influenza vaccine reduced the likelihood of medically attended influenza and influenza-associated hospitalization. CDC recommends annual receipt of an age-appropriate influenza vaccine by all eligible persons aged ≥6 months as long as influenza viruses continue to circulate locally