BACKGROUND: Fluid and vasopressor management in septic shock remains controversial. In this randomized controlled trial, we evaluated the efficacy of dynamic measures (stroke volume change during passive leg raise) to guide resuscitation and improve patient outcome. RESEARCH QUESTION: Will resuscitation that is guided by dynamic assessments of fluid responsiveness in patients with septic shock improve patient outcomes? STUDY DESIGN AND METHODS: We conducted a prospective, multicenter, randomized clinical trial at 13 hospitals in the United States and United Kingdom. Patients presented to EDs with sepsis that was associated hypotension and anticipated ICU admission. Intervention arm patients were assessed for fluid responsiveness before clinically driven fluid bolus or increase in vasopressors occurred. The protocol included reassessment and therapy as indicated by the passive leg raise result. The control arm received usual care. The primary clinical outcome was positive fluid balance at 72 hours or ICU discharge, whichever occurred first. RESULTS: In modified intent-to-treat analysis that included 83 intervention and 41 usual care eligible patients, fluid balance at 72 hours or ICU discharge was significantly lower (À1.37 L favoring the intervention arm; 0.65 AE 2.85 L intervention arm vs 2.02 AE 3.44 L usual care arm; P ¼ .021. Fewer patients required renal replacement therapy (5.1% vs 17.5%; P ¼ .04) or mechanical ventilation (17.7% vs 34.1%; P ¼ .04) in the intervention arm compared with usual care. In the all-randomized intent-to-treat population (102 intervention, 48 usual care), there were no significant differences in safety signals. INTERPRETATION: Physiologically informed fluid and vasopressor resuscitation with the use of the passive leg raise-induced stroke volume change to guide management of septic shock is safe and demonstrated lower net fluid balance and reductions in the risk of renal and respiratory failure. Dynamic assessments to guide fluid administration may improve outcomes for patients with septic shock compared with usual care.

us-map.html ¶ A list of severe manifestations of monkeypox can be found at https://emergency. cdc.gov/han/2022/han00475.asp. ** During the study period and as of October 21, 2022, CDC was notified by state and local jurisdictions of five decedents whose death certificates included monkeypox as a cause of death or contributing factor, six decedents whose cause of death is still under active investigation, and one decedent in whom the death was not monkeypox-related. Additional monkeypox cases involving severe disease or death might not be included in this report if CDC has not yet been notified about the case or if the case occurred outside of the study period.

Background Cigarette smoking is a major risk factor for COPD and COPD severity. Previous genome-wide association studies (GWAS) have identified numerous single nucleotide polymorphisms (SNPs) associated with the number of cigarettes smoked per day (CPD) and a Dopamine Beta-Hydroxylase (DBH) locus associated with smoking cessation in multiple populations. Objective To identify SNPs associated with lifetime average and current CPD, age at smoking initiation, and smoking cessation in COPD subjects. Methods GWAS were conducted in 4 independent cohorts encompassing 3,441 ever-smoking COPD subjects (GOLD stage II or higher). Untyped SNPs were imputed using HapMap (phase II) panel. Results from all cohorts were meta-analyzed. Results Several SNPs near the HLA region on chromosome 6p21 and in an intergenic region on chromosome 2q21 showed associations with age at smoking initiation, both with the lowest p=2×10−7. No SNPs were associated with lifetime average CPD, current CPD or smoking cessation with p<10−6. Nominally significant associations with candidate SNPs within alpha-nicotinic acetylcholine receptors 3/5 (CHRNA3/CHRNA5; e.g. p=0.00011 for SNP rs1051730) and Cytochrome P450 2A6 (CYP2A6; e.g. p=2.78×10−5 for a nonsynonymous SNP rs1801272) regions were observed for lifetime average CPD, however only CYP2A6 showed evidence of significant association with current CPD. A candidate SNP (rs3025343) in the DBH was significantly (p=0.015) associated with smoking cessation. Conclusion We identified two candidate regions associated with age at smoking initiation in COPD subjects. Associations of CHRNA3/CHRNA5 and CYP2A6 loci with CPD and DBH with smoking cessation are also likely of importance in the smoking behaviors of COPD patients.

Objective-This prospective observational study explored the association of hypertensive disorders of pregnancy and small-for-gestational age (SGA) with obstructive sleep apnea (OSA) as determined by screening measures for OSA and sleep studies.Study Design-Two symptom-based screening questionnaires, the Berlin Questionnaire (BQ) and the Epworth Sleepiness Scale (ESS), were administered to enroll 1509 gravidae. Screen positive subjects were referred for polysomnography (PSG). The primary outcome was the occurrence of either gestational hypertension or preeclampsia.[a1]Generalized linear models (GLM) were used to estimate the relative risks of associations.Results-1157 subjects were available for outcomes analysis. Screening positive on the BQ was positively associated with hypertensive disorders in GLM models (aRR=1.90, 95%CI 1.52-2.37).Conclusion-In this large prospective trial, GLM modeling suggest that the BQ but not the ESS demonstrated significant association with measured adverse pregnancy outcomes, and specific items predicted these outcomes better than others. However, causative association of BQ with OSA cannot be assumed.

Scientific Knowledge on the Subject: COPD progresses over decades so little is known about longitudinal changes in individual patients, and whether there are different patterns of disease progression in different patient subgroups.What this Study Adds to the Field: Computational modelling of CT biomarkers suggests there are two patterns of disease progression in COPD. These disease progression patterns or 'subtypes' can be used to stratify individuals into two groups with distinct clinical characteristics, and to stage individuals along their disease time-course. Early stages of both subtypes are identifiable in a proportion of 'healthy smokers' providing a biomarker of early COPD.