Determinants of empiric transfusion in gastrointestinal bleeding in the emergency department.

INTRODUCTION: Current guidelines for the management of GI bleeding (GIB) recommend restrictive transfusion triggers unless patients have shock or specific comorbidities. However, these studies may not be applicable to Emergency Department (ED) patients. Factors determining transfusion decisions in the ED are poorly understood. We compared baseline characteristics and outcomes between ED patients with GI bleeding transfused at lower or higher empiric hemoglobin levels. METHODS: Single center, retrospective analysis of hospital records from a large tertiary care center of ED patients diagnosed with GIB who underwent red blood cell transfusion in the ED. A pre-transfusion hemoglobin cutoff of 7 g/dl was used to divide patients into restrictive and empirically transfused groups. Demographics, mortality, hospital length-of-stay, and mortality risk estimates were compared between groups. RESULTS: 175 patients met inclusion criteria, with 120 restrictive patients (68.5%) and 55 liberal patients (31.4%). The sample was 49.7% male, with mean age 67.2 years, similar between groups. Patients in the empiric transfusion group had more acute emergency severity index scores (2.09 vs. 2.3). No difference was found between groups in triage vital signs, pre-endoscopy Rockall scores or mortality estimates, or length of stay. Most common reasons for empiric transfusion from chart review were hypotension and witnessed large hemorrhage. CONCLUSIONS: Patients that were empirically transfused had similar presentations to patients meeting restrictive guidelines, based on review of triage data. Transfusions above restrictive thresholds occurred frequently in our population. Additional studies are required to clarify appropriate criteria to guide transfusions for GIB in the ED.

The Precision Resuscitation With Crystalloids in Sepsis (PRECISE) Trial: A Trial Protocol.

Importance: Intravenous fluids are an essential part of treatment in sepsis, but there remains clinical equipoise on which type of crystalloid fluids to use in sepsis. A previously reported sepsis subphenotype (ie, group D) has demonstrated a substantial mortality benefit from balanced crystalloids compared with normal saline. Objective: To test the hypothesis that targeting balanced crystalloids to patients with group D sepsis through an electronic health record (EHR) alert will reduce 30-day inpatient mortality. Design, Setting, and Participants: The Precision Resuscitation With Crystalloids in Sepsis (PRECISE) trial is a parallel-group, multihospital, single-blind, pragmatic randomized clinical trial to be conducted at 6 hospitals in the Emory Healthcare system. Patients with suspicion of group D infection in whom a clinician initiates an order for normal saline in the emergency department (ED) or intensive care unit (ICU) will be randomized to usual care and intervention arms. Intervention: An EHR alert that appears in the ED and ICUs to nudge clinicians to use balanced crystalloids instead of normal saline. Main Outcomes and Measures: The primary outcome is 30-day inpatient mortality. Secondary outcomes are ICU admission, in-hospital mortality, receipt of vasoactive drugs, receipt of new kidney replacement therapy, and receipt of mechanical ventilation (vasoactive drugs, kidney replacement therapy, and mechanical ventilation are counted if they occur after randomization and within the 30-day study period). Intention-to-treat analysis will be conducted. Discussion: The PRECISE trial may be one of the first precision medicine trials of crystalloid fluids in sepsis. Using routine vital signs (temperature, heart rate, respiratory rate, and blood pressure), available even in low-resource settings, a validated machine learning algorithm will prospectively identify and enroll patients with group D sepsis who may have a substantial mortality reduction from used of balanced crystalloids compared with normal saline. Results: On finalizing participant enrollment and analyzing the data, the study's findings will be shared with the public through publication in a peer-reviewed journal. Conclusions: With use of a validated machine learning algorithm, precision resuscitation in sepsis could fundamentally redefine international standards for intravenous fluid resuscitation. Trial Registration: ClinicalTrials.gov Identifier: NCT06253585.

Gender differences in lifetime alcohol dependence: results from the national epidemiologic survey on alcohol and related conditions.

BACKGROUND: An extensive clinical literature has noted gender differences in the etiology and clinical characteristics of individuals with alcohol dependence (AD). Despite this knowledge, many important questions remain. METHODS: Using the 2001 to 2002 National Epidemiologic Survey on Alcohol and Related Conditions (n = 43,093), we examined differences in sociodemographic characteristics, psychiatric and medical comorbidities, clinical correlates, risk factors, and treatment-utilization patterns of men (N = 2,974) and women (N = 1,807) with lifetime AD. RESULTS: Men with lifetime AD were more likely than women to be diagnosed with any substance use disorder and antisocial personality disorder, whereas women were more likely to have mood and anxiety disorders. After adjusting for sociodemographic characteristics and gender differences in psychiatric comorbidity in the general population, AD was associated with externalizing disorders and any mood disorder among women only. Men with AD met more criteria, had longer episodes, and were younger at the age of first drink. There were no gender differences in remission rates. Women with AD were more likely to have a family and a spouse with history of alcohol use disorders. Treatment rates were low for both genders, and women were more likely to report social stigmatization as a treatment barrier. CONCLUSIONS: There are important gender differences in the psychiatric comorbidities, risk factors, clinical characteristics, and treatment-utilization patterns among individuals with lifetime AD.

A concise synthesis and antimicrobial activities of 3-polyamino-23,24-bisnorcholanes as steroid-polyamine conjugates.

A series of steroid-polyamine conjugates were synthesized and evaluated for their antimicrobial activity. This study was focused on the effect of stereochemistry at the C-3 and C-5 of steroids and types of polyamine at C-3 on activity against various human pathogens. All the conjugates exhibited strong antimicrobial activities against Gram-positive strains. Compound 18 was found to be the most potent in these series with a MIC value as low as 1 µg/mL against the bacterium Staphylococcus aureus ATCC6538P.

Impact of Targeted Temperature Management on ED Patients with Drug Overdose-Related Cardiac Arrest.

INTRODUCTION: Drug overdose is the leading cause of non-traumatic out-of-hospital cardiac arrest (OHCA) among young adults. This study investigates whether targeted temperature management (TTM) improves hospital survival from presumed overdose-related cardiac arrest. METHODS: Retrospective chart review of consecutive cardiac arrests presenting to an urban tertiary care hospital ED from 2011 to 2015. ED patients with cardiac arrest were included if < 50 years old, and excluded if there was a non-overdose etiology (e.g., trauma, ST-elevation myocardial infarction, subarachnoid hemorrhage). The main intervention was TTM, carried out with a combination of the Arctic Sun device and refrigerated crystalloid/antipyretics (goal temperature 33-36 °C). The primary outcome was survival to hospital discharge; neurologically intact survival was the secondary outcome. RESULTS: Of 923 patients with cardiac arrest, 802 (86.9%) met exclusion criteria, leaving 121 patients for final analysis. There were 29 patients in the TTM group (24.0%) vs 92 patients in the non-TTM group (76.0%). Eleven patients (9.1%) survived to hospital discharge. TTM was associated with increased odds of survival to hospital discharge (OR 11.3, 95% CI 2.8-46.3, p < 0.001), which increased substantially when palliative outcomes were excluded from the cohort (OR 117.3, 95% CI 17.0-808.4, p < 0.001). Despite achieving statistical significance (OR 1.1, 95% CI 1.0-1.3), TTM had no clinically significant effect on neurologically intact survival. CONCLUSIONS: TTM was associated with improved survival in ED patients with presumed drug overdose-related cardiac arrest. The impact of TTM on neurologically intact survival among these patients requires further study.

Synthesis and antimicrobial activity of 7 alpha-amino-23,24-bisnor-5 alpha-cholan-22-ol derivatives.

A series of 7 alpha-aminobisnorsteroids were synthesized and their in vitro antimicrobial activity was evaluated regarding Gram-positive and Gram-negative bacteria. The stereoselective reductive amination of 7-ketosteroid 3 with NH(4)OAc, in the presence of NaBH(3)CN, afforded a high yield of 7 alpha-aminosteroid 4. The 3,7-diaminobisnorsteroids were obtained by the reductive amination of 4 with NH(4)OT(f), Boc-spermidine, and Boc-spermine. 3 alpha,7 alpha-Diaminobisnorsterol dihydrochloride 15 showed the highest antimicrobial activity against Streptococcus pyogenes 308 A with a MIC value of 1.6 microg/mL. Hemolytic activities of the compounds 13-20 were determined. Compound 13 showed MHC value at 100 microg/mL.

Pediatric infectious endophthalmitis: a review.

Infectious endophthalmitis is a rare but severe complication of septecemia, intraocular surgeries, or penetrating eye trauma. The etiology, prognosis, and management of pediatric endophthalmitis resulting from exogenous and endogenous infections are reviewed. Open-globe trauma and glaucoma surgery are the most frequent causes of endophthalmitis in children, whereas endogenous infection is the least common cause. Streptococcus and Staphylococcus species are common bacterial agents in both posttraumatic and postoperative pediatric endophthalmitis, whereas Candida albicans is a commonly reported organism in endogenous endophthalmitis. Additionally, Streptococcus pneumoniae and Haemophilus influenzae appear more likely as pathogens in children than in adults. The clinical manifestations and outcome usually correlate with the virulence of the infecting organism. The visual prognosis of endophthalmitis is generally poor.

Gender differences in cannabis use disorders: results from the National Epidemiologic Survey of Alcohol and Related Conditions.

BACKGROUND: To examine gender differences among individuals diagnosed with DSM-IV lifetime cannabis use disorder (CUD). METHODS: A nationally representative sample of U.S. adults aged 18 years or older that were diagnosed with lifetime CUD (n=3297): Men (n=2080), Women (n=1217). Data were drawn from the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC, n=43,093). The survey response rate was 81%. RESULTS: Nearly all individuals with CUD had a psychiatric comorbidity (95.6% of men, 94.1% of women). Men with lifetime CUD were more likely than women to be diagnosed with any psychiatric disorder, any substance use disorder and antisocial personality disorder, whereas women with CUD had more mood and anxiety disorders. After adjusting for gender differences in sociodemographic correlates and the prevalence of psychiatric disorders in the general population, women with CUD were at greater risk for externalizing disorders. Men with CUD met more criteria for cannabis abuse, had longer episodes of CUD, smoked more joints, and were older at remission when compared to women with CUD. Women experienced telescoping to CUD. Treatment-seeking rates were very low for both genders, and there were no gender differences in types of services used or reasons for not seeking treatment. CONCLUSIONS: There are important gender differences in the clinical characteristics and psychiatric comorbidities among individuals with CUD.

Cross metathesis assisted solid-phase synthesis of glycopeptoids.

A solid-phase synthesis of glycopeptoids was explored through olefin cross metathesis (CM). Peptoids and sugar derivatives with appropriate olefin moieties were coupled in the presence of an olefin metathesis catalyst to afford glycopeptoids in good yields. This systematic solid-phase CM study can provide facile access to the molecular sources of glycopeptidomimetics and postchemical modifications on various molecular scaffolds.

Ring-closing metathesis approaches for the solid-phase synthesis of cyclic peptoids.

Cyclic peptoids were efficiently synthesized on a solid phase in high yields utilizing ring-closing metathesis (RCM). This method should be a valuable tool for easy access to cyclic peptoid libraries and various cyclic compounds.

Generalizability of clinical trials for cannabis dependence to community samples.

There is growing concern that results of tightly controlled clinical trials may not generalize to broader community samples. To assess the proportion of community dwelling adults with cannabis dependence who would have been eligible for a typical cannabis dependence treatment study, we applied a standard set of eligibility criteria commonly used in cannabis outcome studies to a large (N=43,093) representative US adult sample interviewed face-to-face, the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). Approximately 80% of the community sample of adults with a diagnosis of cannabis dependence (N=133) would be excluded from participating in clinical trials by one or more of the common eligibility criteria. Individual study criteria excluded from 0% to 41.0% of the community sample. Legal problems, other illicit drug use disorders, and current use of fewer than 5 joints/week excluded the largest percentage of individuals. These results extend to cannabis dependence concerns that typical clinical trials likely exclude most community dwelling adults with the disorder. The results also support the notion that clinical trials tend to recruit highly selective samples, rather than adults who are representative of typical patients. Clinical trials should carefully evaluate the effects of eligibility criteria on the generalizability of their results. Even in efficacy trials, stringent exclusionary criteria could limit the representativeness of study results.

Synthesis and antimicrobial activity of 7-fluoro-3-aminosteroids.

A series of 7-fluoro-3-aminosteroids were synthesized and their in vitro antimicrobial activities were evaluated against Gram-positive and Gram-negative bacteria. The nucleophilic fluorination of several 7beta-hydroxysteroids by diethylaminosulfur trifluoride in n-pentane, followed by reductive amination of the resulting 7-fluoro-3-ketosteroids with spermidine in the presence of NaBH(3)CN, afforded 7-fluoro-3-aminosteroids in high yield. Compound 25 showed the highest antimicrobial activity against Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus pyogenes, and Escherichia coli.