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Study Objective: To compare guideline‐based fluid resuscitation and need for respiratory support escalation in septic patients with pulmonary hypertension (PH) to those without PH. Design: Single‐center, retrospective cohort study. Setting: Tertiary care academic medical center in Detroit, Michigan. Patients: Adult patients with or without PH hospitalized and diagnosed with sepsis from November 1, 2013 through December 31, 2019. Patients with sepsis were assigned to one of two groups based on a previous PH diagnosis or no PH diagnosis. Intervention: None. Measurements and Main Results: The primary outcome was incidence of respiratory support escalation within 72 h from sepsis time zero. Respiratory support escalation included high‐flow nasal cannula, bilevel positive airway pressure, or intubation. One‐hundred and four patients were included with 52 patients in each study group. Patients with PH were more likely to require escalation of respiratory support compared to non‐PH patients (32.7% vs. 11.5%; p = 0.009). Fewer patients with PH received 30 mL/kg of crystalloid within 6 h of time zero compared with non‐PH patients (3.8% vs. 42.3%; p < 0.001). Vasopressor initiation was more common in patients with PH compared with the non‐PH group (40.4% vs. 19.2%; p = 0.018). PH diagnosis was the only independent predictor of respiratory support escalation. Conclusions: During initial sepsis management when compared with patients without PH, patients with PH had increased instances of respiratory support escalation within 72 h of sepsis time zero despite lower fluid resuscitation volumes. [ABSTRACT FROM AUTHOR]

Background The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) BA.2/BA.2.12.1 and BA.4/BA.5 subvariants have mutations associated with increased capacity to evade immunity when compared with prior variants. We evaluated mRNA monovalent booster dose effectiveness among persons ≥5 years old during BA.2/BA.2.12.1 and BA.4/BA.5 predominance. Methods A test-negative, case-control analysis included data from 12 148 pharmacy SARS-CoV-2 testing sites nationwide for persons aged ≥5 years with ≥1 coronavirus disease-2019 (COVID-19)-like symptoms and a SARS-CoV-2 nucleic acid amplification test from April 2 to August 31, 2022. Relative vaccine effectiveness (rVE) was estimated comparing 3 doses of COVID-19 mRNA monovalent vaccine to 2 doses; for tests among persons ≥50 years, rVE estimates also compared 4 doses to 3 doses (≥4 months since third dose). Results A total of 760 986 test-positive cases and 817 876 test-negative controls were included. Among individuals ≥12 years, rVE of 3 versus 2 doses ranged by age group from 45% to 74% at 1-month post vaccination and waned to 0% by 5–7 months post vaccination during the BA.4/BA.5 period. Adults aged ≥50 years (fourth dose eligible) who received 4 doses were less likely to have symptomatic SARS-CoV-2 infection compared with those with 3 doses; this rVE remained >0% through at least 3 months since last dose. For those aged ≥65 years, rVE of 4 versus 3 doses 1-month post vaccination was higher during BA.2/BA.2.12.1 (rVE = 49%; 95% confidence interval [CI], 43%–53%) than BA.4/BA.5 (rVE = 40%; 95% CI, 36%–44%). In 50- to 64-year-olds, rVE estimates were similar. Conclusions Monovalent mRNA booster doses provided additional protection against symptomatic SARS-CoV-2 infection during BA.2/BA.2.12.1 and BA.4/BA.5 subvariant circulation, but protection waned over time. [ABSTRACT FROM AUTHOR]

In this study, we mapped achievement levels from the National Assessment of Educational Progress (NAEP) onto the score scales for selected assessments from the Trends in International Mathematics and Science Study (TIMSS) and the Program for International Student Achievement (PISA). The mapping was conducted on NAEP, TIMSS, and PISA Mathematics assessments in 2003. A focus of the study was on whether the NAEP achievement levels were set too high. The results indicated that students from many other countries had substantially larger percentages of students meeting NAEP mathematics achievement levels. In general, the findings suggest the NAEP standard for Advanced is high, but not too high when considered within an international context. With respect to the NAEP standard of Proficient, none of the top-performing countries approached 100% proficient, which seems to underscore the different conceptualizations of "Proficient" in NAEP and No Child Left Behind. (Contains 3 footnotes, 6 tables, and 1 figure.)

Inborn errors of metabolism (IEMs) or metabolic disorders are complex conditions involving abnormalities in biochemical and metabolic pathways necessary for healthy human existence. They are often caused by partial or total deficiency of key enzymes and these conditions usually present in infancy or early childhood. Some may not be identified until adolescence or even during the adult years. This discussion reviews some of the IEMs that can become evident in the adolescent years, such as adrenoleukodystrophy, glycogen storage diseases, lysosomal storage diseases, urea cycle disorders, and others. Management focuses on symptomatic treatment and when available as well as affordable, enzyme replacement therapies. Gene therapy and stem cell transplantation are options under current research in addition to finding more replacement enzymes. [ABSTRACT FROM AUTHOR]

Treprostinil diolamine is the first oral dosage preparation of a prostacyclin analogue for use in treatment naive pulmonary arterial hypertension (PAH). This case series and review of the available literature describes the experience of patients with PAH receiving treprostinil by intravenous (IV), subcutaneous (SQ), or inhalation route who were transitioned to treprostinil diolamine. At our institution, 3 patients were transitioned to treprostinil diolamine who received treprostinil administered by each of the alternative routes: IV, SQ, and inhalation. All patients tolerated the transition without significant worsening of disease end points. In the literature, 5 additional reports representing 48 patients were transitioned to treprostinil diolamine from an alternate route of administration. A majority (92%) of patients were hospitalized during the cross-titration phase and tolerated the transition without changes in disease markers or significant adverse effect. Six (13%) patients required reinitiation of parenteral therapy due to clinical decline. The most common dosing frequency utilized for treprostinil diolamine was 3 times per day. In patients with stable PAH receiving parenteral or inhaled treprostinil, a transition to treprostinil diolamine was a safe approach in a highly select population meeting clinical end points. Additional studies are required to further describe this clinical strategy before accepted in clinical practice. [ABSTRACT FROM AUTHOR]

Zachary R. Smith Abstract The secular experience of Sunday in the rhetoric of rock 'n' roll (sex, drugs and subversion) proves Eliade's formulation of the profane readily encapsulates with the [...]

Impella devices are percutaneously inserted ventricular assist devices which require a continuous purge solution that contains heparin to prevent pump thrombosis and device failure. We describe 2 patients with heparin-induced thrombocytopenia (HIT) supported with an Impella device utilizing an argatroban-based purge solution. Case 1 involved an 83-year-old female with biventricular failure which resulted in right ventricle Impella support. The purge solution was changed to include argatroban due to concern of device clotting in the setting of HIT. Case 2 involved a 55-year-old male with worsening cardiogenic shock which resulted in left ventricle Impella support. Due to decreased purge flow rates and concerns for clotting, argatroban was added to the purge solution. Both patients’ total argatroban regimens were monitored and adjusted by pharmacy, resulting in therapeutic anticoagulation without any major bleeding or thrombotic events. Subsequently, a protocol was designed and implemented. These case reports appear to demonstrate the safe and effective use of argatroban purge solutions for the necessary anticoagulation with an Impella device. Further studies are needed to confirm these results and determine the optimal dosing regimen. [ABSTRACT FROM AUTHOR]