Penicillin-Susceptible Streptococcus pneumoniae Meningitis in Adults: Does the Ceftriaxone Dosing Matter?

The recommended empiric ceftriaxone dosing regimen for acute bacterial meningitis in adults is 2 g every 12 h. After penicillin-susceptible Streptococcus pneumoniae is isolated as a causative microorganism, the ceftriaxone dose may be continued or reduced to a single dose of 2 g every 24 h, per institutional preference. There is no clear guidance that indicates the superiority of one regimen over the other. The objective of this study was to evaluate the susceptibility of S. pneumoniae in the cerebral spinal fluid (CSF) of patients with meningitis and the relationship between ceftriaxone dose and clinical outcomes. We identified 52 patients with S. pneumoniae meningitis with positive CSF cultures who were treated at the University Hospital, Bern, Switzerland, over a 19-year period. We collected clinical and microbiological data for evaluation. Broth microdilution and Etest methods were performed to test penicillin and ceftriaxone susceptibility. All isolates were susceptible to ceftriaxone. Ceftriaxone was empirically used in 50 patients, with a starting dosing regimen of 2 g every 24 h in 15 patients and 2 g every 12 h in 35 patients. In 32 patients started on a twice-daily regimen (91%), doses were reduced to once daily after a median of 1.5 (95% CI 1-2) days. The overall in-hospital mortality was 15.4% (n = 8), and 45.7% of patients reported at least one sequela of meningitis at the last follow-up (median 375, 95% CI 189-1585 days). We found no statistical difference in outcome between the 2 g every 24 h and the 2 g every 12 h ceftriaxone dosing regimens. A ceftriaxone total daily dose of 2 g may be associated with similar outcomes to a 4 g total daily dose, provided that the causative organism is highly susceptible to ceftriaxone. The persistence of neurological and infection sequelae at the last follow-up underscores the need for optimal treatment of these complex infections

A Novel Fluorescent Clinical Method to Rapidly Quantify Plasma Volume

Objectives To determine the performance of a rapid fluorescent indicator technique for measuring plasma volume (PV). Methods This was an open-label, observational evaluation of a two-component intravenous visible fluorescent dye technique to rapidly measure PV in 16 healthy subjects and 16 subjects with chronic kidney disease (8 stage 3 and 8 stage 4 CKD), at 2 clinical research sites. The method consisted of a single intravenous injection of 12 mg of a large 150-kDa carboxy-methyl dextran conjugated to a fluorescent rhodamine-derived dye as the PV marker (PVM), and 35 mg of a small 5-kDa carboxy-methyl dextran conjugated to fluorescein, the renal clearance marker. Dye concentrations were quantified 15 min after the injections for initial PV measurements using the indicator-dilution principle. Additional samples were taken over 8 h to evaluate the stability of the PVM as a determinant of PV. Blood volumes (BV) were calculated based on PV and the subject’s hematocrit. Pharmacokinetic parameters were calculated from the plasma concentration data taken over several days using noncompartmental methods (Phoenix WinNonlin®). Linear correlation and Bland-Altman plots were used to compare visible fluorescent injectate-measured PV compared to Nadler’s formula for estimating PV. Finally, 8 healthy subjects received 350 mL infusion of a 5% albumin solution in normal saline over 30 min and a repeat PV determination was then carried out. Results PV and BV varied according to weight and body surface area, with PV ranging from 2,115 to 6,234 mL and 28.6 to 41.9 mL/kg when weight adjusted. Both parameters were stable for > 6 h with repeated plasma measurements of the PVM. There was no difference between healthy subjects and CKD subjects. Overall, there was general agreement with Nadler’s estimation formula for the mean PV in subjects. A 24-h repeat dose measurement in 8 healthy subjects showed PV variability of 98 ± 121 mL (mean = 3.8%). Additionally, following an intravenous bolus of 350 mL of a 5% albumin solution in normal saline in 8 healthy subjects, the mean (SD) measured increase in PV was 356 (±50.0) mL post-infusion. There were no serious adverse events reported during the study. Conclusions This minimally invasive fluorescent dye approach safely allowed for rapid, accurate, and reproducible determination of PV, BV, and dynamic monitoring of changes following fluid administration

Early machine learning prediction of hospitalized patients at low risk of respiratory deterioration or mortality in community-acquired pneumonia: Derivation and validation of a multivariable model

Current prognostic tools for pneumonia predominantly focus on mortality, often neglecting other crucial outcomes such as the need for advanced respiratory support. The objective of this study was to develop and validate a tool that predicts the early risk of non-occurrence of respiratory deterioration or mortality. We conducted a single-center, retrospective cohort study involving hospitalized adult patients with community-acquired pneumonia (CAP) and acute hypoxic respiratory failure from January 2009 to December 2019 (n = 4379). We employed the gradient boosting machine (GBM) learning to create a model that estimates the likelihood of patients requiring advanced respiratory support (high flow nasal cannula [HFNC], non-invasive mechanical ventilation [NIMV], and invasive mechanical ventilation [IMV]) or facing mortality during hospitalization. This model utilized readily available data including demographic, physiologic, and laboratory data, sourced from electronic health records and obtained within the first six hours of admission. Out of the cohort, 890 patients (25.2%) either required advanced respiratory support or died during their hospital stay. Our predictive model displayed superior discrimination and higher sensitivity (cross-validation C-statistic = 0.71; specificity = 0.56; sensitivity = 0.72) compared to the pneumonia severity index (PSI) (C-statistic = 0.65; specificity = 0.91; sensitivity = 0.24; P value < 0.001), while maintaining a negative predictive value (NPV) of approximately 0.85. These data demonstrate that our machine learning model predicted the non-occurrence of respiratory deterioration or mortality among hospitalized CAP patients more accurately than the PSI. The enhanced sensitivity of this model holds potential for reliably excluding low-risk patients from pneumonia clinical trials

PRN OPINION PAPER: Application of precision medicine across pharmacy specialty areas

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149551/1/jac51107_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149551/2/jac51107.pd

Controversies in acute kidney injury: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) conference

In 2012, Kidney Disease: Improving Global Outcomes (KDIGO) published a guideline on the classification and management of acute kidney injury (AKI). The guideline was derived from evidence available through February 2011. Since then, new evidence has emerged that has important implications for clinical practice in diagnosing and managing AKI. In April of 2019, KDIGO held a controversies conference entitled Acute Kidney Injury with the following goals: determine best practices and areas of uncertainty in treating AKI; review key relevant literature published since the 2012 KDIGO AKI guideline; address ongoing controversial issues; identify new topics or issues to be revisited for the next iteration of the KDIGO AKI guideline; and outline research needed to improve AKI management. Here, we present the findings of this conference and describe key areas that future guidelines may address

Repensar els estudis catalans des de la teoria queer

Catalan Studies are basically focused on national/linguistic identity, but recent debate on Catalan identity triggered by the current pro-independent process in Catalonia, may help reshape this academic field. A more diverse approach to Catalan culture should consider sexuality, which has traditionally been banished from literary analysis as a ‘private’ matter. Here, we discussed how queer theory can reframe Catalan Studies mainly by building a specific LGBT literary tradition, identifying queer episodes and characters in the canon, questioning received meanings, promoting interdisciplinary analysis of Catalan culture and exploring the role of queer subjectivity in history

Satellite Remote Sensing: A Tool to Support Harmful Algal Bloom Monitoring and Recreational Health Advisories in a California Reservoir.

Cyanobacterial harmful algal blooms (cyanoHABs) can harm people, animals, and affect consumptive and recreational use of inland waters. Monitoring cyanoHABs is often limited. However, chlorophyll-a (chl-a) is a common water quality metric and has been shown to have a relationship with cyanobacteria. The World Health Organization (WHO) recently updated their previous 1999 cyanoHAB guidance values (GVs) to be more practical by basing the GVs on chl-a concentration rather than cyanobacterial counts. This creates an opportunity for widespread cyanoHAB monitoring based on chl-a proxies, with satellite remote sensing (SRS) being a potentially powerful tool. We used Sentinel-2 (S2) and Sentinel-3 (S3) to map chl-a and cyanobacteria, respectively, classified chl-a values according to WHO GVs, and then compared them to cyanotoxin advisories issued by the California Department of Water Resources (DWR) at San Luis Reservoir, key infrastructure in Californias water system. We found reasonably high rates of total agreement between advisories by DWR and SRS, however rates of agreement varied for S2 based on algorithm. Total agreement was 83% for S3, and 52%-79% for S2. False positive and false negative rates for S3 were 12% and 23%, respectively. S2 had 12%-80% false positive rate and 0%-38% false negative rate, depending on algorithm. Using SRS-based chl-a GVs as an early indicator for possible exposure advisories and as a trigger for in situ sampling may be effective to improve public health warnings. Implementing SRS for cyanoHAB monitoring could fill temporal data gaps and provide greater spatial information not available from in situ measurements alone

Cystatin C: A Primer for Pharmacists

Pharmacists are at the forefront of dosing and monitoring medications eliminated by or toxic to the kidney. To evaluate the effectiveness and safety of these medications, accurate measurement of kidney function is paramount. The mainstay of kidney assessment for drug dosing and monitoring is serum creatinine (SCr)-based estimation equations. Yet, SCr has known limitations including its insensitivity to underlying changes in kidney function and the numerous non-kidney factors that are incompletely accounted for in equations to estimate glomerular filtration rate (eGFR). Serum cystatin C (cysC) is a biomarker that can serve as an adjunct or alternative to SCr to evaluate kidney function for drug dosing. Pharmacists must be educated about the strengths and limitations of cysC prior to applying it to medication management. Not all patient populations have been studied and some evaluations demonstrated large variations in the relationship between cysC and GFR. Use of eGFR equations incorporating cysC should be reserved for drug management in scenarios with demonstrated outcomes, including to improve pharmacodynamic target attainment for antibiotics or reduce drug toxicity. This article provides an overview of cysC, discusses evidence around its use in medication dosing and in special populations, and describes practical considerations for application and implementation

Satellite Remote Sensing: A Tool to Support Harmful Algal Bloom Monitoring and Recreational Health Advisories in a California Reservoir

Abstract Cyanobacterial harmful algal blooms (cyanoHABs) can harm people, animals, and affect consumptive and recreational use of inland waters. Monitoring cyanoHABs is often limited. However, chlorophyll‐a (chl‐a) is a common water quality metric and has been shown to have a relationship with cyanobacteria. The World Health Organization (WHO) recently updated their previous 1999 cyanoHAB guidance values (GVs) to be more practical by basing the GVs on chl‐a concentration rather than cyanobacterial counts. This creates an opportunity for widespread cyanoHAB monitoring based on chl‐a proxies, with satellite remote sensing (SRS) being a potentially powerful tool. We used Sentinel‐2 (S2) and Sentinel‐3 (S3) to map chl‐a and cyanobacteria, respectively, classified chl‐a values according to WHO GVs, and then compared them to cyanotoxin advisories issued by the California Department of Water Resources (DWR) at San Luis Reservoir, key infrastructure in California's water system. We found reasonably high rates of total agreement between advisories by DWR and SRS, however rates of agreement varied for S2 based on algorithm. Total agreement was 83% for S3, and 52%–79% for S2. False positive and false negative rates for S3 were 12% and 23%, respectively. S2 had 12%–80% false positive rate and 0%–38% false negative rate, depending on algorithm. Using SRS‐based chl‐a GVs as an early indicator for possible exposure advisories and as a trigger for in situ sampling may be effective to improve public health warnings. Implementing SRS for cyanoHAB monitoring could fill temporal data gaps and provide greater spatial information not available from in situ measurements alone