The effect of increased collect pump rate on collection efficiency in hematopoietic progenitor cell collection by apheresis in allogeneic adult donors-A single center analysis.

BACKGROUND: Optimizing CD34 recovery while minimizing harm to hematopoietic progenitor cell donors by apheresis (HPC(A) donors) is critical to the success of allogeneic hematopoietic cell transplantation. We examined the efficacy and safety of starting allogeneic HPC(A) donors at a collect pump rate (CPR) of 2 mL/min on the Spectra Optia regardless of the inlet flow rate and/or pre-apheresis white blood cell (WBC) count (high CPR group). STUDY DESIGN AND METHODS: A single-center retrospective study was performed on allogeneic adult donors from 10/2020 to 12/2022. From 10/2020 to 6/19/2022, all donors had CPR of ~1 mL/min (historical group). High CPR group started 6/20/2022. RESULTS: During the study period, 412 donors were in historical group versus 196 (32.2%) in high CPR group. Median CD34 collection efficiency (CE) was higher and more consistent in high CPR group (55.1% vs. 53% in historical group, p < .0001) and remained significant in multivariate analysis. Although product volume was higher in high CPR group, WBC, hematocrit, and platelet concentrations were significantly lower. No difference in engraftment outcomes in patients receiving products from two groups was observed. Moreover, no differences occurred in a significant peri-procedural adverse event or percent decrease in platelets (6.87% decrease in platelets per 100 × 106 CD34 cells collected versus 6.66% in historical group, p = .89). Furthermore, high CPR group had ~26 min less in collection time for every 100 × 106 CD34 cells collected, resulting in less positive fluid balances. CONCLUSIONS: Starting allogeneic HPC(A) donor collection at a CPR of 2 mL/min is safe and effective.

A case-control study analyzing mannitol dosing for prevention of cisplatin-induced acute nephrotoxicity.

BACKGROUND: Mannitol is an osmotic diuretic given routinely as part of cisplatin regimens to prevent nephrotoxicity, but there are limited data on the ideal dosage. At our center, three different doses of mannitol are used: 12, 20, and 40 g per cycle for cisplatin doses of ≥50 mg/m2. The primary objective was to determine if variations in mannitol dosing significantly influence the incidence of cisplatin-induced acute nephrotoxicity. METHODS: A case-control study was performed. Electronic records of 1462 consecutive outpatients who received cisplatin at ≥ 50 mg/m2 per cycle between January 2010 and December 2014 were reviewed. Patients experiencing nephrotoxicity of any grade within 30 days of last cisplatin dose, as defined by NCI CTCAE 4.0, were matched to a minimum of two and maximum of five controls based on the following criteria: age ± 5 years, baseline estimated glomerular filtration rate ± 10 ml/min/1.73 m2, cisplatin dose per cycle, and presence of diabetes. Conditional logistic regression was used to identify baseline predictors of cisplatin-induced acute nephrotoxicity. RESULTS: Of the 1245 included patients, 237 had nephrotoxicity and 1008 were matched controls. Median baseline estimated glomerular filtration rate for cases and controls were 83 and 80 ml/min/1.73 m2, respectively. A total of 3.8% of cases experienced ≥ grade 3 nephrotoxicity. Univariable analysis showed that diabetes, lymphoma, low baseline estimated glomerular filtration rate, and low baseline magnesium level were significantly associated with nephrotoxicity, whereas mannitol dosing did not show any association (odds ratio 1.08; p = 0.29). In multivariable analysis, diabetes and lymphoma retained statistical significance, but baseline estimated glomerular filtration rate and baseline magnesium level showed nonsignificant associations with nephrotoxicity. CONCLUSIONS: Cisplatin-induced acute nephrotoxicity remains common in patients with good baseline renal function despite preventive measures. Diabetes and lymphoma are predictors of nephrotoxicity, whereas mannitol dosing has no significant influence, suggesting that doses may be standardized across cisplatin regimens.

Inhibition of dengue virus RNA synthesis by an adenosine nucleoside.

We recently reported that (2R,3R,4R,5R)-2-(4-amino-pyrrolo[2,3-d]pyrimidin-7-yl)-3-ethynyl-5-hydroxy-methyl-tetrahydro-furan-3,4-diol is a potent inhibitor of dengue virus (DENV), with 50% effective concentration (EC(50)) and cytotoxic concentration (CC(50)) values of 0.7 microM and >100 microM, respectively. Here we describe the synthesis, structure-activity relationship, and antiviral characterization of the inhibitor. In an AG129 mouse model, a single-dose treatment of DENV-infected mice with the compound suppressed peak viremia and completely prevented death. Mode-of-action analysis using a DENV replicon indicated that the compound blocks viral RNA synthesis. Recombinant adenosine kinase could convert the compound to a monophosphate form. Suppression of host adenosine kinase, using a specific inhibitor (iodotubercidin) or small interfering RNA (siRNA), abolished or reduced the compound's antiviral activity in cell culture. Studies of rats showed that (14)C-labeled compound was converted to mono-, di-, and triphosphate metabolites in vivo. Collectively, the results suggest that this adenosine inhibitor is phosphorylated to an active (triphosphate) form which functions as a chain terminator for viral RNA synthesis.

Prevalence of use and the risk of adverse effects associated with complementary and alternative medicine in a cohort of patients receiving warfarin.

BACKGROUND: The use of complementary and alternative medicine (CAM), including orally administered herbals, botanicals, vitamins, and supplements, may pose a risk to patients on warfarin therapy. OBJECTIVE: To estimate the prevalence of CAM use among patients taking warfarin and evaluate the impact of CAM exposure on the risk of warfarin-related adverse effects. METHODS: A survey was administered to hospital inpatients and clinic outpatients on drug exposure (including CAM) over the previous month, self-reported bleeding events, use of alcohol and vitamin K-rich foods, and medical conditions. Prescription medication use was verified, and laboratory records were checked for out-of-range international normalized ratios (INRs) (defined as INR >4 or <2). The use of CAM, including products with reported or theoretical interactions with warfarin, was compared between patients with and without self-reported bleeding or out-of-range INR. RESULTS: Among the 314 patients who completed the survey, 44.3% reported using CAM at least weekly. Potentially interacting CAM was used by 34.1% of all patients, or 18.2% if vitamin E was excluded as an interacting CAM. Vitamin E was used by 24.2% of all patients and 71.0% of those who used potentially interacting CAM. There was no significant difference in CAM use or consumption of vitamin K-rich foods between patients with and without INRs greater than 4 or for patients with and without INRs less than 2. CONCLUSIONS: The use of potentially interacting CAM in this cohort was higher than the use previously reported among patients on warfarin therapy. However, exposure to CAM was not associated with an increase in the risk of self-reported bleeding or out-of-range INR.

The Picture Multiple: Figuring, Thinking, and Knowing in Descartes's Essais (1637).

Throughout his Essais (1637), Descartes appropriated the visual language of practical mathematics in order to forge a new natural philosophy. This article argues that by grafting geometric line onto descriptive figure, the philosopher and his illustrator, Frans van Schooten Jr., underscored doubts about a natural philosophy based on qualities, all the while situating his new epistemology in the 17th-century present and exercising a deep attention to the differences between nature seen, nature pictured, and nature understood.

Effect of Misalignment between Hospital and Provincial Formularies on Medication Discrepancies at Discharge: PPITS (Proton Pump Inhibitor Therapeutic Substitution) Study.

BACKGROUND: Medication discrepancies may occur on admission, transfer, or discharge from hospital. Therapeutic interchange within a drug class is a common practice in hospitals, and orders for specific proton pump inhibitors (PPIs) are often substituted with the hospital's formulary PPI through therapeutic interchange protocols. Rabeprazole is the PPI on the formulary of the British Columbia PharmaCare program. However, different PPIs may appear on the formularies of the province's hospitals. This misalignment and use of therapeutic interchange may lead to increased rates of medication discrepancies at the time of discharge. OBJECTIVE: To evaluate the effect of formulary misalignment for PPIs between St Paul's Hospital in Vancouver and the British Columbia PharmaCare program and use of therapeutic interchange on the occurrence of medication discrepancies at discharge. METHODS: A cohort chart review was performed to compare discharge discrepancy rates for PPI orders between 2 periods: June 2006 to June 2008, when the same PPI appeared on the hospital and provincial formularies, and July 2008 to July 2010, when the designated PPIs differed between the hospital and provincial formularies. Data for the first study period were used to establish the baseline discharge discrepancy rate, and data for the later period represented the discharge discrepancy rate in the presence of misalignment between the hospital and PharmaCare formularies. RESULTS: The discharge discrepancy rate for PPIs was 27.3% (24/88) when the 2 formularies were aligned and 49.1% (81/165) when the formularies were misaligned. This represents an absolute increase of 21.8 percentage points in the risk of discharge discrepancies (95% confidence interval 9.8-33.9 percentage points; p < 0.001) when the hospital and provincial formularies were misaligned and the hospital's therapeutic interchange protocol was used. CONCLUSIONS: Misalignment between the PPIs specified in the hospital and provincial formularies, combined with use of therapeutic interchange, was associated with a significant increase in medication discrepancies at discharge.