A pooled subgroup analysis of glucarpidase treatment in 86 pediatric, adolescent, and young adult patients receiving high-dose methotrexate therapy in open-label trials.

BACKGROUND: Delayed methotrexate elimination can occur in patients undergoing high-dose methotrexate cancer treatment. Effectiveness of glucarpidase for rapidly reducing methotrexate concentrations was shown in compassionate-use trials in patients aged 0-84 years. METHODS: We performed post hoc analyses of infants (≥28 days to <2 years), children (≥2 to <12 years), adolescents (≥12 to <15 years), and young adults (≥15 to <25 years) from four multicenter, open-label, single-arm, glucarpidase compassionate-use trials. Patients had toxic methotrexate levels due to delayed methotrexate elimination and/or renal dysfunction, and received glucarpidase (50 U/kg). The primary endpoint was clinically important reduction (CIR) in plasma methotrexate (methotrexate ≤1 µmol/L at all post-glucarpidase measurements) based on high-performance liquid chromatography. RESULTS: Among 86 patients included in efficacy analyses, CIR was achieved by zero of one infant (0.0%), five of 16 children (31.3%), seven of 24 adolescents (29.2%), and 26/45 young adults (57.8%). Median methotrexate reduction was 98.7% or higher in each group 15 minutes post-glucarpidase. Patients with pre-glucarpidase methotrexate less than 50 µmol/L (35/42, 83.3%) were more likely to achieve CIR than those with methotrexate 50 µmol/L or higher (1/37, 2.7%). The most common treatment-related adverse event was paresthesia, occurring in three adolescents (4.5%) and six young adults (5.2%). No other treatment-related adverse event occurred in 5% or higher of any age group. CONCLUSION: After accounting for pre-glucarpidase methotrexate levels, glucarpidase efficacy at inducing CIR in pediatric/young adult patients was consistent, with efficacy observed in the overall study population (i.e., patients aged 0-84), and no unexpected safety findings were observed. These findings demonstrate glucarpidase (50 U/kg) is an effective and well-tolerated dose for pediatric, adolescent, and young adult patients.

Glucarpidase for Treating Adults with Delayed Methotrexate Elimination Due to Impaired Renal Function: An Economic Simulation Analysis.

Background: Glucarpidase is indicated for treating delayed methotrexate (MTX) elimination due to impaired renal function. Although glucarpidase is capable of rapidly eliminating MTX independent of renal clearance, its cost can be perceived as a barrier to use. However, no published economic analyses have evaluated glucarpidase relative to comparable treatments. Purpose: To assess the economic value of glucarpidase for treating adult patients in the United States (US) who experience delayed MTX elimination due to impaired renal function. Methods: A decision tree model was developed to assess the economic value of glucarpidase. The short-term inpatient management of patients as well as long-term survival were simulated. Costs associated with the use of glucarpidase were compared against other methods for treating delayed MTX elimination due to impaired renal function under two scenarios: current practice (ie, mix of timely/delayed use of glucarpidase, hemodialysis, or supportive care [SC] alone) as compared with proposed practice (ie, timely glucarpidase administration within 60 hours for all eligible patients). Hypothetical practical scenarios for US institutions were also considered. Results: For adult patients with delayed MTX elimination, proposed practice as compared to current practice was associated with an increased cost of $20,024 per patient, not considering any incremental reimbursement associated with glucarpidase administration. Importantly, early treatment with glucarpidase, within 60 hours, was shown to be less expensive per patient than delayed glucarpidase treatment or treating with hemodialysis, but more expensive than SC alone. However, proposed practice was associated with multiple clinical benefits, including shorter hospital length of stay. For hypothetical practical scenarios, minimal shifts in treatment patterns had minimal cost impacts. Conclusion: Treatment of all eligible patients with glucarpidase within 60 hours was associated with an increased cost per patient (relative to current practice) but substantial improvements in clinical outcomes. Timely glucarpidase use was less expensive than delayed glucarpidase or hemodialysis.

Acne Information on Instagram: Quality of Content and the Role of Dermatologists on Social Media.

While it is evident that many patients turn to social media for information about skin care, the quality and content of available information are not well characterized. In this study, we investigated acne-related information available on Instagram, one of the most popular social media platforms. We searched for the “top” Instagram posts using the hashtag #acne and characterized them based on their source and content. Posts were excluded if they were unrelated, not in English, or duplicates. 900 posts were assessed, and 439 were included. A majority of the content (258 posts) was generated by influencers, followed by retailers (97) and non-dermatologist providers (67). Dermatologists were responsible for 17 posts, accounting for <4% of the included content. 124 separate ingredients were mentioned as potential acne treatments. The ingredients with the most mention were beta-hydroxy acids (eg, salicylic acid), alpha-hydroxy acids (eg, glycolic acid), vitamin C, niacinamide, and sunscreen. 254 posts recommended at least one specific intervention, and among these posts only 11% referenced a treatment with grade A evidence based on American Academy of Dermatology guidelines. A vast amount of content is readily available to patients on this platform. This content is heterogeneous in message and quality, and dermatologists are responsible for only a small portion of it. J Drugs Dermatol. 2022;21(3): doi:10.36849/JDD.6411.

Reflectance Confocal Microscopy, Optical Coherence Tomography, and Multiphoton Microscopy in Inflammatory Skin Disease Diagnosis.

BACKGROUND AND OBJECTIVES: Technological advances in medicine have brought about many novel skin imaging devices. This review aims to evaluate the scientific evidence supporting the use of noninvasive optical imaging techniques to aid in the diagnosis and prognosis of inflammatory skin diseases. STUDY DESIGN/MATERIALS AND METHODS: PubMed and Scopus were searched in September 2020 according to PRISMA guidelines for articles using reflectance confocal microscopy (RCM), optical coherence tomography (OCT), and multiphoton microscopy (MPM) in inflammatory skin diseases, excluding studies monitoring treatment efficacy. RESULTS: At the time of the study, there were 66 articles that addressed the utilization of noninvasive imaging in interface, spongiotic, psoriasiform, vesiculobullous, and fibrosing/sclerosing inflammatory skin dermatoses: RCM was utilized in 46, OCT in 16, and MPM in 5 articles. RCM was most investigated in psoriasiform dermatoses, whereas OCT and MPM were both most investigated in spongiotic dermatoses, including atopic dermatitis and allergic contact dermatitis. CONCLUSIONS: There is preliminary evidence to support the diagnostic potential of noninvasive optical imaging techniques in inflammatory skin diseases. Improvements in the devices and further correlation with histology will help broaden their utility. Additional studies are needed to determine the parameters for diagnostic features, disease differentiation, and staging of inflammatory skin conditions. Lasers Surg. Med. © 2021 Wiley Periodicals LLC.

Improving the patient discharge process: implementing actions derived from a soft systems methodology study.

In the period from January 2013 to July 2014, three process change initiatives were undertaken at a major UK hospital to improve the patient discharge process. These initiatives were inspired by the findings of a study of the discharge process using Soft Systems Methodology. The first initiative simplified time-consuming paperwork and the second introduced more regular reviews of patient progress through daily multi-disciplinary "Situation Reports". These two initiatives were undertaken in parallel across the hospital, and for the average patient they jointly led to a 41% reduction between a patient being declared medically stable and their being discharged from the hospital. The third initiative implemented more proactive alerting of Social Care Practitioners to patients with probable social care needs at the front door, and simplified capture of important patient information (using a "SPRING" form). This initiative saw a 20% reduction in total length of stay for 88 patients on three wards where the SPRING form was used, whilst 248 patients on five control wards saw no significant change in total length of stay in the same period. Taken together, these initiatives have reduced total length of stay by 67% from 55.8 days to 18.6 days for the patients studied.

Length of stay, mortality, and readmissions among Medicare cancer patients treated with glucarpidase and conventional care: a retrospective study.

PURPOSE: Glucarpidase (Voraxaze) is used to treat methotrexate (Mtx) toxicity in patients with delayed Mtx clearance due to impaired renal function. We examine hospital length of stay (LOS), mortality, and readmission rates for Medicare cancer patients with delayed clearance of Mtx treated with glucarpidase. METHODS: Using 2010-2017 Medicare claims data, we identified glucarpidase patients as those hospitalized with indications of select lymphomas or leukemia, inpatient chemotherapy, and glucarpidase treatment. We assessed outcomes of glucarpidase patients relative to those experienced by patients treated for presumed Mtx toxicity using other therapies. These nonglucarpidase patients were identified with a diagnosis of primary central nervous system lymphoma, indications of cancer-chemotherapy toxicity, and acute kidney injury during hospitalization (not present on admission), and were divided into two groups: treated with dialysis (dialysis+) and treated with or without dialysis (dialysis+/-). Inverse-probability treatment weighting using propensity scores was used to adjust for differences between groups. RESULTS: Patients treated with glucarpidase (n=30) had an average LOS of 14.7 days. They had inpatient, 30-day, and 90-day mortality rates of 3.3%, 13.3%, and 16.7%, respectively, and a 90-day all-cause unplanned readmission rate of 24.1%. The dialysis+ and dialysis+/- groups, respectively, had higher average LOS (40.2, 21.9), higher inpatient mortality (50.6%, 20.8%), and higher 90-day mortality (58.6%, 37.6%). No statistically significant differences in 30-day mortality or 90-day readmission rates were detected between the glucarpidase group and either of the nonglucarpidase groups. Unobservable differences in patient severity may impact the interpretation of our findings. CONCLUSION: Medicare cancer patients with presumed Mtx toxicity receiving conventional treatment experience long hospitalizations, high intensive-care unit use and high mortality. Glucarpidase patients had lower LOS, inpatient mortality, and 90-day mortality than the non-glucarpidase patients.

Progressive reticulate skin pigmentation and anonychia in a patient with bone marrow failure.

KEY TEACHING POINTS.

Self-Healing and Self-Care for Nurses.

The potential effects of self-care techniques to increase nurses' effectiveness and influence positive patient care outcomes have often been underestimated. Today, nurses experience increased stress as a result of more work hours and greater patient loads. Research studies demonstrate the value to an organization and to individuals of educating nurses about self-care. Studies also show that how being aware of individual reaction patterns is vital to learning more effective coping mechanisms. In this article, we discuss the aspects of body, mind, emotions, and spirit as they relate to self-care; present self-care change techniques; and offer some practical self-care exercises. Most self-care skills can be learned and implemented in a short period of time. Nurses are encouraged to experiment with the various techniques to determine the most effective ones for them.

Conscious Leadership.

Health care leaders need to use leadership methodologies that support safe patient care, satisfy employees, and improve the bottom line. Conscious leaders help create desirable personal and professional life experiences for themselves using specific tools that include mindfulness, context, and the observer-self, and they strive to help their employees learn to use these tools as well. In perioperative nursing, conscious leaders create an environment in which nurses are supported in their aim to provide the highest level of patient care and in which transformations are encouraged to take place; this environment ultimately promotes safety, contributes to fulfilling and meaningful work, and enhances a facility's financial viability. This article discusses some of the key concepts behind conscious leadership, how perioperative leaders can reach and maintain expanded consciousness, and how they can best assist their staff members in their own evolution to a more mindful state.

Digoxin Toxicity and Use of Digoxin Immune Fab: Insights From a National Hospital Database.

OBJECTIVES: This study was developed to determine contemporary management of digoxin toxicity and clinical outcomes. BACKGROUND: Although the use of digoxin in heart failure management has declined, toxicity remains a prevalent complication. METHODS: The Premier Perspective Comparative Hospital Database (Premier Inc., Charlotte, North Carolina) was used to retrospectively identify patients diagnosed with digoxin toxicity and/or who received digoxin immune fab (DIF) over a 5-year period (2007 to 2011). DIF was evaluated using treatment date, number of vials administered, and total cost. Clinical outcomes included length of stay (total hospitalization; days after DIF), cost of hospitalization, and in-hospital mortality. Exploratory multivariate analyses were conducted to determine predictors of DIF and effect on length of stay, adjusting for patient characteristics and selection bias. RESULTS: Digoxin toxicity diagnosis without DIF treatment accounted for 19,543 cases; 5,004 patients received DIF of whom 3086 had a diagnosis of toxicity. Most patients were >65 years old (88%). The predictors of DIF use were urgent/emergent admission, hyperkalemia, arrhythmia associated with digoxin toxicity, acute renal failure, or suicidal intent (odds ratios 1.7, 2.4, 3.6, 2.1, and 3.7, respectively; p < 0.0001 for all). The majority (78%) of DIF was administered on days 1 and 2 of the hospitalization; 10% received treatment after day 7. Digoxin was used after DIF administration in 14% of cases. Among patients who received DIF within 2 days of admission, there was no difference for in-hospital mortality or length of stay compared with patients not receiving DIF. CONCLUSIONS: Digoxin toxicity diagnoses are clustered in the elderly. One-fifth of cases receive treatment with DIF, most within 2 days of admission. Opportunities exist for improved diagnosis and post-DIF management. Prospective data may be required to assess the impact of DIF on length of stay.

Assessment of wear/nonwear time classification algorithms for triaxial accelerometer.

PURPOSE: The objective of this study is to assess the performance of existing wear/nonwear time classification algorithms for accelerometry data collected in the free-living environment using a wrist-worn triaxial accelerometer and a waist-worn uniaxial accelerometer in older adults. METHODS: Twenty-nine adults age 76 to 96 yr wore wrist accelerometers for approximately 24 h per day and waist accelerometers during waking for approximately 7 d of free living. Wear and nonwear times were classified by existing algorithms (Alg([ActiLife]), Alg([Troiano]), and Alg([Choi])) and compared with wear and nonwear times identified by data plots and diary records. With the use of bias and probability of correct classification, the performance of the algorithms, two time windows (60 and 90 min), and vector magnitude (VM) versus vertical axis (V) counts from a triaxial accelerometer were compared. RESULTS: Automated algorithms (Alg([Choi]) and Alg([Troiano])) classified wear/nonwear time intervals more accurately from VM than V counts. The use of the 90-min time window improved wear/nonwear classification accuracy when compared with the 60-min window. The Alg([Choi]) and Alg([Troiano]) performed better than the manufacturer-provided algorithm (Alg([ActiLife])), and the Alg([Choi]) performed better than the Alg([Troiano]) for wear/nonwear time classification using the data collected by both accelerometers. CONCLUSIONS: Triaxial wrist-worn accelerometer can be used for an accurate wear/nonwear time classification in free-living older adults. The use of the 90-min window and the VM counts improves the performance of commonly used algorithms for wear/nonwear classification for both uniaxial and triaxial accelerometers.

Digoxin immune fab treatment for severe preeclampsia.

We evaluated the efficacy, safety, and biological mechanisms of digoxin immune Fab (DIF) treatment of severe preeclampsia. Fifty-one severe preeclamptic patients were randomized in double-blind fashion to DIF ( N = 24) or placebo ( N = 27) for 48 hours. Primary outcomes were change in creatinine clearance (CrCl) at 24 to 48 hours and antihypertensive drug use. Serum sodium pump inhibition, a sequela of endogenous digitalis-like factors (EDLF), was also assessed. CrCl in DIF subjects was essentially unchanged from baseline versus a decrease with placebo (-3 +/- 10 and -34 +/- 10 mL/min, respectively, P = 0.02). Antihypertensive use was similar between treatments (46 and 52%, respectively, P = 0.7). Serum sodium pump inhibition was decreased with DIF compared with placebo at 24 hours after treatment initiation (least squares mean difference, 19 percentage points, P = 0.03). DIF appeared to be well tolerated. These results suggest DIF prevents a decline in renal function in severe preeclampsia by neutralizing EDLF. Sodium pump inhibition was significantly improved. Further research is warranted.

Pharmacokinetics of glucarpidase in subjects with normal and impaired renal function.

Glucarpidase (formerly known as carboxypeptidase G2 or CPG2) is being evaluated for the adjunctive treatment of patients experiencing, or at risk of, methotrexate toxicity attributable to its delayed elimination. Delayed elimination of methotrexate can occur in patients with methotrexate-induced renal toxicity. In this study, glucarpidase pharmacokinetics were assessed in volunteer subjects with normal (n = 8) and severely impaired (n = 4) renal function. Each subject received a single intravenous dose of glucarpidase 50 U/kg (equivalent to 114.5 microg/kg) infused over 5 minutes. The mean maximum serum concentration (C(max)) for glucarpidase in renally impaired subjects was 2.9 microg/mL, the mean half-life (t(1/2)) was 10.0 hours, and the mean area under the serum concentration-time curve from time zero to infinity (AUC(0-infinity)) was 24.5 microg x h/mL. Similar values were found in subjects with normal renal function (mean C(max) 3.1 microg/mL, mean t(1/2) 9.0 hours, and mean AUC(0-infinity) 23.4 microg x h/mL). The results indicated little effect of renal impairment on the serum pharmacokinetics of glucarpidase.