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Background: Continuous infusion vancomycin (CIV) may benefit children who are unable to achieve therapeutic concentrations with intermittent vancomycin dosing and may facilitate outpatient administration by alleviating the burden of frequent dosing intervals. Previous studies have used variable dosing regimens and steady-state concentration goals. The purpose of this study was to evaluate the total daily dose (TDD) of CIV required to achieve therapeutic steady-state concentrations of 15-25 µg/mL in pediatric hematology/oncology patients., Methods: A single-center retrospective study was performed for patients treated with CIV from January 2017 to June 2019. The primary outcome was the TDD required to achieve therapeutic steady-state concentrations on CIV. Secondary outcomes included time to reach therapeutic steady-state concentrations, CIV indications and adverse events associated with CIV., Results: Data were collected for 71 courses of CIV in 60 patients. Median patient age was 4 years (range: 0.4-20 years). The median TDD required to achieve initial therapeutic concentrations was 50.3 mg/kg/d (interquartile range: 38.8-59.2) and was further divided into age-based cohorts. TDD in mg/kg was significantly lower in the older cohort ( P < 0.001), but there was no statistically significant difference between age-based cohorts with TDD in mg/m 2 ( P = 0.97). Median time to achieve first therapeutic concentration was 19.3 hours (range: 8.6-72.3 hours). The most common indication for CIV was ease of outpatient administration (69.0%). Acute kidney injury incidence was minimal (4.2%)., Conclusions: CIV is associated with rapid attainment of target concentrations in pediatric hematology/oncology patients and is safe and well tolerated., Competing Interests: M.A.K. is an editorial board member for Elsevier. S.J.C. is a consultant for Lexicomp (Wolters Kluwer). The remaining authors have no conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

From 8 December 2021 to 26 January 2023, tixagevimab-cilgavimab (T-C) was authorized for pre-exposure prophylaxis of COVID-19. During this period, we used a multidisciplinary team to communicate, screen, approach, and administer T-C to eligible patients. Twenty-seven patients were eligible. Of these, 24 (88.9%) received at least one dose of T-C and three patients received two doses. Majority of patients were White, non-Hispanic, and women. Only two patients had COVID-19 prior to receiving T-C. Seventeen (70.8%) had received two or more doses of SARS-CoV-2 vaccine. No serious adverse events were noted. Seven patients developed SARS-CoV-2 infection within 180 days of receiving T-C (median 102 days; range 28-135), and only one patient developed severe COVID-19 requiring intensive mechanical ventilation in the intensive care unit., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hijano, Ferrolino, Swift, Michaels, Max, Hayden, Wolf, Dallas, Greene, Richardson, Hakim, Morton and Cross.)

Background: Adult survivors of childhood cancer are at risk of developing sleep and neurocognitive problems, yet few efficacious interventions exist targeting these prevalent late effects. Melatonin has known sleep-promoting effects; however, it has not been well studied among childhood cancer survivors., Method: Survivors (n = 580; mean age = 33.5 years; 26 years post-diagnosis) from the St. Jude Lifetime Cohort were randomized (1:1) to a six-month double-blind placebo-controlled trial of 3 mg time-release melatonin within three strata (stratum 1: neurocognitive impairment only; stratum 2: neurocognitive and sleep impairment; stratum 3: sleep impairment only). Neurocognitive performance was assessed at baseline and post-intervention using standardized measures. Sleep was assessed via self-report and actigraphy. Independent sample t tests compared mean change scores from baseline to six months. Post-hoc analyses compared the prevalence of clinically significant treatment responders among melatonin and placebo conditions within and across strata., Results: Intent-to-treat analyses revealed no statistically significant differences in neurocognitive performance or sleep from baseline to post-intervention. However, among survivors with neurocognitive impairment only, a larger proportion randomized to melatonin versus placebo demonstrated a treatment response for visuomotor speed (63% vs 41%, P = 0.02) and nonverbal reasoning (46% vs 28%, P = 0.04). Among survivors with sleep impairment only, a larger proportion treated with melatonin demonstrated a treatment response for shifting attention (44% vs 28%, P = 0.05), short-term memory (39% vs 19%, P = 0.01), and actigraphy-assessed sleep duration (47% vs 29%, P = 0.05)., Conclusion: Melatonin was not associated with improved neurocognitive performance or sleep in our intent-to-treat analyses; however, a subset of survivors demonstrated a clinically significant treatment response., (© 2021 Wiley Periodicals LLC.)

Purpose: The following review is offered as an aid for encouraging deeper understanding by pharmacy graduates of approaches to debt management., Summary: The phenomenon of growing debt for pharmacists and other professionals has been well described. Significant debt is widespread with both pharmacy students and graduates; a recent study described the debt-to-income ratio for pharmacists to have risen by 141% between 2010 and 2016. This increasing debt burden causes significant pressure for these individuals-whether while in training, early in their career, or, increasingly, even in midcareer. Dealing with debt has become a major consideration in the profession. Given that financial education is addressed only minimally, if at all, in pharmacy curricula, pharmacists find it challenging to understand and fully consider the myriad factors influencing the accumulation and repayment of debt in the context of their financial goals. Personal financial, repayment, behavioral, and emotional/psychological factors must be considered to choose an optimal strategy to address debt. This article describes various repayment plans, particularly focusing on those offered with direct loans, and it reviews in some detail 5 comprehensive repayment strategies (using these plans). Three case studies derived from real-life pharmacist-planner interactions illustrate the many factors that must be considered as a pharmacist chooses the optimal approach to debt repayment in their unique life situation., Conclusion: Education of students and pharmacists regarding the various factors related to handling student debt may facilitate decision-making that is both financially and personally beneficial., (© American Society of Health-System Pharmacists 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Posaconazole exhibits broad-spectrum antifungal activity. An IV formulation became available in 2014. Few studies describing the use of this formulation exist in patients under the age of 18 years. This study describes our experience using IV posaconazole in paediatric and young adult cancer patients., Methods: This single-centre retrospective chart review evaluated patients who received IV posaconazole and had at least one posaconazole plasma concentration obtained after five or more days with a consistent dosage. Relationships between doses required to achieve a plasma concentration of ≥1 µg/mL and patient age, weight and body surface area (BSA) were evaluated. The clinical record was reviewed to identify descriptions of any adverse events., Results: Twenty-five patients were analysed, with a median age of 10.5 years (range 1.9-22.9 years; 92% were <18 years). All patients were able to achieve a posaconazole plasma concentration ≥1 µg/mL during their treatment course. The daily mg/kg/day dose required to achieve the target concentration decreased significantly with increasing age of the patient (P = 0.018). Assessment of dosage based on BSA suggested a requirement of 225 mg/m2/day across all age groups <18 years. Adverse events documented in the clinical record were consistent with those described with the oral formulations. No CNS toxicities were observed with use of IV posaconazole., Conclusions: Concentrations ≥1 µg/mL are achievable and a BSA-based dosing approach may allow a consistent empirical dose for patients <18 years of age. Therapeutic drug monitoring is recommended to ensure patients achieve therapeutic concentrations., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

We evaluated pain status change and associations with subsequent opioid/marijuana use among 1208 adult survivors of childhood cancer. Pain status and opioid/marijuana were self-reported at baseline and follow-up evaluation (mean interval = 4.2 years). Over time, 18.7% of survivors endorsed persistent/increasing significant pain; 4.8% and 9.0% reported having used opioids and marijuana at follow-up. Persistent/increased (vs none/decreased) pain, persistent/increased (vs none/decreased) anxiety, and lack of health insurance increased odds of subsequent opioid use by 7.69-fold (95% confidence interval [CI] = 3.71 to 15.95), 2.55-fold (95% CI = 1.04 to 6.24), and 2.50-fold (95% CI = 1.07 to 5.82), respectively. Persistent/increased (vs none/decreased) depression increased odds of subsequent marijuana use by 2.64-fold (95% CI = 1.10 to 6.33)., (© The Author(s) 2020. Published by Oxford University Press.)

Background: Limited information exists regarding the use of posaconazole for treating systemic fungal infections in children, adolescents, and young adults with cancer. At St. Jude Children's Research Hospital, the recommended posaconazole dose in patients weighing less than 34 kg is 18-24 mg/kg daily, given in 4 divided doses. For patients aged 13 years or older or those weighing 34 kg or more, the recommended dose is 800 mg daily, given orally in 4 divided doses., Objective: To determine whether the current posaconazole dosing guidelines achieve target posaconazole plasma concentrations of 0.7 μg/mL or greater., Methods: This retrospective clinical study examined data from patients who received treatment-dose posaconazole and had at least 1 posaconazole plasma concentration measurement., Results: Data from 33 patients who received posaconazole for the treatment of fungal infections were analyzed. The median age of patients was 11.5 years (range 0.5-23.2). Twenty-one of 33 patients (63.6%) had posaconazole concentrations of 0.7 μg/mL or greater (median 1.4; range 0.7-2.98) at the first measurement. The median posaconazole dosage referenced to total body weight in these patients was 20 mg/kg/day. Patients with concentrations less than 0.7 μg/mL (median 0.4; range 0.025-0.69) received lower posaconazole dosages when referenced to body weight (median 12.9 mg/kg/day; p = 0.02). Of the 12 patients with concentrations less than 0.7 μg/mL, 7 (58.3%) were aged 13 years or older., Conclusions: The current dosing approach for posaconazole yielded therapeutic plasma concentrations more frequently in patients younger than 13 years than in those 13 years or older. This difference may be related to the practice of capping adolescent and young adult doses at the suggested maximum adult daily dose. Therefore, we recommend weight-based dosing in all pediatric, adolescent, and young adult patients with cancer, with routine therapeutic drug monitoring to ensure adequate concentrations.

Objective: In developed countries, pharmacists play a crucial role in designing and implementing cancer treatments as part of a multidisciplinary oncology team. However, developing countries have a shortage of pharmacists, and their role is generally limited to dispensing and selling drugs. The aim of this study was to investigate the feasibility of providing clinical pharmacy educational activities via international teleconferencing to improve cancer care in developing countries., Materials and Methods: Meticulous preparation and intense promotion of the workshop were done in Egypt before the telepharmacy conferences began. Multiple connectivity tests were performed to resolve technical problems. Nine telepharmacy conferences were delivered during 3-h sessions that were held on three consecutive days. Talks were subsequently made available via Web streaming. Attendees were requested to complete a survey to measure their satisfaction with the sessions., Results: The teleconference was attended by a total of 345 persons, and it was subsequently reviewed online via 456 log-in sessions from 10 countries. Technical issues (e.g., poor auditory quality) were resolved on the first day of the event. The rate of attendees' responses on the survey was 30.1%, and satisfaction with the event was generally good., Conclusions: Telecommunication is a relatively inexpensive approach that may improve pharmacy practices, especially those used to treat patients with cancer in developing countries. Special attention to patient-based telepharmacy education, including the use of cost-effective technology, should be considered.

Purpose: To investigate the maximum tolerated dose of ranibizumab administered as a single intravitreal injection., Design: Open-label, 5-center, uncontrolled, prospective, dose-ranging, interventional case series., Participants: Twenty-seven patients with subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) with best-corrected Snellen equivalent visual acuity (VA) of 20/100 or worse and considered ineligible for laser photocoagulation or photodynamic therapy., Methods: A single intravitreal injection of ranibizumab was to be administered at 1 of 6 escalating doses (50, 150, 300, 500, 1000, and 2000 microg), with escalation to the next dose level occurring only after the safety and tolerability of the lower dose level was established through postinjection day 14. Follow-up examinations were performed on postinjection days 1, 3, 7, 14, 42, and 90. Enrollment was stopped if > or =2 patients experienced dose-limiting toxicity., Main Outcome Measures: The primary safety measures were changes from baseline in VA, intraocular pressure (IOP), intraocular inflammation, and production of antiranibizumab antibody. Dose-limiting toxicity was defined by intraocular inflammation, elevated IOP, reduced VA, or hemorrhage within 90 days after injection., Results: All patients completed this single intravitreal injection study, and 500 microg of ranibizumab was the maximum tolerated dose. At the higher dose of 1000 microg, significant intraocular inflammation was noted. All adverse events were self-limited, and no infectious endophthalmitis occurred. Aqueous or vitreous ocular inflammation occurred in 12 subjects, with complete resolution within 42 days. In 9 of the subjects, the inflammation was graded as trace to 1+ and required no treatment; in 3 of the subjects, the inflammation was graded as 2+ or 3+, and 2 of the 3 were treated with topical 1% prednisolone acetate. No serum antiranibizumab antibodies were detected. All patients had VA similar or improved compared with baseline values., Conclusion: The maximum tolerated single dose of ranibizumab in neovascular AMD patients was 500 microg. Single intravitreal injections of ranibizumab up to a dose of 500 microg were safe and well tolerated in this small group of patients.

Background: Efalizumab is a humanized IgG(1) mAb against the lymphocyte function antigen-1 (LFA-1) alpha chain, CD11a. Blocking of LFA-1/intercellular adhesion molecule interactions could inhibit asthmatic inflammation by blocking adhesion and activation of LFA-1-positive leukocytes., Objective: A randomized, double-blinded, placebo-controlled, parallel group, multicenter study investigated the effects of efalizumab on allergen-induced airway responsiveness and airway inflammation., Methods: Thirty-five nonsmoking subjects with mild allergic asthma were randomized to receive efalizumab (n = 24) or placebo (n = 11) in 8 weekly subcutaneous doses (0.7 mg/kg conditioning dose followed by 7 weekly doses of 2.0 mg/kg). Allergen challenges were performed at screening and after 4 and 8 weeks of treatment. Samples of sputum (n = 18 subjects) and blood (n = 35 subjects) were collected the day before challenges, and sputum was collected again at 7 and 24 hours after each challenge. Nonparametric tests were used to compare allergen-induced differences between efalizumab and placebo groups., Results: Subjects receiving efalizumab developed headache (48%) and flu syndrome (28%) compared to subjects receiving placebo (0%). After 8 weeks of efalizumab, the maximum late percent fall in FEV(1) (late asthmatic response) was inhibited by 50%, but neither the late response nor the late area under the curve was statistically different than placebo (P =.098 and.062, respectively). Efalizumab had no effect on the maximum early percent fall in FEV(1) (early asthmatic response) or early area under the curve compared to placebo (P >.59). Efalizu-mab significantly reduced the postallergen increase in sputum EG2-positive cells and metachromatic cells (P <.05). No other comparisons were statistically different., Conclusions: Blocking of LFA-1/intercellular adhesion module interactions by efalizumab inhibits the development of allergen-induced cellular inflammatory responses measured in induced sputum and might attenuate the late asthmatic response. Larger studies are needed to confirm this.

Background: Most clinical studies are done to show comparative superiority, but many reports now claim equivalence between the investigated entities. These assertions may not always be supported by the methods used and the results obtained., Purpose: To assess the justification and support for claims of clinical or therapeutic equivalence in medical journals., Data Sources: A search of MEDLINE for articles published from 1992 through 1996., Study Selection: From 1209 citations that contained the word equivalence in the title or abstract or contained the Medical Subject Heading therapeutic equivalency, we excluded 1121 studies reporting nonoriginal research, purely laboratory or other nonhuman research, and studies in which equivalence was not the main claim. The remaining 88 eligible papers were evaluated for five methodologic attributes., Data Synthesis: Only 45 (51%) of the 88 reports were specifically aimed at studying equivalence; the others either tried to show superiority or did not state a research aim. The quantitative distinctions regarded as "equivalent" ranged from 0% to 21% for direct increments and from 0% to 76% for proportionate differences. An equivalence boundary was set and confirmed with an appropriate statistical test in only 23% of reports. In 67% of reports, equivalence was declared after a failed test for comparative superiority, and in 10%, the claim of equivalence was not statistically evaluated. The sample size needed to confirm results had been calculated in advance for only 33% of reports. Sample size was 20 patients per group or fewer in 25% of reports., Conclusions: Many studies of clinical equivalence do not set boundaries for equivalence. Claims of "difference" or "similarity" are often made not by thoughtful examination of the data but by tests of statistical significance that are often misapplied or accompanied by inadequate sample sizes. These methodologic flaws can lead to false claims, inconsistencies, and harm to patients.

Objective: To review the literature that compares zolpidem with triazolam, with an emphasis on efficacy and safety in humans., Data Sources: Information was retrieved from a MEDLINE search (1983-1996) of the English-language literature using the terms triazolam and zolpidem., Study Selection: Reports of clinical trials comparing the safety and efficacy of zolpidem and triazolam were included in this review., Data Extraction: Data were evaluated according to study design, efficacy, and adverse effects. Pertinent information was selected and the data synthesized into a review format., Data Synthesis: Zolpidem and triazolam have similar pharmacokinetic and pharmacodynamic effects in humans. Clinical trials have shown that usually recommended, equipotent dosages of zolpidem and triazolam do not differ with respect to pharmacokinetics, efficacy, tolerability, residual effects, memory impairment, rebound insomnia, abuse potential, or other adverse effects., Conclusions: Zolpidem offers no distinct therapeutic advantage over triazolam for the treatment of insomnia.

Antitrust laws place significant limits on collective action among independent practicing physicians. The lawful options most likely to appeal to physicians include the complete merger of physician practices or the significant involvement of a physician or group in a partially integrated legitimate joint venture, such as a provider-sponsored PPO. Neither activity should be undertaken without the assistance of legal counsel. Change in the overall thrust of antitrust law is unlikely, and physicians must protect themselves from liability through careful business planning and the use of competent legal counsel.

Cimetidine is a widely used antiulcer medication that is also a potent inhibitor of the mixed-function oxidase enzymes in the liver. This effect results in a number of clinically important interactions with other drugs, which are now being appreciated. Other effects of cimetidine, such as raising of gastric pH, alteration of liver blood flow, or alterations in renal secretory mechanisms, may also contribute to or result in clinically significant interactions. Current data document appreciable alterations in the metabolism or excretion of warfarin, theophylline, phenytoin, lidocaine, certain beta-adrenoceptor antagonists, certain benzodiazepines, and probably narcotic analgesics and procainamide. Thus, effects of these drugs and serum levels, where available, should be more closely followed when used in combination with cimetidine. Cimetidine appears to exacerbate the myelosuppressive effects of the nitrosoureas, and may also significantly alter the absorption of ketoconazole. Though other drugs may affect the absorption or elimination of cimetidine, the clinical implication of these effects is uncertain.

Chemoreceptors for oxygen reside within the carotid body, but it is not known which cells actually sense hypoxia and by what mechanisms they transduce this information into afferent signals in the carotid sinus nerve. We have developed systems for the growth of glomus cells of the carotid body in dissociated cell culture. Here we demonstrate that, as in vivo, these cells contain the putative neurotransmitters dopamine, serotonin, and norepinephrine. Oxygen tension regulates the rate of dopamine secretion from the glomus cells. Similar to chemically stimulated catecholamine secretion from other adrenergic cells this hypoxia-stimulated release requires extracellular calcium. These results are compatible with the suggestion that the glomus cells of the carotid body are chemoreceptor cells and that they signal hypoxia by regulated secretion of dopamine.

Although cimetidine is more effective than a placebo for the prophylaxis of stress-induced ulcers, it has no advantage over titrated antacid dosing. Several comparative studies even suggest that combining cimetidine with antacid is no more effective than use of full-dose antacid. Therefore, we recommend prophylactic use of cimetidine only when very large dosages of antacid are required, in order to minimize acid-base disturbances.

The predictive performance of 2 theophylline pharmacokinetic dosing programs (Abbott and Simkin) was evaluated using a group of 44 inpatients who had 2 serum concentrations (TSC) measured during hospitalization. Bias was assessed with the median prediction error (PE) and precision was assessed with the median absolute PE. The Abbott program was significantly less biased than the Simkin program in predicting the first TSC (PEs 0.1 and -1.3 micrograms/ml, respectively; p less than 0.05). No significant difference in bias was observed in predicting the second TSC, or in precision in predicting either the first or second TSC. Both programs exhibited small improvements in prediction precision when the first TSC was used to predict the second. Correlations of predicted versus measured TSC also improved with the second prediction. These programs may be useful in dosing theophylline; however, TSC monitoring and the application of sound clinical judgment are warranted.