Trends in the delivery of care to oncology patients in the United States: Emphasis on the role pharmacists on the healthcare team.

OBJECTIVE: The purpose of this study was to identify trends in oncology care that allow one to forecast workforce supply and demand, the training and skills needed by the oncology pharmacist for the likely future of oncology care. METHODS: Interviews were conducted with experienced oncology pharmacists in leadership roles at 20 organizations balanced by geographic region and type of practice site (academic or community/ambulatory). Results were analyzed using descriptive statistics and theme identification. RESULTS: Practice sites differed widely in numbers of patient visits, practitioner/patient ratios, residency program presence, and other structural features. Despite this, the majority reported an expectation of growth in cancer patients, oncology physicians, oncology pharmacists, pharmacy technicians, oncology nurses, and advanced practice practitioners in the next two to five years. Fifty percent of sites currently support Post Graduate Year 2 (PGY2) oncology residencies. At least 50% reported routine pharmacist involvement in 12 clinical functions. More future involvement was predicted for immunotherapy (80%) and oral oncolytic therapy (90%). Interprofessional involvement was reported for a broad variety of practice-related committees and patient education teams. Limited pharmacist involvement in credentialing, quality measurement, and value-based reimbursement systems was found. CONCLUSION: Anticipated increases in demand for oncology pharmacists strongly suggest the need for more PGY2 oncology residency programs and on-the-job oncology training programs. Oncology pharmacists are currently involved in many clinical and administrative functions including multidisciplinary management. While a core set of clinical functions has been identified, oncology pharmacists must prepare for the increased use of oral oncology agents and immunotherapy. Pharmacist involvement in value-based reimbursement and other data-based quality outcome measurements should be increased to optimize involvement in team-based patient care.

Fosamprenavir with Ritonavir Pharmacokinetics during Pregnancy.

The purpose of this study was to evaluate the pharmacokinetics of ritonavir-boosted fosamprenavir during pregnancy and postpartum. Amprenavir (the active moiety of fosamprenavir) and ritonavir intensive pharmacokinetic evaluations were performed at steady state during the second and third trimesters of pregnancy and postpartum. Plasma concentrations of amprenavir and ritonavir were measured using high-performance liquid chromatography. The target amprenavir area under the concentration-versus-time curve (AUC) was higher than the 10th percentile (27.7 µg · h/ml) of the median area under the curve for ritonavir-boosted fosamprenavir in adults receiving twice-daily fosamprenavir-ritonavir at 700 mg/100 mg. Twenty-nine women were included in the analysis. The amprenavir AUC from time zero to 12 h (AUC0-12) was lower (geometric mean ratio [GMR], 0.60 [confidence interval {CI}, 0.49 to 0.72] [P < 0.001]) while its apparent oral clearance was higher (GMR, 1.68 [CI, 1.38 to 2.03] [P < 0.001]) in the third trimester than postpartum. Similarly, the ritonavir AUC0-12 was lower in the second (GMR, 0.51 [CI, 0.28 to 0.91] [P = 0.09]) and third (GMR, 0.72 [CI, 0.55 to 0.95] [P = 0.005]) trimesters than postpartum, while its apparent oral clearance was higher in the second (GMR, 1.98 [CI, 1.10 to 3.56] [P = 0.06]) and third (GMR, 1.38 [CI, 1.05 to 1.82] [P = 0.009]) trimesters than postpartum. The amprenavir area under the curve exceeded the target for 6/8 (75%) women in the 2nd trimester, 18/28 (64%) in the 3rd trimester, and 19/22 (86.4%) postpartum, and the trough concentrations (Cmin) of amprenavir were 4- to 16-fold above the mean amprenavir-protein-adjusted 50% inhibitory concentration (IC50) of 0.146 µg/ml. Although amprenavir plasma concentrations in women receiving ritonavir-boosted fosamprenavir were lower during pregnancy than postpartum, the reduced amprenavir concentrations were still above the exposures needed for viral suppression.

Retail clinics colocated with pharmacies: A Delphi study of pharmacist impacts and recommendations for optimization.

OBJECTIVES: To identify workforce issues likely to affect pharmacists working in retail clinics (RCs) colocated with community pharmacies and to generate recommendations for optimizing health, cost, and operations outcomes. DESIGN AND PARTICIPANTS: A Delphi expert panel process using researchers with pharmacist workforce research experience was used. Panelists responded to 2 surveys of 3 rounds each. In survey 1, panelists used a 4-point linear numeric scale to rate the importance of 15 impact factors on pharmacists working in the RC/pharmacy setting. In survey 2, panelists used a 3-point linear numeric scale to rate the importance of recommendations for optimal outcomes. Recommendations were structured around elements from collaboration theory, a framework for evaluating critical areas for success in merged operations. MAIN OUTCOME MEASURES: Consensus was defined as ≥ 80% rating an impact "very" or "moderately" important (survey 1) and "very" important (survey 2). Impact factors were rank-ordered by ratings and numeric scoring. Selected comments about consensus items were reported. RESULTS: The 8-person panel had 100% response rates for both surveys. 12 of the 15 impact variables achieved consensus (survey 1). The highest ranking impacts were ability to establish collaborative relationships, relationships with coworkers, including nurse practitioners, and location of the RC relative to the pharmacy. Of 15 recommendations (survey 2), 5 achieved consensus and focused heavily on information sharing and early and ongoing collaboration among all stakeholders. CONCLUSION: Clinical, economic, health care quality, and patient preference data suggest that RCs colocated with pharmacies are likely to play a permanent role in U.S. health care. RCs can affect pharmacists and pharmacies positively or negatively. Positive impacts are most likely where establishing collaborative partnerships with all stakeholders, including patients, throughout planning, implementation, and operation are emphasized. With only about 3% of pharmacy operations colocated with RCs now, attention and resources should be devoted to developing and testing models based on collaboration principles.

Antiretroviral Drug Resistance Among Children and Youth in the United States With Perinatal HIV.

Among 234 US youths with perinatal human immunodeficiency virus, 75% had antiretroviral resistance, substantially higher than that of the reference laboratory overall (36%-44%). Resistance to newer antiretrovirals and to all antiretrovirals in a class was uncommon. The only factor independently associated with future resistance was a higher peak viral load.

Prevalence and Persistence of Varicella Antibodies in Previously Immunized Children and Youth With Perinatal HIV-1 Infection.

BACKGROUND: Two doses of live-attenuated varicella-zoster vaccine are recommended for human immunodeficiency virus 1 (HIV-1)-infected children with CD4% ≥ 15%. We determined the prevalence and persistence of antibody in immunized children with perinatal HIV (PHIV) and their association with number of vaccinations, combination antiretroviral therapy (cART), and HIV status. METHODS: The Adolescent Master Protocol is an observational study of children with PHIV and perinatally HIV-exposed but uninfected (PHEU) children conducted at 15 US sites. In a cross-sectional analysis, we tested participants' most recent stored sera for varicella antibody using whole-cell and glycoprotein enzyme-linked immunosorbent assay. Seropositivity predictors were identified using multivariable logistic regression models and C statistics. RESULTS: Samples were available for 432 children with PHIV and 221 PHEU children; 82% of children with PHIV and 97% of PHEU children were seropositive (P < .001). Seropositivity after 1 vaccine dose among children with PHIV and PHEU children was 100% at <3 years (both), 73% and 100% at 3-<7 years (P < .05), and 77% and 97% at ≥ 7 years (P < .01), respectively. Seropositivity among recipients of 2 vaccine doses was >94% at all intervals. Independent predictors of seropositivity among children with PHIV were receipt of 2 vaccine doses, receipt of 1 dose while on ≥ 3 months of cART, compared with none (adjusted odds ratio [aOR]: 14.0 and 2.8, respectively; P < .001 for overall dose effect), and in those vaccinated ≥ 3 years previously, duration of cART (aOR: 1.29 per year increase, P = .02). CONCLUSIONS: Humoral immune responses to varicella vaccine are best achieved when children with PHIV receive their first dose ≥ 3 months after cART initiation and maintained by completion of the 2-dose series and long-term cART use.

Lower Newborn Bone Mineral Content Associated With Maternal Use of Tenofovir Disoproxil Fumarate During Pregnancy.

BACKGROUND: Fetal bone effects of maternal tenofovir use have not been well studied. We sought to compare whole-body bone mineral content (BMC) of newborns exposed vs not exposed to tenofovir in utero. METHODS: We enrolled participants from April 2011 to June 2013 at 14 US clinical sites. Singleton infants of women with human immunodeficiency virus (HIV) infection who took tenofovir in late pregnancy (tenofovir-exposed) or no tenofovir during pregnancy (tenofovir-unexposed) were enrolled during late pregnancy or within 72 hours of birth. Infants born before 36 weeks gestation or with confirmed HIV infection were excluded. Whole-body BMC was measured in the first month of life and compared with that of the tenofovir-exposed and tenofovir-unexposed newborns, unadjusted and adjusted for covariates. RESULTS: Seventy-four tenofovir-exposed and 69 tenofovir-unexposed infants had evaluable BMC measurements. Tenofovir-exposed mothers were more likely to be married (31% vs 22%; P = .04) and to use boosted protease inhibitors (84% vs 62%; P = .004). Tenofovir-exposed newborns did not differ from unexposed newborns on mean gestational age (38.2 vs 38.1 weeks) or mean length (-0.41 vs -0.18) or weight (-0.71 vs -0.48) Z-scores. The mean (standard deviation) BMC of tenofovir-exposed infants was 12% lower than for unexposed infants (56.0 [11.8] vs 63.8 [16.6] g; P = .002). The adjusted mean bone mineral content was 5.3 g lower (95% confidence interval, -9.5, -1.2; P = .013) in the tenofovir-exposed infants. CONCLUSIONS: Maternal tenofovir use is associated with significantly lower neonatal BMC. The duration and clinical significance of this finding should be evaluated in longitudinal studies. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov NCT01310023.

Mucormycosis in children with cancer and hematopoietic cell transplant-A single center cohort study.

Although mucormycosis is an important cause of morbidity and mortality in children with cancer, our understanding of the typical characteristics of these infections is incomplete. We reviewed all cases of mucormycosis diagnosed at a single pediatric cancer center over 5 decades to identify the clinical features of mucormycosis in pediatric oncology patients and to identify risk factors for mortality. There were 44 cases of mucormycosis diagnosed between 1970-2019. Most patients (89%) had hematological malignancies and a history of prolonged and severe neutropenia (91%). In this series, hyperglycemia and exposure to corticosteroids were common. Pulmonary (36%) and disseminated infections (32%) were most common; rhino-orbital-cerebral infections were relatively infrequent (11%). Rhizopus spp. was the most common etiological agent (40%) followed by Mucor spp. (31%), and Cunninghamella spp. (19%). Overall mortality was 44% and 51% and attributable mortality was 39% and 41% at the end of antifungal therapy and end of follow up, respectively. Attributable mortality fell to 18% in 2010-2019, from 58-60% in previous decades; adjunctive surgery was associated with decreased mortality. Mortality remains unacceptably high despite aggressive antifungal therapy and adjunctive surgery, suggesting novel therapeutic strategies are needed.

Posaconazole therapeutic drug monitoring in pediatric patients and young adults with cancer.

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.

Factors affecting the unmet demand for pharmacists: state-level analysis.

OBJECTIVE: To describe the relationship between state-level Aggregate Demand Index (ADI) data and market factors reflecting both supply and demand: unemployment rates, pharmacy graduates, community pharmacy prescription growth rates, and Medicare Part D. DESIGN: Cross-sectional time series analysis using state-level data. SETTING: U.S. labor market for pharmacists, from 2001 to 2010. INTERVENTION: Model ADI data for states (dependent variable) against five independent variables: previous year ADI, unemployment rates, pharmacy graduates, prescription growth rates, and Medicare Part D. MAIN OUTCOME MEASURES: Significance and predictive ability of the model, sign of the variables studied, and R2. RESULTS: In the two-way (state and time) fixed-effects model, all variables were significant and R2 was 0.79. Contributions to state-level ADIs were, in rank order, previous year ADI, unemployment rates, pharmacy graduates, and prescription growth rates. The model predicted 2010 ADI values for 44 of 51 states within ±10%. The model depicts the independent contributions of each variable for the short (∼1 year) and longer term. Although the nature of ADI data precludes quantitative predictions about the pharmacist job market, the model results show marketplace directions (up or down) and comparative impacts. CONCLUSION: The model demonstrated that unemployment rates, pharmacy graduates, prescription growth rates, and Medicare Part D contributed significantly to state-level ADIs between 2001 and 2010. The relationships uncovered should be monitored and reexamined as new data emerge in order to anticipate the directions of the pharmacist job market.

Metabolic abnormalities and viral replication are associated with biomarkers of vascular dysfunction in HIV-infected children.

OBJECTIVES: HIV-infected children may be at risk for premature cardiovascular disease. We compared levels of biomarkers of vascular dysfunction in HIV-infected children (with and without hyperlipidaemia) with those in HIV-exposed, uninfected (HEU) children enrolled in the Pediatric HIV/AIDS Cohort Study (PHACS), and determined factors associated with these biomarkers. METHODS: A prospective cohort study was carried out. Biomarkers of inflammation [C-reactive protein (CRP), interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP1)], coagulant dysfunction (fibrinogen and P-selectin), endothelial dysfunction [soluble intracellular cell adhesion molecule-1 (sICAM), soluble vascular cell adhesion molecule-1 (sVCAM) and E-selectin], and metabolic dysfunction (adiponectin) were measured in 226 HIV-infected and 140 HEU children. Anthropometry, body composition, lipids, glucose, insulin, HIV disease severity, and antiretroviral therapy were recorded. RESULTS: The median ages of the children were 12.3 years in the HIV-infected group and 10.1 years in the HEU group. Body mass index (BMI) z-scores, waist and hip circumferences, and percentage body fat were lower in the HIV-infected children. Total and non-high-density lipoprotein (HDL) cholesterol and triglycerides were higher in HIV-infected children. HIV-infected children also had higher MCP-1, fibrinogen, sICAM and sVCAM levels. In multivariable analyses in the HIV-infected children alone, BMI z-score was associated with higher CRP and fibrinogen, but lower MCP-1 and sVCAM. Unfavourable lipid profiles were positively associated with IL-6, MCP-1, fibrinogen, and P- and E-selectin, whereas increased HIV viral load was associated with markers of inflammation (MCP-1 and CRP) and endothelial dysfunction (sICAM and sVCAM). CONCLUSIONS: HIV-infected children have higher levels of biomarkers of vascular dysfunction than do HEU children. Risk factors associated with higher biomarkers include unfavourable lipid levels and active HIV replication.

Prevention of Mother-to-Child Human Immunodeficiency Virus Transmission in Resource-Limited Countries.

The first pediatric AIDS cases were reported in 1982. A decade later, the World Health Organization estimated there were more than 500,000 pediatric AIDS cases resulting from mother-to-child transmission, 90% of which were in sub-Saharan Africa. Although the rate of new infections globally has been cut in half since the peak of the pandemic, human immunodeficiency virus (HIV) remains a public health threat, and rates of new infections continue to increase in some regions. Mother-to-child transmission of HIV has now been virtually eliminated in many parts of the world but remains an issue in resource-limited countries.

Board-certified pharmacy specialties: Growth from 2008 to 2020 and projections to 2025.

PURPOSE: To track and analyze the growth of 12 Board of Pharmacy Specialties (BPS) specialties from 2008 to 2020 and, subject to criteria, to project specialty numbers through 2025. The analysis considered residency data and Bureau of Labor Statistics projections. METHODS: BPS data were used to determine numeric growth, growth rates, and trends for 12 BPS specialties from 2008 to 2020. Specialties begun after 2008 were analyzed from their start date. For specialties with more than 2 data points and coefficients of determination greater than 0.80, we calculated projections through 2025. We also estimated the percentage of BPS-certified pharmacists with postgraduate year 1 training. RESULTS: BPS-certified pharmacists grew in number from 3,004 (2008) to 41,802 (2020), an over 13-fold increase. Currently, 4 of the 5 largest specialties (pharmacotherapy, ambulatory care, oncology, and critical care) continue to grow at a fast rate. Pharmacotherapy experienced the largest numeric growth (20,624) despite the ongoing introduction of new specialties. Critical care and infectious diseases had the highest growth rates (both 32%). We were able to make projections for 10 of 12 specialties, with greater than 62,000 certifications projected by 2025. Growth to these projected levels will require more residencies and more certification preparation opportunities. Residency-trained BPS specialists currently constitute slightly less than 50% of the BPS-certified population. CONCLUSION: Specialization in the pharmacy profession is growing at a rapid pace. As more clinical privileges are approved, the demand for more specialized pharmacists will likely continue to increase. Data from this study document the growth of the pharmacy specialty workforce. The data and analysis can be used to estimate potential pharmacist contributions across the healthcare spectrum in clinical areas where BPS-certified pharmacists practice.

Rapid Start of Antiretroviral Therapy in Youth Diagnosed with HIV Infection.

BACKGROUND: Guidelines for the use of antiretroviral agents in adults and adolescents with HIV recommend that antiretroviral therapy (ART) be started as soon as possible. While rapid initiation of ART in adults with HIV has been well-described, there is relatively little information describing this approach for youth. METHODS: On April 1, 2018, St. Jude Children's Research Hospital began offering ART to youth with HIV infection at their first clinic visit. We report the results of a quality improvement initiative that compared patients who offered ART at their first visit to a historical cohort of patients who initiated ART at a subsequent visit. Demographic, HIV biomarker, and visit information were abstracted from medical records, described and compared using univariate statistical methods. RESULTS: There were 124 ART-naive youth (median age 19 years, 91% male, 94% black) first seen during the indicated time period. A total of 54 patients were in the baseline cohort and 70 patients were in the rapid start cohort. 90% of youth in the rapid start cohort started ART on their first clinic visit. Time from first clinic visit to undetectable viral load was significantly higher in the baseline cohort compared with the rapid start cohort (median 54 vs. 41 days; P = 0.01). Retention in care 12 months following the first clinic visit was comparable and overall high (>80%). CONCLUSIONS: Starting ART-naïve youth with HIV infection on ART at their first clinic visit is feasible, has high acceptance, leads to faster viral load suppression, and is associated with high retention in care.

Prospective surveillance for invasive fungal infections in hematopoietic stem cell transplant recipients, 2001-2006: overview of the Transplant-Associated Infection Surveillance Network (TRANSNET) Database.

BACKGROUND: The incidence and epidemiology of invasive fungal infections (IFIs), a leading cause of death among hematopoeitic stem cell transplant (HSCT) recipients, are derived mainly from single-institution retrospective studies. METHODS: The Transplant Associated Infections Surveillance Network, a network of 23 US transplant centers, prospectively enrolled HSCT recipients with proven and probable IFIs occurring between March 2001 and March 2006. We collected denominator data on all HSCTs preformed at each site and clinical, diagnostic, and outcome information for each IFI case. To estimate trends in IFI, we calculated the 12-month cumulative incidence among 9 sequential subcohorts. RESULTS: We identified 983 IFIs among 875 HSCT recipients. The median age of the patients was 49 years; 60% were male. Invasive aspergillosis (43%), invasive candidiasis (28%), and zygomycosis (8%) were the most common IFIs. Fifty-nine percent and 61% of IFIs were recognized within 60 days of neutropenia and graft-versus-host disease, respectively. Median onset of candidiasis and aspergillosis after HSCT was 61 days and 99 days, respectively. Within a cohort of 16,200 HSCT recipients who received their first transplants between March 2001 and September 2005 and were followed up through March 2006, we identified 718 IFIs in 639 persons. Twelve-month cumulative incidences, based on the first IFI, were 7.7 cases per 100 transplants for matched unrelated allogeneic, 8.1 cases per 100 transplants for mismatched-related allogeneic, 5.8 cases per 100 transplants for matched-related allogeneic, and 1.2 cases per 100 transplants for autologous HSCT. CONCLUSIONS: In this national prospective surveillance study of IFIs in HSCT recipients, the cumulative incidence was highest for aspergillosis, followed by candidiasis. Understanding the epidemiologic trends and burden of IFIs may lead to improved management strategies and study design.

Oncology Pharmacists Can Reduce the Projected Shortfall in Cancer Patient Visits: Projections for Years 2020 to 2025.

Based on the projected need for a larger oncology care workforce, we estimated the patient care visits and care activities that Board Certified oncology pharmacists (BCOPs) could contribute to oncology care from 2020-2025. Using projected counts for BCOPs through 2025, we estimated that 2.9-4.1 million 30-min BCOP patient visits were possible at 50% workforce capacity. BCOPs' clinical activities overlapped strongly with those of nurse practitioners (NPs) and physician assistants (PAs) in patient education and treatment management. BCOPs could help reduce provider stress and burnout concerns by spreading these activities across a broader set of providers. BCOPs were more active than NPs and PAs in clinical trials research. Recent advances in immunotherapy, pharmacogenetics, pharmacogenomics, and oral oncolytic agents make the medication-focused training of OPs particularly useful to care teams. Comparison also showed that BCOPs were less active in providing follow-up visits and prescribing. Fulfilling the projected BCOP numbers through 2025 will require continued growth in Postgraduate Year 2 (PGY2) oncology pharmacy resident programs and on-the-job training programs. Our review of the trends in cancer incidence, mortality, and survivorship suggest a sustained need for the activities of BCOPs and other oncology care providers.

Predictors of Viremia in Postpartum Women on Antiretroviral Therapy.

BACKGROUND: HIV-infected, postpartum women on antiretroviral therapy (ART) have high rates of viremia. We examined predictors of postpartum viremia in the PROMISE study. METHODS: Women with pre-ART CD4 T-cell counts ≥400 cells/mm who started ART during pregnancy were randomized postpartum to continue ART (CTART) or discontinue ART (DCART). Viral load and self-reported adherence were collected every 12 weeks, up to 144 weeks. Women in DCART reinitiated therapy when clinically indicated. Viremia was defined as 2 consecutive viral loads >1000 copies/mL after 24 weeks on ART. Adherence was dichotomized as missing versus not missing ART doses in the past 4 weeks. Predictors of viremia were examined using Cox proportional hazards regression with adherence as a time-varying covariate. RESULTS: Among 802 women in the CTART arm, median age at entry was 27 years and median CD4 T-cell count 696 cells/mm. Of 175 women in CTART with viremia (22%), 141 had resistance data, and 12% had resistance to their current regimen. There was an estimated 0.12 probability of viremia by week 48 and 0.25 by week 144. Predictors of viremia included missed ART doses within the past 4 weeks, younger age, shorter duration of pre-entry ART, and being from the South American/Caribbean region. Of 137 women in DCART who reinitiated therapy, probability of viremia was similar to CTART (0.24 by week 96; 0.27 by week 144). CONCLUSIONS: Rates of postpartum viremia are high and viremia is more likely in younger postpartum women who start ART later in pregnancy. Interventions should target these higher-risk women.

Pharmacokinetics and safety of caspofungin in older infants and toddlers.

Although information about the efficacy and safety experience with caspofungin at 50 mg/m(2) daily is available for children and adolescents, the dosing regimen in infants and toddlers 3 to 24 months of age has yet to be established. We studied the pharmacokinetics and safety of caspofungin at 50 mg/m(2) once daily in nine patients 10 to 22 months (median, 13 months) of age with fever and neutropenia who received caspofungin once daily for 2 to 21 (mean, 9.3) days. Plasma caspofungin concentrations were measured by high-performance liquid chromatography assay on days 1 and 4. On day 4, the area under the curve from 0 to 24 h (AUC(0-24)) was 130.3 microg-h/ml, the peak concentration (C(1)) was 17.2 microg/ml, and the trough concentration (C(24)) was 1.6 microg/ml. The day 4 geometric mean ratios (GMRs) and 90% confidence interval (CI) for these parameters in infants/toddlers relative to adults were 1.26 (1.06, 1.50), 1.83 (1.57, 2.14), and 0.81 (0.64, 1.04), respectively. Relative to children (2 to 11 years of age), the day 4 GMRs (and 90% CI) were 1.13 (0.89, 1.44), 1.10 (0.85, 1.42), and 1.12 (0.72, 1.76), respectively. The harmonic mean elimination phase t(1/2) in infants/toddlers (8.8 h) was reduced approximately 33% relative to adults (13.0 h) but was similar to that in children (8.2 h). Clinical adverse events occurred in seven patients (78%); none were considered drug related. Laboratory adverse events occurred in five patients (56%) and were considered drug related in three (33%). There were no infusion-related events or discontinuations due to toxicity. Caspofungin at 50 mg/m(2) daily was well tolerated in infants and toddlers; the AUC and caspofungin C(24) were generally comparable to those in adults receiving caspofungin at 50 mg daily.

Etiology and clinical course of febrile neutropenia in children with cancer.

BACKGROUND: The etiology, clinical course, and outcome of fever and neutropenia (FN) in children with cancer using the current FN guidelines and diagnostic resources in the United States have not been well described. PATIENTS AND METHODS: Medical records of a randomly selected FN episode per patient during 2004-2005 at a pediatric oncology center were reviewed. Patients were managed as per institutional FN guidelines and blood cultures collected in continuously read BACTEC bottles. RESULTS: Of 337 FN episodes, infection was proven in 86 (25%) and probable in 75 (22%). In all, 177 episodes (53%) were judged fever of unknown origin (FUO). Bacteremia accounted for most (41) of the proven bacterial episodes, with viridans streptococci (13), Pseudomonas spp. (6) and Escherichia coli (6) the most frequently isolated organisms. The median time to positivity of blood cultures was 12 hours (range, 5.4-143.7) with 93% positive within 24 hours of incubation. Viral pathogens were identified in 29 (34%) episodes. Compared with other patients, those with FUO had shorter median duration of fever (0.5 vs. 2.0 d; P<0.0001) and hospitalization (3 vs. 6 d; P<0.0001), longer median duration since last chemotherapy (6.0 vs. 4.0 d; P=0.01), and were less likely to have a diagnosis of acute myelogenous leukemia (11% vs. 22%; P=0.009) or develop a clinical complication (5.1% vs. 24.4%; P<0.0001). CONCLUSIONS: Despite currently available diagnostic resources, the majority of patients with FN have FUO marked by a low rate of clinical complications and no infection-related mortality. Emergence of viridans streptococci as the most common blood isolate has affected FN treatment recommendations. Study findings will help further development of strategies for risk stratified management of fever with neutropenia in pediatric patients.

Co-located Retail Clinics and Pharmacies: An Opportunity to Provide More Primary Care.

This paper proposes that co-located retail clinics (RCs) and community pharmacies can increase opportunities to provide more accessible, affordable, and patient-friendly primary care services in the United States. RCs are small businesses of about 150-250 square feet with a clientele of about 10-30 patients each day and most frequently staffed by nurse practitioners (NPs). Community pharmacies in the U.S. at ~67,000 far outnumber RCs at ~2800, thereby opening substantial opportunity for growth. Community pharmacies and pharmacists have been working to increase on-site clinical services, but progress has been slowed by the relative isolation from other practitioners. An ideal merged facility based on an integrated platform is proposed. NPs and pharmacists could share functions that fulfill documented consumer preferences and still maintain separate practice domains. Potential benefits include a broader inventory of clinical services including laboratory tests, immunizations, patient education, and physical assessment, as well as better patient access, interprofessional training opportunities, and economies related to the use of resources, day-to-day operations, and performance metrics. Challenges include the availability of sufficient, appropriately trained staff; limitations imposed by scope of practice and other laws; forging of collaborative relationships between NPs and pharmacists; and evidence that the merged operations provide economic benefits beyond those of separate enterprises.