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.

Imunização da gestante em tempos de pandemia da COVID-19 / Inmunización de mujeres embarazadas en tiempos de pandemia de COVID-19 / Immunization of pregnant women in times of the COVID-19 pandemic

Objetivo: analisar e comparar a imunização de gestantes no período da pandemia da COVID-19 no Oeste do Paraná. Método: pesquisa analítica e transversal, realizada na nona e décima regionais de saúde do Paraná. Participaram 823 puérperas, a coleta de dados foi conduzida por inquérito e informações do prontuário entre setembro a dezembro de 2021. Utilizaram-se análise descritiva e teste de qui-quadrado com nível significância de 5%. Resultados: a nona regional apresentou melhor desempenho na imunização contra Hepatite-B, Influenza, Difteria, Tétano e Coqueluche em comparação à décima regional. A vacinação contra COVID-19 teve baixa adesão em ambas as regionais, cujos motivos foram: medo, opção própria, orientação médica e desejo de esperar o filho nascer. Conclusão: são necessárias novas estratégias e campanhas de sensibilização para aumentar o índice vacinal entre gestantes, sobretudo para a vacina contra COVID-19, considerando as complicações para a saúde materno-infantil.

Objective: analyze and compare the immunization of pregnant women during the COVID-19 pandemic in western Paraná. Method: this is an analytical, cross-sectional study carried out in the ninth and tenth regional health departments of Paraná. A total of 823 puerperal women took part, and data was collected using a survey and information from medical records between September and December 2021. Descriptive analysis and the chi-square test were used, with a significance level of 5%. Results: the ninth region performed better in immunization against Hepatitis-B, Influenza, Diphtheria, Tetanus and Pertussis compared to the tenth region. Vaccination against COVID-19 had low uptake in both regions, the reasons for which were: fear, own choice, medical advice and the wish to wait for the child to be born. Conclusion: new strategies and awareness campaigns are needed to increase the vaccination rate among pregnant women, especially for the COVID-19 vaccine, considering the complications for maternal and child health.

Objetivo: analizar y comparar la inmunización de mujeres embarazadas durante la pandemia de COVID-19 en el Oeste de Paraná. Método: investigación analítica y transversal, realizada en la novena y décima región sanitaria de Paraná. Participaron 823 puérperas. La recolección de datos se realizó mediante encuesta e información de historias clínicas entre septiembre y diciembre de 2021. Se utilizó análisis descriptivo y prueba de chi cuadrado con un nivel de significancia del 5%. Resultados: la novena región presentó mejor desempeño en inmunización contra Hepatitis B, Influenza, Difteria, Tétanos y Tos Ferina en comparación con la décima región. La vacunación contra la COVID-19 tuvo baja adherencia en ambas regiones y los motivos fueron: miedo, elección personal, consejo médico y deseo de esperar a que nazca el niño. Conclusión: son necesarias nuevas estrategias y campañas de sensibilización para aumentar la tasa de vacunación entre las mujeres embarazadas, especialmente de la vacuna contra la COVID-19, considerando las complicaciones para la salud materna e infantil.

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.

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.

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.

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.

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.

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.

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.

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.

Efficient and effective precepting of pharmacy students in acute and ambulatory care rotations: A Delphi expert panel study.

PURPOSE: Using the Delphi process, a panel of experienced preceptors achieved consensus on best practices to increase preceptor efficiency and effectiveness. METHODS: The Delphi panelists completed 3 survey rounds and a face-to-face meeting. Survey questions covered several topics, including preparation of students for rotations, preceptor efficiency and effectiveness, potential resident contributions to precepting, methods of developing critical-thinking skills and providing assessment and feedback, precepting time metrics, and barriers to preceptor effectiveness. Panel consensus was defined as agreement of ≥80%. RESULTS: Fifteen of 36 invited preceptors (42%) completed all 3 survey rounds. The expert panel reached consensus on 6 essentials for effective rotations, 8 precepting contributions that could be made by appropriately trained residents, precepting barriers, 4 strategies for teaching critical thinking, and 5 valuable characteristics of the One Minute Preceptor model. Panelists reported on time spent with students presenting new patient cases (median, 10 minutes per case), time devoted to assessment of students' clinical performance (median, 22 minutes per student weekly), and time dedicated to student professional development (median, 20 minutes per student weekly). CONCLUSION: Important strategies for preceptors identified by the panel included (1) a thorough orientation to logistics, expectations, and scheduling of activities, (2) using appropriately trained residents in student training, (3) providing opportunities for critical thinking and therapeutic decision-making, (4) giving frequent, quality feedback on clinical activities, and (5) giving feedback to learners on a regular basis.

Blood lead levels and neurodevelopmental function in perinatally HIV-exposed, uninfected children in a US-based longitudinal cohort study.

BACKGROUND: While children's exposure to environmental lead in the U.S. has decreased, areas of elevated levels remain. Because lead exposure is a risk factor for developmental delays, it should be considered when studying neurodevelopmental effects of in-utero antiretroviral medication (ARV) exposure in the growing population of perinatally HIV-exposed, uninfected children (PHEU). We compared blood lead levels (BPb) in PHEU children enrolled in the Surveillance Monitoring of ART Toxicities (SMARTT) Study to U.S. children, assessed associations with neurodevelopment, and explored whether associations between in-utero ARV and neurodevelopment are modified by BPb. METHODS: Prevalence of elevated BPb (≥5 µg/dL) at ages 1-2 years was calculated by year and race/ethnicity and compared to that for children in the National Health and Nutrition Examination Survey (NHANES 2002-2010). Associations between elevated BPb and neurodevelopment at 1 and 3 years were assessed. Associations between ARVs (tenofovir disopropil fumarate [TDF]; atazanavir) and neurodevelopment were evaluated within BPb level (≥5 vs. <5 µg/dL). RESULTS: Mean BPb in SMARTT decreased from 5.9 to 2.7 µg/dL between 1998-2014; prevalence of elevated BPb decreased from 50% to 4%. Both were consistently higher than in NHANES. Elevated BPb was associated with cognitive delay at age 3 (adjusted odds ratio: 1.64; 95% CI: 0.95, 2.90). At age 1, TDF was associated with delay only among those with elevated BPb. CONCLUSIONS: PHEU children more often had elevated BPb than the general U.S. pediatric population. Exposure to environmental lead is one of several factors that may place these children at higher risk for neurodevelopmental delay.

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.

Board-Certified Oncology Pharmacists: Their Potential Contribution to Reducing a Shortfall in Oncology Patient Visits.

PURPOSE: With an aging US population, the number of patients who need cancer treatment will increase significantly by 2020. On the basis of a predicted shortage of oncology physicians, nonphysician health care practitioners will need to fill the shortfall in oncology patient visits, and nurse practitioners and physician assistants have already been identified for this purpose. This study proposes that appropriately trained oncology pharmacists can also contribute. The purpose of this study is to estimate the supply of Board of Pharmacy Specialties-certified oncology pharmacists (BCOPs) and their potential contribution to the care of patients with cancer through 2020. METHODS: Data regarding accredited oncology pharmacy residencies, new BCOPs, and total BCOPs were used to estimate oncology residencies, new BCOPs, and total BCOPs through 2020. A Delphi panel process was used to estimate patient visits, identify patient care services that BCOPs could provide, and study limitations. RESULTS: By 2020, there will be an estimated 3,639 BCOPs, and approximately 62% of BCOPs will have completed accredited oncology pharmacy residencies. Delphi panelists came to consensus (at least 80% agreement) on eight patient care services that BCOPs could provide. Although the estimates given by our model indicate that BCOPs could provide 5 to 7 million 30-minute patient visits annually, sensitivity analysis, based on factors that could reduce potential visit availability resulted in 2.5 to 3.5 million visits by 2020 with the addition of BCOPs to the health care team. CONCLUSION: BCOPs can contribute to a projected shortfall in needed patient visits for cancer treatment. BCOPs, along with nurse practitioners and physician assistants could substantially reduce, but likely not eliminate, the shortfall of providers needed for oncology patient visits.

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.

A Prospective, International Cohort Study of Invasive Mold Infections in Children.

BACKGROUND: Invasive mold infections (IMIs) are a leading cause of mortality in immunocompromised children, yet there has never been an international epidemiologic investigation of pediatric IMIs. METHODS: This international, prospective cohort study was performed to characterize the epidemiology, antifungal therapy, and outcomes of pediatric IMIs. Children (≤18 years) with proven or probable IMIs were enrolled between August 2007 and May 2011 at 22 sites. Risk factors, underlying diagnoses, and treatments were recorded. Outcomes were assessed at 12 weeks after diagnosis using European Organization for Research and Treatment of Cancer/Mycoses Study Group response criteria. RESULTS: One hundred thirty-one pediatric patients with IMIs were enrolled; the most common IMI was invasive aspergillosis ([IA] 75%). Children with IA and those with other types of IMIs had similar underlying risk factors, except that children with IMIs caused by non-Aspergillus species were more likely to have received mold-active antifungal agents preceding diagnosis. The most commonly used antifungal classes after diagnosis were triazoles (82%) and polyenes (63%). Combination therapy was used in 53% of patients. Use of combination therapy was associated with an increased risk of adverse events (risk ratio, 1.98; 95% confidence interval, 1.06-3.68; P = .031), although there was no detectable difference in outcome. CONCLUSIONS: Although risk factors for IMIs are similar across specific subtypes, preceding antifungal therapy may be an important modifier. Combination antifungal therapy requires further study to determine its true risks and benefits.

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.