bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment of inoperable elderly head and neck cancer patients
Authors: Guigay Joël , Le Caer Hervé , Ortholan Cécile , Aupérin Anne , Michel Cécile , Mertens Cécile 
Published: April 2019

Purpose of review
Elderly head and neck cancer (HNC) patients are very rarely enrolled in clinical trials, and even more so in dedicated trials in curative or palliative setting. As a result, no standards of treatment exist for this population and thus, adaptation of standard treatments is commonly used.

Recent findings
The choice between a monotherapy and a platinum–cetuximab combination is based on the performance status, which is not suitable and/or sufficient to evaluate the patient ability to receive a systemic treatment combined or not with radiotherapy. The evaluation of functional age using geriatric assessment is recommended. However, access to comprehensive geriatric assessment is limited in many centers, and the choice of the type of treatment is often not based on objective and reproducible criteria. As a result, fragile elderly HNC patients may be overtreated with a risk of increased toxicity and fit patients proposed for suboptimal treatment with a risk of failure of tumor control.

Summary
It is therefore crucial to develop and evaluate customized treatments by enrolling elderly HNC patients in dedicated therapeutics trials, such as the ELAN (Elderly Head and Neck Cancer) studies or new approaches involving promising immunotherapies. To administer the most suitable therapy, a simple and reproducible geriatric assessment could efficiently guide practitioners.
Attention-Deficit Hyperactivity Disorder in Pediatric Patients With Type 1 Diabetes Mellitus: Clinical Outcomes and Diabetes Control
Authors: Vinker-Shuster Michal , Golan-Cohen Avivit , Merhasin Ilia , Merzon Eugene 
Published: April 2019

ABSTRACT:

Objective:
To assess the interactions between attention-deficit hyperactivity disorder (ADHD) and type 1 diabetes mellitus (T1DM), including diabetes outcomes and patients' general health status.

Methods:
Primary care and hospital records of patients aged 5 to 18 years with T1DM were analyzed using the Leumit Health Services database. The diabetic control and general health of patients with T1DM and ADHD diagnoses were compared with those of patients with T1DM alone in a cross-sectional study. The ADHD group included patients with ADHD diagnosis who purchased at least 3 prescriptions of psychostimulant agents and nootropics. Parameters including demographic, clinical, and laboratory data were collected and assessed.

Results:
The study included 230 patients with T1DM; of them, 24 had ADHD (10.4%). Twenty of 24 patients with ADHD (83.3%) had hemoglobin A1C of 9% and higher versus 87 of 206 patients with diabetes alone (43.3%) (p < 0.05). The ADHD group had significantly higher annual emergency department admissions [15/24 (62.5%) vs 77/201 (37.4%); p < 0.05], higher annual hospitalization rates [18/24 (75%) vs 78/206 (37.9%); p < 0.05], and longer hospitalization stays (mean, 2.21 vs 0.65 days; p < 0.05). The total medical annual costs per patient were twice as high in the ADHD group (p < 0.05). In multivariate analysis, these unfavorable outcomes of the ADHD group were preserved.

Conclusion:
In this study, having ADHD and T1DM comorbidity was associated with a higher complications rate and poorer diabetes control in comparison to having T1DM alone. Although further research is needed, our data suggest that this group requires special care and attention of the medical staff.
Having an Adult Child in the United States, Physical Functioning, and Unmet Needs for Care Among Older Mexican Adults
Authors: Torres Jacqueline M. , Rudolph Kara E. , Sofrygin Oleg , Wong Rebeca , Walter Louise C. , Glymour M. Maria 
Published: April 2019

Background:
Migration of adult children may impact the health of aging parents who remain in low- and middle-income countries. Prior studies have uncovered mixed associations between adult child migration status and physical functioning of older parents; none to our knowledge has examined the impact on unmet caregiving needs.

Methods:
Data come from a population-based study of Mexican adults ≥50 years. We used longitudinal targeted maximum likelihood estimation to estimate associations between having an adult child US migrant and lower-body functional limitations, and both needs and unmet needs for assistance with basic or instrumental activities of daily living (ADLs/IADLs) for 11,806 respondents surveyed over an 11-year period.

Results:
For women, having an adult child US migrant at baseline and 2-year follow-up was associated with fewer lower-body functional limitations [marginal risk difference (RD) = −0.14, 95% confidence interval (CI) = −0.26, −0.01] and ADLs/IADLs (RD = −0.08, 95% CI = −0.16, −0.001) at 2-year follow-up. Having an adult child US migrant at all waves was associated with a higher prevalence of functional limitations at 11-year follow-up (RD = 0.04, 95% CI = 0.01, 0.06). Having an adult child US migrant was associated with a higher prevalence of unmet needs for assistance at 2 (RD = 0.13, 95% CI = 0.04, 0.21) and 11-year follow-up for women (RD = 0.07, 95% CI = −0.02, 0.15) and 11-year follow-up for men (RD = 0.08, 95% CI = 0.00, 0.16).

Conclusion:
Having an adult child US migrant had mixed associations with physical functioning, but substantial adverse associations with unmet caregiving needs for a cohort of older adults in Mexico.
Metabolic Syndrome and the Effectiveness of Low-dose Aspirin on Reproductive Outcomes
Authors: Nobles Carrie J. , Mendola Pauline , Mumford Sunni L. , Kim Keewan , Sjaarda Lindsey , Hill Micah , Silver Robert M. , Naimi Ashley I. , Perkins Neil J. , Schisterman Enrique F. 
Published: April 2019

Background:
Metabolic syndrome is associated with increases in both inflammation and aspirin resistance, but effectiveness of aspirin in improving reproductive health among women with metabolic syndrome is unknown. We evaluated the effectiveness of low-dose aspirin in improving reproductive outcomes across metabolic syndrome score.

Methods:
The EAGeR trial randomly assigned 1228 women with a history of pregnancy loss to receive 81 mg aspirin or placebo for up to six menstrual cycles of attempting pregnancy and, if they became pregnant, throughout pregnancy. We assessed components of metabolic syndrome at enrollment, including: waist circumference ≥88 cm, triglycerides ≥150 mg/dl, high-density lipoprotein ≤50 mg/dl, blood pressure ≥130 mmHg systolic or ≥85 mmHg diastolic, and glucose ≥100 mg/dl. We summed components to calculate metabolic syndrome score.

Results:
A total of 229 participants (20%) met full criteria for metabolic syndrome, 207 (18%) had two components, 366 (31%) one component, and 372 (32%) no components. Among those without any component of metabolic syndrome, aspirin was associated with 10.7 [95% confidence interval (CI) = 1.2, 20.2] more pregnancies and 13.7 (95% CI = 3.3, 24.0) more live births per 100 couples. Effects were attenuated as metabolic syndrome score increased and we observed no clear effect of aspirin on pregnancy or live birth among women with metabolic syndrome.

Conclusions:
Low-dose aspirin is most effective in increasing pregnancy and live birth among women with no or few components of metabolic syndrome. Reduced effectiveness among women with metabolic syndrome may be due to differences in effective dose or aspirin resistance.
Can Hyperparameter Tuning Improve the Performance of a Super Learner?
Authors: Wong Jenna , Manderson Travis , Abrahamowicz Michal , Buckeridge David L , Tamblyn Robyn 
Published: April 2019

Background:
Super learning is an ensemble machine learning approach used increasingly as an alternative to classical prediction techniques. When implementing super learning, however, not tuning the hyperparameters of the algorithms in it may adversely affect the performance of the super learner.

Methods:
In this case study, we used data from a Canadian electronic prescribing system to predict when primary care physicians prescribed antidepressants for indications other than depression. The analysis included 73,576 antidepressant prescriptions and 373 candidate predictors. We derived two super learners: one using tuned hyperparameter values for each machine learning algorithm identified through an iterative grid search procedure and the other using the default values. We compared the performance of the tuned super learner to that of the super learner using default values (“untuned”) and a carefully constructed logistic regression model from a previous analysis.

Results:
The tuned super learner had a scaled Brier score (R
2) of 0.322 (95% [confidence interval] CI = 0.267, 0.362). In comparison, the untuned super learner had a scaled Brier score of 0.309 (95% CI = 0.256, 0.353), corresponding to an efficiency loss of 4% (relative efficiency 0.96; 95% CI = 0.93, 0.99). The previously-derived logistic regression model had a scaled Brier score of 0.307 (95% CI = 0.245, 0.360), corresponding to an efficiency loss of 5% relative to the tuned super learner (relative efficiency 0.95; 95% CI = 0.88, 1.01).

Conclusions:
In this case study, hyperparameter tuning produced a super learner that performed slightly better than an untuned super learner. Tuning the hyperparameters of individual algorithms in a super learner may help optimize performance.
Characterizing the joint effects of pesticide exposure and criteria ambient air pollutants on pediatric asthma morbidity in an agricultural community
Authors: Benka-Coker Wande O. , Loftus Christine , Karr Catherine , Magzamen Sheryl 
Published: April 2019

Background:
Environmental contributions to pediatric asthma morbidity have been studied extensively in urban settings; exposures characteristic of agricultural and rural communities have received less attention despite a comparable burden of morbidity.

Methods:
We obtained repeated urine samples (n = 139) from 16 school-age children with asthma in the Yakima Valley of Washington State between July and October 2012. Biomarkers of organophosphate (OP) pesticide exposure (dialkyl phosphates [DAPs]) and asthma exacerbation (leukotriene E4 [LTE4]) were analyzed in samples. Corresponding 24-hour average particulate matter <2.5 μg (PM2.5) and maximum 8-hour ozone concentration data for the study period were available from local monitoring stations. We evaluated the independent and multi-pollutant associations between LTE4 and exposure to ambient air pollutants and DAPs using generalized estimating equations. For multi-domain and multi-pollutant models, we created categorized pollution combination levels and estimated the relative health impact of exposure to pollutant mixtures.

Results:
In single-pollutant models, an interquartile range increase in exposures to DAPs was associated with increase in LTE4 levels (β: 4.1 [0.6–7.6] pg/mg). PM2.5 and ozone were also associated with increase in LTE4, though confidence intervals contained the null value. Increase in LTE4 levels was consistently associated with increase in median-dichotomized multi-pollutant combination exposures; the highest effect estimates were observed with joint highest (vs. the lowest) category of the three-pollutant exposure (PM2.5, ozone, and OP; β: 53.5, 95% confidence interval = 24.2, 82.8 pg/mg).

Conclusion:
Concurrent short-term exposure to criteria air pollutants and OPs in an agricultural community was associated with an increase in a marker of asthma morbidity.
Pharmacokinetics of Anticancer Drugs Used in Treatment of Older Adults With Colorectal Cancer: A Systematic Review
Authors: Shafiei Mohsen , Yoon Robert , McLachlan Andrew , Boddy Alan , Beale Philip , Blinman Prunella 
Published: April 2019

Purpose:
Older adults with cancer experience more toxicity from anticancer therapy, possibly because of age-related changes in the pharmacokinetic (PK) profile of anticancer drugs. We aimed to evaluate studies investigating the effect of aging on the PK of anticancer therapies used in the treatment of colorectal cancer (CRC).

Methods:
A systematic literature search of EMBASE and PubMed was performed to find eligible studies that assessed the effect of age on the PK of anticancer therapies used in the treatment of CRC.

Results:
The 21 eligible studies included 17 prospective studies and 4 pooled analyses of prospective studies. Of these, PK of 5-fluorouracil (5-FU) was determined in 7 studies, oxaliplatin in 2 studies, capecitabine in 3 studies, irinotecan in 4 studies, bevacizumab in 1 study, cetuximab in 3 studies, and panitumumab in 1 study. Studies included a median of 44 patients and had varying definitions for older adults: 65 years or older (3 studies), older than 70 years (3 studies), or older than 75 years (1 study). Increasing age significantly affected the PK parameters of irinotecan with a 7%–8% reduction in CL (P < 0.001) for every 10 years in patients older than 60 years and an increase in area under the curve (r = 0.44, P = 0.007) and Cmax (r = 0.42, P = 0.009).

Conclusions:
Older age mainly influences PK of irinotecan and, to some extent, that of capecitabine, 5-FU, and panitumumab, but there is limited evidence for age-related changes in PK of other anticancer therapies used in the management of older adults with CRC. Factors other than PK may be responsible for the greater toxicity of these agents experienced by older adults.
Effect of Radiation Dose Rate on Cancer Mortality among Nuclear Workers: Reanalysis of Hanford Data
Authors: Sasaki Michiya , Kudo Shin’ichi , Furuta Hiroshige 
Published: April 2019

Abstract
The excess relative risk of mortality for all cancers excluding leukemia among nuclear workers was reanalyzed by taking the annual dose as the dose rate into consideration using publicly available epidemiological data from the Hanford site dedicated to the cohort study of nuclear workers in the United States, the United Kingdom, and Canada (Three Countries Study). Values of the dose rate (cut points) were chosen at 2 mSv y−1 intervals from 2 to 40 mSv y−1, and risk estimates were made for 32,988 workers, considering doses accumulated below the cut point and above the cut point to have different effects. Although the procedure to extract the study population and the methodology used for analysis basically followed those in the Three Countries Study, additional examinations were also carried out for different risk models, lag periods, and impacts of adjusting the monitoring period to find the effect of the dose rate. As a result, no statistically significant difference in dose rate was found among the excess relative risks under different calculation conditions.
The Clinical Presentation of Pediatric Mycoplasma pneumoniae Infections—A Single Center Cohort
Authors: Gordon Oren , Oster Yonatan , Michael-Gayego Ayelet , Marans Rachel S. , Averbuch Dina , Engelhard Dan , Moses Allon E. , Nir-Paz Ran 
Published: April 2019

Background:

Mycoplasma pneumoniae (MP) is a major cause of community-acquired upper and lower respiratory infections in school-age children; however, there is increasing recognition that younger children are also affected. Clinical manifestations vary from asymptomatic, to severe complicated pneumonia sometimes with extrapulmonary manifestations.

Methods:
We reviewed the medical records of all MP positive pediatric patients admitted to the Hadassah-Hebrew University Medical Center. MP positive case was defined if MP polymerase chain reaction was positive from an oropharyngeal swab sent from 2007 to 2017.

Results:
During the study period, we identified 353 MP positive pediatric cases, of which 51.3% (181 of 353) were younger than 6 years old. Full clinical data were available for 332 of 353 (94%). The median age was 5.7 years (range, 3 weeks to 18 years). Disease presentation differed between younger and older children. Children older than 6 years were more likely to have chest radiograph confirmed pneumonia (66% vs. 52%; P = 0.009), while younger children were more likely to have other respiratory manifestations (37% vs. 25%; P = 0.017). The duration of hospitalization and pediatric intensive care unit admission rate, however, did not differ between age groups. The rate of extrapulmonary manifestations were also similar.

Conclusions:
MP-associated infection is a significant cause of hospitalization in the pediatric population including younger children (<6 years old). However, the clinical presentation in younger age is less typical than is thought. These findings should prompt clinicians to consider MP infections also in children younger than 6 admitted with fever even without pneumonia.
Outcomes of a Comprehensive Retention Strategy for Youth With HIV After Transfer to Adult Care in the United States
Authors: Griffith David , Jin Lillian , Childs Jocelyn , Posada Roberto , Jao Jennifer , Agwu Allison 
Published: April 2019

Background:
The retention of youth living with HIV (YLHIV) in adult care after transfer from pediatric care in the United States is a challenge. A targeted comprehensive retention strategy (CRS) may improve retention among YLHIV.

Methods:
A retrospective cohort study of YLHIV after transfer from pediatric to adult care for patients with at least 1 adult visit at 2 urban HIV care programs in the United States employing CRSs with internal medicine/pediatrics-trained providers, peer navigators, social workers and mental health resources. Primary outcomes were successful retention in care after transfer (≥2 provider visits in the adult clinic ≥90 days apart within 1 year of transfer) and successful transition (successful retention plus a stable HIV viral load (VL) defined as VL 1 year after transfer that was less than or equal to the VL obtained at or immediately before transfer). Logistic regression assessed factors associated with successful transition. A subgroup analysis was performed to examine rates of successful transfer and linkage from pediatric to adult clinics (attending at least 1 adult visit after transition).

Results:
Of the 89 patients included in the study, 79 (89%) patients had successful retention and 53 (60%) had successful transition to the adult program. Factors associated with successful transition included non-African American race [adjusted odds ratio (aOR) = 11.26, 95% confidence interval (CI): 1.32–95.51], perinatal HIV (aOR = 8.00, 95% CI: 1.39–46.02) and CD4 count > 500 cells/mm3 (aOR = 5.22, 95% CI: 1.54–17.70). Of those who were retained, 53/79 (67%) had stable or improved virologic control at 1 year after transition. In a subgroup analysis, 54/56 (96%) patients who were targeted to transition successfully linked to adult care.

Conclusions:
Overall, YLHIV in the United States engaged in a CRS program appear to have high retention rates but suboptimal virologic control after transfer from pediatric HIV care.
Children With Noncritical Infections Have Increased Intestinal Permeability, Endotoxemia and Altered Innate Immune Responses
Authors: Sturgeon Jonathan P. , Bourke Claire D. , Prendergast Andrew J. 
Published: April 2019

Background:
Children with critical illness have increased intestinal permeability and a period of immunoparalysis, mediated by elevated circulating endotoxin. Whether children with less severe infections have similar changes is uncertain.

Methods:
We conducted a proof-of-concept pilot study, enrolling children 6–59 months of age hospitalized for noncritical infections (cases, n = 11) and noninfected controls (n = 19). Intestinal permeability was measured by lactulose–mannitol recovery. Plasma endotoxin, blood monocyte and neutrophil immunophenotypes and cytokine elaboration following 24-hour whole-blood culture with antigens targeting distinct innate pathogen recognition receptor signaling pathways were evaluated.

Results:
Cases had higher intestinal permeability and plasma endotoxin levels than controls. Among cases versus controls, fewer monocytes expressed human leukocyte antigen DR isotype (HLA-DR) (87.1% vs. 96.4%, P = 0.001), and more expressed CD64 (99.6% vs. 97.6%, P = 0.041). Following zymosan stimulation of whole blood, cases versus controls produced less interleukin 1 beta (IL-1β) (median 1101 vs. 2604 pg/mL, P = 0.048) and tumor necrosis factor alpha (TNF-α) (2342 vs. 5130 pg/mL, P = 0.031). Children with higher (≥0.1 endotoxin unit (EU)/mL) versus lower (<0.1 EU/mL) circulating endotoxin had fewer monocytes expressing CD86 (69.8% vs. 92.4%, P = 0.003) and less expression of CD64 following 24-hour zymosan stimulation (median fluorescence intensity (MFI) 1514 vs. 2196, P = 0.022).

Conclusions:
Children hospitalized with noncritical infections had increased intestinal permeability, endotoxemia and altered monocyte phenotype and function. Collectively, these changes are typical of immunoparalysis seen in children with critical illness and may increase the risk of subsequent infections.
In Utero Efavirenz Exposure and Neurodevelopmental Outcomes in HIV-exposed Uninfected Children in Botswana
Authors: Cassidy Adam R. , Williams Paige L. , Leidner Jean , Mayondi Gloria , Ajibola Gbolahan , Makhema Joseph , Holding Penny A. , Powis Kathleen M. , Batlang Oganne , Petlo Chipo , Shapiro Roger , Kammerer Betsy , Lockman Shahin 
Published: April 2019

Background:
Minimal data exist related to neurodevelopment after in utero exposure to Efavirenz (EFV). We sought to compare neurodevelopmental outcomes in HIV-exposed/uninfected (HEU) children with in utero exposure to EFV-based triple antiretroviral treatment (ART) versus non-EFV-based ART, and to examine whether timing of initial EFV exposure is associated with neurodevelopment deficits.

Methods:
Women living with HIV who had received EFV-based ART during pregnancy and whose HEU newborn participated in a prior study were reconsented for their HEU toddler to undergo neurodevelopmental testing at 24 months old. We administered the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III), Developmental Milestones Checklist (DMC) and Profile of Social Emotional Development (PSED). We compared outcomes to previously-collected data from a cohort of 24-month-old HEU children with in utero exposure to non-EFV-based ART. Adjusted general linear models were used to compare mean outcomes.

Results:
Our analysis included 493 HEU children (126 EFV-exposed, 367 EFV-unexposed). Adjusted mean scores for the EFV-exposed group were worse than the EFV-unexposed group on BSID-III Receptive Language (adjusted means = 21.5 vs. 22.5, P = 0.05), DMC Locomotor (30.7 vs. 32.0, P < 0.01) and Fine Motor scales (17.8 vs. 19.2, P < 0.01); and PSED (11.7 vs. 9.9, P = 0.02); but better on the DMC Language scale (17.6 vs. 16.5, P = 0.01). Earlier (vs. later) EFV exposure was associated with worse scores on the BSID-III Receptive Language scale (20.7 vs. 22.2, P = 0.02).

Conclusions:
HEU children exposed in utero to EFV-based ART may be at higher risk for neurodevelopmental and social-emotional deficits than HEU children exposed to non-EFV-based ART.