bluuebunny/crossref_metadata_2025 huggingface dataset:
The diagnostic performance of dual energy CT for diagnosing gout: a systematic literature review and meta-analysis
Authors: Gamala Mihaela , Jacobs Johannes W G , van Laar Jaap M
Published: April 2019

Objective

This study aimed to assess the utility of dual energy CT (DECT) for diagnosing gout.

Methods

A systematic literature search was performed in PubMed, EMBASE and Cochrane Library. Studies evaluating the utility of DECT for diagnosing gout were included. Reference standards were detection of monosodium urate crystals at SF assessment or a validated set of criteria. The methodological quality of studies was evaluated according to the Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 criteria. Data from person-based and joint-/localization-based evaluations were pooled separately, and subgroup analyses for disease stage/duration and reference standard were performed.

Results

Ten studies were included; in person-based evaluations, the pooled (95% CI) sensitivity and specificity were 0.81 (0.77, 0.86) and 0.91 (0.85, 0.95), respectively. In joint-based evaluations, they were 0.83 (0.79, 0.86) and 0.88 (0.83, 0.92), respectively. At short disease duration (⩽6 weeks), the pooled (95% CI) sensitivity and specificity at the joint level were 0.55 (0.46, 0.64) and 0.89 (0.84, 0.94), respectively.

Conclusion

DECT has a high diagnostic accuracy in established gout, but its diagnostic sensitivity is low in subjects with recent onset gout.
0936 Sleep Disturbances in Wolfram Syndrome
Authors: Licis Amy K , Davis Gabriel , Eisenstein Sarah , Lugar Heather , Hershey Tamara
Published: April 2019

Introduction

Wolfram syndrome is a rare disorder associated with diabetes mellitus, diabetes insipidus, optic nerve atrophy, hearing and vision loss, and neurodegeneration. Sleep complaints are common but have not been studied with objective measures. Our goal was to assess rates of sleep apnea and objective and self-reported measures of sleep quality, and to determine the relationship of sleep pathology to other clinical variables in Wolfram syndrome patients.

Methods

Genetically confirmed Wolfram syndrome patients were evaluated at the 2015 and 2016 Washington University Wolfram Syndrome Research Clinics. Patients wore an actigraphy device and a type III ambulatory sleep study device and completed the Epworth Sleepiness Scale (ESS), the Pittsburgh Sleep Quality Index (PSQI) and/or the Pediatric Sleep Questionnaire (PSQ). PSQI and PSQ questionnaire data were compared to a previously collected group of controls. Patients were characterized clinically with the Wolfram Unified Rating Scale (WURS) and a subset underwent magnetic resonance imaging (MRI) for brain volume measurements.

Results

Twenty-one patients were evaluated ranging from age 8.9 - 29.7 years. Five of 17 (29%) adult patients fit the criteria for obstructive sleep apnea (OSA; apnea-hypopnea index [AHI] ≥ 5) and all 4 of 4 (100%) children aged 12 years or younger fit the criteria for obstructive sleep apnea (AHI’s ≥1). Higher AHI was related to greater disease severity (higher WURS Physical scores). Higher mixed apnea scores were related to lower brainstem and cerebellar volumes. Patients’ scores on the PSQ were higher than those of controls, indicating greater severity of childhood obstructive sleep-related breathing disorders.

Conclusion

Wolfram syndrome patients had a high rate of OSA. Further study would be needed to assess how these symptoms change over time. Addressing sleep disorders in Wolfram syndrome patients would likely improve their overall health and quality of life.

Support (If Any)

This work was supported by the NICHD (HD070855; Hershey, PI) and supported by CTSA (UL1 RR024992) and Diabetes Research Center (DK 020579).
A comparative atlas of the skull osteology of European lizards (Reptilia: Squamata)
Authors: Villa Andrea , Delfino Massimo
Published: April 2019

The fossil record provides evidence of a long evolutionary history of European lizards. Since fossil lizards are regularly represented by bone remains, the knowledge of the origins of extant taxa and their distribution in time and space is hindered by the fact that their comparative osteology is not yet completely and adequately known. In spite of a rising interest in this topic since the end of the 20th century, a gap in our knowledge is still evident. We here report the first broad-scale comparative osteological analysis of the skulls of extant European lizards, highlighting significant differences that can be used in identification. This comparative study, including as many European species as possible, leads to the creation of a detailed diagnostic key for each single bone. Also, our data significantly improve the recognizability of extant European non-snake squamates, with 54% of the current diversity to be recognized based on the new results contra the previously estimated 31%. This recognizability is expected to further increase in the future, with new studies focusing on species that are either missing or poorly represented here, or applying promising advanced methodologies.
CE: Assessing a Child's Pain
Authors: Freund Debra , Bolick Beth N.
Published: April 2019

Effective pain assessment is a necessary component of successful pain management and the pursuit of optimal health outcomes for patients of all ages. In the case of children, accurate pain assessment is particularly important, because children exposed to prolonged or repeated acute pain, including procedural pain, are at elevated risk for such adverse outcomes as subsequent medical traumatic stress, more intense response to subsequent pain, and development of chronic pain.

As with adults, a child's self-report of pain is considered the most accurate and reliable measure of pain. But the assessment of pain in children is challenging, because presentation is influenced by developmental factors, and children's responses to certain features of pain assessment tools are unlike those commonly observed in adults.

The authors describe the three types of assessment used to measure pain intensity in children and the tools developed to address the unique needs of children that employ each. Such tools take into account the child's age as well as special circumstances or conditions, such as ventilation requirements, cognitive impairment, and developmental delay. The authors also discuss the importance of proxy pain reporting by the parent or caregiver and how nurses can improve communication between the child, caregiver, and health care providers, thereby promoting favorable patient outcomes.
What Are the Attitudes and Beliefs of Oncologists Regarding Potential Cancer Rehabilitation in a Tertiary Cancer Center?
Authors: Francis George J. , Fu Jack B.
Published: April 2019

Introduction:

Cancer rehabilitation (CR) is an emerging field in physical medicine and rehabilitation. Current literature highlights the effectiveness of CR in improving functional outcomes, shorter length of hospital stay, and improved quality of life. Despite this, there are very few formalized CR programs across all of North America.

Methods:

We conducted a survey at a tertiary cancer center without a formalized CR program to assess the perceived need of such a program and its potential development.

Results:

This survey of medical, surgical, radiation, and pediatric oncologists demonstrated that 92.3% of 39 respondents felt CR was somewhat to very important, particularly for their patients' issues of fatigue, deconditioning, pain management, and disposition planning.

Conclusion:

These findings highlight the value seen by oncologists in the need for further CR access and formalized program development in order to meet patient needs for improving functional deficits, activities of daily living, and quality of life.
Lateral versus medial offset design for reverse shoulder replacement
Authors: Ho Jason C. , Kane Liam T. , Abboud Joseph A.
Published: April 2019

Reverse total shoulder arthroplasty (RTSA) has become significantly more popular in recent years due to expanding indications and successful long-term outcomes being reported. RTSA has undergone several iterations throughout history that has led to modern-day designs. What initially started as a salvage procedure for cuff-deficient shoulders is now commonly used for a variety of reconstructive shoulder problems not limited just to those without a functioning rotator cuff. The goal of this article was to compare and contrast lateral and medial offset designs for RTSA. Details of both glenoid and humeral-sided design characteristics are discussed as well as existing biomechanical and clinical literature for both designs.
Detection of Intestinal Tissue Perfusion by Real-Time Breath Methane Analysis in Rat and Pig Models of Mesenteric Circulatory Distress
Authors: Szűcs Szilárd , Bari Gábor , Ugocsai Melinda , Lashkarivand Reza Ali , Lajkó Norbert , Mohácsi Árpád , Szabó Anna , Kaszaki József , Boros Mihály , Érces Dániel , Varga Gabriella
Published: April 2019

Objectives:

Methane (CH4) breath test is an established diagnostic method for gastrointestinal functional disorders. Our aim was to explore the possible link between splanchnic circulatory changes and exhaled CH4 in an attempt to recognize intestinal perfusion failure.

Design:

Randomized, controlled in vivo animal study.

Setting:

University research laboratory.

Subjects:

Anesthetized, ventilated Sprague-Dawley rats (280 ± 30 g) and Vietnamese minipigs (31 ± 7 kg).

Interventions:

In the first series, CH4 was administered intraluminally into the ileum before 45 minutes mesenteric ischemia or before reperfusion in non-CH4 producer rats to test the appearance of the gas in the exhaled air. In the porcine experiments, the superior mesenteric artery was gradually obstructed during consecutive, 30-minute flow reductions and 30-minute reperfusions achieving complete occlusion after four cycles (n = 6), or nonocclusive mesenteric ischemia was induced by pericardial tamponade (n = 12), which decreased superior mesenteric artery flow from 351 ± 55 to 182 ± 67 mL/min and mean arterial pressure from 96.7 ± 18.2 to 41.5 ± 4.6 mm Hg for 60 minutes.

Measurements and Main Results:

Macrohemodynamics were monitored continuously; RBC velocity of the ileal serosa or mucosa was recorded by intravital videomicroscopy. The concentration of exhaled CH4 was measured online simultaneously with high-sensitivity photoacoustic spectroscopy. The intestinal flow changes during the occlusion-reperfusion phases were accompanied by parallel changes in breath CH4 output. Also in cardiac tamponade-induced nonocclusive intestinal ischemia, the superior mesenteric artery flow and RBC velocity correlated significantly with parallel changes in CH4 concentration in the exhaled air (Pearson’s r = 0.669 or r = 0.632, respectively).

Conclusions:

we report a combination of in vivo experimental data on a close association of an exhaled endogenous gas with acute mesenteric macro- and microvascular flow changes. Breath CH4 analysis may offer a noninvasive approach to follow the status of the splanchnic circulation.
Reducing Iatrogenic Pneumothoraces: Using Real-Time Ultrasound Guidance for Pleural Procedures
Authors: Helgeson Scott A. , Fritz Ashley V. , Tatari Mehmet M. , Daniels Craig E. , Diaz-Gomez Jose L.
Published: April 2019

Objectives:

Awareness of the impact of bedside ultrasound to reduce iatrogenic pneumothoraces while performing bedside pleural procedures has increased but with little understanding in how ultrasound is used for these procedures.

Design and Setting:

We conducted a retrospective chart review at a tertiary referral center in the United States from January 1, 2014, to March 31, 2017. Our study assessed adverse effect rates between real-time ultrasound-guided and ultrasound-marked thoracenteses and thoracostomy tube placements.

Patients:

Three-hundred ninety-four ICU patients were included in this study.

Measurements and Main Results:

There was a significant difference in the rate of adverse effects between real-time ultrasound-guided (0.63% [95% CI, 0.11–3.4%]) and ultrasound-marked (6.89% [95% CI, 4.15–11.24%]; p ≤ 0.01) procedures. More specifically, the rate of pneumothoraces was different between the two procedures (0.63% [95% CI, 0.11–3.4%] vs 4.43% [95% CI, 2.35–8.21%]; p = 0.02). In patients mechanically ventilated, there was a significant difference in overall adverse effect rates between groups of ultrasound use (p = 0.01).

Conclusions:

The use of real-time ultrasound guidance was associated with a lower rate of iatrogenic pneumothoraces.
Adrenal tumors: when to search for a germline abnormality?
Authors: Gimenez-Roqueplo Anne-Paule
Published: April 2019

Purpose of review

Over the last 20 years, the genetic landscape of adrenal tumours has been transformed by the identification of multiple susceptibility genes for the various tumour types. We review these recent developments here, and describe current recommendations for genetic testing in patients with tumours of the adrenal medulla and extra-adrenal paraganglia or the adrenal cortex.

Recent findings

Phaeochromocytomas (adrenal medulla tumours) and paragangliomas, aldosterone-producing adenomas, primary macronodular adrenal hyperplasia, primary pigmented nodular adrenocortical disease and adrenocortical carcinoma (adrenal cortex tumours) may all be caused by a germline mutation in a specific gene, regardless of the presence/absence of a family history or syndromic disease at initial diagnosis. Dedicated genetic testing is now indicated in all these conditions, and in patients with clinical features suggestive of a specific inherited disease.

Genetic testing should be considered in all patients with adrenal tumours, and is crucial for correct management. The identification of a germline mutation in a susceptibility gene guides treatment in patients with adrenal cancer and will facilitate risk-adapted screening/surveillance protocols in mutation carriers.
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.

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.
Racial and Socioeconomic Disparities in the Delivery of Immunotherapy for Metastatic Melanoma in the United States
Authors: Haque Waqar , Verma Vivek , Butler Edward Brian , Teh Bin S.
Published: April 2019

Immunotherapy for metastatic melanoma has rapidly expanded, but racial and/or socioeconomic factors often impact the type of therapies delivered for cancer care. This study addressed a crucial public health priority by evaluating disparities in administration of immunotherapy for metastatic melanoma. The National Cancer Database was queried for newly diagnosed metastatic melanoma. Patients were dichotomized based on receipt of immunotherapy based on National Cancer Database coding. Multivariable logistic regression ascertained factors associated with immunotherapy delivery. Subgroup analysis evaluated the interaction between race, insurance status, and income. Secondarily, Cox multivariate and propensity-matched Kaplan-Meier analyses assessed overall survival based on immunotherapy receipt. Of 15,941 patients meeting the selection criteria, 2448 (15.4%) received immunotherapy, and 13,493 (84.6%) did not. Temporal trends showed that utilization of immunotherapy was 8%–12% of patients between 2004 and 2010, with utilization increasing to 29.7% of patients in 2014. Immunotherapy was more likely administered to younger and healthier patients, at academic centers, and in the absence of chemotherapy and brain metastases (P<0.05 for all). African Americans, along with patients with Medicaid and lower incomes were less likely to receive immunotherapy (P<0.05 for all). As expected, immunotherapy was associated with improved overall survival (median 16.3 vs. 8.3 mo, P<0.001). Although immunotherapy for metastatic melanoma is markedly escalating, not all populations experience this rise equally. Because immunotherapy utilization is expected to amplify even further in the future, these public health and economic issues are essential to identify and address appropriately, and have implications on public health policy, pharmaceutical and insurance companies, and value-based oncology. Methods to address these inequalities are also discussed.
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

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.
Burnout Woman-Style: The Female Face of Burnout in Obstetrics and Gynecology
Authors: FRONEK HELANE , BRUBAKER LINDA
Published: April 2019

This summary will address important information on women physicians, focusing on those practicing OG. We will review traits more commonly found in women, societal influences that make women physicians more susceptible to burnout, as well as the unique features of the medical profession that affect women differently. We conclude with a discussion of the shared responsibilities of both individuals and institutions for implementing interventions that will effectively improve women’s resilience, identification of and recovery from burnout.
The retrograde tracheal intubation technique for difficult airway management: old but still working
Authors: Marchello Vincenzo , Corso Ruggero M. , Piraccini Emanuele , Del Gaudio Alfredo , Mincolelli Giuseppe , Cattano Davide
Published: April 2019

Tracheal intubation performed with direct laryngoscopy remains a preferred choice for securing the airway. In maxillofacial surgery patients, difficult airway may require using alternative techniques. Retrograde tracheal intubation (RTI) technique is an effective and safe option for some of these cases. We report our experience with a modified RTI technique in a 72-year-old man (body mass index, 20.3) affected by a pleomorphic adenoma of the lower jaw extending to the oropharynx and rhinopharynx. Our RTI technique included a 17-G Fantoni modified tracheal needle, a 150 cm long Teflon guide wire (SG), and an 83 cm long Cook airway exchange catheter. Preserving spontaneous breathing with a combination of propofol and remifentanil infusion, we performed RTI using a 17-G Fantoni cricothyrotomy needle inserted between first and second tracheal ring. The patient remained breathing spontaneously for the duration of the procedure, and his vital signs were maintained within normal limits. This case report offers an opportunity to discuss our experience and use of retrograde tracheal intubation. The RTI can be an alternative to awake intubation, and maintaining proficiency and training is necessary to guarantee favorable outcomes.
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

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.
Efficacy of a transdiagnostic emotion–focused exposure treatment for chronic pain patients with comorbid anxiety and depression: a randomized controlled trial
Authors: Boersma Katja , Södermark Martin , Hesser Hugo , Flink Ida K. , Gerdle Björn , Linton Steven J.
Published: April 2019

The comorbidity between chronic pain and emotional problems has proven difficult to address with current treatment options. This study addresses the efficacy of a transdiagnostic emotion–focused exposure treatment (“hybrid”) for chronic pain patients with comorbid emotional problems. Adults (n = 115) with chronic musculoskeletal pain and functional and emotional problems were included in a 2-centre, parallel randomized controlled, open-label trial comparing this treatment to an active control condition receiving a guided Internet-delivered pain management treatment based on CBT principles (iCBT). The hybrid treatment (n = 58, 10-16 sessions) integrates exposure in vivo for chronic pain based on the fear-avoidance model with an emotion-regulation approach informed by procedures in Dialectical Behavior Therapy. The iCBT (n = 57; 8 treatment modules) addresses topics such as pain education, coping strategies, relaxation, problem solving, stress, and sleep management using standard CBT techniques. Patient-reported outcomes were assessed before and after treatment as well as at a 9-month primary end point. Across conditions, 78% participants completed post-treatment and 81% follow-up assessment. Intent-to-treat analyses showed that the hybrid had a significantly better post-treatment outcome on pain catastrophizing (d = 0.39) and pain interference (d = 0.63) and significantly better follow-up outcomes on depression (d = 0.43) and pain interference (d = 0.51). There were no differences on anxiety and pain intensity. Observed proportions of clinically significant improvement favoured the hybrid on all but one comparison, but no statistically significant differences were observed. We conclude that the hybrid emotion–focused treatment may be considered an acceptable, credible, and efficacious treatment option for chronic pain patients with comorbid emotional problems.
OPRM1 rs1799971, COMT rs4680, and FAAH rs324420 genes interact with placebo procedures to induce hypoalgesia
Authors: Colloca Luana , Wang Yang , Martinez Pedro E. , Chang Yen-Pei C. , Ryan Kathleen A. , Hodgkinson Colin , Goldman David , Dorsey Susan G.
Published: April 2019

Genetics studies on the placebo hypoalgesic effect highlight a promising link between single nucleotide polymorphisms (SNPs) in the dopamine, opioid, and endocannabinoid genes and placebo hypoalgesia. However, epistasis and replication studies are missing. In this study, we expanded on previous findings related to the 3 SNPs in the opioid receptor mu subunit (OPRM1 rs1799971), catechol-O-methyltransferase (COMT rs4680), and fatty acid amide hydrolase (FAAH rs324420) genes associated with placebo hypoalgesia and tested the effect of a 3-way interaction on placebo hypoalgesia. Using 2 well-established placebo procedures (verbal suggestion and learning paradigm), we induced significant placebo hypoalgesic effects in 160 healthy participants. We found that individuals with OPRM1 AA combined with FAAH Pro/Pro and those carrying COMT met/met together with FAAH Pro/Pro showed significant placebo effects. Participants with COMT met/val alleles showed significant placebo effects independently of OPRM1 and FAAH allele combinations. Finally, the model that included the placebo procedure and genotypes predicted placebo responsiveness with a higher accuracy (area under the curve, AUC = 0.773) as compared to the SNPs alone indicating that genetic variants can only partially explain the placebo responder status. Our results suggest that the endogenous mu-opioid system with a larger activation in response to pain in the met/val allele carriers as well as the synergism between endogenous mu-opioid system and cannabinoids might play the most relevant role in driving hypoalgesic responses. Future epistasis studies with larger sample sizes will help us to fully understand the complexity of placebo effects and explain the mechanisms that underlie placebo responsiveness.
Cortisol affects pain sensitivity and pain-related emotional learning in experimental visceral but not somatic pain: a randomized controlled study in healthy men and women
Authors: Benson Sven , Siebert Carsten , Koenen Laura R. , Engler Harald , Kleine-Borgmann Julian , Bingel Ulrike , Icenhour Adriane , Elsenbruch Sigrid
Published: April 2019

Despite growing interest in the role of stress mediators in pain chronicity, the effects of the stress hormone cortisol on acute pain remain incompletely understood. In a randomized, double-blind, placebo-controlled study with N = 100 healthy volunteers, we tested the effects of oral hydrocortisone (20 mg) in 2 widely used pain models for the visceral and somatic modality. Salivary cortisol was increased in the hydrocortisone group (time × group: P < 0.001). For the visceral modality, assessed using pressure-controlled rectal distensions, hydrocortisone decreased the pain threshold from before to after treatment (time × group: P = 0.011), an effect primarily driven by women (time × sex: P = 0.027). For the somatic modality, cutaneous heat pain thresholds remained unaffected by hydrocortisone. Hydrocortisone did not alter perceived pain intensity or unpleasantness of either modality. Conditioned pain-related fear in response to predictive cues was only observed for the visceral modality (time × modality: P = 0.026), an effect that was significantly reduced by hydrocortisone compared with placebo (time × group: P = 0.028). This is the first psychopharmacological study to support that acutely increased cortisol enhances pain sensitivity and impairs pain-related emotional learning within the visceral, but not the somatic pain modality. Stress-induced visceral hyperalgesia and deficits in emotional pain-related learning could play a role in the pathophysiology of chronic visceral pain.