bluuebunny/crossref_metadata_2025 huggingface dataset:
Association Between Mean Arterial Pressure and Acute Kidney Injury and a Composite of Myocardial Injury and Mortality in Postoperative Critically Ill Patients: A Retrospective Cohort Analysis
Authors: Khanna Ashish K. , Maheshwari Kamal , Mao Guangmei , Liu Liu , Perez-Protto Silvia E. , Chodavarapu Praneeta , Schacham Yehoshua N. , Sessler Daniel I.
Published: April 2019

Objectives:

Hypotension thresholds that provoke renal injury, myocardial injury, and mortality in critical care patients remain unknown. We primarily sought to determine the relationship between hypotension and a composite of myocardial injury (troponin T ≥ 0.03 ng/mL without nonischemic cause) and death up to 7 postoperative days. Secondarily, we considered acute kidney injury (creatinine concentration ≥ 0.3 mg/dL or 1.5 times baseline).

Design:

Retrospective cohort.

Setting:

Surgical ICU at an academic medical center.

Patients:

Two-thousand eight-hundred thirty-three postoperative patients admitted to the surgical ICU.

Interventions:

A Cox proportional hazard survival model was used to assess the association between lowest mean arterial pressure on each intensive care day, considered as a time-varying covariate, and outcomes. In sensitivity analyses hypotension defined as pressures less than 80 mm Hg and 70 mm Hg were also considered.

Measurements and Main Results:

There was a strong nonlinear (quadratic) association between the lowest mean arterial pressure and the primary outcome of myocardial injury after noncardiac surgery or mortality, with estimated risk increasing at lower pressures. The risk of myocardial injury after noncardiac surgery or mortality was an estimated 23% higher at the 25th percentile (78 mm Hg) of lowest mean arterial pressure compared with at the median of 87 mm Hg, with adjusted hazard ratio (95% CI) of 1.23 (1.12–1.355; p < 0.001). Overall results were generally similar in sensitivity analyses based on every hour of mean arterial pressure less than 80 mm Hg and any mean arterial pressure less than 70 mm Hg. Post hoc analyses showed that the relationship between ICU hypotension and outcomes depended on the amount of intraoperative hypotension. The risk of acute kidney injury increased over a range of minimum daily pressures from 110 mm Hg to 50 mm Hg, with an adjusted hazard ratio of 1.27 (95% CI, 1.18–1.37; p < 0.001).

Conclusions:

Increasing amounts of hypotension (defined by lowest mean arterial pressures per day) were strongly associated with myocardial injury, mortality, and renal injury in postoperative critical care patients.
Staged Implementation of Awakening and Breathing, Coordination, Delirium Monitoring and Management, and Early Mobilization Bundle Improves Patient Outcomes and Reduces Hospital Costs*
Authors: Hsieh S. Jean , Otusanya Olufisayo , Gershengorn Hayley B. , Hope Aluko A. , Dayton Christopher , Levi Daniela , Garcia Melba , Prince David , Mills Michele , Fein Dan , Colman Silvie , Gong Michelle Ng
Published: April 2019

Objectives:

To measure the impact of staged implementation of full versus partial ABCDE bundle on mechanical ventilation duration, ICU and hospital lengths of stay, and cost.

Design:

Prospective cohort study.

Setting:

Two medical ICUs within Montefiore Healthcare Center (Bronx, NY).

Patients:

One thousand eight hundred fifty-five mechanically ventilated patients admitted to ICUs between July 2011 and July 2014.

Interventions:

At baseline, spontaneous (B)reathing trials (B) were ongoing in both ICUs; in period 1, (A)wakening and (D)elirium (AD) were implemented in both full and partial bundle ICUs; in period 2, (E)arly mobilization and structured bundle (C)oordination (EC) were implemented in the full bundle (B-AD-EC) but not the partial bundle ICU (B-AD).

Measurements and Main Results:

In the full bundle ICU, 95% patient days were spent in bed before EC (period 1). After EC was implemented (period 2), 65% of patients stood, 54% walked at least once during their ICU stay, and ICU-acquired pressure ulcers and physical restraint use decreased (period 1 vs 2: 39% vs 23% of patients; 30% vs 26% patient days, respectively; p < 0.001 for both). After adjustment for patient-level covariates, implementation of the full (B-AD-EC) versus partial (B-AD) bundle was associated with reduced mechanical ventilation duration (–22.3%; 95% CI, –22.5% to –22.0%; p < 0.001), ICU length of stay (–10.3%; 95% CI, –15.6% to –4.7%; p = 0.028), and hospital length of stay (–7.8%; 95% CI, –8.7% to –6.9%; p = 0.006). Total ICU and hospital cost were also reduced by 24.2% (95% CI, –41.4% to –2.0%; p = 0.03) and 30.2% (95% CI, –46.1% to –9.5%; p = 0.007), respectively.

Conclusions:

In a clinical practice setting, the addition of (E)arly mobilization and structured (C)oordination of ABCDE bundle components to a spontaneous (B)reathing, (A)wakening, and (D) elirium management background led to substantial reductions in the duration of mechanical ventilation, length of stay, and cost.
The tumor microenvironment in renal cell cancer
Authors: Mier James W.
Published: April 2019

Purpose of review

In addition to the provision of nutrients and growth factors that facilitate tumor cell proliferation and metastasis, the tumor microenvironment (MEV) restricts immune surveillance of tumor-associated antigens and limits the efficacy of immune checkpoint inhibitors, tumor vaccines, and other immune therapies. This review will focus on the immunosuppressive mechanisms operative within the tumor MVE of renal cell carcinoma.

Recent findings

Several of the immunosuppressive mechanisms within the tumor MEV have been identified and are potentially druggable. Clinical trials with agents that target several of these inhibitory pathways are currently underway.

Although renal cell carcinoma is one of several tumor types responsive to immune checkpoint inhibitors, the effectiveness of these agents is likely to be limited by the various tumor-infiltrating bone marrow-derived myeloid cells that comprise the MEV. Several strategies to combat the recruitment of these cells into tumor tissue or to neutralize their immunosuppressive function have shown encouraging results in animal tumor models and clinical trials.
A Machine Learning Strategy for Autism Screening in Toddlers
Authors: Achenie Luke E. K. , Scarpa Angela , Factor Reina S. , Wang Tao , Robins Diana L. , McCrickard D. Scott
Published: April 2019

Objective:

Autism spectrum disorder (ASD) screening can improve prognosis via early diagnosis and intervention, but lack of time and training can deter pediatric screening. The Modified Checklist for Autism in Toddlers, Revised (M-CHAT-R) is a widely used screener but requires follow-up questions and error-prone human scoring and interpretation. We consider an automated machine learning (ML) method for overcoming barriers to ASD screening, specifically using the feedforward neural network (fNN).

Methods:

The fNN technique was applied using archival M-CHAT-R data of 14,995 toddlers (age 16–30 months, 46.51% male). The 20 M-CHAT-R items were inputs, and ASD diagnosis after follow-up and diagnostic evaluation (i.e., ASD or not ASD) was the output. The sample was divided into subgroups by race (i.e., white and black), sex (i.e., boys and girls), and maternal education (i.e., below and above 15 years of education completed) to examine subgroup differences. Each subgroup was evaluated for best-performing fNN models.

Results:

For the total sample, best results yielded 99.72% correct classification using 18 items. Best results yielded 99.92% correct classification using 14 items for white toddlers and 99.79% correct classification using 18 items for black toddlers. In boys, best results yielded 99.64% correct classification using 18 items, whereas best results yielded 99.95% correct classification using 18 items in girls. For the case when maternal education is 15 years or less (i.e., associate degree and below), best results were 99.75% correct classification when using 16 items. Results were essentially the same when maternal education was 16 years or more (i.e., above associate degree); that is, 99.70% correct classification was obtained using 16 items.

Conclusion:

The ML method was comparable to the M-CHAT-R with follow-up items in accuracy of ASD diagnosis while using fewer items. Therefore, ML may be a beneficial tool in implementing automatic, efficient scoring that negates the need for labor-intensive follow-up and circumvents human error, providing an advantage over previous screening methods.
Epidemiology of Incarceration
Authors: Camplain Ricky , Warren Meghan , Baldwin Julie A. , Camplain Carolyn , Fofanov Viacheslav Y. , Trotter Robert T.
Published: April 2019

Background:

Each year, 9 million individuals cycle in and out of jails. The under-characterization of incarceration as an exposure poses substantial challenges to understanding how varying levels of exposure to jail may affect health. Thus, we characterized levels of jail incarceration including recidivism, number of incarcerations, total and average number of days incarcerated, and time to reincarceration.

Methods:

We created a cohort of 75,203 individuals incarcerated at the Coconino County Detention Facility in Flagstaff, Arizona, from 2001 to 2018 from jail intake and release records.

Results:

The median number of incarcerations during the study period was one (interquartile range [IQR] = 1–2). Forty percent of individuals had >1 incarceration. The median length of stay for first observed incarcerations was 1 day (IQR = 0–5). The median total days incarcerated was 3 (IQR = 1–23). Average length of stay increased by number of incarcerations. By 18 months, 27% of our sample had been reincarcerated.

Conclusion:

Characteristics of jail incarceration have been largely left out of public health research. A better understanding of jail incarcerations can help design analyses to assess health outcomes of individuals incarcerated in jail. Our study is an early step in shaping an understanding of jail incarceration as an exposure for future epidemiologic research. See video abstract at, http://links.lww.com/EDE/B536.
Estimating the Human Papillomavirus Genotype Attribution in Screen-detected High-grade Cervical Lesions
Authors: Lissenberg-Witte Birgit I. , Bogaards Johannes A. , Quint Wim G. V. , Berkhof Johannes
Published: April 2019

Background:

Genotype attribution in high-grade cervical lesions (CIN3+) can be calculated by the hierarchical or proportional method, but these do not account for the genotype distribution in the general population and cannot assess the number of genotype-specific high-grade cervical lesions (CIN3+).

Methods:

We present a statistical method for estimating genotype-specific CIN3+ risks and genotype attribution in CIN3+ from cervical screening samples. A key assumption is that genotype-specific infections in women with multiple infections have independent progression risks. We applied the method to 512 human papillomavirus (HPV)-positive women referred for colposcopy and validated it by laser-capture microscopy-polymerase chain reaction. We also compared performance by simulation.

Results:

For endpoint CIN3+, the summed deviation of attributable fractions between the estimated genotype-specific attributable fractions and laser-capture microscopy polymerase chain reaction-based attributable fractions was similar for the three methods: 0.17 for the new method (95% confidence interval [CI] = 0.091, 0.28), 0.19 (95% CI = 0.11, 0.33) for the hierarchical method and 0.15 (95% CI = 0.085, 0.26) for the proportional method. Simulations indicated that the new method outperformed the other methods for endpoint CIN3+ when the number of HPV-positive women was large. Exclusion of HPV16-positive women had only a small effect on the estimated genotype-specific risks, supporting the independence assumption.

Conclusions:

Genotype-specific attribution in CIN3+ can be accurately predicted by a model that assumes independence between genotypes with respect to disease progression. The method can be used to monitor HPV vaccine effectiveness for prevention of genotype-specific CIN3+ and to assess disease risk after vaccination.
Association between blood lead level and subsequent Alzheimer’s disease mortality
Authors: Horton Christelene Jack , Weng Hsin-Yi , Wells Ellen M.
Published: April 2019

Background:

Previous studies suggest that cumulative lead exposure is associated with cognitive decline, but its relation with Alzheimer’s disease (AD) remains unclear. Therefore, this study investigated the longitudinal association between blood lead level (BLL) and AD mortality.

Methods:

This study included 8,080 elders (60 years or older) with BLL data from the 1999 to 2008 US National Health and Nutrition Examination Survey. Mortality was determined from linked 1999–2014 National Death Index data. A causal diagram presented causal assumptions and identified a sufficient set of confounders: age, sex, poverty, race/ethnicity, and smoking. Cox proportional hazard models were used to determine the association between BLL and subsequent AD mortality. Impacts of competing risks and design effect were also assessed. Adjusted hazard rate ratio (HRR) and 95% confidence interval (CI) were reported.

Results:

Follow-up ranged from <1 to 152 months (median, 74). Eighty-one participants died from AD over 632,075 total person-months at risk. An increase in BLL was associated with an increase in AD mortality after adjusting for identified confounders. We estimated that those with BLL of 1.5 and 5 μg/dl had 1.2 (95% CI = 0.70, 2.1) and 1.4 (95% CI = 0.54, 3.8) times the rate of AD mortality compared to those with BLL of 0.3 μg/dl, respectively, after accounting for competing risks. Adjusted HRRs were 1.5 (95% CI = 0.81, 2.9) and 2.1 (95% CI = 0.70, 6.3), respectively, after considering design effect.

Conclusions:

This longitudinal study demonstrated a positive, albeit not statistically significant, association between BLL and AD mortality after adjustment for competing risks or design effect.
Relative toxicities of major particulate matter constituents on birthweight in Massachusetts
Authors: Fong Kelvin C. , Di Qian , Kloog Itai , Laden Francine , Coull Brent A. , Koutrakis Petros , Schwartz Joel D.
Published: April 2019

Background:

Maternal exposure to fine particulate air pollution (PM2.5) during pregnancy has been linked to lower newborn birthweight, making it a toxic exposure because lower birthweight is a risk factor for chronic disease and mortality. However, the toxicity of major constituents of PM2.5 and how they compare to each other remain uncertain.

Methods:

We assigned address-specific exposure to PM2.5, elemental carbon (EC), organic carbon (OC), nitrate, and sulfate averaged over the entire period of pregnancy for each birth in Massachusetts from 2001 to 2012 using a high-resolution exposure model. Using multivariate regression adjusted for total PM2.5, we estimated the relative toxicity of each constituent on continuous birthweight.

Results:

EC was more toxic per interquartile range increase compared with remaining PM2.5 in single constituent models that estimated the effect of a constituent with adjustment for PM2.5. OC, nitrate, and sulfate were each less toxic than their respective remaining PM2.5 per interquartile range increase. When all constituents and total PM2.5 were included in the same model, EC was most toxic, followed by nitrate, then OC and sulfate with similar toxicities. Sensitivity analyses using term low birth weight and small for gestational age also showed that EC was most detrimental as did averaging exposures over the third trimester of pregnancy. Scaling to unit mass increases also showed EC to be most toxic.

Conclusion:

Four major constituents of PM2.5 had different relative toxicities on continuous birthweight. Our findings suggest that EC was most toxic, followed by nitrate, OC, and sulfate.
Interlaboratory Analysis of Isavuconazole Plasma Concentration Assays Among European Laboratories
Authors: Pea Federico , Krause Robert , Müller Carsten , Hennart Benjamin , Richardson Malcolm , Meinitzer Andreas , Wiesen Martin H. J. , Wiktorowicz Tatiana , Spickermann Jochen , Henriksen Anne S.
Published: April 2019

Background:

Under certain circumstances, clinicians treating patients with isavuconazole for invasive aspergillosis or mucormycosis may use therapeutic drug monitoring. However, the accuracy and reproducibility of the various assays used by different laboratories for the quantification of isavuconazole plasma concentrations have yet to be determined.

Methods:

Human plasma samples spiked with known concentrations of isavuconazole were provided to 27 European laboratories that took part in a “round-robin” test (an interlaboratory test performed independently at least 2 times; 2 rounds performed in the current study). Assay methods included liquid chromatography–tandem mass spectrometry (LC-MS/MS), LC with ultraviolet detection (LC-UV), LC with fluorescence detection (LC-FL), and bioassay. The accuracy and reproducibility compared with the known concentrations for each sample in each round were compared overall, between assays, and between laboratories.

Results:

Twenty-seven laboratories participated in the study (LC-MS/MS, n = 15; LC-UV; n = 9; LC-FL, n = 1; bioassay, n = 2). In round 1, for nominal concentrations of 1000, 1700, 2500, and 4000 ng/mL, the mean (SD) determined concentrations were 1007 (183), 1710 (323), 2528 (540), and 3898 (842) ng/mL, respectively. In round 2, for nominal concentrations of 1200, 1800, 2400, and 4000 ng/mL, the mean (SD) determined concentrations were 1411 (303), 2111 (409), 2789 (511), and 4723 (798) ng/mL, respectively. Over both rounds, determined concentrations were consistently within 15% of the nominal concentrations for 10 laboratories (LC-MS/MS, n = 4; LC-UV, n = 5; bioassay, n = 1) and consistently exceeded the upper 15% margin for 7 laboratories (LC-MS/MS and LC-UV, n = 3 each; LC-FL, n = 1).

Conclusions:

Alignment of methodologies among laboratories may be warranted to improve the accuracy and reproducibility of therapeutic drug measurements.
Simultaneous Quantification of Free Adalimumab and Infliximab in Human Plasma Using a Target-Based Sample Purification and Liquid Chromatography–Tandem Mass Spectrometry
Authors: El Amrani Mohsin , Bosman Sabine M. , Egas Annelies C. , Hack C. Erik , Huitema Alwin D. R. , van Maarseveen Erik M.
Published: April 2019

Background:

Therapeutic drug monitoring of tumor necrosis factor alpha (TNF-α) inhibitors such as adalimumab (ADM) and infliximab (IFX) is considered of added value for patients with systemic inflammatory diseases. In contrast to enzyme-linked immunosorbent assay methods, liquid chromatography–tandem mass spectrometry methods allow for simultaneous quantification of multiple target antibodies in 1 run and thus providing a higher sample throughput. We describe a fast sample work-up strategy for the absolute and simultaneous quantification of ADM and IFX therapeutic monoclonal antibodies in human plasma samples using a target-specific sample purification in combination with liquid chromatography–tandem mass spectrometry.

Methods:

The sample purification was based on the selective capture of ADM and IFX in human plasma or serum using biotinylated TNF-α (b-TNF-α), which was coated on a streptavidin 96-well plate. After elution, analytes were heat denatured and trypsin digested to obtain signature peptides for quantification. Stable isotopically labeled ADM and IFX were introduced as internal standard before sample purification.

Results:

The method was successfully validated following current European medicines agency guidelines. The linear dynamic rage for both analytes were 1–32 mcg/mL with an excellent mean coefficient of determination, R2 = 0.9994 for ADM and 0.9996 for IFX. Within-run and between-run imprecision and accuracy were within acceptance criteria. Cross-validation against enzyme-linked immunosorbent assay method showed a high between-method correlation R2 = 0.962 for ADM and R2 = 0.982 for IFX.

Conclusions:

This method provides an easy, efficient, and cost-effective workflow for therapeutic drug monitoring patients treated with ADM or IFX.
Impact of Cachexia and Opioid Analgesic Cotreatment on Pregabalin Pharmacokinetics and Central Nervous System Symptoms in Cancer Patients
Authors: Yoshikawa Nozomi , Naito Takafumi , Yagi Tatsuya , Kawakami Junichi
Published: April 2019

Background:

Patients with cancer receiving pregabalin potentially have a high incidence of central nervous system (CNS) symptoms. The purpose of this study was to explore clinical factors influencing the incidence of CNS symptoms, including plasma pregabalin exposure, cancer cachexia, and opioid analgesic cotreatment.

Methods:

Sixty-eight patients with cancer receiving twice-daily pregabalin were enrolled. Plasma concentrations of pregabalin, clinical laboratory data, opioid analgesic cotreatment, and the Glasgow Prognostic Score, which is an inflammation-based cachexia score, were considered as clinical factors. The incidence of CNS symptoms was collected from the patients' medical records. The predose plasma concentrations of pregabalin at steady state were determined by ultra-high-performance liquid chromatography.

Results:

The steady-state trough plasma pregabalin concentrations showed a large variability with an interquartile range of 0.43–1.2 mg/L per mg/kg and were negatively correlated with an estimated glomerular filtration rate (eGFR). C-reactive protein (standardized partial regression coefficient, β = 0.31) and opioid analgesic cotreatment (β = 0.24) were also identified in addition to eGFR (β = −0.60) in the multiple regression analysis. The incidence of CNS symptoms was significantly increased with opioid analgesic cotreatment and a higher Glasgow Prognostic Score but not with the absolute value of plasma pregabalin concentrations, eGFR, or other clinical laboratory data.

Conclusions:

In patients with cancer, steady-state trough plasma pregabalin concentrations were altered with renal function, systemic inflammation, and opioid analgesic cotreatment. However, a higher incidence of CNS symptoms observed in patients with cancer on pregabalin was more related to cachexia and opioid analgesic cotreatment than to altered pregabalin concentrations.
Hypothyroidism in Pregnancy
Authors: SULLIVAN SCOTT A.
Published: April 2019

Hypothyroidism in pregnancy is defined as the presence of an elevated thyroid stimulating hormone during gestation, affecting 2% to 3% of the population. Overt hypothyroidism is diagnosed by a decreased FT4, while patients with a normal FT4 are considered to have subclinical disease. Poorly controlled disease is associated with both pregnancy complications and developmental delays in the offspring. Treatment consists of replacement with levothyroxine and regular monitoring. Most pregnant women will require an increase in their dosing from 25% to 30%. While treatment for SCH remains controversial, current recommendations do not support universal screening of low-risk women during pregnancy.
Physician Work-Life Integration: Challenges and Strategies for Improvement
Authors: KARAKASH SCARLETT , SOLONE MICHELLE , CHAVEZ JORDAN , SHANAFELT TAIT
Published: April 2019

Increasing evidence shows that physician well-being is linked to patient outcomes, patient and physician satisfaction, and workforce retention. Physician well-being is a broad construct that includes various dimensions of distress (stress, anxiety, fatigue, burnout) and professional fulfillment (meaning in work, engagement). Work-life integration (WLI) is one important component of physician well-being. We will review the current state of WLI among physicians as well as some strategies to improve this aspect of physician well-being. We address this topic through the lens of obstetrics and gynecology, including a discussion of specialty-specific characteristics that present unique challenges and opportunities to improve WLI.
Multiple Facets of the Poisson Distribution Applicable to Health Physics Measurements
Authors: Justus Alan L.
Published: April 2019

This paper discusses several ways to view the standard Poisson distribution as applied to health physics scaler counts. The intent is not so much to present calculational details but rather to present some underlying concepts. Examples are provided that illustrate the various concepts for several types of specific measurements. The concepts presented involve purely Poisson-based contributions to variance; extra-Poisson variance is presently ignored, and any counting system would be presumed to function properly and without counting loss.
An Investigation of Procedural Radiation Dose Level Awareness and Personal Training Experience in Communicating Ionizing Radiation Examinations Benefits and Risks to Patients in Two European Cardiac Centers
Authors: Banerjee I. , McNulty J. P. , Catania D. , Maccagni D. , Masterson L. , Portelli J. L. , Rainford L.
Published: April 2019

Purpose: Cardiac interventional practitioners need to be appropriately informed regarding radiation dose quantities and risks. Communicating benefit-risk information to patients requires attention as specified in Basic Safety Standards Directive 2013/59/Eurotom. This study investigated the awareness of procedural radiation dose levels and the impact of personal training experience in communicating ionizing radiation benefit-risks to patients. Methodology: A questionnaire, consisting of 28 questions, was distributed directly to adult and pediatric interventional cardiology specialists at specialized cardiovascular imaging centers in Dublin, Ireland and Milan, Italy. Results: A total of 18 interventional cardiologists (senior registrar to consultant grades with between 2 y to over 21 y experience in cardiac imaging) participated. The majority of participants (n = 17) stated that parents of pediatric and adult patients should be informed of the potential benefits and risk. All participants indicated they had radiation safety training; however, 50% had not received training in radiation examination benefit-risk communication. Despite this, 77.8% (n = 14) participants indicated a high confidence level in successfully explaining risks and/or benefits of cardiac imaging procedures. When asked to estimate effective dose (ED) values for common cardiac imaging procedures less than 50% identified appropriate dose ranges. All participants underestimated procedural dose values based on recent European data. 50% (n = 9) participants answered all questions correctly for a number of true or false radiation risk statements. Conclusion: Benefit-risk communication training deficits and inaccurate understanding of radiation dose levels was identified. Further research and training to support clinicians using radiation on a daily basis is required.
Design of a Do-It-Yourself Geiger-Muller Counter With Smartphone Mapping Application
Authors: Xiao Jeffery B. , Seekamp James M. , Chung Long Kiu , El-Amir Issa N. , Schiefer Kai C. , Trimas David J. , Tuey Regina , Kearfott Kimberlee J.
Published: April 2019

Legacy Geiger-Muller (GM) survey meters recovered from fallout shelters have been used by several nuclear scientific societies as part of high school outreach programs. A donated antique instrument helps teachers demonstrate radiological principles, but fails to develop student's electronics skills, generate excitement for nuclear careers, or provide individuals with their own devices to explore the radioactive planet. A simple, affordable GM survey meter built by each student would increase direct engagement while providing hands-on experience with circuit-building, soldering, and computer programming. The inclusion of an affordable single-board computer as a component in the survey meter would enable students to tackle more various computer science and electronics projects, thereby potentially recruiting more students into technology and engineering. This paper details the challenges faced by an interdisciplinary undergraduate team designing an easy-to-assemble smart GM survey meter. Their iterative research, design, and testing process included modification to a basic circuit to enable use of different tube types, component cost reduction, application development, and data communication. The ultimate product of the team's efforts, a survey meter with affordable components and a smartphone application capable of creating radiation maps, is detailed in full.
Towards a New Concept of Low Dose
Authors: Mothersill Carmel , Rusin Andrej , Seymour Colin
Published: April 2019

When people discuss the risks associated with low doses of ionizing radiation, central to the discussion is the definition of a low dose and the nature of harm. Standard answers such as “doses below 0.1 Gy are low” or “cancer is the most sensitive measure of harm” obscure the complexity within these seemingly simple questions. This paper will discuss some of the complex issues involved in determining risks to human and nonhuman species from low-dose exposures. Central to this discussion will be the role of communicable responses to all stressors (often referred to as bystander responses), which include recently discovered epigenetic and nontargeted mechanisms. There is a growing consensus that low-dose exposure to radiation is but one of many stressors to impact populations. Many of these stressors trigger responses that are generic and not unique to radiation. The lack of a unique radiation signature makes absolute definition of radiation risk difficult. This paper examines a possible new way of defining low dose based on the systemic response to the radiation. Many factors will influence this systemic response and, because it is inherently variable, it is difficult to predict and so makes low-dose responses very uncertain. Rather than seeking to reduce uncertainty, it might be valuable to accept the variability in outcomes, which arise from the complexity and multifactorial nature of responses to stressors.
A Monte Carlo t Test to Evaluate Mesothelioma and Radiation in the US Transuranium and Uranium Registries
Authors: Zhou Joey Y. , McComish Stacey L. , Tolmachev Sergei Y.
Published: April 2019

A cluster of nine mesothelioma cases was observed among 341 registrants’ deaths in the US Transuranium and Uranium Registries. Descriptive analysis showed that mesothelioma cases had the highest average cumulative external radiation dose compared with lung cancer, other cancer, and noncancer deaths. Further analysis indicated that the mesothelioma cluster was very different demographically from lung cancer, other cancer, and noncancer deaths. Therefore, an internally matched case-control approach was applied to evaluate the differences in an average cumulative external radiation dose between mesothelioma deaths and other causes of death. A Monte Carlo t test was used to examine the statistical significance of the differences. The results showed that there were no significant statistical differences in an average cumulative external radiation dose between mesothelioma and lung cancer, other cancers, or noncancers for the internally matched cases and controls.
SARILUMAB FOR RECALCITRANT CYSTOID MACULAR EDEMA IN NON-PARANEOPLASTIC AUTOIMMUNE RETINOPATHY
Authors: Grewal Dilraj S. , Jaffe Glenn J. , Keenan Robert T.
Published: April 2019

Purpose:

To demonstrate a rapid improvement of recalcitrant cystoid macular edema (CME) and perivascular leakage, in a patient with non-paraneoplastic autoimmune retinopathy and autoimmune optic neuropathy after treatment with sarilumab, a human anti-interleukin-6 (IL-6) receptor antibody.

Methods:

Observational case report.

Results:

A 29-year-old woman was diagnosed with non-paraneoplastic autoimmune retinopathy and autoimmune optic neuropathy and followed over 1.5 years. She had recalcitrant CME despite local corticosteroid and immunosuppressive therapy that included azathioprine and adalimumab. Subcutaneous sarilumab was initiated at a dose of 200 mg every 2 weeks. Cystoid macular edema significantly decreased after two injections and resolved after four injections with associated improvement in visual acuity and significant improvement in perivascular leakage on fluorescein angiography. There was a sustained visual and anatomical improvement at 6 months along with mild improvement in electroretinogram responses. The patient tolerated the medication with no side effects.

Conclusion:

Management of CME in non-paraneoplastic autoimmune retinopathy is challenging, and long-term immunosuppression is often employed with varying degrees of success. The improvement in refractory CME and perivascular leakage in this case supports the potential role of an IL-6 inhibitor to treat CME associated with non-paraneoplastic autoimmune retinopathy suggesting the role.
COMBINED PHACOEMULSIFICATION SURGERY WITH MULTIFOCAL INTRAOCULAR LENS IMPLANTATION AND PARS PLANA VITRECTOMY FOR SYMPTOMATIC VITREOUS OPACITIES
Authors: Patel Sunny B. , Snyder Michael E. , Riemann Christopher D. , Osher James M. , Mi Cindy W. , Sisk Robert A.
Published: April 2019

Purpose:

To report surgical outcomes of combined vitrectomy for vitreous floaters and phacoemulsification surgery with multifocal intraocular lens implantation.

Methods:

Retrospective, interventional, noncomparative case series of five eyes from five patients who underwent same-day combined phacoemulsification surgeries with apodized, diffractive multifocal intraocular lens implantation for cataract and pars plana vitrectomy for symptomatic vitreous opacities, that is, floaters. Primary outcomes were distance and near visual acuities, and resolution of symptoms. Secondary outcomes included intraocular pressure, refractive outcomes, and surgical complications.

Results:

Mean logarithm of the minimum angle of resolution glare distance visual acuity improved from 0.36 (best-corrected Snellen 20/47) preoperatively to an uncorrected distance visual acuity of 0.05 (Snellen 20/23) at 6 months postoperatively (P = 0.042). All but one patient achieved multifocality with a near visual acuity of J2 or better. All patients noted subjective improvement in symptoms from floaters postoperatively. Mean intraocular pressure remained stable during follow-up. Two eyes ultimately required YAG capsulotomies for symptomatic posterior capsular opacification, one of which additionally received LASEK for refractive correction.

Conclusion:

Multifocality and improvement in symptoms from symptomatic vitreous opacities were observed in this pilot series of carefully selected patients who underwent combined phacovitrectomy with multifocal intraocular lens implantation. A high rate of retinal tears was found in these patients. Appropriate caution should be taken in preoperative assessment and patient selection for the combined procedure.
FUNDUS AUTOFLUORESCENCE PREDICTING GROWTH OF A CHOROIDAL OSTEOMA IN A 13–YEAR-OLD GIRL
Authors: Desai Symmarana U. , Desai Uday R.
Published: April 2019

Purpose:

To describe multimodal imaging findings, including fundus autofluorescence, in a patient with a growing choroidal osteoma.

Methods:

Case report.

Results:

A 13-year-old girl presented with an asymptomatic lesion in the superonasal macula of her left eye. Vision was correctable to 20/20 in both eyes, and the only significant finding on examination was the yellow flat lesion in the left macula. It measured 0.8-disk areas in size. Ocular coherence tomography showed a space occupying lesion in the choroid that had horizontal hyper-reflective lines consistent with cancellous bone. Re-examination in a year showed enlargement. Fundus autofluorescence showed no abnormalities in either eye. Ultrasonography showed a hyper-reflective lesion with associated shadowing that was consistent with a choroidal osteoma.

Conclusion:

Normal fundus autofluorescence was seen in this young girl with a growing choroidal osteoma. Fundus autofluorescence is a proxy for the health of the retinal pigment epithelium. Normal retinal pigment epithelium is the only factor found to be predictive of future growth of a choroidal osteoma. This noninvasive test may prove useful as a guide to determine frequency of examinations especially in younger patients who might be prone to more rapid growth.
NOVEL SURGICAL TECHNIQUE TO REMOVE RETAINED SUBFOVEAL PERFLUOROCARBON LIQUID
Authors: Hanout Mostafa , Muni Rajeev H.
Published: April 2019

Purpose:

To describe a novel surgical technique to remove retained subfoveal perfluorocarbon liquid (PFCL).

Methods:

After setting up for 23-G pars plana vitrectomy, a 38-G flexible-tip macular hydrodissection cannula connected to the automated viscous fluid infusion kit was used to create a small retinotomy approximately 700 μm to 800 μm inferior to the fovea and induce macular detachment involving the retained PFCL bubble. The flexible cannula was bent at its junction with the shaft and was carefully advanced through the same retinotomy into the subretinal space to access and directly aspirate the retained subfoveal PFCL bubble. Fluid–air exchange was then performed, and surgery was concluded.

Results:

The retained subfoveal PFCL bubble was successfully removed with restoration of normal foveal architecture on optical coherence tomography and with objective and subjective improvement of central vision.

Conclusion:

We report a novel surgical technique combining macular detachment with direct aspiration of the retained subfoveal PFCL without direct perforation of the foveal center. This technique may provide an alternative approach to manage this difficult complication.
Incidence, Risk Factors and Outcomes Among Children With Acute Flaccid Myelitis: A Population-based Cohort Study in a California Health Network Between 2011 and 2016
Authors: Kane Miranda S. , Sonne Chris , Zhu Shiyun , Malhotra Amit , Van Haren Keith , Messacar Kevin , Glaser Carol A.
Published: April 2019

Background:

Acute flaccid myelitis (AFM) is defined as an acute onset of limb weakness with longitudinal spinal gray matter lesions. Reporting bias and misdiagnosis confound epidemiologic studies of AFM. We mitigated these confounders by using a large data set to assess AFM incidence, risk factors and outcomes in a fixed population.

Methods:

A retrospective cohort study was conducted within Kaiser Permanente Northern California population among children 1–18 years. Cases met radiographic and clinical criteria for AFM and were confirmed by two clinicians. Clinical and demographic data were assessed.

Results:

A total of 28 patients met study criteria for AFM between January 1, 2011 and December 31, 2016, an overall rate of 1.46 per 100,000 person-years. Incidence increased from 0.30 to 1.43 cases/per 100,000 person-years between 2011 and 2016, respectively. Median age was 9 years. Risk factors included male sex, Asian ancestry and history of asthma, atopic dermatitis or head injury. Risk factors associated with poliomyelitis were absent. Prodromal illness was common; enterovirus was the most common pathogen detected (n = 5). Among the 27 patients with 12-month follow-up, most demonstrated some improvement, 11 (41.0%) had full recovery, but several had significant deficits with one death reported after the study period.

Conclusions:

We employed a closed-population study to generate AFM incidence, risk and outcome data. Our findings support previous reports of male sex and atopy as risk factors. Interval increase in incidence, predisposing Asian ancestry and history of head injury were unique findings to this study. Overall prognosis was better than prior reports, but recovery was incomplete in several patients.
Bacterial Colonization of the Hospitalized Newborn: Competition Between Staphylococcus aureus and Staphylococcus epidermidis
Authors: Lee Daniel C. , Kananurak Anchasa , Tran Michelle TN , Connolly Patricia A. , Polage Christopher R. , Iwase Tadayuki , Bevins Charles L. , Underwood Mark A.
Published: April 2019

Background:

In adults, Staphylococcus epidermidis and Staphylococcus aureus compete for colonization of the nasal mucosa and S. epidermidis strains that produce the Esp serine protease eradicate S. aureus nasal colonization. Whether similar phenomena are seen in newborn infants is unknown.

Methods:

Nasal swabs were obtained on admission and discharge from newborn infants (n = 90 and 83, respectively) in the neonatal intensive care unit at UC Davis Children’s Hospital. Swabs were cultured for S. aureus and S. epidermidis. S. epidermidis isolates were tested for Esp expression, overall secreted protease activity and biofilm inhibition.

Results:

No infant had S. aureus on admission. S. epidermidis colonization was rare on admission in inborn infants (2.5%), but common in infants transferred from referring hospitals (50%). At discharge, most infants (96%) were colonized by staphylococci. S. aureus colonization was less common in infants with S. epidermidis colonization (9%) and more common in infants without S. epidermidis (77%) (relative risk of S. aureus colonization in infants colonized with S. epidermidis 0.18, 95% confidence interval: 0.089–0.34, P < 0.0001). Compared with S. epidermidis strains from infants without S. aureus, S. epidermidis from infants co-colonized with S. aureus had lower total proteolytic enzyme activity and decreased biofilm inhibition capacity, but did not have lower frequency of Esp positivity.

Conclusions:

In hospitalized neonates, S. epidermidis colonization has a protective effect against S. aureus colonization. Secretion of proteases by S. epidermidis is a possible mechanism of inhibition of S. aureus colonization; however, in this cohort of neonates, the source of major protease activity is likely other than Esp.
Enterovirus D68 Causing Acute Respiratory Infection: Clinical Characteristics and Differences With Acute Respiratory Infections Associated With Enterovirus Non-D68
Authors: Montes Milagrosa , Oñate Eider , Muguruza Ainhoa , Tamayo Esther , Carrera Itxaso Martí , Iturzaeta Ana , Cilla Gustavo
Published: April 2019

Background:

Enterovirus (EV) D68 is mainly associated with acute respiratory infection (ARI). Since 2014, when outbreaks in different countries were observed, this emerging virus was considered a potential threat to public health.

Methods:

During 2015–2017, the presence of enterovirus RNA was investigated in all respiratory samples of children younger than 15 years of age with ARI, obtained for virologic studies in the Pediatric Emergency Care Units and wards of 2 hospitals in Gipuzkoa (Spain), using a commercial multiplex real-time polymerase chain reaction. When enterovirus was detected, a polymerase chain reaction to amplify a specific viral polyprotein (VP1) gene region of EV-D68 was performed.

Results:

In 2016, EV-D68 circulation was associated to ARI, with the highest incidence in the spring months. EV-D68 was detected in 44 children, mean age 30.1 ± 31.7 months old, 23 (52.3%) of them females and 17 (38.6%) with underlying respiratory medical conditions. Thirty-two patients (72%) required hospital admission, receiving the discharge diagnosis of recurrent wheezing (37.5%), asthmatic crisis (37.5%) or bronchiolitis (12.5%). Seven children (15.9%) needed the support of the pediatric intensive care unit. When coinfections were excluded, children with EV-D68 infection presented with increased work of breathing, recurrent wheezing or asthmatic crisis, more frequently than those with ARI associated with EV non-D68. Moreover, clinical outcomes (hospitalization, respiratory support) were more severe. All 44 EV-D68 strains detected belonged to lineage B3.

Conclusions:

EV-D68 circulated widely in Gipuzkoa during 2016 and was associated with severe ARI. In children with severe ARI of unknown etiology, the presence of EV-D68 should be considered.
Respiratory Syncytial Virus Prophylaxis in Neurologic and Muscular Disorders in the Canadian Respiratory Syncytial Virus Evaluation Study of Palivizumab
Authors: Wang Daniel Y. , Saleem Mahwesh , Paes Bosco A. , Mitchell Ian , Li Abby , Lanctôt Krista L.
Published: April 2019

Background:

This study aimed to examine the risk of respiratory-related hospitalization in children with neurologic and muscular disorders (NMDs) who received respiratory syncytial virus (RSV) prophylaxis in the Canadian RSV Evaluation Study of Palivizumab.

Methods:

Canadian RSV Evaluation Study of Palivizumab is a prospective registry of children who received ≥1 palivizumab injection among 32 Canadian sites. Demographic data were collected at enrollment, and respiratory events were documented monthly. Cox proportional hazard analyses were conducted to compare respiratory illness-related hospitalization (RIH) and RSV-related hospitalization (RSVH) among children with NMD and those prophylaxed for standard indications (SI) and complex medical disorders.

Results:

Group differences were found in enrollment age and weight, birth weight, household crowding, neonatal stay and supplemental oxygen requirement (all P < 0.05). RIH and RSVH incidences were 19.2%, 3.3% (NMD, n = 605); 6.0%, 1.5% (SI, n = 20,335), 9.4%, 1.6% (complex medical disorders, n = 4063), respectively. Children with NMD had a higher risk of RIH (hazard ratio [HR]: 1.90; 95% confidence interval (CI): 1.41–2.56; P < 0.0005) than those with SI. RSVH risk was greater in children with NMD compared with both the SI (HR: 2.26; 95% CI: 1.38–3.72; P = 0.001) and complex medical disorders groups (HR: 2.74; 95% CI: 1.55–4.84; P = 0.001). Children with more severe infantile onset NMD had a higher risk of RIH than those with general hypotonic disorders (HR: 1.69; 95% CI: 1.06–2.68; P = 0.027) but not RSVH.

Conclusions:

Children with NMD who received palivizumab had a higher risk of both RIH and RSVH. Our results imply that all children with NMD, regardless of disease severity, are at risk for respiratory-related illness and RSV infection.
Intrafamilial Transmission of Hepatitis C Virus Among Families of Infected Pediatric Oncology Patients
Authors: Sherief Laila M. , Beshir Mohamed Refaat , Salem Ghada Muhammad , Sherbiny Hanan S. , Soliman Attia Abdelwehab , El-komy Mohamed A. , Arafa Muhammed , Kamal Naglaa M.
Published: April 2019

Background:

Hepatitis C virus (HCV) is the most commonly encountered blood transmittable hepatitis among cancer patients. Several studies have reported clustering of HCV infections in families or household contacts of infected cases. Data about the epidemiologic aspects of intrafamilial transmission from pediatric cancer patients are scarce and still debated. We aimed to identify the magnitude of horizontal intrafamilial transmission of HCV from infected pediatric oncology patients; its prevalence, risk factors and possible routes of transmission.

Methods:

One hundred fifty-seven (86 HCV positive, 71 HCV negative) pediatric oncology patients who received treatment and follow-up at Zagazig university Hospital-Egypt and their household family contacts (751) were enrolled in this cross-sectional case-control study. Blood samples were collected from 450 relatives of HCV infected cases (group 1) and 301 household contacts of HCV-negative cases (group 2) for analysis of HCV antibodies and HCV RNA to confirm positivity. Family contacts of HCV-infected cases were interviewed, and close-ended questionnaire was completed for each participant to determine risk factors and possible routes of HCV intrafamilial transmission.

Results:

Significantly higher HCV prevalence and chronicity rates were documented among relatives of HCV-infected cases as compared with contacts of HCV-negative cases (12.6% and 10.6% for group 1 vs. 7% and 5.3% for group 2, respectively). Risk factors of infection were calculated by univariate and logistic regression analysis among contacts of HCV-infected cases. Female caregivers, particularly mother (OR 5.1, 95% CI: 2–13.5), contact with index cases blood, either directly without using personal protective equipment (OR 7.8, 95% CI: 2.9–23.8) or indirectly through common use of sharps (razors, scissors) (OR 8.9, 95% CI: 3.5–20.5) and nail clippers (OR 2.1, 95% CI: 1.1–5.4) and giving care to infected cases (OR 2.9, 95% CI: 1.3–16.6) represented the real predictors of intrafamilial HCV infection.

Conclusions:

Intrafamilial transmission of HCV from infected children to their relatives does occur. Parenteral route is the only documented way of transmission either directly or indirectly.