Publications by authors named "Mark Reid"

83 Publications

Evaluation of high-definition video smart glasses for real-time telemedicine strabismus consultations.

J AAPOS 2021 Apr 23. Epub 2021 Apr 23.

The Vision Center at Children's Hospital Los Angeles, Los Angeles, California;; USC Roski Eye Institute, Keck School of Medicine of USC, University of Southern California, Los Angeles;. Electronic address:

Purpose: To evaluate the use of high-definition, wireless video recording Pivothead glasses in streamed strabismus examinations.

Methods: A pediatric ophthalmologist wearing Pivothead glasses simultaneously performed and recorded strabismus examinations, which were completed in primary gaze, with and without correction, and at distance and near. Parameters included category of strabismus, angle measurements, and ocular motility. Another pediatric ophthalmologist, masked to clinical findings, reviewed and graded live video feed. At least 3 months later, both pediatric ophthalmologists graded the stored videos. Agreement was determined by unweighted kappa for categorical variables, intraclass coefficient for continuous variables, and percent agreement.

Results: A total of 100 videos were recorded for 37 enrolled patients aged 4-16 years. Agreement between streamed and in-person examinations was perfect for both horizontal and vertical (κ = 1.0) deviations. Agreement for degree manifest (tropia vs intermittent tropia vs phoria) was almost perfect for all deviations (κ = 0.94). Agreement was excellent for angle measurements of both horizontal (ICC = 0.95) and vertical (ICC = 0.91) deviations. Inferior and superior oblique agreement was 93% and 98%, respectively. Similar agreement was also observed between store-and-forward versus gold standard examinations.

Conclusions: Real-time video feed obtained with video glasses can be read with a high degree of reliability for detecting strabismus category, angle, and extraocular motility.
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http://dx.doi.org/10.1016/j.jaapos.2020.11.016DOI Listing
April 2021

Psychosocial outcomes in young adolescents with type 1 diabetes participating in shared medical appointments.

Pediatr Diabetes 2021 Apr 10. Epub 2021 Apr 10.

Center for Endocrinology, Diabetes, and Metabolism, Children's Hospital Los Angeles, Los Angeles, California, USA.

For youth with type 1 diabetes (T1D), the early adolescent period is associated with worsening diabetes management and high rates of negative psychosocial issues, including depressive symptoms and family conflict. Alternative clinical models may help improve both diabetes and psychosocial outcomes. Our study aims to investigate whether Team Clinic, a shared medical appointment model developed specifically for adolescents with T1D, will improve psychosocial outcomes for middle school-aged youth. Youth with T1D, 11-13 years of age, and their caregivers, participated in a randomized controlled trial comparing Team Clinic to traditional clinic visits (control group). Diabetes characteristics were obtained at every visit. Participants and caregivers completed depression screening and family conflict questionnaires at baseline and end of study. Changes in mean scores on clinical and psychosocial outcomes from baseline to end of study were compared between groups using linear mixed-effects models. Eighty-six youth (51% female; 74% White; 10% Hispanic) completed at least one visit during the 12-month study period. At the end of the study, control group participants reported increases in Emotional Problems compared to Team Clinic participants, including higher levels of Negative Mood/Physical Symptoms (p = 0.02). Team Clinic participants reported reduced family conflict surrounding diabetes at study end, compared to control group participants (p = 0.03). Caregivers did not report change in depressive symptoms or family conflict during the study. Hemoglobin A1C levels did not change over time in either group. Participation in Team Clinic was associated with improved psychosocial outcomes in middle school-aged participants with T1D.
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http://dx.doi.org/10.1111/pedi.13212DOI Listing
April 2021

Establishing the Clinical Utility of ctDNA Analysis for Diagnosis, Prognosis, and Treatment Monitoring of Retinoblastoma: The Aqueous Humor Liquid Biopsy.

Cancers (Basel) 2021 Mar 13;13(6). Epub 2021 Mar 13.

The Vision Center at Children's Hospital Los Angeles, Los Angeles, CA 90027, USA.

Because direct tumor biopsy is prohibited for retinoblastoma (RB), eye-specific molecular biomarkers are not used in clinical practice for RB. Recently, we demonstrated that the aqueous humor (AH) is a rich liquid biopsy source of cell-free tumor DNA. Herein, we detail clinically-relevant molecular biomarkers from the first year of prospective validation data. Seven eyes from 6 RB patients who had AH sampled at diagnosis and throughout therapy with ≥12 months of follow-up were included. Cell-free DNA (cfDNA) from each sample was isolated and sequenced to assess genome-wide somatic copy number alterations (SCNAs), followed by targeted resequencing for pathogenic variants using a and custom hybridization panel. Tumoral genomic information was detected in 100% of diagnostic AH samples. Of the seven diagnostic AH samples, 5/7 were positive for RB SCNAs. Mutational analysis identified variants in 5/7 AH samples, including the 2 samples in which no SCNAs were detected. Two eyes failed therapy and required enucleation; both had poor prognostic biomarkers (chromosome 6p gain or amplification) present in the AH at the time of diagnosis. In the context of previously established pre-analytical, analytical, and clinical validity, this provides evidence for larger, prospective studies to further establish the clinical utility of the AH liquid biopsy and its applications to precision oncology for RB.
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http://dx.doi.org/10.3390/cancers13061282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8001323PMC
March 2021

Reliability of telemedicine for real-time paediatric ophthalmology consultations.

Br J Ophthalmol 2021 Mar 15. Epub 2021 Mar 15.

The Vision Center, Children's Hospital Los Angeles, Los Angeles, California, USA

Background/aims: To assess the accuracy of real-time telemedicine to diagnose and manage paediatric eye conditions.

Methods: Prospective, non-inferiority study analysing agreement in diagnoses and management plans between telemedicine and in-person examinations. Paediatric ophthalmology clinic. Children 0-17 years, English-speaking or Spanish-speaking, able to participate in age-appropriate manner, either previously seen by the optometrist and required ophthalmology referral or newly referred from outside source. Paediatric optometrist conducted examinations using digital equipment and streamed live to a paediatric ophthalmologist who recorded diagnoses and management plans, then re-examined patients in-person. Subjects were masked to the fact they would see the ophthalmologist in-person, same-day. Discrepancy in management plan or diagnosis between telemedicine and in-person examinations. Non-inferiority threshold was <1.5% for management plan or <15% for diagnosis discrepancies.

Results: 210 patients participated in 348 examinations. 131 (62.4%) had strabismus as primary diagnosis. In these patients, excellent and almost perfect agreement was observed for angle measurements (intraclass correlation coefficients=0.98-1.00) and disease categorisation (kappa=0.94-1.00) (p<0.0001 in all cases). No primary diagnoses changed, and no management plans changed following in-person examination. 54/55 patients who consented for surgery at the initial visit did so while masked to receiving an in-person examination. Families felt comfortable with the quality of the telemedicine examination (98.5%) and would participate in another in the future (97.1%).

Conclusion: Paediatric ophthalmic conditions can be reliably diagnosed and managed via telemedicine. Access for underserved populations may be improved by collaboration between ophthalmologists and optometrists using this technology.
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http://dx.doi.org/10.1136/bjophthalmol-2020-318385DOI Listing
March 2021

Cygnus X-1 contains a 21-solar mass black hole-Implications for massive star winds.

Science 2021 03 18;371(6533):1046-1049. Epub 2021 Feb 18.

Dr. Karl Remeis-Sternwarte and Erlangen Centre for Astroparticle Physics, Friedrich-Alexander-Universität Erlangen-Nürnberg, 96049 Bamberg, Germany.

The evolution of massive stars is influenced by the mass lost to stellar winds over their lifetimes. These winds limit the masses of the stellar remnants (such as black holes) that the stars ultimately produce. We used radio astrometry to refine the distance to the black hole x-ray binary Cygnus X-1, which we found to be [Formula: see text] kiloparsecs. When combined with archival optical data, this implies a black hole mass of 21.2 ± 2.2 solar masses, which is higher than previous measurements. The formation of such a high-mass black hole in a high-metallicity system (within the Milky Way) constrains wind mass loss from massive stars.
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http://dx.doi.org/10.1126/science.abb3363DOI Listing
March 2021

Evaluation of digital slit-lamp videos for paediatric anterior segment telemedicine consultations.

J Telemed Telecare 2021 Feb 3:1357633X21990991. Epub 2021 Feb 3.

The Vision Center at Children's Hospital Los Angeles, USA.

Introduction: This study aimed to assess the validity of telemedicine consultations using digital slit-lamp videos to detect anterior segment pathology in a paediatric population.

Methods: A paediatric anterior segment specialist simultaneously performed and recorded anterior segment examinations using the Topcon digital-ready slit lamp. Components of the examination included the eyelids/eyelashes, conjunctiva/sclera, cornea, anterior chamber, iris and lens. Masked to clinical findings, a paediatric ophthalmologist reviewed and graded the live video feed transmitted at 4 Mbps. At least three months later, both ophthalmologists graded the stored videos. We compared the sensitivity, specificity, percent agreement and weighted kappa (κ) of diagnosing anterior segment pathologies via live-streamed and store-and-forward video clips compared to the in-person standard examination.

Results: Examinations of 89 eyes from 45 children (5-17 years old) with known anterior segment pathology were included. Agreement between live-streamed and in-person standard examinations for conjunctiva/sclera, anterior chamber, iris and lens findings was almost perfect (sensitivity 89-96%, specificity 95-100%, κ = 0.87-0.97). Substantial agreement was found for cornea pathology (sensitivity 88%, specificity 90%, κ = 0.72), and moderate agreement was found for eyelids/eyelashes pathology (sensitivity 54%, specificity 92%, κ = 0.46). Store-and-forward results were similar, though slightly better for eyelids/eyelashes and slightly worse for conjunctiva/sclera.

Discussion: Digital slit-lamp videos hold promise for synchronous and asynchronous telemedicine in diagnosing paediatric anterior segment pathologies.
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http://dx.doi.org/10.1177/1357633X21990991DOI Listing
February 2021

Feasibility of asynchronous video-based telemedicine in the diagnosis and management of paediatric blepharoptosis.

J Telemed Telecare 2021 Jan 20:1357633X20985394. Epub 2021 Jan 20.

The Vision Center at Children's Hospital Los Angeles, USA.

Introduction: The purpose of this study was to assess the validity of using video glasses as part of an asynchronous telemedicine screening protocol for paediatric blepharoptosis.

Methods: A physician assistant wearing Pivothead SMART Series glasses recorded videos of paediatric patients referred for blepharoptosis in primary, down and upgaze while holding a ruler next to the eyes. An oculoplastic surgeon viewed the stored videos and recorded margin-reflex distance 1 and levator function. Using these measurements, the surgeon determined whether surgical intervention was recommended and, if so, which procedure was recommended. The surgeon recorded the same parameters for each patient based on an in-person examination performed later that day. Videos were reviewed eight months later and the same parameters were recorded.

Results: Twenty-nine children ( = 58 eyes) were enrolled. Margin-reflex distance 1 and levator function measurements based on same-day video review agreed with in-person examination 94.8% (intraclass correlation coefficient = 0.82) and 98.3% (intraclass correlation coefficient = 0.96) of the time, respectively. Margin-reflex distance 1 and levator function measurements based on later video review agreed with in-person examination 93.1% (intraclass correlation coefficient = 0.85) and 94.8% (intraclass correlation coefficient = 0.93) of the time, respectively. Agreement in identifying surgical candidates was almost perfect (= = 0.93) for same-day video review and substantial (= = 0.73) for later video review. Sensitivity of identifying surgical patients was 100% for both same-day video review and later video review; though specificity was lower at 94.1% for same-day video review and 76.5% for later video review.

Discussion: Asynchronous telemedicine encounters employing video glasses are a useful screening modality for identifying surgical paediatric blepharoptosis patients.
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http://dx.doi.org/10.1177/1357633X20985394DOI Listing
January 2021

Intravitreal Melphalan for Retinoblastoma: The Impact of Toxicity on Recurrence and Ultimate Globe Salvage.

Ocul Oncol Pathol 2020 Dec 25;6(6):388-394. Epub 2020 Aug 25.

The Vision Center at Children's Hospital Los Angeles, Los Angeles, California, USA.

Introduction: Intravitreal melphalan (IVM) has emerged as an efficacious treatment for vitreous seeding in retinoblastoma. Although rarely severe, IVM-related toxicity may be treatment limiting. There is paucity of data on the impact of IVM toxicity on new tumor formation and ultimate globe salvage.

Objectives: To investigate whether the grade of retinal toxicity post-IVM impacts retinal and seeding tumor recurrence, as well as the overall ability to salvage the eye.

Methods: A single-institution retrospective chart review was performed on 47 eyes of 42 patients who received systemic intravenous chemotherapy followed by IVM as salvage treatment for persistent or recurrent vitreous seeding. Chorioretinal toxicity was graded from 0 to 5.

Results: Toxicity grade was inversely associated with the risk of recurrence, where a one-unit increase in toxicity grade correlated with nearly a 54% reduction in the odds of tumor recurrence (OR 0.46 [0.25-0.84], = 0.01). Similarly, toxicity grade was related to enucleation, where a one-unit increase in toxicity grade was associated with a 31% reduction in the odds of undergoing enucleation (OR 0.69 [0.40-1.18], = 0.17).

Conclusions: While retinoblastoma therapy aims to limit toxicity, especially visually significant toxicity, eyes with higher grades of post-IVM toxicity are less likely to have retinal and seeding tumor recurrence.
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http://dx.doi.org/10.1159/000509080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7772881PMC
December 2020

Core Outcome Measures for Trials in People With Coronavirus Disease 2019: Respiratory Failure, Multiorgan Failure, Shortness of Breath, and Recovery.

Crit Care Med 2021 03;49(3):503-516

Nova Medical School, CHRC, New University of Lisbon, Polyvalent Intensive Care Unit, Sao Francisco Xavier Hospital, CHLO, Lisbon, Portugal.

Objectives: Respiratory failure, multiple organ failure, shortness of breath, recovery, and mortality have been identified as critically important core outcomes by more than 9300 patients, health professionals, and the public from 111 countries in the global coronavirus disease 2019 core outcome set initiative. The aim of this project was to establish the core outcome measures for these domains for trials in coronavirus disease 2019.

Design: Three online consensus workshops were convened to establish outcome measures for the four core domains of respiratory failure, multiple organ failure, shortness of breath, and recovery.

Setting: International.

Patients: About 130 participants (patients, public, and health professionals) from 17 countries attended the three workshops.

Interventions: None.

Measurements And Main Results: Respiratory failure, assessed by the need for respiratory support based on the World Health Organization Clinical Progression Scale, was considered pragmatic, objective, and with broad applicability to various clinical scenarios. The Sequential Organ Failure Assessment was recommended for multiple organ failure, because it was routinely used in trials and clinical care, well validated, and feasible. The Modified Medical Research Council measure for shortness of breath, with minor adaptations (recall period of 24 hr to capture daily fluctuations and inclusion of activities to ensure relevance and to capture the extreme severity of shortness of breath in people with coronavirus disease 2019), was regarded as fit for purpose for this indication. The recovery measure was developed de novo and defined as the absence of symptoms, resumption of usual daily activities, and return to the previous state of health prior to the illness, using a 5-point Likert scale, and was endorsed.

Conclusions: The coronavirus disease 2019 core outcome set recommended core outcome measures have content validity and are considered the most feasible and acceptable among existing measures. Implementation of the core outcome measures in trials in coronavirus disease 2019 will ensure consistency and relevance of the evidence to inform decision-making and care of patients with coronavirus disease 2019.
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http://dx.doi.org/10.1097/CCM.0000000000004817DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7892260PMC
March 2021

Post-Weld Heat Treatment of API 5L X70 High Strength Low Alloy Steel Welds.

Materials (Basel) 2020 Dec 18;13(24). Epub 2020 Dec 18.

School of Mechanical Engineering, the University of Adelaide, Adelaide, SA 5005, Australia.

High Strength Low Alloy (HSLA) steels are the materials of choice in pipeline construction with the API X70 grade as the steel for the majority of pipeline networks constructed during the late 20th and early this century. This paper reports on the influence of Post-Weld Heat Treatment (PWHT) on the reduction of residual stresses, resulting changes in the microstructure, and mechanical properties of a multi-pass, X70 HSLA steel, weld joints made by a combined Modified Short Arc Welding (MSAW) and Flux Cored Arc Welding (FCAW) processes. Neutron diffraction results highlighted high magnitude of tensile residual stresses, in excess of yield strength of both parent and weld metal, in the as-welded specimen (~650 MPa), which were decreased substantially as a result of applying PWHT (~144 MPa). Detailed microstructural studies are reported to confirm the phase transformation during PWHT and its interrelationship with mechanical properties. Transmission Electron Microscopy (TEM) analysis showed polygonization and formation of sub-grains in the PWHT specimen which justifies the reduction of residual stress in the heat-treated weld joints. Furthermore, microstructural changes due to PWHT justify the improvement in ductility (increase in the elongations) with a slight reduction in yield and tensile strength for the PWHT weld joint.
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http://dx.doi.org/10.3390/ma13245801DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7767025PMC
December 2020

Core Outcomes Set for Trials in People With Coronavirus Disease 2019.

Crit Care Med 2020 11;48(11):1622-1635

Nova Medical School, CHRC, New University of Lisbon, Polyvalent Intensive Care Unit, Sao Francisco Xavier Hospital, CHLO, Lisbon, Portugal.

Objectives: The outcomes reported in trials in coronavirus disease 2019 are extremely heterogeneous and of uncertain patient relevance, limiting their applicability for clinical decision-making. The aim of this workshop was to establish a core outcomes set for trials in people with suspected or confirmed coronavirus disease 2019.

Design: Four international online multistakeholder consensus workshops were convened to discuss proposed core outcomes for trials in people with suspected or confirmed coronavirus disease 2019, informed by a survey involving 9,289 respondents from 111 countries. The transcripts were analyzed thematically. The workshop recommendations were used to finalize the core outcomes set.

Setting: International.

Subjects: Adults 18 years old and over with confirmed or suspected coronavirus disease 2019, their family members, members of the general public and health professionals (including clinicians, policy makers, regulators, funders, researchers).

Interventions: None.

Measurements: None.

Main Results: Six themes were identified. "Responding to the critical and acute health crisis" reflected the immediate focus on saving lives and preventing life-threatening complications that underpinned the high prioritization of mortality, respiratory failure, and multiple organ failure. "Capturing different settings of care" highlighted the need to minimize the burden on hospitals and to acknowledge outcomes in community settings. "Encompassing the full trajectory and severity of disease" was addressing longer term impacts and the full spectrum of illness (e.g. shortness of breath and recovery). "Distinguishing overlap, correlation and collinearity" meant recognizing that symptoms such as shortness of breath had distinct value and minimizing overlap (e.g. lung function and pneumonia were on the continuum toward respiratory failure). "Recognizing adverse events" refers to the potential harms of new and evolving interventions. "Being cognizant of family and psychosocial wellbeing" reflected the pervasive impacts of coronavirus disease 2019.

Conclusions: Mortality, respiratory failure, multiple organ failure, shortness of breath, and recovery are critically important outcomes to be consistently reported in coronavirus disease 2019 trials.
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http://dx.doi.org/10.1097/CCM.0000000000004585DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7448717PMC
November 2020

International Survey to Establish Prioritized Outcomes for Trials in People With Coronavirus Disease 2019.

Crit Care Med 2020 11;48(11):1612-1621

Department of Pulmonology Hospital Clinic. University of Barcelona, CIBERES, IDIBAPS, ICREA, Barcelona, Spain.

Objectives: There are over 4,000 trials conducted in people with coronavirus disease 2019. However, the variability of outcomes and the omission of patient-centered outcomes may diminish the impact of these trials on decision-making. The aim of this study was to generate a consensus-based, prioritized list of outcomes for coronavirus disease 2019 trials.

Design: In an online survey conducted in English, Chinese, Italian, Portuguese, and Spanish languages, adults with coronavirus disease 2019, their family members, health professionals, and the general public rated the importance of outcomes using a 9-point Likert scale (7-9, critical importance) and completed a Best-Worst Scale to estimate relative importance. Participant comments were analyzed thematically.

Setting: International.

Subjects: Adults 18 years old and over with confirmed or suspected coronavirus disease 2019, their family members, members of the general public, and health professionals (including clinicians, policy makers, regulators, funders, and researchers).

Interventions: None.

Measurements: None.

Main Results: In total, 9,289 participants from 111 countries (776 people with coronavirus disease 2019 or family members, 4,882 health professionals, and 3,631 members of the public) completed the survey. The four outcomes of highest priority for all three groups were: mortality, respiratory failure, pneumonia, and organ failure. Lung function, lung scarring, sepsis, shortness of breath, and oxygen level in the blood were common to the top 10 outcomes across all three groups (mean > 7.5, median ≥ 8, and > 70% of respondents rated the outcome as critically important). Patients/family members rated fatigue, anxiety, chest pain, muscle pain, gastrointestinal problems, and cardiovascular disease higher than health professionals. Four themes underpinned prioritization: fear of life-threatening, debilitating, and permanent consequences; addressing knowledge gaps; enabling preparedness and planning; and tolerable or infrequent outcomes.

Conclusions: Life-threatening respiratory and other organ outcomes were consistently highly prioritized by all stakeholder groups. Patients/family members gave higher priority to many patient-reported outcomes compared with health professionals.
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http://dx.doi.org/10.1097/CCM.0000000000004584DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7448718PMC
November 2020

Team clinic: Expansion of a multidisciplinary care model for adolescents with type 1 diabetes.

Contemp Clin Trials 2020 08 4;95:106079. Epub 2020 Jul 4.

Center for Endocrinology, Diabetes, & Metabolism, Children's Hospital Los Angeles, United States of America. Electronic address:

Background: Adolescent and young adults (AYA) with Type 1 Diabetes (T1D) experience more difficulty with glycemic control than patients in all other age groups. The shared medical appointment (SMA) model has been effective in multiple healthcare populations, but the feasibility and effectiveness of SMA in AYA patients with T1D is unclear.

Methods: This research leverages the team's multidisciplinary expertise to develop an engaging intervention toolkit and test the implementation of the Team Clinic care model for the treatment of T1D among middle school adolescents in a large urban children's hospital serving an economically, racially and ethnically diverse population. In Phase 1, the team will manualize the Team Clinic care model into an engaging, age-appropriate educational and intervention toolkit. In Phase 2, the team will conduct a randomized clinical trial to test the feasibility and usability of the toolkit from the provider perspective (team member satisfaction; clinical efficiency; compliance with American Diabetes Association, American Association of Diabetes Educators, and California Children's Services standards; and payor-level cost data) and the preliminary efficacy of the intervention toolkit on patient- and family-level outcomes (attendance, acceptability/satisfaction with care, patient-level cost data, diabetes outcomes, diabetes family conflict, diabetes distress, and depression).

Discussion: AYA patients with T1D often receive care in clinics and institutions with limited resources and time. This research tests the feasibility and efficacy of an innovative and potentially cost-effective SMA model to address the unique needs of underserved populations, while meeting national and state clinical standards. Trial registration The study is registered with ClinicalTrials.gov (Protocol Record: NCT04190368).
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http://dx.doi.org/10.1016/j.cct.2020.106079DOI Listing
August 2020

Chromosome 6p Amplification in Aqueous Humor Cell-Free DNA Is a Prognostic Biomarker for Retinoblastoma Ocular Survival.

Mol Cancer Res 2020 08 20;18(8):1166-1175. Epub 2020 May 20.

The Vision Center at Children's Hospital Los Angeles, Los Angeles, California.

Aqueous humor contains tumor-derived cell-free DNA (cfDNA) and can serve as a liquid biopsy for retinoblastoma. We previously associated somatic copy-number alteration (SCNA) 6p gain with a 10-fold increased risk of enucleation. Here we provide a 2-year update to further explore 6p gain as a prognostic biomarker for ocular survival. Patients diagnosed with retinoblastoma from December 2014 to July 2019 from whom aqueous humor was sampled were included. cfDNA was extracted and shallow whole-genome sequencing performed to identify highly recurrent retinoblastoma SCNAs (gain of 1q, 2p, 6p, loss of 13q, 16q). 116 aqueous humor samples from 50 eyes of 46 patients were included: 27 eyes were salvaged, 23 were enucleated. Highly recurrent retinoblastoma SCNAs were found in 66% eyes. 6p gain was the most prevalent SCNA (50% eyes). It was particularly more prevalent in enucleated eyes (73.9%) than in salvaged eyes (29.6%; = 0.004). 6p gain in aqueous humor cfDNA portended nearly 10-fold increased odds of enucleation (OR = 9.87; 95% confidence interval = 1.75-55.65; = 0.009). In the enucleated eyes, 6p gain was associated with aggressive histopathologic features, including necrosis, higher degrees of anaplasia, and focal invasion of ocular structures. With extended follow-up and nearly double the aqueous humor samples, we continue to demonstrate 6p gain as a potential prognostic biomarker for retinoblastoma. IMPLICATIONS: Aqueous humor is a high-yield source of tumor-derived DNA in retinoblastoma eyes. Detection of 6p gain in the aqueous humor allows for targeted, patient-centered therapies based on this molecular prognostic marker. Prospective, multicenter studies with aqueous humor sampled from all eyes at diagnosis are warranted to validate these findings.
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http://dx.doi.org/10.1158/1541-7786.MCR-19-1262DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7415535PMC
August 2020

VISUAL AND ANATOMIC OUTCOMES OF PEDIATRIC ENDOSCOPIC VITRECTOMY IN 326 CASES.

Retina 2020 Nov;40(11):2083-2090

Department of Surgery, The Vision Center, Children's Hospital Los Angeles, Los Angeles, California.

Purpose: To report on the indications, outcomes, and complications of endoscopic vitrectomy in a large cohort of pediatric vitreoretinal patients.

Methods: This is a retrospective interventional case series consisting of 244 eyes of 211 patients aged 18 years or younger undergoing a total of 326 endoscopic vitrectomies from 2008 to 2017. A 23-gauge vitrectomy was performed with use of a 19-gauge endoscope.

Results: Two hundred and eleven patients with a mean age of 7.5 years (range: 0-18 years) and median follow-up since last surgery of 28 months (range: 3 months-8.7 years) were included. The most common indication for endoscopic vitrectomy was retinal detachment (234/326; 72%) with proliferative vitreoretinopathy (162/234; 69%). Other diagnoses included trauma (25%), retinopathy of prematurity (15%), and glaucoma (9%). Twenty-five percent of surgeries (80/326) were performed on eyes with significant corneal opacities. Retinal reattachment was achieved in 67% of eyes with retinal detachment (119/178). Visual acuity improved in 26% of retinal detachment eyes versus 53% of nonretinal detachment eyes (P = 0.005). Surgical complications included band keratopathy (15%), hypotony (8%), cataract (7%), and elevated intraocular pressure (3%).

Conclusion: In this large series of pediatric endoscopic vitreoretinal surgeries, anatomic outcomes and complication rates were comparable with previous studies.
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http://dx.doi.org/10.1097/IAE.0000000000002746DOI Listing
November 2020

Adapting home telehealth group appointment model (CoYoT1 clinic) for a low SES, publicly insured, minority young adult population with type 1 diabetes.

Contemp Clin Trials 2020 01 18;88:105896. Epub 2019 Nov 18.

Chan Division of Occupational Science and Occupational Therapy, University of Southern California, USA.

As more individuals from diverse backgrounds are diagnosed with Type 1 Diabetes (T1D), the need to address resulting disparities in diabetes outcomes among these populations also escalates. Although young adulthood proves challenging for all patients with diabetes, young adults (YA) from racial/ethnic minorities and low socioeconomic backgrounds face even greater T1D management obstacles. The poorer outcomes in these populations drive an urgent need for alternative care models to improve YA's engagement in their T1D clinical care and address barriers to improved health outcomes. Previous telemedicine initiatives for T1D have yielded positive diabetes care results, especially in YA, offering one promising way to reach this high-risk population. To serve these patients better, an established and successful home telehealth group appointment model, "CoYoT1 Clinic" (Colorado Young Adults with T1D), was adapted to provide care to YA with T1D at a large urban children's hospital in Southern California. At this location, ~70% of patients have public/no insurance, and 85% are racial/ethnic minorities. In this paper, we report the process of adapting the CoYoT1 Clinic model and designing a randomized controlled trial (RCT) to evaluate its efficacy. The adapted model uses meticulous study-design methods that incorporate patient advisors, quantitative and qualitative data collection, collaboration with local stakeholders, intervention development, and patient randomization into a factorial design analyzing telemedicine versus in-person and patient-centered versus standard care. The new model addresses the needs of high-risk YA in Southern California, with the goal of increasing access to care, improving follow-up frequency, and strengthening patient and provider satisfaction. The study is registered with ClinicalTrials.gov (Clinical Trials Number: NCT03793673).
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http://dx.doi.org/10.1016/j.cct.2019.105896DOI Listing
January 2020

Estimating the Health-Related Quality of Life of Twitter Users Using Semantic Processing.

Stud Health Technol Inform 2019 Aug;264:1065-1069

Department of Radiological Sciences, University of California, Los Angeles, Los Angeles, CA, USA.

Social media presents a rich opportunity to gather health information with limited intervention through the analysis of completely unstructured and unlabeled microposts. We sought to estimate the health-related quality of life (HRQOL) of Twitter users using automated semantic processing methods. We collected tweets from 878 Twitter users recruited through online solicitation and in-person contact with patients. All participants completed the four-item Centers for Disease Control Healthy Days Questionnaire at the time of enrollment and 30 days later to measure "ground truth" HRQOL. We used a combination of document frequency analysis, sentiment analysis, topic analysis, and concept mapping to extract features from tweets, which we then used to estimate dichotomized HRQOL ("high" vs. "low") using logistic regression. Binary HRQOL status was estimated with moderate performance (AUC = 0.64). This result indicates that free-range social media data only offers a window into HRQOL, but does not afford direct access to current health status.
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http://dx.doi.org/10.3233/SHTI190388DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081585PMC
August 2019

Home Telemedicine (CoYoT1 Clinic): A Novel Approach to Improve Psychosocial Outcomes in Young Adults With Diabetes.

Diabetes Educ 2019 08 27;45(4):420-430. Epub 2019 Jun 27.

Children's Hospital Los Angeles, University of Southern California, Keck School of Medicine, Los Angeles, California.

Purpose: To assess the impact of a home telemedicine clinic model (CoYoT1 Clinic) on psychosocial and behavioral outcomes designed for young adults (YAs) with type 1 diabetes (T1D).

Methods: YAs self-selected to participate in the CoYoT1 Clinic or serve as a usual care control. CoYoT1 Clinic visits consisted of an individual appointment with a provider and a group appointment with other YAs with T1D using home telemedicine. Psychosocial and behavioral functioning was assessed by 4 measures: Diabetes Distress Scale, Self-Efficacy for Diabetes Scale, Self-Management of Type 1 Diabetes in Adolescence Scale, and Center for Epidemiologic Studies Depression Scale.

Results: Forty-two patients participated in the CoYoT1 Clinic and 39 patients served as controls. CoYoT1 participants reported lower levels of distress ( = .03), increased diabetes self-efficacy ( = .01), and improved ability to communicate with others about diabetes ( = .04) over the study period compared to controls. YA males in the control group reported increases in depressive symptoms ( = .03) during the study period, but CoYoT1 participants showed no changes.

Conclusion: Group home telemedicine for YAs with T1D positively affects diabetes distress, self-efficacy, and diabetes-specific communication. These positive findings have the potential to also affect the YAs' long-term diabetes outcomes. Further investigation of the model is needed.
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http://dx.doi.org/10.1177/0145721719858080DOI Listing
August 2019

Cost-effectiveness of Shared Telemedicine Appointments in Young Adults With T1D: CoYoT1 Trial.

Diabetes Care 2019 08 12;42(8):1589-1592. Epub 2019 Jun 12.

Section of General Internal Medicine, The University of Chicago, Chicago, IL.

Objective: Young adults with type 1 diabetes (T1D) often struggle to achieve glycemic control and maintain routine clinic visits. We aimed to evaluate the societal cost-effectiveness of the Colorado young adults with T1D (CoYoT1) Clinic, an innovative care model of shared medical appointments through home telehealth.

Research Design And Methods: Patients self-selected into the CoYoT1 ( = 42) or usual care ( = 39) groups.

Results: Within the trial, we found no significant differences in 9-month quality-adjusted life; however, the control group had a larger decline from baseline in utility than the CoYoT1 group, indicating a quality of life (QoL) benefit of the intervention (difference in difference mean ± SD: 0.04 ± 0.09; = 0.03). CONCLUSIONS: The CoYoT1 care model may help young adults with T1D maintain a higher QoL with no increase in costs.
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http://dx.doi.org/10.2337/dc19-0363DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6647044PMC
August 2019

Gender bias in publishing.

Lancet 2018 10;392(10157):1514-1515

Department of Rehabilitation, Nutrition and Sport, La Trobe University, Bundoora, VIC, Australia.

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http://dx.doi.org/10.1016/S0140-6736(18)32000-2DOI Listing
October 2018

Blood Schizonticidal Activity and Safety of Tafenoquine When Administered as Chemoprophylaxis to Healthy, Nonimmune Participants Followed by Blood Stage Plasmodium falciparum Challenge: A Randomized, Double-blind, Placebo-controlled Phase 1b Study.

Clin Infect Dis 2019 07;69(3):480-486

60P Australia Pty Ltd, Sydney, New South Wales.

Background: Tafenoquine was recently approved for chemoprophylaxis of malaria. Its specific activity against liver and blood stages of Plasmodium species has been separately characterized in animals but not in humans.

Methods: In this randomized, double-blind, placebo-controlled study, 16 malaria-naive, glucose-6-phosphate dehydrogenase-normal participants aged 20-42 years received tafenoquine chemoprophylaxis prior to challenge with blood stage Plasmodium falciparum. Participants were randomly assigned to either tafenoquine (n = 12) or placebo (n = 4) and took blinded study medication (single 200-mg dose) on days 1, 2, 3, and 10, followed by intravenous inoculation with approximately 2800 P. falciparum parasitized erythrocytes on day 13. The primary endpoint was the number of participants requiring rescue treatment with artemether/lumefantrine due to the onset of parasitemia as determined by quantitative polymerase chain reaction.

Results: None of the 12 participants who received tafenoquine developed parasitemia, whereas all placebo participants developed parasitemia (P = .0005). Two cases of mild hemoglobin decrease and a single case of mild hyperbilirubinemia occurred in the tafenoquine group.

Conclusions: Tafenoquine chemoprophylaxis is safe and effective in preventing malaria in healthy nonimmune participants challenged with blood stage P. falciparum.

Clinical Trials Registration: Australian and New Zealand Clinical Trials Registry (ANZCTR): ACTRN12617000102370.
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http://dx.doi.org/10.1093/cid/ciy939DOI Listing
July 2019

Critical deposition height for sustainable restoration via laser additive manufacturing.

Sci Rep 2018 Oct 3;8(1):14726. Epub 2018 Oct 3.

Australian Nuclear Science and Technology Organization, New Illawarra Rd, Lucas Heights NSW, 2234, Sydney, Australia.

Laser material deposition based restoration of high-value components can be a revolutionary technology in remanufacturing. The deposition process induces residual stresses due to thermomechanical behavior and metallurgical transformations. The presence of tensile residual stresses in the deposited layer will compromise the fatigue life of the restored component. We have developed a novel fully coupled metallurgical, thermal and mechanical (metallo-thermomechanical) model to predict residual stresses and identified a critical deposition height, which ensures compressive residual stresses in the deposited layer. Any lower deposition height will result in tensile residual stresses and higher deposition height will result in excessive dilution (substrate melting). We have validated the model using neutron and micro-focus X-ray diffraction measurements. This study highlights that the critical deposition height corresponds to the minimum cooling rate during solidification. It addresses one of the major outstanding problems of additive manufacturing and paves a way for "science-enabled-technology" solutions for sustainable restoration/remanufacturing.
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http://dx.doi.org/10.1038/s41598-018-32842-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6170464PMC
October 2018

Developmental stage-specific proliferation and retinoblastoma genesis in RB-deficient human but not mouse cone precursors.

Proc Natl Acad Sci U S A 2018 10 13;115(40):E9391-E9400. Epub 2018 Sep 13.

The Vision Center, Children's Hospital Los Angeles, Los Angeles, CA 90027;

Most retinoblastomas initiate in response to the inactivation of the gene and loss of functional RB protein. The tumors may form with few additional genomic changes and develop after a premalignant retinoma phase. Despite this seemingly straightforward etiology, mouse models have not recapitulated the genetic, cellular, and stage-specific features of human retinoblastoma genesis. For example, whereas human retinoblastomas appear to derive from cone photoreceptor precursors, current mouse models develop tumors that derive from other retinal cell types. To investigate the basis of the human cone-specific oncogenesis, we compared developmental stage-specific cone precursor responses to RB loss in human and murine retina cultures and in cone-specific -knockout mice. We report that RB-depleted maturing (ARR3) but not immature (ARR3) human cone precursors enter the cell cycle, proliferate, and form retinoblastoma-like lesions with Flexner-Wintersteiner rosettes, then form low or nonproliferative premalignant retinoma-like lesions with fleurettes and p16 and p130 expression, and finally form highly proliferative retinoblastoma-like masses. In contrast, in murine retina, only RB-depleted immature (Arr3) cone precursors entered the cell cycle, and they failed to progress from S to M phase. Moreover, whereas intrinsically highly expressed MDM2 and MYCN contribute to RB-depleted maturing (ARR3) human cone precursor proliferation, ectopic MDM2 and Mycn promoted only immature (Arr3) murine cone precursor cell-cycle entry. These findings demonstrate that developmental stage-specific as well as species- and cell type-specific features sensitize to inactivation and reveal the human cone precursors' capacity to model retinoblastoma initiation, proliferation, premalignant arrest, and tumor growth.
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http://dx.doi.org/10.1073/pnas.1808903115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6176579PMC
October 2018

Phase 1b study of obinutuzumab, ibrutinib, and venetoclax in relapsed and refractory chronic lymphocytic leukemia.

Blood 2018 10 15;132(15):1568-1572. Epub 2018 Aug 15.

Division of Hematology.

Targeted therapies including the engineered afucosylated anti-CD20 monoclonal antibody obinutuzumab, Bruton's tyrosine kinase inhibitor ibrutinib, and B-cell lymphoma protein 2 inhibitor venetoclax have demonstrated significant clinical activity in chronic lymphocytic leukemia (CLL) and, based on their complementary mechanisms, are ideal for combination. However, combining venetoclax with other active agents raises safety concerns, as it may increase the risk for tumor lysis syndrome. To minimize this risk, we designed and implemented a fixed-duration regimen using sequentially administered obinutuzumab followed by ibrutinib (cycle 2) and venetoclax (cycle 3), for a total of fourteen 28-day cycles. This phase 1b study included 12 patients with relapsed or refractory CLL. We tested 3 dose levels of venetoclax and identified the doses of all 3 agents approved by the US Food and Drug Administration for use in the combination. Adverse events were consistent with known toxicities of the individual agents, with hematologic adverse events being most frequent. No clinically significant tumor lysis syndrome occurred. The overall response rate was 92% (95% confidence interval, 62%-100%), with 42% (5/12) achieving a complete remission or complete remission with incomplete marrow recovery. There were 6 patients with no detectable CLL in both the blood and bone marrow at the end of treatment. We found this regimen to be safe and tolerable in CLL, and capable of inducing deep responses, justifying future study in our ongoing phase 2 cohorts of relapsed or refractory and treatment-naive patients, as well as larger phase 3 trials currently in planning. This trial was registered at www.clinicaltrials.gov as #NCT02427451.
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http://dx.doi.org/10.1182/blood-2018-05-853564DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6182267PMC
October 2018

Genomic cfDNA Analysis of Aqueous Humor in Retinoblastoma Predicts Eye Salvage: The Surrogate Tumor Biopsy for Retinoblastoma.

Mol Cancer Res 2018 11 30;16(11):1701-1712. Epub 2018 Jul 30.

Department of Biological Sciences, Dornsife College of Letters, Arts, and Sciences, University of Southern California, Los Angeles, California.

Tumor-derived cell-free DNA (cfDNA) has biomarker potential; therefore, this study aimed to identify cfDNA in the aqueous humor (AH) of retinoblastoma eyes and correlate somatic chromosomal copy-number alterations (SCNA) with clinical outcomes, specifically eye salvage. AH was extracted via paracentesis during intravitreal injection of chemotherapy or enucleation. Shallow whole-genome sequencing was performed using isolated cfDNA to assess for highly recurrent SCNAs in retinoblastoma including gain of 1q, 2p, 6p, loss of 13q, 16q, and focal amplification. Sixty-three clinical specimens of AH from 29 eyes of 26 patients were evaluated; 13 eyes were enucleated and 16 were salvaged (e.g., saved). The presence of detectable SCNAs was 92% in enucleated eyes versus 38% in salvaged eyes ( = 0.006). Gain of chromosome 6p was the most common SCNA found in 77% of enucleated eyes, compared with 25% of salvaged eyes ( = 0.0092), and associated with a 10-fold increased odds of enucleation (OR, 10; 95% CI, 1.8-55.6). The median amplitude of 6p gain was 1.47 in enucleated versus 1.07 in salvaged eyes ( = 0.001). The presence of AH SCNAs was correlated retrospectively with eye salvage. The probability of ocular salvage was higher in eyes without detectable SCNAs in the AH ( = 0.0028), specifically 6p gain. This is the first study to correlate clinical outcomes with SCNAs in the AH from retinoblastoma eyes, as such these findings indicate that 6p gain in the aqueous humor is a potential prognostic biomarker for poor clinical response to therapy. The correlation of clinical outcomes and SCNAs in the AH identified in the current study requires prospective studies to validate these finding before SCNAs, like 6p gain, can be used to predict clinical outcomes at diagnosis. .
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http://dx.doi.org/10.1158/1541-7786.MCR-18-0369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6214755PMC
November 2018

CoYoT1 Clinic: Home Telemedicine Increases Young Adult Engagement in Diabetes Care.

Diabetes Technol Ther 2018 05 19;20(5):370-379. Epub 2018 Apr 19.

6 Department of Pediatrics, Division of Endocrinology, Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California , Los Angeles, California.

Background: Young adults with type 1 diabetes (T1D) experience poor glycemic control, disengagement in care, and are often lost to the medical system well into their adult years. Diabetes providers need a new approach to working with the population. The goal of this study was to determine whether an innovative shared telemedicine appointment care model (CoYoT1 Clinic [pronounced as "coyote"; Colorado Young Adults with T1D]) for young adults with T1D improves care engagement, satisfaction, and adherence to American Diabetes Association (ADA) guidelines regarding appointment frequency.

Subjects And Methods: CoYoT1 Clinic was designed to meet the diabetes care needs of young adults (18-25 years of age) with T1D through home telemedicine. Visits occurred every 3 months over the 1-year study (three times by home telemedicine and one time in-person). Outcomes were compared to patients receiving treatment as usual (control).

Results: Compared with controls, CoYoT1 patients attended significantly more clinic visits (P < 0.0001) and increased their number of clinic visits from the year before the intervention. Seventy-four percent of CoYoT1 patients were seen four times over the 12-month study period, meeting ADA guidelines, but none in the control group met the ADA recommendation. CoYoT1 patients used diabetes technologies more frequently and reported greater satisfaction with care compared with controls.

Conclusions: Delivering diabetes care by home telemedicine increases young adults' adherence to ADA guidelines and usage of diabetes technologies, and improves retention in care when compared to controls. Home telemedicine may keep young adults engaged in their diabetes care during this challenging transition period.
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http://dx.doi.org/10.1089/dia.2017.0450DOI Listing
May 2018

Porous orbital implant after enucleation in retinoblastoma patients: indications and complications.

Orbit 2018 Dec 20;37(6):438-443. Epub 2018 Feb 20.

a USC Roski Eye Institute , Keck School of Medicine of the University of Southern California , Los Angeles , CA , USA.

This study aims to identify risk factors associated with complications in retinoblastoma patients following primary and secondary enucleations with porous implant placement. A retrospective case-control study was performed between 2010 and 2015. Data pertaining to subjects' demographics, medical history, clinical, and pathological findings, implant characteristics and complications were collected. The analysis included 103 eyes of 101 patients age 27.8 ± 21.9 months undergoing enucleation for retinoblastoma. Postoperatively, 19/103 (18%) eyes developed exposure, extrusion, or hematoma requiring subsequent surgery. Exposure was the most common postoperative complication (12/19, 63%). Age at enucleation 24 months or younger, Hispanic ethnicity, female gender, and intravenous chemotherapy prior to enucleation were associated with increased odds of implant complications. In contrast, patients who were given intravitreal melphalan (IM), subtenons carboplatin (SC), or external beam radiation therapy (EBRT) did not demonstrate an increased risk of complications. In this cohort of retinoblastoma patients undergoing primary or secondary enucleation with porous implants, implant exposure was the most common postoperative complication. Our findings suggest that female gender, Hispanic ethnicity, age at enucleation 24 months or younger, and intravenous chemotherapy prior to enucleation may increase the risk of complications.
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http://dx.doi.org/10.1080/01676830.2018.1440605DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6613564PMC
December 2018

Major Depression Comorbid with Medical Conditions: Analysis of Quality of Life, Functioning, and Depressive Symptom Severity.

Psychopharmacol Bull 2018 01;48(1):8-25

Drs. IsHak, Dang, Vanle, Elzahaby, Reid, Sumner, Danovitch, and Ms. Klimowicz, Kauzor, Cedars-Sinai Medical Center, Los Angeles, California, USA. Dr. Steiner, University of California, Los Angeles, California, USA. Ms. Klimowicz, Western University of Health Sciences, California, USA. Ms. Kauzor, California State University, Northridge, California, USA.

Background: The presence of Major Depressive Disorder (MDD) is often comorbid in patients with a variety of general medical conditions (GMCs) which could lead to less favorable outcomes.

Objective: The goal of this analysis is to examine functional outcomes of QOL and functioning before and after antidepressant treatment among patients with MDD with and without GMCs.

Methods: We performed a secondary analysis based on the STAR*D database. The analysis included two patient groups from the STAR*D trial: 1,198 patients comorbid with MDD and GMCs (MDD + GMC) and 1,082 patients with MDD and no GMCs (MDDnoGMC), as defined by the Cumulative Illness Rating Scale. We analyzed depressive symptom severity, functioning and quality of life (QOL) before and after level 1 treatment with citalopram.

Results: At baseline, the MDD + GMC group had significantly lower QOL (p < 0.001) and functioning (p = 0.001) than the MDDnoGMC group, although depressive symptom severity was not significantly different. Following antidepressant treatment, QOL, functioning and depressive symptom severity significantly improved for both MDD + GMC and MDDnoGMC groups. However, patients with MDD + GMC were more likely to experience severe impairments in QOL in (56.8% vs. 43.5% for MDDnoGMC, p < 0.001) and functioning (42.5% vs. 29.3% for MDDnoGMC, p < 0.001) following treatment. The remission rate was significantly lower for MDD + GMC (30.6% vs. 41.1% for MDDnoGMC, p < 0.001).

Conclusions: Our findings suggest that antidepressant treatment had a positive impact on patients with and without GMCs. However, those with GMCs experienced not only a lower remission rate, but also continued to experience more significantly severe impairments in QOL and functioning.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5765436PMC
January 2018

Mapping spiral structure on the far side of the Milky Way.

Science 2017 10;358(6360):227-230

Max-Planck-Institut für Radioastronomie, Auf dem Hügel 69, 53121 Bonn, Germany.

Little is known about the portion of the Milky Way lying beyond the Galactic center at distances of more than 9 kiloparsec from the Sun. These regions are opaque at optical wavelengths because of absorption by interstellar dust, and distances are very large and hard to measure. We report a direct trigonometric parallax distance of kiloparsec obtained with the Very Long Baseline Array to a water maser source in a region of active star formation. These measurements allow us to shed light on Galactic spiral structure by locating the Scutum-Centaurus spiral arm as it passes through the far side of the Milky Way and to validate a kinematic method for determining distances in this region on the basis of transverse motions.
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http://dx.doi.org/10.1126/science.aan5452DOI Listing
October 2017