The Human Tumor Atlas Network: Charting Tumor Transitions across Space and Time at Single-Cell Resolution.

Crucial transitions in cancer-including tumor initiation, local expansion, metastasis, and therapeutic resistance-involve complex interactions between cells within the dynamic tumor ecosystem. Transformative single-cell genomics technologies and spatial multiplex in situ methods now provide an opportunity to interrogate this complexity at unprecedented resolution. The Human Tumor Atlas Network (HTAN), part of the National Cancer Institute (NCI) Cancer Moonshot Initiative, will establish a clinical, experimental, computational, and organizational framework to generate informative and accessible three-dimensional atlases of cancer transitions for a diverse set of tumor types. This effort complements both ongoing efforts to map healthy organs and previous large-scale cancer genomics approaches focused on bulk sequencing at a single point in time. Generating single-cell, multiparametric, longitudinal atlases and integrating them with clinical outcomes should help identify novel predictive biomarkers and features as well as therapeutically relevant cell types, cell states, and cellular interactions across transitions. The resulting tumor atlases should have a profound impact on our understanding of cancer biology and have the potential to improve cancer detection, prevention, and therapeutic discovery for better precision-medicine treatments of cancer patients and those at risk for cancer.

Muscle activation patterns during active external rotation after reverse total shoulder arthroplasty: an electrophysiological study of the teres minor and associated musculature.

BACKGROUND: Preoperative teres minor insufficiency has been identified as a risk factor for poor restoration of external rotation (ER) after reverse total shoulder arthroplasty (RTSA). However, there has been little investigation regarding muscle activation patterns generating ER. This prospective study sought to determine the timing and activation levels of the shoulder girdle musculature during ER in well-functioning RTSAs with an intact teres minor using a lateralized design. METHODS: Patients who underwent RTSA ≥1 year previously with functional ER, an American Shoulder and Elbow Surgeons (ASES) score >70, superior rotator cuff deficiency, and an intact teres minor were identified. Electrophysiological and kinematic analyses were performed during ER in the modified neutral position (arm at side with 90° of elbow flexion) and in abduction (AB) (shoulder abducted 90° with 90° of elbow flexion). Dynamometer-recorded torque and position were pattern matched to electromyography during ER. The root-mean-square and integrated electromyography (in microvolts × milliseconds with standard deviation [SD]), as well as median frequency (MF) (in hertz with SD), were calculated to determine muscle recruitment. Pair-wise t test analysis compared muscle activation (P < .05 indicated significance). RESULTS: After an a priori power analysis, 16 patients were recruited. The average ASES score, visual analog scale pain score, and ASES subscore for ER in AB ("comb hair") were 87.7, 0.5, and 2.75 of 3, respectively. In AB, muscle activation began with the upper trapezius, middle trapezius, and latissimus dorsi, followed by the anterior deltoid activating to neutral. With ER beyond neutral, the teres major (9.6 µV × ms; SD, 9.2 µV × ms) initiated ER, followed by the teres minor (14.1 µV × ms; SD, 18.2 µV × ms) and posterior deltoid (11.1 µV × ms; SD, 9.3 µV × ms). MF analysis indicated equal contributions of the teres major (1.1 Hz; SD, 0.5 Hz), teres minor (1.2 Hz; SD, 0.4 Hz), and posterior deltoid (1.1 Hz; SD, 0.4 Hz) in ER beyond neutral. In the modified neutral position, the upper trapezius and middle trapezius were not recruited to the same level as in AB. For ER beyond neutral, the teres major (9.5 µV × ms [SD, 9 µV × ms]; MF, 1.1 Hz [SD, 0.5 Hz]), teres minor (11.4 µV × ms [SD, 15.1 µV × ms]; MF, 1.1 Hz [SD, 0.5 Hz]), and posterior deltoid (8.5 µV × ms [SD, 8 µV × ms]; MF, 1.2 Hz [SD, 0.3 Hz]) were activated in similar sequence and intensity as AB. No differences in muscle activation duration or intensity were noted among the teres major, teres minor, and posterior deltoid (P > .05). CONCLUSION: Active ER after RTSA is complex and is not governed by a single muscle-tendon unit. This study establishes a sequence, duration, and intensity of muscle activation for ER in well-functioning RTSAs. In both tested positions, the teres major, teres minor, and posterior deltoid function equally and sequentially to power ER.

Evenings with Molly: Adult Couples' Use of MDMA for Relationship Enhancement.

Within the modern resurgence of psychedelics as medicinal agents for a range of conditions, the story of MDMA (Ecstasy, Molly) has been re-narrated from a dangerous street drug to a breakthrough mental health therapy. Even still, the story of MDMA remains incomplete within a binary discourse of deviant recreational use versus psychotherapeutic-medical use. The present research aimed to uncover an emerging model of MDMA use grounded in the experiences of adult couples using MDMA privately and in the context of their committed relationships. Eight adult couples who self-reported active MDMA use were recruited for confidential in-depth interviews exploring questions related to drug, set, and setting as a general framework for understanding their private experiences with MDMA. A general inductive coding process was used to arrive at four overarching themes: Conscious Use, A Tool for Exploring, Planned Recovery, and Difficult Experiences. Couples reported making purposeful decisions about MDMA use, collaborating together on becoming physically and emotionally "set" for their drug experience. Couples described positive effects on communication, intimate bonding, and providing a relationship "tune up," among other durable changes to the relationship. An emerging cognitive-relational model of "evenings with Molly" contrasts with existing models of use by suggesting the possibility of informed, non-problematic adult use of the drug for cognitive and relational enhancement. With a small, homogenous sample reporting generally positive experiences with MDMA self-administration, findings from this study cannot be generalized. It remains unknown what proportion of the total MDMA user population might align with the non-problematic adult use of MDMA explored in this study. Additional focused investigations might examine the prevalence and varieties of non-clinical use among adults in order to arrive at rational, science-based regulatory frameworks.

A profile of practice: The occupational therapy process in community aged care in Australia.

INTRODUCTION: Occupational therapists working in community aged care play a key role in service provision because of their expertise in considering the person, their occupations, and environmental context. To further understand occupational therapy practice in community aged care, this study aimed to explore the approaches, models, frames of reference, assessments, interventions, and outcome evaluation methods being used by Australian occupational therapists in aged care. METHODS: An online questionnaire was developed, piloted, and delivered to occupational therapists working in community aged care in Australia. Responses to closed-ended questions were analysed using descriptive statistics, and a summative approach to content analysis was applied to open-ended questions. RESULTS: Seventy-one occupational therapists employed in community aged care across Australia participated in the questionnaire. Almost half of the respondents were employed in private practice. All respondents used a compensatory approach to practice, whereas just over three-quarters used a restorative approach. The Person-Environment-Occupation (PEO) model was the most frequently used occupation-focused model (n = 45). The biomechanical and rehabilitative frames of reference were each used by over two thirds of respondents. Cognitive assessments were most common, followed by functional and environmental assessments. The interventions of equipment and home modifications were very common followed by remedial therapy. CONCLUSION: Community aged care occupational therapists show coherence in theory-to-practice application, but there is wide diversity in practice decisions and possibly gaps in practice. Occupational therapists remain firmly client centred but apply compensatory approaches more than reablement approaches. This trend may be due to the influence of aged care funding models and limits on time. In addition to reacting to crisis, there is scope for occupational therapists to have a greater focus on early intervention to support dementia care and prevent falls.

A Holistic Self-learning Approach for Young Adult Depression and Anxiety Compared to Medication-Based Treatment-As-Usual.

A package of biopsychosocial services for young adults experiencing psychological distress was evaluated and compared to usual outpatient psychiatric care. Young adults (18-25) with moderate-to-severe symptoms of depression and/or anxiety (n = 26) were enrolled in a 13-week intervention consisting of nutritional coaching and multi-vitamin supplements, weekly educational and peer support groups, and a modest financial stipend to engage with physical or expressive activities. A comparison group (n = 13) continued with their usual medication-based outpatient care. Program participants reported significantly improved depression, anxiety, severity of distress, overall quality of life, and empowerment over 4 months, with progress maintained or further improved at 2-month follow-up. No evidence of change on any outcome was observed for comparison group participants. Although long-term impacts on mental health trajectories and reliance on psychotropic medications remain unknown, a holistic self-learning approach is a viable alternative to standard outpatient psychiatric care for young adults.

An Intragastric Fecal Microbiota Transplantation Program for Treatment of Recurrent Clostridium difficile in Children is Efficacious, Safe, and Inexpensive.

OBJECTIVE: To assess the safety, efficacy, and relative expense of a nurse-led fecal microbiota transplantation (FMT) program for the treatment of recurrent Clostridium difficile infection (CDI). STUDY DESIGN: Retrospective cohort study design in children aged 1-18 years with recurrent CDI. The intervention was an intragastric FMT with stool derived from a donor stool bank. Primary outcome was resolution of diarrhea at 3 months post-transplantation. A secondary analysis compared charge data associated with FMT by intragastric delivery vs administration by colonoscopy or nasoduodenal tube. RESULTS: A total of 47 intragastric FMT procedures were performed in 42 children (median age 9 years) with recurrent CDI. Response to treatment varied by disease status, with 94% success in previously healthy children, 75% in medically complex children, and 54% in children with inflammatory bowel disease (P = .04). FMT via intragastric delivery showed lower facility and professional charges by 85% and 78% compared with delivery via colonoscopy and radiology-placed nasoduodenal tube, respectively. The use of stool derived from a donor stool bank decreased charges by 49% compared with charges associated with the use of a donor who was a relative. CONCLUSION: A nurse-led intragastric FMT procedure using stool derived from a donor stool bank is a relatively inexpensive and efficacious treatment for recurrent CDI in children. Intragastric FMT success in children was attenuated by the presence of underlying disease, particularly inflammatory bowel disease.

The National Cancer Institute Investment in Biomechanics in Oncology Research.

The qualitative description of tumors feeling stiffer than surrounding normal tissue has been long appreciated in the clinical setting. These empirical observations have been corroborated by the precise measurement and characterization of mechanical properties of cancerous tissues. Much of the advancement in our understanding of mechanics in oncology has been enabled by the development of innovative technologies designed to probe cells and tissues as well as integrative software analysis tools that facilitate biological interpretation and generation of testable hypotheses. While some mechanics in oncology research has been investigator-initiated and supported by the National Cancer Institute (NCI), several NCI programs described herein have helped to foster the growth of the burgeoning field. Programs highlighted in this chapter include Innovative Molecular Analysis Technologies (IMAT), Physical Sciences-Oncology Network (PS-ON), Tumor Microenvironment Network (TMEN), Integrative Cancer Biology Program (ICBP), and the Cancer Systems Biology Consortium (CSBC). This chapter showcases the scientific contributions of these programs to the field of biomechanics in oncology.

A needs assessment of health department employees in Puerto Rico and Florida.

Public health training centers were established to enhance competencies in skills required to meet 21st-century public health challenges. In 2011, the Puerto Rico-Florida Public Health Training Center conducted surveys to assess the training needs of two populations of public health workers serving Hispanic communities: Florida Department of Health employees and workers at the regional and central offices of the Puerto Rico Department of Health. The two surveys were similar, but not identical in content and administration. A 52.6% response rate was achieved in the Commonwealth of Puerto Rico, where limited computer access necessitated use of a pen-and-paper survey. A 20.7% response rate was achieved in Florida, where an online survey was used and incomplete responses were problematic. Puerto Rico respondents (n = 1,414) were similar in age (Mdn age = 48 years) to Hispanic Florida respondents (n = 546, Mdn age =45 years). They also reported higher levels of academic achievement and more years of experience in public health. Nevertheless, self-assessed public health competency scores were in the low- to mid-range for Hispanic respondents in both locales. Although self-assessed training priorities differed, Hispanic employees in both jurisdictions preferred hands-on and face-to-face training to distance learning. Findings indicate a need for training based on adult learning theory, targeted to entry-level employees, and addressing the top five self-assessed training needs, especially health promotion and disease prevention and public health law and policy, which emerged as priority training areas in both survey populations.

PreCancer Atlas: Present and Future.

Precancer atlases have the potential to revolutionize how we think about the topographic and morphologic structures of precancerous lesions in relation to cellular, molecular, genetic, and pathophysiologic states. This mini review uses the Human Tumor Atlas Network (HTAN), established by the National Cancer Institute (NCI), to illustrate the construction of cellular and molecular three-dimensional atlases of human cancers as they evolve from precancerous lesions to advanced disease. We describe the collaborative nature of the network and the research to determine how and when premalignant lesions progress to invasive cancer, regress or obtain a state of equilibrium. We have attempted to highlight progress made by HTAN in building precancer atlases and discuss possible future directions. It is hoped that the lessons from our experience with HTAN will help other investigators engaged in the construction of precancer atlases to crystallize their thoughts on logistics, rationale, and implementation.

Nurses' Perceptions of Medical Laboratory Scientists: Mistaken Identity and Misplaced Regard.

INTRODUCTION: The medical laboratory science (MLS) profession is an integral part of the healthcare team, providing diagnostic laboratory results used to determine directives in the treatment and management of disease processes. There is a scarcity of literature describing other healthcare professionals' perceptions of medical laboratory scientists. Research also suggests MLS professionals feel unrecognized for contributions to patient care. PURPOSE: A pilot study to describe intensive care unit (ICU) nurses' perceptions of medical laboratory scientists and their role in healthcare. METHODS: Five ICU nurses were interviewed using open-ended questions. Data were analyzed using phenomenological research inquiry to develop themes. RESULTS: Four themes were identified: professional practice, visibility, professional entry, and interprofessional learning. DISCUSSION: While participants were aware of the medical laboratory, they were unaware of the scope of practice, educational requirements, and professional credentials of medical laboratory scientists. Findings also showed misconceptions of the MLS scope of practice that overlaps with phlebotomists and medical laboratory technicians (MLTs). CONCLUSION: This study found that the intensive care nurse participants demonstrated an overall positive perception of medical laboratory scientists but a low level of knowledge of the MLS profession and expertise. Implications for interdisciplinary education to create a more comprehensive healthcare delivery team were presented.

Can online consumers contribute to drug knowledge? A mixed-methods comparison of consumer-generated and professionally controlled psychotropic medication information on the internet.

BACKGROUND: Ongoing initiatives to filter online health searches exclude consumer-generated content from search returns, though its inferiority compared with professionally controlled content is not demonstrated. The antidepressant escitalopram and the antipsychotic quetiapine have ranked over the last 5 years as top-selling agents in their respective drug classes. Both drugs have various off-label mental health and non-mental health uses, ranging from the relief of insomnia and migraines to the treatment of severe developmental disorders. OBJECTIVE: Our objective was to describe the most frequently reported effects of escitalopram and quetiapine in online consumer reviews, to compare them with effects described in professionally controlled commercial health websites, and to gauge the usability of online consumer medication reviews. METHODS: A stratified simple random sample of 960 consumer reviews was selected from all 6998 consumer reviews of the two drugs in 2 consumer-generated (www.askapatient.com and www.crazymeds.us) and 2 professionally controlled (www.webmd.com and www.revolutionhealth.com) health websites. Professional medication descriptions included all standard information on the medications from the latter 2 websites. All textual data were inductively coded for medication effects, and intercoder agreement was assessed. Chi-square was used to test for associations between consumer-reported effects and website origination. RESULTS: Consumers taking either escitalopram (n = 480) or quetiapine (n = 480) most frequently reported symptom improvement (30.4% or 146/480, 24.8% or 119/480) or symptom worsening (15.8% or 76/480, 10.2% or 49/480), changes in sleep (36% or 173/480, 60.6% or 291/480) and changes in weight and appetite (22.5% or 108/480, 30.8% or 148/480). More consumers posting reviews on consumer-generated rather than professionally controlled websites reported symptom worsening on quetiapine (17.3% or 38/220 versus 5% or 11/220, P < .001), while more consumers posting on professionally controlled websites reported symptom improvement (32.7% or 72/220 versus 21.4% or 47/220, P = .008). Professional descriptions more frequently listed physical adverse effects and warnings about suicidal ideation while consumer reviews emphasized effects disrupting daily routines and provided richer descriptions of effects in context. The most recent 20 consumer reviews on each drug from each website (n = 80) were comparable to the full sample of reviews in the frequency of commonly reported effects. CONCLUSION: Consumer reviews and professional medication descriptions generally reported similar effects of two psychotropic medications but differed in their descriptions and in frequency of reporting. Professional medication descriptions offer the advantage of a concise yet comprehensive listing of drug effects, while consumer reviews offer greater context and situational examples of how effects may manifest in various combinations and to varying degrees. The dispersion of consumer reviews across websites limits their integration, but a brief browsing strategy on the two target medications nonetheless retrieved representative consumer content. Current strategies for filtering online health searches to return only trusted or approved websites may inappropriately address the challenge to identify quality health sources on the Internet because such strategies unduly limit access to an entire complementary source for health information.

Education and Outreach in Physical Sciences in Oncology.

Physical sciences are often overlooked in the field of cancer research. The Physical Sciences in Oncology Initiative was launched to integrate physics, mathematics, chemistry, and engineering with cancer research and clinical oncology through education, outreach, and collaboration. Here, we provide a framework for education and outreach in emerging transdisciplinary fields.

Valuing whole complex lives: Young adults' experiences of recovery-related principles in mental healthcare in the United States.

One in five young adults (aged 18-25 years) in the United States experiences a past year mental disorder, commonly including depression or anxiety. Yet, 1.5 million each year do not receive needed mental health services and are unlikely, in general, to seek formal mental healthcare. We aimed to inform the development of a novel programme for young adult mental health by first eliciting their positive and negative prior experiences with mental health providers. Four focus groups with 19 young adults (aged 19-26 years) recruited from the community and with moderate to severe depression and/or anxiety were conducted in 2018 in a western US state. Participants' prior experiences with services/providers were elicited along six pre-defined recovery-related concepts: feeling listened to and validated, inclusivity, full information and consent, hope and optimism, connectedness, and change. Focus groups were audio-recorded, transcribed verbatim and uploaded into NVivo version 12 software. Two independent coders used deductive thematic analysis to identify patterned responses. Feeling listened to and validated appeared as a cornerstone of other recovery concepts. Participants discussed past negative experiences with psychiatrists and regret for being put on medications in their teenage years without information or options. Hope and optimism were low because of a general focus by professionals to address immediate symptom-based issues, rather than on improving their overall lives. Service providers' focus on medication-taking, and other one-size-fits-all tools, was interpreted as lacking a sincere desire to help. Young adults were particularly sensitive to inauthentic interactions and superficial strategies, which left them craving care that incorporated their whole lives, acknowledged biopsychosocial interconnections and prioritised improving their lives over 'feeling better' in a given moment. Mental health providers should consider developing programmes that shift focus away from an exclusively medical understanding of distress and towards holistic, educational or relational approaches that value body, mind, self-exploration and authentic connection.

Cannabidiol in the Treatment of Post-Traumatic Stress Disorder: A Case Series.

OBJECTIVES: Cannabidiol (CBD) is a non-psychotomimetic cannabinoid compound that is found in plants of the genus Cannabis. Preclinical research has suggested that CBD may have a beneficial effect in rodent models of post-traumatic stress disorder (PTSD). This effect is believed to be due to the action of CBD on the endocannabinoid system. CBD has seen a recent surge in research regarding its potential value in a number of neuro-psychiatric conditions. This is the first study to date examining the clinical benefit of CBD for patients with PTSD. METHODS: This retrospective case series examines the effect of oral CBD administration on symptoms of PTSD in a series of 11 adult patients at an outpatient psychiatry clinic. CBD was given on an open-label, flexible dosing regimen to patients diagnosed with PTSD by a mental health professional. Patients also received routine psychiatric care, including concurrent treatment with psychiatric medications and psychotherapy. The length of the study was 8 weeks. PTSD symptom severity was assessed every 4 weeks by patient-completed PTSD Checklist for the DSM-5 (PCL-5) questionnaires. RESULTS: From the total sample of 11 patients, 91% (n = 10) experienced a decrease in PTSD symptom severity, as evidenced by a lower PCL-5 score at 8 weeks than at their initial baseline. The mean total PCL-5 score decreased 28%, from a mean baseline score of 51.82 down to 37.14, after eight consecutive weeks of treatment with CBD. CBD was generally well tolerated, and no patients discontinued treatment due to side effects. CONCLUSIONS: Administration of oral CBD in addition to routine psychiatric care was associated with PTSD symptom reduction in adults with PTSD. CBD also appeared to offer relief in a subset of patients who reported frequent nightmares as a symptom of their PTSD. Additional clinical investigation, including double-blind, placebo-controlled trials, would be necessary to further substantiate the response to CBD that was observed in this study.

Cannabidiol in Anxiety and Sleep: A Large Case Series.

CONTEXT: Cannabidiol (CBD) is one of many cannabinoid compounds found in cannabis. It does not appear to alter consciousness or trigger a "high." A recent surge in scientific publications has found preclinical and clinical evidence documenting value for CBD in some neuropsychiatric disorders, including epilepsy, anxiety, and schizophrenia. Evidence points toward a calming effect for CBD in the central nervous system. Interest in CBD as a treatment of a wide range of disorders has exploded, yet few clinical studies of CBD exist in the psychiatric literature. OBJECTIVE: To determine whether CBD helps improve sleep and/or anxiety in a clinical population. DESIGN: A large retrospective case series at a psychiatric clinic involving clinical application of CBD for anxiety and sleep complaints as an adjunct to usual treatment. The retrospective chart review included monthly documentation of anxiety and sleep quality in 103 adult patients. MAIN OUTCOME MEASURES: Sleep and anxiety scores, using validated instruments, at baseline and after CBD treatment. RESULTS: The final sample consisted of 72 adults presenting with primary concerns of anxiety (n = 47) or poor sleep (n = 25). Anxiety scores decreased within the first month in 57 patients (79.2%) and remained decreased during the study duration. Sleep scores improved within the first month in 48 patients (66.7%) but fluctuated over time. In this chart review, CBD was well tolerated in all but 3 patients. CONCLUSION: Cannabidiol may hold benefit for anxiety-related disorders. Controlled clinical studies are needed.

Spatial and temporal tools for building a human cell atlas.

Improvements in the sensitivity, content, and throughput of microscopy, in the depth and throughput of single-cell sequencing approaches, and in computational and modeling tools for data integration have created a portfolio of methods for building spatiotemporal cell atlases. Challenges in this fast-moving field include optimizing experimental conditions to allow a holistic view of tissues, extending molecular analysis across multiple timescales, and developing new tools for 1) managing large data sets, 2) extracting patterns and correlation from these data, and 3) integrating and visualizing data and derived results in an informative way. The utility of these tools and atlases for the broader scientific community will be accelerated through a commitment to findable, accessible, interoperable, and reusable data and tool sharing principles that can be facilitated through coordination and collaboration between programs working in this space.

Clinical Experiences: Navigating the Intricacies of Student Placement Requirements.

Clinical apprenticeships, also called clinical experiences, are integral to most allied health (AH) student professional education. Clinical experiences begin the process of enculturating students into a healthcare profession where higher cognitive mastery of learned skills is supported through social interaction and scaffolding with an AH professional. In AH programs, clinical experiences for students are a necessity for programmatic accreditation; however, clinical sites have developed a range of requirements for students, which lead to a myriad of issues. These requirements may include drug screens, criminal background checks, and HIPAA training prior to a student beginning their clinical experience. Because of differing interpretation of policy, there is variability of requirements imposed on students before beginning these clinical experiences. This variability can create a financial burden on the student, who likely pays out-of-pocket for criminal background checks, vaccines, or drug screens. It also creates an administrative burden for clinical coordinators, who must know what each of the hundreds of clinical sites require, and they must follow up with each site to determine if these requirements have changed. Some strategies exist that may help clinical coordinators to manage clinical site requirements for student placement.

Effect of dietary lutein and zeaxanthin on plasma carotenoids and their transport in lipoproteins in age-related macular degeneration.

BACKGROUND: Low dietary intakes and low plasma concentrations of lutein and zeaxanthin are associated with an increased risk of age-related macular degeneration (AMD). No studies have challenged AMD patients with a diet high in lutein and zeaxanthin. OBJECTIVE: The objective was to examine the effect of diets low or high in lutein and zeaxanthin on plasma carotenoids and their transport in AMD patients. DESIGN: Seven AMD patients and 5 control subjects were fed a low-lutein, low-zeaxanthin diet ( approximately 1.1 mg/d) for 2 wk, which was followed by a high-lutein, high-zeaxanthin diet ( approximately 11 mg/d) for 4 wk. Ten subjects continued the diet for 8 wk. Plasma and lipoprotein carotenoids were measured by HPLC. RESULTS: The high-lutein, high-zeaxanthin diet resulted in 2- to 3-fold increases in plasma concentrations of lutein and zeaxanthin and other carotenoids, except lycopene, in the AMD patients and the control subjects. With this diet, 52% of the lutein and 44% of the zeaxanthin were transported by HDL; approximately 22% of lutein and zeaxanthin was transported by LDL. Only 20-25% of alpha-carotene, beta-carotene, and lycopene was transported by HDL; 50-57% was transported by LDL. CONCLUSIONS: The AMD patients and control subjects responded similarly to a diet high in lutein and zeaxanthin; plasma carotenoid concentrations increased greatly in both groups, and the transport of carotenoids by lipoproteins was not significantly different between the groups. This finding suggests that abnormalities in the metabolism of lutein and zeaxanthin in AMD may reside in the uptake of lutein and zeaxanthin from the plasma and transport into the retina.

Adverse effects and treatment satisfaction among online users of four antidepressants.

Adverse effects (AEs) are an important factor in antidepressant treatment decision-making, though common AE profiles from clinical trial research highlight physical AEs to the neglect of emotional and behavioral AEs. First-hand accounts of antidepressant users on the Internet can supplement AE profiles with information gained from real-world treatment experiences. We examined online user reviews of two older (escitalopram; duloxetine) and two newer (vilazodone; vortioxetine) antidepressants for differences in their AE profiles and determined which categories of AEs were associated with users' satisfaction. A codebook of 60 physical, emotional, and behavioral AEs was used for line-by-line coding of effects reported among 3243 user reviews from three popular health websites. Emotional and behavioral effects were commonly reported (41%), followed by sleep (31.9%) and gastrointestinal (25.0%) effects. Specific AEs statistically significantly varied across drugs, creating potentially meaningful differences in AE profiles. Users of newer drugs more often reported emotional instability, while users of older drugs reported more emotional blunting. Emotional and behavioral AEs demonstrated moderate to substantial relationships with users' satisfaction, whereas gastrointestinal, metabolic, or sexual AEs were minimally related. More specific and systematic assessment of a broader range of AEs is needed in both research and practice.

Adverse event assessment methods in published trials of psychotropic drugs: Poor reporting and neglect of emerging safety concerns.

BACKGROUND: Actual assessment methods for identifying adverse events (AEs) in clinical trials have received less scrutiny than underreporting of AEs. OBJECTIVE: To investigate whether AE assessment has changed over time for three psychotropic drugs with turbulent histories of safety concerns since their U.S. approval. METHODS: From industry-funded published trials of atomoxetine, duloxetine, and olanzapine retrieved from PubMed for 1996-2004 (n = 33) and 2009-2014 (n = 40), verbatim AE assessment and numbers of words describing efficacy and safety assessment were extracted. RESULTS: Closest to drug approval (1996-2004), 77.8% of atomoxetine trials used open-ended questioning only, 50% of duloxetine trials used spontaneous self-report or clinician observation only, and 66.7% of olanzapine trials used a scale (primarily for extrapyramidal symptoms) and one former method. Recent studies (2009-2014) showed less rigor and transparency: 35.3% of atomoxetine and 64.7% of duloxetine studies reported no AE assessment method and 50% of olanzapine studies no longer used scales. Overall, the mean number of words describing efficacy assessment increased from 202 to 309 but decreased from 83 to 63 for safety. CONCLUSION: Trial methodology for assessing psychotropic drug safety remains an underdeveloped area with major public health implications.