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Background Bicuspid aortic valves (BAV) and related aortopathy remain an intriguing topic. Not all BAVs get diseased and around 40% would develop aortic dilatation in their lifetime. If haemodynamic theory is to be believed, then leaflet fusion pattern should have an impact. This study sought to compare the association of aortic morphologies and rate of growth in a set of 102 BAV acropathies operated at a single centre, based on the fusion patterns. Methods Data on aortic valve replacements over a 10-year period was analysed from a prospectively maintained database. Of the 198 BAV undergoing surgery, 102 had aortic dilatation above 40 mm on echocardiogram. These underwent computed tomography (CT) aortograms and were followed up as a part of a database. The impact of leaflet fusion patterns on aortic dilatation pattern and rate was analysed. Results Of the 102, two patients had type 0 pathology and one had left-noncoronary (LN) leaflet fusion. Seventy-four (74) had type 1A or left-right (RL) fusion and 25 had type 1B right-noncoronary (RN) fusion. RL fusion had more males, were taller, bigger and had more proportion of aortic stenosis (AS). Aortic diameters, angles and growth rates at root, ascending/descending aorta and arch were not different. Regression analyses for size or growth did not show any significant impact of fusion pattern. Conclusions Left-right fusion pattern comprised three-quarters of BAV in this cohort and these patients were bigger, taller and had a greater proportion of males with increased rate of aortic stenosis. Despite these differences, there was no significant impact of fusion pattern on aortic size or rate of growth.

A few tumours are exceptionally stubborn to oral chemotherapy. The endurance of tumours in a few cases is helped by checkpoint immunomodulation to keep up the unevenness between resistant reconnaissance and disease cell division.

Serogroup B meningococcal disease (MenB) causes almost 60% of meningitis cases among adolescents and young adults. Yet, MenB vaccine coverage among adolescents remains below 10%. Since parents are the primary medical decision makers for adolescents, we examined MenB vaccination rates and parent attitudes about meningitis and the MenB vaccine. In 2018, in conjunction with a county-wide, school-based immunization campaign, we conducted a mixed methods study among parents of 16- to 17-year-olds. We facilitated focus groups asking parents about their knowledge of meningitis and reactions to educational materials and sent behavioral surveys based on Health Belief Model constructs to parents through the county high school system. Parents in three focus groups (n = 8; participation rate = 13%) expressed confusion about their child’s need to receive the MenB vaccine in addition to the meningococcal conjugate vaccine (MenACWY), but conveyed strong trust in their physicians’ recommendation. Among survey participants (n = 170), 70 (41%) had heard of the MenB vaccine. Among those 70 parents, the most common barriers to vaccination were concerns about side effects (55%) and uncertainty of susceptibility due to receipt of the MenACWY vaccine (30%). The percentage of teens that received at least one dose of the MenB vaccine was 50% (n = 35) by parent report and 23% (n = 16) by state vaccination records. Parents demonstrated uncertainty and confusion about the MenB vaccine particularly due to the existence of another meningitis vaccine and limited health care provider recommendations. Confirmatory studies of parent confusion about the MenB vaccine are needed to develop interventions.

PURPOSE: Patients are frequently asked to share their personal health information. The objective of this study was to compare the effects on patient experiences of 3 electronic consent (e-consent) versions asking patients to share their health records for research. METHODS: A multi-arm randomized controlled trial was conducted from November 2017 through November 2018. Adult patients (n = 734) were recruited from 4 family medicine clinics in Florida. Using a tablet computer, participants were randomized to (1) a standard e-consent (standard), (2) an e-consent containing standard information plus hyperlinks to additional interactive details (interactive), or (3) an e-consent containing standard information, interactive hyperlinks, and factual messages about data protections and researcher training (trust-enhanced). Satisfaction (1 to 5), subjective understanding (0 to 100), and other outcomes were measured immediately, at 1 week, and at 6 months. RESULTS: A majority of participants (94%) consented to future uses of their health record information for research. No differences in study outcomes between versions were observed at immediate or 1-week follow-up. At 6-month follow-up, compared with the standard e-consent, participants who used the interactive e-consent reported greater satisfaction (B = 0.43; SE = 0.09; P

OBJECTIVES To report the 3-year follow-up of a Phase I study of magnetic resonance imaging (MRI)-guided transurethral ultrasound ablation (TULSA) in 30 men with localised prostate cancer. Favourable 12-month safety and ablation precision were previously described. PATIENTS AND METHODS As a mandated safety criterion, TULSA was delivered as near whole-gland ablation, applying 3-mm margins sparing 10% of peripheral prostate tissue in 30 men. After 12-month biopsy and MRI, biannual follow-up included prostate-specific antigen (PSA), adverse events (AEs), and functional quality-of-life assessment, with repeat systematic biopsy at 3 years. RESULTS A 3-year follow-up was completed by 22 patients. Between 1 and 3 years, there were no new serious or severe AEs. Urinary and bowel function remained stable. Erectile function recovered by 1 year and was stable at 3 years. The PSA level decreased 95% to a median (interquartile range) nadir of 0.33 (0.1-0.4) ng/mL, stable to 0.8 (0.4-1.6) ng/mL at 3 years. Serial biopsies identified clinically significant disease in 10/29 men (34%) and any cancer in 17/29 (59%). By 3 years, seven men had recurrence (four histological, three biochemical) and had undergone salvage therapy without complications (including six prostatectomies). At 3 years, three of 22 men refused biopsy, and two of the 22 (9%) had clinically significant disease (one new, one persistent). Predictors of salvage therapy requirement included less extensive ablation coverage and higher PSA nadir. CONCLUSION With 3-year Phase I follow-up, TULSA demonstrates safe and precise ablation for men with localised prostate cancer, providing predictable PSA and biopsy outcomes, without affecting functional abilities or precluding salvage therapy.

BACKGROUND: The objective of this qualitative study is to better understand primary care clinician decision making for managing chronic pain. Specifically, we focus on the factors that influence changes to existing chronic pain management plans. Limitations in guidelines and training leave clinicians to use their own judgement and experience in managing the complexities associated with treating patients with chronic pain. This study provides insight into those judgments based on clinicians’ first-person accounts. Insights gleaned from this study could inspire innovations aimed at supporting primary care clinicians (PCCs) in managing chronic pain. METHODS: We conducted 89 interviews with PCCs to obtain their first-person perspective of the factors that influenced changes in treatment plans for their patients. Interview transcripts were analyzed thematically by a multidisciplinary team of clinicians, cognitive scientists, and public health researchers. RESULTS: Seven themes emerged through our analysis of factors that influenced a change in chronic pain management: (1) change in patient condition, (2) outcomes related to treatment, (3) non-adherent patient behavior, (4) insurance constraints, (5) change in guidelines, laws, or policies, (6) approaches to new patients, and (7) specialist recommendations. CONCLUSIONS: Our analysis sheds light on the factors that lead PCCs to change treatment plans for patients with chronic pain. An understanding of these factors can inform the types of innovations needed to support PCCs in providing chronic pain care. We highlight key insights from our analysis and offer ideas for potential practice innovations.

Kristin Kostka,1,2 Talita Duarte-Salles,3 Albert Prats-Uribe,4 Anthony G Sena,5,6 Andrea Pistillo,3 Sara Khalid,4 Lana YH Lai,7 Asieh Golozar,8,9 Thamir M Alshammari,10 Dalia M Dawoud,11 Fredrik Nyberg,12 Adam B Wilcox,13,14 Alan Andryc,5 Andrew Williams,15 Anna Ostropolets,16 Carlos Areia,17 Chi Young Jung,18 Christopher A Harle,19 Christian G Reich,1,2 Clair Blacketer,5,6 Daniel R Morales,20 David A Dorr,21 Edward Burn,3,4 Elena Roel,3,22 Eng Hooi Tan,4 Evan Minty,23 Frank DeFalco,5 Gabriel de Maeztu,24 Gigi Lipori,19 Hiba Alghoul,25 Hong Zhu,26 Jason A Thomas,13 Jiang Bian,19 Jimyung Park,27 Jordi Martínez Roldán,28 Jose D Posada,29 Juan M Banda,30 Juan P Horcajada,31 Julianna Kohler,32 Karishma Shah,33 Karthik Natarajan,16,34 Kristine E Lynch,35,36 Li Liu,37 Lisa M Schilling,38 Martina Recalde,3,22 Matthew Spotnitz,14 Mengchun Gong,39 Michael E Matheny,40,41 Neus Valveny,42 Nicole G Weiskopf,21 Nigam Shah,29 Osaid Alser,43 Paula Casajust,42 Rae Woong Park,27,44 Robert Schuff,21 Sarah Seager,1 Scott L DuVall,35,36 Seng Chan You,45 Seokyoung Song,46 Sergio Fernández-Bertolín,3 Stephen Fortin,5 Tanja Magoc,19 Thomas Falconer,16 Vignesh Subbian,47 Vojtech Huser,48 Waheed-Ul-Rahman Ahmed,33,49 William Carter,38 Yin Guan,50 Yankuic Galvan,19 Xing He,19 Peter R Rijnbeek,6 George Hripcsak,16,34 Patrick B Ryan,5,16 Marc A Suchard,51 Daniel Prieto-Alhambra4 1IQVIA, Cambridge, MA, USA; 2OHDSI Center at The Roux Institute, Northeastern University, Portland, ME, USA; 3Fundació Institut Universitari per a la recerca a l’Atenció Primà ria de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain; 4Centre for Statistics in Medicine, NDORMS, University of Oxford, Oxford, UK; 5Janssen Research & Development, Titusville, NJ, USA; 6Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, The Netherlands; 7School of Medical Sciences, University of Manchester, Manchester, UK; 8Regeneron Pharmaceuticals, Tarrytown, NY, USA; 9Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; 10College of Pharmacy, Riyadh Elm University, Riyadh, Saudi Arabia; 11National Institute for Health and Care Excellence, London, UK; 12School of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; 13Department of Biomedical Informatics and Medical Education, University of Washington, Seattle, WA, USA; 14Unviersity of Washington Medicine, Seattle, WA, USA; 15Tufts Institute for Clinical Research and Health Policy Studies, Boston, MA, USA; 16Department of Biomedical Informatics, Columbia University Irving Medical Center, New York, NY, USA; 17Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK; 18Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, Daegu Catholic University Medical Center, Daegu, South Korea; 19University of Florida Health, Gainesville, FL, USA; 20Division of Population Health and Genomics, University of Dundee, Dundee, UK; 21Department of Medical Informatics & Clinical Epidemiology, Oregon Health & Science University, Portland, OR, USA; 22Universitat Autònoma de Barcelona, Barcelona, Spain; 23O’Brien Institute for Public Health, Faculty of Medicine, University of Calgary, Calgary, Canada; 24IOMED, Barcelona, Spain; 25Faculty of Medicine, Islamic University of Gaza, Gaza, Palestine; 26Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 27Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon, South Korea; 28Director of Innovation and Digital Transformation, Hospital del Mar, Barcelona, Spain; 29Department of Medicine, School of Medicine, Stanford University, Redwood City, CA, USA; 30Georgia State University, Department of Computer Science, Atlanta, GA, USA; 31Department of Infectious Diseases, Hospital del Mar, Institut Hospital del Mar d’Investigació Mèdica (IMIM), Universitat Autònoma de Barcelona, Universitat Pompeu Fabra, Barcelona, Spain; 32United States Agency for International Development, Washington, DC, USA; 33Botnar Research Centre, NDORMS, University of Oxford, Oxford, UK; 34New York-Presbyterian Hospital, New York, NY, USA; 35VA Informatics and Computing Infrastructure, VA Salt Lake City Health Care System, Salt Lake City, UT, USA; 36Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA; 37Biomedical Big Data Center, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 38Data Science to Patient Value Program, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; 39Institute of Health Management, Southern Medical University, Guangzhou, People’s Republic of China; 40Tennessee Valley Healthcare System, Veterans Affairs Medical Center, Nashville, TN, USA; 41Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, USA; 42Real-World Evidence, TFS, Barcelona, Spain; 43Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; 44Department of Biomedical Informatics, Ajou University School of Medicine, Suwon, South Korea; 45Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, South Korea; 46Department of Anesthesiology and Pain Medicine, Catholic University of Daegu, School of Medicine, Daegu, South Korea; 47College of Engineering, The University of Arizona, Tucson, AZ, USA; 48National Library of Medicine, National Institutes of Health, Bethesda, MD, USA; 49College of Medicine and Health, University of Exeter, St Luke’s Campus, Exeter, UK; 50DHC Technologies Co. Ltd., Beijing, People’s Republic of China; 51Departments of Biostatistics, Computational Medicine, and Human Genetics, University of California, Los Angeles, CA, USACorrespondence: Daniel Prieto-Alhambra, Botnar Research Centre, Windmill Road, Oxford, OX37LD, UK, Email daniel.prietoalhambra@ndorms.ox.ac.ukPurpose: Routinely collected real world data (RWD) have great utility in aiding the novel coronavirus disease (COVID-19) pandemic response. Here we present the international Observational Health Data Sciences and Informatics (OHDSI) Characterizing Health Associated Risks and Your Baseline Disease In SARS-COV-2 (CHARYBDIS) framework for standardisation and analysis of COVID-19 RWD.Patients and Methods: We conducted a descriptive retrospective database study using a federated network of data partners in the United States, Europe (the Netherlands, Spain, the UK, Germany, France and Italy) and Asia (South Korea and China). The study protocol and analytical package were released on 11th June 2020 and are iteratively updated via GitHub. We identified three non-mutually exclusive cohorts of 4,537,153 individuals with a clinical COVID-19 diagnosis or positive test, 886,193 hospitalized with COVID-19, and 113,627 hospitalized with COVID-19 requiring intensive services.Results: We aggregated over 22,000 unique characteristics describing patients with COVID-19. All comorbidities, symptoms, medications, and outcomes are described by cohort in aggregate counts and are readily available online. Globally, we observed similarities in the USA and Europe: more women diagnosed than men but more men hospitalized than women, most diagnosed cases between 25 and 60 years of age versus most hospitalized cases between 60 and 80 years of age. South Korea differed with more women than men hospitalized. Common comorbidities included type 2 diabetes, hypertension, chronic kidney disease and heart disease. Common presenting symptoms were dyspnea, cough and fever. Symptom data availability was more common in hospitalized cohorts than diagnosed.Conclusion: We constructed a global, multi-centre view to describe trends in COVID-19 progression, management and evolution over time. By characterising baseline variability in patients and geography, our work provides critical context that may otherwise be misconstrued as data quality issues. This is important as we perform studies on adverse events of special interest in COVID-19 vaccine surveillance.Keywords: OHDSI, OMOP CDM, descriptive epidemiology, real world data, real world evidence, open science

Background The rapid spread of COVID-19 renewed the focus on how health systems across the globe are financed, especially during public health emergencies. Development assistance is an important source of health financing in many low-income countries, yet little is known about how much of this funding was disbursed for COVID-19. We aimed to put development assistance for health for COVID-19 in the context of broader trends in global health financing, and to estimate total health spending from 1995 to 2050 and development assistance for COVID-19 in 2020. Methods We estimated domestic health spending and development assistance for health to generate total health-sector spending estimates for 204 countries and territories. We leveraged data from the WHO Global Health Expenditure Database to produce estimates of domestic health spending. To generate estimates for development assistance for health, we relied on project-level disbursement data from the major international development agencies' online databases and annual financial statements and reports for information on income sources. To adjust our estimates for 2020 to include disbursements related to COVID-19, we extracted project data on commitments and disbursements from a broader set of databases (because not all of the data sources used to estimate the historical series extend to 2020), including the UN Office of Humanitarian Assistance Financial Tracking Service and the International Aid Transparency Initiative. We reported all the historic and future spending estimates in inflation-adjusted 2020 US$, 2020 US$ per capita, purchasing-power parity-adjusted US$ per capita, and as a proportion of gross domestic product. We used various models to generate future health spending to 2050. Findings In 2019, health spending globally reached $8. 8 trillion (95% uncertainty interval [UI] 8.7-8.8) or $1132 (1119-1143) per person. Spending on health varied within and across income groups and geographical regions. Of this total, $40.4 billion (0.5%, 95% UI 0.5-0.5) was development assistance for health provided to low-income and middle-income countries, which made up 24.6% (UI 24.0-25.1) of total spending in low-income countries. We estimate that $54.8 billion in development assistance for health was disbursed in 2020. Of this, $13.7 billion was targeted toward the COVID-19 health response. $12.3 billion was newly committed and $1.4 billion was repurposed from existing health projects. $3.1 billion (22.4%) of the funds focused on country-level coordination and $2.4 billion (17.9%) was for supply chain and logistics. Only $714.4 million (7.7%) of COVID-19 development assistance for health went to Latin America, despite this region reporting 34.3% of total recorded COVID-19 deaths in low-income or middle-income countries in 2020. Spending on health is expected to rise to $1519 (1448-1591) per person in 2050, although spending across countries is expected to remain varied. Interpretation Global health spending is expected to continue to grow, but remain unequally distributed between countries. We estimate that development organisations substantially increased the amount of development assistance for health provided in 2020. Continued efforts are needed to raise sufficient resources to mitigate the pandemic for the most vulnerable, and to help curtail the pandemic for all. For complete list of authors see http://dx.doi.org/10.1016/S0140-6736(21)01258-7

BackgroundPhotoplethysmography (PPG) sensors, typically found in wrist-worn devices, can continuously monitor heart rate (HR) in large populations in real-world settings. Resting heart rate (RHR) is an important biomarker of morbidities and mortality, but no universally accepted definition nor measurement criteria exist. In this study, we provide a working definition of RHR and describe a method for accurate measurement of this biomarker, recorded using PPG derived from wristband measurement across a 24 hour cycle. Methods433 healthy subjects wore a wrist device that measured activity and HR for up to 3 months. HR during inactivity was recorded and the duration of inactivity needed for HR to stabilise was ascertained. We identified the lowest HR during each 24-hour cycle (true RHR) and examined the time of day or night this occurred. The variation of HR during inactivity through the 24-hour cycle was also assessed. The sample was also subdivided according to daily activity levels for subset analysis. FindingsAdequate data was obtained for 19,242 days and 18,520 nights. HR stabilised in most subjects after 4 minutes of inactivity. Mean (SD) RHR for the sample was 54.5 (8.0) bpm (day) and 50.5 (7.6) bpm (night). RHR values were highest in the least active group (lowest MET quartile). A circadian variation of HR during inactivity was confirmed, with the lowest values being between 0300 and 0700 hours for most subjects. InterpretationRHR measured using a PPG-based wrist-worn device is significantly lower at night than in the day, and a circadian rhythm of HR during inactivity was confirmed. Since RHR is such an important health metric, clarity on the definition and measurement methodology used is important. A minimum rest time of 4 minutes provides a reliable measurement of HR during inactivity and true RHR in a 24-hour cycle is best measured between 0300 and 0700 hours. FundingThis study was funded by Google. O_TEXTBOXResearch In contextResting heart rate is one of the most fundamental and relevant biomarkers in health and disease. Its measurement, particularly in large population studies, is increasingly reliant on sensor devices. No universally accepted definition nor measurement criteria exist. In this study, we provide a working definition of RHR and describe a method for measurement of RHR recorded using PPG derived from wristband measurement. We make recommendations to support future studies of resting heart rate using wearable sensors. C_TEXTBOX

Severe mitral annular calcification poses a significant challenge, particularly in higher risk, frail, elderly patients with multivalvular disease. Both surgical and transcatheter options exist but remain fraught with risks of paravalvular leak, atrioventricular groove disruption, patient prosthesis mismatch, and left ventricular outflow tract obstruction. We present an innovative hybrid surgical approach to manage severe aortic and mitral valve disease in a Jehovah’s Witness patient with severe circumferential mitral annular calcification.

Objective Disparities in adult patient portal adoption are well-documented; however, less is known about disparities in portal adoption in pediatrics. This study examines the prevalence and factors associated with patient portal activation and the use of specific portal features in general pediatrics. Materials and methods We analyzed electronic health record data from 2012 to 2020 in a large academic medical center that offers both parent and adolescent portals. We summarized portal activation and use of select portal features (messaging, records access and management, appointment management, visit/admissions summaries, and interactive feature use). We used logistic regression to model factors associated with patient portal activation among all patients along with feature use and frequent feature use among ever users (ie, ≥1 portal use). Results Among 52 713 unique patients, 39% had activated the patient portal, including 36% of patients aged 0–11, 41% of patients aged 12–17, and 62% of patients aged 18–21 years. Among activated accounts, ever use of specific features ranged from 28% for visit/admission summaries to 92% for records access and management. Adjusted analyses showed patients with activated accounts were more likely to be adolescents or young adults, white, female, privately insured, and less socioeconomically vulnerable. Individual feature use among ever users generally followed the same pattern. Conclusions Our findings demonstrate that important disparities persist in portal adoption in pediatric populations, highlighting the need for strategies to promote equitable access to patient portals.

Purpose: CYP2D6 bioactivates codeine and tramadol, with intermediate and poor metabolizers (IMs and PMs) expected to have impaired analgesia. This pragmatic proof-of-concept trial tested the effects of CYP2D6-guided opioid prescribing on pain control. Methods: Participants with chronic pain (94% on an opioid) from 7 clinics were enrolled into CYP2D6-guided (n=235) or usual care (n=135) arms using a cluster design. CYP2D6 phenotypes were assigned based on genotype and CYP2D6 inhibitor use, with recommendations for opioid prescribing made in the CYP2D6-guided arm. Pain was assessed at baseline and 3 months using PROMIS® measures. Results: On stepwise multiple linear regression, the primary outcome of composite pain intensity (composite of current pain and worst and average pain in the past week) among IM/PMs initially prescribed tramadol/codeine (n=45) had greater improvement in the CYP2D6-guided versus usual care arm (−1.01±1.59 versus −0.40±1.20; adj-P=0.016); 24% of CYP2D6-guided versus 0% of usual care participants reported ≥30% (clinically meaningful) reduction in the composite outcome. In contrast, among normal metabolizers prescribed tramadol or codeine at baseline, there was no difference in the change in composite pain intensity at 3 months between CYP2D6-guided (−0.61±1.39) and usual care (−0.54±1.69) groups (adj-P=0.540). Conclusion: These data support the potential benefits of CYP2D6-guided pain management.

Introduction: Idiopathic pulmonary fibrosis (IPF) is a debilitating, progressive, and fatal fibrotic pulmonary disease with a prognosis comparable to that of lung cancer. IPF management is a complex process that involves pharmacological and nonpharmacological interventions, extensive patient education, and addressing patient needs that change through the course of the illness. Areas covered: This review summarizes the key aspects of a multifaceted, multidisciplinary, individualized approach to IPF care that incorporates available treatment options, strategies to improve compliance with antifibrotic therapies, pulmonary rehabilitation, and the integration of palliative care for symptom management. Aspects of care discussed include the use of antifibrotic therapy and nonpharmacological treatments, targeted education and psychosocial support, evaluation and management of comorbidities, and early integration of palliative care. Expert opinion: By incorporating this comprehensive approach to disease management, physicians can address most aspects of care for a patient with IPF to optimize survival and quality of life.

Objective In the context of patient broad consent for future research uses of their identifiable health record data, we compare the effectiveness of interactive trust-enhanced e-consent, interactive-only e-consent, and standard e-consent (no interactivity, no trust enhancement). Materials and Methods A randomized trial was conducted involving adult participants making a scheduled primary care visit. Participants were randomized into 1 of the 3 e-consent conditions. Primary outcomes were patient-reported satisfaction with and subjective understanding of the e-consent. Secondary outcomes were objective knowledge, perceived voluntariness, trust in medical researchers, consent decision, and time spent using the application. Outcomes were assessed immediately after use of the e-consent and at 1-week follow-up. Results Across all conditions, participants (N = 734) reported moderate-to-high satisfaction with consent (mean 4.3 of 5) and subjective understanding (79.1 of 100). Over 94% agreed to share their health record data. No statistically significant differences in outcomes were observed between conditions. Irrespective of condition, black participants and those with lower education reported lower satisfaction, subjective understanding, knowledge, perceived voluntariness, and trust in medical researchers, as well as spent more time consenting. Conclusions A large majority of patients were willing to share their identifiable health records for research, and they reported positive consent experiences. However, incorporating optional additional information and messages designed to enhance trust in the research process did not improve consent experiences. To improve poorer consent experiences of racial and ethnic minority participants and those with lower education, other novel consent technologies and processes may be valuable. (An Interactive Patient-Centered Consent for Research Using Medical Records; NCT03063268)

Prespecified exploratory biomarker analyses of the phase II/III GATSBY study (NCT01641939) assessed whether patient subgroups experienced a survival benefit from trastuzumab emtansine (T-DM1) versus taxane therapy, and to advance understanding of HER2-positive advanced gastric/gastroesophageal junction cancer (AGC) disease biology. Adults with HER2-positive AGC whose disease progressed during/after first-line therapy were enrolled and randomized to receive T-DM1 [Stage 1: 3.6 mg/kg q3w, 2.4 mg/kg qw, or taxane (docetaxel/paclitaxel); Stage 2: 2.4 mg/kg qw or taxane]. Primary efficacy endpoint was overall survival (OS). Prespecified exploratory biomarkers included HER2, HER3, PTEN, PIK3CA mutation status, FcγR, and cMET. Tumor samples from patients who received 2.4 mg/kg T-DM1 (n = 228) or taxane (n = 117) were included. Median OS was longer in subgroups with HER2 immunohistochemistry (IHC) 3+ [9.5 versus 8.3 months for T-DM1 versus taxane; hazard ratio (HR) 0.99 (95% CI 0.68–1.43)] versus HER2 IHC 2+/in situ hybridization-positive [5.2 versus 9.2 months for T-DM1 versus taxane; HR 1.53 (95% CI 0.94–2.50)] tumors. Trends towards increased median OS were also observed in subgroups with > versus ≤ median HER2 mRNA expression, higher versus lower HER2 gene copy number, HER2 gene ratio and H score, and homogenous or nonfocal HER2 IHC staining. T-DM1 was not associated with superior OS versus taxane in any subgroup. Patients with previously treated HER2-positive AGC with higher HER2 expression experienced a better treatment effect from T-DM1 than those with lower HER2 expression and may derive comparable survival benefits from T-DM1 and taxane therapy. NCT01641939 ( https://clinicaltrials.gov/ct2/show/NCT01641939 ).

The recipients of NIH’s Clinical and Translational Science Awards (CTSA) have worked for over a decade to build informatics infrastructure in support of clinical and translational research. This infrastructure has proved invaluable for supporting responses to the current COVID-19 pandemic through direct patient care, clinical decision support, training researchers and practitioners, as well as public health surveillance and clinical research to levels that could not have been accomplished without the years of ground-laying work by the CTSAs. In this paper, we provide a perspective on our COVID-19 work and present relevant results of a survey of CTSA sites to broaden our understanding of the key features of their informatics programs, the informatics-related challenges they have experienced under COVID-19, and some of the innovations and solutions they developed in response to the pandemic. Responses demonstrated increased reliance by healthcare providers and researchers on access to electronic health record (EHR) data, both for local needs and for sharing with other institutions and national consortia. The initial work of the CTSAs on data capture, standards, interchange, and sharing policies all contributed to solutions, best illustrated by the creation, in record time, of a national clinical data repository in the National COVID-19 Cohort Collaborative (N3C). The survey data support seven recommendations for areas of informatics and public health investment and further study to support clinical and translational research in the post-COVID-19 era.

Dedifferentiation and transdifferentiation are rare and only poorly understood phenomena in cutaneous melanoma. To study this disease more comprehensively we have retrieved 11 primary cutaneous melanomas from our pathology archives showing biphasic features characterized by a conventional melanoma and additional areas of de-/trans-differentiation as defined by a lack of immunohistochemical expression of all conventional melanocytic markers (S-100 protein, SOX10, Melan- A, and HMB-45). The clinical, histologic, and immunohistochemical findings were recorded and follow-up was obtained. The patients were mostly elderly (median: 81 years ; range: 42–86 years) without significant gender predilection, and the sun-exposed skin of the head and neck area was most commonly affected. The tumors were deeply invasive with a mean depth of 7 mm (range: 4–80 mm). The dedifferentiated component showed atypical fibroxanthoma-like features in the majority of cases (7), while additional rhabdomyosarcomatous and epithelial transdifferentiation was noted histologically and/or immunohistochemically in two tumors each. The background conventional melanoma component was of desmoplastic (4), superficial spreading (3), nodular (2), lentigo maligna (1), or spindle cell (1) types. For the seven patients with available follow-up data (median follow-up period of 25 months ; range: 8–36 months), two died from their disease, and three developed metastases. Next- generation sequencing of the cohort revealed somatic mutations of established melanoma drivers including mainly NF1 mutations (5) in the conventional component, which was also detected in the corresponding de-/trans-differentiated component. In summary, the diagnosis of primary cutaneous de-/trans-differentiated melanoma is challenging and depends on the morphologic identification of conventional melanoma. Molecular analysis is diagnostically helpful as the mutated gene profile is shared between the conventional and de-/trans-differentiated components. Importantly, de-/trans-differentiation does not appear to confer a more aggressive behavior.

Objective: At a large public university, we aimed to evaluate an intervention designed to increase serogroup B meningococcal (MenB) vaccine uptake and awareness. Methods: Using a pretest-posttest design with a double posttest, we evaluated an intervention conducted by a local foundation and the Florida Department of Health that distributed MenB vaccine on campus and conducted an educational campaign. Prior to intervention activities, we recruited students to complete a survey about their MenB knowledge and attitudes. For survey participants who provided contact information, we sent two follow-up surveys and assessed MenB vaccine records. We used chi-square tests, adjusted for nonindependence, to compare preintervention to postintervention (three-month and one-year) vaccination and attitudes. Results: Among the 686 students with accessible vaccine records, MenB vaccine initiation increased 9% (from 24% to 33%) and completion increased 8% (from 13% to 21%) from before the intervention to one year after the intervention. When restricting to students who completed the relevant follow-up surveys, the percentage of students who heard of the MenB vaccine increased by 15% (p > .001) from before the intervention to three months after (n = 188 students) and maintained a 10% increase (p > .001) one year after the intervention (n = 261 students). Among students that heard of the MenB vaccine, the percentage of students who thought they needed the MenB vaccine even though they received the MenACWY increased 14% (p = .03) by the three-month postintervention survey and up to 18% by the one-year follow-up (p = .002). Conclusions: A university-wide, on-campus vaccination and educational campaign increased college students’ MenB vaccine initiation, completion, and knowledge. Clinicaltrials.gov ID: NCT02975596.

ObjectivesThis study examined knowledge and perceptions of COVID-19, prevalence of pre-existing conditions and access to essential resources among residents of internally displaced person (IDP) camps in Somalia, where overcrowded settlements with weakened infrastructure, inadequate water, sanitation, and hygiene facilities, and limited access to health services make this vulnerable population particularly susceptible to a COVID-19 outbreak.DesignA descriptive, cross-sectional survey.SettingTwelve IDP camps across six areas of the Lower Shabelle region in Somalia.Participants401 adult Somali IDP camp residents.ResultsThe majority of participants were female (86%) and had received no formal education (89%). While 58% reported being in ‘good’ health, half of the participants reported having one or more pre-existing conditions. Though 77% of respondents reported taking at least one COVID-19 preventative public health measure, respondents reported a lack of access to adequate sanitation, an inability to practice social distancing and nearly universal inability to receive a COVID-19 screening exam. Questions assessing knowledge surrounding COVID-19 prevention and treatment yielded answers of ‘I don’t know’ for roughly 50% of responses. The majority of participants were not familiar with basic information about the virus or confident that they could receive medical services if infected. 185 (47%) respondents indicated that camp living conditions needed to change to prevent the spread of COVID-19.ConclusionThis study highlights low levels of COVID-19 knowledge and limited access to essential prevention and treatment resources among individuals living in Somali IDP camps. A massive influx of additional resources is required to adequately address COVID-19 in Somalia, starting with codesigning interventions to educate those individuals most vulnerable to infection.

Background The 2016 Centers for Disease Control and Prevention guideline for prescribing opioids for chronic pain (Guideline hereafter) emphasized tapering patients from long-term opioid therapy (LTOT) when the harms outweigh the benefits. Methods To examine tapering from LTOT before and after the Guideline release, we conducted a retrospective cohort study of adults with high-dose LTOT (mean of >50 Morphine Milligram Equivalents [MME]/day) from 2014 to 2018 from one Midwest state's Health Information Exchange. We identified tapering (dose reductions in mean MME/day greater than 15%, 30%, 50%) and rapid discontinuation episodes (reduction to zero MME/day) over a 6-month follow-up period relative to a 3-month baseline period. We used segmented regressions to estimate outcomes adjusted for time trends and relevant state laws limiting opioid prescribing. Results The Guideline release was associated with statistically significant immediate increase in the patient likelihood of experiencing tapering (15%: 1.8% point [95% confidence interval (CI): 1.2–2.6; 30%: 1.4% point, 95% CI: 0.7–2.2; 50%: 0.8% point, 95% CI: 0.2–1.4) and rapid discontinuation episodes (0.006% point, 95% CI: 0.001–0.01). After the Guideline release, the patient likelihood of tapering increased over time (15%: 0.4% point/month, 95% CI: 0.3–0.5; 30%: 0.3% point/month, 95% CI:0.2–0.4; 50%: 0.3% point/month, 95% CI: 0.2–0.3; rapid discontinuation: 0.01% point/month, 95% CI: 0.007–0.01). Tapering and rapid discontinuation trends was similar among gender and race categories. Conclusion The Guideline may be a useful tool in altering opioid prescribing practices, particularly for patients on shorter durations of LTOT.

BackgroundElectronic health records (EHRs) hold great potential for longitudinal mother-baby studies, ranging from assessing study feasibility to facilitating patient recruitment to streamlining study visits and data collection. Existing studies on the perspectives of pregnant and breastfeeding women on EHR use have been limited to the use of EHRs to engage in health care rather than to participate in research.ObjectiveThe aim of this study is to explore the perspectives of pregnant and breastfeeding women on releasing their own and their infants’ EHR data for longitudinal research to identify factors affecting their willingness to participate in research.MethodsWe conducted semistructured interviews with pregnant or breastfeeding women from Alachua County, Florida. Participants were asked about their familiarity with EHRs and EHR patient portals, their comfort with releasing maternal and infant EHR data to researchers, the length of time of the data release, and whether individual research test results should be included in the EHR. The interviews were transcribed verbatim. Transcripts were organized and coded using the NVivo 12 software (QSR International), and coded data were thematically analyzed using constant comparison.ResultsParticipants included 29 pregnant or breastfeeding women aged between 22 and 39 years. More than half of the sample had at least an associate degree or higher. Nearly all participants (27/29, 93%) were familiar with EHRs and had experience accessing an EHR patient portal. Less than half of the participants (12/29, 41%) were willing to make EHR data available to researchers for the duration of a study or longer. Participants’ concerns about sharing EHRs for research purposes emerged in 3 thematic domains: privacy and confidentiality, transparency by the research team, and surrogate decision-making on behalf of infants. The potential release of sensitive or stigmatizing information, such as mental or sexual health history, was considered in the decisions to release EHRs. Some participants viewed the simultaneous use of their EHRs for both health care and research as potentially beneficial, whereas others expressed concerns about mixing their health care with research.ConclusionsThis exploratory study indicates that pregnant and breastfeeding women may be willing to release EHR data to researchers if researchers adequately address their concerns regarding the study design, communication, and data management. Pregnant and breastfeeding women should be included in EHR-based research as long as researchers are prepared to address their concerns.

BACKGROUNDThe authors present a case of selective hypothermia used for neuroprotection during clipping of a giant partially thrombosed middle cerebral artery (MCA) aneurysm. Although these cases have traditionally required deep hypothermic cardiac arrest, this case illustrates a novel and entirely endovascular solution that avoids cardiac standstill and whole-body cooling.OBSERVATIONSThis is, to the authors’ knowledge, the first case in human surgery of a catheter-based selective hypothermic circuit used to facilitate MCA trapping for almost 30 minutes. Core temperatures never dropped below 34°C, and the patient recovered uneventfully and has been well for over 5 years.LESSONSThe technical nuances and physiological changes unique to selective hypothermia are discussed.

OBJECTIVE: To examine the association between receipt of opioids and patient care experiences among nonsurgical hospitalized adults. DATA SOURCES: A total of 17 691 patient‐level responses to the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) patient care experience survey linked to medical records from nonsurgical hospitalizations in an 11‐hospital health care system in a Midwestern state, years 2011‐2016. STUDY DESIGN: We conducted a pooled cross‐sectional study that used propensity score matching analyses and logistic regression to estimate the relationship between patients’ care experience measures (overall and pain‐specific) and their receipt of opioids while hospitalized. In supplementary analyses, we used the same propensity score matching methods to estimate the relationship between patient care experience measures and receipt of opioids in four patient subgroups based on average patient‐reported pain during hospitalization (no pain; mild pain; moderate pain; and severe pain). PRINCIPAL FINDINGS: Receipt of opioids was not associated with patient care experience measures in our main analysis. In our supplementary analysis, we found lower ratings for pain control among hospitalizations for patients who reported moderate pain (Marginal Effects = −4.5 percent; P value = .015). CONCLUSIONS: Counter to some previous studies, we observed that receipt of opioids was not associated with patient care experience measures for nonsurgical hospitalized adults. These findings may be due to different pain experiences of adults hospitalized for nonsurgical versus surgical reasons.

BackgroundPatients diagnosed with cancer face many challenges and need a good understanding of their diagnosis and proposed treatments to make informed decisions about their care. Health literacy plays an important role in this and low health literacy has been associated with poorer outcomes. The aims of this review are to identify which outcomes relate to health literacy in patients with cancer, and to combine this through a mixed studies approach with the patient experience as described through qualitative studies.MethodsFour electronic databases were searched in January 2021 to identify records relating to health literacy and patients with cancer. Records were independently screened then assessed for inclusion by two reviewers according to the following criteria: patients aged ≥18 years with cancer, English language publication AND health literacy measured with validated tool and measured outcome associated with health literacy OR qualitative study exploring the role of health literacy as patients make decisions about health. Quality was independently assessed by two reviewers. A narrative synthesis was performed, and findings integrated through concept mapping. This systematic review was registered with PROSPERO, entry CRD42020166454.Results4441 records were retrieved. Following de-duplication, 2496 titles and abstracts were screened and full texts of 405 papers were reviewed for eligibility. 66 papers relating to 60 studies met the eligibility criteria. Lower health literacy was associated with greater difficulties understanding and processing cancer related information, poorer quality of life and poorer experience of care. Personal and situational influences contributed to how participants processed information and reached decisions about their care.ConclusionThis review highlights the important role of health literacy for patients with cancer. Outcomes are poorer for those who experience difficulties with health literacy. Further efforts should be made to facilitate understanding, develop health literacy and support patients to become more involved in their care.

Background: Targeted therapies (TTs) have revolutionised cancer treatment with their enhanced specificity of action. Compared with conventional therapies, TTs are delivered over a longer period and often have unusual symptom profiles. Patient-reported outcome measures such as symptom side-effect lists need to be developed in a time-efficient manner to enable a rapid and full evaluation of new treatments and effective clinical management Objective: The aim of this study was to develop a set of TT-related symptoms and identify the optimal method for developing symptom lists. Patients and Methods: Symptoms from TT treatment in the context of Chronic Myeloid Leukaemia (CML), HER2-positive breast cancer, or Gastrointestinal Stromal Tumours (GIST) were identified through literature reviews, interviews with healthcare professionals (HCPs) and patients, and patient focus groups. The symptom set was then pilot tested in patients across the three cancer diagnoses: The number of items derived from each source (literature, patients, or HCPs) were compared. Results: A total of 316 patients and 86 HCPs from 16 countries participated. An initial set of 209 symptoms was reduced to 61 covering 12 symptom categories. Patient interviews made the greatest contribution to the item set. Conclusions: Symptom lists should be created based on input from patients. The item set described will be applicable to the assessment of new TTs, and in monitoring treatment.

Objective To evaluate the acceptability of early palliative care (EPC) among patients with advanced ovarian cancer and to determine the feasibility of larger-scale phase III trials. Methods We performed a randomized controlled pilot study of adult women ( > 18 years) with pathologically confirmed epithelial ovarian cancer that had recurred or progressed on first-line therapy and had no immediate need for palliative care. We randomly assigned patients to either EPC or standard oncologic care (SOC), and collected patient-reported outcomes (PRO) at baseline, 3 months, and 6 months; end-of-life care quality indicators were collected at study completion. Study endpoints were rates of enrollment, EPC adherence, and PRO completion. Results Of 32 eligible patients approached, 23 enrolled (72%; 95% CI 53–86) and were randomly assigned to either EPC (n = 12) or SOC (n = 11). At baseline, participants had poor physical and emotional wellbeing, high rates of depression (65%), and understood that their disease was not curable (87%). Eleven patients (92%; 95% CI 62–100) attended their EPC consultation, and all visits took place within 4 weeks of enrollment. However, PRO completion was low due to deaths by 3 (5/23) and 6 months (9/23). Conclusion Patients had accurate perceptions of their disease status, were willing to be randomly assigned to EPC, and attended scheduled appointments. However, a definitive trial in this group is not feasible without major adjustments to eligibility criteria and a multicentre, international effort. We propose that EPC be considered routinely at progression or recurrence given patients’ symptom burden and clear acceptance of the intervention, as well as evidence of benefit from adequately powered trials in other malignancies.

Background: The PI3K/AKT and androgen-receptor pathways are dysregulated in metastatic castration-resistant prostate cancers (mCRPCs); tumours with functional PTEN-loss status have hyperactivated AKT signalling. Dual pathway inhibition with AKT inhibitor ipatasertib plus abiraterone might have greater benefit than abiraterone alone. We aimed to compare ipatasertib plus abiraterone with placebo plus abiraterone in patients with previously untreated mCRPC with or without tumour PTEN loss. Methods: We did a randomised, double-blind, phase 3 trial at 200 sites across 26 countries or regions. Patients aged 18 years or older with previously untreated asymptomatic or mildly symptomatic mCRPC who had progressive disease and Eastern Collaborative Oncology Group performance status of 0 or 1 were randomly assigned (1:1; permuted block method) to receive ipatasertib (400 mg once daily orally) plus abiraterone (1000 mg once daily orally) and prednisolone (5 mg twice a day orally) or placebo plus abiraterone and prednisolone (with the same dosing schedule). Patients received study treatment until disease progression, intolerable toxicity, withdrawal from the study, or study completion. Stratification factors were previous taxane-based therapy for hormone-sensitive prostate cancer, type of progression, presence of visceral metastasis, and tumour PTEN-loss status by immunohistochemistry. Patients, investigators, and the study sponsor were masked to the treatment allocation. The coprimary endpoints were investigator-assessed radiographical progression-free survival in the PTEN-loss-by-immunohistochemistry population and in the intention-to-treat population. This study is ongoing and is registered with ClinicalTrials.gov, NCT03072238. Findings: Between June 30, 2017, and Jan 17, 2019, 1611 patients were screened for eligibility and 1101 (68%) were enrolled; 554 (50%) were assigned to the placebo–abiraterone group and 547 (50%) to the ipatasertib–abiraterone group. At data cutoff (March 16, 2020), median follow-up duration was 19 months (range 0–33). In the 521 (47%) patients who had tumours with PTEN loss by immunohistochemistry (261 in the placebo–abiraterone group and 260 in the ipatasertib–abiraterone group), median radiographical progression-free survival was 16·5 months (95% CI 13·9–17·0) in the placebo–abiraterone group and 18·5 months (16·3–22·1) in the ipatasertib–abiraterone group (hazard ratio [HR] 0·77 [95% CI 0·61–0·98]; p=0·034; significant at α=0·04). In the intention-to-treat population, median progression-free survival was 16·6 months (95% CI 15·6–19·1) in the placebo–abiraterone group and 19·2 months (16·5–22·3) in the ipatasertib–abiraterone group (HR 0·84 [95% CI 0·71–0·99]; p=0·043; not significant at α=0·01). Grade 3 or higher adverse events occurred in 213 (39%) of 546 patients in the placebo–abiraterone group and in 386 (70%) of 551 patients in the ipatasertib–abiraterone group; adverse events leading to discontinuation of placebo or ipatasertib occurred in 28 (5%) in the placebo–abiraterone group and 116 (21%) in the ipatasertib–abiraterone group. Deaths due to adverse events deemed related to treatment occurred in two patients (

Objective To assess the practice- and market-level factors associated with the amount of provider health information exchange (HIE) use. Materials and Methods Provider and practice-level data was drawn from the Meaningful Use Stage 2 Public Use Files from the Centers for Medicare and Medicaid Services, the Physician Compare National Downloadable File, and the Compendium of US Health Systems, among other sources. We analyzed the relationship between provider HIE use and practice and market factors using multivariable linear regression and compared primary care providers (PCPs) to non-PCPs. Provider volume of HIE use is measured as the percentage of referrals sent with electronic summaries of care (eSCR) reported by eligible providers attesting to the Meaningful Use electronic health record (EHR) incentive program in 2016. Results Providers used HIE in 49% of referrals; PCPs used HIE in fewer referrals (43%) than non-PCPs (57%). Provider use of products from EHR vendors was negatively related to HIE use, while use of Athenahealth and Greenway Health products were positively related to HIE use. Providers treating, on average, older patients and greater proportions of patients with diabetes used HIE for more referrals. Health system membership, market concentration, and state HIE consent policy were unrelated to provider HIE use. Discussion HIE use during referrals is low among office-based providers with the capability for exchange, especially PCPs. Practice-level factors were more commonly associated with greater levels of HIE use than market-level factors. Conclusion This furthers the understanding that market forces, like competition, may be related to HIE adoption decisions but are less important for use once adoption has occurred.

Rationale: Effective cough treatments are a significant unmet need in patients with lung cancer. Aprepitant is a licensed treatment for nausea and vomiting, which blocks substance P activation of NK-1 (neurokinin 1) receptors, a mechanism also implicated in cough. Objectives: To assess aprepitant in patients with lung cancer with cough and evaluate mechanisms in vagal nerve tissue. Methods: Randomized double-blind crossover trial of patients with lung cancer and bothersome cough. They received 3 days of aprepitant or matched placebo; after a 3-day washout, patients crossed to the alternative treatment. The primary endpoint was awake cough frequency measured at screening and Day 3 of each treatment; secondary endpoints included patient-reported outcomes. In vitro, the depolarization of isolated guinea pig and human vagus nerve sections in grease-gap recording chambers, indicative of sensory nerve activation, was measured to evaluate the mechanism. Measurements and Main Results: Twenty patients with lung cancer enrolled, with a mean age 66 years (67.7); 60% were female and 80% had non–small cell cancer, 50% had advanced stage, and 55% had World Health Organization performance status 1. Cough frequency improved with aprepitant, reducing by 22.2% (95% confidence interval [CI], 2.8–37.7%) over placebo while awake (P = 0.03), 30.3% (95% CI, 12.7–44.3) over 24 hours (P = 0.002), and 59.8% (95% CI, 15.1–86.0) during sleep (P = 0.081). Patient-reported outcomes all significantly improved. Substance P depolarized both guinea pig and human vagus nerve. Aprepitant significantly inhibited substance P–induced depolarization by 78% in guinea pig (P = 0.0145) and 94% in human vagus (P = 0.0145). Conclusions: Substance P activation of NK-1 receptors appears to be an important mechanism driving cough in lung cancer, and NK-1 antagonists show promise as antitussive therapies.

Background: Lung cancer causes impairment of health-related quality of life (QoL), but little is known about gender aspects in QoL and symptom burden of lung cancer patients. The aim of this study was to investigate gender differences in QoL as assessed by the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and the updated lung cancer module. Methods: In a prospective, international, cross-cultural, multicenter study that was undertaken to update the lung cancer-specific module EORTC QLQ-LC13, patients filled in the core questionnaire EORTC QLQ-C30 and the updated lung cancer module. Gender differences were calculated for all QoL scores using ANCOVAs that controlled for known and suspected confounders. Comparisons with historic data were drawn. Results: A total of 200 patients (82 female and 118 male, median age 65 years) were recruited. With the exception of coughing (estimated marginal means: women 33.86 and men 43.52, P=0.022) and diarrhea (estimated marginal means: women 26.01 and men 17.93, P=0.038) there were no significant QoL gender differences. Fatigue was the most pronounced symptom in both, men and women, outpacing typical respiratory symptoms. Quite generally, our sample of lung cancer patients showed considerably worse QoL in all scores when compared to EORTC reference data (lung cancer and combined cancer diagnoses, mean differences up to 13.70 and 21.54 score points, respectively) and to a German norm reference sample (up to 35.37 score points). Conclusions: This study adds to the literature in showing that the typical QoL gender difference effect (women doing worse than men) may not be generalizable across all patient samples.

BackgroundThree million internally displaced Somalis live in overcrowded settlements with weakened infrastructure, insufficient access to WASH facilities, and inaccessible health services. This vulnerable population is especially susceptible to COVID-19, which is expected to have worsened health outcomes and exacerbate existing structural challenges in the implementation of public health measures. This study examines knowledge of COVID-19, self-reported prevalence of preexisting conditions, and access to essential health services among residents of internally displaced persons (IDP) camps in Somalia.MethodsA descriptive, cross-sectional survey design assessing demographics, current health profiles, knowledge and perceptions of COVID-19, and access to resources was used. 401 Somali IDP camp residents completed the survey.ResultsThough 77% of respondents reported taking at least one COVID-19 preventative public health measure, respondents reported a severe lack of access to adequate sanitation, an inability to practice social distancing, and nearly universal inability to receive a COVID-19 screening exam. Questions assessing knowledge surrounding COVID-19 prevention and treatment yielded answers of “I don’t know” for roughly 50% of responses. The majority were not familiar with basic information about the virus or confident that they could receive medical services if infected. Those who perceived their health status to be “fair,” as opposed to “good,” showed 5.69 times higher odds of being concerned about contracting COVID-19. Respondents who felt more anxious or nervous and those who introduced one behavioral change to protect against COVID-19 transmission showed 10.16 and 5.20 times increased odds of being concerned about disease contraction, respectively.ConclusionThis study highlights immense gaps in the knowledge and perceptions of COVID-19 and access to treatment and preventative services among individuals living in Somali IDP camps. A massive influx of additional resources is required to adequately address COVID-19 in Somalia, starting with educating those individuals most vulnerable to infection.What is already known?There are no studies to date examining COVID-19 symptoms, as well as attitudes and perceptions, in Somali IDP camps.Investigations performed in other camp-like humanitarian settings have demonstrated high prevalence of COVID-19 symptoms.What are the new findings?People living in Somali IDP camps are generally unfamiliar with basic COVID-19 information, such as the possibility of transmission by asymptomatic individuals.A majority of respondents displayed at least one symptom consistent with COVID-19, and the vast majority were unable to access COVID-19 screening services.Older age, having implemented one behavioral change to protect against contraction, new stress or anxiety, and a “fair” health perception were significant predictors of being concerned about contracting COVID-19.What do the new findings imply?There is a significant gap in the knowledge and perception of COVID-19 by those in Somali IDP camps.Utilizing trusted sources of information may be an effective way of disseminating COVID-19 related information among Somali IDP camp residents.

Background Specialised Independent Prescribing (IP) community optometrists provided acute eye care during the COVID-19 crisis ensuring that over-stretched hospital emergency eye care was supported, therefore local overall urgent eye care provision was not affected. Subjects/methods Number of cases seen by hospital Rapid Access Clinic (RAC) between January 2020 and June 2020 were compared to number of cases seen by IP optometrists in community Acute Primary Care Ophthalmology Service (APCOS) during the same time period. Specifically, comparisons were made between the number of cases seen in RAC and the number of cases seen by APCOS during the period before COVID-19 emergency (January–March 2020) and for a similar timeframe thereafter (April–June 2020). Numbers treated by APCOS alone and those referred to RAC were also determined. The change in case numbers between the different healthcare settings was also studied. Results Increase in cases seen by APCOS between April (n = 391) and June (n = 641). Number of cases seen by RAC declined from 652 in March to 372 in April, increasing to 610 by June. This was still below maximum number of monthly cases seen by RAC pre-lockdown in January (861). Most of the cases seen by APCOS were managed in the community with 4% referred to RAC. Conclusions Ophthalmology services delivered by IP specialised optometrists can safely and efficiently treat and manage the vast majority of urgent cases and mitigate the reduced capacity within hospital emergency eye clinics. Our experience provides insights into care pathways for urgent eye cases in the future.

Background The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Lung Cancer 13 (QLQ-LC13) assesses quality of life (QOL) in patients with lung cancer and was the first EORTC module developed for use in international clinical trials. Since its publication in 1994, major treatment advances with possible effects on QOL have occurred. These changes called for an update of the module and its international psychometric validation. We aimed to investigate the scale structure and psychometric properties of the updated lung cancer module, QLQ-LC29, in patients with lung cancer. Methods This international, observational field study was done in 19 hospitals across 12 countries. Patients aged older than 18 years with a confirmed diagnosis of lung cancer and no other previous primary tumour, and who were mentally fit with sufficient language skills to understand and complete the questionnaire were included. Patients were asked during a hospital visit to fill in the paper versions of the core questionnaire EORTC QLQ-C30 plus QLQ-LC29, and investigators selected half of these patients to complete the questionnaire again 2-4 weeks later. Our primary aim was to assess the scale structure and psychometric properties of EORTC QLQ-LC29. We analysed scale structure using confirmatory factor analysis; reliability using Cronbach's a value (internal consistency) and intra-class coefficient (test-retest reliability); sensitivity using independent t tests stratified by Karnofsky performance status; and responsiveness to change over time by ANOVA. This study is registered with ClinicalTrials.gov, NCT02745691. Findings Between April 12, 2016, and Sept 26, 2018, 523 patients with a confirmed diagnosis of either non-small-cell lung cancer (n=442) or small-cell lung cancer (n=81) were recruited. Confirmatory factor analysis provided a solution composed of five multi-item scales (coughing, shortness of breath, fear of progression, hair problems, and surgery-related symptoms) plus 15 single symptom or side-effect items: chi(2)=370.233, root mean square error of approximation=0.075, and comparative-fit index=0.901. Cronbach's alpha for internal consistencies of all multi-item scales were above the threshold of 0.70. Intra-class coefficients for test retest reliabilities ranged between 0.82 and 0.97. Three (shortness of breath, fear of progression, and hair problems) of the five multi-item scales showed responsiveness to change over time (p values

BACKGROUND: Little is known about how primary care clinicians (PCCs) approach chronic pain management in the current climate of rapidly changing guidelines and the growing body of research about risks and benefits of opioid therapy. OBJECTIVE: To better understand PCCs’ approaches to managing patients with chronic pain and explore implications for technological and administrative interventions. DESIGN: We conducted adapted critical decision method interviews with 20 PCCs. Each PCC participated in 1–5 interviews. PARTICIPANTS: PCCs interviewed had a mean of 14 years of experience. They were sampled from 13 different clinics in rural, suburban, and urban health settings across the state of Indiana. APPROACH: Interviews included discussion of participants’ general approach to managing chronic pain, as well as in-depth discussion of specific patients with chronic pain. Interviews were audio recorded. Transcripts were analyzed thematically. KEY RESULTS: PCCs reflected on strategies they use to encourage and motivate patients. We identified four associated strategic themes: (1) developing trust, (2) eliciting information from the patient, (3) diverting attention from pain to function, and (4) articulating realistic goals for the patient. In discussion of chronic pain management, PCCs often explained their beliefs about opioid therapy. Three themes emerged: (1) Opioid use tends to reduce function, (2) Opioids are often not effective for long-term pain treatment, and (3) Response to pain and opioids is highly variable. CONCLUSIONS: PCC beliefs about opioid therapy generally align with the clinical evidence, but may have some important gaps. These findings suggest the potential value of interventions that include improved access to research findings; organizational changes to support PCCs in spending time with patients to develop rapport and trust, elicit information about pain, and manage patient expectations; and the need for innovative clinical cognitive support. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11606-020-06178-2) contains supplementary material, which is available to authorized users.

Background There is absence of literature related to cough prevalence and its characteristics in lung cancer patients, with information deriving only from broader symptoms occurrence studies. The aims of this study were to provide a snapshot of the prevalence of all-cause-cough in lung cancer patients and to characterise cough in terms of its impact and severity. Methods A cross-sectional study recruiting consecutive lung cancer patients over a pre-defined period of time and using cough-specific validated tools in a tertiary referral centre in the UK, including a cough severity VAS and the Manchester Cough in Lung Cancer scale (MCLCS). Results Data was collected from 202 patients. All-cause cough prevalence was 57% (through VAS) both in the screened (N = 223) and research (N = 202) population or 67% (through the MCLCS), and cough severity was moderate at a mean of 32 mm (in a 100 mm VAS). Age, sex, smoking status, lung cancer histology, stage and comorbidities were not associated with cough prevalence. The only variable associated with lower cough reports was being ‘on anticancer treatment’; fewer patients on treatment reported a cough (40%) compared to those off treatment (54%) (p = 0.04). The impact of cough (as measured by MCLCS) was also significant (mean score = 22). About 18% of patients felt moderate/severe distress from their cough and about 15% often or always reported disturbed sleep due to coughing. Half the patients felt their cough warranted treatment. Conclusions Cough is a common symptom in lung cancer with considerable impact on patients’ lives. Cough presence and severity should regularly be assessed in clinical practice. There is an urgent need to focus on developing more potent antitussive treatments and improve the management of this complex and distressing symptom.

Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background Research into major bleeding during cardiac surgery is challenging due to variability in how it is scored. Two consensus-based clinical scores for major bleeding: the Universal definition of perioperative bleeding and the European Coronary Artery Bypass Graft (E-CABG) bleeding severity grade, were compared in this substudy of the Transfusion Avoidance in Cardiac Surgery (TACS) trial. Methods As part of TACS, 7,402 patients underwent cardiac surgery at 12 hospitals from 2014 to 2015. We examined content validity by comparing scored items, construct validity by examining associations with redo and complex procedures, and criterion validity by examining 28-day in-hospital mortality risk across bleeding severity categories. Hierarchical logistic regression models were constructed that incorporated important predictors and categories of bleeding. Results E-CABG and Universal scores were correlated (Spearman ρ = 0.78, P < 0.0001), but E-CABG classified 910 (12.4%) patients as having more severe bleeding, whereas the Universal score classified 1,729 (23.8%) as more severe. Higher E-CABG and Universal scores were observed in redo and complex procedures. Increasing E-CABG and Universal scores were associated with increased mortality in unadjusted and adjusted analyses. Regression model discrimination based on predictors of perioperative mortality increased with additional inclusion of the Universal score (c-statistic increase from 0.83 to 0.91) or E-CABG (c-statistic increase from 0.83 to 0.92). When other major postoperative complications were added to these models, the association between Universal or E-CABG bleeding with mortality remained. Conclusions Although each offers different advantages, both the Universal score and E-CABG performed well in the validity assessments, supporting their use as outcome measures in clinical trials.

Purpose: Guidelines recommend that oncologists discuss goals of care (GOC) with patients who have advanced cancer and that these patients be referred for early palliative care (PC). An audit of practice between 2010 and 2015 at the Cancer Centre of Southeastern Ontario suggested that these rates were suboptimal. We sought to improve the rate of documentation of GOC and referral to PC through the implementation of a quality improvement (QI) initiative. Methods: Patients receiving palliative systemic treatment of lung, pancreatic, colorectal, and breast cancer were identified via electronic pharmacy records and the electronic patient care system. Using the Define, Measure, Analyze, Improve, Control QI methodology, we drafted a guideline for GOC documentation and PC referral and designed a standardized documentation system. E-mail reminders were sent to physicians and a QI scorecard was displayed to document overall and individual physician rates of GOC documentation. Data were analyzed monthly and presented on statistical process control P charts. Results: Between May 2016 and November 2017, a total of 303 unique patients were identified (52%, 21%, 17%, and 10% with lung, breast, colorectal, and pancreatic cancer, respectively). GOC documentation increased significantly over the study period (baseline, 0%; passive phase, 3%; active phase, 31%); this increase was likely because of our intervention. PC referral rates also increased over the study period (baseline, 36%; passive phase, 35%; active phase 48%). We did not identify any patient, physician, or disease factors that were associated with GOC discussion or referral to PC. Conclusion: Our QI initiative was successful in improving rates of GOC documentation in patients with advanced cancer.

Objective To identify the prevalence, frequency of use, and effects of analgesic pain management strategies used in elite athletes. Design Systematic literature review. Data sources Six databases: Ovid/Medline, SPORTDiscus, CINAHL, Embase, Cochrane Library, and Scopus. Eligibility criteria for selecting studies Empirical studies involving elite athletes and focused on the use or effects of medications used for pain or painful injury. Studies involving recreational sportspeople or those that undertake general exercise were excluded. Main results Of 70 articles found, the majority examined the frequency with which elite athletes use pain medications, including nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, anesthetics, and opioids. A smaller set of studies assessed the effect of medications on outcomes such as pain, function, and adverse effects. Oral NSAIDs are reported to be the most common medication, being used in some international sporting events by over 50% of athletes. Studies examining the effects of pain medications on elite athletes typically involved small samples and lacked control groups against which treated athletes were compared. Conclusions Existing empirical research does not provide a sufficient body of evidence to guide athletes and healthcare professionals in making analgesic medication treatment decisions. Based on the relatively robust evidence regarding the widespread use of NSAIDs, clinicians and policymakers should carefully assess their current recommendations for NSAID use and adhere to a more unified consensus-based strategy for multidisciplinary pain management in elite athletes. In the future, we hope to see more rigorous, prospective studies of various pain management strategies in elite athletes, thus enabling a shift from consensus-based recommendations to evidence-based recommendations.

Ewing sarcoma is a highly aggressive small round cell malignant neoplasm of bone and soft tissue that typically is manifested in children and young adults. It is most commonly a primary bone tumor; however, extraosseous cases have been increasingly reported. We report a case of metastatic extraosseous Ewing sarcoma with the primary lesion occurring within a limb affected by primary lymphedema. Lymphedema, in this case, played a role not only in the genesis of the tumor because of the relative local immunosuppression but also in masking the development of the lower limb mass. Keywords: Ewing sarcoma, Lymphedema, Lymphatic disorders, Histopathology, Oncology, Radiology

Chronic pain leads to reduced quality of life for patients, and strains health systems worldwide. In the U.S. and some other countries, the complexities of caring for chronic pain are exacerbated by individual and public health risks associated with commonly used opioid analgesics. To help understand and improve pain care, this article uses the data-frame theory of sensemaking to explore how primary care clinicians in the U.S. manage their patients with chronic noncancer pain. We conducted Critical Decision Method interviews with 10 primary care clinicians about 30 individual patients with chronic pain. In these interviews, we identified several patient, social/environmental, and clinician factors that influence the frames clinicians use to assess their patients and determine a pain management plan. Findings suggest significant ambiguity and uncertainty in clinical pain management decision making. Therefore, interventions to improve pain care might focus on supporting sensemaking in the context of clinical evidence rather than attempting to provide clinicians with decontextualized and/or algorithm-based decision rules. Interventions might focus on delivering convenient and easily interpreted patient and social/environmental information in the context of clinical practice guidelines.

ObjectiveWidespread health information exchange (HIE) is a national objective motivated by the promise of improved care and a reduction in costs. Previous reviews have found little rigorous evidence that HIE positively affects these anticipated benefits. However, early studies of HIE were methodologically limited. The purpose of the current study is to review the recent literature on the impact of HIE.MethodsWe used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to conduct our systematic review. PubMed and Scopus databases were used to identify empirical articles that evaluated HIE in the context of a health care outcome.ResultsOur search strategy identified 24 articles that included 63 individual analyses. The majority of the studies were from the United States representing 9 states; and about 40% of the included analyses occurred in a handful of HIEs from the state of New York. Seven of the 24 studies used designs suitable for causal inference and all reported some beneficial effect from HIE; none reported adverse effects.ConclusionsThe current systematic review found that studies with more rigorous designs all reported benefits from HIE. Such benefits include fewer duplicated procedures, reduced imaging, lower costs, and improved patient safety. We also found that studies evaluating community HIEs were more likely to find benefits than studies that evaluated enterprise HIEs or vendor-mediated exchanges. Overall, these finding bode well for the HIEs ability to deliver on anticipated improvements in care delivery and reduction in costs.

Purpose Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) may provide benefit to patients in refractory cardiac arrest and cardiogenic shock. We aim to summarize our center's 6-year experience with resuscitative VA-ECMO. Materials and methods A retrospective medical record review (April 2009 to 2015) was performed on consecutive non-cardiotomy patients who were managed with VA-ECMO due to refractory in- or out-of-hospital cardiac (IHCA/OHCA) arrest (E-CPR) or refractory cardiogenic shock (E-CS) with or without preceding cardiac arrest. Our primary outcome was survival to hospital discharge and good neurological status (Cerebral Performance Category 1–2). Results There were a total of 22 patients who met inclusion criteria of whom 9 received E-CPR (8 IHCA, 1 OHCA) and 13 received E-CS. The median age for E-CPR patients was 52 [IQR 45, 58] years, and 54 [IQR 38, 64] years for E-CS patients. Cardiac arrest duration was 70.33 (SD 39.56) min for the E-CPR patients, and 24.67 (SD 26.73) min for the 9 patients treated with E-CS who had previously arrested. Initial cardiac arrest rhythms were pulseless electrical activity (39%), ventricular fibrillation (33%), or ventricular tachycardia (28%). A total of 18/22 patients were successfully weaned from VA-ECMO (78%); 16 patients survived to hospital discharge (73%) with 15 in good neurological condition. Conclusion The initiation of VA-ECMO at our center for treatment of refractory cardiac arrest and cardiogenic shock yielded a high proportion of survivors and favorable neurological outcomes.

Background Somalia is considered severely underprepared to contain an outbreak of COVID-19, with critical shortages in healthcare personnel and treatment resources. In limited-resource settings such as Somalia, providing healthcare workers with adequate information on COVID-19 is crucial to improve patient outcomes and mitigate the spread of the SARS-CoV-2 virus. This study assessed the knowledge of, preparedness for, and perceptions toward COVID-19 prevention and treatment among Somali healthcare workers. Methods A descriptive, cross-sectional survey was completed by 364 Somali healthcare workers in summer of 2020 utilizing a convenience sampling method. Results Participants’ most accessed sources of COVID-19 information were from social media (64.8%), official government and international health organization websites (51.1%,), and traditional media sources such as radio, TV, and newspapers (48.1%). A majority of participants demonstrated strong knowledge of treatment of COVID-19, the severity of COVID-19, and the possible outcomes of COVID-19, but only 5 out of 10 symptoms listed were correctly identified by more than 75% of participants. Although participants indicated seeing a median number of 10 patients per week with COVID-19 related symptoms, access to essential medical resources, such as N95 masks (30.2%), facial protective shields (24.5%), and disposable gowns (21.4%), were limited. Moreover, 31.3% agreed that Somalia was in a good position to contain an emerging outbreak of COVID-19. In addition, 40.4% of participants agreed that the Somali government’s response to the pandemic was sufficient to protect Somali healthcare professionals. Conclusion This study provides evidence for the need to equip Somali healthcare providers with more information, personal protective equipment, and treatment resources such that they can safely and adequately care for COVID-19 patients and contain the spread of the virus. Social media and traditional news outlets may be effective outlets to communicate information regarding COVID-19 and the Somali government’s response to frontline healthcare workers.

Introduction Carcinoid syndrome is a relatively rare condition that may affect the liver and the right heart. Some of these cases may require surgical treatment with a multidisciplinary approach. Case report We report the case of a patient with progressive dyspnoea, arterial hypotension and facial flushing, diagnosed with liver and cardiac involvement from carcinoid syndrome. The patient was taken to surgery in two different occasions, first for metastatic liver resection, and then to subsequent cardiac surgery for tricuspid valve replacement. Conclusions We report here a case review, including the clinical course, the intra-operative management, and the information available in the literature regarding which procedure to perform initially in these types of cases which are not very common in clinical practice.

Depression is the most common psychiatric comorbidity among people living with HIV/AIDS (PLWHA). Little is known about the comparative effectiveness between different types of antidepressants used to treat depression in this population. We compared the effectiveness of dual-action and single-action antidepressants in PLWHA for achieving remission from depression.We used data from the Centers for AIDS Research Network of Integrated Clinic Systems to identify 1175 new user dual-action or single-action antidepressant treatment episodes occurring from 2005 to 2014 for PLWHA diagnosed with depression. The primary outcome was remission from depression defined as a Patient Health Questionnaire-9 (PHQ-9) score5. Mean difference in PHQ-9 depressive symptom severity was a secondary outcome. The main approach was an intent-to-treat (ITT) evaluation complemented with a per protocol (PP) sensitivity analysis. Generalized linear models were fitted to estimate treatment effects.In ITT analysis, 32% of the episodes ended in remission for both dual-action and single-action antidepressants. The odds ratio (OR) of remission was 1.02 (95%CI=0.63,1.67). In PP analysis, 40% of dual-action episodes ended in remission compared to 32% in single-action episodes. Dual-action episodes had 1.33 times the odds of remission (95%CI=0.55,3.21), however the result was not statistically significant. Non-significant differences were also observed for depressive symptom severity.Missing data was common but was addressed with inverse probability weights.Results suggest that single-action and dual-action antidepressants are equally effective in PLWHA. Remission was uncommon highlighting the need to identify health service delivery strategies that aid HIV providers in achieving full remission of their patients' depression.

Summary Background Although trastuzumab plus chemotherapy is the standard of care for first-line treatment of HER2-positive advanced gastric cancer, there is no established therapy in the second-line setting. In GATSBY, we examined the efficacy and tolerability of trastuzumab emtansine in patients previously treated for HER2-positive advanced gastric cancer (unresectable, locally advanced, or metastatic gastric cancer, including adenocarcinoma of the gastro-oesophageal junction). Methods This is the final analysis from GATSBY, a randomised, open-label, adaptive, phase 2/3 study, done at 107 centres (28 countries worldwide). Eligible patients had HER2-positive advanced gastric cancer and progressed during or after first-line therapy. In stage one of the trial, patients were randomly assigned to treatment groups (2:2:1) to receive intravenous trastuzumab emtansine (3·6 mg/kg every 3 weeks or 2·4 mg/kg weekly) or physician's choice of a taxane (intravenous docetaxel 75 mg/m 2 every 3 weeks or intravenous paclitaxel 80 mg/m 2 weekly). In stage two, patients were randomly assigned to treatment groups (2:1) to receive the independent data monitoring committee (IDMC)-selected dose of trastuzumab emtansine (2·4 mg/kg weekly) or a taxane (same regimen as above). We used permuted block randomisation, stratified by world region, previous HER2-targeted therapy, and previous gastrectomy. The primary endpoint (overall survival) was assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01641939. Findings Between Sept 3, 2012, and Oct 14, 2013, 70 patients were assigned to receive trastuzumab emtansine 3·6 mg/kg every 3 weeks, 75 to receive trastuzumab emtansine 2·4 mg/kg weekly, and 37 to receive a taxane in the stage 1 part of the trial. At the pre-planned interim analysis (Oct 14, 2013), the IDMC selected trastuzumab emtansine 2·4 mg/kg weekly as the dose to proceed to stage 2. By Feb 9, 2015, a further 153 patients had been randomly assigned to receive trastuzumab emtansine 2·4 mg/kg weekly and a further 80 to receive a taxane. At data cutoff, median follow-up was 17·5 months (IQR 12·1–23·0) for the trastuzumab emtansine 2·4 mg/kg weekly group and 15·4 months (9·2–18·1) in the taxane group. Median overall survival was 7·9 months (95% CI 6·7–9·5) with trastuzumab emtansine 2·4 mg/kg weekly and 8·6 months (7·1–11·2) with taxane treatment (hazard ratio 1·15, 95% CI 0·87–1·51, one-sided p=0·86). The trastuzumab emtansine 2·4 mg/kg group had lower incidences of grade 3 or more adverse events (134 [60%] of 224 patients treated with trastuzumab emtansine vs 78 [70%] of 111 patients treated with a taxane), and similar incidences of adverse events leading to death (eight [4%] vs four [4%]), serious adverse events (65 [29%] vs 31 [28%]), and adverse events leading to treatment discontinuation (31 [14%] vs 15 [14%]) than did taxane treatment. The most common grade 3 or more adverse events in the trastuzumab emtansine 2·4 mg/kg weekly group were anaemia (59 [26%]) and thrombocytopenia (25 [11%]) compared with neutropenia (43 [39%]), and anaemia (20 [18%]), in the taxane group. The most common serious adverse events were anaemia (eight [4%]), upper gastrointestinal haemorrhage (eight [4%]), pneumonia (seven [3%]), gastric haemorrhage (six [3%]), and gastrointestinal haemorrhage (five [2%]) in the trastuzumab emtansine 2·4 mg/kg weekly group compared with pneumonia (four [4%]), febrile neutropenia (four [4%]), anaemia (three [3%]), and neutropenia (three [3%]) in the taxane group. Interpretation Trastuzumab emtansine was not superior to taxane in patients with previously treated, HER2-positive advanced gastric cancer. There is still an unmet need in this patient group and therapeutic options remain limited. Funding F Hoffmann-La Roche.

Objective Hybrid coronary revascularization offers and combines the advantages of both surgical and percutaneous revascularization and eliminates at the same time the disadvantages of both procedures. The objective of this study was to assess graft and stent patency at 6 months, rate of bleeding, intensive care unit and hospital stay, rate of reintervention, and long-term clinical follow-up. Methods From March 2004 to November 2015, a total of 203 patients underwent robotic-assisted minimally invasive direct coronary artery bypass graft of the left internal thoracic artery to the left anterior descending artery and PCI of a non-left anterior descending vessel in a single or two stage, at three different centers. Patients underwent 6-month angiographic follow-up. The mean ± SD clinical follow-up was 77.82 ±41.4 months. Results Successful hybrid coronary revascularization occurred in 196 of the 203 patients. One hundred forty-six patients underwent simultaneous surgical and percutaneous intervention. Nineteen patients underwent PCI before surgery, and 38 patient underwent PCI after surgery. No in-hospital mortality occurred. The mean ± SD ICU stay was 1 ± 1 days and the mean ± SD hospital stay was 5 ± 2 days. Only 13.3% of the patients required a blood transfusion. Six-month angiographic follow-up has been performed in the 95 patients, and it demonstrated a left internal thoracic artery anastomotic patency of 97.9% and stent patency of 92.6%. A total of 77.8 ± 41.4-month clinical follow-up demonstrated 95.1% survival, 92.6% freedom from angina, and 90.7% freedom from any form of coronary revascularization. Conclusions Hybrid coronary revascularization seems to be a promising and safe revascularization strategy. It provides selected patients with an alternative, functionally complete revascularization with minimal surgical trauma and good long-term clinical outcomes.