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During the COVID-19 pandemic, telehealth rapidly emerged as an essential health care service and became particularly important for patients with cancer and chronic conditions. However, the benefits of telehealth have not been fully realized for some of the most vulnerable populations due to inequitable access to telehealth capable technology.This study aimed to assess accessibility and satisfaction with telehealth technology by vulnerable patients with cancer and pulmonary disease.A paper survey and internet-based survey were developed and administered to adult (≥18 years) cancer and pulmonary clinic patients (July 1, 2020 to October 30, 2020).Descriptive statistics and Fisher exact test were performed. Two hundred eleven patients completed the survey. Adults ≥50 years old (older) had reduced access to smartphone video capability and internet connection compared with adults less than 50 years old (59% vs. 90%, p.01). Older adults reported more challenges with telehealth visits compared with younger adults (50.3%, 28.6%; p.01). No difference in access to technology and preferences for telehealth versus in-person care was found by race, gender, or education level.Nearly all patients (95%) who had a previous experience with a telehealth visit felt confident in the quality of care they received via telehealth. Younger adults preferred video visits compared with older adults (75% vs. 50.6%, p.01). Older adults were less likely to have access to smartphones with internet access, have more challenges with telehealth visits, and were less likely to prefer audio-video telehealth visits compared with younger adults.Ensuring equitable access to all health care delivery modalities by telehealth, including audio-only visits for patients across the age continuum, is paramount.

Summary Background Data on patients with COVID-19 who have cancer are lacking. Here we characterise the outcomes of a cohort of patients with cancer and COVID-19 and identify potential prognostic factors for mortality and severe illness. Methods In this cohort study, we collected de-identified data on patients with active or previous malignancy, aged 18 years and older, with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection from the USA, Canada, and Spain from the COVID-19 and Cancer Consortium (CCC19) database for whom baseline data were added between March 17 and April 16, 2020. We collected data on baseline clinical conditions, medications, cancer diagnosis and treatment, and COVID-19 disease course. The primary endpoint was all-cause mortality within 30 days of diagnosis of COVID-19. We assessed the association between the outcome and potential prognostic variables using logistic regression analyses, partially adjusted for age, sex, smoking status, and obesity. This study is registered with ClinicalTrials.gov, NCT04354701, and is ongoing. Findings Of 1035 records entered into the CCC19 database during the study period, 928 patients met inclusion criteria for our analysis. Median age was 66 years (IQR 57–76), 279 (30%) were aged 75 years or older, and 468 (50%) patients were male. The most prevalent malignancies were breast (191 [21%]) and prostate (152 [16%]). 366 (39%) patients were on active anticancer treatment, and 396 (43%) had active (measurable) cancer. At analysis (May 7, 2020), 121 (13%) patients had died. In logistic regression analysis, independent factors associated with increased 30-day mortality, after partial adjustment, were: increased age (per 10 years; partially adjusted odds ratio 1·84, 95% CI 1·53–2·21), male sex (1·63, 1·07–2·48), smoking status (former smoker vs never smoked: 1·60, 1·03–2·47), number of comorbidities (two vs none: 4·50, 1·33–15·28), Eastern Cooperative Oncology Group performance status of 2 or higher (status of 2 vs 0 or 1: 3·89, 2·11–7·18), active cancer (progressing vs remission: 5·20, 2·77–9·77), and receipt of azithromycin plus hydroxychloroquine (vs treatment with neither: 2·93, 1·79–4·79; confounding by indication cannot be excluded). Compared with residence in the US-Northeast, residence in Canada (0·24, 0·07–0·84) or the US-Midwest (0·50, 0·28–0·90) were associated with decreased 30-day all-cause mortality. Race and ethnicity, obesity status, cancer type, type of anticancer therapy, and recent surgery were not associated with mortality. Interpretation Among patients with cancer and COVID-19, 30-day all-cause mortality was high and associated with general risk factors and risk factors unique to patients with cancer. Longer follow-up is needed to better understand the effect of COVID-19 on outcomes in patients with cancer, including the ability to continue specific cancer treatments. Funding American Cancer Society, National Institutes of Health, and Hope Foundation for Cancer Research.

PARP inhibitors are approved for treatment of cancers with BRCA1 or BRCA2 defects. In this study, we prepared and characterized a very long-acting PARP inhibitor. Synthesis of a macromolecular prodrug of talazoparib (TLZ) was achieved by covalent conjugation to a PEG40kDa carrier via a β-eliminative releasable linker. A single injection of the PEG∼TLZ conjugate was as effective as ∼30 daily oral doses of TLZ in growth suppression of homologous recombination-defective tumors in mouse xenografts. These included the KT-10 Wilms' tumor with a PALB2 mutation, the BRCA1-deficient MX-1 triple-negative breast cancer, and the BRCA2-deficient DLD-1 colon cancer; the prodrug did not inhibit an isogenic DLD-1 tumor with wild-type BRCA2. Although the half-life of PEG∼TLZ and released TLZ in the mouse was only ∼1 day, the exposure of released TLZ from a single safe, effective dose of the prodrug exceeded that of oral TLZ given daily over one month. μPET/CT imaging showed high uptake and prolonged retention of an 89Zr-labeled surrogate of PEG∼TLZ in the MX-1 BRCA1-deficient tumor. These data suggest that the long-lasting antitumor effect of the prodrug is due to a combination of its long t1/2, the high exposure of TLZ released from the prodrug, increased tumor sensitivity upon continued exposure, and tumor accumulation. Using pharmacokinetic parameters of TLZ in humans, we designed a long-acting PEG∼TLZ for humans that may be superior in efficacy to daily oral TLZ and would be useful for treatment of PARP inhibitor-sensitive cancers in which oral medications are not tolerated. Significance: These findings demonstrate that a single injection of a long-acting prodrug of the PARP inhibitor talazoparib in murine xenografts provides tumor suppression equivalent to a month of daily dosing of talazoparib.

Non-Hispanic Black individuals experience a higher burden of COVID-19 than the general population; hence, there is an urgent need to characterize the unique clinical course and outcomes of COVID-19 in Black patients with cancer.To investigate racial disparities in severity of COVID-19 presentation, clinical complications, and outcomes between Black patients and non-Hispanic White patients with cancer and COVID-19.This retrospective cohort study used data from the COVID-19 and Cancer Consortium registry from March 17, 2020, to November 18, 2020, to examine the clinical characteristics and outcomes of COVID-19 in Black patients with cancer. Data analysis was performed from December 2020 to February 2021.Black and White race recorded in patient's electronic health record.An a priori 5-level ordinal scale including hospitalization intensive care unit admission, mechanical ventilation, and all-cause death.Among 3506 included patients (1768 women [50%]; median [IQR] age, 67 [58-77] years), 1068 (30%) were Black and 2438 (70%) were White. Black patients had higher rates of preexisting comorbidities compared with White patients, including obesity (480 Black patients [45%] vs 925 White patients [38%]), diabetes (411 Black patients [38%] vs 574 White patients [24%]), and kidney disease (248 Black patients [23%] vs 392 White patients [16%]). Despite the similar distribution of cancer type, cancer status, and anticancer therapy at the time of COVID-19 diagnosis, Black patients presented with worse illness and had significantly worse COVID-19 severity (unweighted odds ratio, 1.34 [95% CI, 1.15-1.58]; weighted odds ratio, 1.21 [95% CI, 1.11-1.33]).These findings suggest that Black patients with cancer experience worse COVID-19 outcomes compared with White patients. Understanding and addressing racial inequities within the causal framework of structural racism is essential to reduce the disproportionate burden of diseases, such as COVID-19 and cancer, in Black patients.

Therapeutic drug monitoring (TDM) involves frequent measurements of drug concentrations to ensure levels remain within a therapeutic window, and it is especially useful for drugs with narrow therapeutic indices or extensive interindividual pharmacokinetic variability. This technique has never been applied to immuno-oncology drugs, but, given recent examinations of clinical data (both exposure and response) on a number of these drugs, further investigations into TDM may be justified to reduce costs as well as potentially reducing the severity and/or duration of immune-related adverse events. Specifically, all but one of the approved PD-1 and PD-L1 inhibitors (pembrolizumab, nivolumab, cemiplimab-rwlc, atezolizumab, avelumab, durvalumab) have been shown to exhibit a plateaued exposure-response (E-R) curve at doses evaluated extensively to date, as well as time-dependent changes in drug exposure. Furthermore, responders have a greater decrease in drug clearance over time and would, therefore, have supratherapeutic serum concentrations. With frequent trough measurements, it is possible to use pharmacokinetic modelling and simulation to estimate drug clearance via Bayesian methods. Based on patient-specific estimates for clearance, optimal alternative dosing strategies can be simulated to lower drug and cost burden yet maintain therapeutic levels, especially as the clearance of the drug decreases over time. This review will comprehensively discuss each of the FDA approved PD-1, PD-L1/2 and CTLA-4 inhibitors regarding their indications and current recommended dosing, with evidence supporting the investigation of these types of TDM strategies.

Herein, we describe the covalent attachment of resveratrol, a naturally occurring antioxidant, to the surface of stainless-steel as a model for designing a novel bare-metal stent to treat coronary artery disease. Resveratrol has been shown to reduce oxidative stress in dysfunctional endothelial cells, and stimulate arterial healing. Resveratrol treatments, however, are limited by low water solubility, such that a localized delivery to the site of arterial narrowing via a coated stent presents a promising strategy for improving stent outcomes. Our attachment strategy utilizes zirconium vapor deposition to lay down a thin layer of zirconium oxide with labile hydrocarbon groups at the surface. Resveratrol can displace these hydrocarbons in aprotic solvent to afford a covalently attached layer of resveratrol. We evaluated the release of resveratrol under a range of pH levels, including physiological conditions (pH = 7.4 and 37 °C). Furthermore, we established that endothelial cells grown on a resveratrol-bound surface release elevated nitric oxide levels compared to controls, a key endothelial signaling molecule responsible for arterial health. These results are promising toward the development of a resveratrol-coated bare-metal stent to improve patient outcomes.

Made available in DSpace on 2019-10-04T12:41:37Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-07-02 National Health and Medical Research Council of Australia Background-The uptake of proven stroke treatments varies widely. We aimed to determine the association of evidence-based processes of care for acute ischemic stroke (AIS) and clinical outcome of patients who participated in the HEADPOST (Head Positioning in Acute Stroke Trial), a multicenter cluster crossover trial of lying flat versus sitting up, head positioning in acute stroke. Methods and Results-Use of 8 AIS processes of care were considered: reperfusion therapy in eligible patients; acute stroke unit care; antihypertensive, antiplatelet, statin, and anticoagulation for atrial fibrillation; dysphagia assessment; and physiotherapist review. Hierarchical, mixed, logistic regression models were performed to determine associations with good outcome (modified Rankin Scale scores 0-2) at 90 days, adjusted for patient and hospital variables. Among 9485 patients with AIS, implementation of all processes of care in eligible patients, or defect-free care, was associated with improved outcome (odds ratio, 1.40; 95% CI, 1.18-1.65) and better survival (odds ratio, 2.23; 95% CI, 1.62-3.09). Defect-free stroke care was also significantly associated with excellent outcome (modified Rankin Scale score 0-1) (odds ratio, 1.22; 95% CI, 1.04-1.43). No hospital characteristic was independently predictive of outcome. Only 1445 (15%) of eligible patients with AIS received all processes of care, with significant regional variations in overall and individual rates. Conclusions-Use of evidence-based care is associated with improved clinical outcome in AIS. Strategies are required to address regional variation in the use of proven AIS treatments. Univ New South Wales, Fac Med, George Inst Global Hlth, Sydney, NSW, Australia Ctr Estudios Clin, Inst Ciencias & Innovac Med, Santiago, Chile Clin Alemana Univ Desarrollo, Fac Med, Serv Neurol, Dept Neurol & Psiquiatria, Santiago, Chile Peking Univ, Hlth Sci Ctr, George Inst Global Hlth, Beijing, Peoples R China Australian Catholic Univ, Nursing Res Inst, St Vincents Hlth Australia Sydney, Sydney, NSW, Australia Univ Cent Lancashire, Fac Hlth & Wellbeing, Preston, Lancs, England Univ Chile, Fac Med, Dept Ciencias Neurol, Santiago, Chile Univ Sao Paulo, Ribeirao Preto Med Sch, Stroke Serv Neurol Div, Ribeirao Preto, Brazil Fukuoka Univ, Fac Med, Dept Prevent Med & Publ Hlth, Fukuoka, Fukuoka, Japan Univ Leicester, Dept Cardiovasc Sci, Leicester Biomed Res Ctr, Leicester, Leics, England Univ Leicester, Natl Inst Hlth Res, Leicester Biomed Res Ctr, Leicester, Leics, England Univ Edinburgh, Ctr Clin Brain Sci, Edinburgh, Midlothian, Scotland George Inst Global Hlth, Sydney, NSW, Australia Univ Desarrollo, Serv Neurol, Dept Neurol & Psiquiatria Clin Alemana Santiago, Santiago, Chile St Vincents Hlth Australia Sydney, Sydney, NSW, Australia Australian Catholic Univ, Sydney, NSW, Australia Univ Cent Lancashire, Stroke Practice Res Unit, Sch Hlth, Lancashire Clin Trials Unit, Preston, Lancs, England Univ Leicester, Dept Cardiovasc Sci, Cardiovasc Res Ctr, British Heart Fdn, Leicester, Leics, England Univ Kelaniya, Dept Pharmacol, Fac Med, Colombo, Sri Lanka Christian Med Coll & Hosp, Dept Neurol, Ludhiana, India Kaohsiung Med Univ & Hosp, Dept Neurol, Kaohsiung, Taiwan Linkou Chang Gung Mem Hosp, Dept Neurol, Taipei, Taiwan Peking Union Med Coll Hosp, Beijing, Peoples R China Univ Sao Paulo, Ribeirao Preto Sch Med, Ribeirao Preto, Brazil Monash Univ, Dept Epidemiol & Prevent Med, Melbourne, Vic, Australia Univ Cent Lancashire, Sch Hlth Sci, Coll Hlth & Wellbeing, Preston, Lancs, England Univ Desarrollo, Santiago, Chile Univ New South Wales, Neurosci Res Australia, Sydney, NSW, Australia Natl Univ Singapore, Dept Pharmacol, Singapore, Singapore Bradford Royal Infirm, Bradford Inst Hlth Res, Leeds, W Yorkshire, England Christian Med College, Ludhiana, Punjab, India RemediumOne Pvt Ltd, Kandy, Sri Lanka Kaohsiung Med Univ, Chung Ho Mem Hosp, Kaohsiung, Taiwan Calvary Publ Hosp Bruce, Bruce, Australia Royal North Shore Hosp, St Leonards, NSW, Australia Royal Prince Alfred Hosp, Camperdown, NSW, Australia Concord Repatriat Gen Hosp, Camperdown, NSW, Australia Fiona Stanley Hosp, Camperdown, NSW, Australia Macquarie Base Hosp, Melbourne, Vic, Australia Univ Sao Paulo, Fac Med Ribeirao Preto, Hosp Clin, Sao Paulo, Brazil Hosp Governador Celso Ramos, Florianopolis, SC, Brazil Sao Paulo State Univ, Hosp Fac Med Botucatu, UNESP, Sao Paulo, Brazil Yangquan Coalmine Grp Gen Hosp, Yangquan, Peoples R China Nanjing Med Univ, Nanjing Hosp 1, Nanjing, Jiangsu, Peoples R China 85 Hosp Peoples Liberat Army, Beijing, Peoples R China Chifeng Univ, Affiliated Hosp, Chifeng, Peoples R China Beijing Pinggu Hosp, Beijing, Peoples R China Wenzhou Med Univ, Affiliated Hosp 1, Wenzhou, Peoples R China Soochow Univ, Affiliated Hosp 2, Suzhou, Peoples R China Hebei Med Univ, Hosp 3, Shijiazhuang, Hebei, Peoples R China Capital Med Univ, Xuanwu Hosp, Beijing, Peoples R China Jining Med Univ, Affiliated Hosp, Jining, Peoples R China Third Peoples Hosp Huizhou, Huizhou, Peoples R China Second Cangzhou Cent Hosp, Cangzhou, Peoples R China Shanghai Jiao Tong Univ, Hosp Affiliated, Sch Med, Shanghai, Peoples R China Baogang Hosp, Baotou, Peoples R China Harbin Med Univ, Affiliated Hosp 1, Harbin, Heilongjiang, Peoples R China Shanghai Jiao Tong Univ Sch, Tong Ren Hosp, Peoples Hosp Hejian City, Shanghai, Peoples R China Peking Univ, Shougang Hosp, Beijing, Peoples R China Guangzhou Med Univ, Affiliated Hosp 3, Guangzhou, Guangdong, Peoples R China Second Hosp Nanchang, Nanchang, Jiangxi, Peoples R China Bethune Int Peace Hosp, Beijing, Peoples R China Hua Henan Prov Peoples Hosp, Beijing, Peoples R China Hua Henan Prov Peoples Hosp, Zhengzhou, Henan, Peoples R China Shanghai Jiao Tong Univ, Sch Med, Shanghai Ninth Peoples Hosp, Shanghai, Peoples R China Shijiazhuang Cent Hosp, Shijiazhuang, Hebei, Peoples R China Hosp Base San Jos de Osorno, Osorno, Chile Christian Med Coll & Hosp, Ludhiana, Punjab, India Unit Narayana Hrudayalaya Ltd, Mazumdar Shaw Med Ctr, Bangalore, Karnataka, India Dr Ramesh Cardiac & Multispecial Hosp Pvt Ltd, Guntur, India Post Grad Inst Med Educ & Res, Chandigarh, India Baby Mem Hosp Ltd, Calicut, Kerala, India Sree Chitra Tirunal Inst Med Sci & Technol, Thiruvananthapuram, Kerala, India Sri Jayawardenepura Gen Hosp, Sri Jayawardenepura Kott, Sri Lanka Colombo North Teaching Hosp, Colombo, Sri Lanka Colombo South Coching Hosp, Colombo, Sri Lanka Linkou Chang Gung Mem Hosp, Taoyuan, Taiwan Taipei Med Univ, Shuang Ho Hosp, Taipei, Taiwan En Chu Kong Hosp, New Taipei, Taiwan Natl Cheng Kung Univ Hosp, Tainan, Taiwan Queen Alexandra Hosp, Portsmouth, Hants, England Portsmouth Hosp NHS Natl Hlth Serv iTrust, Portsmouth, Hants, England Univ Coll London Hosp NHS Fdn Trust, London, England Univ Hosp Birmingham NHS Fdn Trust, Queen Elizabeth Hosp Birmingham, Birmingham, W Midlands, England Southend Univ Hosp NHS Fdn Trust, Southend On Sea, England Kings Coll Hosp London, London, England York Teaching Hosp NHS Fdn Trust, York, N Yorkshire, England Nottingham Univ Hosp NHS Trust, Nottingham, England Blackpool Teaching Hosp NHS Fdn Trust, Blackpool, England Gloucestershire Hosp NHS Fdn Trust, Gloucestershire Royal Hosp, Gloucester, England Teaching Hospi NHS Fdn Trust, London, England Royal Cornwall Hosp NHS Trust, Truro, England Royal London Hosp, Barts Hlth NHS Trust, London, England Sheffield Teaching Hosp NHS Fdn Trust, Sheffield, S Yorkshire, England Cambridge Univ Hosp NHS Fdn Trust, Addenbrookes Hosp, Cambridge, England Royal Victoria Hosp, Belfast Hlth & Social Care Trust, London, England Pinderfields Gen Hosp, Mid Yorkshire Hosp NHS Trust, Wakefield, England Royal Devon & Exeter NHS Fdn Trust, London, England Bradford Teaching Hosp NHS Fdn Trust, Bradford, W Yorkshire, England Great Western Hosp NHS Fdn Trust, Swindon, Wilts, England Watford Dist Gen Hosp, Watford, England Imperial Coll Healthcare NHS Trust, London, England Medway NHS Fdn Trust, Gillingham, England Royal Liverpool & Broadgreen Univ NHS Trust, Liverpool, Merseyside, England Calderdale & Huddersfield NHS Fdn Trust, Huddersfield, W Yorkshire, England Hywel Dda Univ Hlth Board, Haverfordwest, Wales Chesterfield Royal Hosp NHS Fdn Trust, Calow, England Luton & Dunstable Univ Hosp NHS Fdn Trust, Luton, Beds, England Countess Chester Hosp NHS Fdn Trust, Chester, Cheshire, England Peterborough City Hosp, Peterborough, Cambs, England Univ Hosp Leicester NHS Trust, Leicester Royal Infirm, Leicester, Leics, England Dist Hosp NHS Fdn Trust, London, England Barnsley Hosp NHS Fdn Trust, Barnsley, England Dorset Cty Hosp NHS Fdn Trust, Dorchester, England Royal Bournemouth & Christchurch Hosp NHS Fdn Tru, Royal Bournemouth Hosp, Bournemouth, Dorset, England Southern Hlth & Social Care Trust, Craigavon Area Hosp, Portadown, England United Lincolnshire Hosp NHS Trust, Pilgrim Hosp, Lincoln, England Bedford Hosp NHS Trust, Bedford, England Sao Paulo State Univ, Hosp Fac Med Botucatu, UNESP, Sao Paulo, Brazil National Health and Medical Research Council of Australia: 1066966

Nanomaterials (NMs) have revolutionized multiple aspects of medicine by enabling novel sensing, diagnostic, and therapeutic approaches. Advancements in processing and fabrication have also allowed significant expansion in the applications of the major classes of NMs based on polymer, metal/metal oxide, carbon, liposome, or multi-scale macro-nano bulk materials. Concomitantly, concerns regarding the nanotoxicity and overall biocompatibility of NMs have been raised. These involve putative negative effects on both patients and those subjected to occupational exposure during manufacturing. In this review, we describe the current state of testing of NMs including those that are in clinical use, in clinical trials, or under development. We also discuss the cellular and molecular interactions that dictate their toxicity and biocompatibility. Specifically, we focus on the reciprocal interactions between NMs and host proteins, lipids, and sugars and how these induce responses in immune and other cell types leading to topical and/or systemic effects.

Remdesivir, formerly GS-5734, has recently become the first antiviral drug approved by the U.S. Food and Drug Administration (FDA) to treat COVID-19, the disease caused by SARS-CoV-2. Therapeutic dosing and pharmacokinetic studies require a simple, sensitive, and selective validated assay to quantify drug concentrations in clinical samples. Therefore, we developed a rapid and sensitive LC-MS/MS assay for the quantification of remdesivir in human plasma with its deuterium-labeled analog, remdesivir-2H5, as the internal standard. Chromatographic separation was achieved on a Phenomenex® Synergi™ HPLC Fusion-RP (100 × 2 mm, 4 µm) column by gradient elution. Excellent accuracy and precision (

Sugar-rich diets and poor dental hygiene promote the formation of a biofilm (plaque) that strongly adheres to the dental enamel surface and fosters the evolution of aciduric bacteria. The acid contributes to demineralization of the exterior tooth enamel, which accelerates after the pH drops below a critical value (∼5.5) for extended time periods resulting in the need for restorative procedures. Preventative techniques to alert the dentist and caries-susceptible patients regarding vulnerability to dental decay require a clinical measure of plaque activity. Therefore, there is a need to evaluate the acid production capability of plaque deposits in the pits and fissures of occlusal and interproximal regions. A ratiometric fluorescence pH-sensing device has been developed using an FDA-approved dye and LED excitation. Fluorescein spectral profiles were collected using a spectrometer and analyzed with a spectral unmixing algorithm for calibration over the pH range of 4.5 to 7. An in vivo pilot study on human subjects was performed using a sucrose rinse to accelerate bacterial metabolism and to measure the time-dependent drop in pH. The optical system is relatively immune to confounding factors such as photobleaching, dye concentration, and variation in excitation intensity associated with earlier dye-based pH measurement techniques.