Search

Activities involved in the production of certain advanced therapy medicinal products (ATMPs) require standardized approaches to mononuclear cell procurement to ensure the highest product quality, safety and process efficiency. These aims must be achieved while meeting regulatory and accreditation requirements for the procurement of mononuclear cells as starting materials. Mononuclear cells constitute the starting materials for many ATMPs, and this article sets out recommendations for procurement by clinical apheresis, addressing the variation among existing working practices and different manufacturers' requirements that currently poses a challenge when managing multiple different protocols.

PURPOSECoronavirus-2019 (COVID-19) mortality is higher in patients with cancer than in the general population, yet the cancer-associated risk factors for COVID-19 adverse outcomes are not fully characterized.PATIENTS AND METHODSWe reviewed clinical characteristics and outcomes from patients with cancer and concurrent COVID-19 at Memorial Sloan Kettering Cancer Center until March 31, 2020 (n = 309), and observed clinical end points until April 13, 2020. We hypothesized that cytotoxic chemotherapy administered within 35 days of a COVID-19 diagnosis is associated with an increased hazard ratio (HR) of severe or critical COVID-19. In secondary analyses, we estimated associations between specific clinical and laboratory variables and the incidence of a severe or critical COVID-19 event.RESULTSCytotoxic chemotherapy administration was not significantly associated with a severe or critical COVID-19 event (HR, 1.10; 95% CI, 0.73 to 1.60). Hematologic malignancy was associated with increased COVID-19 severity (HR, 1.90; 95% CI, 1.30 to 2.80). Patients with lung cancer also demonstrated higher rates of severe or critical COVID-19 events (HR, 2.0; 95% CI, 1.20 to 3.30). Lymphopenia at COVID-19 diagnosis was associated with higher rates of severe or critical illness (HR, 2.10; 95% CI, 1.50 to 3.10). Patients with baseline neutropenia 14-90 days before COVID-19 diagnosis had worse outcomes (HR, 4.20; 95% CI, 1.70 to 11.00). Findings from these analyses remained consistent in a multivariable model and in multiple sensitivity analyses. The rate of adverse events was lower in a time-matched population of patients with cancer without COVID-19.CONCLUSIONRecent cytotoxic chemotherapy treatment was not associated with adverse COVID-19 outcomes. Patients with active hematologic or lung malignancies, peri–COVID-19 lymphopenia, or baseline neutropenia had worse COVID-19 outcomes. Interactions among antineoplastic therapy, cancer type, and COVID-19 are complex and warrant further investigation.

Patients with high-grade serous ovarian cancer suffer poor prognosis and variable response to treatment. Known prognostic factors for this disease include homologous recombination deficiency status, age, pathological stage and residual disease status after debulking surgery. Recent work has highlighted important prognostic information captured in computed tomography and histopathological specimens, which can be exploited through machine learning. However, little is known about the capacity of combining features from these disparate sources to improve prediction of treatment response. Here, we assembled a multimodal dataset of 444 patients with primarily late-stage high-grade serous ovarian cancer and discovered quantitative features, such as tumor nuclear size on staining with hematoxylin and eosin and omental texture on contrast-enhanced computed tomography, associated with prognosis. We found that these features contributed complementary prognostic information relative to one another and clinicogenomic features. By fusing histopathological, radiologic and clinicogenomic machine-learning models, we demonstrate a promising path toward improved risk stratification of patients with cancer through multimodal data integration.

Aim OsteoArthritis Hip and Knee Service (OAHKS) clinics involve assessment and triage by advanced musculoskeletal physiotherapists for patients referred to orthopaedic clinics in public hospitals. This study explored the feasibility of implementing an OAHKS clinic in a community setting. Methods The domains of feasibility explored in this mixed methods study were acceptability (patient, general practitioner and orthopaedic surgeon), demand (referrals, waiting times) efficacy potential (management decision, conversion-to-surgery rates) and practicality (number and type of discussions between advanced musculoskeletal physiotherapist and doctors, adverse events). Results from a community-based OAHKS were compared with hospital-based OAHKS over a 9-month period in the same metropolitan health region. Results A total of 91 eligible patients attended an OAHKS clinic (40 community-based, 51 hospital-based). Both the community-based and hospital-based OAHKS had high patient and general practitioner satisfaction, with small differences in favour of community-based OAHKS. Waiting times were significantly shorter in community-based OAHKS for both initial appointment [community-based OAHKS mean 17 days (SD11), hospital-based OAHKS mean 155 days (SD38)] and commencing non-surgical management [community-based OAHKS mean 32 days (SD22), hospital-based OAHKS mean 67 days (SD32)]. Referral rate to orthopaedics was substantially lower from community-based OAHKS (3%) compared with hospital-based OAHKS (33%) [odds ratio 0.05 (95% CI 0.01–0.41)]. There were no adverse events. Conclusion Community-based OAHKS is feasible, and acceptable to patients and general practitioners, with potential benefits indicated in this study including shorter waiting times for assessment and commencing non-surgical management programs.

Managing blood glucose levels for type 1 diabetes patients is an absolute necessity to better glycemic control. In this paper, we present a predictive model that uses physiological measurements and physical activity to predict continuous glucose levels and help patients reduce and prevent hyperglycemia and hypoglycemia exposure, conditions that are harmful to patient health.The data of this research includes 4 months of physiological measurements, physical activity, and nutrition information collected from 93 patients with diabetes using the Medtronic MiniMed™ 530G insulin delivery system with Enlite™ sensor. After data preprocessing, missing value imputation, feature extraction, and feature selection, a set of 180 features were derived to represent the raw data. Then, an appropriate predictive model was developed based on machine-learning algorithms to predict continuous glucose levels. The prediction accuracy and error have been calculated to evaluate the performance of the system. The results demonstrated that the predicted glucose levels closely followed the actual sensor glucose (SG) values measured by subcutaneous glucose sensor.

To explore the perceptions of people with severe knee osteoarthritis and increased cardiovascular risk about participating in a walking program.Qualitative study using semistructured interviews for people with severe knee osteoarthritis and increased cardiovascular risk who participated in a 12-week walking program. Interviews were audiotaped, transcribed verbatim, member-checked, coded and themes developed using thematic analysis. Findings were triangulated with quantitative data including pain, function and cardiovascular risk factors from previously reported data.Twenty-one participants were interviewed after the completion of the walking program. The main theme identified was the preoccupation with the knee including pain, damage and the view that surgery was required. Three subthemes to emerge were (i) the perception of functional, cardiovascular and psychosocial benefits with the walking program; (ii) that supervision, monitoring and commitment were important enablers; and (iii) external factors such as ill-health, weather and the environment were key barriers. The perceived functional and cardiovascular benefits converged with results from quantitative data.Even when patients with severe osteoarthritis of the knee report other benefits from participating in a walking program, the core theme to emerge was their preoccupation with knee pain, knee damage and the view that they needed a knee replacement. Implications for Rehabilitation Patients with severe osteoarthritis of the knee and moderate cardiovascular risk reported functional, cardiovascular and psychosocial benefits from participating in a walking program. Despite patients reporting functional, cardiovascular and psychosocial benefits, the core theme to emerge was their preoccupation with knee pain, knee damage and the view that they needed a knee replacement. The core theme highlights the challenges in promoting physical activity for patients with severe knee osteoarthritis.

Human cancers arise from environmental, heritable, and somatic factors. While each has been studied extensively, how these factors interact to drive tumorigenesis and disease phenotypes is poorly understood. Here, we integrated germline pathogenicity with somatic alterations inferred from the prospective sequencing of 17,152 advanced cancer patients across 55 cancer types to explore their interplay in tumorigenesis. Leveraging expert curated germline variant calls from 5,358 patients, we developed a combined machine learning and risk stratification-based approach for pathogenicity assessment. Overall, 10.3% of patients harbored a pathogenic allele with penetrance levels ranging from high to low, and an additional 6.3% with a variant of uncertain penetrance. Integrating high-precision zygosity inference in the concomitant cancer diagnoses, we found that only carriers of high penetrance germline pathogenic alleles that are biallelically inactivated in their tumors had an earlier age of onset (51y in carriers vs. 58y in germline WT, p-value=3.5e-12), and an elevated rate of multiple independent cancer diagnoses (23% in carriers vs 13% in germline WT, p-value=1.6e-7). Broadly, penetrance dictated somatic dependence, with only those higher penetrant germline pathogenic alleles associated with lineage-dependent selective pressure for somatic biallelic inactivation (p-value Citation Format: Chaitanya Bandlamudi, Preethi Srinivasan, Philip Jonsson, Yelena M. Kemel, Shweta S. Chavan, Allison L. Richards, Alex Penson, Craig M. Bielski, Chris Fong, Aijazuddin Syed, Gowtham Jayakumaran, Meera Prasad, Jason Hwee, Nikolaus Schultz, Semanti Mukherjee, Vijai Joseph, Diana Mandelkar, Ozge Birsoy, Liying Zhang, Jinru Shia, Ahmet Zehir, Marc Ladanyi, David M. Hyman, Kenneth Offit, Mark E. Robson, David B. Solit, Zsofia K. Stadler, Michael F. Berger, Barry S. Taylor. Zygosity, lineage, and penetrance dictate the role of germline pathogenicity in tumorigenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 729.

Background Low back pain is a major clinical and public health problem, with limited evidence-based treatments. Low-dose antidepressants are commonly used to treat pain in chronic low back pain. However, their efficacy is unproven. The aim of this pragmatic, double-blind, randomised, placebo-controlled trial is to determine whether low-dose amitriptyline (an antidepressant) is more effective than placebo in reducing pain in individuals with chronic low back pain. Methods/design One hundred and fifty individuals with chronic low back pain will be recruited through hospital and private medical and allied health clinics, advertising in local media and posting of flyers in community locations. They will be randomly allocated to receive either low-dose amitriptyline (25 mg) or an active placebo (benztropine mesylate, 1 mg) for 6 months. The primary outcome measure of pain intensity will be assessed at baseline, 3 and 6 months using validated questionnaires. Secondary measures of self-reported low back disability, work absence and hindrance in the performance of paid/unpaid work will also be examined. Intention-to-treat analyses will be performed. Discussion This pragmatic, double-blind, randomised, placebo-controlled trial will provide evidence regarding the effectiveness of low-dose antidepressants compared with placebo in reducing pain, disability, work absenteeism and hindrance in work performance in individuals with chronic low back pain. This trial has major public health and clinical importance as it has the potential to provide an effective approach to the management of chronic low back pain. Trial registration Australian New Zealand Clinical Trials Registry: ACTRN12612000131853; registered on 30 January 2012. Electronic supplementary material The online version of this article (doi:10.1186/s13063-016-1637-1) contains supplementary material, which is available to authorized users.

OBJECTIVE: Plasmakinetic vaporesection of the prostate (PKVP) using normal saline irrigation has the theoretical advantage of avoiding transurethral resection syndrome and minimizing blood loss. It may also shorten the operative time since tissue is resected instead of just vaporized. The aim of this study was to evaluate the efficiency, safety and advantages of PKVP compared with standard transurethral resection of the prostate (TURP) at a regional acute hospital. METHODS: A total of 60 consecutive men admitted from a waiting list for surgery for benign prostatic hyperplasia (BPH) were prospectively randomized to either PKVP or TURP. Peri- and postoperative outcome data at 3 months were obtained. RESULTS: The PKVP loop achieved a fast and sharp cutting action similar to that with the traditional TURP loop. Data analysis was based on 51 patients. There were no significant differences between the methods in resection time, postoperative catheterization time and hospital stay. The mean reductions in serum sodium 2 hours after PKVP and on postoperative day 1 were 0.52 mmol/L and 3.35 mmol/L, respectively, while mean reductions in haemoglobin were 0.36 g/dL and 0.24 g/dL, respectively. There was no significant difference in haemoglobin reductions between PKVP and TURP (p = 0.326 at 2 hours; p = 0.192 on day 1) and serum sodium (p = 0.757 at 2 hours; p = 0.888 on day 1). Both groups achieved comparable improvement in International Prostate Symptom Score (p = 0.862), quality-of-life score (p = 0.169) and peak flow rate (p = 0.96) at 3-month follow-up. CONCLUSION: PKVP achieved comparable results to traditional TURP and was an effective and safe procedure. However, it did not demonstrate obvious advantages over TURP in this acute regional hospital regular TURP list setting. [Asian J Surg 2005;28(1):24–8]