An International Comparison of Presentation, Outcomes and CORONET Predictive Score Performance in Patients with Cancer Presenting with COVID-19 across Different Pandemic Waves.

Patients with cancer have been shown to have increased risk of COVID-19 severity. We previously built and validated the COVID-19 Risk in Oncology Evaluation Tool (CORONET) to predict the likely severity of COVID-19 in patients with active cancer who present to hospital. We assessed the differences in presentation and outcomes of patients with cancer and COVID-19, depending on the wave of the pandemic. We examined differences in features at presentation and outcomes in patients worldwide, depending on the waves of the pandemic: wave 1 D614G (n = 1430), wave 2 Alpha (n = 475), and wave 4 Omicron variant (n = 63, UK and Spain only). The performance of CORONET was evaluated on 258, 48, and 54 patients for each wave, respectively. We found that mortality rates were reduced in subsequent waves. The majority of patients were vaccinated in wave 4, and 94% were treated with steroids if they required oxygen. The stages of cancer and the median ages of patients significantly differed, but features associated with worse COVID-19 outcomes remained predictive and did not differ between waves. The CORONET tool performed well in all waves, with scores in an area under the curve (AUC) of >0.72. We concluded that patients with cancer who present to hospital with COVID-19 have similar features of severity, which remain discriminatory despite differences in variants and vaccination status. Survival improved following the first wave of the pandemic, which may be associated with vaccination and the increased steroid use in those patients requiring oxygen. The CORONET model demonstrated good performance, independent of the SARS-CoV-2 variants.

Establishment of CORONET, COVID-19 Risk in Oncology Evaluation Tool, to Identify Patients With Cancer at Low Versus High Risk of Severe Complications of COVID-19 Disease On Presentation to Hospital.

PURPOSE: Patients with cancer are at increased risk of severe COVID-19 disease, but have heterogeneous presentations and outcomes. Decision-making tools for hospital admission, severity prediction, and increased monitoring for early intervention are critical. We sought to identify features of COVID-19 disease in patients with cancer predicting severe disease and build a decision support online tool, COVID-19 Risk in Oncology Evaluation Tool (CORONET). METHODS: Patients with active cancer (stage I-IV) and laboratory-confirmed COVID-19 disease presenting to hospitals worldwide were included. Discharge (within 24 hours), admission (≥ 24 hours inpatient), oxygen (O2) requirement, and death were combined in a 0-3 point severity scale. Association of features with outcomes were investigated using Lasso regression and Random Forest combined with Shapley Additive Explanations. The CORONET model was then examined in the entire cohort to build an online CORONET decision support tool. Admission and severe disease thresholds were established through pragmatically defined cost functions. Finally, the CORONET model was validated on an external cohort. RESULTS: The model development data set comprised 920 patients, with median age 70 (range 5-99) years, 56% males, 44% females, and 81% solid versus 19% hematologic cancers. In derivation, Random Forest demonstrated superior performance over Lasso with lower mean squared error (0.801 v 0.807) and was selected for development. During validation (n = 282 patients), the performance of CORONET varied depending on the country cohort. CORONET cutoffs for admission and mortality of 1.0 and 2.3 were established. The CORONET decision support tool recommended admission for 95% of patients eventually requiring oxygen and 97% of those who died (94% and 98% in validation, respectively). The specificity for mortality prediction was 92% and 83% in derivation and validation, respectively. Shapley Additive Explanations revealed that National Early Warning Score 2, C-reactive protein, and albumin were the most important features contributing to COVID-19 severity prediction in patients with cancer at time of hospital presentation. CONCLUSION: CORONET, a decision support tool validated in health care systems worldwide, can aid admission decisions and predict COVID-19 severity in patients with cancer.

Assessing the tolerability and efficacy of first-line chemotherapy in elderly patients with metastatic HER2-ve breast cancer.

BACKGROUND: In metastatic breast cancer (MBC), there is no consensus regarding the optimal regimen sequence and whether adults >65 years old (OA) are at increased risk from chemotherapy toxicity. Treatment decisions are often driven by the ability to tolerate treatment and maintain the quality of life. This study was designed to assess current practice in an oncology hospital in the UK. METHODS: Retrospective data were collected about treatments used for 87 OA with MBC in a single centre between 2009 and 2016 to assess the tolerability and efficacy of first-line chemotherapy. Student's T-tests and Kaplan-Meier statistical methods were applied. RESULTS: 70% of patients were commenced on standard dose (SD) of chemotherapy; 84% (21/25) of the anthracycline group (AG), 65% (20/31) of the capecitabine group (CG), 48% (10/21) of the taxane group (TG) and 100% (10/10) of other agents. 32% of patients had dose reductions; 16% in AG, 19% in TG and 58% in CG. Overall 30% of patients received six cycles of SD of chemotherapy; 36% in AG, 29% in CG and 14% in TG. 23% of patients suffered ≥grade 3 toxicity; 28% in AG, 29% in CG and 10% in TG. There were four treatment-related deaths; two in AG and one in both CG and TG. 61% of the CG received 6+ cycles with a mean on treatment time of 445 days (1-2,150). There was no statistical significance in progression- free survival (PFS) between groups. The median PFS for all patients was 244 days (87-381). Performance status, haemoglobin and estimated glomerular filtration rates prior to starting chemotherapy were all useful in predicting PFS. CONCLUSIONS: A relevant number of patients required dose reduction but dose-reduced chemotherapy was tolerated well. Anthracycline-based regimens were used in patients who had not received adjuvant chemotherapy. Capecitabine required the most dose reductions. Taxanes were generally started at reduced doses, resulting in fewer grade 3+ toxicities. As well as age, underlying physiological reserve, current performance status and co-morbidities should guide physicians who should consider lower starting doses in OA and recognise that dose reductions may be required to improve tolerability. The PFS of all regimens were similar in this study. This study highlights the need for further research to define the optimal first-line chemotherapy and starting dose in OA with MBC.

Sorting Through the Safety Data Haystack: Using Machine Learning to Identify Individual Case Safety Reports in Social-Digital Media.

INTRODUCTION: There is increasing interest in social digital media (SDM) as a data source for pharmacovigilance activities; however, SDM is considered a low information content data source for safety data. Given that pharmacovigilance itself operates in a high-noise, lower-validity environment without objective 'gold standards' beyond process definitions, the introduction of large volumes of SDM into the pharmacovigilance workflow has the potential to exacerbate issues with limited manual resources to perform adverse event identification and processing. Recent advances in medical informatics have resulted in methods for developing programs which can assist human experts in the detection of valid individual case safety reports (ICSRs) within SDM. OBJECTIVE: In this study, we developed rule-based and machine learning (ML) models for classifying ICSRs from SDM and compared their performance with that of human pharmacovigilance experts. METHODS: We used a random sampling from a collection of 311,189 SDM posts that mentioned Roche products and brands in combination with common medical and scientific terms sourced from Twitter, Tumblr, Facebook, and a spectrum of news media blogs to develop and evaluate three iterations of an automated ICSR classifier. The ICSR classifier models consisted of sub-components to annotate the relevant ICSR elements and a component to make the final decision on the validity of the ICSR. Agreement with human pharmacovigilance experts was chosen as the preferred performance metric and was evaluated by calculating the Gwet AC1 statistic (gKappa). The best performing model was tested against the Roche global pharmacovigilance expert using a blind dataset and put through a time test of the full 311,189-post dataset. RESULTS: During this effort, the initial strict rule-based approach to ICSR classification resulted in a model with an accuracy of 65% and a gKappa of 46%. Adding an ML-based adverse event annotator improved the accuracy to 74% and gKappa to 60%. This was further improved by the addition of an additional ML ICSR detector. On a blind test set of 2500 posts, the final model demonstrated a gKappa of 78% and an accuracy of 83%. In the time test, it took the final model 48 h to complete a task that would have taken an estimated 44,000 h for human experts to perform. CONCLUSION: The results of this study indicate that an effective and scalable solution to the challenge of ICSR detection in SDM includes a workflow using an automated ML classifier to identify likely ICSRs for further human SME review.

Does leg predomination affect measuring vasti muscle onsets during single leg squatting? A reliability study.

INTRODUCTION: Although measuring vasti muscle onset may reveal whether pain relief is associated with altering this parameter during activities in subjects with patellofemoral pain syndrome (PFPS), it may be necessary to determine whether the inherent properties of the dominant leg influences the reliability of measuring VMO-VL muscle onset. The aim of the present study was to examine the effect of leg predomination on reliability testing of the VMO-VL muscle onset measurement during single leg squatting in healthy subjects. METHODS: The onset of VMO and VL muscles of ten healthy subjects with a right dominant leg was assessed during single leg squatting. Data was collected from the muscle bellies of the VMO and VL. This procedure was performed on the both legs, during three separate single leg squats from a neutral position to a depth of approximately 30° of knee flexion. Subjects were then asked to repeat the test procedure after a minimum of a week's interval. The full wave rectified onsets of VMO and VL were then calculated. RESULTS: There was no significant difference between the VMO-VL onset mean values of paired test of right and left knees. The ICC (intra class correlation coefficient) values during within and between sessions tests showed the poor reliability of these measurements on both knees. CONCLUSION: The low intratester reliability of within and between sessions measurement of VMO-VL onset on the both dominant and non-dominant legs revealed that repeatability of these measurements have little accepted reliability, however similar values of these measurements indicated that leg predomination does not affect the measurements during single leg squatting.

Brain imaging before primary lung cancer resection: a controversial topic.

OBJECTIVE: International and national recommendations for brain imaging in patients planned to undergo potentially curative resection of non-small-cell lung cancer (NSCLC) are variably implemented throughout the United Kingdom [Hudson BJ, Crawford MB, and Curtin J et al (2015) Brain imaging in lung cancer patients without symptoms of brain metastases: a national survey of current practice in EnglandClin Radiol https://doi.org/10.1016/j.crad.2015.02.007]. However, the recommendations are not based on high-quality evidence and do not take into account cost implications and local resources. Our aim was to determine local practice based on historic outcomes in this patient cohort. METHODS: This retrospective study took place in a regional thoracic surgical centre in the United Kingdom. Pathology records for all patients who had undergone lung resection with curative intent during the time period January 2012-December 2014 were analysed in October 2015. Electronic pathology and radiology reports were accessed for each patient and data collected about their histological findings, TNM stage, resection margins, and the presence of brain metastases on either pre-operative or post-operative imaging. From the dates given on imaging, we calculated the number of days post-resection that the brain metastases were detected. RESULTS: 585 patients were identified who had undergone resection of their lung cancer. Of these, 471 had accessible electronic radiology records to assess for the radiological evidence of brain metastases. When their electronic records were evaluated, 25/471 (5.3%) patients had radiological evidence of brain metastasis. Of these, five patients had been diagnosed with a brain metastasis at initial presentation and had undergone primary resection of the brain metastasis followed by resection of the lung primary. One patient had been diagnosed with both a primary lung and a primary bowel adenocarcinoma; on review of the case, it was felt that the brain metastasis was more likely to have originated from the bowel cancer. One had been clinically diagnosed with a cerebral abscess while the radiology had been reported as showing a metastatic deposit. Of the remaining 18/471 (3.8%) patients who presented with brain metastases after their surgical resection, 12 patients had adenocarcinoma, four patients had squamous cell carcinoma, one had basaloid, and one had large-cell neuroendocrine. The mean number of days post-resection that the brain metastases were identified was 371 days, range 14-1032 days, median 295 days (date of metastases not available for two patients). CONCLUSION: The rate of brain metastases identified in this study was similar to previous studies. This would suggest that preoperative staging of the central nervous system may change the management pathway in a small group of patients. However, for this group of patients, the change would be significant either sparing them non-curative surgery or allowing aggressive management of oligometastatic disease. Therefore, we would recommend pre-operative brain imaging with MRI for all patients undergoing potentially curative lung resection.

Does leg predomination affect the measurement of vasti muscle activity during single leg squatting? A reliability study.

INTRODUCTION: Although measuring vasti muscle activity may reveal whether pain relief is associated with altering this parameter during functional activities in subjects with patellofemoral pain syndrome (PFPS), it may be necessary to determine whether the inherent properties of the dominant leg influences the reliability of measuring VMO/VL amplitude. The aim of the present study was to examine the effect of leg predomination on reliability testing of the VMO/VL amplitude measurement during single leg squatting in healthy subjects. METHODS: Using an electromyography (EMG) unit, the ratio amplitudes of VMO and VL muscles of ten healthy subjects with a right dominant leg was assessed during single leg squatting. Data was collected from two silver-silver surface electrodes placed over the muscle bellies of the VMO and VL. This procedure was performed on the both right and left legs, during three separate single leg squats from a neutral position to a depth of approximately 30° of knee flexion. Subjects were then asked to repeat the test procedure after a minimum of a week's interval. The amplitude of VMO and VL were then calculated using root mean square (RMS). RESULTS: There was no significant difference between the VMO/VL amplitude mean values of paired test of right (mean, SD of 0.85, 0.10) and left knees (mean, SD of 0.82, 0.10) (p > 0.05). The CV (coefficient of variation) values during within and between session tests, revealed the high repeatability and reproducibility of VMO/VL amplitude measurements on both knees. The ICC (intra class correlation coefficient) values during within and between sessions tests showed the high reliability of these measurements on both knees. CONCLUSION: The high reliability of VMO/VL amplitude measurements on both dominant and non-dominant legs of healthy subjects suggests that the VMO/VL amplitude measurement would not be influenced by the leg predomination during single leg squatting.

Reliability testing of vasti activity measurements in taped and untaped patellofemoral conditions during single leg squatting in healthy subjects: a pilot study.

INTRODUCTION: Measuring vasti muscles activity may provide reliable evidence for patellar taping to correct probable malalignment in subjects with patellofemoral pain syndrome (PFPS). The aim of present study was to examine the reliability of vasti activity measurements in different patellofemoral conditions during squatting in healthy subjects. METHODS: Using an electromyography (EMG) unit, the ratio amplitudes and onsets of VMO and VL muscles of twelve healthy subjects were assessed during single leg squatting. Data was collected from surface electrodes placed over the muscle bellies of the VMO and VL. This procedure was performed on the right knees, before (BT), during (WT) and shortly after patellar taping (SAT). RESULTS: While the CV (coefficient of variation), ICC (intra class correlation coefficient), LSD (least significant difference) and SEM (standard error of measurement) values revealed the high reliability of the VMO/VL amplitude measurements during single leg squatting (p < 0.05), the related values demonstrated poor to moderate reliability of VMO-VL onset measurements during the similar activity (p > 0.05). CONCLUSION: Reliability tests conducted during the current study showed that, while the relative amplitude of vasti could be used as highly reliable parameter, the muscle onsets of vasti had poor to moderate reliability.

Human viruses: discovery and emergence.

There are 219 virus species that are known to be able to infect humans. The first of these to be discovered was yellow fever virus in 1901, and three to four new species are still being found every year. Extrapolation of the discovery curve suggests that there is still a substantial pool of undiscovered human virus species, although an apparent slow-down in the rate of discovery of species from different families may indicate bounds to the potential range of diversity. More than two-thirds of human viruses can also infect non-human hosts, mainly mammals, and sometimes birds. Many specialist human viruses also have mammalian or avian origins. Indeed, a substantial proportion of mammalian viruses may be capable of crossing the species barrier into humans, although only around half of these are capable of being transmitted by humans and around half again of transmitting well enough to cause major outbreaks. A few possible predictors of species jumps can be identified, including the use of phylogenetically conserved cell receptors. It seems almost inevitable that new human viruses will continue to emerge, mainly from other mammals and birds, for the foreseeable future. For this reason, an effective global surveillance system for novel viruses is needed.

Current practices in determining return to play following head injury in professional football in the UK.

OBJECTIVE: To investigate the awareness of English football team doctors of the 'Consensus in Sport' (CIS) guidelines for the assessment and management of concussion, and to identify adherence to these internationally accepted recommendations. METHOD: A questionnaire was sent to Club Medical Officers of all the 92 English Football league teams. RESULTS: The majority (55.6%) of teams in the English Football Association (FA) do not routinely follow the CIS guidelines. Only 21% of teams routinely record an approved preseason cognitive score and only 42% complete a recommended postconcussion assessment. One-third are still using outdated fixed periods of abstinence following a concussion. CONCLUSIONS: FA players are not being treated according to the guidelines recommended by International sporting organisations. The endorsement of the CIS guidelines by the English FA would ensure that all medical teams have a sound and safe protocol for managing concussed players and making return to play decisions.

Does leg predomination affect the measurement of patellofemoral joint reaction force (PFJRF) during single leg squatting?: a reliability study.

INTRODUCTION: Although measuring patellofemoral joint reaction forces (PFJRF) may provide reliable evidence for conservative treatments to correct probable malalignment in subjects with patellofemoral pain syndrome (PFPS), it may be necessary to determine whether the inherent properties of the dominant leg influences the reliability of measuring PFJRF. The aim of the present study was to examine the effect of leg predomination on reliability testing of the PFJRF measurement during single leg squatting in healthy subjects. METHODS: Using a motion analysis system and one force plate, PFJRF of 10 healthy subjects with a right dominant leg was assessed during single leg squatting. Data was collected from superficial markers taped to selected landmarks. This procedure was performed on the both right and left legs, during three separate single leg squats from a neutral position to a depth of approximately 30° of knee flexion. Subjects were then asked to repeat the test procedure after a minimum of a week's interval. The PFJRF was calculated using a biomechanical model of the patellofemoral joint. RESULTS: There was significant difference between the PFJRF mean values of paired test of right (mean, SD of 1887.7, 325.1 N) and left knees (mean, SD of 2022.6, 270.5 N) (p < 0.05). The CV (coefficient of variation) values during within and between session tests, revealed the high repeatability and reproducibility of PFJRF measurements on both knees. The ICC (intra class correlation coefficient) values during within and between sessions tests showed the high reliability of these measurements on both knees. CONCLUSION: The high reliability of PFJRF measurements on both dominant and non-dominant legs of healthy subjects suggests that the PFJRF measurement would not be influenced by the leg predomination during single leg squatting.

Reliability testing of the patellofemoral joint reaction force (PFJRF) measurement during double-legged squatting in healthy subjects: a pilot study.

INTRODUCTION: Anterior knee pain or patellofemoral pain syndrome (PFPS) is supposed to be related to patellofemoral joint reaction forces (PFJRF). Measuring these forces may therefore provide reliable evidence for conservative treatments to correct probable malalignment in subjects with PFPS. The aim of the present study was to examine the reliability of PFJRF measurements during double-legged squatting in healthy subjects. METHODS: Using a motion analysis system and one forceplate, PFJRF of 10 healthy subjects were assessed during double-legged squatting. Data were collected from superficial markers taped to selected landmarks. This procedure was performed on the right knees, at three different knee flexion angles of 30, 45 and 60° during three separate double-legged squats. Subjects were then requested to repeat this test procedure on two separate test sessions at different occasions. The PFJRF was calculated using a biomechanical model of the patellofemoral joint. RESULTS: The data reveal an increase in PFJRF values (from mean, SD of 425.2, 35.5N to 1075.4, 70.1N)with an increase in the tibiofemoral joint angle during double-legged squatting. The CV (coefficient of variation) values during within and between session tests, revealed the high repeatability and reproducibility of PFJRF measurements, while the ICC (intra class correlation coefficient) values showed the low reliability of these measurements. CONCLUSION: The low reliability of PFJRF measurements suggests that the PFJRF measurement during double-legged squatting should be performed with caution with improving the method of kinetic measurement of the patellofemoral joint in healthy subjects.

Reliability testing of the patellofemoral joint reaction force (PFJRF) measurement in taped and untaped patellofemoral conditions during single leg squatting: a pilot study.

INTRODUCTION: Measuring patellofemoral joint reaction forces (PFJRF) may provide reliable evidence for patellar taping to correct probable malalignment in subjects with anterior knee pain, or patellofemoral pain syndrome (PFPS). The aim of the present study was to examine the reliability of PFJRF measurements in different patellofemoral conditions during squatting in healthy subjects. METHODS: Using a motion analysis system and one forceplate, PFJRF of eight healthy subjects was assessed during single leg squatting. Data was collected from superficial markers taped to selected landmarks. This procedure was performed on the right knees, before (BT), during (WT) and shortly after patellar taping (SAT). The PFJRF was calculated using a biomechanical model of the patellofemoral joint. RESULTS: The results revealed that, there were no significant differences between the PFJRF mean values for three conditions of BT (2100.55 ± 455.25), WT (2026.20 ± 516.45) and SAT (2055.35 ± 669.30) (p > 0.05). The CV (coefficient of variation), ICC (intra class correlation coefficient), LSD (least significant difference) and SEM (standard error of measurement) values revealed the high reliability of PFJRF measurements during single leg squatting (p < 0.05). CONCLUSION: The high reliability of PFJRF measurements reveals that the future studies could rely on these measurements during single leg squatting.