Robleshull2235

Despite the extensive use of the combination of cytotoxic chemotherapy and programmed cell death protein 1/programmed death-ligand 1 checkpoint inhibitors for cancer treatment, the incidence and characteristics of pneumonitis caused by this combination therapy have not been examined in clinical settings.

We conducted a 36-centre, retrospective cohort study in patients with chemo-naïve advanced non-squamous non-small cell lung cancer who received a combination of platinum, pemetrexed and pembrolizumab between December 2018 and June 2019.

The study comprised 299 patients. The most frequent grade ≥3 non-hematologic adverse event was pneumonitis. There were 37 patients (12.4%, 95% CI 8.9-16.7) with all-grade pneumonitis and 10 (3.3%, 95% CI 1.6-6.1) with grade ≥3 pneumonitis. Of these, 21 (7.0%, 95% CI 4.4-10.5) and 9 patients (3.0%, 95% CI 1.4-5.6) developed all-grade and grade ≥3 pneumonitis within 90 days after initiating the combination therapy, respectively. The median time to treatment failure and progression-free survival was 5.9 (95% CI 5.0-6.8) and 7.5 (95% CI 6.5-8.7) months, respectively. In the survival analysis after adjusting for immortal time bias, pneumonitis was independently associated with shorter progression-free survival (HR 1.99, 95% CI 1.07-3.69, P=0.03) and overall survival (HR 3.03, 95% CI 1.12-8.20, P=0.03).

Treatment-related pneumonitis occurred at a higher rate in the real-world population than that reported previously; it led to worse survival outcomes. Pneumonitis requires more attention. Additional studies are required to improve the safety of this combination therapy.

UMIN000038084.

UMIN000038084.

AcSé-ESMART is a European multicentre, proof-of-concept multiarm phase I/II platform trial in paediatric patients with relapsed/refractory cancer. Arm G assessed the activity and safety of nivolumab in combination with metronomic cyclophosphamide +/- irradiation.

Following a Phase II Simon two-stage design, nivolumab was administered intravenously at 3mg/kg every 2 weeks of a 28-day cycle, oral cyclophosphamide at 25mg/m

twice a day, 1 week on/1 week off. The primary endpoint was objective response rate. Irradiation/radioablation of primary tumour or metastasis could be administered as per physician's choice. Biomarker evaluation was performed by tumour immunohistochemistry, whole exome and RNA sequencing, and immunophenotyping of peripheral blood by flow cytometry.

Thirteen patients were treated with a median age of 15 years (range 5.5-19.4). The main histologies were high-grade glioma, neuroblastoma, and desmoplastic small round cell tumour (DSRCT). The safety profile was similar to those of single-agent nivolumab, albeit haematologic toxicity, mainly lymphocytopenia, was commonly reported with the addition of cyclophosphamide +/- irradiation. Two patients with DSRCT and ependymoma presented unconfirmed partial response and prolonged disease stabilisation. Low mutational load with modest intratumour CD3+ T-cell infiltration and immunosuppressive tumour microenvironment were observed in the tumour samples. Under combined treatment, no positive modulation of circulating T cells was displayed, while derived neutrophil-to-lymphocyte ratio increased.

Nivolumab in combination with cyclophosphamide was well tolerated but had limited activity in this paediatric setting. Metronomic cyclophosphamide did not modulate systemic immune response that could compensate limited T-cell infiltration and the immunosuppressive tumour microenvironment. CLINICALTRIALS.

NCT2813135.

NCT2813135.

Cancer disease burden is commonly assessed radiologically in solid tumours in support of response assessment via the RECIST criteria. These longitudinal data are amenable to mathematical modelling and these models characterise the initial tumour size, initial tumour shrinkage in responding patients and rate of regrowth as patient's disease progresses. Knowing how these parameters vary between patient populations and treatments would inform translational modelling approaches from non-clinical data as well as clinical trial design.

Here a meta-analysis of reported model parameter values is reported. Appropriate literature was identified via a PubMed search and the application of text-based clustering approaches. The resulting parameter estimates are examined graphically and with ANOVA.

Parameter values from a total of 80 treatment arms were identified based on 80 trial arms containing a total of 34,881 patients. Parameter estimates are generally consistent. It is found that a significant proportion of the variation in rates of tumour shrinkage and regrowth are explained by differing cancer and treatment cancer type accounts for 66% of the variation in shrinkage rate and 71% of the variation in reported regrowth rates. Mean average parameter values by cancer and treatment are also reported.

Mathematical modelling of longitudinal data is most often reported on a per clinical trial basis. However, the results reported here suggest that a more integrative approach would benefit the development of new treatments as well as the further optimisation of those currently used.

Mathematical modelling of longitudinal data is most often reported on a per clinical trial basis. However, the results reported here suggest that a more integrative approach would benefit the development of new treatments as well as the further optimisation of those currently used.

Hypertension has become a major public health issue as the prevalence and risk of premature death and disability among adults due to hypertension has increased globally. The main objective is to characterize the risk factors of hypertension among adults in Bangladesh using machine learning (ML) algorithms.

The hypertension data was derived from Bangladesh demographic and health survey, 2017-18, which included 6965 people aged 35 and above. Two most promising risk factor identification methods, namely least absolute shrinkage operator (LASSO) and support vector machine recursive feature elimination (SVMRFE) are implemented to detect the critical risk factors of hypertension. Additionally, four well-known ML algorithms as artificial neural network, decision tree, random forest, and gradient boosting (GB) have been used to predict hypertension. Performance scores of these algorithms were evaluated by accuracy, precision, recall, F-measure, and area under the curve (AUC).

The results clarify that age, BMI, wealth index, working status, and marital status for LASSO and age, BMI, marital status, diabetes and region for SVMRFE appear to be the top-most five significant risk factors for hypertension. Our findings reveal that the combination of SVMRFE-GB gives the maximum accuracy (66.98%), recall (97.92%), F-measure (78.99%), and AUC (0.669) compared to others.

GB-based algorithm confirms the best performer for prediction of hypertension, at an early stage in Bangladesh. Therefore, this study highly suggests that the policymakers make proper judgments for controlling hypertension using SVMRFE-GB-based combination to save time and reduce cost for Bangladeshi adults.

GB-based algorithm confirms the best performer for prediction of hypertension, at an early stage in Bangladesh. Therefore, this study highly suggests that the policymakers make proper judgments for controlling hypertension using SVMRFE-GB-based combination to save time and reduce cost for Bangladeshi adults.

Long COVID is the collective term to denote persistence of symptoms in those who have recovered from SARS-CoV-2 infection.

WE searched the pubmed and scopus databases for original articles and reviews. Based on the search result, in this review article we are analyzing various aspects of Long COVID.

Fatigue, cough, chest tightness, breathlessness, palpitations, myalgia and difficulty to focus are symptoms reported in long COVID. It could be related to organ damage, post viral syndrome, post-critical care syndrome and others. Clinical evaluation should focus on identifying the pathophysiology, followed by appropriate remedial measures. In people with symptoms suggestive of long COVID but without known history of previous SARS-CoV-2 infection, serology may help confirm the diagnosis.

This review will helps the clinicians to manage various aspects of Long COVID.

This review will helps the clinicians to manage various aspects of Long COVID.

Despite the trend of rising Emergency Department (ED) visits over the past decade, researchers have observed drastic declines in number of ED visits due to the COVID-19 pandemic. The purpose of the current study was to examine the impact of the COVID-19 pandemic and governor mandated Stay at Home Order on ED super utilizers.

This was a retrospective chart review of patients presenting to the 12 emergency departments of the Franciscan Mission of Our Lady Hospital System in Louisiana between January 1, 2018 and December 31, 2020. Patients who were 18 years of age or older and had four ED visits within a one-year period (2018, 2019, or 2020) were classified as super-utilizers. We examined number and category of visits for the baseline period (January 2018 - March 2020), the governor's Stay at Home Order, and the subsequent Reopening Phases through December 31, 2020.

The number of visits by super utilizers decreased by over 16% when the Stay at Home Order was issued. The average number of visits per week rote ED use.

Significant declines in emergent visits raise concerns that individuals who needed ED treatment did not seek it due to COVID-19. However, the finding that super utilizers with non-emergent visits continued to visit the ED less after the Stay at Home Order was lifted raises questions for future research that may inform policy and interventions for inappropriate ED use.It is known that coordination between joint movements is crucial for the achievement of motor tasks and has been studied extensively. Especially, in sports biomechanics, researchers are interested in determining which joint movements are coordinated to achieve a motor task. However, this issue cannot be easily addressed with the methods employed in previous studies. V-9302 molecular weight Therefore, we aimed to propose a method for identifying joint coordination. Subsequently, we examined which joint movements were coordinated using accurate overhead throwing, which required reduction in vertical hand velocity variability. Fourteen baseball players participated by attempting throwing using a motion capture system. The index of coordination for each joint movement and the effect of deviation of one joint movement on vertical hand velocity were quantified. Our results showed that the shoulder internal/external rotation angle (θ1-IE) and the other joint movements or the shoulder horizontal flexion/extension angular velocity (ω1-FE) and the other joint movements were coordinated. These results could be explained by the fact that the effects of the deviation of the shoulder internal rotation angle (θ1-I) and shoulder horizontal flexion angular velocity (ω1-F) on vertical hand velocity were larger than those of the other joint movements. This meant that it was necessary to cancel the deviations of θ1-IE and ω1-FE by the other joint movements. These findings indicate that the method proposed in this study enables the identification of which joint movements are coordinated in multiple degrees of freedom.