scholarly journals Predictive modeling of therapeutic response to chondroitin sulfate/glucosamine hydrochloride in knee osteoarthritis

2019 ◽  
Vol 10 ◽  
pp. 204062231987001 ◽  
Author(s):  
Francisco J. Blanco ◽  
María Camacho-Encina ◽  
Lucía González-Rodríguez ◽  
Ignacio Rego-Pérez ◽  
Jesús Mateos ◽  
...  

Background: In the present study, we explored potential protein biomarkers useful to predict the therapeutic response of knee osteoarthritis (KOA) patients treated with pharmaceutical grade Chondroitin sulfate/Glucosamine hydrochloride (CS+GH; Droglican, Bioiberica), in order to optimize therapeutic outcomes. Methods: A shotgun proteomic analysis by iTRAQ labelling and liquid chromatography–mass spectrometry (LC-MS/MS) was performed using sera from 40 patients enrolled in the Multicentre Osteoarthritis interVEntion trial with Sysadoa (MOVES). The panel of proteins potentially useful to predict KOA patient’s response was clinically validated in the whole MOVES cohort at baseline ( n = 506) using commercially available enzyme-linked immunosorbent assays kits. Logistic regression models and receiver-operating-characteristics (ROC) curves were used to analyze the contribution of these proteins to our prediction models of symptomatic drug response in KOA. Results: In the discovery phase of the study, a panel of six putative predictive biomarkers of response to CS+GH (APOA2, APOA4, APOH, ITIH1, C4BPa and ORM2) were identified by shotgun proteomics. Data are available via ProteomeXchange with identifier PXD012444. In the verification phase, the panel was verified in a larger set of KOA patients ( n = 262). Finally, ITIH1 and ORM2 were qualified by a blind test in the whole MOVES cohort at baseline. The combination of these biomarkers with clinical variables predict the patients’ response to CS+GH with a specificity of 79.5% and a sensitivity of 77.1%. Conclusions: Combining clinical and analytical parameters, we identified one biomarker that could accurately predict KOA patients’ response to CS+GH treatment. Its use would allow an increase in response rates and safety for the patients suffering KOA.

BMJ Open ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. e044500
Author(s):  
Yauhen Statsenko ◽  
Fatmah Al Zahmi ◽  
Tetiana Habuza ◽  
Klaus Neidl-Van Gorkom ◽  
Nazar Zaki

BackgroundDespite the necessity, there is no reliable biomarker to predict disease severity and prognosis of patients with COVID-19. The currently published prediction models are not fully applicable to clinical use.ObjectivesTo identify predictive biomarkers of COVID-19 severity and to justify their threshold values for the stratification of the risk of deterioration that would require transferring to the intensive care unit (ICU).MethodsThe study cohort (560 subjects) included all consecutive patients admitted to Dubai Mediclinic Parkview Hospital from February to May 2020 with COVID-19 confirmed by the PCR. The challenge of finding the cut-off thresholds was the unbalanced dataset (eg, the disproportion in the number of 72 patients admitted to ICU vs 488 non-severe cases). Therefore, we customised supervised machine learning (ML) algorithm in terms of threshold value used to predict worsening.ResultsWith the default thresholds returned by the ML estimator, the performance of the models was low. It was improved by setting the cut-off level to the 25th percentile for lymphocyte count and the 75th percentile for other features. The study justified the following threshold values of the laboratory tests done on admission: lymphocyte count <2.59×109/L, and the upper levels for total bilirubin 11.9 μmol/L, alanine aminotransferase 43 U/L, aspartate aminotransferase 32 U/L, D-dimer 0.7 mg/L, activated partial thromboplastin time (aPTT) 39.9 s, creatine kinase 247 U/L, C reactive protein (CRP) 14.3 mg/L, lactate dehydrogenase 246 U/L, troponin 0.037 ng/mL, ferritin 498 ng/mL and fibrinogen 446 mg/dL.ConclusionThe performance of the neural network trained with top valuable tests (aPTT, CRP and fibrinogen) is admissible (area under the curve (AUC) 0.86; 95% CI 0.486 to 0.884; p<0.001) and comparable with the model trained with all the tests (AUC 0.90; 95% CI 0.812 to 0.902; p<0.001). Free online tool at https://med-predict.com illustrates the study results.


2017 ◽  
Vol 46 (5) ◽  
pp. 390-396 ◽  
Author(s):  
Rakesh Malhotra ◽  
Xia Tao ◽  
Yuedong Wang ◽  
Yuqi Chen ◽  
Rebecca H. Apruzzese ◽  
...  

Background: The surprise question (SQ) (“Would you be surprised if this patient were still alive in 6 or 12 months?”) is used as a mortality prognostication tool in hemodialysis (HD) patients. We compared the performance of the SQ with that of prediction models (PMs) for 6- and 12-month mortality prediction. Methods: Demographic, clinical, laboratory, and dialysis treatment indicators were used to model 6- and 12-month mortality probability in a HD patients training cohort (n = 6,633) using generalized linear models (GLMs). A total of 10 nephrologists from 5 HD clinics responded to the SQ in 215 patients followed prospectively for 12 months. The performance of PM was evaluated in the validation (n = 6,634) and SQ cohorts (n = 215) using the areas under receiver operating characteristics curves. We compared sensitivities and specificities of PM and SQ. Results: The PM and SQ cohorts comprised 13,267 (mean age 61 years, 55% men, 54% whites) and 215 (mean age 62 years, 59% men, 50% whites) patients, respectively. During the 12-month follow-up, 1,313 patients died in the prediction model cohort and 22 in the SQ cohort. For 6-month mortality prediction, the GLM had areas under the curve of 0.77 in the validation cohort and 0.77 in the SQ cohort. As for 12-month mortality, areas under the curve were 0.77 and 0.80 in the validation and SQ cohorts, respectively. The 6- and 12-month PMs had sensitivities of 0.62 (95% CI 0.35–0.88) and 0.75 (95% CI 0.56–0.94), respectively. The 6- and 12-month SQ sensitivities were 0.23 (95% CI 0.002–0.46) and 0.35 (95% CI 0.14–0.56), respectively. Conclusion: PMs exhibit superior sensitivity compared to the SQ for mortality prognostication in HD patients.


2018 ◽  
Vol 48 (11-12) ◽  
pp. 1213-1231 ◽  
Author(s):  
Toer W. Stevens ◽  
Mijntje Matheeuwsen ◽  
Maria H. Lönnkvist ◽  
Claire E. Parker ◽  
Manon E. Wildenberg ◽  
...  

1998 ◽  
Vol 6 ◽  
pp. 39-46 ◽  
Author(s):  
Daniel Uebelhart ◽  
Eugene J.-M.A. Thonar ◽  
Pierre D. Delmas ◽  
Alex Chantraine ◽  
Eric Vignon

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