Introduction Patients with lower-leg cast immobilization and patients undergoing knee arthroscopy have an increased risk of venous thrombosis (VT). Guidelines are ambiguous about thromboprophylaxis... Show moreIntroduction Patients with lower-leg cast immobilization and patients undergoing knee arthroscopy have an increased risk of venous thrombosis (VT). Guidelines are ambiguous about thromboprophylaxis use, and individual risk factors for developing VT are often ignored. To assist in VT risk stratification and guide thromboprophylaxis use, various prediction models have been developed. These models depend largely on clinical factors and provide reasonably good C-statistics of around 70%. We explored using protein levels in blood plasma measured by multiplexed quantitative targeted proteomics to predict VT. Our aim was to assess whether a VT risk prediction model based on absolute plasma protein quantification is possible. Methods We used internal standards to quantify proteins in less than 10 mu l plasma. We measured 270 proteins in samples from patients scheduled for knee arthroscopy or with lower-leg cast immobilization. The two prospective POT-(K)CAST trails allow complementary views of VT signature in blood, namely pre and post trauma, respectively. From approximately 3000 patients, 31 patients developed VT who were included and matched with double the number of controls. Results Top discriminating proteins between cases and controls included APOC3, APOC4, APOC2, ATRN, F13B, and F2 in knee arthroscopy patients and APOE, SERPINF2, B2M, F13B, AFM, and C1QC in patients with lower-leg cast. A logistic regression model with cross-validation resulted in C-statistics of 88.1% (95% CI: 85.7-90.6%) and 79.6% (95% CI: 77.2-82.0%) for knee arthroscopy and cast immobilization groups respectively. Conclusions Promising C-statistics merit further exploration of the value of proteomic tests for predicting VT risk upon additional validation. Show less
Tabyshova, A.; Hurst, J.R.; Soriano, J.B.; Checkley, W.; Huang, E.W.C.; Trofor, A.C.; ... ; J.F.M. van boven 2021
BACKGROUND: Guidelines are critical for facilitating cost-effective COPD care. Development and implementation in low-and middle-income countries (LMICs) is challenging. To guide future strategy, an... Show moreBACKGROUND: Guidelines are critical for facilitating cost-effective COPD care. Development and implementation in low-and middle-income countries (LMICs) is challenging. To guide future strategy, an overview of current global COPD guidelines is required.RESEARCH QUESTION: We systematically reviewed national COPD guidelines, focusing on worldwide availability and identification of potential development, content, context, and quality gaps that may hamper effective implementation.STUDY DESIGN AND METHODS: Scoping review of national COPD management guidelines. We assessed: (1) global guideline coverage; (2) guideline information (authors, target audience, dissemination plans); (3) content (prevention, diagnosis, treatments); (4) ethical, legal, and socioeconomic aspects; and (5) compliance with the eight Institute of Medicine (IOM) guideline standards. LMICs guidelines were compared with those from high-income countries (HICs).RESULTS: Of the 61 national COPD guidelines identified, 30 were from LMICs. Guidelines did not cover 1.93 billion (30.2%) people living in LMICs, whereas only 0.02 billion (1.9%) in HICs were without national guidelines. Compared with HICs, LMIC guidelines targeted fewer health-care professional groups and less often addressed case finding and co-morbidities. More than 90% of all guidelines included smoking cessation advice. Air pollution reduction strategies were less frequently mentioned in both LMICs (47%) and HICs (42%). LMIC guidelines fulfilled on average 3.37 (42%) of IOM standards, compared with 5.29 (66%) in HICs (P <.05). LMICs scored significantly lower compared with HICs regarding conflicts of interest management, updates, articulation of recommendations, and funding transparency (all, P <.05).INTERPRETATION: Several development, content, context, and quality gaps exist in COPD guidelines from LMICs that may hamper effective implementation. Overall, COPD guidelines in LMICs should be more widely available and should be transparently developed and updated. Guidelines may be further enhanced by better inclusion of local risk factors, case findings, and co-morbidity management, preferably tailored to available financial and staff resources. Show less
BackgroundInternational normalized ratio (INR) is traceable to World Health Organization (WHO) International Standards for thromboplastins. International Standards must be used with a manual tilt... Show moreBackgroundInternational normalized ratio (INR) is traceable to World Health Organization (WHO) International Standards for thromboplastins. International Standards must be used with a manual tilt tube technique (MTT) for prothrombin time (PT) determination. An important part of the total variability of INR is due to poor harmonization of MTT across WHO reference laboratories.ObjectivesTo determine the origins of PT differences between operators performing MTT and to develop a harmonized MTT.MethodsTwo workshops were held where WHO reference laboratory operators could compare their PTs using MTT and the same equipment. A harmonized MTT was used by seven operators in the second workshop.ResultsDifferences have been observed in tilting frequency and in the height of pipetting plasma in the test tube. At the beginning of the first workshop, the tilting cycle time varied between 1.1 and 2.7 seconds. The mean PT of normal plasma obtained by pipetting plasma at the top of the tube was 14.3 seconds but was 12.9 seconds when plasma was pipetted at the bottom of the tube. When using the harmonized MTT for WHO International Standard rTF/16, the differences between operators were not greater than 1.1 seconds in normal plasma, and not greater than 1.3 seconds in patient plasma with average INR of 3.0. INR between‐operator coefficient of variation was 2.3%.ConclusionApplication of a harmonized MTT in three reference laboratories resulted in substantial reduction of between‐operator variation of PT and INR. The harmonized MTT is proposed as Candidate Reference Measurement Procedure. Show less
Background International normalized ratio (INR) is traceable to World Health Organization (WHO) International Standards for thromboplastins. International Standards must be used with a manual tilt... Show moreBackground International normalized ratio (INR) is traceable to World Health Organization (WHO) International Standards for thromboplastins. International Standards must be used with a manual tilt tube technique (MTT) for prothrombin time (PT) determination. An important part of the total variability of INR is due to poor harmonization of MTT across WHO reference laboratories. Objectives To determine the origins of PT differences between operators performing MTT and to develop a harmonized MTT. Methods Two workshops were held where WHO reference laboratory operators could compare their PTs using MTT and the same equipment. A harmonized MTT was used by seven operators in the second workshop. Results Differences have been observed in tilting frequency and in the height of pipetting plasma in the test tube. At the beginning of the first workshop, the tilting cycle time varied between 1.1 and 2.7 seconds. The mean PT of normal plasma obtained by pipetting plasma at the top of the tube was 14.3 seconds but was 12.9 seconds when plasma was pipetted at the bottom of the tube. When using the harmonized MTT for WHO International Standard rTF/16, the differences between operators were not greater than 1.1 seconds in normal plasma, and not greater than 1.3 seconds in patient plasma with average INR of 3.0. INR between-operator coefficient of variation was 2.3%. Conclusion Application of a harmonized MTT in three reference laboratories resulted in substantial reduction of between-operator variation of PT and INR. The harmonized MTT is proposed as Candidate Reference Measurement Procedure. Show less
