Tutorial: dos and don'ts in clinical prediction research for venous thromboembolism.

Clinical prediction modeling has become an increasingly popular domain of venous thromboembolism research in recent years. Prediction models can help healthcare providers make decisions regarding starting or withholding therapeutic interventions, or referrals for further diagnostic workup, and can form a basis for risk stratification in clinical trials. The aim of the current guide is to assist in the practical application of complicated methodological requirements for well-performed prediction research by presenting key dos and don'ts while expanding the understanding of predictive research in general for (clinical) researchers who are not specifically trained in the topic; throughout we will use prognostic venous thromboembolism scores as an exemplar.

Using real-world evidence to complement evidence from randomized controlled trials on oral anticoagulants for stroke prevention.

Mark J. R. Smeets and Suzanne C. Cannegieter discuss the use of real world data to complement data generated by clinical trials of systemic anticoagulants.

Risks of major bleeding and venous thromboembolism in patients undergoing total hip or total knee arthroplasty using therapeutic dosages of DOACs.

About 1.5% of patients undergoing total hip (THA) or total knee arthroplasty (TKA) still develop postoperative venous thromboembolism (VTE), indicating that the current thromboprophylaxis strategy is not optimal. To evaluate the feasibility of therapeutic dosages of direct oral anticoagulants (DOACs) as thromboprophylaxis for high VTE risk patients, we determined the risks of major bleeding and VTE in patients who underwent THA/TKA and were treated with DOACs in therapeutic dosages for atrial fibrillation (AF). We conducted a registry-based cohort study from 2010 to 2018 in Denmark and included AF patients on therapeutic DOACs dose who underwent THA/TKA. AF patients were utilized as proxy since they have a life-long indication for therapeutic anticoagulant medication. The 49-days cumulative incidence (with death as competing risk) of major bleeding was assessed. The same was done for VTE at 49- and 90-days. 1,354 THA and TKA procedures were included. The 49-days cumulative incidence of major bleeding was 1.40% (95%Confidence Interval[CI] 0.88-2.14%). Most bleeding events occurred at the surgical site. The cumulative incidence of VTE at 49-days was 0.59% (95%CI 0.28-1.13%) and 0.74% (95%CI 0.38-1.32%) at 90-days. The incidence of major bleeding in THA/TKA patients on DOACs in therapeutic dosages was in line with previously reported incidences among THA/TKA patients on thromboprophylaxis dosages, while the incidence of VTE was relatively low. These data provide a solid basis for the design of randomized controlled trials to establish the safety and efficacy of therapeutic dosages of DOACs to prevent VTE in high-risk patients.

Development and validation of a clinical prediction model for 90-day venous thromboembolism risk following total hip and total knee arthroplasty: a multinational study.

BACKGROUND: The risk of venous thromboembolism (VTE) following total hip arthroplasty (THA) and total knee arthroplasty (TKA) is 1.0% to 1.5%, despite uniform thromboprophylaxis. OBJECTIVES: To develop and validate a prediction model for 90-day VTE risk. METHODS: A multinational cohort study was performed. For model development, records were used from the Oxford Royal College of General Practitioners Research and Surveillance Centre linked to Hospital Episode Statistics and Office of National Statistics UK routine data. For external validation, data were used from the Danish Hip and Knee Arthroplasty Registry, the National Patient Registry, and the National Prescription Registry. Binary multivariable logistic regression techniques were used for development. RESULTS: In the UK data set, 64 032 THA/TKA procedures were performed and 1.4% developed VTE. The prediction model consisted of age, body mass index, sex, cystitis within 1 year before surgery, history of phlebitis, history of VTE, presence of varicose veins, presence of asthma, history of transient ischemic attack, history of myocardial infarction, presence of hypertension and THA or TKA. The area under the curve of the model was 0.65 (95% CI, 0.63-0.67). Furthermore, 36 169 procedures were performed in the Danish cohort, of whom 1.0% developed VTE. Here, the area under the curve was 0.64 (95% CI, 0.61-0.67). The calibration slope was 0.92 in the validation study and 1.00 in the development study. CONCLUSION: This clinical prediction model for 90-day VTE risk following THA and TKA performed well in both development and validation data. This model can be used to estimate an individual's risk for VTE following THA/TKA.

Daily disease severity in patients with COVID-19 admitted to the hospital: The SCODA (severity of coronavirus disease assessment) score.

BACKGROUND: A multitude of diagnostic and predictive algorithms have been designed for COVID-19. However, currently no score can accurately quantify and track day-to-day disease severity in hospitalised patients with COVID-19. We aimed to design such a score to improve pathophysiological insight in COVID-19. METHODS: Development of the Severity of COronavirus Disease Assessment (SCODA) score was based on the 4C Mortality score but patient demographic variables that remain constant during admission were excluded. Instead, parameters associated with breathing and oxygenation were added to reflect the daily condition. The SCODA score was subsequently applied to the BEAT-COVID cohort to describe COVID-19 severity over time and to determine the timing of clinical recovery for each patient, an important marker in pathophysiological studies. The BEAT-COVID study included patients with PCR confirmed COVID-19 who were hospitalized between April 2020 and March 2021 in the Leiden University Medical Center, The Netherlands. RESULTS: The SCODA score consists of 6 clinical and 2 routine lab parameters. 191 patients participated in the BEAT-COVID study. Median age was 66, and 74.4% was male. The modal timepoint at which recovery was clinically initiated occurred on days 8 and 24 since symptom onset for non-ICU and ICU-patients, respectively. CONCLUSIONS: We developed a daily score which can be used to track disease severity of patients admitted due to COVID-19. This score is useful for improving insight in COVID-19 pathophysiology, its clinical course and to evaluate interventions. In a future stage this score can also be used in other (emerging) infectious respiratory diseases.

Quasi-Static Mechanical Response of Density-Graded Polyurea Elastomeric Foams.

Density gradation of foam structures has been investigated and found to be a practical approach to improve the mechanical efficacy of protective padding in several applications based on nature-based evidence of effectiveness. This research aims to disclose a discrete gradation approach without adhesives by relying on the properties of the frothed foam slurry to bond and penetrate through previously cured foam sheets naturally. As confirmed by electron microscopy observations, bilayer- and trilayer-graded elastomeric polyurea foam sheets were fabricated, resulting in seamless interfaces. The mechanical performance of seamless, graded foam samples was compared with monolayer, mono-density benchmark foam, considered the industry standard for impact mitigation. All foam samples were submitted to compressive loading at a quasi-static rate, reporting key performance indicators (KPIs) such as specific energy absorption, efficiency, and ideality. Polyurea foams, irrespective of gradation and interface type, outperformed benchmark foam in several KPIs despite the drastic difference in the effective or average density. The average compressive stress-strain curves were fitted into empirical constitutive models to reveal critical insights into the elastic, plateau, and densification behaviors of the tested foam configuration. The novelty of these outcomes includes (1) a fabrication approach to adhesive-free density-graded foam structures, (2) implementation of a diverse set of KPIs to assess the mechanical efficacy of foams, and (3) elucidation of the superiority of polyurea foam-based lightweight protective paddings. Future research will focus on assessing the dynamic performance of these graded foam structures under impact loading conditions at a wide range of velocities.

The risk of venous thromboembolism after minor surgical procedures: A population-based case-control study.

BACKGROUND: Surgery is a well-known risk factor for venous thromboembolism (VTE). However, for several minor surgical procedures, thromboprophylaxis is not advised. OBJECTIVES: These "low-risk" procedures include a wide variation of interventions for which we estimated the VTE risk to verify their "low-risk" status. PATIENTS/METHODS: We used data from a large population-based case-control study (Multiple Environment and Genetic Assessment study) into causes of VTE, and linked these to the Dutch Hospital Data Registry to identify exposure to surgical procedures. Logistic regression was used to calculate odds ratios for the 90-day and 1-year relative risks of VTE following these procedures, which were adjusted for body mass index (BMI), sex, age, comorbidities, and infection/inflammation. RESULTS: We included 4247 patients with VTE and 5538 control subjects. Median age and BMI were 48.5 years and 25.5 m2/kg, respectively. Nine unique procedures or groups of procedures were analyzed. One hundred twenty-three participants-90 cases and 33 controls-had undergone a minor procedure within 90 days of the index date, resulting in a 3.5-fold (OR, 3.5; 95% CI, 2.3-5.3) overall increased VTE risk. Furthermore, venous stripping (OR, 7.2; 95% CI, 2.4-21.2), open abdominal/inguinal hernia repair (OR, 3.7; 95% CI, 1.2-11.6), and laparoscopic cholecystectomy (OR, 3.2; 95% CI, 1.0-10.6) were associated with an increased risk. Other minor procedures were less strongly or not associated with an increased risk. In the 1-year period before the index date, all odds ratios were lower. CONCLUSION: Of the "low-risk" procedures, we found that venous stripping, open abdominal/inguinal hernia repair, and laparoscopic cholecystectomy were associated with a clearly increased risk of VTE within 90 postoperative days.

No Uniformity in the References of Clinical Practice Guidelines for Bariatric Surgery: a Review of 3 Similar Guidelines Published in 2020.

In 2020, updated versions of the clinical practice guidelines of the European Association for Endoscopic Surgery, the Canadian Adult Obesity Clinical Practice Guidelines and the Dutch Federation for Medical Specialist clinical practice guidelines on bariatric surgery were published. We systematically reviewed and compared them on recommendations and references. Although the authors would have had access to the same literature, only 5 out of 655 unique references were used by all 3 guidelines and just 49 references by any combination of 2 guidelines. These findings attest to the subjectivity involved in clinical practice guidelines development and could be the cause for the observed differences in recommendations. International cooperation in guideline development might be a conceivable solution.