Tailored anticoagulant treatment after a first venous thromboembolism:protocol of the Leiden Thrombosis Recurrence Risk Prevention (L-TRRiP) study - cohort-based randomised controlled trial

Introduction: Patients with a first venous thromboembolism (VTE) are at risk of recurrence. Recurrent VTE (rVTE) can be prevented by extended anticoagulant therapy, but this comes at the cost of an increased risk of bleeding. It is still uncertain whether patients with an intermediate recurrence risk or with a high recurrence and high bleeding risk will benefit from extended anticoagulant treatment, and whether a strategy where anticoagulant duration is tailored on the predicted risks of rVTE and bleeding can improve outcomes. The aim of the Leiden Thrombosis Recurrence Risk Prevention (L-TRRiP) study is to evaluate the outcomes of tailored duration of long-term anticoagulant treatment based on individualised assessment of rVTE and major bleeding risks.Methods and analysis: The L-TRRiP study is a multicentre, open-label, cohort-based, randomised controlled trial, including patients with a first VTE. We classify the risk of rVTE and major bleeding using the L-TRRiP and VTE-BLEED scores, respectively. After 3 months of anticoagulant therapy, patients with a low rVTE risk will discontinue anticoagulant treatment, patients with a high rVTE and low bleeding risk will continue anticoagulant treatment, whereas all other patients will be randomised to continue or discontinue anticoagulant treatment. All patients will be followed up for at least 2 years. Inclusion will continue until the randomised group consists of 608 patients; we estimate to include 1600 patients in total. The primary outcome is the combined incidence of rVTE and major bleeding in the randomised group after 2 years of follow-up. Secondary outcomes include the incidence of rVTE and major bleeding, functional outcomes, quality of life and cost-effectiveness in all patients.Ethics and dissemination: The protocol was approved by the Medical Research Ethics Committee Leiden-Den Haag-Delft. Results are expected in 2028 and will be disseminated through peer-reviewed journals and during (inter)national conferences.</p

Elective surgery system strengthening: development, measurement, and validation of the surgical preparedness index across 1632 hospitals in 119 countries

Background: The 2015 Lancet Commission on global surgery identified surgery and anaesthesia as indispensable parts of holistic health-care systems. However, COVID-19 exposed the fragility of planned surgical services around the world, which have also been neglected in pandemic recovery planning. This study aimed to develop and validate a novel index to support local elective surgical system strengthening and address growing backlogs. Methods: First, we performed an international consultation through a four-stage consensus process to develop a multidomain index for hospital-level assessment (surgical preparedness index; SPI). Second, we measured surgical preparedness across a global network of hospitals in high-income countries (HICs), middle-income countries (MICs), and low-income countries (LICs) to explore the distribution of the SPI at national, subnational, and hospital levels. Finally, using COVID-19 as an example of an external system shock, we compared hospitals' SPI to their planned surgical volume ratio (SVR; ie, operations for which the decision for surgery was made before hospital admission), calculated as the ratio of the observed surgical volume over a 1-month assessment period between June 6 and Aug 5, 2021, against the expected surgical volume based on hospital administrative data from the same period in 2019 (ie, a pre-pandemic baseline). A linear mixed-effects regression model was used to determine the effect of increasing SPI score. Findings: In the first phase, from a longlist of 103 candidate indicators, 23 were prioritised as core indicators of elective surgical system preparedness by 69 clinicians (23 [33%] women; 46 [67%] men; 41 from HICs, 22 from MICs, and six from LICs) from 32 countries. The multidomain SPI included 11 indicators on facilities and consumables, two on staffing, two on prioritisation, and eight on systems. Hospitals were scored from 23 (least prepared) to 115 points (most prepared). In the second phase, surgical preparedness was measured in 1632 hospitals by 4714 clinicians from 119 countries. 745 (45·6%) of 1632 hospitals were in MICs or LICs. The mean SPI score was 84·5 (95% CI 84·1–84·9), which varied between HIC (88·5 [89·0–88·0]), MIC (81·8 [82·5–81·1]), and LIC (66·8 [64·9–68·7]) settings. In the third phase, 1217 (74·6%) hospitals did not maintain their expected SVR during the COVID-19 pandemic, of which 625 (51·4%) were from HIC, 538 (44·2%) from MIC, and 54 (4·4%) from LIC settings. In the mixed-effects model, a 10-point increase in SPI corresponded to a 3·6% (95% CI 3·0–4·1; p<0·0001) increase in SVR. This was consistent in HIC (4·8% [4·1–5·5]; p<0·0001), MIC (2·8 [2·0–3·7]; p<0·0001), and LIC (3·8 [1·3–6·7%]; p<0·0001) settings. InterpBackground The 2015 Lancet Commission on global surgery identified surgery and anaesthesia as indispensable parts of holistic health-care systems. However, COVID-19 exposed the fragility of planned surgical services around the world, which have also been neglected in pandemic recovery planning. This study aimed to develop and validate a novel index to support local elective surgical system strengthening and address growing backlogs. Methods: First, we performed an international consultation through a four-stage consensus process to develop a multidomain index for hospital-level assessment (surgical preparedness index; SPI). Second, we measured surgical preparedness across a global network of hospitals in high-income countries (HICs), middle-income countries (MICs), and low-income countries (LICs) to explore the distribution of the SPI at national, subnational, and hospital levels. Finally, using COVID-19 as an example of an external system shock, we compared hospitals' SPI to their planned surgical volume ratio (SVR; ie, operations for which the decision for surgery was made before hospital admission), calculated as the ratio of the observed surgical volume over a 1-month assessment period between June 6 and Aug 5, 2021, against the expected surgical volume based on hospital administrative data from the same period in 2019 (ie, a pre-pandemic baseline). A linear mixed-effects regression model was used to determine the effect of increasing SPI score. Findings: In the first phase, from a longlist of 103 candidate indicators, 23 were prioritised as core indicators of elective surgical system preparedness by 69 clinicians (23 [33%] women; 46 [67%] men; 41 from HICs, 22 from MICs, and six from LICs) from 32 countries. The multidomain SPI included 11 indicators on facilities and consumables, two on staffing, two on prioritisation, and eight on systems. Hospitals were scored from 23 (least prepared) to 115 points (most prepared). In the second phase, surgical preparedness was measured in 1632 hospitals by 4714 clinicians from 119 countries. 745 (45·6%) of 1632 hospitals were in MICs or LICs. The mean SPI score was 84·5 (95% CI 84·1–84·9), which varied between HIC (88·5 [89·0–88·0]), MIC (81·8 [82·5–81·1]), and LIC (66·8 [64·9–68·7]) settings. In the third phase, 1217 (74·6%) hospitals did not maintain their expected SVR during the COVID-19 pandemic, of which 625 (51·4%) were from HIC, 538 (44·2%) from MIC, and 54 (4·4%) from LIC settings. In the mixed-effects model, a 10-point increase in SPI corresponded to a 3·6% (95% CI 3·0–4·1; p<0·0001) increase in SVR. This was consistent in HIC (4·8% [4·1–5·5]; p<0·0001), MIC (2·8 [2·0–3·7]; p<0·0001), and LIC (3·8 [1·3–6·7%]; p<0·0001) settings. Interpretation: The SPI contains 23 indicators that are globally applicable, relevant across different system stressors, vary at a subnational level, and are collectable by front-line teams. In the case study of COVID-19, a higher SPI was associated with an increased planned surgical volume ratio independent of country income status, COVID-19 burden, and hospital type. Hospitals should perform annual self-assessment of their surgical preparedness to identify areas that can be improved, create resilience in local surgical systems, and upscale capacity to address elective surgery backlogs.retation The SPI contains 23 indicators that are globally applicable, relevant across different system stressors, vary at a subnational level, and are collectable by front-line teams. In the case study of COVID-19, a higher SPI was associated with an increased planned surgical volume ratio independent of country income status, COVID-19 burden, and hospital type. Hospitals should perform annual self-assessment of their surgical preparedness to identify areas that can be improved, create resilience in local surgical systems, and upscale capacity to address elective surgery backlogs

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Passible polyphony:An extensive team-reflexivity process for hierarchical, transdisciplinary research teams

This article showcases an extensive team-reflexivity process of an embarking transdisciplinary research team in psychiatry. It explores a multilayered tension between the authors, five Dutch researchers with different embodied positions, from diverse research traditions and at different stages of their careers. This article represents a meaningful collision between the rise of horizontalizing participatory research practices, and persistent traditional hierarchies in academic psychiatry. We show how this played out in a hierarchical, transdisciplinary research team, including its emotion work and power ambiguities. Such an intensive and shared reflexivity process is novel, that is, not typical of a responsive research design. The value of this article is that we show and analyze what we have come to call our ‘passible polyphony’: a thorough grappling with multiple perspectives in often disharmonious interactions

Young adults' self-sufficiency in daily life: the relationship with contextual factors and health indicators

Background: Certain factors, such as depressive symptoms and binge drinking, may be linked to young adults' ability to attain an acceptable level of functioning on specific life-domains (i.e. self-sufficiency). We studied the association of contextual factors and health indicators with self-sufficiency in young adults. Methods: We used both baseline (n = 755) and 6-months follow-up (n = 200) self-reported questionnaire data of intermediate vocational education students (16-26 years). The questionnaire included the adapted Dutch self-sufficiency matrix (SSM-D), which addresses self-sufficiency regarding 11 life-domains (e.g. finances and housing). The questionnaire also included potentially associated contextual factors (e.g. socio-demographic characteristics) and health indicators (e.g. sickness absence from school). Ordinal (overall self-sufficiency: self-sufficient on 11, 10, 9 or ≤ 8 life-domains), and logistic (self-sufficiency per life-domain: self-sufficient yes/no) regression models were applied. Results: The studied population was 18.6 years on average (SD 2.04), and 73.6% were female. Cannabis use was associated with a lower overall self-sufficiency category at baseline (OR = 0.57, 95% CI = 0.33-0.99), as were an increase in sick days (OR = 0.94, 95% CI = 0.91-0.98) and an increase on the scale of depressive symptoms (OR = 0.87, 95% CI = 0.85-0.89). An increase in sick days and an increase on the scale of depressive symptoms were associated with lower odds of being self-sufficient on three and ten life-domains, respectively (p < 0.05). An increase on the scale of depressive symptoms was associated with a lower overall self-sufficiency category 6-months post-baseline (OR = 0.90, 95% CI = 0.86-0.93). Conclusions: Our findings underline the importance of addressing self-sufficiency, sickness absence, and depressive symptoms, preferably before the transition from adolescence to young adulthood has begun

Young adults’ self-sufficiency in daily life: the relationship with contextual factors and health indicators

Abstract Background Certain factors, such as depressive symptoms and binge drinking, may be linked to young adults’ ability to attain an acceptable level of functioning on specific life-domains (i.e. self-sufficiency). We studied the association of contextual factors and health indicators with self-sufficiency in young adults. Methods We used both baseline (n = 755) and 6-months follow-up (n = 200) self-reported questionnaire data of intermediate vocational education students (16–26 years). The questionnaire included the adapted Dutch self-sufficiency matrix (SSM-D), which addresses self-sufficiency regarding 11 life-domains (e.g. finances and housing). The questionnaire also included potentially associated contextual factors (e.g. socio-demographic characteristics) and health indicators (e.g. sickness absence from school). Ordinal (overall self-sufficiency: self-sufficient on 11, 10, 9 or ≤ 8 life-domains), and logistic (self-sufficiency per life-domain: self-sufficient yes/no) regression models were applied. Results The studied population was 18.6 years on average (SD 2.04), and 73.6% were female. Cannabis use was associated with a lower overall self-sufficiency category at baseline (OR = 0.57, 95% CI = 0.33–0.99), as were an increase in sick days (OR = 0.94, 95% CI = 0.91–0.98) and an increase on the scale of depressive symptoms (OR = 0.87, 95% CI = 0.85–0.89). An increase in sick days and an increase on the scale of depressive symptoms were associated with lower odds of being self-sufficient on three and ten life-domains, respectively (p &lt; 0.05). An increase on the scale of depressive symptoms was associated with a lower overall self-sufficiency category 6-months post-baseline (OR = 0.90, 95% CI = 0.86–0.93). Conclusions Our findings underline the importance of addressing self-sufficiency, sickness absence, and depressive symptoms, preferably before the transition from adolescence to young adulthood has begun. </jats:sec

Patients' Willingness to Take Multiple-Tablet Antiretroviral Therapy Regimens for Treatment of HIV

The costs of combination antiretroviral therapy (cART) for HIV, consisting of separate, particularly generic, components (multiple-tablet regimens, MTR) are generally much lower than those of single-tablet regimens (STR) comprising the same active ingredients. To assess whether patients would be willing to take MTR, once-daily, instead of STR, with the goal of reducing general healthcare costs. In addition, we aimed to examine whether willingness was associated with particular patient characteristics. Data from the ATHENA cohort database in The Netherlands of adult HIV-1-infected patients in care and taking cART ≥6 months were used to select 1000 potential participants for an online patient survey on patient preferences and satisfaction. Participants were asked whether they would be willing to take three pills with the equivalent active ingredients simultaneously instead of STR to reduce costs. Multivariate logistic regression was used to examine associations between patient characteristics and willingness to take MTR instead of STR. Forty-seven percent (n = 152) of the 322 respondents answered 'yes' and 26 % (n = 83) answered 'maybe' when asked whether they would be willing to take three pills with the equivalent active ingredients simultaneously to reduce costs. Non-Dutch patients were significantly more likely to answer 'no' (OR: 2.49; 95 % CI: 1.17-5.30) or 'maybe' (OR: 2.63; 95 % CI: 1.24-5.60). Answering 'no' was less common among patients who had been taking cART ≥15 years (OR: 0.23; 95 % CI: 0.09-0.58). Commonly reported concerns included the dosing frequency, efficacy and tolerability of MTR. HIV-infected patients do not necessarily oppose the decision to prescribe MTR instead of STR to reduce healthcare costs. However, the potential trade-off in terms of convenience should be carefully weighed against the projected saving

Platelet Transfusions for Thrombocytopenic Preterm Neonates: The Monet Study

Abstract Introduction Limited evidence supports the widely used practice of administering platelet transfusions to prevent major bleeding in preterm thrombocytopenic neonates. Only 1 randomized controlled trial addressed this issue, but used thresholds higher than those currently used in clinical practice. In order to assess the impact of platelet transfusions on bleeding risk, the primary objective of this study was to develop a prediction model for bleeding. Platelet transfusion was included as variable in this model. In these secondary analyses, we further explored the impact of platelet transfusions on bleeding risk. Materials and methods In this multicenter cohort study, neonates with a gestational age (GA) &amp;lt;34 weeks at birth, admitted to a neonatal intensive care unit (NICU) who developed a platelet count &amp;lt;50x109/L were included. The main study endpoint was major bleeding, defined as intraventricular hemorrhage (IVH) grade 3, IVH with parenchymal involvement, other types of intracranial hemorrhage visible on ultrasound scans, pulmonary hemorrhage or any other type of bleeding requiring immediate interventions. The prediction model was developed using landmarking, in which multiple cox models at regular time-points were combined into 1 supermodel. To further explore the impact of platelet transfusions on bleeding risk, we performed 3 sensitivity analyses by selecting specific transfusions (instead of all transfusions). Sensitivity analysis 1 : transfusions according to protocol, defined as transfusions for platelet counts &amp;gt;20x109/L only allowed in case of GA&amp;lt;32 weeks and &amp;lt;1500 grams and presence of NEC, sepsis, or treatment with mechanical ventilation, or in case of invasive procedures. Sensitivity analysis 2: transfusions with fair increments, defined as platelet count ≥50x109/L within 24 hours. Sensitivity analysis 3: transfusion dose 11 ml/kg or higher. Results A total of 640 neonates were included with a median gestational age of 28 weeks. 70 neonates developed a major bleed. IUGR, postnatal age, platelet count and mechanical ventilation were independent predictors of bleeding. The model allowed calculation of two bleeding risks for individual neonates: one in case of platelet transfusion and one in case of no platelet transfusion. 1361 platelet transfusions were administered to 449 of 640 (70%) neonates, of which 87 were hyperconcentrates. The hazard ratio for transfusion in the original model was 1.0, indicating no predictive power. Sensitivity analysis 1: 704 (52%) transfusions were given according to protocol. When selecting these transfusions, the hazard ratio for transfusion changed from 1.0 to 0.5, but the p-value remained &amp;gt; 0.05.Sensitivity analysis 2: 764 (56%) of transfusions resulted in a count &amp;gt;50x109/L within 24 hours. When selecting these transfusions, the hazard ratio for transfusion changed from 1.0 to 0.25, but the p-value remained &amp;gt;0.05. 115 (8%) transfusions did not have a follow up platelet count within 24 hours. Sensitivity analysis 3: of the non-hyperconcentrated platelet transfusions, 517 of 1274 (41%) transfusions were ≥ 11 ml/kg. When selecting these transfusions, the hazard ratio for transfusion changed from 1.0 to 0.1, with a p-value of 0.05. Conclusion With this tool, absolute risk of bleeding in individual preterm thrombocytopenic neonates can be calculated. Additionally, risk of bleeding can be assessed for 2 scenarios: with and without platelet transfusion. This can help clinicians in deciding whether or not to transfuse a patient. In the primary model, platelet transfusion was not a predictor for bleeding risk. However, the findings of the sensitivity analyses suggest that transfusions with a dose &amp;gt; 11ml/kg may have a more profound effect on bleeding risk. Disclosures No relevant conflicts of interest to declare. </jats:sec