ULMONARY EMBOLISM IS A COMmon and serious medical condition leading to the hospitalization or death of more than 250 000 people in the United States each year. 1 It is the third leading cause of cardiovascular mortality and is estimated to result in 5% to 10% of all deaths in US hospitals. 2 Despite the potentially lethal nature of this condition, pulmonary embolism remains one of the most difficult conditions for clinicians to diagnose accurately. 3 Given the high mortality of untreated pulmonary embolism, timely accurate diagnostic tests are essential to enable the For editorial comment see p 2788.
Identifying which individuals benefit most from particular treatments or other interventions underpins so-called personalised or stratified medicine. However, single trials are typically underpowered for exploring whether participant characteristics, such as age or disease severity, determine an individual’s response to treatment. A meta-analysis of multiple trials, particularly one where individual participant data (IPD) are available, provides greater power to investigate interactions between participant characteristics (covariates) and treatment effects. We use a published IPD meta-analysis to illustrate three broad approaches used for testing such interactions. Based on another systematic review of recently published IPD meta-analyses, we also show that all three approaches can be applied to aggregate data as well as IPD. We also summarise which methods of analysing and presenting interactions are in current use, and describe their advantages and disadvantages. We recommend that testing for interactions using within-trials information alone (the deft approach) becomes standard practice, alongside graphical presentation that directly visualises this.
Bone marrow is an important extranodal site in diffuse large B-cell lymphoma (DLBCL), and marrow histology has been incorporated into the new National Comprehensive Cancer Network international prognostic index. Marrow involvement demonstrated histologically confers poor prognosis but is identified by staging PET in more cases. How information from staging PET and biopsy should be combined to optimize outcome prediction remains unclear. Methods: The International Atomic Energy Agency sponsored a prospective international cohort study to better define the use of PET in DLBCL. As a planned subsidiary analysis, we examined the interplay of marrow involvement identified by PET and biopsy on clinical outcomes. Results: Eight countries contributed 327 cases with a median follow-up of 35 mo. The 2-y outcomes of cases with no evidence of marrow involvement (n 5 231) were 81% (95% confidence interval [CI], 76%-86%) for event-free survival (EFS) and 88% (83%-91%) for overall survival (OS); cases identified only on PET (n 5 61), 81% (69%-89%) for EFS and 88% (77%-94%) for OS; cases indentified only on biopsy (n 5 10), 80% (41%-95%) for EFS and 100% for OS; or cases identified by both PET and biopsy (n 5 25), 45% (25%-64%) for EFS and 55% (32%-73%) for OS. The hazard ratios for PET-negative/biopsy-negative cases versus PET-positive/ biopsy-positive cases were 2.67 (95% CI, 1.48-4.79) for ) for OS. Conclusion: This large study demonstrates that positive iliac crest biopsy histology only confers poor prognosis for patients who also have abnormal marrow 18 F-FDG uptake identified on the staging PET scan. Abnormal 18 F-FDG uptake in marrow, when iliac crest biopsy histology is normal, has no adverse effect on outcomes.
Rapid urbanisation is a key characteristic of the modern world, interacting with and reinforcing other global mega trends, including armed conflict, climate change, crime, environmental degradation, financial and economic instability, food shortages, underemployment, volatile commodity prices, and weak governance. Displaced people also are affected by and engaged in the process of urbanisation. Increasingly, refugees, returnees, and internally displaced persons (IDPs) are to be found not in camps or among host communities in rural areas, but in the towns and cities of developing and middle-income countries. The arrival and long-term settlement of displaced populations in urban areas needs to be better anticipated, understood, and planned for, with a particular emphasis on the establishment of new partnerships. Humanitarian actors can no longer liaise only with national governments; they must also develop urgently closer working relationships with mayors and municipal authorities, service providers, urban police forces, and, most importantly, the representatives of both displaced and resident communities. This requires linking up with those development actors that have established such partnerships already.
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