Understanding crossovers and potential ways to mitigate the problem: Lessons from influential trials on lumbar microdiscectomy.

BACKGROUND: Lumbar microdiscectomy is the most frequent surgical intervention used in the treatment of sciatica from herniated lumbar discs. Many discectomy trials have been plagued with an excessive number of crossovers that have rendered results inconclusive. METHODS: We review the design and results of influential lumbar microdiscectomy trials. We also discuss the various strategies that have been used to decrease the number of crossovers or to mitigate the effects of crossovers on analyses. RESULTS: Randomized trials on lumbar discectomy were affected by crossover rates of 8% to 42%. Various strategies that have been used to decrease that number or to mitigate the effects on results include: patient selection, blinding (placebo-controlled trials), an immediate access to surgery for the surgical group (but limited access to surgery for the conservative group), shortening the follow-up period necessary to reach the primary outcome measure, postponing crossovers to surgery after determination of the primary outcome, and modifying the primary outcome measure to include treatment failures. Crossovers should be anticipated and compensated for by increasing the number of participants. CONCLUSION: Non-adherence to randomly allocated management options can deprive trials of the statistical power needed to inform clinical care. Crossovers and ways to mitigate related problems should be anticipated at the time of trial design.

Understanding how the research question impacts trial design: Examples from discectomy trials.

BACKGROUND: Formulating a pertinent research question is of the utmost importance in clinical research. An ill-conceived question may lead to an erroneous trial design, which may adversely affect the care of patients and provide uninformative or even misleading results. METHODS: We review the research question of a randomized trial on the timing of lumbar discectomy. We compare the resulting design with other trials, real or hypothetical, that would have been more appropriate. RESULTS: The RCT we examine randomly allocated patients to early or delayed surgery to answer a theoretical question of the effect of time on the efficacy of surgery. The trial was interpreted to have shown that early surgery was associated with better clinical and functional outcomes as compared to delayed surgery. This conclusion is clinically misleading. Valid comparisons between groups should be performed on intent-to-treat analyses and at the same time points after randomization (and not at a fixed follow-up period after surgery). The clinically pertinent comparison is not between the theoretical efficacy of surgery performed at various times, but between surgery and conservative management in patients presenting at various times. Better-designed trials on the clinical benefits of lumbar discectomy, including the treatment of chronic sciatica, have been published. CONCLUSION: Theoretical research questions inspired from observational data can lead to erroneous trial design. Prospective randomized trials impact practice immediately: they are unique occasions to address clinical problems and optimize care under uncertainty in real time. However, they require the research question to be formulated with great care.

Short- and potential long-term adverse health outcomes of COVID-19: a rapid review.

The coronavirus disease 2019 (COVID-19) pandemic has resulted in millions of patients infected worldwide and indirectly affecting even more individuals through disruption of daily living. Long-term adverse outcomes have been reported with similar diseases from other coronaviruses, namely Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS). Emerging evidence suggests that COVID-19 adversely affects different systems in the human body. This review summarizes the current evidence on the short-term adverse health outcomes and assesses the risk of potential long-term adverse outcomes of COVID-19. Major adverse outcomes were found to affect different body systems: immune system (including but not limited to Guillain-Barré syndrome and paediatric inflammatory multisystem syndrome), respiratory system (lung fibrosis and pulmonary thromboembolism), cardiovascular system (cardiomyopathy and coagulopathy), neurological system (sensory dysfunction and stroke), as well as cutaneous and gastrointestinal manifestations, impaired hepatic and renal function. Mental health in patients with COVID-19 was also found to be adversely affected. The burden of caring for COVID-19 survivors is likely to be huge. Therefore, it is important for policy makers to develop comprehensive strategies in providing resources and capacity in the healthcare system. Future epidemiological studies are needed to further investigate the long-term impact on COVID-19 survivors.