Individualized Net Benefit estimation and meta-analysis using generalized pairwise comparisons in N-of-1 trials.

BACKGROUND: The Net Benefit (Δ) is a measure of the benefit-risk balance in clinical trials, based on generalized pairwise comparisons (GPC) using several prioritized outcomes and thresholds of clinical relevance. We extended Δ to N-of-1 trials, with a focus on patient-level and population-level Δ. METHODS: We developed a Δ estimator at the individual level as an extension of the stratum-specific Δ, and at the population-level as an extension of the stratified Δ. We performed a simulation study mimicking PROFIL, a series of 38 N-of-1 trials testing sildenafil in Raynaud's phenomenon, to assess the power for such an analysis with realistic data. We then reanalyzed PROFIL using GPC. This reanalysis was finally interpreted in the context of the main analysis of PROFIL which used Bayesian individual probabilities of efficacy. RESULTS: Simulations under the null showed good size of the test for both individual and population levels. The test lacked power when being simulated from the true PROFIL data, even when increasing the number of repetitions up to 140 days per patient. PROFIL individual-level estimated Δ were well correlated with the probabilities of efficacy from the Bayesian analysis while showing similarly wide confidence intervals. Population-level estimated Δ was not significantly different from zero, consistently with the previous Bayesian analysis. CONCLUSION: GPC can be used to estimate individual Δ which can then be aggregated in a meta-analytic way in N-of-1 trials. GPC ability to easily incorporate patient preferences allow for more personalized treatment evaluation, while needing much less computing time than Bayesian modeling.

Prevalence of cerebral palsy comorbidities in China: a systematic review and meta-analysis.

Objectives: This systematic review aimed to comprehensively understand the comorbidity of cerebral palsy (CP) in China. Methods: We searched through databases in both Chinese and English until December 2022 to gather cross-sectional studies on the comorbidity of CP in China. After two reviewers independently screened the articles, collected the data, and assessed the bias risk, a meta-analysis was conducted using the Stata 17.0 software. Results: A total of 73 articles were included. Of these, 16 articles reported total comorbidity, with a prevalence of 79.7% (95% CI: 73.8-85.7%); 56 articles reported epilepsy, with a prevalence of 17.9% (95% CI: 15.4-20.4%); 48 articles reported intellectual disability, with a prevalence of 58.0% (95% CI: 51.8-64.3%); 32 articles reported speech disorders, with a prevalence of 48.0% (95% CI: 41.6-54.4%); 41 articles reported hearing disorders, with a prevalence of 17.2% (95% CI: 13.0-21.4%); and 35 articles reported vision disorders, with a prevalence of 23.1% (95% CI: 16.3-29.8%). The topographical type of CP was the primary source of heterogeneity in the prevalence of epilepsy. Diagnostic criteria for CP, clinical type of CP, GMFCS, publishing time, and topographical type of CP were the primary sources of heterogeneity in the prevalence of intellectual disability. Clinical type of CP and topographical type were the primary sources of heterogeneity in the prevalence of speech disorders. Finally, the region was the primary source of heterogeneity in the prevalence of hearing disorders. Conclusion: The prevalence of comorbidities in CP is high in China. Comorbidities are related to the characteristics, severity, and risk factors of brain insult and have a particular relationship with regional economic development and medical and health levels.

Global lessons learned from naturalistic driving studies to advance traffic safety and operation research: A systematic review.

The state of practice of investigating traffic safety and operation is primarily based on traditional data sources, such as spot sensors, loop detectors, and historical crash data. Recently, researchers have utilized transportation data from instrumented vehicles, driving simulators, and microsimulation modeling. However, these data sources might not represent the actual driving environment at a trajectory level and might introduce bias due to their experimental control. The shortcomings of these data sources can be overcome via Naturalistic Driving Studies (NDSs) considering the fact that NDS provides detailed real-time driving data that would help investigate the safety and operational impacts of human behavior along with other factors related to weather, traffic, and roadway geometry in a naturalistic setting. With the enormous potential of the NDS data, this study leveraged the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) approach to shortlist the most relevant naturalistic studies out of 2304 initial studies around the world with a focus on traffic safety and operation over the past fifteen years (2005-2020). A total of 117 studies were systematically reviewed, which were grouped into seven relevant topics, including driver behavior and performance, crash/near-crash causation, driver distraction, pedestrian/bicycle safety, intersection/traffic signal related studies, detection and prediction using NDSs data, based on their frequency of appearance in the keywords of these studies. The proper deployment of Connected and Autonomous Vehicles (CAV) require an appropriate level of human behavior integration, especially at the intimal stages where both CAV and human-driven vehicles will interact and share the same roadways in a mixed traffic environment. In order to integrate the heterogeneous nature of human behavior through behavior cloning approach, real-time trajectory-level NDS data is essential. The insights from this study revealed that NDSs could be effectively leveraged to perfect the behavior cloning to facilitate rapid and safe implementation of CAV.

Tigeciclina en infecciones de piel y tejidos blandos complicadas / Tigecycline in complicated skin and soft-tissue infection

Objetivo: evaluar la mejor evidencia actual disponible para generar recomendaciones con respecto a la efectividad y seguridad del uso de tigeciclina en adultos con infección de piel y tejidos blandos (IPTB). Materiales y métodos: se realizó una revisión sistemática de la literatura, seleccionando los metaanálisis y experimentos clínicos controlados (ECCs), los cuales se valoraron utilizando la herramienta SIGN (Scottish Intercollegiate Guidelines Network.), con el fin de generar tablas de evidencia según GRADE de los estudios de tigeciclina en la indicación de IPTB, para posteriormente utilizar un proceso Delphi modificado para calificar las diferentes recomendaciones. Resultados: la revisión sistemática se incluyeron 9 metaanálisis que incluyeron 5 estudios clínicos aleatorizados con 1873 pacientes, y de ellos 952 asignados al brazo de tigeciclina, no mostró inferioridad frente a los comparadores en curación clínica (RR= 0.76 IC95% 0,57 - 1.03), curación microbiológica (RR= 0.92 IC95% 0,61 - 1.38), eventos adversos serios RR 1,41 (IC95%0,97 a 2,35), ni mortalidad RR 1,9 (IC95%0,84 a 4,3). La tigeciclina puede relacionarse con mayor frecuencia de eventos adversos leves de origen gastrointestinal. Conclusión: en pacientes adultos con IPTB, se considera que el uso de tigeciclina en monoterapia en pacientes no críticamente enfermos es equivalente en eficacia a otras opciones terapéuticas antimicrobianas. Se debe considerar especialmente como terapia de ajuste en pacientes con infecciones polimicrobianas.

Objective: To assess current best evidence available to generate recommendations regarding the effectiveness and safety of tigecycline use in adults with skin and soft-tissue infections (SSTIs). Materials and methods: A systematic review of the literature was conducted by selecting meta-analyzes and controlled clinical trials (CCTs), which were assessed using the SIGN tool (Scottish Intercollegiate Guidelines Network) in order to generate evidence tables according to GRADE of studies of tigecycline in the SSTIs indication, and then using a modified Delphi Method to score the different recommendations. Results: Nine meta-analyzes were included compounded by five randomized clinical trials with a sample size of 1873 patients, where 952 patients were assigned to tigecycline. The group of patients with tigecycline showed no inferiority to the comparator in clinical cure (RR = 0.76 95% CI 0.57 - 1.03), microbiologic cure (RR = 0.92 95% CI 0.61 - 1.38), serious adverse events RR 1, 41 (95% CI 0.97 to 2.35) or mortality RR 1.9 (95% CI 0.84 to 4.3). Tigecycline may be related to increased frequency of minor adverse events of gastrointestinal origin. Conclusion: In adult patients with SSTIs, it is considered that the use of tigecycline in monotherapy in non-critically ill patients is equivalent in effectiveness to other antimicrobial treatment options. It should be especially considered as an adjustment therapy in patients with polymicrobial infections.