Natural experiments: An overview of methods, approaches, and contributions to public health intervention research

Population health interventions are essential to reduce health inequalities and tackle other public health priorities, but they are not always amenable to experimental manipulation. Natural experiment (NE) approaches are attracting growing interest as a way of providing evidence in such circumstances. One key challenge in evaluating NEs is selective exposure to the intervention. Studies should be based on a clear theoretical understanding of the processes that determine exposure. Even if the observed effects are large and rapidly follow implementation, confidence in attributing these effects to the intervention can be improved by carefully considering alternative explanations. Causal inference can be strengthened by including additional design features alongside the principal method of effect estimation.NEstudies often rely on existing (including routinely collected) data. Investment in such data sources and the infrastructure for linking exposure and outcome data is essential if the potential for such studies to inform decision making is to be realized

Mapping genetic interactions in cancer: a road to rational combination therapies.

The discovery of synthetic lethal interactions between poly (ADP-ribose) polymerase (PARP) inhibitors and BRCA genes, which are involved in homologous recombination, led to the approval of PARP inhibition as a monotherapy for patients with BRCA1/2-mutated breast or ovarian cancer. Studies following the initial observation of synthetic lethality demonstrated that the reach of PARP inhibitors is well beyond just BRCA1/2 mutants. Insights into the mechanisms of action of anticancer drugs are fundamental for the development of targeted monotherapies or rational combination treatments that will synergize to promote cancer cell death and overcome mechanisms of resistance. The development of targeted therapeutic agents is premised on mapping the physical and functional dependencies of mutated genes in cancer. An important part of this effort is the systematic screening of genetic interactions in a variety of cancer types. Until recently, genetic-interaction screens have relied either on the pairwise perturbations of two genes or on the perturbation of genes of interest combined with inhibition by commonly used anticancer drugs. Here, we summarize recent advances in mapping genetic interactions using targeted, genome-wide, and high-throughput genetic screens, and we discuss the therapeutic insights obtained through such screens. We further focus on factors that should be considered in order to develop a robust analysis pipeline. Finally, we discuss the integration of functional interaction data with orthogonal methods and suggest that such approaches will increase the reach of genetic-interaction screens for the development of rational combination therapies

Use of Medicinal Cannabis and Synthetic Cannabinoids in Posttraumatic Stress Disorder (PTSD): a systematic review

Background and Objectives: Post-traumatic stress disorder (PTSD) is a common psychiatric disorder resulting from a traumatic event, is manifested through hyperarousal, anxiety, depressive symptoms, and sleep disturbances. Despite several therapeutic approaches being available, both pharmacological and psychological, recently a growing interest has developed in using cannabis and synthetic cannabinoids stems from their consideration as more efficient and better tolerated alternatives for the treatment of this condition. The present paper aims to evaluate the clinical and therapeutic potentials of medical cannabis and synthetic cannabinoids in treating PTSD patients. Methods: A systematic electronic search was performed, including all papers published up to May 2019, using the following keywords (((cannabis[Title/Abstract]) OR (synthetic cannabinoids [Title/Abstract])) AND ((PTSD[Title/Abstract]) OR (Posttraumatic stress disorder[Title/Abstract]))) for the topics ‘Cannabis’, ‘Synthetic Cannabinoids’, ‘PTSD’, and MESH terms, on the PubMed, Cochrane Library, and Web of Science online databases. For data gathering purposes, PRISMA guidelines were followed. Results were organized into two groups, considering cannabis and synthetic cannabinoids as different therapeutic approaches for PTSD. Results: Present data show that cannabis and synthetic cannabinoids, both acting on the endocannabinoids system, may have a potential therapeutic use for improving PTSD symptoms, e.g., reducing anxiety, modulating memory-related processes, and improving sleep. Conclusions: Even though the current literature suggests that cannabis and synthetic cannabinoids may have a role in the treatment of PTSD, there is currently limited evidence regarding their safety and efficacy. Therefore, additional research is needed in order to better understand the effectiveness and therapeutic usage of these drug classes and monitor their safety.Peer reviewe

Randomised controlled trials of complex interventions and large-scale transformation of services

Complex interventions and large-scale transformations of services are necessary to meet the health-care challenges of the 21st century. However, the evaluation of these types of interventions is challenging and requires methodological development. Innovations such as cluster randomised controlled trials, stepped-wedge designs, and non-randomised evaluations provide options to meet the needs of decision-makers. Adoption of theory and logic models can help clarify causal assumptions, and process evaluation can assist in understanding delivery in context. Issues of implementation must also be considered throughout intervention design and evaluation to ensure that results can be scaled for population benefit. Relevance requires evaluations conducted under real-world conditions, which in turn requires a pragmatic attitude to design. The increasing complexity of interventions and evaluations threatens the ability of researchers to meet the needs of decision-makers for rapid results. Improvements in efficiency are thus crucial, with electronic health records offering significant potential

Beyond Personalization: Research Directions in Multistakeholder Recommendation

Recommender systems are personalized information access applications; they are ubiquitous in today's online environment, and effective at finding items that meet user needs and tastes. As the reach of recommender systems has extended, it has become apparent that the single-minded focus on the user common to academic research has obscured other important aspects of recommendation outcomes. Properties such as fairness, balance, profitability, and reciprocity are not captured by typical metrics for recommender system evaluation. The concept of multistakeholder recommendation has emerged as a unifying framework for describing and understanding recommendation settings where the end user is not the sole focus. This article describes the origins of multistakeholder recommendation, and the landscape of system designs. It provides illustrative examples of current research, as well as outlining open questions and research directions for the field.Comment: 64 page