Determining the most effective insomnia medication for patients may require therapeutic trials of different medications. In addition, medication side effects, interactions with co-administered medications, and declining therapeutic efficacy can necessitate switching between different insomnia medications or deprescribing altogether. Currently, little guidance exists regarding the safest and most effective way to transition from one medication to another. Thus, we developed evidence-based guidelines to inform clinicians regarding best practices when deprescribing or transitioning between insomnia medications. Five U.S.-based sleep experts reviewed the literature involving insomnia medication deprescribing, tapering, and switching and rated the quality of evidence. They used this evidence to generate recommendations through discussion and consensus. When switching or discontinuing insomnia medications, we recommend benzodiazepine hypnotic drugs be tapered while additional CBT-I is provided. For Z-drugs zolpidem and eszopiclone (and not zaleplon), especially when prescribed at supratherapeutic doses, tapering is recommended with a 1-2-day delay in administration of the next insomnia therapy when applicable. There is no need to taper DORAs, doxepin, and ramelteon. Lastly, off-label antidepressants and antipsychotics used to treat insomnia should be gradually reduced when discontinuing. In general, offering individuals a rationale for deprescribing or switching and involving them in the decision-making process can facilitate the change and enhance treatment success.

While evidence supports the benefits of medications for the treatment of chronic insomnia, there is ongoing debate regarding their appropriate duration of use. A panel of sleep experts conducted a clinical appraisal regarding the use of insomnia medications, as it relates to the evidence supporting the focus statement, "No insomnia medication should be used on a daily basis for durations longer than 3 weeks at a time". The panelists' assessment was also compared to findings from a national survey of practicing physicians, psychiatrists, and sleep specialists. Survey respondents revealed a wide range of opinions regarding the appropriateness of using the US Food and Drug Administration (FDA)-approved medications for the treatment of insomnia lasting more than 3 weeks. After discussion of the literature, the panel unanimously agreed that some classes of insomnia medications, such as non-benzodiazepines hypnotics, have been shown to be effective and safe for long-term use in the appropriate clinical setting. For eszopiclone, doxepin, ramelteon and the newer class of dual orexin receptor antagonists, the FDA label does not specify that their use should be of a limited duration. Thus, an evaluation of evidence supporting the long-term safety and efficacy of newer non-benzodiazepine hypnotics is timely and should be considered in practice recommendations for the duration of pharmacologic treatment of chronic insomnia.

Gene fusions are known to play critical roles in tumor pathogenesis. Yet, sensitive and specific algorithms to detect gene fusions in cancer do not currently exist. In this paper, we present a new statistical algorithm, MACHETE (Mismatched Alignment CHimEra Tracking Engine), which achieves highly sensitive and specific detection of gene fusions from RNA-Seq data, including the highest Positive Predictive Value (PPV) compared to the current state-of-the-art, as assessed in simulated data. We show that the best performing published algorithms either find large numbers of fusions in negative control data or suffer from low sensitivity detecting known driving fusions in gold standard settings, such as EWSR1-FLI1. As proof of principle that MACHETE discovers novel gene fusions with high accuracy in vivo, we mined public data to discover and subsequently PCR validate novel gene fusions missed by other algorithms in the ovarian cancer cell line OVCAR3. These results highlight the gains in accuracy achieved by introducing statistical models into fusion detection, and pave the way for unbiased discovery of potentially driving and druggable gene fusions in primary tumors.

Insomnia is a significant, highly prevalent, persistent public health problem but often remains undiagnosed and untreated. Current treatment practices are not always evidence-based. When insomnia is comorbid with anxiety or depression, treatment often targets that comorbid condition with the expectation that improvement of the mental health condition will generalize to sleep symptoms. An expert panel of seven members conducted a clinical appraisal of the literature regarding the treatment of insomnia when comorbid anxiety or depression are also present. The clinical appraisal consisted of the review, presentation, and assessment of current published evidence as it relates to the panel's predetermined clinical focus statement, "Whenever chronic insomnia is associated with another condition, such as anxiety or depression, that psychiatric condition should be the only focus of treatment as the insomnia is most likely a symptom of the condition". The results from an electronic national survey of US-based practicing physicians, psychiatrists, and sleep (N = 508) revealed that >40% of physicians agree "at least somewhat" that treatment of comorbid insomnia should focus solely on the psychiatric condition. Whereas 100% of the expert panel disagreed with the statement. Thus, an important gap exists between current clinical practices and evidence-based guidelines and more awareness is needed so that insomnia is treated distinctly from comorbid anxiety and depression.

A scientific advisory panel of seven U.S. and Canadian sleep experts performed a clinical appraisal by comparing general medical opinion, assessed via a survey of practicing clinicians, regarding insomnia treatment, with the available scientific evidence. This clinical appraisal focuses on the specific statement, "Treatments for insomnia have uniformly been shown to significantly improve the associated daytime impairment seen with insomnia." The advisory panel reviewed and discussed the available body of evidence within the published medical literature to determine what discrepancies may exist between the currently published evidence base and general medical opinion. The advisory panels' evaluation of this statement was also compared with the results of a national survey of primary care physicians, psychiatrists, nurse practitioners, physician assistants, and sleep specialists in the United States. Contrary to general medical opinion, the expert advisory panel concluded that the medical literature did not support the statement. This gap highlights the need to educate the general medical community regarding insomnia treatment efficacy in pursuit of improved treatment outcomes.

During adolescence, internal circadian rhythms and biological sleep drive change to result in later sleep and wake times. As a result of these changes, early middle school and high school start times curtail sleep, hamper a students preparedness to learn, negatively impact physical and mental health, and impair driving safety. Furthermore, a growing body of evidence shows that delaying school start times positively impacts student achievement, health, and safety. Public awareness of the hazards of early school start times and the benefits of later start times are largely unappreciated. As a result, the American Academy of Sleep Medicine is calling on communities, school boards, and educational institutions to implement start times of 8:30 AM or later for middle schools and high schools to ensure that every student arrives at school healthy, awake, alert, and ready to learn.

The American Academy of Sleep Medicine and Sleep Research Society recently released a Consensus Statement regarding the recommended amount of sleep to promote optimal health in adults. This paper describes the methodology, background literature, voting process, and voting results for the consensus statement. In addition, we address important assumptions and challenges encountered during the consensus process. Finally, we outline future directions that will advance our understanding of sleep need and place sleep duration in the broader context of sleep health.

The American Academy of Sleep Medicine and Sleep Research Society recently released a Consensus Statement regarding the recommended amount of sleep to promote optimal health in adults. This paper describes the methodology, background literature, voting process, and voting results for the consensus statement. In addition, we address important assumptions and challenges encountered during the consensus process. Finally, we outline future directions that will advance our understanding of sleep need and place sleep duration in the broader context of sleep health.

The SARS-CoV-2 pandemic has differentially impacted populations across race and ethnicity. A multi-omic approach represents a powerful tool to examine risk across multi-ancestry genomes. We leverage a pandemic tracking strategy in which we sequence viral and host genomes and transcriptomes from nasopharyngeal swabs of 1049 individuals (736 SARS-CoV-2 positive and 313 SARS-CoV-2 negative) and integrate them with digital phenotypes from electronic health records from a diverse catchment area in Northern California. Genome-wide association disaggregated by admixture mapping reveals novel COVID-19-severity-associated regions containing previously reported markers of neurologic, pulmonary and viral disease susceptibility. Phylodynamic tracking of consensus viral genomes reveals no association with disease severity or inferred ancestry. Summary data from multiomic investigation reveals metagenomic and HLA associations with severe COVID-19. The wealth of data available from residual nasopharyngeal swabs in combination with clinical data abstracted automatically at scale highlights a powerful strategy for pandemic tracking, and reveals distinct epidemiologic, genetic, and biological associations for those at the highest risk.