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Kate Romero,1,2 Balaji Goparaju,1,2 Kathryn Russo,1,2 M Brandon Westover,1 Matt T Bianchi1,2 1Neurology Department, Massachusetts General Hospital, 2Division of Sleep Medicine, Harvard Medical School, Boston, MA, USA Abstract: Insomnia is a common symptom, with chronic insomnia being diagnosed in 5–10% of adults. Although many insomnia patients use prescription therapy for insomnia, the health benefits remain uncertain and adverse risks remain a concern. While similar effectiveness and risk concerns exist for herbal remedies, many individuals turn to such alternatives to prescriptions for insomnia. Like prescription hypnotics, herbal remedies that have undergone clinical testing often show subjective sleep improvements that exceed objective measures, which may relate to interindividual heterogeneity and/or placebo effects. Response heterogeneity can undermine traditional randomized trial approaches, which in some fields has prompted a shift toward stratified trials based on genotype or phenotype, or the so-called n-of-1 method of testing placebo versus active drug in within-person alternating blocks. We reviewed six independent compendiums of herbal agents to assemble a group of over 70 reported to benefit sleep. To bridge the gap between the unfeasible expectation of formal evidence in this space and the reality of common self-medication by those with insomnia, we propose a method for guided self-testing that overcomes certain operational barriers related to inter- and intraindividual sources of phenotypic variability. Patient-chosen outcomes drive a general statistical model that allows personalized self-assessment that can augment the open-label nature of routine practice. The potential advantages of this method include flexibility to implement for other (nonherbal) insomnia interventions. Keywords: insomnia, over the counter, alternative remedy, herbal, supplement

Matt T Bianchi,1,2 Kathryn Russo,1 Harriett Gabbidon,1 Tiaundra Smith,1 Balaji Goparaju,1 M Brandon Westover1 1Neurology Department, Massachusetts General Hospital, 2Division of Sleep Medicine, Harvard Medical School, Boston, MA, USA Abstract: Clinical polysomnography (PSG) databases are a rich resource in the era of “big data” analytics. We explore the uses and potential pitfalls of clinical data mining of PSG using statistical principles and analysis of clinical data from our sleep center. We performed retrospective analysis of self-reported and objective PSG data from adults who underwent overnight PSG (diagnostic tests, n=1835). Self-reported symptoms overlapped markedly between the two most common categories, insomnia and sleep apnea, with the majority reporting symptoms of both disorders. Standard clinical metrics routinely reported on objective data were analyzed for basic properties (missing values, distributions), pairwise correlations, and descriptive phenotyping. Of 41 continuous variables, including clinical and PSG derived, none passed testing for normality. Objective findings of sleep apnea and periodic limb movements were common, with 51% having an apnea–hypopnea index (AHI) >5 per hour and 25% having a leg movement index >15 per hour. Different visualization methods are shown for common variables to explore population distributions. Phenotyping methods based on clinical databases are discussed for sleep architecture, sleep apnea, and insomnia. Inferential pitfalls are discussed using the current dataset and case examples from the literature. The increasing availability of clinical databases for large-scale analytics holds important promise in sleep medicine, especially as it becomes increasingly important to demonstrate the utility of clinical testing methods in management of sleep disorders. Awareness of the strengths, as well as caution regarding the limitations, will maximize the productive use of big data analytics in sleep medicine. Keywords: polysomnography, sleep disorders, subjective symptoms, correlation, plotting, statistics

Lidia MVR Moura,1,2 M Brandon Westover,1,2 David Kwasnik,1 Andrew J Cole,1,2 John Hsu3–5 1Massachusetts General Hospital, Department of Neurology, Epilepsy Service, Boston, MA, USA; 2Harvard Medical School, Boston, MA, USA; 3Massachusetts General Hospital, Mongan Institute, Boston, MA, USA; 4Harvard Medical School, Department of Medicine, Boston, MA, USA; 5Harvard Medical School, Department of Health Care Policy, Boston, MA, USA Abstract: The elderly population faces an increasing number of cases of chronic neurological conditions, such as epilepsy and Alzheimer’s disease. Because the elderly with epilepsy are commonly excluded from randomized controlled clinical trials, there are few rigorous studies to guide clinical practice. When the elderly are eligible for trials, they either rarely participate or frequently have poor adherence to therapy, thus limiting both generalizability and validity. In contrast, large observational data sets are increasingly available, but are susceptible to bias when using common analytic approaches. Recent developments in causal inference-analytic approaches also introduce the possibility of emulating randomized controlled trials to yield valid estimates. We provide a practical example of the application of the principles of causal inference to a large observational data set of patients with epilepsy. This review also provides a framework for comparative-effectiveness research in chronic neurological conditions. Keywords: epilepsy, epidemiology, neurostatistics, causal inference

Objective: Clinical intuition suggests that risk-reducing treatments are more beneficial for patients with greater risk of disease. This intuition contributes to our rationale for tolerating greater adverse event risk in the setting of secondary prevention of certain diseases such as myocardial infarction or stroke. However, under certain conditions treatment benefits may be greater in primary prevention, even when the treatment carries harmful adverse effect potential.Study Design and Setting: We present simple decision-theoretic models that illustrate conditions of risk and benefit under which a treatment is predicted to be more beneficial in primary than in secondary prevention.Results: The models cover a spectrum of possible clinical circumstances, and demonstrate that net benefit in primary prevention can occur despite no benefit (or even net harm) in secondary prevention.Conclusion: This framework provides a rationale for extending the familiar concept of balancing risks and benefits to account for disease-specific considerations of primary vs. secondary prevention. [ABSTRACT FROM AUTHOR]