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INTRODUCTION: Genetic testing is used across medical disciplines leading to unprecedented demand for genetic services. This has resulted in excessive waitlists and unsustainable pressure on the standard model of genetic healthcare. Alternative models are needed; e-health tools represent scalable and evidence-based solution. We aim to evaluate the effectiveness of the Genetics Navigator, an interactive patient-centred digital platform that supports the collection of medical and family history, provision of pregenetic and postgenetic counselling and return of genetic testing results across paediatric and adult settings. METHODS AND ANALYSIS: We will evaluate the effectiveness of the Genetics Navigator combined with usual care by a genetics clinician (physician or counsellor) to usual care alone in a randomised controlled trial. One hundred and thirty participants (adults patients or parents of paediatric patients) eligible for genetic testing through standard of care will be recruited across Ontario genetics clinics. Participants randomised into the intervention arm will use the Genetics Navigator for pretest and post-test genetic counselling and results disclosure in conjunction with their clinician. Participants randomised into the control arm will receive usual care, that is, clinician-delivered pretest and post-test genetic counselling, and results disclosure. The primary outcome is participant distress 2 weeks after test results disclosure. Secondary outcomes include knowledge, decisional conflict, anxiety, empowerment, quality of life, satisfaction, acceptability, digital health literacy and health resource use. Quantitative data will be analysed using statistical hypothesis tests and regression models. A subset of participants will be interviewed to explore user experience; data will be analysed using interpretive description. A cost-effectiveness analysis will examine the incremental cost of the Navigator compared with usual care per unit reduction in distress or unit improvement in quality of life from public payer and societal perspectives. ETHICS AND DISSEMINATION: This study was approved by Clinical Trials Ontario. Results will be shared through stakeholder workshops, national and international conferences and peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT06455384.

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STUDY OBJECTIVES: To investigate whether neurobehavioral impairments are exacerbated during successive cycles of sleep restriction and recovery in young adults, and whether a variable short sleep schedule can mitigate these impairments relative to a stable one. METHODS: Fifty-two healthy young adults (25 males, aged: 21-28) were randomly assigned to the stable short sleep group, the variable short sleep group, or the control group in this laboratory-based study. They underwent two baseline nights of 8-hour time-in-bed (TIB), followed by two cycles of "weekday" sleep opportunity manipulation and "weekend" recovery (8-hour TIB). During each manipulation period, the stable short sleep and the control groups received 6- and 8-hour TIBs each night respectively, while the variable short sleep group received 8-hour, 4-hour, 8-hour, 4-hour, and 6-hour TIBs from the first to the fifth night. Neurobehavioral functions were assessed five times each day. RESULTS: The stable short sleep group showed faster vigilance deterioration in the second week of sleep restriction as compared to the first. This effect was not observed in the variable short sleep group. Subjective alertness and practice-based improvement in processing speed were attenuated in both short sleep groups. CONCLUSIONS: In young adults, more variable short sleep schedules incorporating days of prophylactic or recovery sleep might mitigate compounding vigilance deficits resulting from recurrent cycles of sleep restriction. However, processing speed and subjective sleepiness were still impaired in both short sleep schedules. Getting sufficient sleep consistently is the only way to ensure optimal neurobehavioral functioning. CLINICAL TRIAL: Performance, Mood, and Brain and Metabolic Functions During Different Sleep Schedules (STAVAR), https://www.clinicaltrials.gov/study/NCT04731662, NCT04731662.

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The increasing incidence of hypercholesterolemia-related diseases even in the presence of the currently available cholesterol-lowering drugs indicates a need to discover new therapeutic drugs. This study aimed to investigate the hypocholesterolemic potential of two triterpenoids isolated from Protorhus longifolia stem bark. In silico techniques and in vitro enzyme assays were used to evaluate the potential inhibition of cholesterol esterase and HMG-CoA reductase by the triterpenoids (ARM-2 and RA-5). The toxicity, modulation of low-density lipoprotein (LDL) uptake, and associated gene expression were determined in HepG2 hepatocytes. In silico molecular docking revealed that ARM-2 compared with RA-5 has a relatively stronger binding affinity for both enzymes. Both triterpenoids further demonstrated promising in silico drug-likeness properties and favorable ADMET profiles characterized by high intestinal absorption and lack of CYP450 enzyme inhibition. The compounds further showed, to varying degrees of efficacy, inhibition of cholesterol micellization as well as both cholesterol esterase and HMG-CoA reductase activities with IC50 values ranging from 16.4 to 41.1 µM. Moreover, enhanced hepatic cellular LDL uptake and the associated upregulation of the LDL-R and SREBP-2 gene expression were observed in the triterpenoid-treated HepG2 cells. It is evident that the triterpenoids, especially ARM-2, possess hypocholesterolemic properties, and these molecules can serve as leads or structural templates for the development of new hypocholesterolemic drugs.

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Secondary findings (SFs) identified through genomic sequencing (GS) can offer a wide range of health benefits to patients. Resource and capacity constraints pose a challenge to their clinical management; therefore, clinical workflows are needed to optimise the health benefits of SFs. In this paper, we describe a model we created for the return and referral of all clinically significant SFs, beyond medically actionable results, from GS. As part of a randomised controlled trial evaluating the outcomes and costs of disclosing all clinically significant SFs from GS, we consulted genetics and primary care experts to determine a feasible workflow to manage SFs. Consensus was sought to determine appropriate clinical recommendations for each category of SF and which clinician specialist would provide follow-up care. We developed a communication and referral plan for each category of SFs. This involved referrals to specialised clinics, such as an Adult Genetics clinic, for highly penetrant medically actionable findings. Common and non-urgent SFs, such as pharmacogenomics and carrier status results for non-family planning participants, were directed back to the family physician (FP). SF results and recommendations were communicated directly to participants to respect autonomy and to their FPs to support follow-up of SFs. We describe a model for the return and referral of all clinically significant SFs to facilitate the utility of GS and promote the health benefits of SFs. This may serve as a model for others returning GS results transitioning participants from research to clinical settings.

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We aimed to describe patient preferences for a broad range of secondary findings (SF) from genomic sequencing (GS) and factors driving preferences. We assessed preference data within a trial of the Genomics ADvISER, (SF decision aid) among adult cancer patients. Participants could choose from five categories of SF: (1) medically actionable; (2) polygenic risks; (3) rare diseases; (4) early-onset neurological diseases; and (5) carrier status. We analyzed preferences using descriptive statistics and drivers of preferences using multivariable logistic regression models. The 133 participants were predominantly European (74%) or East Asian or mixed ancestry (13%), female (90%), and aged > 50 years old (60%). The majority chose to receive SF. 97% (129/133) chose actionable findings with 36% (48/133) choosing all 5 categories. Despite the lack of medical actionability, participants were interested in receiving SF of polygenic risks (74%), carrier status (75%), rare diseases (59%), and early-onset neurologic diseases (53%). Older participants were more likely to be interested in receiving results for early-onset neurological diseases, while those exhibiting lower decisional conflict were more likely to select all categories. Our results highlight a disconnect between cancer patient preferences and professional guidelines on SF, such as ACMG's recommendations to only return medically actionable secondary findings. In addition to clinical evidence, future guidelines should incorporate patient preferences.

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OBJECTIVES: To quantify school-age children's sleep and parent-associated factors on weekdays and weekends in Singapore, and investigate school-related and parent-related factors associated with short sleep. METHODS: In an online survey, 251 parents with a child aged 7-12 y in Singapore reported their child's sleep duration and school start time. Parent-related factors including sleep hygiene (e.g., parent-set bedtime), sleep priority (the amount of sleep respondents allowed their children to trade for other activities), and both parents' sleep durations, were also reported. RESULTS: The prevalence of short sleep among the children was 64.5% on weekdays and 19.5% on weekends. Children's sleep duration increased from 8.42 h on weekdays to 9.45 h on weekends (p < .001). Relative to weekdays, on weekends, parents showed similar increases in sleep durations (p < .001), imposed poorer sleep hygiene on their children (reduced likelihood of setting bedtimes and increased pre-bedtime electronic device use; p < .001), and allowed their children to trade more sleep for interacting with family and friends, social media, gaming, and TV / videos (p < .001). Shorter sleep duration in children was significantly associated with earlier school start time (B = 0.80, p = .02) and poorer sleep hygiene on weekdays (B = 0.16, p < .001), but lower sleep priority (B = 0.05, p = .002) and shorter parental sleep duration on weekends (maternal: B = 0.18, p < .001, paternal: B = 0.17, p = .002). CONCLUSIONS: Delaying school start times may be effective in increasing school-age children's sleep duration on weekdays, while family-based interventions designed to enhance sleep hygiene, priority of sleep over other activities, and parents' sleep durations can benefit children's sleep duration on both weekdays and weekends.

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PURPOSE: Adherence to 24-hour movement guidelines of ≥60 minutes of physical activity, ≤2 hours of screen time, and 9-11 hours of sleep has been shown to benefit cognitive, physical, and psychosocial health in children and young adolescents aged 5-13 years. However, these findings have mostly been based on cross-sectional studies or relatively small samples and the associations between adherence to guidelines and brain structure remain to be evaluated. METHODS: Data from the Adolescent Brain Cognitive Development℠ (ABCD) study of 10,574 early adolescents aged 9-14 years from September 2016 to January 2021 were used to examine whether adherence to 24-hour movement guidelines benefits cognition (general cognitive ability, executive function, and learning/memory assessed by the National Institutes of Health Toolbox neurocognitive battery), body mass index, psychosocial health (internalizing, externalizing, and total problems from the parent-reported Child Behavior Checklist), and magnetic resonance imaging-derived brain morphometric measures at baseline (T1), ∼2 years later (T2), and longitudinally from T1 to T2 (T2-T1). Multivariable linear mixed models were used, with adjustments for sociodemographic confounders. Time elapsed and T1 outcome measures were also controlled for in longitudinal models. RESULTS: Better cognitive scores, fewer behavioral problems, lower adiposity levels, and greater gray matter volumes were observed in those who met both sleep and screen time recommendations compared to those who met none. Longitudinal follow-up further supports these findings; participants who met both recommendations at T1 and T2 evidenced better outcome measures than those who met none. DISCUSSION: These findings support consideration of integrated rather than isolated movement recommendations across the day in early adolescence for better cognitive, physical and psychosocial health. Although the associations between physical activity and health indicators were less consistent in this study, the significant findings from sleep and screen time demonstrate the importance of considering movement recommendations in an integrated rather than isolated manner for adolescent health. It is recommended that movement behaviors be simultaneously targeted for better developmental outcomes.

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Laboratory-based sleep manipulations show asymmetries between positive and negative affect, but say little about how more specific moods might change. We report extensive analyzes of items from the Positive and Negative Affect Scale (PANAS) during days following nights of chronic sleep restriction (6 h sleep opportunity), during 40 h of acute sleep deprivation under constant routine conditions, and during a week-long forced desynchrony protocol in which participants lived on a 28-h day. Living in the laboratory resulted in medium effects sizes on all positive moods (Attentiveness, General Positive Affect, Joviality, Assuredness), with a general deterioration as the days wore on. These effects were not found with negative moods. Sleep restriction reduced some positive moods, particularly Attentiveness (also General Positive), and increased Hostility. A burden of chronic sleep loss also led to lower positive moods when participants confronted the acute sleep loss challenge, and all positive moods, as well as Fearfulness, General Negative Affect and Hostility were affected. Sleeping at atypical circadian phases resulted in mood changes: all positive moods reduced, Hostility and General Negative Affect increased. Deteriorations increased the further participants slept from their typical nocturnal sleep. In most cases the changes induced by chronic or acute sleep loss or mistimed sleep waxed or waned across the waking day, with linear or various non-linear trends best fitting these time-awake-based changes. While extended laboratory stays do not emulate the fluctuating emotional demands of everyday living, these findings demonstrate that even in controlled settings mood changes systematically as sleep is shortened or mistimed.

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The Omicron severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant led to a dramatic global epidemic wave following detection in South Africa in November 2021. The BA.1 Omicron lineage was dominant and responsible for most SARS-CoV-2 outbreaks in countries around the world during December 2021-January 2022, while other Omicron lineages, including BA.2, accounted for the minority of global isolates. Here, we describe the Omicron wave in the Philippines by analysing genomic data. Our results identify the presence of both BA.1 and BA.2 lineages in the Philippines in December 2021, before cases surged in January 2022. We infer that only the BA.2 lineage underwent sustained transmission in the country, with an estimated emergence around 18 November 2021 (95 per cent highest posterior density: 6-28 November), while despite multiple introductions, BA.1 transmission remained limited. These results suggest that the Philippines was one of the earliest areas affected by BA.2 and reiterate the importance of whole genome sequencing for monitoring outbreaks.

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PURPOSE: Electronic consultation (eConsult) is a freely-available secure online platform connecting primary care providers (PCPs) to geneticists. Our purpose was to determine whether eConsult is effective in improving genetics service delivery in primary care. METHODS: PCP questionnaires regarding eConsult's utility, geneticists' tracking form assessments of eConsult type and appropriateness, and geneticists' interviews on implementing eConsult were carried out. RESULTS: In 2 regions of Ontario, Canada, from January 2019 to June 2020, there were 305 genetics eConsults. For 169 (55%), PCPs indicated receiving good advice for a new course of action; for 110 (36%), referral was now avoided; and for 261 (86%), eConsult was perceived valuable for patient management. Of the 131 geneticist-completed tracking forms, cancer questions were most common (68, 52%). For 63 (48%), geneticists disagreed/strongly disagreed PCPs should know the answer to the referral question. From the interview data, it was observed that geneticists described eConsult positively and suggested how it might improve access and efficiencies if integrated into genetic service delivery. Dealing with eConsults virtually could reduce waitlists, and suggesting appropriate investigations for PCPs could improve efficiencies. CONCLUSION: eConsult offers a potential solution for receiving timely genetics advice and avoiding unnecessary patient referrals, however, greater effect on access and wait times will need systematic integration into PCP and geneticist practice.

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Naps are increasingly considered a means to boost cognitive performance. We quantified the cognitive effects of napping in 60 samples from 54 studies. 52 samples evaluated memory. We first evaluated effect sizes for all tests together, before separately assessing their effects on memory, vigilance, speed of processing and executive function. We next examined whether nap effects were moderated by study features of age, nap length, nap start time, habituality and prior sleep restriction. Naps showed significant benefits for the total aggregate of cognitive tests (Cohen's d = 0.379, CI95 = 0.296-0.462). Significant domain specific effects were present for declarative (Cohen's d = 0.376, CI95 = 0.269-0.482) and procedural memory (Cohen's d = 0.494, CI95 = 0.301-0.686), vigilance (Cohen's d = 0.610, CI95 = 0.291-0.929) and speed of processing (Cohen's d = 0.211, CI95 = 0.052-0.369). There were no significant moderation effects of any of the study features. Nap effects were of comparable magnitude across subgroups of each of the 5 moderators (Q values = 0.009 to 8.572, p values > 0.116). Afternoon naps have a small to medium benefit over multiple cognitive tests. These effects transcend age, nap duration and tentatively, habituality and prior nocturnal sleep.

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Polyphenols are inversely associated with the incidence of chronic diseases, but therapeutic use is limited by poor stability and bioaccessibility. Encapsulation has been shown to overcome some of these limitations. A selection of polyphenols (catechin, gallic acid, and epigallocatechin gallate) and their combinations were encapsulated in beta-cyclodextrin (ßCD). Encapsulation was characterized and the thermal and storage stability was evaluated using the 2,2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assay. The samples were then subjected to in vitro digestion using a simple digestion (SD) model (gastric and duodenal phases) and a more complex digestion (CD) model (oral, gastric, and duodenal phases). Thereafter, the chemical (oxygen radical absorbance capacity assay) and cellular (dichlorofluorescein diacetate assay in Caco-2 cells) antioxidant and antiglycation (advanced glycation end-products assay) activities were determined. Inclusion complexes formed at a 1:1 molar ratio with a high encapsulation yield and efficiency. Encapsulation altered the morphology of the samples, increased the thermal stability of some and the storage stability of all samples. Encapsulation maintained the antioxidant activity of all samples and significantly improved the antiglycation and cellular antioxidant activities of some polyphenols following SD. In conclusion, the formed inclusion complexes of ßCD with polyphenols had greater storage stability, without altering the beneficial cellular effects of the polyphenols.

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Genomic sequencing (GS) can reveal secondary findings (SFs), findings unrelated to the reason for testing, that can be overwhelming to both patients and providers. An effective approach for communicating all clinically significant primary and secondary GS results is needed to effectively manage this large volume of results. The aim of this study was to develop a comprehensive approach to communicate all clinically significant primary and SF results. A genomic test report with accompanying patient and provider letters were developed in three phases: review of current clinical reporting practices, consulting with genetic and non-genetics experts, and iterative refinement through circulation to key stakeholders. The genomic test report and consultation letters present a myriad of clinically relevant GS results in distinct, tabulated sections, including primary (cancer) and secondary findings, with in-depth details of each finding generated from exome sequencing. They provide detailed variant and disease information, personal and familial risk assessments, clinical management details, and additional resources to help support providers and patients with implementing healthcare recommendations related to their GS results. The report and consultation letters represent a comprehensive approach to communicate all clinically significant SFs to patients and providers, facilitating clinical management of GS results.

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The Omicron SARS-CoV-2 variant led to a dramatic global epidemic wave following detection in South Africa in November, 2021. The Omicron lineage BA.1 was dominant and responsible for most domestic outbreaks during December 2021-January 2022, whilst other Omicron lineages including BA.2 accounted for the minority of global isolates. Here, we describe the Omicron wave in the Philippines by analysing genomic data. Our results identify the presence of both BA.1 and BA.2 lineages in the Philippines in December 2021, before cases surged in January 2022. We infer that only lineage BA.2 underwent sustained transmission in the country, with an estimated emergence around November 18th, 2021 [95% highest posterior density: November 6-28th], whilst despite multiple introductions BA.1 transmission remained limited. These results suggest the Philippines was one of the earliest areas affected by BA.2, and reiterate the importance of whole-genome sequencing for monitoring outbreaks.

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INTRODUCTION: The high demand for genetic tests and limited supply of genetics professionals has created a need for alternative service delivery models. Digital tools are increasingly being used to support multiple points in the genetic testing journey; however, none are transferable across multiple clinical specialties and settings nor do they encompass the entire trajectory of the journey. We aim to evaluate the effectiveness of the Genetics Adviser, an interactive, patient-facing, online digital health tool that delivers pre-test counselling, provides support during the waiting period for results, and returns results with post-test counselling, encompassing the entire patient genetic testing journey. METHODS AND ANALYSIS: We will compare the Genetics Adviser paired with a brief genetic counselling session to genetic counselling alone in a randomised controlled trial. One hundred and forty patients who previously received uninformative genetic test results for their personal and family history of cancer will be recruited from familial cancer clinics in Toronto and offered all clinically significant results from genomic sequencing. Participants randomised into the intervention arm will use the Genetics Adviser to learn about genomic sequencing, receive pre-test counselling, support during the waiting period and results, supplemented with brief counselling from a genetic counsellor. Participants in the control arm will receive standard pre-test and post-test counselling for genomic sequencing from a genetic counsellor. Our primary outcome is decisional conflict following pre-test counselling from the Genetics Adviser+genetic counsellor or counsellor alone. Secondary outcomes include: knowledge, satisfaction with decision-making, anxiety, quality of life, psychological impact of results, empowerment, acceptability and economic impact for patients and the health system. A subset of patients will be interviewed to assess user experience. ETHICS AND DISSEMINATION: This study has been approved by Clinical Trials Ontario Streamlined Research Ethics Review System (REB#20-035). Results will be shared through stakeholder workshops, national and international conferences and peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04725565.

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STUDY OBJECTIVES: Gains in cognitive test performance that occur during adolescence are associated with brain maturation. Cortical thinning and reduced sleep slow wave activity (SWA) are markers of such developmental changes. Here we investigate whether they mediate age-related improvements in cognition. METHODS: 109 adolescents aged 15-19 years (49 males) underwent magnetic resonance imaging, polysomnography (PSG), and a battery of cognitive tasks within a 2-month time window. Cognitive tasks assessed nonverbal intelligence, sustained attention, speed of processing and working memory and executive function. To minimize the effect of sleep history on SWA and cognitive performance, PSG and test batteries were administered only after at least 8 nights of 9-h time-in-bed (TIB) sleep opportunity. RESULTS: Age-related improvements in speed of processing (r = 0.33, p = 0.001) and nonverbal intelligence (r = 0.24, p = 0.01) domains were observed. These cognitive changes were associated with reduced cortical thickness, particularly in bilateral temporoparietal regions (rs = -0.21 to -0.45, ps < 0.05), as well as SWA (r = -0.35, p < 0.001). Serial mediation models found that ROIs in the middle/superior temporal cortices, together with SWA mediated the age-related improvement observed on cognition. CONCLUSIONS: During adolescence, age-related improvements in cognition are mediated by reductions in cortical thickness and sleep SWA.

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Study Objectives: We attempted to predict vigilance performance in adolescents during partial sleep deprivation using task summary metrics and drift diffusion modelling measures (DDM) derived from baseline vigilance performance. Methods: In the Need for Sleep studies, 57 adolescents (age = 15-19 years) underwent two baseline nights of 9-h time-in-bed (TIB), followed by two cycles of weekday sleep-restricted nights (5-h or 6.5-h TIB) and weekend recovery nights (9-h TIB). Vigilance was assessed daily with the Psychomotor Vigilance Task (PVT), with the number of lapses (response times ≥ 500 ms) as the primary outcome measure. The two DDM predictors were drift rate, which quantifies the speed of information accumulation and determines how quickly an individual derives a decision response, and non-decision time range, which indicates within-subject variation in physical, non-cognitive responding, e.g. motor actions. Results: In the first week of sleep curtailment, faster accumulation of lapses was significantly associated with more lapses at baseline (p = .02), but not the two baseline DDM metrics: drift and non-decision time range (p > .07). On the other hand, faster accumulation of lapses and greater increment in reaction time variability from the first to the second week of sleep restriction were associated with lower drift (p < .007) at baseline. Conclusions: Among adolescents, baseline PVT lapses can predict inter-individual differences in vigilance vulnerability during 1 week of sleep restriction on weekdays, while drift more consistently predicts vulnerability during more weeks of sleep curtailment. Clinical Trial Information: Effects of Napping in Sleep-Restricted Adolescents, clinicaltrials.gov, NCT02838095. The Cognitive and Metabolic Effects of Sleep Restriction in Adolescents (NFS4), clinicaltrials.gov, NCT03333512.

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Primary care providers will increasingly be tasked with managing most secondary findings from genomic sequencing, but literature exploring their capacity to manage findings beyond conventional genetic testing is limited. This study aimed to explore primary care providers' challenges and potential solutions for managing secondary findings. Providers were recruited in two groups. Group 1 providers had a patient in their practice who received secondary findings and all potential group 1 providers were invited to participate. Group 2 providers were provided with the secondary findings of a hypothetical patient and were purposefully sampled for maximal variation in sex, practice setting, and geographic location. Providers were interviewed about their challenges and solutions managing secondary findings from a patient in their practice or a hypothetical patient. Using interpretive description methodology, transcripts were analysed thematically complemented by constant comparison. Out of the fifty-five providers invited, 15 family physicians participated across community and academic settings in Ontario, Canada (range 6-40 years in practice; 10/15 female). Providers described a responsibility to manage secondary findings, but limited capacity for this, describing practice, knowledge, and technical challenges. Providers expressed concern that compared to other incidental findings, secondary genomic findings might be reported directly to patients and result in longer-term anxiety. Potential solutions were a structured letter with categorized results and summary tables highlighting key secondary findings with follow-up recommendations and resources, as well as electronic medical records (EMRs) that store and integrate genomic information for prescribing or referrals. These solutions were deemed essential to address knowledge and technical challenges faced by primary care physicians and ultimately promote clinical utility of secondary findings.

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Most secondary genomic findings (SFs) fall in the scope of primary care practice. However, primary care providers' (PCPs) capacity to manage these findings is not well understood. We explored PCPs' views and experiences of managing SFs through a qualitative study. PCPs participated in semi-structured interviews about SFs from a patient in their practice or a hypothetical patient. The interpretive descriptive methodology was used to analyze transcripts thematically through constant comparison. Fifteen family physicians from Ontario, Canada participated (ten females; 6-40 years in practice across community and academic settings). PCPs made sense of SFs through the lens of actionability: they actively looked for clinical relevance by considering a wide range of immediate and future actions, including referrals, genetic testing, screening, lifestyle changes, counseling about family planning, informing family members, future medication choice, increased vigilance/surveillance, and managing results in the electronic medical record. PCPs saw clinical actionability as the main benefit mitigating the potential harms of learning SFs, namely patient anxiety and unnecessary investigations. PCPs conceptualized actionability more broadly than it is traditionally defined in medical genetics. Further research will be needed to determine if PCPs' emphasis on actionability conflicts with patients' expectations of SFs and if it leads to overutilization of healthcare resources.

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