Digital biomarkers: 3PM approach revolutionizing chronic disease management - EPMA 2024 position.

Non-communicable chronic diseases (NCDs) have become a major global health concern. They constitute the leading cause of disabilities, increased morbidity, mortality, and socio-economic disasters worldwide. Medical condition-specific digital biomarker (DB) panels have emerged as valuable tools to manage NCDs. DBs refer to the measurable and quantifiable physiological, behavioral, and environmental parameters collected for an individual through innovative digital health technologies, including wearables, smart devices, and medical sensors. By leveraging digital technologies, healthcare providers can gather real-time data and insights, enabling them to deliver more proactive and tailored interventions to individuals at risk and patients diagnosed with NCDs. Continuous monitoring of relevant health parameters through wearable devices or smartphone applications allows patients and clinicians to track the progression of NCDs in real time. With the introduction of digital biomarker monitoring (DBM), a new quality of primary and secondary healthcare is being offered with promising opportunities for health risk assessment and protection against health-to-disease transitions in vulnerable sub-populations. DBM enables healthcare providers to take the most cost-effective targeted preventive measures, to detect disease developments early, and to introduce personalized interventions. Consequently, they benefit the quality of life (QoL) of affected individuals, healthcare economy, and society at large. DBM is instrumental for the paradigm shift from reactive medical services to 3PM approach promoted by the European Association for Predictive, Preventive, and Personalized Medicine (EPMA) involving 3PM experts from 55 countries worldwide. This position manuscript consolidates multi-professional expertise in the area, demonstrating clinically relevant examples and providing the roadmap for implementing 3PM concepts facilitated through DBs.

The paradigm change from reactive medical services to 3PM in ischemic stroke: a holistic approach utilising tear fluid multi-omics, mitochondria as a vital biosensor and AI-based multi-professional data interpretation.

Worldwide stroke is the second leading cause of death and the third leading cause of death and disability combined. The estimated global economic burden by stroke is over US$891 billion per year. Within three decades (1990-2019), the incidence increased by 70%, deaths by 43%, prevalence by 102%, and DALYs by 143%. Of over 100 million people affected by stroke, about 76% are ischemic stroke (IS) patients recorded worldwide. Contextually, ischemic stroke moves into particular focus of multi-professional groups including researchers, healthcare industry, economists, and policy-makers. Risk factors of ischemic stroke demonstrate sufficient space for cost-effective prevention interventions in primary (suboptimal health) and secondary (clinically manifested collateral disorders contributing to stroke risks) care. These risks are interrelated. For example, sedentary lifestyle and toxic environment both cause mitochondrial stress, systemic low-grade inflammation and accelerated ageing; inflammageing is a low-grade inflammation associated with accelerated ageing and poor stroke outcomes. Stress overload, decreased mitochondrial bioenergetics and hypomagnesaemia are associated with systemic vasospasm and ischemic lesions in heart and brain of all age groups including teenagers. Imbalanced dietary patterns poor in folate but rich in red and processed meat, refined grains, and sugary beverages are associated with hyperhomocysteinaemia, systemic inflammation, small vessel disease, and increased IS risks. Ongoing 3PM research towards vulnerable groups in the population promoted by the European Association for Predictive, Preventive and Personalised Medicine (EPMA) demonstrates promising results for the holistic patient-friendly non-invasive approach utilising tear fluid-based health risk assessment, mitochondria as a vital biosensor and AI-based multi-professional data interpretation as reported here by the EPMA expert group. Collected data demonstrate that IS-relevant risks and corresponding molecular pathways are interrelated. For examples, there is an evident overlap between molecular patterns involved in IS and diabetic retinopathy as an early indicator of IS risk in diabetic patients. Just to exemplify some of them such as the 5-aminolevulinic acid/pathway, which are also characteristic for an altered mitophagy patterns, insomnia, stress regulation and modulation of microbiota-gut-brain crosstalk. Further, ceramides are considered mediators of oxidative stress and inflammation in cardiometabolic disease, negatively affecting mitochondrial respiratory chain function and fission/fusion activity, altered sleep-wake behaviour, vascular stiffness and remodelling. Xanthine/pathway regulation is involved in mitochondrial homeostasis and stress-driven anxiety-like behaviour as well as molecular mechanisms of arterial stiffness. In order to assess individual health risks, an application of machine learning (AI tool) is essential for an accurate data interpretation performed by the multiparametric analysis. Aspects presented in the paper include the needs of young populations and elderly, personalised risk assessment in primary and secondary care, cost-efficacy, application of innovative technologies and screening programmes, advanced education measures for professionals and general population-all are essential pillars for the paradigm change from reactive medical services to 3PM in the overall IS management promoted by the EPMA.

A Systematic Review and Meta-Analysis of Cognitive Effects of rTMS in Caucasian Patients with Mild Cognitive Impairment.

In recent years, repetitive transcranial magnetic stimulation (rTMS) has received much attention as a non-invasive, effective treatment modality for mild cognitive impairment (MCI). Although several meta-analyses have reported that rTMS can improve cognitive abilities, improvements in individual memory domains (speech, language, concentration, and memory) are poorly understood. In addition, stimulation parameters may be flawed in studies of global populations because of ethnic differences between Caucasians and Asians. This meta-analysis aimed to systematically characterize the efficacy of different combinations of rTMS parameters on different cognitive domains in Caucasian patients with MCI. We conducted a systematic literature search in Medline PubMed, Pubpsych, and Embase on the use of rTMS in MCI patients through November 2022. Randomized, double-blind, and sham-controlled trials (RCTs) from the Caucasian patient population were included. The studies reported outcome measures for different domains of cognition, such as language, concentration, or memory. Possible effects of covariates were examined using meta-regressions. The search yielded five publications. The analyses found that rTMS improved cognitive functions, memory, concentration, and language in patients with MCI and treatment with rTMS compared with the sham stimulation group. The statistical analysis results of the studies showed that rTMS could improve various cognitive functions, such as memory and concentration, in Caucasian MCI patients. A particular effect was found at a frequency of 10 Hz and stimulation of the LDLPFC. However, further studies are needed to validate these findings and explore more effective stimulation protocols and targets.

rTMS in mental health disorders.

Transcranial magnetic stimulation (TMS) is an innovative and non-invasive technique used in the diagnosis and treatment of psychiatric and neurological disorders. Repetitive TMS (rTMS) can modulate neuronal activity, neuroplasticity and arousal of the waking and sleeping brain, and, more generally, overall mental health. Numerous studies have examined the predictors of the efficacy of rTMS on clinical outcome variables in various psychiatric disorders. These predictors often encompass the stimulated brain region's location, electroencephalogram (EEG) activity patterns, potential morphological and neurophysiological anomalies, and individual patient's response to treatment. Most commonly, rTMS is used in awake patients with depression, catatonia, and tinnitus. Interestingly, rTMS has also shown promise in inducing slow-wave oscillations in insomnia patients, opening avenues for future research into the potential beneficial effects of these oscillations on reports of non-restorative sleep. Furthermore, neurophysiological measures emerge as potential, disease-specific biomarkers, aiding in predicting treatment response and monitoring post-treatment changes. The study posits the convergence of neurophysiological biomarkers and individually tailored rTMS treatments as a gateway to a new era in psychiatric care. The potential of rTMS to induce slow-wave activity also surfaces as a significant contribution to personalized treatment approaches. Further investigations are called for to validate the imaging and electrophysiological biomarkers associated with rTMS. In conclusion, the potential for rTMS to significantly redefine treatment strategies through personalized approaches could enhance the outcomes in neuropsychiatric disorders.

Comparative effectiveness of three versions of a stepped care model for insomnia differing in the amount of therapist support in internet-delivered treatment: study protocol for a pragmatic cluster randomised controlled trial (GET Sleep).

INTRODUCTION: It is unclear how internet-delivered cognitive-behavioural therapy for insomnia (CBT-I) can be integrated into healthcare systems, and little is known about the optimal level of therapist guidance. The aim of this study is to investigate three different versions of a stepped care model for insomnia (IG1, IG2, IG3) versus treatment as usual (TAU). IG1, IG2 and IG3 rely on treatment by general practitioners (GPs) in the entry level and differ in the amount of guidance by e-coaches in internet-delivered CBT-I. METHODS AND ANALYSIS: In this randomised controlled trial, 4268 patients meeting International Classification of Diseases, Tenth Revision (ICD-10) criteria for insomnia will be recruited. The study will use cluster randomisation of GPs with an allocation ratio of 3:3:3:1 (IG1, IG2, IG3, TAU). In step 1 of the stepped care model, GPs will deliver psychoeducational treatment; in step 2, an internet-delivered CBT-I programme will be used; in step 3, GPs will refer patients to specialised treatment. Outcomes will be collected at baseline, and 4 weeks, 12 weeks and 6 months after baseline assessment. The primary outcome is insomnia severity at 6 months. An economic evaluation will be conducted and qualitative interviews will be used to explore barriers and facilitators of the stepped care model. ETHICS AND DISSEMINATION: The study protocol was approved by the Ethics Committee of the Medical Centre-University of Freiburg. The results of the study will be published irrespective of the outcome. TRIAL REGISTRATION NUMBER: DRKS00021503.

Restless Legs Syndrome Prevalence and Clinical Correlates Among Psychiatric Inpatients: A Multicenter Study.

Background: There are only limited reports on the prevalence of restless legs syndrome (RLS) in patients with psychiatric disorders. The present study aimed to evaluate the prevalence and clinical correlates in psychiatric inpatients in Germany and Switzerland. Methods: This is a multicenter cross-sectional study of psychiatric inpatients with an age above 18 years that were diagnosed and evaluated face-to-face using the International RLS Study Group criteria (IRLSSG) and the International RLS severity scale (IRLS). In addition to sociodemographic and biometric data, sleep quality and mood were assessed using the Pittsburgh Sleep Quality Index (PSQI), the Insomnia Severity Index (ISI), the Epworth Sleepiness Scale (ESS), and the Patient Health Questionnaire (PHQ-9). In addition to univariate statistics used to describe and statistically analyze differences in variables of interest between patients with and without RLS, a logistic model was employed to identify predictors for the occurrence of RLS. Results: The prevalence of RLS in a sample of 317 psychiatric inpatients was 16.4%, and 76.9% of these were diagnosed with RLS for the first time. RLS severity was moderate to severe (IRLS ± SD: 20.3 ± 8.4). The prevalences in women (p = 0.0036) and in first-degree relatives with RLS (p = 0.0108) as well as the body mass index (BMI, p = 0.0161) were significantly higher among patients with RLS, while alcohol consumption was significantly lower in the RLS group. With the exception of atypical antipsychotics, treatment with psychotropic drugs was not associated with RLS symptoms. Regarding subjective sleep quality and mood, scores of the PSQI (p = 0.0007), ISI (p = 0.0003), and ESS (p = 0.0005) were higher in patients with RLS, while PHQ-9 scores were not different. A logistic regression analysis identified gender (OR 2.67; 95% CI [1.25; 5.72]), first-degree relatives with RLS (OR 3.29; 95% CI [1.11; 9.73], ESS score (OR 1.09; 95% CI [1.01; 1.17]), and rare alcohol consumption (OR 0.45; 95% CI [0.22; 0.94] as predictors for RLS. Conclusions: Clinically significant RLS had a high prevalence in psychiatric patients. RLS was associated with higher BMI, impaired sleep quality, and lower alcohol consumption. A systematic assessment of restless legs symptoms might contribute to improve the treatment of psychiatric patients.

Cognitive function in soccer athletes determined by sleep disruption and self-reported health, yet not by decision-reinvestment.

Background: Sleep disruption (SD) increases sympathetic activity and cortisol secretion, and delays cognitive functions such as reaction-time (RT). Sympathetic activity of disturbed sleepers, is similar to those of so-called decision-reinvesters. Decision-reinvestment refers to traits in individuals with greater tendency to ruminate and reinvest in their decisions, with significant decrease in both motor-control and cognitive performance. Decision-making quality is a crucial attribute to athletic performance which relies on RT. Consequently, SD affects pitch-performance negatively, particularly in decision-reinvesters. This observational pilot-study examined the relationship between SD and cognitive function, perceived health, as well as reinvestment strategies. The hypothesis was that athletes with lower SD perceive their health better, report lower stress levels, perform better in cognitive tasks, and show lower tendency for decision-reinvestment. Methods: Twenty-one football player recorded their sleep with fit-trackers for 7 nights. Participants self-reported their mental and physical health, decision-reinvestment strategy, sleep behaviour, and perceived stress levels. Athletes then performed a set of cognitive tests to examine memory function (Backwards Corsi), selective attention (STROOP), and cognitive flexibility (Wisconsin Card Sorting Test, WCST). Normality was tested with a Shapiro-Wilk test, and analysed with a Pearson's or Spearman's correlation test. Results: Significant correlation appeared between extended sleep-interruptions and Backwards Corsi RT, r = 0.66, p = 0.010, as further in total sleep time and wellbeing r = 0.50, p = 0.029. A negative correlation exist in regard of pain scores and Backwards Corsi scores r = -0.57, p = 0.110. Physical health correlated with error-rates in the WCST, r = 0.69, p ≤ 0.001. Also, reinvestment negatively correlated with physical health, r = -0.80, p ≤ 0.001. Conclusion: Wellbeing relies on total sleep-time. Athletes with extended sleep-interruptions are slower in recalling memory, and those with greater reported pain have lower memory scores. Participants who rate physical health greater, have more error-rates in the WCST; indicating that cognitive flexibility is enhanced in individuals with inferior perceived health. However, individuals with lower physical health scores also have greater tendency to ruminate and reinvest in decisions, suggesting interrelation between reinvestment and physical health.

Sleep Disorders in Cancer-A Systematic Review.

INTRODUCTION: Sleep disorders, especially insomnia, are very common in different kinds of cancers, but their prevalence and incidence are not well-known. Disturbed sleep in cancer is caused by different reasons and usually appears as a comorbid disorder to different somatic and psychiatric diagnoses, psychological disturbances and treatment methods. There can be many different predictors for sleep disturbances in these vulnerable groups, such as pre-existing sleep disorders, caused by the mental status in cancer or as side effect of the cancer treatment. METHODS: A systematic literature review of 8073 studies was conducted on the topic of sleep and sleep disorders in cancer patients. The articles were identified though PubMed, PsycInfo and Web of Knowledge, and a total number of 89 publications were qualified for analysis. RESULTS: The identified eighty-nine studies were analyzed on the topic of sleep and sleep disorders in cancer, twenty-six studies on sleep and fatigue in cancer and sixty-one studies on the topic of sleep disorders in cancer. The prevalence of sleep disturbences and/or sleep disorders in cancer was up to 95%. DISCUSSION: Sleep disturbances and sleep disorders (such as insomnia, OSAS, narcolepsy and RLS; REM-SBD) in cancer patients can be associated with different conditions. Side effects of cancer treatment and cancer-related psychological dysfunctions can be instigated by sleep disturbances and sleep disorders in these patients, especially insomnia and OSAS are common. An evidence-based treatment is necessary for concomitant mental and/or physical states.

Wrist actigraphic approach in primary, secondary and tertiary care based on the principles of predictive, preventive and personalised (3P) medicine.

ABSTRACT: Sleep quality and duration as well as activity-rest-cycles at individual level are crucial for maintaining physical and mental health. Although several methods do exist to monitor these parameters, optimal approaches are still under consideration and technological development. Wrist actigraphy is a non-invasive electro-physical method validated in the field of chronobiology to record movements and to allow for monitoring human activity-rest-cycles. Based on the continuous recording of motor activity and light exposure, actigraphy provides valuable information about the quality and quantity of the sleep-wake rhythm and about the amount of motor activity at day and night that is highly relevant for predicting a potential disease and its targeted prevention as well as personalisation of medical services provided to individuals in suboptimal health conditions and patients. Being generally used in the field of sleep medicine, actigraphy demonstrates a great potential to be successfully implemented in primary, secondary and tertiary care, psychiatry, oncology, and intensive care, military and sports medicines as well as epidemiological monitoring of behavioural habits as well as well-being medical support, amongst others. PREDICTION OF DISEASE DEVELOPMENT AND INDIVIDUAL OUTCOMES: Activity-rest-cycles have been demonstrated to be an important predictor for many diseases including but not restricted to the development of metabolic, psychiatric and malignant pathologies. Moreover, activity-rest-cycles directly impact individual outcomes in corresponding patient cohorts. TARGETED PREVENTION: Data acquired by actigraphy are instrumental for the evidence-based targeted prevention by analysing individualised patient profiles including light exposure, sleep duration and quality, activity-rest-cycles, intensity and structure of motion pattern. PERSONALISED THERAPY: Wrist actigraphic approach is increasingly used in clinical care. Personalised measurements of sedation/agitation rhythms are useful for ICU patients, for evaluation of motor fatigue in oncologic patients, for an individual enhancement of performance in military and sport medicine. In the framework of personalised therapy intervention, patients can be encouraged to optimise their behavioural habits improving recovery and activity patterns. This opens excellent perspectives for the sleep-inducing medication and stimulants replacement as well as for increasing the role of participatory medicine by visualising and encouraging optimal behavioural patterns of the individual.

["Coronasomnia"-promoting resilience through insomnia treatment]. / "Coronasomnia" ­ Resilienzförderung durch Insomniebehandlung.

Background: The term "coronasomnia" is used in popular science to describe sleep disorders associated with the COVID-19 pandemic. These disorders may also affect part of the population in the aftermath of the pandemic. Early scientific evidence suggests that COVID-19-associated insomnia and insomniac symptoms can become chronic and will continue to preoccupy the sleep medicine community even after the pandemic has ended. Methods: A literature review was conducted in Medline and Google Scholar using the following combination of keywords: "insomnia and COVID-19", "insomnia and long COVID", "insomnia, PTSD and COVID-19", and "fatigue and insomnia in long COVID". In addition, the authors reviewed several recent articles published by members of the European Insomnia Network. Results: Studies on insomnia and COVID-19 show significant associations between acute infection and insomnia in affected individuals. The prevalence of insomnia symptoms in COVID-19-affected individuals was 36 to 88%, which is significantly higher than the estimated 10 to 40% prevalence of insomnia in the general population. Conclusion: Digital therapy as a current treatment option for insomnia can be offered to patients regardless of physical distance. Accordingly, not only early approval of therapy apps, but also person-led, digital therapy options for insomnia would be recommended. The inclusion of personalised and sleep-coaching measures in the area of occupational health management is encouraged.

Anonymous online cognitive behavioral therapy for sleep disorders in shift workers-a study protocol for a randomized controlled trial.

BACKGROUND: Many shift workers suffer from sleep issues, which negatively affect quality of life and performance. Scientifically evaluated, structured programs for prevention and treatment are scarce. We developed an anonymous online cognitive behavioral therapy for insomnia (CBT-I) program. After successful completion of a feasibility study, we now start this prospective, randomized, controlled superiority trial to compare outcomes of two parallel groups, namely an intervention group and a waiting-list control-group. Additionally, we will compare these outcomes to those of a face-to-face CBT-I outpatient sample. METHODS: Collaborating companies will offer our anonymous online intervention to their shift-working employees. Company physicians and counseling services will screen those interested for inclusion and exclusion criteria. Participants will receive access to our online service, where they will complete psychometric assessment and receive random assignment to either the intervention group or the waiting-list control group. Participants and providers will be aware of the group assignment. We aim to allocate at least N = 60 participants to the trial. The intervention consists of psychoeducation, sleep restriction, stimulus control, relaxation techniques, and individual feedback delivered via four e-mail contacts. During the intervention, as well as during the waiting period, participants will fill out weekly sleep diaries. Immediately after completion of the program, the post-intervention assessment takes place. Participants in the control group will be able to participate in the program after all study assessments. To recruit an additional sample, collaborating outpatient sleep clinics will provide six sessions of standard face-to-face CBT-I to an ad hoc sample of shift working patients. We expect both the online and the face-to-face CBT-I interventions to have beneficial effects compared to the control group on the following primary outcomes: self-reported symptoms of depression and insomnia, sleep quality, and daytime sleepiness. CONCLUSIONS: The online intervention allows shift workers to follow a CBT-I program independently of their working schedule and location. Forthcoming results might contribute to further improvement of prevention and therapy of sleep issues in shift workers. TRIAL REGISTRATION: German Clinical Trials Register DRKS DRKS00017777 . Registered on 14 January 2020-retrospectively registered.

Sleep quality and COVID-19 outcomes: the evidence-based lessons in the framework of predictive, preventive and personalised (3P) medicine.

Sleep quality and duration play a pivotal role in maintaining physical and mental health. In turn, sleep shortage, deprivation and disorders are per evidence the risk factors and facilitators of a broad spectrum of disorders, amongst others including depression, stroke, chronic inflammation, cancers, immune defence insufficiency and individual predisposition to infection diseases with poor outcomes, for example, related to the COVID-19 pandemic. Keeping in mind that COVID-19-related global infection distribution is neither the first nor the last pandemic severely affecting societies around the globe to the costs of human lives accompanied with enormous economic burden, lessons by predictive, preventive and personalised (3P) medical approach are essential to learn and to follow being better prepared to defend against global pandemics. To this end, under extreme conditions such as the current COVID-19 pandemic, the reciprocal interrelationship between the sleep quality and individual outcomes becomes evident, namely, at the levels of disease predisposition, severe versus mild disease progression, development of disease complications, poor outcomes and related mortality for both - population and healthcare givers. The latter is the prominent example clearly demonstrating the causality of severe outcomes, when the long-lasting work overload and shift work rhythm evidently lead to the sleep shortage and/or deprivation that in turn causes immune response insufficiency and strong predisposition to the acute infection with complications. This article highlights and provides an in-depth analysis of the concerted risk factors related to the sleep disturbances under the COVID-19 pandemic followed by the evidence-based recommendations in the framework of predictive, preventive and personalised medical approach.

Insomnia Associated with Tinnitus and Gender Differences.

Chronic tinnitus causes a decrease in well-being and can negatively affect sleep quality. It has further been indicated that there are clinically relevant gender differences, which may also have an impact on sleep quality. By conducting a retrospective and explorative data analysis for differences in patients with tinnitus and patients diagnosed with tinnitus and insomnia, hypothesized differences were explored in the summed test scores and on item-level of the validated psychometric instruments. A cross-sectional study was conducted collecting data from a sample of tinnitus patients (n = 76). Insomnia was diagnosed in 49 patients. Gender differences were found on aggregated test scores of the MADRS and BDI with men scoring higher than women, indicating higher depressive symptoms in men. Women stated to suffer more from headaches (p < 0.003), neck pain (p < 0.006) and nervousness as well as restlessness (p < 0.02). Women also reported an increase in tinnitus loudness in response to stress compared to men (p < 0.03). Male individuals with tinnitus and insomnia have higher depression scores and more clinically relevant depressive symptoms than women, who suffer more from psychosomatic symptoms. The results indicate a need for a targeted therapy of depressive symptoms in male patients and targeted treatment of psychosomatic symptoms, stress-related worsening of insomnia and tinnitus in women.

Shiftwork and Alcohol Consumption: A Systematic Review of the Literature.

INTRODUCTION: Shiftwork can be a risk factor for a number of different somatic and psychological health conditions, especially sleep disorders. Shiftworkers sleep less than dayworkers, and 20-40% of them suffer from difficulties initiating and maintaining sleep, which result in reduced capacity for work and social life. A common coping strategy might be the use of alcohol, which presents a health and safety hazard as it further impairs sleep quality and exacerbates sleepiness in the workplace. This review aimed to assess the extent of such possible connections. METHODS: We performed a systematic search of the scientific literature on shiftwork and alcohol consumption in PubMed, PsycInfo, and Cochrane Library. Only original studies comparing shiftworkers with non-shiftworkers were included. The recommendations of the Preferred Reporting Items of Systematic Reviews and Meta-Analyses were followed. RESULTS: Fourteen articles are included in this review. Six studies report some kind of connection between shift- or nightwork and alcohol consumption, especially as a sleep aid. Conflicting or negative results are reported by 3 studies. DISCUSSION: Shiftwork, especially working at night and in rotation shifts, is associated with binge drinking disorder in different professions. The reasons for pathological consumption of alcohol can be self-medication of sleep problems or coping with stress and psychosocial problems typical for shiftwork. Nurses aged over 50 years represent one important risk group. These results can be important for preventive programs against sleep disorders, including measures other than drinking alcohol as a sleep aid in the workplace of shiftworkers.

Sleep disorders in migrants and refugees: a systematic review with implications for personalized medical approach.

BACKGROUND: Sleep disorders are very common in migrants and refugees, often as a comorbid disorder to different somatic or psychiatric diagnoses and psychological disturbances such as metabolic syndrome, post-traumatic stress disorder, depression, and anxiety disorders. OBJECTIVES: To review published prevalence rates as well as possible predictors for sleep disturbances in these vulnerable groups, including pre-migration stress, acculturation, and trauma before, during, and after migration, integration, and lifestyle in the host country with implications for predictive, preventive, and personalized medical approach (3PM). DATA SOURCES: Electronic databases PubMed, PsycInfo, and Web of Knowledge were searched using (combined) search terms "migrant," "asylum seeker," "refugee," "sleep disturbances," "sleep disorder," "insomnia," and "sleep wake disorder." STUDY ELIGIBILITY CRITERIA: Peer-reviewed studies from 2000 to 2018 reporting data on prevalence and/or predictors of any measure of sleep disturbance were included. PARTICIPANTS: Studies on international migrants and refugees, as well as internally displaced populations, were included. METHODS: We conducted a systematic review on the topic of sleep disorders in migrant and refugee populations. Only published articles and reviews in peer-reviewed journals were included. RESULTS: We analyzed five studies on sleep disorders in migrants, five studies on adult refugees, and three on refugee children and adolescents. Prevalence of sleep disorders in migrants and refugees ranges between 39 and 99%. In migrant workers, stress related to integration and adaptation to the host society is connected to higher risks of snoring, metabolic diseases, and insomnia. Sleep disturbances in refugees are predicted by past war experience. Sleep difficulties in adult and child refugees are strongly correlated to trauma. Torture of parents and grandparents can predict sleep disorders in refugee children, while being accompanied by parents to the host country has a protective effect on children's sleep. CONCLUSIONS AND IMPLICATIONS: Considering the differences in risk factors, vulnerability, and traumatic life events for different migrant populations, origins of sleep difficulties vary, depending on the migrant populations. Effects on sleep disturbances and sleep quality may be a result of integration in the host country, including changes of lifestyle, such as diet and working hours with implication for OSAS (obstructive sleep apnea) and insomnia. Compared with migrant populations, sleep disturbances in refugee populations are more correlated with mental health symptoms and disorders, especially PTSD (post-traumatic stress disorder), than with psychosocial problems. In juvenile refugee populations, psychological problems and disturbed sleep are associated with traumatic experiences during their journey to the host country. Findings highlight the need for expert recommendations for development of 3P approach stratified in the following: (1) prediction, including structured exploration of predisposing and precipitating factors that may trigger acute insomnia, screening of the according sleep disorders by validated translated questionnaires and sleep diaries, and a face-to-face or virtual setting and screening of OSAS; (2) target prevention by sleep health education for female and male refugees and migrant workers, including shift workers; and (3) personalized medical approach, including translated cognitive behavioral treatment for insomnia (CBT-I) and imagery rehearsal therapy for refugees and telehealth programs for improved CPAP adherence in migrants, with the goal to enable better sleep health quality and improved health economy.