Vagal nerve biofeedback intervention for improving health outcomes among Ukrainian forced migrants: A proof-of-concept study

Vagal nerve biofeedback intervention for improving health outcomes among Ukrainian forced migrants: A proof-of-concept study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Vagal nerve biofeedback intervention for improving health outcomes among Ukrainian forced migrants: A proof-of-concept study Yori Gidron, Einav Levy, Chen Hanna Ryder, Sharon Shaul, Rita Sirota, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4947313/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background - The ongoing conflict in Ukraine has forced numerous migrants into neighboring countries, many suffering from pre-existing or newly acquired physical and mental health conditions. Addressing these complex challenges in humanitarian settings requires innovative, evidence-based interventions that are cost-effective and easy to administer. Drawing upon research highlighting the vagus nerve's role in regulating well-being, we hypothesized that vagal nerve activation could offer a promising therapeutic approach. Method - We conducted a proof-of-concept study in which 21 Ukrainian forced migrants were trained in a biofeedback-guided paced breathing intervention designed to stimulate the vagus nerve and promote self-regulation of stress response systems. Changes in pain perception, perceived stress, blood pressure, and heart rate variability (an established marker of vagal tone) were assessed before and after the vagal breathing intervention using t-test. These multi-dimensional outcome measures were chosen to capture both subjective and objective physical and mental well-being indicators. Correlations were examined at baseline. Results- Statistically significant improvements were observed in all measures except systolic blood pressure, providing preliminary evidence for the efficacy of vagal nerve activation in alleviating stress-related health symptoms. Conclusions- This study demonstrates the feasibility and therapeutic potential of a vagal nerve-activating intervention in a humanitarian setting. These findings warrant replication in larger, controlled trials. If substantiated, this low-cost, scalable intervention could help mitigate health burdens among forced migrant populations worldwide. This intervention is relevant to south global countries which face an epidemiological shift from infectious to non-communicable diseases. Ukraine conflict Health conditions Vagal nerve Paced breathing Humanitarian action Introduction The Russian invasion of Ukraine on the 24th of February 2022 marked the beginning of the fastest and largest forced migration movement in Europe since the Second World War. As of June, 2022, the ongoing conflict has displaced over 4.2 million Ukrainians, compelling them to seek refuge in neighboring countries (UNHCR, 2022a). Poland, Slovakia, Hungary, and Romania have emerged as the primary destinations for these forced migrants, with the European Union (EU) granting them official recognition as war refugees (European Commission, 2022). Notably, Poland has received the largest influx of people of concern (POC) crossing the border, owing to its 500km shared border with Ukraine, close familial ties, and linguistic familiarity (UNHCR, 2022b). The demographic composition of this refugee population is heavily skewed, with women and children accounting for 90% of the POC, as Ukrainian legislation mandates military service for men aged 18–60 (UNWOMEN, 2022). Upon crossing the borders, these forced migrants are provided with basic humanitarian support, including food, clothing, shelter, medical care, and psychosocial assistance, in specially established centers and transit camps. In contexts where migrants have undergone a treacherous journey, the profile of medical conditions they present with is shaped by a complex interplay of factors. These include pre-existing health risks and conditions in their country of origin (e.g., hygiene, diet, genetic susceptibility), exposure to war-related injuries and atrocities, and health issues acquired during their perilous voyage (Levy et al., 2017 ). Additionally, sociodemographic variables such as age, gender, and lifestyle contribute to the diverse health profiles observed among forced migrant populations. For instance, a study conducted among 1550 Syrian refugees residing outside camps in Jordan found that the leading chronic diseases were hypertension (9.7%), arthritis (6.8%), diabetes (5.3%), cardiovascular diseases (3.7%), and respiratory diseases (3.1%) (Doocy et al., 2015 ). Similarly, research on the morbidity of forced migrants along the Balkan route (Greece, North Macedonia, Serbia, and Croatia), who fled the Middle East due to the Syrian conflict and its regional repercussions, indicates that infectious diseases are the most prevalent health concern among these refugees (Ozaras et al., 2016 ). Alongside the physical toll of forced migration, such experiences can lead to a wide range of mental health sequelae, including psychopathology. Numerous studies have documented elevated rates of psychological disorders, particularly post-traumatic stress disorder (PTSD), among refugee and forced migrant populations (Hammel et al., 2011 ). For example, a study of Syrian refugees in Turkey revealed a PTSD prevalence of 33.5% (Alpak et al., 2015 ), while another investigation of 781 Syrian refugees found that 83.4% met criteria for probable PTSD and 37.4% for probable depression (Acarturk et al., 2017 ). These high rates of psychopathology have been consistently observed across various settings and age groups. A study of 38 Yazidi children found that all participants exhibited psychiatric symptoms, with 71% reporting sleep disturbances, 36.8% screening positive for depression, and 10.5% for PTSD (Ceri et al., 2016 ). Similarly, a study of Yazidi children revealed that 36.4% met criteria for PTSD, 32.7% for depression, and 7.3% for anxiety (Nasıroglu & Çeri, 2016 ). Among 847 Somali refugees living in southeast Ethiopia, 38.3% were found to be depressed (Feyera et al., 2015 ). This pattern was also observed in a study of 200 male forced migrants from West Sub-Saharan Africa, which reported a PTSD prevalence of 12% (Sacchetti et al., 2020 ). It is important to note that the aforementioned studies were conducted among refugees and forced migrants who were primarily located in close proximity to their country of origin. The variation in prevalence rates across studies may be attributed to differences in sampling methods, assessment tools, and the duration of time elapsed since exposure to war-related trauma or atrocities. While there is a growing body of evidence supporting the effectiveness of mental health and psychosocial support (MHPSS) interventions, the tools currently in use often lack cultural adaptation, necessitating a critical examination of these findings (Hillel, 2023 ). Global south countries have been shifting epidemiologically from infectious diseases to non-communicable diseases (NCD). 2. During humanitarian crises, these is a need to detect and treat quickly and inexpensively previous existing NCD or those who may have developed from a crisis-stress such as hypertension or diabetes. 3. However, developing countries and those facing mass disasters or war may not have sufficient economic resources to treat such diseases. 4. Numerous studies show that low vagal nerve activity is related to risk of many NCD and to poorer prognosis. Activating the vagus has emerging clinical benefits in several NCD. 5. It costs very little to measure heart-rate variability (HRV), the vagal index, and it costs very little to activate the vagal nerve by paced slow breathing with biofeedback. 6. Health professionals must be educated about these, worldwide and these could be implemented on a routine basis in developing countries towards early detection, prevention and possible treatment of NCD for the benefit of global health. The case of Ukraine Prior to the outbreak of war, the five leading causes of mortality in Ukraine, accounting for 84% of all deaths, were cancer, chronic obstructive pulmonary disease (COPD), cardiovascular disease, diabetes, and mental disorders (WHO, March, 2022). Hypertension affected 35% of the Ukrainian population, with 85% of cases being uncontrolled (WHO, March, 2022), highlighting the urgent need for medical management of this serious health risk. Cancer was responsible for 13% of deaths in Ukraine, with colorectal, breast, and lung cancer being the most common types. Diabetes had a prevalence of approximately 7% among Ukrainians (WHO, March, 2022), although the true figure is likely higher, as a quarter of the population had never undergone blood tests. Regarding mental health, 12.4% of Ukrainians had depression prior to the war, but only 3.2% had ever received treatment for this condition (WHO, March, 2022). The psychological impact of the conflict is expected to compound this burden, with increased rates of anxiety, PTSD, and grief, further straining the already limited healthcare resources (Budosan et al., 2023 ). Following the outbreak of the war with Russia, several humanitarian agencies have been providing support to forced migrants in the surrounding countries, as mentioned earlier. The most common health conditions encountered include acute illnesses (e.g., upper respiratory infections, injuries) and chronic diseases (e.g., hypertension, diabetes). These conditions are typically managed with basic medical care, such as medication (e.g., beta-blockers, antibiotics) and wound dressings. However, this approach to treatment is not without challenges. First, the lack of resources and infrastructure in humanitarian settings precludes the use of advanced diagnostic measures (e.g., echocardiography, X-rays, blood tests, and brain imaging) to assess clinical outcomes. Second, the transient nature of the POC population, as they continue their onward journey, hinders long-term treatment, therapeutic effectiveness evaluation, monitoring of biomarker changes (e.g., liver function, insulin levels), and management of medication side effects. Finally, the limited financial capacity of humanitarian organizations constrains their ability to provide comprehensive mental and physical healthcare and evaluation. Consequently, there is an urgent need to develop and implement a logistically simple, cost-effective intervention that can address many of the aforementioned health conditions and their underlying pathology, ideally without side effects. Moreover, it is crucial that patients can self-administer the treatment, reducing their dependence on a constantly changing roster of healthcare providers in the context of migration. Finally, it is of high importance to identify a protective factor that is common to many diseases and that is easy to monitor its activity and to activate it. A common denominator of these health problems: The vagal nerve The vagus nerve emerges as a common protective neurobiological factor that is correlated with the health conditions mentioned above, via plausible evidence-based biological mechanisms. The vagus nerve, the tenth cranial nerve, originates in the brainstem and descends to the viscera, innervating most organs. Its activity can be measured non-invasively through heart rate variability (HRV), reflecting fluctuations in the intervals between normal heart-beats. HRV has a strong correlation with actual vagal nerve activity (r = 0.88; Kuo et al., 2005 ). Crucially, low HRV is predictive of the onset of hypertension (Singh et al., 1998 ) and a review of 25 studies found that HRV is consistently lower in individuals with diabetes mellitus (Benichou et al., 2018 ). High HRV is associated with a lower risk of developing myocardial infarction (MI) (Song et al., 2014 ), and a four-fold increase in post-MI survival, as demonstrated by a review of 21 studies (Buccelletti et al., 2009 ). Similarly, in cancer, high HRV is linked to better prognosis and survival, independent of confounding factors (De Couck et al., 2018 ; Zhou et al., 2016 ). With regard to mental health, a review of 36 studies found that HRV is reduced in generalized anxiety disorder, panic disorder, and PTSD (Chalmers et al., 2014 ). Furthermore, a review of 21 studies revealed that HRV is also lower in depression (Koch et al., 2019 ). HRV has been found to be positively correlated with prefrontal cortical activity (Thayer et al., 2012 ), which is often underactive in many mental disorders (e.g., Koenigs & Grafman, 2009). The biological mechanisms linking vagal activity to these health conditions can be understood through the lens of neuroimmunology. Inflammation is a key contributing factor in many of the aforementioned health problems (e.g., Greten & Grivennikov, 2019 ). The vagus nerve plays a pivotal role in communicating peripheral inflammation to the brain (Ek et al., 1998 ) and subsequently inhibiting it through two pathways. First, vagal activation stimulates the hypothalamic-pituitary-adrenal axis, resulting in the release of cortisol, which suppresses inflammation (Tracey, 2009 ). Second, descending vagal efferents reach the celiac ganglion, where they transition to a sympathetic branch that innervates the spleen. There, beta-adrenergic receptors on a subset of resident T-cells receive the sympathetic signal and, in response, secrete acetylcholine. Acetylcholine then binds to alpha-7 nicotinic acetylcholine receptors on splenic macrophages, that inhibits the production of pro-inflammatory cytokines (Rosas-Ballina et al., 2011 ). Electrical stimulation of the vagus nerve has been shown to reduce infarct size (Arimura et al., 2017 ), alleviate chronic pain (Johnson & Wilson, 2018 ), and enhance antiviral immunity, including increased NK cell and CD8 T-cell counts (Mihaylova et al., 2014 ). Importantly, the vagus nerve can be non-invasively activated through HRV biofeedback (HRV-B). In HRV-B, patients learn to perform paced breathing while receiving real-time feedback on their HRV level via a mobile phone screen. Within seconds, they learn to increase their own HRV, which is empowering and fosters a sense of control over their health. This sense of control is particularly crucial in the context of crisis, uncertainty, and helplessness. Furthermore, the simplicity of this approach and its low cost, make it highly relevant and attractive in contexts of treating patients with little resources. Several reviews found that HRV biofeedback improves emotional and physical health (Lehrer et al., 2020 ; Laborde et al. 2022 ; Gitler et al., 2023;). Moreover, HRV biofeedback and vagal breathing have been shown to reduce inflammation, pain, and anxiety (e.g., Berry et al., 2014 ; Steffen et al., 2017 ; Chin & Kales, 2019 ). However, to the best of our knowledge, the effects of HRV-B have not been systematically examined in humanitarian contexts or across the multiple medical conditions discussed above. The following study represents a proof-of-concept intervention within the context of the Ukrainian humanitarian crisis. Due to the ethical imperative and medical necessity of providing care to all those in need, this study was not designed as a formal randomized controlled trial. Nevertheless, we obtained ethical approval from the [institution name] (#BLIND TO REVIEWERS, Ref number 9 − 6/2022) to collect the reported data, which were gathered for medical purposes and shared with patients as part of standard good clinical practice (GCP). Informed consent was obtained from all participants, with forms provided in their native language, outlining the study's objectives, applications, and contact information for the principal investigator. Methods The worldwide disaster relief non-governmental organization (NGO) NATAN, originally based in Israel, has been operating in Poland since March 2022, providing emergency medical and psychosocial support through a clinic located in a transit camp in Przemysl. During the period in which the intervention took place, the transit center housed approximately 4,000 people of concern (POC) at any given time, with an average length of stay of 1.5 days. The clinic, staffed by physicians, nurses, and social workers, many of whom were proficient in Russian or Ukrainian, offered round-the-clock primary care. The standard operating procedure involved patient registration, collection of demographic information (age, gender) and medical history, diagnostic assessment, and provision of treatment based on clinical judgment and available resources. The primary health concerns addressed at the NATAN clinic encompassed a range of acute and chronic conditions, including infectious diseases (particularly gastroenteritis and upper respiratory tract infections [URTI]), minor traumatic injuries and wounds, musculoskeletal complaints, headaches, and psychopathology (e.g., anxiety, depression, and sleep disturbances). Additionally, the clinic managed cardiovascular issues, such as acute exacerbations of ischemic heart disease, congestive heart failure, and asthma. Treatment modalities included oral medications such as paracetamol, nonsteroidal anti-inflammatory drugs (NSAIDs), antibiotics, and pharmacotherapies for the symptomatic relief of cold, flu, diarrhea, nausea, and vomiting, as well as antidepressants and anxiolytics. In emergency situations, intravenous medications, including Fusid and steroids, and inhaled therapies, such as Ventolin and Aerovent, were administered. The clinic also provided ongoing care and follow-up for chronic conditions, including hypertension, diabetes, arthritis, hypothyroidism, epilepsy, malignancies, and gastrointestinal disorders such as peptic ulcers and heartburn. Patients The sample comprised 21 Ukrainian patients who sought care at the NATAN humanitarian organization's clinic in Przemysl. Table 1 presents the prevalence of their primary health concerns. Participants ranged in age from 10 to 80 years, with a mean (SD) age of 41.33 (20.01) years. The sample included 9 males (42.9%) and 12 females (57.1%). Measures Data collected included patients' age, gender, and the primary health complaint that prompted their clinic visit. Additionally, perceived stress and current subjective pain levels were assessed using a 0–10 rating scale. Blood pressure, including systolic blood pressure (SBP) and diastolic blood pressure (DBP), was measured using a Life Ltd electronic blood pressure monitor (model number KD-558). To measure heart rate variability (HRV), we employed the I-feelwell photoplethysmograph (PPG) device, which records HRV, heart rate, and oxygen saturation via a sensor attached to the left index finger. This device provides two time-domain HRV parameters: the standard deviation of normal-to-normal (SDNN) interbeat intervals and the root mean square of successive differences (RMSSD) between adjacent normal-to-normal intervals. A recent study found that HRV measured using this device significantly predicted episodes of Crohn's disease in children (Yerushalmy-Feler et al., 2022 ). Interventions The intervention consisted of an educational component and training in a 3-minute paced vagal breathing technique. First, we used clear, laminated visual aids to explain to each patient how vagal nerve activation relates to their specific health condition. These materials included a diagram illustrating the connection between their condition and the vagus nerve, along with a summary of research demonstrating the benefits of vagal breathing for that particular health concern. Next, we provided instructions on the vagal breathing technique and gave patients a laminated summary card in Russian (the language spoken by most or all Ukrainian participants), which was also used by our healthcare staff. Patients then practiced the 3-minute deep, paced breathing exercise as follows: inhale through the nose for a count of 1–5, hold the breath for a count of 1–2, and exhale through pursed lips for a count of 1–5. This breathing technique has been shown to increase HRV and improve decision-making (De Couck et al., 2019 ). Procedure All patients underwent a baseline assessment of perceived pain and stress, SBP, DBP, and HRV during a 30-second resting period. They then received the educational explanation and performed the 3-minute paced breathing exercise. Immediately following the intervention, perceived pain and stress, SBP, DBP, and HRV were reassessed during another 30-second resting period. Statistical analysis We report descriptive statistics, including means for continuous variables and percentages for categorical variables. The effects of vagal breathing on all outcome measures were evaluated using paired t-tests. Additionally, we examined correlations between the baseline measures to validate the assessments and gain further insight into the relationships among the collected variables. Results Regarding the distribution of categorical variables, 42.9% of the participants were male, and 57.1% were female. Nearly half of the sample (47.6%) had a chronic systemic disease, including hypertension (n = 8), epilepsy (n = 1), or peripheral numbness (n = 1). Chronic pain was reported by 28.6% of the participants, while 23.8% experienced anxiety or severe stress. Table 1 presents the means (SD) of all continuous variables before and after the vagal breathing intervention. All outcome measures, with the exception of SBP, showed significant improvements following the vagal breathing exercise. Specifically, DBP (t(19) = 1.96, p < 0.05, one-tailed), pain (t(11) = 2.78, p < 0.05), and perceived stress (t(12) = 4.77, p < 0.001) were significantly reduced post-intervention. In contrast, RMSSD (t(17) = 2.5, p < 0.05) and SDNN (t(17) = 4.69, p < 0.001) significantly increased following the vagal breathing exercise. Table 2 presents the correlations between the outcome variables at baseline. We focused on the SDNN HRV parameter, as it was highly correlated with RMSSD (r = 0.90, p < 0.01) and demonstrated more consistent associations with the other variables. Both SBP and DBP exhibited strong, positive, and significant correlations with perceived stress. SDNN was negatively and significantly correlated with both pain and perceived stress. Interestingly, pain and perceived stress were not significantly correlated with each other. Discussion This pioneering project represents the first application of neuroimmunology and psychophysiological principles in a humanitarian context. Specifically, we tested the effects of an evidence-based heart rate variability biofeedback (HRV-B) intervention on multiple health conditions among Ukrainian forced migrants. Our findings demonstrate significant improvements in five out of six outcome measures, encompassing both objective and subjective indices. In particular, diastolic blood pressure (DBP), pain, and perceived stress were reduced, while two HRV parameters were increased significantly following the intervention. The observed correlations between the vagal index and other outcomes, as well as the effects of HRV-B on medical and subjective measures, underscore the integrative and comprehensive roles of the vagus nerve in health. This notion is supported by the neurovisceral integration model (Thayer et al., 2009 ) and by a neuroimmunological model of chronic diseases (Gidron et al., 2018 ). The neurovisceral integration model highlights the central role of the vagus nerve, as indexed by HRV, in mediating the relationship between frontal brain activity and the regulation of cardiac function. The neuroimmunological model of chronic diseases synthesizes evidence linking vagal activity to healthier behaviors (e.g., reduced smoking), the predictive value of its marker (HRV) for lower risk and better survival in chronic diseases, and the regulation of biological disease mechanisms (e.g., inflammation). Our results align with the findings of Lehrer et al. ( 2020 ) and Gitler et al. ( 2022 ), who reviewed the effects of HRV-B on various health conditions, including hypertension, chronic pain, and heart disease. Specifically, our observations are consistent with studies demonstrating that HRV-B reduces blood pressure and pain (Berry et al., 2014 ; Steffen et al., 2017 ). Furthermore, our findings concur with a meta-analysis of 24 studies showing that HRV biofeedback reduces and anxiety (Goessl et al., 2017 ). Conclusions and implications to policy This proof-of-concept intervention study supports the acceptability and effectiveness of self-activation in the humanitarian contexts. This preliminary study needs to be replicated in a larger sample with a control group, respecting the unique ethical challenges of humanitarian contexts. If replicated, this novel psycho-physiological approach may offer a simple but not simplistic intervention for a wide range of health problems. Limitations The present project was first of all a humanitarian project, and as such, it naturally has several limitations. First, the sample size was small and heterogeneous, and there was no control group. However, given that this initiative was conducted during a humanitarian crisis, it was not feasible to design a controlled study while at the same time adhering to good clinical practice principles. Moreover, the primary purpose of data collection was to provide patients with feedback on their HRV-B performance rather than to conduct a formal study. Finally, the long-term effects of this intervention remain unknown. Strengths of the study Despite these limitations, the intervention is evidence-based, drawing upon extensive findings from neuroimmunology and health psychology research. Moreover, it is simple yet effective, inexpensive, and without any known adverse side effects. To the best of our knowledge, this approach has seldom been applied in humanitarian contexts. Implications for policy Humanitarian crises present a wide range of health challenges for affected populations, including distress related to displacement, witnessing the death and injury of loved ones, personal injury, and lack of treatment for pre-existing health conditions. Measuring HRV and performing vagal breathing with biofeedback are inexpensive interventions that can address many of these health concerns and can be easily taught to staff and patients. Furthermore, patients can practice the technique independently, without relying on the healthcare system, thereby promoting a sense of empowerment. People of concern can engage in HRV-B while on the move and at any given time and place. If replicated, this intervention could be widely disseminated and easily adopted in multiple humanitarian settings worldwide. The potential impact of such an intervention is substantial, as it may improve the quality of life and health outcomes for a large number of individuals affected by humanitarian crises. Health professionals must be educated about the protective roles of the vagal nerve in fatal and chronic diseases and on how to monitor and activate it in a minimum cost. These could be implemented on a routine basis in global south countries towards early detection, prevention and possible treatment of NCD for the benefit of global health. Abbreviations COPD - Chronic Obstructive Pulmonary Disease DBP - Diastolic Blood Pressure EU - European Union GI - Gastrointestinal HRV - Heart Rate Variability MHPSS - Mental Health and Psychosocial Support MI - Myocardial Infarction NSAIDs - Non-Steroidal Anti-Inflammatory Drugs POC - People of Concern PPG - Photoplethysmography PTSD - Post-Traumatic Stress Disorder SBP - Systolic Blood Pressure SDNN - Standard Deviation of Normal-to-Normal Intervals RMSSD - Root Mean Square of Successive Differences UNHCR - United Nations High Commissioner for Refugees URTI - Upper Respiratory Tract Infections Declarations Ethics approval and consent to participate- Ethical approval was granted by the IRB committee of Tel Hai Academic College and consent was given. It is to confirm that all methods in this study, were performed in accordance with the ethical standards as laid down in the Declaration of Helsinki and its later amendments. It is to confirm that written informed consent was obtained from all participants. Consent for publication- Written informed consent for publication was obtained. Availability of data and materials- The data that support the findings of this study are available from the corresponding author, but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission of the corresponding author. Competing interest- Author A declares that he has no conflict of interest. Author B declares that he has no conflict of interest. Author C declares that she has no conflict of interest. Author D declares that she has no conflict of interest. Author E declares that she has no conflict of interest. Author F declares that she has no conflict of interest. Authors' contributions - Y.G. and E.L made substantial contributions to the conception, designed the work, analyzed and have drafted the work and substantively revised it. C.R. analyzed and have drafted the work. S.S., R.S. and D.A. made substantial contributions to the conception. Funding was received from OLAM TOGETHER and from NATAN- worldwide international relief. Acknowledgements – we would like to thank the management of the transition camo in Przemysl, Poland for enabling us to perform this study. References Acarturk C, Cetinkaya M, Senay I, Gulen B, Aker T, Hinton D. Prevalence and predictors of posttraumatic stress and depression symptoms among Syrian refugees in a refugee camp. J Nerv Ment Dis. 2017;206(1):40-45. Alpak G, Unal A, Bulbul F, Sagaltici E, Bez Y, Altindag A, Savas HA. Post-traumatic stress disorder among Syrian refugees in Turkey: A cross-sectional study. Int J Psychiatry Clin Pract. 2015;19(1):45-50. 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Medical conditions and treatment in a transit camp in Serbia for Syrian, Afghani, and Iraqi migrants. J Int Humanit Action. 2017;2(1):1-6. doi:10.1186/s41018-017-0028-3. Nasıroglu S, Çeri V. Posttraumatic stress and depression in Yazidi refugees. Neuropsychiatr Dis Treat. 2016;12:2941. doi:10.2147/NDT.S115288. Mihaylova S, Schweighöfer H, Hackstein H, Rosengarten B. Effects of anti-inflammatory vagus nerve stimulation in endotoxemic rats on blood and spleen lymphocyte subsets. Inflamm Res. 2014;63(8):683-690. doi:10.1007/s00011-014-0755-5. Ozaras R, Leblebicioglu H, Sunbul M, Tabak F, Balkan II, Yemisen M, et al. The Syrian conflict and infectious diseases. Expert Rev Anti Infect Ther. 2016;14(6):547-555. doi:10.1080/14787210.2016.1185420. Rosas-Ballina M, Olofsson PS, Ochani M, Valdés-Ferrer SI, Levine YA, Reardon C, et al. Acetylcholine-synthesizing T cells relay neural signals in a vagus nerve circuit. Science. 2011;334(6052):98-101. doi:10.1126/science.1209985. Sacchetti E, Garozzo A, Mussoni C, Liotta D, Novelli G, Tamussi E, et al. Post-traumatic stress disorder and subthreshold post-traumatic stress disorder in recent male asylum seekers: An expected but overlooked “European” epidemic. Stress Health. 2020;36(1):37-50. doi:10.1002/smi.2908. Singh JP, Larson MG, Tsuji H, Evans JC, O’Donnell CJ, Levy D. Reduced heart rate variability and new-onset hypertension: insights into pathogenesis of hypertension: the Framingham Heart Study. Hypertension. 1998;32(2):293-297. doi:10.1161/01.hyp.32.2.293. Song T, Qu XF, Zhang YT, Cao W, Han BH, Li Y, et al. Usefulness of the heart-rate variability complex for predicting cardiac mortality after acute myocardial infarction. BMC Cardiovasc Disord. 2014;14(1):1-8. doi:10.1186/1471-2261-14-1. Steffen PR, Austin T, DeBarros A, Brown T. The impact of resonance frequency breathing on measures of heart rate variability, blood pressure, and mood. Front Public Health. 2017;5:222. doi:10.3389/fpubh.2017.00222. Thayer JF, Hansen AL, Saus-Rose E, Johnsen BH. Heart rate variability, prefrontal neural function, and cognitive performance: the neurovisceral integration perspective on self-regulation, adaptation, and health. Ann Behav Med. 2009;37(2):141-153. doi:10.1007/s12160-009-9101-z. Thayer JF, Åhs F, Fredrikson M, Sollers JJ 3rd, Wager TD. A meta-analysis of heart rate variability and neuroimaging studies: implications for heart rate variability as a marker of stress and health. Neurosci Biobehav Rev. 2012;36(2):747-756. doi:10.1016/j.neubiorev.2011.11.009. Tracey KJ. Reflex control of immunity. Nat Rev Immunol. 2009;9(6):418-428. doi:10.1038/nri2566. UNHCR Operational Data Portal. June, 2022. https://data.unhcr.org/en/situations/ukraine. Accessed June 20, 2024. UNHCR. Poland welcomes more than two million refugees from Ukraine. 2022. https://www.unhcr.org/news/press/2022/3/6234811a4/poland-welcomes-million-refugees-ukraine.html. Accessed June 20, 2024. UNWOMEN. Collecting data and analysis on how the war in Ukraine is impacting women and girls. 2022. https://www.unwomen.org/en/news-stories/news/2022/04/collecting-data-and-analysis-on-how-the-war-in-ukraine-is-impacting-women-and-girls. Accessed June 20, 2024. Yerushalmy-Feler A, Cohen S, Lubetzky R, Moran-Lev H, Ricon-Becker I, Ben-Eliyahu S, Gidron Y. Heart rate variability as a predictor of disease exacerbation in pediatric inflammatory bowel disease. J Psychosom Res. 2022;158:110911. doi:10.1016/j.jpsychores.2022.110911. Zhou X, Ma Z, Zhang L, Zhou S, Wang J, Wang B, Fu W. Heart rate variability in the prediction of survival in patients with cancer: a systematic review and meta-analysis. J Psychosom Res. 2016;89:20-25. doi:10.1016/j.jpsychores.2016.08.006. Tables Table 1- Mean and Standard deviation of main outcome variables Pre Post Variable Mean SD Mean SD --------------------------------------------------------------------------------------------- SBP 148.6 22.5 143.6 22.1 DBP 90.5 12.6 86.5*# 12.3 RMSSD 37.7 27.5 55.3* 49.7 SDNN 48.4 39.2 73.1*** 48.3 PAIN 3.9 2.4 2.7* 2.4 STRESS 5.8 2.4 3.1*** 2.2 --------------------------------------------------------------------------------------------- SBP= Systolic blood pressure; DBP- Diastolic blood pressure; RMSSD= Route mean square of successive differences; SDNN= Standard deviation of normal to normal intervals; # p<0.05 (one tailed); *p<0.05; ***p<0.001; Table 2- Correlations between outcome variables: SBP DBP SDNN Pain Stress DBP 0.58** 1 -0.27 0.12 0.71** SDNN -0.29 0.27 1 -0.62* -0.61* Pain 0.28 0.12 -0.62* 1 0.19 Stress 0.86** 0.71** -0.61* 0.19 1 *p<0.05; **p<0.01 Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4947313","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":346516586,"identity":"5c0c32aa-b2e5-4722-8815-44032f19de32","order_by":0,"name":"Yori Gidron","email":"","orcid":"","institution":"University of Haifa","correspondingAuthor":false,"prefix":"","firstName":"Yori","middleName":"","lastName":"Gidron","suffix":""},{"id":346516587,"identity":"b837a48d-9d5c-48c2-93d5-d1e577dd0b05","order_by":1,"name":"Einav Levy","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA00lEQVRIiWNgGAWjYBACPhiDH0QkFBChhQ3GkGwAaTEgRYvBATBJjBb2HjPJLzU28sbnVyd+eGDAIM8vdoCAFp4zZtIyx9IMt914u1kC6DDDmbMTCGiRSEuTlmA7zLjtxtkNIC0JBrcJaZF/BtTy77/95hlnN/8gTosE8zHJj20HEjfw924j0hae5MPWjH3JyTNu8G6zSDCQIOwXfvaDjTd/fLOz7e8/u/nmjwobeX5pAlqAgEWaB0RJgFVKEFQOAswff4DtO0CU6lEwCkbBKBiBAABRQ0I3fvsaCgAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0001-6278-8364","institution":"Tel-Hai College","correspondingAuthor":true,"prefix":"","firstName":"Einav","middleName":"","lastName":"Levy","suffix":""},{"id":346516588,"identity":"50801a5f-9c11-47f5-871e-9910db173792","order_by":2,"name":"Chen Hanna Ryder","email":"","orcid":"","institution":"Western Galilee College","correspondingAuthor":false,"prefix":"","firstName":"Chen","middleName":"Hanna","lastName":"Ryder","suffix":""},{"id":346516589,"identity":"925657ca-b8bc-4009-a087-cae8dfcd8d49","order_by":3,"name":"Sharon Shaul","email":"","orcid":"","institution":"Clalit Health Services","correspondingAuthor":false,"prefix":"","firstName":"Sharon","middleName":"","lastName":"Shaul","suffix":""},{"id":346516590,"identity":"4c0cc77e-bd24-4e96-bb2c-e0fc843869bc","order_by":4,"name":"Rita Sirota","email":"","orcid":"","institution":"Carmel Hospital","correspondingAuthor":false,"prefix":"","firstName":"Rita","middleName":"","lastName":"Sirota","suffix":""},{"id":346516591,"identity":"e8463655-837b-444d-bc23-f8e055a81917","order_by":5,"name":"Drorit Atias","email":"","orcid":"","institution":"The Hebrew University of Jerusalem Hadassah Medical School: Hebrew University of Jerusalem School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Drorit","middleName":"","lastName":"Atias","suffix":""}],"badges":[],"createdAt":"2024-08-20 20:48:38","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4947313/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4947313/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":67181048,"identity":"f54d9d25-d91c-45de-b519-700ce80b0411","added_by":"auto","created_at":"2024-10-22 06:19:57","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":364223,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4947313/v1/130df511-0148-4bce-8389-70e436126714.pdf"}],"financialInterests":"","formattedTitle":"Vagal nerve biofeedback intervention for improving health outcomes among Ukrainian forced migrants: A proof-of-concept study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe Russian invasion of Ukraine on the 24th of February 2022 marked the beginning of the fastest and largest forced migration movement in Europe since the Second World War. As of June, 2022, the ongoing conflict has displaced over 4.2\u0026nbsp;million Ukrainians, compelling them to seek refuge in neighboring countries (UNHCR, 2022a). Poland, Slovakia, Hungary, and Romania have emerged as the primary destinations for these forced migrants, with the European Union (EU) granting them official recognition as war refugees (European Commission, 2022). Notably, Poland has received the largest influx of people of concern (POC) crossing the border, owing to its 500km shared border with Ukraine, close familial ties, and linguistic familiarity (UNHCR, 2022b). The demographic composition of this refugee population is heavily skewed, with women and children accounting for 90% of the POC, as Ukrainian legislation mandates military service for men aged 18\u0026ndash;60 (UNWOMEN, 2022). Upon crossing the borders, these forced migrants are provided with basic humanitarian support, including food, clothing, shelter, medical care, and psychosocial assistance, in specially established centers and transit camps.\u003c/p\u003e\n\u003cp\u003eIn contexts where migrants have undergone a treacherous journey, the profile of medical conditions they present with is shaped by a complex interplay of factors. These include pre-existing health risks and conditions in their country of origin (e.g., hygiene, diet, genetic susceptibility), exposure to war-related injuries and atrocities, and health issues acquired during their perilous voyage (Levy et al., \u003cspan class=\"CitationRef\"\u003e2017\u003c/span\u003e). Additionally, sociodemographic variables such as age, gender, and lifestyle contribute to the diverse health profiles observed among forced migrant populations. For instance, a study conducted among 1550 Syrian refugees residing outside camps in Jordan found that the leading chronic diseases were hypertension (9.7%), arthritis (6.8%), diabetes (5.3%), cardiovascular diseases (3.7%), and respiratory diseases (3.1%) (Doocy et al., \u003cspan class=\"CitationRef\"\u003e2015\u003c/span\u003e). Similarly, research on the morbidity of forced migrants along the Balkan route (Greece, North Macedonia, Serbia, and Croatia), who fled the Middle East due to the Syrian conflict and its regional repercussions, indicates that infectious diseases are the most prevalent health concern among these refugees (Ozaras et al., \u003cspan class=\"CitationRef\"\u003e2016\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003eAlongside the physical toll of forced migration, such experiences can lead to a wide range of mental health sequelae, including psychopathology. Numerous studies have documented elevated rates of psychological disorders, particularly post-traumatic stress disorder (PTSD), among refugee and forced migrant populations (Hammel et al., \u003cspan class=\"CitationRef\"\u003e2011\u003c/span\u003e). For example, a study of Syrian refugees in Turkey revealed a PTSD prevalence of 33.5% (Alpak et al., \u003cspan class=\"CitationRef\"\u003e2015\u003c/span\u003e), while another investigation of 781 Syrian refugees found that 83.4% met criteria for probable PTSD and 37.4% for probable depression (Acarturk et al., \u003cspan class=\"CitationRef\"\u003e2017\u003c/span\u003e). These high rates of psychopathology have been consistently observed across various settings and age groups. A study of 38 Yazidi children found that all participants exhibited psychiatric symptoms, with 71% reporting sleep disturbances, 36.8% screening positive for depression, and 10.5% for PTSD (Ceri et al., \u003cspan class=\"CitationRef\"\u003e2016\u003c/span\u003e). Similarly, a study of Yazidi children revealed that 36.4% met criteria for PTSD, 32.7% for depression, and 7.3% for anxiety (Nasıroglu \u0026amp; \u0026Ccedil;eri, \u003cspan class=\"CitationRef\"\u003e2016\u003c/span\u003e). Among 847 Somali refugees living in southeast Ethiopia, 38.3% were found to be depressed (Feyera et al., \u003cspan class=\"CitationRef\"\u003e2015\u003c/span\u003e). This pattern was also observed in a study of 200 male forced migrants from West Sub-Saharan Africa, which reported a PTSD prevalence of 12% (Sacchetti et al., \u003cspan class=\"CitationRef\"\u003e2020\u003c/span\u003e). It is important to note that the aforementioned studies were conducted among refugees and forced migrants who were primarily located in close proximity to their country of origin. The variation in prevalence rates across studies may be attributed to differences in sampling methods, assessment tools, and the duration of time elapsed since exposure to war-related trauma or atrocities. While there is a growing body of evidence supporting the effectiveness of mental health and psychosocial support (MHPSS) interventions, the tools currently in use often lack cultural adaptation, necessitating a critical examination of these findings (Hillel, \u003cspan class=\"CitationRef\"\u003e2023\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003eGlobal south countries have been shifting epidemiologically from infectious diseases to non-communicable diseases (NCD).\u003c/p\u003e\n\u003cp\u003e\u003cspan\u003e2. During humanitarian crises, these is a need to detect and treat quickly and inexpensively previous existing NCD or those who may have developed from a crisis-stress such as hypertension or diabetes.\u003cbr\u003e\u003c/span\u003e\u003cspan\u003e3. However, developing countries and those facing mass disasters or war may not have sufficient economic resources to treat such diseases.\u003cbr\u003e\u003c/span\u003e\u003cspan\u003e4. Numerous studies show that low vagal nerve activity is related to risk of many NCD and to poorer prognosis. Activating the vagus has emerging clinical benefits in several NCD.\u003cbr\u003e\u003c/span\u003e\u003cspan\u003e5. It costs very little to measure heart-rate variability (HRV), the vagal index, and it costs very little to activate the vagal nerve by paced slow breathing with biofeedback.\u003cbr\u003e\u003c/span\u003e\u003cspan\u003e6. Health professionals must be educated about these, worldwide and these could be implemented on a routine basis in developing countries towards early detection, prevention and possible treatment of NCD for the benefit of global health.\u003cbr\u003e\u003c/span\u003e\u003c/p\u003e\n\u003ch3\u003eThe case of Ukraine\u003c/h3\u003e\n\u003cp\u003ePrior to the outbreak of war, the five leading causes of mortality in Ukraine, accounting for 84% of all deaths, were cancer, chronic obstructive pulmonary disease (COPD), cardiovascular disease, diabetes, and mental disorders (WHO, March, 2022). Hypertension affected 35% of the Ukrainian population, with 85% of cases being uncontrolled (WHO, March, 2022), highlighting the urgent need for medical management of this serious health risk. Cancer was responsible for 13% of deaths in Ukraine, with colorectal, breast, and lung cancer being the most common types. Diabetes had a prevalence of approximately 7% among Ukrainians (WHO, March, 2022), although the true figure is likely higher, as a quarter of the population had never undergone blood tests.\u003c/p\u003e\n\u003cp\u003eRegarding mental health, 12.4% of Ukrainians had depression prior to the war, but only 3.2% had ever received treatment for this condition (WHO, March, 2022). The psychological impact of the conflict is expected to compound this burden, with increased rates of anxiety, PTSD, and grief, further straining the already limited healthcare resources (Budosan et al., \u003cspan class=\"CitationRef\"\u003e2023\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003eFollowing the outbreak of the war with Russia, several humanitarian agencies have been providing support to forced migrants in the surrounding countries, as mentioned earlier. The most common health conditions encountered include acute illnesses (e.g., upper respiratory infections, injuries) and chronic diseases (e.g., hypertension, diabetes). These conditions are typically managed with basic medical care, such as medication (e.g., beta-blockers, antibiotics) and wound dressings.\u003c/p\u003e\n\u003cp\u003eHowever, this approach to treatment is not without challenges. First, the lack of resources and infrastructure in humanitarian settings precludes the use of advanced diagnostic measures (e.g., echocardiography, X-rays, blood tests, and brain imaging) to assess clinical outcomes. Second, the transient nature of the POC population, as they continue their onward journey, hinders long-term treatment, therapeutic effectiveness evaluation, monitoring of biomarker changes (e.g., liver function, insulin levels), and management of medication side effects. Finally, the limited financial capacity of humanitarian organizations constrains their ability to provide comprehensive mental and physical healthcare and evaluation.\u003c/p\u003e\n\u003cp\u003eConsequently, there is an urgent need to develop and implement a logistically simple, cost-effective intervention that can address many of the aforementioned health conditions and their underlying pathology, ideally without side effects. Moreover, it is crucial that patients can self-administer the treatment, reducing their dependence on a constantly changing roster of healthcare providers in the context of migration. Finally, it is of high importance to identify a protective factor that is common to many diseases and that is easy to monitor its activity and to activate it.\u003c/p\u003e\n\u003ch3\u003eA common denominator of these health problems: The vagal nerve\u003c/h3\u003e\n\u003cp\u003eThe vagus nerve emerges as a common protective neurobiological factor that is correlated with the health conditions mentioned above, via plausible evidence-based biological mechanisms.\u003c/p\u003e\n\u003cp\u003eThe vagus nerve, the tenth cranial nerve, originates in the brainstem and descends to the viscera, innervating most organs. Its activity can be measured non-invasively through heart rate variability (HRV), reflecting fluctuations in the intervals between normal heart-beats. HRV has a strong correlation with actual vagal nerve activity (r\u0026thinsp;=\u0026thinsp;0.88; Kuo et al., \u003cspan class=\"CitationRef\"\u003e2005\u003c/span\u003e). Crucially, low HRV is predictive of the onset of hypertension (Singh et al., \u003cspan class=\"CitationRef\"\u003e1998\u003c/span\u003e) and a review of 25 studies found that HRV is consistently lower in individuals with diabetes mellitus (Benichou et al., \u003cspan class=\"CitationRef\"\u003e2018\u003c/span\u003e). High HRV is associated with a lower risk of developing myocardial infarction (MI) (Song et al., \u003cspan class=\"CitationRef\"\u003e2014\u003c/span\u003e), and a four-fold increase in post-MI survival, as demonstrated by a review of 21 studies (Buccelletti et al., \u003cspan class=\"CitationRef\"\u003e2009\u003c/span\u003e). Similarly, in cancer, high HRV is linked to better prognosis and survival, independent of confounding factors (De Couck et al., \u003cspan class=\"CitationRef\"\u003e2018\u003c/span\u003e; Zhou et al., \u003cspan class=\"CitationRef\"\u003e2016\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003eWith regard to mental health, a review of 36 studies found that HRV is reduced in generalized anxiety disorder, panic disorder, and PTSD (Chalmers et al., \u003cspan class=\"CitationRef\"\u003e2014\u003c/span\u003e). Furthermore, a review of 21 studies revealed that HRV is also lower in depression (Koch et al., \u003cspan class=\"CitationRef\"\u003e2019\u003c/span\u003e). HRV has been found to be positively correlated with prefrontal cortical activity (Thayer et al., \u003cspan class=\"CitationRef\"\u003e2012\u003c/span\u003e), which is often underactive in many mental disorders (e.g., Koenigs \u0026amp; Grafman, 2009).\u003c/p\u003e\n\u003cp\u003eThe biological mechanisms linking vagal activity to these health conditions can be understood through the lens of neuroimmunology. Inflammation is a key contributing factor in many of the aforementioned health problems (e.g., Greten \u0026amp; Grivennikov, \u003cspan class=\"CitationRef\"\u003e2019\u003c/span\u003e). The vagus nerve plays a pivotal role in communicating peripheral inflammation to the brain (Ek et al., \u003cspan class=\"CitationRef\"\u003e1998\u003c/span\u003e) and subsequently inhibiting it through two pathways. First, vagal activation stimulates the hypothalamic-pituitary-adrenal axis, resulting in the release of cortisol, which suppresses inflammation (Tracey, \u003cspan class=\"CitationRef\"\u003e2009\u003c/span\u003e). Second, descending vagal efferents reach the celiac ganglion, where they transition to a sympathetic branch that innervates the spleen. There, beta-adrenergic receptors on a subset of resident T-cells receive the sympathetic signal and, in response, secrete acetylcholine. Acetylcholine then binds to alpha-7 nicotinic acetylcholine receptors on splenic macrophages, that inhibits the production of pro-inflammatory cytokines (Rosas-Ballina et al., \u003cspan class=\"CitationRef\"\u003e2011\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003eElectrical stimulation of the vagus nerve has been shown to reduce infarct size (Arimura et al., \u003cspan class=\"CitationRef\"\u003e2017\u003c/span\u003e), alleviate chronic pain (Johnson \u0026amp; Wilson, \u003cspan class=\"CitationRef\"\u003e2018\u003c/span\u003e), and enhance antiviral immunity, including increased NK cell and CD8 T-cell counts (Mihaylova et al., \u003cspan class=\"CitationRef\"\u003e2014\u003c/span\u003e). Importantly, the vagus nerve can be non-invasively activated through HRV biofeedback (HRV-B).\u003c/p\u003e\n\u003cp\u003eIn HRV-B, patients learn to perform paced breathing while receiving real-time feedback on their HRV level via a mobile phone screen. Within seconds, they learn to increase their own HRV, which is empowering and fosters a sense of control over their health. This sense of control is particularly crucial in the context of crisis, uncertainty, and helplessness. Furthermore, the simplicity of this approach and its low cost, make it highly relevant and attractive in contexts of treating patients with little resources. Several reviews found that HRV biofeedback improves emotional and physical health (Lehrer et al., \u003cspan class=\"CitationRef\"\u003e2020\u003c/span\u003e; Laborde et al. \u003cspan class=\"CitationRef\"\u003e2022\u003c/span\u003e; Gitler et al., 2023;). Moreover, HRV biofeedback and vagal breathing have been shown to reduce inflammation, pain, and anxiety (e.g., Berry et al., \u003cspan class=\"CitationRef\"\u003e2014\u003c/span\u003e; Steffen et al., \u003cspan class=\"CitationRef\"\u003e2017\u003c/span\u003e; Chin \u0026amp; Kales, \u003cspan class=\"CitationRef\"\u003e2019\u003c/span\u003e). However, to the best of our knowledge, the effects of HRV-B have not been systematically examined in humanitarian contexts or across the multiple medical conditions discussed above.\u003c/p\u003e\n\u003cp\u003eThe following study represents a proof-of-concept intervention within the context of the Ukrainian humanitarian crisis. Due to the ethical imperative and medical necessity of providing care to all those in need, this study was not designed as a formal randomized controlled trial. Nevertheless, we obtained ethical approval from the [institution name] (#BLIND TO REVIEWERS, Ref number 9\u0026thinsp;\u0026minus;\u0026thinsp;6/2022) to collect the reported data, which were gathered for medical purposes and shared with patients as part of standard good clinical practice (GCP). Informed consent was obtained from all participants, with forms provided in their native language, outlining the study\u0026apos;s objectives, applications, and contact information for the principal investigator.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThe worldwide disaster relief non-governmental organization (NGO) NATAN, originally based in Israel, has been operating in Poland since March 2022, providing emergency medical and psychosocial support through a clinic located in a transit camp in Przemysl.\u003c/p\u003e \u003cp\u003eDuring the period in which the intervention took place, the transit center housed approximately 4,000 people of concern (POC) at any given time, with an average length of stay of 1.5 days. The clinic, staffed by physicians, nurses, and social workers, many of whom were proficient in Russian or Ukrainian, offered round-the-clock primary care. The standard operating procedure involved patient registration, collection of demographic information (age, gender) and medical history, diagnostic assessment, and provision of treatment based on clinical judgment and available resources.\u003c/p\u003e \u003cp\u003eThe primary health concerns addressed at the NATAN clinic encompassed a range of acute and chronic conditions, including infectious diseases (particularly gastroenteritis and upper respiratory tract infections [URTI]), minor traumatic injuries and wounds, musculoskeletal complaints, headaches, and psychopathology (e.g., anxiety, depression, and sleep disturbances). Additionally, the clinic managed cardiovascular issues, such as acute exacerbations of ischemic heart disease, congestive heart failure, and asthma.\u003c/p\u003e \u003cp\u003eTreatment modalities included oral medications such as paracetamol, nonsteroidal anti-inflammatory drugs (NSAIDs), antibiotics, and pharmacotherapies for the symptomatic relief of cold, flu, diarrhea, nausea, and vomiting, as well as antidepressants and anxiolytics. In emergency situations, intravenous medications, including Fusid and steroids, and inhaled therapies, such as Ventolin and Aerovent, were administered. The clinic also provided ongoing care and follow-up for chronic conditions, including hypertension, diabetes, arthritis, hypothyroidism, epilepsy, malignancies, and gastrointestinal disorders such as peptic ulcers and heartburn.\u003c/p\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003ePatients\u003c/h2\u003e \u003cp\u003eThe sample comprised 21 Ukrainian patients who sought care at the NATAN humanitarian organization's clinic in Przemysl. Table\u0026nbsp;1 presents the prevalence of their primary health concerns. Participants ranged in age from 10 to 80 years, with a mean (SD) age of 41.33 (20.01) years. The sample included 9 males (42.9%) and 12 females (57.1%).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eMeasures\u003c/h2\u003e \u003cp\u003eData collected included patients' age, gender, and the primary health complaint that prompted their clinic visit. Additionally, perceived stress and current subjective pain levels were assessed using a 0\u0026ndash;10 rating scale. Blood pressure, including systolic blood pressure (SBP) and diastolic blood pressure (DBP), was measured using a Life Ltd electronic blood pressure monitor (model number KD-558).\u003c/p\u003e \u003cp\u003eTo measure heart rate variability (HRV), we employed the I-feelwell photoplethysmograph (PPG) device, which records HRV, heart rate, and oxygen saturation via a sensor attached to the left index finger. This device provides two time-domain HRV parameters: the standard deviation of normal-to-normal (SDNN) interbeat intervals and the root mean square of successive differences (RMSSD) between adjacent normal-to-normal intervals. A recent study found that HRV measured using this device significantly predicted episodes of Crohn's disease in children (Yerushalmy-Feler et al., \u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e2022\u003c/span\u003e).\u003c/p\u003e \u003cdiv id=\"Sec7\" class=\"Section3\"\u003e \u003ch2\u003eInterventions\u003c/h2\u003e \u003cp\u003eThe intervention consisted of an educational component and training in a 3-minute paced vagal breathing technique. First, we used clear, laminated visual aids to explain to each patient how vagal nerve activation relates to their specific health condition. These materials included a diagram illustrating the connection between their condition and the vagus nerve, along with a summary of research demonstrating the benefits of vagal breathing for that particular health concern. Next, we provided instructions on the vagal breathing technique and gave patients a laminated summary card in Russian (the language spoken by most or all Ukrainian participants), which was also used by our healthcare staff. Patients then practiced the 3-minute deep, paced breathing exercise as follows: inhale through the nose for a count of 1\u0026ndash;5, hold the breath for a count of 1\u0026ndash;2, and exhale through pursed lips for a count of 1\u0026ndash;5. This breathing technique has been shown to increase HRV and improve decision-making (De Couck et al., \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e2019\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section3\"\u003e \u003ch2\u003eProcedure\u003c/h2\u003e \u003cp\u003eAll patients underwent a baseline assessment of perceived pain and stress, SBP, DBP, and HRV during a 30-second resting period. They then received the educational explanation and performed the 3-minute paced breathing exercise. Immediately following the intervention, perceived pain and stress, SBP, DBP, and HRV were reassessed during another 30-second resting period.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eWe report descriptive statistics, including means for continuous variables and percentages for categorical variables. The effects of vagal breathing on all outcome measures were evaluated using paired t-tests. Additionally, we examined correlations between the baseline measures to validate the assessments and gain further insight into the relationships among the collected variables.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eRegarding the distribution of categorical variables, 42.9% of the participants were male, and 57.1% were female. Nearly half of the sample (47.6%) had a chronic systemic disease, including hypertension (n\u0026thinsp;=\u0026thinsp;8), epilepsy (n\u0026thinsp;=\u0026thinsp;1), or peripheral numbness (n\u0026thinsp;=\u0026thinsp;1). Chronic pain was reported by 28.6% of the participants, while 23.8% experienced anxiety or severe stress. Table\u0026nbsp;1 presents the means (SD) of all continuous variables before and after the vagal breathing intervention.\u003c/p\u003e \u003cp\u003eAll outcome measures, with the exception of SBP, showed significant improvements following the vagal breathing exercise. Specifically, DBP (t(19)\u0026thinsp;=\u0026thinsp;1.96, p\u0026thinsp;\u0026lt;\u0026thinsp;0.05, one-tailed), pain (t(11)\u0026thinsp;=\u0026thinsp;2.78, p\u0026thinsp;\u0026lt;\u0026thinsp;0.05), and perceived stress (t(12)\u0026thinsp;=\u0026thinsp;4.77, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) were significantly reduced post-intervention. In contrast, RMSSD (t(17)\u0026thinsp;=\u0026thinsp;2.5, p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) and SDNN (t(17)\u0026thinsp;=\u0026thinsp;4.69, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) significantly increased following the vagal breathing exercise.\u003c/p\u003e \u003cp\u003eTable\u0026nbsp;2 presents the correlations between the outcome variables at baseline. We focused on the SDNN HRV parameter, as it was highly correlated with RMSSD (r\u0026thinsp;=\u0026thinsp;0.90, p\u0026thinsp;\u0026lt;\u0026thinsp;0.01) and demonstrated more consistent associations with the other variables. Both SBP and DBP exhibited strong, positive, and significant correlations with perceived stress. SDNN was negatively and significantly correlated with both pain and perceived stress. Interestingly, pain and perceived stress were not significantly correlated with each other.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis pioneering project represents the first application of neuroimmunology and psychophysiological principles in a humanitarian context. Specifically, we tested the effects of an evidence-based heart rate variability biofeedback (HRV-B) intervention on multiple health conditions among Ukrainian forced migrants.\u003c/p\u003e \u003cp\u003eOur findings demonstrate significant improvements in five out of six outcome measures, encompassing both objective and subjective indices. In particular, diastolic blood pressure (DBP), pain, and perceived stress were reduced, while two HRV parameters were increased significantly following the intervention.\u003c/p\u003e \u003cp\u003eThe observed correlations between the vagal index and other outcomes, as well as the effects of HRV-B on medical and subjective measures, underscore the integrative and comprehensive roles of the vagus nerve in health. This notion is supported by the neurovisceral integration model (Thayer et al., \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e2009\u003c/span\u003e) and by a neuroimmunological model of chronic diseases (Gidron et al., \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e2018\u003c/span\u003e). The neurovisceral integration model highlights the central role of the vagus nerve, as indexed by HRV, in mediating the relationship between frontal brain activity and the regulation of cardiac function. The neuroimmunological model of chronic diseases synthesizes evidence linking vagal activity to healthier behaviors (e.g., reduced smoking), the predictive value of its marker (HRV) for lower risk and better survival in chronic diseases, and the regulation of biological disease mechanisms (e.g., inflammation).\u003c/p\u003e \u003cp\u003eOur results align with the findings of Lehrer et al. (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e2020\u003c/span\u003e) and Gitler et al. (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e2022\u003c/span\u003e), who reviewed the effects of HRV-B on various health conditions, including hypertension, chronic pain, and heart disease. Specifically, our observations are consistent with studies demonstrating that HRV-B reduces blood pressure and pain (Berry et al., \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e2014\u003c/span\u003e; Steffen et al., \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e2017\u003c/span\u003e). Furthermore, our findings concur with a meta-analysis of 24 studies showing that HRV biofeedback reduces and anxiety (Goessl et al., \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e2017\u003c/span\u003e).\u003c/p\u003e "},{"header":"Conclusions and implications to policy","content":"\u003cp\u003eThis proof-of-concept intervention study supports the acceptability and effectiveness of self-activation in the humanitarian contexts. This preliminary study needs to be replicated in a larger sample with a control group, respecting the unique ethical challenges of humanitarian contexts. If replicated, this novel psycho-physiological approach may offer a simple but not simplistic intervention for a wide range of health problems.\u003c/p\u003e\u003ch2\u003eLimitations\u003c/h2\u003e\u003cp\u003eThe present project was first of all a humanitarian project, and as such, it naturally has several limitations. First, the sample size was small and heterogeneous, and there was no control group. However, given that this initiative was conducted during a humanitarian crisis, it was not feasible to design a controlled study while at the same time adhering to good clinical practice principles. Moreover, the primary purpose of data collection was to provide patients with feedback on their HRV-B performance rather than to conduct a formal study. Finally, the long-term effects of this intervention remain unknown.\u003c/p\u003e\u003ch2\u003eStrengths of the study\u003c/h2\u003e\u003cp\u003eDespite these limitations, the intervention is evidence-based, drawing upon extensive findings from neuroimmunology and health psychology research. Moreover, it is simple yet effective, inexpensive, and without any known adverse side effects. To the best of our knowledge, this approach has seldom been applied in humanitarian contexts.\u003c/p\u003e\u003ch2\u003eImplications for policy\u003c/h2\u003e\u003cp\u003eHumanitarian crises present a wide range of health challenges for affected populations, including distress related to displacement, witnessing the death and injury of loved ones, personal injury, and lack of treatment for pre-existing health conditions. Measuring HRV and performing vagal breathing with biofeedback are inexpensive interventions that can address many of these health concerns and can be easily taught to staff and patients. Furthermore, patients can practice the technique independently, without relying on the healthcare system, thereby promoting a sense of empowerment. People of concern can engage in HRV-B while on the move and at any given time and place.\u003c/p\u003e\u003cp\u003eIf replicated, this intervention could be widely disseminated and easily adopted in multiple humanitarian settings worldwide. The potential impact of such an intervention is substantial, as it may improve the quality of life and health outcomes for a large number of individuals affected by humanitarian crises. Health professionals must be educated about the protective roles of the vagal nerve in fatal and chronic diseases and on how to monitor and activate it in a minimum cost. These could be implemented on a routine basis in global south countries towards early detection, prevention and possible treatment of NCD for the benefit of global health.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eCOPD - Chronic Obstructive Pulmonary Disease\u003c/p\u003e\n\u003cp\u003eDBP - Diastolic Blood Pressure\u003c/p\u003e\n\u003cp\u003eEU - European Union\u003c/p\u003e\n\u003cp\u003eGI - Gastrointestinal\u003c/p\u003e\n\u003cp\u003eHRV - Heart Rate Variability\u003c/p\u003e\n\u003cp\u003eMHPSS - Mental Health and Psychosocial Support\u003c/p\u003e\n\u003cp\u003eMI - Myocardial Infarction\u003c/p\u003e\n\u003cp\u003eNSAIDs - Non-Steroidal Anti-Inflammatory Drugs\u003c/p\u003e\n\u003cp\u003ePOC - People of Concern\u003c/p\u003e\n\u003cp\u003ePPG - Photoplethysmography\u003c/p\u003e\n\u003cp\u003ePTSD - Post-Traumatic Stress Disorder\u003c/p\u003e\n\u003cp\u003eSBP - Systolic Blood Pressure\u003c/p\u003e\n\u003cp\u003eSDNN - Standard Deviation of Normal-to-Normal Intervals\u003c/p\u003e\n\u003cp\u003eRMSSD - Root Mean Square of Successive Differences\u003c/p\u003e\n\u003cp\u003eUNHCR - United Nations High Commissioner for Refugees\u003c/p\u003e\n\u003cp\u003eURTI - Upper Respiratory Tract Infections\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eEthics approval and consent to participate-\u003c/p\u003e\n\u003cp\u003eEthical approval was granted by the IRB committee of Tel Hai Academic College and consent was given.\u003c/p\u003e\n\u003cp\u003eIt is to confirm that all methods in this study, were performed in accordance with the ethical standards as laid down in the Declaration of Helsinki and its later amendments.\u003cbr\u003eIt is to confirm that written informed consent was obtained from all participants.\u003c/p\u003e\n\u003cp\u003eConsent for publication- Written informed consent for publication was obtained.\u003c/p\u003e\n\u003cp\u003eAvailability of data and materials- The data that support the findings of this study are available from the corresponding author, but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission of the corresponding author.\u003c/p\u003e\n\u003cp\u003eCompeting interest- Author A declares that he has no conflict of interest. Author B declares that he has no conflict of interest.\u0026nbsp;Author C declares that she has no conflict of interest.\u0026nbsp;Author D declares that she has no conflict of interest. Author E declares that she has no conflict of interest.\u0026nbsp;Author F declares that she has no conflict of interest.\u003c/p\u003e\n\u003cp\u003eAuthors\u0026apos; contributions\u0026nbsp;- Y.G. and E.L made substantial contributions to the conception, designed the work, analyzed and have drafted the work and substantively revised it. C.R. \u0026nbsp;analyzed and\u0026nbsp;have drafted the work. S.S., R.S. and D.A. made substantial contributions to the conception.\u003c/p\u003e\n\u003cp\u003eFunding was received from OLAM TOGETHER and from NATAN- worldwide international relief.\u003c/p\u003e\n\u003cp\u003eAcknowledgements \u0026ndash; we would like to thank the management of the transition camo in Przemysl, Poland for enabling us to perform this study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eAcarturk C, Cetinkaya M, Senay I, Gulen B, Aker T, Hinton D. Prevalence and predictors of posttraumatic stress and depression symptoms among Syrian refugees in a refugee camp. J Nerv Ment Dis. 2017;206(1):40-45.\u003c/li\u003e\n\u003cli\u003eAlpak G, Unal A, Bulbul F, Sagaltici E, Bez Y, Altindag A, Savas HA. Post-traumatic stress disorder among Syrian refugees in Turkey: A cross-sectional study. Int J Psychiatry Clin Pract. 2015;19(1):45-50.\u003c/li\u003e\n\u003cli\u003eArimura T, Saku K, Kakino T, Nishikawa T, Tohyama T, Sakamoto T, et al. 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BMC Cardiovasc Disord. 2014;14(1):1-8. doi:10.1186/1471-2261-14-1.\u003c/li\u003e\n\u003cli\u003eSteffen PR, Austin T, DeBarros A, Brown T. The impact of resonance frequency breathing on measures of heart rate variability, blood pressure, and mood. Front Public Health. 2017;5:222. doi:10.3389/fpubh.2017.00222.\u003c/li\u003e\n\u003cli\u003eThayer JF, Hansen AL, Saus-Rose E, Johnsen BH. Heart rate variability, prefrontal neural function, and cognitive performance: the neurovisceral integration perspective on self-regulation, adaptation, and health. Ann Behav Med. 2009;37(2):141-153. doi:10.1007/s12160-009-9101-z.\u003c/li\u003e\n\u003cli\u003eThayer JF, \u0026Aring;hs F, Fredrikson M, Sollers JJ 3rd, Wager TD. A meta-analysis of heart rate variability and neuroimaging studies: implications for heart rate variability as a marker of stress and health. Neurosci Biobehav Rev. 2012;36(2):747-756. doi:10.1016/j.neubiorev.2011.11.009.\u003c/li\u003e\n\u003cli\u003eTracey KJ. Reflex control of immunity. Nat Rev Immunol. 2009;9(6):418-428. doi:10.1038/nri2566.\u003c/li\u003e\n\u003cli\u003eUNHCR Operational Data Portal. June, 2022. https://data.unhcr.org/en/situations/ukraine. Accessed June 20, 2024.\u003c/li\u003e\n\u003cli\u003eUNHCR. Poland welcomes more than two million refugees from Ukraine. 2022. https://www.unhcr.org/news/press/2022/3/6234811a4/poland-welcomes-million-refugees-ukraine.html. Accessed June 20, 2024.\u003c/li\u003e\n\u003cli\u003eUNWOMEN. Collecting data and analysis on how the war in Ukraine is impacting women and girls. 2022. https://www.unwomen.org/en/news-stories/news/2022/04/collecting-data-and-analysis-on-how-the-war-in-ukraine-is-impacting-women-and-girls. Accessed June 20, 2024.\u003c/li\u003e\n\u003cli\u003eYerushalmy-Feler A, Cohen S, Lubetzky R, Moran-Lev H, Ricon-Becker I, Ben-Eliyahu S, Gidron Y. Heart rate variability as a predictor of disease exacerbation in pediatric inflammatory bowel disease. J Psychosom Res. 2022;158:110911. doi:10.1016/j.jpsychores.2022.110911.\u003c/li\u003e\n\u003cli\u003eZhou X, Ma Z, Zhang L, Zhou S, Wang J, Wang B, Fu W. Heart rate variability in the prediction of survival in patients with cancer: a systematic review and meta-analysis. J Psychosom Res. 2016;89:20-25. doi:10.1016/j.jpsychores.2016.08.006.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp dir=\"LTR\"\u003eTable 1- Mean and Standard deviation of main outcome variables\u003c/p\u003e\n\u003cp dir=\"LTR\"\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Pre\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Post\u003c/p\u003e\n\u003cp dir=\"LTR\"\u003eVariable\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Mean\u0026nbsp; \u0026nbsp;\u0026nbsp;SD\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Mean\u0026nbsp; \u0026nbsp;\u0026nbsp;SD\u003c/p\u003e\n\u003cp dir=\"LTR\"\u003e---------------------------------------------------------------------------------------------\u003c/p\u003e\n\u003cp dir=\"LTR\"\u003eSBP \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;148.6 \u0026nbsp; \u0026nbsp;22.5\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;143.6 \u0026nbsp; \u0026nbsp; \u0026nbsp;22.1\u003c/p\u003e\n\u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp dir=\"LTR\"\u003eDBP\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;90.5 \u0026nbsp; \u0026nbsp; \u0026nbsp;12.6\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;86.5*# \u0026nbsp; \u0026nbsp;12.3\u003c/p\u003e\n\u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp dir=\"LTR\"\u003eRMSSD\u0026nbsp;\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;37.7 \u0026nbsp; \u0026nbsp; \u0026nbsp;27.5\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;55.3* \u0026nbsp; \u0026nbsp; \u0026nbsp;49.7\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp dir=\"LTR\"\u003eSDNN\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;48.4 \u0026nbsp; \u0026nbsp; \u0026nbsp;39.2\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;73.1*** 48.3\u003c/p\u003e\n\u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp dir=\"LTR\"\u003ePAIN\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;3.9 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;2.4\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;2.7* \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; 2.4\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/p\u003e\n\u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp dir=\"LTR\"\u003eSTRESS\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;5.8 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;2.4\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;3.1*** \u0026nbsp; \u0026nbsp; 2.2\u003c/p\u003e\n\u003cp dir=\"LTR\"\u003e---------------------------------------------------------------------------------------------\u003c/p\u003e\n\u003cp dir=\"LTR\"\u003eSBP= Systolic blood pressure; DBP- Diastolic blood pressure;\u003c/p\u003e\n\u003cp dir=\"LTR\"\u003eRMSSD= Route mean square of \u0026nbsp;successive differences;\u003c/p\u003e\n\u003cp dir=\"LTR\"\u003eSDNN= Standard deviation of normal to normal intervals;\u003c/p\u003e\n\u003cp dir=\"LTR\"\u003e# p\u0026lt;0.05 (one tailed); *p\u0026lt;0.05; ***p\u0026lt;0.001;\u003c/p\u003e\n\u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp dir=\"LTR\"\u003e\u0026nbsp;Table 2- Correlations between outcome variables:\u003c/p\u003e\n\u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp dir=\"LTR\"\u003eSBP\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;DBP\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;SDNN\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Pain\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Stress\u003c/p\u003e\n\u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp dir=\"LTR\"\u003eDBP\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;0.58**\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;1\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;-0.27\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;0.12\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;0.71**\u003c/p\u003e\n\u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp dir=\"LTR\"\u003eSDNN\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;-0.29\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;0.27\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;1\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;-0.62*\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;-0.61*\u003c/p\u003e\n\u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp dir=\"LTR\"\u003ePain\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;0.28\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;0.12\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;-0.62*\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;1\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;0.19\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp dir=\"LTR\"\u003eStress\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;0.86**\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;0.71**\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;-0.61*\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;0.19\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;1\u003c/p\u003e\n\u003cp dir=\"LTR\"\u003e*p\u0026lt;0.05; **p\u0026lt;0.01\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Ukraine conflict, Health conditions, Vagal nerve, Paced breathing, Humanitarian action","lastPublishedDoi":"10.21203/rs.3.rs-4947313/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4947313/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e \u003cb\u003eBackground -\u003c/b\u003e The ongoing conflict in Ukraine has forced numerous migrants into neighboring countries, many suffering from pre-existing or newly acquired physical and mental health conditions. Addressing these complex challenges in humanitarian settings requires innovative, evidence-based interventions that are cost-effective and easy to administer. Drawing upon research highlighting the vagus nerve's role in regulating well-being, we hypothesized that vagal nerve activation could offer a promising therapeutic approach.\u003c/p\u003e \u003cp\u003e \u003cb\u003eMethod\u003c/b\u003e- We conducted a proof-of-concept study in which 21 Ukrainian forced migrants were trained in a biofeedback-guided paced breathing intervention designed to stimulate the vagus nerve and promote self-regulation of stress response systems.\u003c/p\u003e \u003cp\u003eChanges in pain perception, perceived stress, blood pressure, and heart rate variability (an established marker of vagal tone) were assessed before and after the vagal breathing intervention using t-test. These multi-dimensional outcome measures were chosen to capture both subjective and objective physical and mental well-being indicators. Correlations were examined at baseline.\u003c/p\u003e \u003cp\u003e \u003cb\u003eResults-\u003c/b\u003e Statistically significant improvements were observed in all measures except systolic blood pressure, providing preliminary evidence for the efficacy of vagal nerve activation in alleviating stress-related health symptoms.\u003c/p\u003e \u003cp\u003e \u003cb\u003eConclusions-\u003c/b\u003e This study demonstrates the feasibility and therapeutic potential of a vagal nerve-activating intervention in a humanitarian setting. These findings warrant replication in larger, controlled trials. If substantiated, this low-cost, scalable intervention could help mitigate health burdens among forced migrant populations worldwide. This intervention is relevant to south global countries which face an epidemiological shift from infectious to non-communicable diseases.\u003c/p\u003e","manuscriptTitle":"Vagal nerve biofeedback intervention for improving health outcomes among Ukrainian forced migrants: A proof-of-concept study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-09-27 08:41:04","doi":"10.21203/rs.3.rs-4947313/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"2e71b631-40be-41dd-85e3-0547d594e9d8","owner":[],"postedDate":"September 27th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-10-22T06:11:46+00:00","versionOfRecord":[],"versionCreatedAt":"2024-09-27 08:41:04","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4947313","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4947313","identity":"rs-4947313","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}