Patterns of adolescent perceived social support and inflammation in adulthood within major racial groups: Findings from a longitudinal, nationally representative sample.

Inflammation, the body's protective response to injury and infection, plays a critical role in physical and mental health outcomes. Elevated chronic inflammation is implicated as a predictor of disease and all-cause mortality and is linked with several psychological disorders. Given that social support is associated with lower rates of mortality and psychopathology, the links between inflammation and social support are well-studied. However, there are many significant gaps related to both the specificity and generalizability of extant findings. There is a paucity of research on the association between social support and inflammation within different racial groups. Additionally, more research is warranted to understand whether social support from different sources uniquely contributes to inflammation, above and beyond other sources of support. Thus, the current study examined whether perceived emotional social support during adolescence predicted inflammation during adulthood within several racial groups. Participants (n = 3,390) were drawn from the National Longitudinal Study of Adolescent to Adult Health (Add Health), identified as either Asian, Black, Latinx, White, or Multiracial, and had complete data on study variables. Consistent with our hypotheses and previous research, greater perceived support during adolescence was associated with lower inflammation during adulthood, but only for White participants. Contrastingly, greater perceived support during adolescence was associated with higher inflammation during adulthood for individuals who identified as Asian, Latinx, Black, or Multiracial. Furthermore, patterns of social support and inflammation within each racial group varied by relationship type. These results highlight the importance of studying relationship processes and health outcomes within racial groups to understand their unique, lived experiences.

Psychological and spiritual outcomes during the COVID-19 pandemic: A prospective longitudinal study of adults with chronic disease.

OBJECTIVE: This prospective longitudinal study examined whether coronavirus disease 2019 (COVID-19) has led to changes in psychological and spiritual outcomes among adults with chronic disease. METHOD: Participants (N = 302) were a stratified, nonrandom sample of adults (Mage = 64.46, SD = 10.86, 45.7% female). The sample was representative of the chronically ill, U.S. adult population in gender, race/ethnicity, region, and religious affiliation but older in age and higher in socioeconomic status. Participants completed online-administered measures 1 month before the March 11 pandemic declaration (T1) and then 1 and 3 months after it (T2 and T3). At T1 through T3, they completed measures of depression, anxiety, personal suffering, psychological well-being, trait resilience, optimism, hope, grit, spiritual struggles, spiritual fortitude, and positive religious coping. At T2 and T3, they also completed measures of social support, physical health, resource loss, perceived stress, and COVID-19 fears and exposure. RESULTS: Overall, people did not change substantially in psychological or spiritual outcomes over time. However, trait resilience increased and personal suffering declined. People highest in prepandemic suffering increased in spiritual fortitude. Racial/ethnic minorities increased in religious importance. Roughly half (48.9%) of participants exhibited psychological resilience (no/minimal depression or anxiety symptoms) at both T2 and T3. Perceived stress and psychological resource loss were associated with adverse mental health outcomes, but social support and physical health were not. COVID-19 fears contributed more to mental health than COVID-19 exposure. CONCLUSIONS: Even among vulnerable populations such as adults with chronic disease, during pandemic conditions like COVID-19, many people may exhibit-or even increase slightly in-psychological and spiritual resilience. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

The Many Roles of Pediatric Integrated Behavioral Health Specialists.

The primary care pediatric setting is intended to provide continuous and comprehensive care throughout a child's life, ensuring overall well-being. Routinely scheduled well-child visits are ideal to assess developmental progress, environmental health, behavior/psychosocial issues, and other concerns. Delivering integrated behavioral health (IBH) in the primary care setting may aid in identifying any early concerns or difficulties and provides resources and support when these issues first emerge; thus, promoting the child's well-being. IBH should be engaged early and often to establish a relationship with families and follow them as the child develops, regardless of the presence of a precipitating behavior concern.

Translation and psychometric validation of the traditional Chinese version of patient-reported outcomes measurement information system Pediatric-25 Profile version 2.0 (PROMIS-25) in Chinese Children with Cancer in Hong Kong.

PURPOSE: To translate and cross-cultural validate the PROMIS Pediatric-25 Profile 2.0 (PROMIS-25) into traditional Chinese, and to investigate its psychometric properties in children with cancer in Hong Kong. METHODS: The Functional Assessment of Chronic Illness Therapy translation methodology was adopted in this study. Three panel members evaluated the semantic equivalence and content validity. The psychometric properties were tested with 103 children with cancer (10-18 years). Internal consistency and structural validity were examined by Cronbach's alpha and Rasch analysis. Convergent and divergent validity were assessed by correlating it with traditional Chinese pediatric quality of life inventory™ 4.0 domains (traditional Chinese PedsQL™ 4.0), traditional Chinese Health Questionnaire-9 (C-PHQ-9), and the numeric pain rating scale (NPRS). RESULTS: The semantic equivalence score and content validity index were both 100%. All domains indicated good internal consistency (α = 0.83-0.88) and unidimensionality (variance explained > 55.5% and 1st contrast eigenvalues < 2.0). All items showed good item fit (0.6-1.4). For convergent validity, the traditional Chinese PROMIS-25 domains demonstrated moderate-to-large correlations with traditional Chinese PedsQL™ 4.0 domains (r ≥ ± 0.69), C-PHQ-9 Item-4 and total score (r = 0.75-0.80), except NPRS (r = 0.44). For divergent validity, traditional Chinese PROMIS-25 had low correlations with traditional Chinese PedsQL™ 4.0 domains (r < ± 0.21), C-PHQ-9 item-4 (r = 0.3), and NPRS (r = - 0.12). The traditional Chinese PROMIS-25 fatigue domain was weakly correlated with NPRS (r = 0.39). CONCLUSION: The traditional Chinese PROMIS-25 is semantically and conceptually like the original PROMIS-25 with satisfactory internal consistency, structural validity, and construct validity.

Impact of Homeopathic Treatment on the Quality of Life of Women with Chronic Diseases: A Randomized Controlled Pragmatic Trial.

BACKGROUND: Despite the increasing demand for complementary and integrative medicine, only a few studies have evaluated the effect of these types of treatments on the quality of life (QoL) of patients with chronic diseases. The objective of this study was to evaluate the QoL of women treated with homeopathy within the Public Health System of Belo Horizonte, Brazil. METHODS: This is a prospective randomized controlled pragmatic trial. The patients were divided into two independent groups, one group underwent homeopathic treatment in the first 6-month period and the other did not receive any homeopathic treatment. In both randomized groups, patients maintained their conventional medical treatment when necessary. The World Health Organization Quality of Life abbreviated questionnaire (WHOQOL-BREF) was used for QoL analysis prior to treatment and 6 months later. RESULTS: Randomization afforded similar baseline results in three domains of QoL analysis for both groups. After 6 months' treatment, there was a statistically significant difference between groups in the physical domain of WHOQOL-BREF: the average score improved to 63.6 ± (SD) 15.8 in the homeopathy group, compared with 53.1 ± (SD) 16.7 in the control group. CONCLUSIONS: Homeopathic treatment showed a positive impact at 6 months on the QoL of women with chronic diseases. Further studies should be performed to determine the long-term effects of homeopathic treatment on QoL and its determinant factors.

Chronic conditions, multimorbidity, and quality of life among patients attending monk healers and primary care clinics in Thailand.

BACKGROUND: The study aimed to assess chronic diseases, multimorbidity, and QoL among patients attending two different treatment settings in Thailand. METHODS: In all, 1409 attendees of three monk healer or three health centres were assessed with self-reported measures on chronic conditions and Quality of Life (QoL). RESULTS: Results indicate that the most common chronic conditions were common mental disorder (25.2%), followed by hypertension (22.8%), high blood cholesterol (18.0%), fatigue disorder (14.4%), diabetes (14.0%), migraine headaches (13.7%), sleeping problem (12.2%), and ulcer (11.0%). In all, 40.6% had multimorbidity (two or more chronic conditions) (42.4% in the monk healer and 38.9% in the primary care setting). In ANCOVA analysis, adjusted for sex, age, employment status, marital status, education, economic status, comorbidity, and health care setting, the poorest overall QoL was found among clients with common mental disorders (58.5 mean score), followed by emphysema or asthma (60.2), sleeping problem (61.5), migraine headaches (62.7), fatigue disorder (63.3), substance use disorder (63.6) and ulcer (64.3). The overall QoL was poorer among monk healer clients (66.5) than primary care patients (68.8). In adjusted logistical regression analysis, being a monk healer attendee, older age (55-93 years), and high debt were positively, and being employed and better overall quality of life were negatively associated with multimorbidity, overall, for the monk healer and primary care setting. In adjusted linear regression analyses, primary health care attenders, older age, were employed and post-secondary education increased the odds of better overall QoL. CONCLUSION: Multimorbidity was higher among clients attending monk healers than those attending primary care facilities and QoL was poorer among clients seeking care from monk healers than those attending primary care. High multimorbidity was found and major chronic conditions were found to have poor QoL. Determinants of multimorbidity and QoL in two different treatment settings provide information to improve the management of chronic conditions.

The effect of spiritual well-being on adaptation to chronic illness among people with chronic illnesses.

PURPOSE: This study aimed to identify the effect of spiritual well-being on the adaptation to chronic illness, among people with chronic illnesses. DESIGN AND METHODS: The study comprised of 466 patients hospitalized in the internal medicine clinics of internal diseases, cardiology, neurology, and chest diseases, at the training and research hospital of a university. FINDINGS: There was a significant positive relationship between spiritual well-being and adaptation and how spiritual well-being affected patients' adaptation to chronic illness. PRACTICE IMPLICATION: Study results indicated that adaptation to chronic illness increased in direct relation to an increased level of spiritual well-being, among people with chronic illnesses.

Mindfulness and Acceptance Interventions for Parents of Children and Adolescents Diagnosed with Chronic Medical Conditions: A Systematic Review.

Background: Mindfulness and acceptance interventions (MAIs) have been identified as potentially beneficial for parents of children and adolescents diagnosed with chronic medical conditions. Objective: The objective of this review was to provide a descriptive summary of the existing literature on MAIs delivered to parents of children and adolescents diagnosed with chronic medical conditions. Data sources: Electronic searches were conducted by a Library Information Specialist familiar with the field by using EMBASE, MEDLINE, PsycINFO, EBM Reviews Databases, and Cochrane Database of Systematic Reviews. Study eligibility, participants, and interventions: Peer-reviewed journal articles of MAIs delivered to parents of children and adolescents (birth to 18 years of age) diagnosed with a chronic medical condition were eligible for inclusion. Study appraisal and synthesis methods: A total of 18 studies involving 793 parents met inclusion criteria and thus were included in this review. The majority of studies were either pre/post design (n = 8) or randomized controlled trials (n = 6). Most interventions were delivered within a group (n = 6) or individually (n = 5). Nearly all studies (n = 14) reported statistically significant outcomes following the MAI intervention. Conclusions and implications of key findings: Descriptive information yielded from this review provides promising evidence that MAIs are being delivered to parents across the world and many researchers are using similar outcome measures when assessing the psychological flexibility, acceptance, and mindfulness skills following participation in MAIs among this population of parents.

Religiosity and Spirituality in the Stages of Recovery From Persistent Mental Disorders.

ABSTRACT: The impact of religiosity and spirituality (R/S) on mental health and the importance of incorporating R/S in mental health treatment have been previously explored. However, clarification is needed regarding the effects of R/S in the process of recovery from persistent mental disorders (PMDs). This study identifies how different R/S factors correlate with the stages of recovery, while considering individual psychological well-being and perceived social support. Seventy-five individuals who use Madrid's public services for people with PMD completed questionnaires assessing those factors. We found that during the recovery process, R/S correlated with psychological well-being and perceived social support, and that these variables were associated with the five stages of recovery differently. We further identified the importance of gratitude, compassion, inner peace, and connection with life in the recovery process. Overall, our findings highlight the importance of these R/S variables in particular recovery stages for individuals with PMD.

Effectiveness of hospital clowns for symptom management in paediatrics: systematic review of randomised and non-randomised controlled trials.

OBJECTIVE: To evaluate evidence from randomised controlled trials and non-randomised controlled trials on the effectiveness of hospital clowns for a range of symptom clusters in children and adolescents admitted to hospital with acute and chronic conditions. DESIGN: Systematic review of randomised and non-randomised controlled trials. DATA SOURCES: Medline, ISI of Knowledge, Cochrane Central Register of Controlled Trials, Science Direct, Scopus, American Psychological Association PsycINFO, Cumulative Index to Nursing and Allied Health Literature, and Latin American and Caribbean Health Sciences Literature. STUDY SELECTION: Randomised and non-randomised controlled trials were peer reviewed using the following eligibility criteria: children and adolescents who were admitted to hospital for acute conditions or chronic disorders, studies comparing use of hospital clowns with standard care, and studies evaluating the effect of hospital clowns on symptom management of inpatient children and adolescents as a primary outcome. DATA EXTRACTION AND SYNTHESIS: Two investigators independently screened studies, extracted data, and appraised the risk of bias. Methodological appraisal was assessed by two investigators independently using the Jadad scale, the revised Cochrane risk-of-bias tool for randomised controlled trials (RoB 2), and the risk of bias in non-randomised studies (ROBINS-I) tool for non-randomised controlled trials. RESULTS: 24 studies (n=1612) met the inclusion criteria for data extraction and analysis. Most studies were randomised controlled trials (n=13). Anxiety was the most frequently analysed symptom (n=13), followed by pain (n=9), psychological and emotional responses and perceived wellbeing (n=4), stress (n=4), cancer related fatigue (n=3), and crying (n=2). Five studies used biomarkers, mainly cortisol, to assess stress or fatigue outcome following hospital clowns. Most of the randomised controlled trials (n=11; 85%) were rated as showing some concerns, and two trials were rated with a high risk of bias. Most non-randomised controlled trials (n=6; 55%) were rated with a moderate risk of bias according to ROBINS-I tool. Studies showed that children and adolescents who were in the presence of hospital clowns, either with or without a parent present, reported significantly less anxiety during a range of medical procedures, as well as improved psychological adjustment (P<0.05). Three studies that evaluated chronic conditions showed favourable results for the intervention of hospital clowns with significant reduction in stress, fatigue, pain, and distress (P<0.05). CONCLUSIONS: These findings suggest that the presence of hospital clowns during medical procedures, induction of anaesthesia in the preoperative room, and as part of routine care for chronic conditions might be a beneficial strategy to manage some symptom clusters. Furthermore, hospital clowns might help improve psychological wellbeing in admitted children and adolescents with acute and chronic disorders, compared with those who received only standard care. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018107099.

Examining Associations between Community Health Worker-Rated Health and Mental Health among Latino Adults with Chronic Disease.

Latinos with chronic disease often experience comorbid depression, but confront barriers to mental health treatment. Community health workers (CHWs) develop trusting relationships with the communities they serve, and may be uniquely positioned to identify Latinos with mental health care needs. Research has not examined whether their rating of clients' health is indicative of their mental health. This mixed-methods study examines CHWs' appraisals of Latino adults' health and their relation to mental health outcomes, and explores factors informing CHWs' rating of health status. The current study utilized baseline data from the Linking Individual Needs to Community and Clinical Services (LINKS) study. We assessed associations between CHW-rated health (CHWRH), or rating of health status as poor-excellent, and mental health outcomes with multilevel linear regression modelling. We qualitatively analyzed CHWs' written perceptions of participants' health status to understand what influenced their health rating. The quantitative results showed that CWHRH was significantly related to depressive symptoms and emotional problems severity. The qualitative results showed that CHWs took a holistic and ecological approach in rating health. The findings suggest that CHWRH could be indicative of mental health among Latino adults. Further studies investigating CHWRH as an independent indicator of mental health are warranted.

Mindfulness, Stress, and Aging.

Mindfulness has been applied in several adaptations, including Mindfulness-Based Stress Reduction and Mindfulness-Based Cognitive Therapy, to treat chronic conditions in older adults. Older adults may be particularly well suited for mindfulness interventions, because they bring decades of life experience to this contemplative therapy. Mindfulness is also an appealing intervention for older adults as it is inexpensive, effective over time, and easy to access. This article examines mental and physical chronic conditions proven responsive to mindfulness, including cognitive function, anxiety, depression, sleep quality, loneliness, posttraumatic stress disorder, cardiovascular conditions, diabetes, rheumatoid arthritis, Parkinson's disease, urge urinary incontinence, and chronic pain.

Support preferences for Arabic people with a chronic condition living in Australia: A descriptive survey.

Chronic diseases are becoming increasingly common and are a priority for action in the Australian health sector. This study investigated the models of support groups preferred by Arab Australians living with chronic conditions. Two hundred fifty-one Arab people with chronic conditions completed a descriptive survey. More than half of participants thought that information on palliative care, financial advice and guidance, social and emotional support for self and family, complementary therapies, and being involved in treatment decisions were extremely useful. Conversely, information about palliative care, financial advice and guidance, and complementary therapies was seen as least useful. Eighty-five percent of participants reported willingness to attend a support program. Participants indicated they preferred the program to be held at a local community organization and facilitated by health care professionals. There was a high level of agreement in the views of Arab participants about the preferred location, type of facilitator, and content of a support program. These findings should inform the design of future programs for Arab immigrants with chronic conditions.

The influence of trait mindfulness on depression in multiple sclerosis: potential implications for treatment.

PURPOSE: This study seeks to add to existing literature on depression and illness intrusiveness in chronic disorders by examining, (1) how the perceived intrusiveness of multiple sclerosis (MS) leads to depression, (2) and the mediating role trait mindfulness plays in this relationship METHODS: Participants (N = 755) were persons with MS (PwMS) recruited through the North American Research Committee on MS (NARCOMS) registry (a larger study). Participants completed the Illness Intrusiveness Ratings Scale, the Hospital Anxiety and Depression Scale and the Mindful Attention Awareness Scale. A mediation model assessed if trait mindfulness mediates the relationship between illness intrusiveness and depression RESULTS: Illness intrusiveness predicted trait mindfulness (a = - 4.54; p < .001), trait mindfulness predicted depression (b = - .04; p < .001); there was a direct effect of illness intrusiveness on depression (c' = 2.53; p < .001) and an indirect effect on depression (ab = .17, 95% BCa CI [.10, .25]) when trait mindfulness was in the model, which represented a medium size effect, R2med = .10 [95% CI .07, .14] CONCLUSION: Trait mindfulness mediates the relationship between illness intrusiveness and depression in PwMS. Providers could provide psychoeducation on the benefits of mindfulness and mindfulness-based interventions.

Safety and effectiveness of a Tai Chi-based cardiac rehabilitation programme for chronic coronary syndrom patients: study protocol for a randomised controlled trial.

INTRODUCTION: Preliminary evidence from clinical observations suggests that Tai Chi exercise may offer potential benefits for patients with chronic coronary syndrom (CCS). However, the advantages for CCS patients to practice Tai Chi exercise as rehabilitation have not been rigorously tested and there is a lack of consensus on its benefits. This study aims to develop an innovative Tai Chi Cardiac Rehabilitation Program (TCCRP) for CCS patients and to assess the efficacy, safety and acceptability of the programme. METHODS AND ANALYSIS: We propose to conduct a multicentre randomised controlled clinical trial comprising of 150 participants with CCS. The patients will be randomly assigned in a 1:1 ratio into two groups. The intervention group will participate in a supervised TCCRP held three times a week for 3 months. The control group will receive supervised conventional exercise rehabilitation held three times a week for 3 months. The primary and secondary outcomes will be assessed at baseline, 1 month, 3 months after intervention and after an additional 3-month follow-up period. Primary outcome measures will include a score of 36-Item Short Form Survey and Chinese Perceived Stress Scale. The secondary outcome measures will include body composition, cardiopulmonary exercise test, respiratory muscle function, locomotor skills, echocardiogram, New York Heart Association classification, heart rate recovery time and laboratory examination. Other measures also include Seattle Angina Scale, Pittsburgh Sleep Quality Index, Patient Health Questionnaire-9, Generalized Anxiety Disorder-7 and Berg Balance Scale. All adverse events will be recorded and analysed. ETHICS AND DISSEMINATION: This study conforms to the principles of the Declaration of Helsinki and relevant ethical guidelines. Ethical approval has been obtained from the Ethics Committee of Chinese People's Libration Army General Hospital (approval number: S2019-060-02). Findings from this study will be published and presented at conferences for widespread dissemination of the results. TRIAL REGISTRATION NUMBER: NCT03936504.

Mindfulness-Based Interventions for Symptom Management in Children and Adolescents With Cancer: A Systematic Review.

Psychological interventions have shown benefit in reducing symptoms in children and adolescents with cancer. More recently, mindfulness-based interventions (MBIs) have been shown to be a promising approach to symptom intervention in adolescents with chronic illnesses. In this systematic review, we aimed to describe MBIs or focused-breathing interventions that have been used to treat symptoms in children receiving cancer therapy. A systematic review was conducted using MEDLINE/PubMed, EMBASE, CINAHL, and PsycINFO from inception to September 2019. We identified relevant articles in which MBIs or focused-breathing interventions were the primary interventions delivered to improve symptoms in children or adolescents with cancer. Six studies met the inclusion criteria. MBIs included controlled breathing and belly breathing. Intervention effects were found to be beneficial with regard to symptoms that included procedural pain, distress, and quality of life. The interventions were generally well accepted and beneficial. All studies suffered limitations because of methodological flaws, including the lack of randomization, and small sample sizes. Despite the small numbers of studies and participants, MBIs delivered to children with cancer may have beneficial effects on certain symptoms. Implications for future research include interventions tailored to the specific symptom burden. Studies must aim to increase sample sizes as well as to include individuals at high risk for severe symptoms.

A Pilot Study of Mindfulness-Based Cognitive Therapy to Improve Well-Being for Health Professionals Providing Chronic Disease Care.

OBJECTIVE: To assess the efficacy of mindfulness-based cognitive therapy delivered onsite during work hours in reducing stress and improving well-being in an interdisciplinary chronic care health care team. STUDY DESIGN: A longitudinal, mixed methods, observational pilot study using a survey created from validated assessment tools to measure effectiveness of training. Surveys were completed before training, and 1 and 15 months after training. Twenty-four professionals in the cystic fibrosis Centers at Cincinnati Children's Hospital and the University of Cincinnati participated in 6 mindfulness-based cognitive therapy training sessions. Sessions incorporated mindfulness, cognitive therapy, and experiential exercises for processing feelings related to stress and burnout. RESULTS: The presurvey and 1-month postsurvey responses revealed statistically significant improvements for empathy, perceived stress, depersonalization, anxiety, perspective taking, resilience, and negative affect. Sustained effects were seen at 15 months for empathy, perspective taking, and depressive symptoms. The 1-month post-training surveys reported a quarter of respondents (25%) practiced skills at least 5 times in between sessions; at 15 months, 35% reported practicing at the same frequency. Participants reported using mindfulness skills for personal stressful events (74%), work-related general stress (65%), patient-related stress (30%), sleep or general relaxation (22%), and wellness (13%). CONCLUSIONS: Group mindfulness-based cognitive therapy training was feasible and effective in decreasing stress for interdisciplinary cystic fibrosis care team members who elected to participate. Further investigation is needed to determine optimal dose of training, durability of perceived benefits, and generalizability to health care professionals working with other chronic disorders.

Effectiveness of the integrated care model Salut+Social in patients with chronic conditions: A mixed methods study protocol.

INTRODUCTION: Integrated care models aim to provide solutions to fragmentation of care by improving coordination. This study will evaluate the effectiveness of a new integrated care model (Salut + Social), which will promote the coordination and communication between social and healthcare services in southern Catalonia (Spain) to improve quality of life, adherence to treatment and access to medical services for patients with chronic conditions, and also to reduce caregiver burden. Additionally, we will evaluate the experience of caregivers, health professionals and social workers with the new model implemented. METHODS AND ANALYSIS: A clinical trial using mixed methodology will be carried out. The intervention consists of improving the coordination between the social and healthcare sectors during a 6-month period, by means of information and communication technology (ICT) tools that operate as an interface for the integrated care model. The study subjects are primary care patients with chronic health and social conditions that can benefit from a collaborative and coordinated approach. A sample size of 141 patients was estimated. Questionnaires that assess quality of life, treatment adherence, medical service and caregiver burden will be used at baseline and at 6, 9, and 12 months after the beginning of the study. The principal variable is quality of life. For statistical analysis, comparisons of means and proportions at different time points will be performed. A discussion group and semi-structured interviews will be conducted with the aim of improving the care model taking into account the opinions of professionals and caregivers. A thematic content analysis will be carried out. ETHICS AND DISSEMINATION: This study protocol has been approved by the Clinical Research Ethics Committee of the Fundació Institut Universitari per a la Recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (code P17/100). Articles will be published in international, peer-reviewed scientific journals. TRIAL REGISTRATION: Clinical-Trials.gov: NCT04164160.