Managing a patient with acute colonic diverticulitis.

ABSTRACT: Acute diverticulitis is a common condition in Western society with the potential for substantial patient morbidity. Depending on the severity, the patient's clinical presentation and treatment options vary considerably, leaving uncertainty about optimal management. Traditionally, surgery was recommended to prevent complications, persistent symptoms, and recurrent episodes. Improvements in the understanding of the disease's natural history, diagnostic imaging, and long-term outcomes have prompted changes to diagnosis and treatment guidelines.

Revisiting pharmacy-based naloxone with pharmacists and naloxone consumers in 2 states: 2017 perspectives and evolving approaches.

OBJECTIVES: Pharmacies provide accessible sources of naloxone to caregivers, patients taking opioids, and individuals using drugs. While laws permit expanded pharmacy naloxone access, prior work identified barriers like concerns about stigma of addiction and time constraints that inhibit scale-up. We sought to examine similarities and differences in experiences obtaining naloxone at the pharmacy over a 1-year period in 2 states, and to explore reactions from people with opioid use disorder, patients taking opioids for chronic pain, caregivers of opioid users, and pharmacists to communication tools and patient outreach materials designed to improve naloxone uptake. DESIGN: Eight focus groups (FGs) held December 2016 to April 2017 in Massachusetts and Rhode Island. SETTING AND PARTICIPANTS: Participants were recruited from pharmacies, health clinics, and community organizations; pharmacists were recruited from professional organizations and pharmacy colleges. OUTCOME MEASURES: The FGs were led by trained qualitative researchers using a topic guide and prototypes designed for input. Five analysts applied a coding scheme to transcripts. Thematic analysis involved synthesis of coded data and connections between themes, with comparisons across groups and to first-year findings. RESULTS: A total of 56 individuals participated: patients taking opioids for chronic pain (n = 13), people with opioid use disorders (n = 15), caregivers (n = 13), and pharmacists (n = 16). Fear of future consequences and stigma in the pharmacy was a prominent theme from the previous year. Four new themes emerged: experience providing pharmacy naloxone, clinician-pharmacist-partnered approaches, naloxone coprescription, and fentanyl as motivator for pharmacy naloxone. Prototypes for prompting consumers about naloxone availability, materials facilitating naloxone conversations, and posters designed to address stigma were well received. CONCLUSIONS: Experiences dispensing naloxone are quickly evolving, and a greater diversity of patients are obtaining pharmacy naloxone. Persistent stigma-related concerns underscore the need for tools to help pharmacists offer naloxone, facilitate patient requests, and provide reassurance when getting naloxone.

Pharmacist attitudes toward pharmacy-based naloxone: A cross-sectional survey study.

OBJECTIVE: The aim of this study was to evaluate pharmacist attitudes regarding recommending pharmacy-based naloxone (PBN). The influence of gender, practice setting, the number of years of practice, state, and PBN involvement were explored. Barriers to, and facilitators of, provision of PBN were also assessed. DESIGN: A 71-question survey was designed to assess experience with, and attitudes toward, PBN. We employed a cross-sectional study design and utilized the online survey site Qualtrics (Qualtrics International Inc, Provo, UT). SETTING AND PARTICIPANTS: The survey was e-mailed to approximately 2900 licensed pharmacists from all practice settings in Massachusetts (approximately 1400) and Rhode Island (approximately 1500) and was open from April 5, 2016, until July 13, 2016. OUTCOME MEASURES: Attitudes toward opioid overdose prevention (12 questions) were used to develop the Opioid Overdose Prevention Attitude (OOPA) scale which consisted of 3 subscales: Opioid Overdose Prevention Attitude, Public Health Attitude, and Naloxone Dispensing Attitude. RESULTS: Of the approximately 2900 pharmacists who received the survey, 402 responded (13%), and 245 (137 from Massachusetts and 108 from Rhode Island) were included in the analyses. The majority (79%) identified as White or Caucasian, and 127 (51.8%) stated they had ever dispensed naloxone. Of those, 85 (67%) had done so in the past 30 days. We examined differences in the OOPA subscales by pharmacists' characteristics and pharmacy practice settings. Working in a pharmacy that had a standing order or collaborative practice agreement allowing pharmacists to dispense naloxone without a physician's prescription, or in a pharmacy that stocked naloxone resulted in more positive attitudes toward opioid overdose prevention and public health prevention. CONCLUSION: Respondents who practiced in a pharmacy with a standing order or collaborative practice agreement were more likely to have dispensed naloxone. Both stocking naloxone and ever having dispensed naloxone were associated with higher OOPA scores. More research is needed to better understand how pharmacist attitudes influence the distribution of naloxone.

Beliefs Associated with Pharmacy-Based Naloxone: a Qualitative Study of Pharmacy-Based Naloxone Purchasers and People at Risk for Opioid Overdose.

Drug overdose is the leading cause of unintentional death in the USA and the majority of deaths involve an opioid. Pharmacies are playing an increasingly important role in getting naloxone-the antidote to an opioid overdose-into the community. The aim of the current study was to understand, from the perspective of those who had obtained naloxone at the pharmacy, whose drug using status and pain patient status was not known until the interviews were conducted, as well as those who had not obtained naloxone at the pharmacy but were at risk for overdose, factors that impact the likelihood of obtaining pharmacy-based naloxone (PBN). Fifty-two participants from two New England states were interviewed between August 2016 and April 2017. We used a phenomenological approach to investigate participants' beliefs about pharmacy-based naloxone. The social contextual model was chosen to structure the collection and analysis of the qualitative data as it takes into account individual, interpersonal, organizational (pharmacy), community, and societal influences on a specific health behavior. Of the 52 people interviewed, 24 participants had obtained naloxone from the pharmacy in the past year, of which 4% (n = 1) self-disclosed during the interview current illicit drug use and 29% (n = 7) mentioned using prescribed opioid pain medication. Of the 28 people who had not obtained naloxone from the pharmacy, 46% (n = 13) had obtained an over the counter syringe from a pharmacy in the past month and had used an opioid in the past month, and 54% (n = 15) had used a prescribed opioid pain medication in the past month but did not report a syringe purchase. Several main themes emerged from the interview data. Individual-level themes were as follows: helplessness and fear, naloxone as empowerment to help, and past experiences at the pharmacy. Interpersonal-level themes were as follows: concern for family and friends, and sources of harm reduction information. Themes associated with pharmacy-level influence were as follows: perceived stigma from pharmacists, confusion at the pharmacy counter, and receptivity to pharmacists' offer of naloxone; community-level themes were as follows: community caretaking and need for education and training. Finally, themes at the societal-level of influence were as follows: generational crisis, and frustration at lack of response to opioid crisis. Overall our findings reveal factors at multiple levels which may play a role in likelihood of obtaining naloxone at the pharmacy. These factors can be used to inform interventions seeking to increase provision of pharmacy-based naloxone.

Feasibility and Acceptance Testing of a Mobile Application Providing Psychosocial Support for Parents of Children and Adolescents With Chronic Pain: Results of a Nonrandomized Trial.

Objective To conduct a single-arm pilot study assessing the feasibility and acceptability of a 30-day parent-focused mindfulness and psychosocial support mobile app intervention for parents of children with chronic pain. Methods Thirty parents completed the intervention, which included a mindfulness curriculum, peer support videos, and written psychoeducational content. Twelve healthcare providers also assessed the app and provided feedback. Feasibility was assessed by server-side documented usage on ≥50% of the days in the intervention period and completion of ≥70% of the mindfulness content. Parent and provider acceptance were assessed by ≥70% of participants rating each acceptance test question as ≥5 on a 7-point Likert scale. Parents completed measures of solicitousness, stress, mindful parenting, and resilience prior to and following the intervention. Results Feasibility results were mixed: parents completed mindfulness content on an average of 11.2 days during the intervention period, slightly under the pre-established criterion. However, parents completed an average of 72.1% of the content, which met feasibility criterion. Acceptance criteria were met for the majority of parent acceptance test questions and all of the provider acceptance test questions. Exploratory analyses of the psychosocial measures revealed significant decreases in parental solicitous behavior and perceived stress, and a significant increase in mindful parenting. Conclusions The current study extends the emerging body of research on mindfulness-based interventions for parents of children with chronic illness and suggests that it may be acceptable to deliver this content through a mobile device. Future research is needed to assess the intervention's efficacy compared to standard of care.

Pediatric Irritable Bowel Syndrome: Perspectives on Pain and Adolescent Social Functioning.

OBJECTIVE: The goal of the study was to describe the experiences of adolescents with irritable bowel syndrome (IBS) from the perspective of adolescents, their parents, and health care providers who treat adolescents who have IBS. DESIGN: The study consisted of semistructured interviews. SETTING: Participants were recruited from multidisciplinary pain clinics. SUBJECTS: Thirty-six people participated in the study: 12 adolescents, 12 parents, and 12 health care providers. RESULTS: Two main themes associated with the impact of IBS on adolescents' social functioning emerged from the qualitative interview data: 1) disconnection from peers and 2) strain on family relationships, with subthemes reflecting the perspectives of adolescents, parents, and health care providers. CONCLUSIONS: Participants in our study described that adolescents with IBS encounter significant peer- and family-related social stress. Helpful interventions may be those that focus on social support from other adolescents with similar conditions, as well as family-based therapeutic interventions.

Ethnic and racial diversity in eating disorder prevention trials.

Recruiting diverse samples for prevention trials is challenging, but essential. This paper provides baseline data for four racial/ethnic groups from a randomized controlled trial of a mobile-based prevention intervention and systematically reviews recruitment trends in diversity across technology-based prevention studies. Female emerging adults completed measures of appearance esteem, body image flexibility, appearance comparison, and self-compassion. White participants reported lower body esteem and body image flexibility, and higher appearance comparison compared to Black and Asian participants. Latina participants evidenced higher appearance comparison compared to Black participants. The literature review revealed that while rates of diversity in previous trials vary, the majority of the participants were White. Efforts are needed to increase diversity in prevention trials.

BodiMojo: Efficacy of a Mobile-Based Intervention in Improving Body Image and Self-Compassion among Adolescents.

Mobile interventions promoting positive body image are lacking. This study presents a randomized controlled evaluation of BodiMojo, a mobile application (app) intervention grounded in self-compassion to promote positive body image. A sample of 274 adolescents, mean (SD) age = 18.36 (1.34) years, 74% female, were allocated to a control group or used BodiMojo for 6 weeks. Appearance esteem, body image flexibility, appearance comparison, mood, and self-compassion were assessed at baseline, 6, and 12 weeks. Significant time by group interactions emerged for appearance esteem and self-compassion, with appearance esteem and self-compassion increasing in the intervention relative to the control group. These findings provide preliminary support for BodiMojo, a cost-effective mobile app for positive body image.

Beliefs About a Complementary and Alternative Therapy-Based Chronic Pain Management Program for a Medicaid Population.

OBJECTIVE: Rhode Island Medicaid offers high emergency department utilizers the opportunity to take part in the Chronic Pain Program, an integrated treatment approach that includes free complementary therapies (massage, chiropractic, and acupuncture). The aim of the current analysis was to understand beliefs about the Rhode Island Chronic Pain Program from the perspective of the patient receiving services, the provider delivering services, and the administrator implementing the program. DESIGN: A qualitative interview-based study. SUBJECTS: Patients (N = 24), providers (N = 13), and administrators (N = 11) who were already involved, or were eligible to be involved, in the Chronic Pain Program. METHODS: Semistructured interviews were conducted to elicit information about experiences with the program. Transcriptions of audio recordings were analyzed according to principles of deductive thematic analysis. RESULTS: Patient interviews revealed five themes: 1) relationship between stress and pain, 2) trusting patient-provider relationships, 3) increased quality of life, 4) temporary pain relief, and 5) anxiety and discomfort associated with acupuncture. Provider interviews revealed three themes: 1) a way to reach the disenfranchised, 2) not enough visits with patients, and 3) opportunity to build relationships with patients. Administrator interviews revealed two themes: 1) a means to offer a range of support services to complicated patients and 2) unanswered questions over whether the program adequately serves patients with the greatest needs. CONCLUSIONS: Key stakeholders in this new initiative agree that the Rhode Island Chronic Pain Program shows promise and that the holistic approach may be a good match for this hard-to-reach population.

Brief report: Feasibility of a mindfulness and self-compassion based mobile intervention for adolescents.

The aim of the study was to test the feasibility of a mindfulness and self-compassion based program for adolescents, to be delivered though mobile phones. Twenty racially and ethnically diverse US adolescents enrolled in a study to use the app for 30 days, after which they provided satisfaction data and participated in focus groups to describe their experiences and offer suggestions for improving the app. Usage data were also captured. Results indicated that participants used the app on the majority of days over the intervention period, reported finding it helpful for managing stress, and provided suggestions for substantive areas for improvement. These findings suggest that a mobile app may be a feasible way to disseminate a mindfulness and selfcompassion based program widely among adolescents.

Using a Lean Six Sigma Approach to Yield Sustained Pressure Ulcer Prevention for Complex Critical Care Patients.

BACKGROUND: Under value-based purchasing, Medicare withholds reimbursements for hospital-acquired pressure ulcer occurrence and rewards hospitals that meet performance standards. With little evidence of a validated prevention process, nurse managers are challenged to find evidence-based interventions. OBJECTIVE: The aim of this study was to reduce the unit-acquired pressure ulcer (UAPU) rate on targeted intensive care and step-down units by 15% using Lean Six Sigma (LSS) methodology. METHODS: An interdisciplinary team designed a pilot program using LSS methodology to test 4 interventions: standardized documentation, equipment monitoring, patient out-of-bed-to-chair monitoring, and a rounding checklist. RESULTS: During the pilot, the UAPU rate decreased from 4.4% to 2.8%, exceeding the goal of a 15% reduction. The rate remained below the goal through the program control phase at 2.9%, demonstrating a statistically significant reduction after intervention implementation. CONCLUSIONS: The program significantly reduced UAPU rates in high-risk populations. LSS methodologies are a sustainable approach to reducing hospital-acquired conditions that should be broadly tested and implemented.

Boabom: A Feasible and Acceptable Approach to Helping College Students Manage Stress.

Objective: College students in the United States report high rates of psychological health concerns. Psychological and physical complementary health approaches have been found to be protective for college students. The aims of this study were to assess the feasibility and acceptability of Boabom, a martial art, with college students and to explore any changes in psychosocial outcomes. Participants: Twenty-six college students (25 females; mean age 21.73 years) participated in an 8-week Boabom intervention. Methods: Feasibility measures were attendance and retention of participants; acceptability was based on participants' cognitive and emotional responses to Boabom and was determined through analysis of focus group data. Psychosocial outcomes were assessed through analyses of pre- and postintervention measures of mindfulness, perceived stress, anxiety, depression, resilience, perceived health, and life satisfaction. Results: The Boabom intervention was feasible as 23 of 26 participants attended at least six of eight classes, and 22 participants attended the last class. Students found the intervention acceptable, with three themes emerging from the focus group data to describe the participants' experience with Boabom: (1) disengaging from constant, daily stress and breathing and moving as a group leads to sense of calm, (2) empowerment through incremental mastery of skills, and (3) recognition of the value of health benefits to be gained. Participants reported positive changes in mindfulness, perceived stress, anxiety, depression, resilience, perceived health, and life satisfaction from pre- to postintervention. Conclusions: Boabom may be a feasible and acceptable offering for college students; still, further piloting with other college student populations is recommended.

The acceptability of Songs of Love for youth living with chronic pain.

OBJECTIVES: Music is helpful to young people in healthcare contexts, but less is known about the acceptability of music-based interventions for youth living at home with chronic pain who may be struggling to attend school and participate in social activities. The Songs of Love (SOL) foundation is a national nonprofit organization that creates free, personalized, original songs for youth facing health challenges. The aims of this study were (1) to assess acceptability of SOL from the perspective of youth with chronic pain receiving a song and singer-songwriters who created the songs, and (2) to explore the role of music more generally in the lives of young people living with pain. METHODS: Twenty-three people participated. Fifteen youth (mean age 16.8) were interviewed and received a song, and six singer-songwriters were interviewed about creating the songs. (Two additional people participated in pilot interviews.) Acceptability was assessed by (1) proportion of youth who participated in a second interview about their song and (2) results of reflexive thematic analysis (RTA) to determine acceptability. Themes addressing the role of music in the lives of youth with pain were also explored using RTA. RESULTS: The program was acceptable as 12 of 15 youth (80 %) participated in second interviews and themes met the definition of acceptability. Three themes addressing the role of music in the lives of youth living with pain were identified. CONCLUSIONS: This is the first report of the acceptability and experience of SOL and contributes to research on the benefits of music for pain management.

A qualitative analysis of adolescent, caregiver, and clinician perceptions of the impact of migraines on adolescents' social functioning.

Migraines dramatically affect adolescents' quality of life. One area of particular importance is the impact of migraines on adolescents' social functioning. To understand the impact of migraines on adolescents' social functioning from multiple informants, we performed semistructured interviews with adolescents who have migraines, their caregivers, and clinicians who treat adolescents who have migraines. Three major themes related to social functioning were identified from the adolescent interviews: The need to be alone; lack of support from siblings; and the feeling of not being understood by others. The caregiver interviews yielded three main themes related to family functioning: that plans can change quickly; that family life revolves around helping the child with the migraine; and parents' feelings of inadequacy in helping their child. There were two main themes derived from the clinician interviews related to perception of family functioning: the importance of parental involvement; and the role of adolescents' school and social lives in migraine prevention. There are a number of unmet needs among adolescents with recurrent migraine and their families. Interviews with adolescents, caregivers, and clinicians suggest a number of areas for intervention.

Psychological flexibility as a predictor of mental health outcomes in parents of pre-school children during the COVID-19 pandemic: A two-year longitudinal study.

In light of the adverse mental health impacts of the COVID-19 pandemic for parents of preschool-aged children, it is important to identify modifiable protective factors that can inform interventions for parents who continue to struggle. The present study examined prospective and concurrent associations of parental psychological flexibility (acceptance, defusion, and committed action) with measures of parental stress and depression symptoms in an international sample of parents of preschoolers assessed at three time points over the first two years of the COVID-19 pandemic: The start of the pandemic (T1) as well as the end of the first (T2) and second (T3) year of the pandemic. Consistent with hypotheses, the three measures of parent psychological flexibility (assessed at T2) prospectively predicted parenting stress levels one year later (T3) (p < .05). Defusion and Committed Action also prospectively predicted lower levels of depression symptoms one year later [p < .05]. Comparable concurrent analyses of data of parents who provided data at T1 and T2 (N = 79) are also presented with acceptance and defusion negatively associated with parental stress (p < .001) and defusion negatively associated with depression (p < .05). This study contributes longitudinal evidence for the value of psychological flexibility for parents and suggests that Acceptance and Commitment Therapy interventions may help to support parental mental health during sustained periods of stress such as the COVID-19 pandemic.

Feasibility and acceptability of implementing the Making Friends with Yourself intervention on a college campus.

Objective: To assess the feasibility and acceptability of Making Friends with Yourself (MFY): A Mindful Self-Compassion Program for Teens and Young Adults with a sample of college students. A secondary objective was to explore changes in psychosocial outcomes. Participants: Twenty-five students (23 females; mean age 20.35 years) enrolled in the 8-week intervention. Methods: Feasibility was measured by attendance and retention of participants; acceptability was determined through analysis of focus group data. Psychosocial outcomes were assessed through analyses of pre- and post-intervention measures. Results: The intervention was feasible as 20 students attended at least seven of eight classes, and 21 completed the program. Students found the intervention acceptable and reported significant increases in mindfulness and self-compassion and decreased perceived stress from pre- to post-intervention. However, academic stress increased. Conclusions: MFY may be a feasible and acceptable program to offer to college students. Further piloting in college student populations is recommended.

Cutting the cord? Parenting emerging adults with chronic pain.

The role of parent factors, such as distress and protective behaviors, on pain and functional outcomes of emerging adults living with chronic pain has been largely unexplored. The effects of helicopter parenting and developmental changes occurring during this transition period between adolescence and adulthood (commonly defined as the ages between 18 and 30 years) may exacerbate the pain experience and have the potential to influence chronic pain management. Clinical practice, with an additional focus on supporting the parent(s), may aid in meeting the needs of this population. In this paper, we review the available literature on (a) the socio-cultural shift in parenting over the past decade with a focus on helicopter parenting; (b) the impact of this parenting style on the pain experience and outcomes of emerging adults living with chronic pain; (c) provide recommendations for chronic pain management with a focus on the parent-emerging adult dyad; and (d) conclude with future research recommendations. This narrative review is the first to consider the impacts and outcomes of helicopter parenting on emerging adults with chronic pain.

The acceptability of photovoice as a method for incorporating resilience-enhancing factors into pediatric pain research.

Recurrent or chronic pain affects 11-38% of children and adolescents. Pediatric pain research typically focuses on risk factors, such as anxiety and parent functional disability, but resilience-building, protective factors also play an important role in the pain experience. New methods to incorporate resilience-enhancing factors into pain research are needed. Photovoice is a highly participatory research method, where participants take photos to address a common question, caption their photos, and discuss the meaning of the photos in a group. The main objective of this study was to determine whether photovoice is an acceptable method to young people living with chronic pain for identifying and sharing sources of joy. Another objective was to explore sources of joy. Sixteen adolescents and young adults participated, which involved meeting in a group to discuss the goal of the study, taking photographs of self-identified sources of joy over a two-week period, and meeting as a group again to discuss the photographs and participate in a focus group about the experience. Results suggest that photovoice is an acceptable method, as all participants took photographs and attended both meetings, and three themes from the focus group data suggested the participants considered photovoice to be appropriate: 1.) Relief associated with meeting peers, 2.) Potential to benefit young people living with pain, and 3.) Potential to raise awareness. Three themes emerged from the discussion of the photographs to describe sources of joy: 1.) Gratitude for everyday pleasures and accomplishments, 2.) Support from pets, and 3.) Journey of acceptance. Results add to the strengths-based literature on pediatric pain by identifying an acceptable method that could be further explored for use as an intervention to enhance protective factors such as positive affect, gratitude, and social support and to compare the experiences of different populations of youth living with pain.

The Role of Social Media in Providing Support from Friends for Adolescent and Young Adult (AYA) Patients and Survivors of Sarcoma: Perspectives of AYA, Parents, and Providers.

Purpose: The aims of the current study were to better understand, from the perspective of adolescents and young adults (AYAs) with sarcoma, parents, and providers, the friendship support needs of AYAs with bone and soft tissue sarcoma and the role of social media in facilitating social support for AYAs with sarcoma. Methods: Semistructured interviews were conducted with 21 participants. AYA (n = 10) ranged in age from 14 to 23 years (mean 19.3, standard deviation 3.4 years; 50% female). All AYAs reported a current or past diagnosis of sarcoma, except for one patient who had another cancer diagnosis but was receiving treatment through the sarcoma clinic. Five parents of the adolescent participants were interviewed, as well as six health care providers. Data analysis was conducted using theory-driven immersion/crystallization, incorporating the Resilience in Illness Model as a framework to guide interpretation of the data. Results: Four main themes associated with social support from friends and social media were identified: (1) Social media provides a way to feel normal and connected to friends; (2) Social media accentuates the frustration of being left behind; (3) Social media facilitates the need to be understood by peers who have experienced sarcoma, and (4) Social media can lead to despair, and also provide hope for the future. Conclusions: Connecting with peers through social media can play an important role in providing support for AYAs with sarcoma, but it may also amplify feelings of frustration and anxiety. Future work is needed to determine intervention components that can maximize the benefits of social media for social support of AYAs with sarcoma. Clinical Trial Registration number: NCT03130751.

Dystrophin involvement in peripheral circadian SRF signalling.

Absence of dystrophin, an essential sarcolemmal protein required for muscle contraction, leads to the devastating muscle-wasting disease Duchenne muscular dystrophy. Dystrophin has an actin-binding domain, which binds and stabilises filamentous-(F)-actin, an integral component of the RhoA-actin-serum-response-factor-(SRF) pathway. This pathway plays a crucial role in circadian signalling, whereby the suprachiasmatic nucleus (SCN) transmits cues to peripheral tissues, activating SRF and transcription of clock-target genes. Given dystrophin binds F-actin and disturbed SRF-signalling disrupts clock entrainment, we hypothesised dystrophin loss causes circadian deficits. We show for the first time alterations in the RhoA-actin-SRF-signalling pathway, in dystrophin-deficient myotubes and dystrophic mouse models. Specifically, we demonstrate reduced F/G-actin ratios, altered MRTF levels, dysregulated core-clock and downstream target-genes, and down-regulation of key circadian genes in muscle biopsies from Duchenne patients harbouring an array of mutations. Furthermore, we show dystrophin is absent in the SCN of dystrophic mice which display disrupted circadian locomotor behaviour, indicative of disrupted SCN signalling. Therefore, dystrophin is an important component of the RhoA-actin-SRF pathway and novel mediator of circadian signalling in peripheral tissues, loss of which leads to circadian dysregulation.