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The administration of intermittent parathyroid hormone (iPTH) is anabolic to the skeleton. Recent studies with cultured osteoblasts have revealed that the expression of PHOSPHO1, a bone-specific phosphatase essential for the initiation of mineralisation, is regulated by PTH. Therefore, this study sought to determine whether the bone anabolic response to iPTH involves modulation of expression of Phospho1 and of other enzymes critical for bone matrix mineralisation. To mimic iPTH treatment, primary murine osteoblasts were challenged with 50 nM PTH for 6 h in every 48 h period for 8 days (4 cycles), 14 days (7 cycles) and 20 days (10 cycles) in total. The expression of both Phospho1 and Smpd3 was almost completely inhibited after 4 cycles, whereas 10 cycles were required to stimulate a similar response in Alpl expression. To explore the in vivo role of PHOSPHO1 in PTH-mediated osteogenesis, the effects of 14- and 28-day iPTH (80 µg/kg/day) administration was assessed in male wild-type (WT) and Phospho1

BACKGROUND: Variation in Lamin A/C results in a spectrum of clinical disease, including arrhythmias and cardiomyopathy. Benign variation is rare, and classification of LMNA missense variants via in silico prediction tools results in a high rate of variants of uncertain significance (VUS). OBJECTIVE: Use a machine learning (ML) approach for in silico prediction of LMNA pathogenic variation. METHODS: Genetic sequencing was performed on family members with conduction system disease and patient cell lines examined for LMNA expression. In silico predictions of conservation and pathogenicity of published LMNA variants were visualized with Uniform Manifold Approximation and Projection (UMAP). K-means clustering was used to identify variant groups with similarly projected scores, allowing the generation of statistically supported risk categories. RESULTS: We discovered a novel LMNA variant (c.408C>A:p.Asp136Glu) segregating with conduction system disease in a multi-generation pedigree, which was reported as a VUS by a commercial testing company. Additional familial analysis and in vitro testing found it to be pathogenic, which prompted the development of a ML algorithm that used in silico predictions of pathogenicity for known LMNA missense variants. This identified three clusters of variation, each with a significantly different incidence of known pathogenic variants (38.8%, 15.0%, and 6.1%). 339/415 (81.7%) head/rod domain variants, including p.Asp136Glu, were in clusters with highest proportions of pathogenic variants. CONCLUSION: An unsupervised ML method successfully identified clusters enriched for pathogenic LMNA variants including a novel variant associated with conduction system disease. Our ML method may assist in identifying high risk VUS when familial testing is unavailable.

The Matsigenka people living traditional lifestyles in remote areas of the Amazon rely on a fish-based diet that exposes them to methylmercury (MeHg) at levels that have been associated with decreased IQ scores. In this study, the association between Hg levels and working memory was explored using the framework of the Multicomponent Model. Working memory tasks were modified to fit the culture and language of the Matsigenka when needed and included measures for verbal storage (Word Span) visuospatial storage (Corsi Block Task) and a measure of executive functions, the Self-Ordered Pointing Task (SOPT). An innovation of the Trail Making Tests A & B (TMT A & B) was pilot tested as another potential measure of executive functions. The mean hair Hg levels of 30 participants, ages 12 to 55 years, from three different communities (Maizal, Cacaotal and Yomibato) was 7.0 ppm (sd = 2.40), well above the World Health Organization (WHO) limit for hair of 2.0 ppm and ranged from 1.8 to 14.2 ppm, with 98% of a broader sample of 152 individuals exceeding the WHO limit. Hair Hg levels showed significant associations with cognitive performance, but the degree varied in magnitude according to the type of task. Hg levels were negatively associated with executive functioning performance (SOPT errors), while Hg levels and years of education predicted visuospatial performance (Corsi Block accuracy). Education was the only predictor of Word Span accuracy. The results show that Hg exposure is negatively associated with working memory performance when there is an increased reliance on executive functioning. Based on our findings and the review of the experimental research, we suggest that the SOPT and the Corsi Block have the potential to be alternatives to general intelligence tests when studying remote groups with extensive cultural differences.

Aim/Purpose: The purpose of this paper is to detail the experiential learning processes of an 11-week doctoral-level intermediate mixed methods research (MMR) course in which student-researchers conceptualized and implemented an MMR study to apply theoretical and methodological learning in a practical manner. Our aim is to emphasize the value of an applied MMR course for improved student learning and curriculum planning for faculty by highlighting meaningful insights on study design, data integration, team collaboration, and the challenges and opportunities involved in project execution within a time-limited academic course. Background: MMR courses are increasingly being integrated into graduate programs, yet few offer intermediate or advanced courses that go beyond introductory topics and engage students in applied learning. Furthermore, most articles on MMR courses are written from the instructor perspective and not from the student perspective. Methodology: This article is organized by each week of the course curriculum, and the output of the research project, couched within reflections of the applied process, is presented. While this paper is grounded in an experiential reflection of learning, the research project itself is referred to frequently to help elucidate and capture this learning in a systematic way. The applied study employed an explanatory sequential mixed methods design to examine career satisfaction and career preference changes over time in doctoral candidates and graduates. Contribution: This paper contributes to higher education by providing a student-led exemplar of applied learning in MMR pedagogy for doctoral students irrespective of discipline and research topic. It provides a sample research project, executed start to finish with a guiding blueprint that can be adapted by faculty and students in various academic departments, within a quarter or semester long course. Findings: Ultimately, this course led to increased confidence and preparation to conduct interdisciplinary mixed methods research. Unique to mixed methods research, the areas in which we witnessed the most growth included developing mixed methods research questions, choosing a design based on these questions, and engaging in data integration. Recommendations for Practitioners: We provide the following recommendations to instructors interested in developing intermediate- or advanced-level MMR courses: a) obtain input from students on what they are most interested in learning during course conceptualization or early on in implementation; b) consider that a great deal of time outside of the classroom may need to be dedicated to the class project, which may impact the feasibility and successful execution of an experiential course; and c) sufficient class time is dedicated to data integration from quantitative and qualitative inputs. Recommendation for Researchers: Researchers interested in further examining learning and proficiency garnered from MMR and other research courses may benefit from including students as co-researchers. In addition, engaging in systematic qualitative research on student and professor experiences in learning and teaching MMR courses could highlight further areas for course refinement and topics for future research. Impact on Society: Given the increasing prevalence of MMR being included in research funding announcements as a preferred methodology, it is imperative to rigorously train researchers in mixed methods research at varying levels of advancement (i.e., introductory, intermediate, and advanced). Future Research: Our small explanatory sequential mixed methods study began as a class project, yet highlighted areas that could be studied further for doctoral candidates and graduates in clinically oriented fields, such as learning what types or qualities of training and mentorship may yield more career preparedness and satisfaction.

INTRODUCTION: Treatment manuals play an essential role in clinical trials that aim to determine the efficacy of an intervention. Yet, the idea of needing to adhere to a treatment manual may seem counterintuitive to many music therapy clinicians. The purpose of this article is to offer clinician, supervisor, and researcher perspectives on the process of developing and executing a manualized music therapy treatment protocol in a randomized controlled trial. METHOD: After describing the purpose of treatment manuals in clinical trials, we present the experience of developing a treatment manual through clinician and researcher collaborations. The concept of treatment fidelity and quality assurance monitoring within clinical trials is detailed to provide an inside look at an integral aspect of enacting treatment manuals in efficacy research. We then share reflections from a research clinician and supervisor to demonstrate the opportunities and challenges when working within the guidelines of manualized clinical practice. RESULTS: Providing a reflective perspective on implementation of a manualized treatment protocol allows for a more thorough understanding of the clinical and research processes in the conduct of randomized controlled trials. DISCUSSION: Collaboration of researchers, clinicians and supervisors is of critical importance for the successful implementation of treatment manuals in clinical trials.

In this article, music therapy researchers and clinicians share lessons learned through engaging in collaborative research with healthcare providers in community settings. Practical aspects of conducting research in community health settings are discussed, including consulting on-site music therapists, healthcare providers, and administrators in the earliest stages of research planning; integration of research team members with community healthcare providers; and strategies for successful study implementation. We present our experiences of challenges surrounding the aspects of study implementation, such as recruitment, obtaining consent, and collecting outcome data, as well as opportunities that have resulted from our work, such as increased visibility for music therapy services, collaboration on protocol refinement, and continuing music therapy services beyond the study. Throughout the article, we refer to two research studies that illustrate the collaborative process as well as offer practical examples of challenges and problem-solving.

Proton pump inhibitors (PPIs) have been associated with an increased risk of fragility fractures in pharmaco-epidemiological studies. The mechanism is unclear, but it has been speculated that by neutralising gastric acid, they may reduce intestinal calcium absorption, causing secondary hyperparathyroidism and bone loss. Here we investigated that hypothesis that the skeletal effects of PPI might be mediated by inhibitory effects on the bone-specific phosphatase PHOSPHO1. We found that the all PPIs tested inhibited the activity of PHOSPHO1 with IC50 ranging between 0.73 µM for esomeprazole to 19.27 µM for pantoprazole. In contrast, these PPIs did not inhibit TNAP activity. We also found that mineralisation of bone matrix in primary osteoblast cultures was inhibited by several PPIs in a concentration dependent manner. In contrast, the histamine-2 receptor antagonists (H2RA) nizatidine, famotidine, cimetidine and ranitidine had no inhibitory effects on PHOSPHO1 activity. Our experiments show for the first time that PPIs inhibit PHOSPHO1 activity and matrix mineralisation in vitro revealing a potential mechanism by which these widely used drugs are associated with the risk of fractures.

Objective Clinical instructors play a key role in physical therapist professional education but may serve with minimal preparation and without clearly defined expectations for their teaching performance. The objective of this study was to utilize a consensus-building process to establish core competencies of clinical teaching within physical therapist education. Methods A modified Delphi approach was used to identify core competencies of clinical teaching. An expert panel consisted of clinical instructors, site coordinators of clinical education, and directors of clinical education, representing multiple geographic regions in the United States. The panel assessed the relevance of 30 original competencies. Criteria for consensus included 75% of participants perceiving the competency as very or extremely relevant and a median score of 2 (very relevant) on a 5-point Likert scale. Consistent with a Modified Delphi approach, quantitative and qualitative data analysis were completed for each of the 3 rounds. Revised surveys were used in Rounds 2 and 3 based on the results from previous data analysis. Results Twenty-four competencies achieved final consensus. The competencies were categorized within 3 domains: learner-centered educator (n = 8), assessor/evaluator (n = 7), and professional role model (n = 9). Conclusion The 24 competencies and 3 domains provide the foundation for a competency framework for clinical teaching in physical therapy. This framework provides clarity for the expected knowledge, skills, and attitudes of clinical instructors in physical therapist professional education. Impact This is the first study, to our knowledge, to utilize a consensus-building strategy to clearly define competencies of clinical teaching in physical therapist professional education. Like efforts in nursing and medical education, adoption of these competencies could promote consistency in clinical instructor teaching behaviors and contribute to the creation of assessment and professional development mechanisms for clinical instructors, positively impacting the preparation of the next generation of excellent physical therapist clinicians.

Objective The aim of this mini-systematic review was to evaluate the evidence reporting speech, language, and auditory behavioral outcome measures for children with a diagnosis of auditory neuropathy spectrum disorder (ANSD) who received cochlear implants (CIs) prior to 3 years of age. Method A mini-systematic review of the literature supporting evidence-based practices was performed. Two databases were searched utilizing a search strategy derived from the PICO (patient, intervention, comparison, outcome) framework. Peer-reviewed articles published between 2009 and 2019 evaluating children with a diagnosis of ANSD who were implanted prior to 3 years of age with a range of speech, language, and auditory behavioral outcomes were included. Four articles meeting inclusion criteria were critically appraised for reputable research design and risks of bias. Each of the four studies was assigned a level of evidence for effectiveness and quality assessment rating. Results Evidence supports cochlear implantation as an appropriate intervention for children with ANSD. Improvements in outcome performance were observed in all the included studies. Children with ANSD fit with CIs can achieve outcomes similar to children with sensorineural hearing loss and CIs, despite the heterogeneity of ANSD. Conclusion These findings have implications for clinical practice and for future research with current CI technology for facilitating parent education, counseling, and realistic expectations for children with ANSD and CIs.

Introduction: Contemporary theories for adolescent bereavement have challenged the idea that bereavement is experienced through a set of specific stages, tasks, or phases and instead consid...

Much has been learnt about British horticulture in the early years of the seventeenth century in terms of garden design, plant availability and classification. Recently, greater attention has also ...

Music therapy research with youth who are grieving often reports on a combination of interventions, such as lyric analysis, improvisation, and/or songwriting. Unfortunately, the lack of theoretical transparency in how and why these interventions affect targeted outcomes limits interpretation and application of this important research. In this exploratory study, the authors evaluated the impact of an 8-session, theory-driven group songwriting program on protective factors in adolescent bereavement, and also sought to better understand adolescents' experiences of the program. Using a single-group, pretest-posttest convergent mixed methods design, participants were enrolled from three study sites and included 10 adolescents (five girls and five boys), ages 11–17 years, who self-identified as grieving a loss. Outcomes measured included grief, coping, emotional expression, self-esteem, and meaning making. Qualitative data were captured through in-session journaling and semi-structured interviews. There were no statistically significant improvements for grief, self-esteem, coping, and meaning making. Individual score trends suggested improvements in grief. The majority of the participants reported greater inhibition of emotional expression, and this was statistically significant. Thematic findings revealed that the program offered adolescents a sense of togetherness, a way to safely express grief-related emotions and experiences verbally and nonverbally, and opportunities for strengthening music and coping skills. These findings suggest that engaging in collaborative therapeutic songwriting with grieving peers may decrease levels of grief, enhance creative expression, and provide social support. More research is needed on measuring self-esteem, emotional expression, coping, and meaning making outcomes in ways that are meaningful to adolescents.

Proton pump inhibitors (PPIs) have been associated with an increased risk of fragility fractures in pharmaco-epidemiological studies. The mechanism is unclear but it has been speculated that by neutralising gastric acid, they may reduce intestinal calcium absorption, causing secondary hyperparathyroidism and bone loss. Here we investigated that hypothesis that the skeletal effects of PPI might be mediated by inhibitory effects on the bone-specific phosphatase PHOSPHO1. We found that the all PPI tested potential inhibited the activity of PHOSPHO1 with IC50 ranging between 0.73μM for esomeprazole to 19.27μM for pantoprazole. In contrast, these PPIs did not inhibit TNAP activity. We also found that mineralisation of bone matrix in primary osteoblast cultures inhibited by several PPI in a concentration dependent manner. In contrast, the histamine-2 receptor antagonists (H2RA) nizatidine, famotidine, cimetidine and ranitidine had no inhibitory effects on PHOSPHO1 activity. Our experiments shown for the first time that PPI inhibit PHOSPHO1 activity and matrix mineralisation in vitro revealing a potential mechanism by which these widely used drugs are associated with the risk of fractures.

Purpose: There is a potential link between the clinical education phase of a physical therapist’s education and increased incidence of student mental health challenges. The Director of Clinical Education (DCE) has a complex role in supporting students and clinical sites during clinical education experiences (CEEs.) The purposes of this study were to explore DCE’s experiences and perceptions with supporting students with mental health challenges during CEEs. Methods: Two-hundred-twenty DCEs from accredited Doctor of Physical Therapy programs were invited to participate in an electronic survey. Survey questions included demographics, institutional and curricular characteristics, and current perceptions/experiences with student mental health challenges. DCEs (n = 106; 48.2%) responded and were included in the analyses. Analyses included descriptive statistics, simple frequencies, and binary logistic regression. Incident coding processes analyzed responses of open-ended questions. Results: Seventy-four percent of respondents indicated awareness of a student(s) experiencing a mental health concern during a full-time clinical experience in the past 3 years. Regression analyses showed that length of terminal clinical experience, out-of-state placement, cohort size, and availability of online/video counseling were related to prevalence of DCE’s experience. Forty-six percent of DCEs indicated feeling prepared to deal with these issues, while 35% were ‘unsure’. DCEs indicated experience, training, and workload support as contributors to successfully supporting students. Conclusion: Results contribute to the emerging understanding of the prevalence of student mental health challenges in physical therapist education from the DCE’s perspective. Our findings suggest that institutional and curricular characteristics are potential contributors to the prevalence of this issue. We recommend training and institutional support for the DCE in these situations.

Adults with Down syndrome (DS) represent a unique population who are in need of clinical guidelines to address their medical care. The United States Preventive Service Task Force (USPSTF) has developed criteria for prioritizing conditions of public health importance with the potential for providing screening recommendations to improve clinical care. The quality of existing evidence needed to inform clinical guidelines has not been previously reviewed. Using the National Library of Medicine (NLM) database PubMed, we first identified 18 peer reviewed articles that addressed co-occurring medical conditions in adults with DS. Those conditions discussed in over half of the articles were prioritized for further review. Second, we performed detailed literature searches on these specific conditions. To inform the search strategy and review process a series of key questions were formulated a priori. The quality of available evidence was then graded and knowledge gaps were identified. The number of participating adults and the design of clinical studies varied by condition and were often inadequate for answering all of our key questions. We provide data on thyroid disease, cervical spine disease, hearing impairment, overweight-obesity, sleep apnea, congenital heart disease, and osteopenia-osteoporosis. Minimal evidence demonstrates massive gaps in our clinical knowledge that compromises clinical decision-making and management of these medically complex individuals. The development of evidence-based clinical guidance will require an expanded clinical knowledge-base in order to move forward.

Continuing bonds with deceased persons is discussed in grief literature, especially in children who are grieving the death of a parent or caregiver. The body is often described as important to the experience of grief, yet few studies have investigated the bodily experience of grief or continuing bonds in children, outside the context of pathology. The objective of this phenomenological research study was to describe the experience of body memory in those who lost a parent or caregiver in childhood or adolescence. Three individuals participated in a movement elicitation followed by a semi-structured interview. Textual data were analyzed using Moustakas’ (1994) phenomenology, revealing nine universal themes. Five themes pertained to the nature of body memory: a sense of reliving the experience; body memory being foreign but familiar; the experience of age in body memory; embodying leads to understanding; and the immediacy and frequency of body memory. Two themes described specific body sensations: a sense of falling and oscillation between opposing states. The remaining two themes connected the body to emotions: the emotional charge of body memory moves toward resilience and the relationship between tension and emotion. Implications for future study and integration of thematic findings in grief work in dance/movement therapy are provided.

Junior physicians describe mentoring relationships as integral to their career development and success. Current evidence suggests that mentoring is under-utilized despite interest from trainees. The purpose of this study is to describe the mentoring practices in developmental-behavioral pediatric (DBP) fellowship programs and identify mentoring needs of DBP fellows and recent graduates.DBP fellows and recent graduates less than 5 years out of training from US-based DBP fellowship programs were contacted to complete a survey on their mentoring experiences in fellowship and early career.A total of 90 respondents completed the entire survey including 47 current DBP fellows and 43 recent graduates. Only 52% of respondents reported having a formal faculty mentor during their fellowship. Only 45% of recent graduates reported that they currently have a mentor, of those without a current mentor 83% said they would like to have a mentor. Adequate mentoring during fellowship was lowest for career development and research (34% and 27%). Satisfaction with mentoring was associated with having a formal mentor (p.001) and receiving mentoring in multiple areas (p.001). Qualitative responses suggested that effective mentoring addresses the mentee's career goals, provides insight into being a developmental-behavioral pediatrician, assists in navigating academics, and involves a personal relationship.Results suggest opportunities for improved mentoring in DBP fellowship programs, particularly in the areas of career development and research and that there is a significant need for mentorship among recent graduates. Findings from this study can inform program improvement in mentoring for DBP fellows and recent graduates.

Adults with Down syndrome (DS) represent a unique population who are in need of clinical guidelines to address their medical care. The United States Preventive Service Task Force (USPSTF) has developed criteria for prioritizing conditions of public health importance with the potential for providing screening recommendations to improve clinical care. The quality of existing evidence needed to inform clinical guidelines has not been previously reviewed. Using the National Library of Medicine (NLM) database PubMed, we first identified 18 peer reviewed articles that addressed co-occurring medical conditions in adults with DS. Those conditions discussed in over half of the articles were prioritized for further review. Second, we performed detailed literature searches on these specific conditions. To inform the search strategy and review process a series of key questions were formulated a priori. The quality of available evidence was then graded and knowledge gaps were identified. The number of participating adults and the design of clinical studies varied by condition and were often inadequate for answering all of our key questions. We provide data on thyroid disease, cervical spine disease, hearing impairment, overweight-obesity, sleep apnea, congenital heart disease, and osteopenia-osteoporosis. Minimal evidence demonstrates massive gaps in our clinical knowledge that compromises clinical decision-making and management of these medically complex individuals. The development of evidence-based clinical guidance will require an expanded clinical knowledge-base in order to move forward.

Background Adolescents born preterm have altered hypothalamic-pituitary-adrenal axis function with a blunted cortisol stress response, however, the influences of intrauterine growth restriction and race are unclear. Methods We measured salivary cortisol before and 20 min after a maximal-exercise stress test and calculated the cortisol stress response. We used linear regression to compare cortisol stress responses between preterm and term groups, adjusting for birth weight z-score and maternal hypertension, and examined effect modification by race and sex. Results We evaluated 171 adolescents born preterm with very low birth weight and 50 born term. Adolescents born preterm had reduced cortisol stress response compared to term (0.03 vs. 0.08 μg/dL, p = 0.04). This difference was race dependent: non-Black adolescents born preterm had significantly reduced cortisol stress response compared to those born at term (adjusted β: -0.74; 95% CI -1.34, -0.15), while there was no difference in Black adolescents (0.53; -0.16, 1.22). Sex did not modify the relationship. Conclusions Adolescents born preterm exhibit a reduced salivary cortisol response to exercise stress, suggesting long-term alterations in the hypothalamic-pituitary-adrenal axis. This relationship was evident in non-Black but not in Black adolescents, suggesting that race may modify the influence of preterm birth on stress alterations of the hypothalamic-pituitary-adrenal axis.

Purpose: The most common approach to physical therapy clinical education is the one-to-one (1:1) model. The collaborative clinical education model (CCEM) offers an alternative and beneficial approach to education but is not widely utilized within physical therapy. The primary aim of this study was to explore the experiences and perceptions of clinical instructors (CIs) teaching within the CCEM while also receiving structured support from an academic program. Methods: This study used semi-structured interviews before and after the CCEM experience to explore CI perceptions. CIs received formalized support that included pre-experience meetings, a CCEM Toolkit resource, scheduled follow-ups during the experience, and a post-clinical debriefing. Interview transcripts were analyzed using a qualitative data analysis program and collaborative coding process. Results: CIs’ perceptions of the CCEM shifted following participation. Participants noted a need to be prepared with appropriate teaching strategies, have frequent communication with the academic program, and have a supportive clinical environment. Conclusion: CI participation in the CCEM is challenged by negative perceptions and lack of experience with collaborative learning. CI perceptions of the CCEM can become more positive after actually teaching in the CCEM; therefore, perceived challenges need to be addressed to increase CI participation. The CCEM may be more widely accepted if CIs’ perceived challenges are addressed in partnership with an academic program with intentional CCEM training and support strategies.

This paper relays the Human Factor in the propagation of Computer Worms, and gives a report on the results of the effects of training on users knowledge on deterrence of Computer worms.

The Resilience Songwriting Program (RSP) for adolescent bereavement aims to offer a space for adolescents to nurture strengths and inner resources while also processing grief alongside peers. This study explored the feasibility and acceptability of the RSP with five males and five females (ages 11–17 years) who self-identified as grieving. Implemented as eight, 90-minute sessions at two community-based settings and as eight, 60-minute sessions at a middle school, feasibility data included tracking referrals, enrollment, attendance per site, reasons for missed sessions, and reasons for withdrawal. Input from three music therapists on barriers to and facilitators of successful RSP implementation was also collected. Acceptability data were obtained through individual post-program qualitative interviews and journaling completed during RSP sessions. The adolescents found the RSP acceptable, relevant, and meaningful. Recruitment was most feasible in the school setting, yet the music therapist found it challenging to complete the RSP protocol within the 60-minute session time frame. Music therapists in the community-based settings found the RSP protocol feasible to implement in the 90-minute session time frame. Future studies on the RSP should consider group composition, participants’ readiness to share song recordings with non-group members, and the clinical appropriateness of taking home song recordings.

e14085 Background: Chronic pain related to advanced cancer is difficult to treat. In addition to traditional analgesics, non-pharmacological interventions, such as music therapy, may help alleviate pain in this population. Research studies to test the efficacy of these non-pharmacological interventions are necessary and important. However, recruiting patients with advanced cancer to participate in such interventions can be challenging. Identifying effective sources of referrals and barriers to participation may help increase recruitment rates in the future. Methods: We recruited patients with advanced cancer (stage III or IV) with chronic pain from two major hospital systems to participate in a pain management interventional study. The experimental group received individualized music therapy, while the control group received talk therapy. Participants attended six weekly sessions at the hospital and were compensated for time and travel. Recruitment methods included referrals from care teams, advertisement through flyers and posters, EMR chart reviews, and in-person recruitment at multiple infusion centers. Missing data was excluded from analyses. Chi-square tests assessed significant differences between groups. Results: Of 594 patients that were referred to the study, 7% enrolled (n = 40), 35% declined (n = 208), and 58% were ineligible (n = 346). Forty-seven percent (n = 19) of enrolled participants were female; race/ethnic distributions were the following: African American/Black (55%; n = 22), Caucasian/White (28%; n = 11), or other (17%; n = 7). The most effective recruitment method was through self-referral; of the 40 patients enrolled in the study, 9 (23%) were enrolled through this method. There were no statistically significant differences between referral source and enrollment. The top three reasons patients declined to participate included lack of interest (32%; n = 67), lack of time and/or energy (28%; n = 59), and lack of transportation (16%, n = 34). Conclusions: Although there were no differences in referral sources, more patients were enrolled through self-referral or in-person recruitment, showing the power of personal motivation and personal touch. While lack of participation due to interest, time, or energy are hard to overcome, future research should consider campaigns to reach patients who are motivated to participate. In addition to referrals, resources for in-person recruitment and transportation to help alleviate barriers to research participation should be considered.

BackgroundNicotine preloading means using nicotine replacement therapy prior to a quit date while smoking normally. The aim is to reduce the drive to smoke, thereby reducing cravings for smoking after quit day, which are the main cause of early relapse. A prior systematic review showed inconclusive and heterogeneous evidence that preloading was effective and little evidence of the mechanism of action, with no cost-effectiveness data.ObjectivesTo assess (1) the effectiveness, safety and tolerability of nicotine preloading in a routine NHS setting relative to usual care, (2) the mechanisms of the action of preloading and (3) the cost-effectiveness of preloading.DesignOpen-label randomised controlled trial with examination of mediation and a cost-effectiveness analysis.SettingNHS smoking cessation clinics.ParticipantsPeople seeking help to stop smoking.InterventionsNicotine preloading comprised wearing a 21 mg/24 hour nicotine patch for 4 weeks prior to quit date. In addition, minimal behavioural support was provided to explain the intervention rationale and to support adherence. In the comparator group, participants received equivalent behavioural support. Randomisation was stratified by centre and concealed from investigators.Main outcome measuresThe primary outcome was 6-month prolonged abstinence assessed using the Russell Standard. The secondary outcomes were 4-week and 12-month abstinence. Adverse events (AEs) were assessed from baseline to 1 week after quit day. In a planned analysis, we adjusted for the use of varenicline (Champix®; Pfizer Inc., New York, NY, USA) as post-cessation medication. Cost-effectiveness analysis took a health-service perspective. The within-trial analysis assessed health-service costs during the 13 months of trial enrolment relative to the previous 6 months comparing trial arms. The base case was based on multiple imputation for missing cost data. We modelled long-term health outcomes of smoking-related diseases using the European-study on Quantifying Utility of Investment in Protection from Tobacco (EQUIPT) model.ResultsIn total, 1792 people were eligible and were enrolled in the study, with 893 randomised to the control group and 899 randomised to the intervention group. In the intervention group, 49 (5.5%) people discontinued preloading prematurely and most others used it daily. The primary outcome, biochemically validated 6-month abstinence, was achieved by 157 (17.5%) people in the intervention group and 129 (14.4%) people in the control group, a difference of 3.02 percentage points [95% confidence interval (CI) –0.37 to 6.41 percentage points; odds ratio (OR) 1.25, 95% CI 0.97 to 1.62;p = 0.081]. Adjusted for use of post-quit day varenicline, the OR was 1.34 (95% CI 1.03 to 1.73;p = 0.028). Secondary abstinence outcomes were similar. The OR for the occurrence of serious AEs was 1.12 (95% CI 0.42 to 3.03). Moderate-severity nausea occurred in an additional 4% of the preloading group compared with the control group. There was evidence that reduced urges to smoke and reduced smoke inhalation mediated the effect of preloading on abstinence. The incremental cost-effectiveness ratio at the 6-month follow-up for preloading relative to control was £710 (95% CI –£13,674 to £23,205), but preloading was dominant at 12 months and in the long term, with an 80% probability that it is cost saving.LimitationsThe open-label design could partially account for the mediation results. Outcome assessment could not be blinded but was biochemically verified.ConclusionsUse of nicotine-patch preloading for 4 weeks prior to attempting to stop smoking can increase the proportion of people who stop successfully, but its benefit is undermined because it reduces the use of varenicline after preloading. If this latter effect could be overcome, then nicotine preloading appears to improve health and reduce health-service costs in the long term. Future work should determine how to ensure that people using nicotine preloading opt to use varenicline as cessation medication.Trial registrationCurrent Controlled Trials ISRCTN33031001.FundingThis project was funded by the NIHR Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 22, No. 41. See the NIHR Journals Library website for further project information.

Active-duty military service members have a significant risk of sustaining physical and psychological trauma resulting in traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD). Within an interdisciplinary treatment approach at the National Intrepid Center of Excellence, service members participated in mask making during art therapy sessions. This study presents an analysis of the mask-making experiences of service members (n = 370) with persistent symptoms from combat- and mission-related TBI, PTSD, and other concurrent mood issues. Data sources included mask images and therapist notes collected over a five-year period. The data were coded and analyzed using grounded theory methods. Findings indicated that mask making offered visual representations of the self related to individual personhood, relationships, community, and society. Imagery themes referenced the injury, relational supports/losses, identity transitions/questions, cultural metaphors, existential reflections, and conflicted sense of self. These visual insights provided an increased understanding of the experiences of service members, facilitating their recovery.

Sustained exposure to high levels of parathyroid hormone (PTH), as observed in hyperparathyroidism, is catabolic to bone. The increase in the RANKL/OPG ratio in response to continuous PTH, resulting in increased osteoclastogenesis, is well established. However, the effects of prolonged PTH exposure on key regulators of skeletal mineralisation have yet to be investigated. This study sought to examine the temporal expression of PHOSPHO1, TNAP and nSMase2 in mineralising osteoblast-like cell cultures and to investigate the effects of continuous PTH exposure on the expression of these enzymes in vitro. PHOSPHO1, nSMase2 and TNAP expression in cultured MC3T3-C14 cells significantly increased from day 0 to day 10. PTH induced a rapid downregulation of Phospho1 and Smpd3 gene expression in MC3T3-C14 cells and cultured hemi-calvariae. Alpl was differentially regulated by PTH, displaying upregulation in cultured MC3T3-C14 cells and downregulation in hemi-calvariae. PTH was also able to abolish the stimulatory effects of bone morphogenic protein 2 (BMP-2) on Smpd3 and Phospho1 expression. The effects of PTH on Phospho1 expression were mimicked with the cAMP agonist forskolin and blocked by the PKA inhibitor PKI (5-24), highlighting a role for the cAMP/PKA pathway in this regulation. The potent down-regulation of Phospho1 and Smpd3 in osteoblasts in response to continuous PTH may provide a novel explanation for the catabolic effects on the skeleton of such an exposure. Furthermore, our findings support the hypothesis that PHOSPHO1, nSMase2 and TNAP function cooperatively in the initiation of skeletal mineralisation.

Aims The NHS Stop Smoking Service (NHS-SSS) helps approximately half its clients to quit for 4 weeks. However, most initially successful quitters relapse within 6 months. Short message service (SMS) texting has been shown to facilitate stopping smoking. We describe the development, implementation and subsequent evaluation, in terms of practicability and client response, of an SMS text-based relapse prevention intervention (RPI) delivered within routine community and specialist National Health Service (NHS) Stop Smoking Service (SSS) provision in four Primary Care Trusts. Design Text messages aimed at motivation to remain abstinent, preventing careless lapses and continuing the full course of medicine for smoking cessation were developed and sent weekly to clients' mobile phones for 12 weeks and fortnightly for 6 months. They were asked to respond to some of the texts and contact the NHS SSS if they lapsed. They were also offered free nicotine mini lozenges to be sent via the mail on three occasions. Setting NHS SSS. Participants 202 clients who had been abstinent for 4 weeks. Measurements Feasibility of introducing RPI into routine care; response to interactive messages and requests for the medication; rating of the helpfulness of RPI; self-reported and carbon monoxide (CO)-validated smoking status for up to 26 weeks. Findings A text-based RPI was easy to implement within the NHS SSS provided by specialist advisers, but enrolment of clients from services provided by a network of pharmacists was difficult because client contact details were often lacking. Where records of the number of people invited to RPI were available, 94% of eligible participants enrolled. The RPI was well received by both SSS clients and staff, with 70% (n = 63) of clients who completed follow-up considering the intervention helpful. Eighty-five per cent (n = 172) of clients responded to at least one of the nine interactive text messages. Sixty-four clients (32% of the total, 47% of those we managed to contact) reported continuous abstinence at 6 months. Eighteen (9%) clients who relapsed to smoking used the RPI to re-engage with the NHS SSS and 10 (5%) successfully re-established abstinence. Conclusions In smokers attending National Health Service Stop Smoking Services who are abstinent 4 weeks after their quit date, a relapse prevention intervention based on SMS text messaging was well received, and can be implemented economically and rapidly. A controlled trial is needed to establish whether it has a significant impact on relapse.

The NHS Stop Smoking Service (NHS-SSS) helps approximately half its clients to quit for 4 weeks. However, most initially successful quitters relapse within 6 months. Short message service (SMS) texting has been shown to facilitate stopping smoking. We describe the development, implementation and subsequent evaluation, in terms of practicability and client response, of an SMS text-based relapse prevention intervention (RPI) delivered within routine community and specialist National Health Service (NHS) Stop Smoking Service (SSS) provision in four Primary Care Trusts.Text messages aimed at motivation to remain abstinent, preventing careless lapses and continuing the full course of medicine for smoking cessation were developed and sent weekly to clients' mobile phones for 12 weeks and fortnightly for 6 months. They were asked to respond to some of the texts and contact the NHS SSS if they lapsed. They were also offered free nicotine mini lozenges to be sent via the mail on three occasions.NHS SSS.202 clients who had been abstinent for 4 weeks.Feasibility of introducing RPI into routine care; response to interactive messages and requests for the medication; rating of the helpfulness of RPI; self-reported and carbon monoxide (CO)-validated smoking status for up to 26 weeks.A text-based RPI was easy to implement within the NHS SSS provided by specialist advisers, but enrollment of clients from services provided by a network of pharmacists was difficult because client contact details were often lacking. Where records of the number of people invited to RPI were available, 94% of eligible participants enrolled. The RPI was well received by both SSS clients and staff, with 70% (n = 63) of clients who completed follow-up considering the intervention helpful. Eighty-five per cent (n = 172) of clients responded to at least one of the nine interactive text messages. Sixty-four clients (32% of the total, 47% of those we managed to contact) reported continuous abstinence at 6 months. Eighteen (9%) clients who relapsed to smoking used the RPI to re-engage with the NHS SSS and 10 (5%) successfully re-established abstinence.In smokers attending National Health Service Stop Smoking Services who are abstinent 4 weeks after their quit date, a relapse prevention intervention based on SMS text messaging was well received, and can be implemented economically and rapidly. A controlled trial is needed to establish whether it has a significant impact on relapse.

BACKGROUND: This is an update of the review published on the Cochrane Library in 2016, Issue 8. Having cancer may result in extensive emotional, physical and social suffering. Music interventions have been used to alleviate symptoms and treatment side effects in people with cancer. This review includes music interventions defined as music therapy offered by trained music therapists, as well as music medicine, which was defined as listening to pre‐recorded music offered by medical staff. OBJECTIVES: To assess and compare the effects of music therapy and music medicine interventions for psychological and physical outcomes in people with cancer. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 3) in the Cochrane Library, MEDLINE via Ovid, Embase via Ovid, CINAHL, PsycINFO, LILACS, Science Citation Index, CancerLit, CAIRSS, Proquest Digital Dissertations, ClinicalTrials.gov, Current Controlled Trials, the RILM Abstracts of Music Literature, http://www.wfmt.info/Musictherapyworld/ and the National Research Register. We searched all databases, except for the last two, from their inception to April 2020; the other two are no longer functional, so we searched them until their termination date. We handsearched music therapy journals, reviewed reference lists and contacted experts. There was no language restriction. SELECTION CRITERIA: We included all randomized and quasi‐randomized controlled trials of music interventions for improving psychological and physical outcomes in adults and pediatric patients with cancer. We excluded patients undergoing biopsy and aspiration for diagnostic purposes. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted the data and assessed the risk of bias. Where possible, we presented results in meta‐analyses using mean differences and standardized mean differences. We used post‐test scores. In cases of significant baseline difference, we used change scores. We conducted separate meta‐analyses for studies with adult participants and those with pediatric participants. Primary outcomes of interest included psychological outcomes and physical symptoms and secondary outcomes included physiological responses, physical functioning, anesthetic and analgesic intake, length of hospitalization, social and spiritual support, communication, and quality of life (QoL) . We used GRADE to assess the certainty of the evidence. MAIN RESULTS: We identified 29 new trials for inclusion in this update. In total, the evidence of this review rests on 81 trials with a total of 5576 participants. Of the 81 trials, 74 trials included adult (N = 5306) and seven trials included pediatric (N = 270) oncology patients. We categorized 38 trials as music therapy trials and 43 as music medicine trials. The interventions were compared to standard care. Psychological outcomes The results suggest that music interventions may have a large anxiety‐reducing effect in adults with cancer, with a reported average anxiety reduction of 7.73 units (17 studies, 1381 participants; 95% confidence interval (CI) ‐10.02 to ‐5.44; very low‐certainty evidence) on the Spielberger State Anxiety Inventory scale (range 20 to 80; lower values reflect lower anxiety). Results also suggested a moderately strong, positive impact of music interventions on depression in adults (12 studies, 1021 participants; standardized mean difference (SMD): −0.41, 95% CI −0.67 to −0.15; very low‐certainty evidence). We found no support for an effect of music interventions on mood (SMD 0.47, 95% CI −0.02 to 0.97; 5 studies, 236 participants; very low‐certainty evidence). Music interventions may increase hope in adults with cancer, with a reported average increase of 3.19 units (95% CI 0.12 to 6.25) on the Herth Hope Index (range 12 to 48; higher scores reflect greater hope), but this finding was based on only two studies (N = 53 participants; very low‐certainty evidence). Physical outcomes We found a moderate pain‐reducing effect of music interventions (SMD −0.67, 95% CI −1.07 to −0.26; 12 studies, 632 adult participants; very low‐certainty evidence). In addition, music interventions had a small treatment effect on fatigue (SMD −0.28, 95% CI −0.46 to −0.10; 10 studies, 498 adult participants; low‐certainty evidence). The results suggest a large effect of music interventions on adult participants' QoL, but the results were highly inconsistent across studies, and the pooled effect size was accompanied by a large confidence interval (SMD 0.88, 95% CI −0.31 to 2.08; 7 studies, 573 participants; evidence is very uncertain). Removal of studies that used improper randomization methods resulted in a moderate effect size that was less heterogeneous (SMD 0.47, 95% CI 0.06 to 0.88, P = 0.02, I(2) = 56%). A small number of trials included pediatric oncology participants. The findings suggest that music interventions may reduce anxiety but this finding was based on only two studies (SMD −0.94, 95% CI −1.9 to 0.03; very low‐certainty evidence). Due to the small number of studies, we could not draw conclusions regarding the effects of music interventions on mood, depression, QoL, fatigue or pain in pediatric participants with cancer. The majority of studies included in this review update presented a high risk of bias, and therefore the overall certainty of the evidence is low. For several outcomes (i.e. anxiety, depression, pain, fatigue, and QoL) the beneficial treatment effects were consistent across studies for music therapy interventions delivered by music therapists. In contrast, music medicine interventions resulted in inconsistent treatment effects across studies for these outcomes. AUTHORS' CONCLUSIONS: This systematic review indicates that music interventions compared to standard care may have beneficial effects on anxiety, depression, hope, pain, and fatigue in adults with cancer. The results of two trials suggest that music interventions may have a beneficial effect on anxiety in children with cancer. Too few trials with pediatric participants were included to draw conclusions about the treatment benefits of music for other outcomes. For several outcomes, music therapy interventions delivered by a trained music therapist led to consistent results across studies and this was not the case for music medicine interventions. Moreover, evidence of effect was found for music therapy interventions for QoL and fatigue but not for music medicine interventions. Most trials were at high risk of bias and low or very low certainty of evidence; therefore, these results need to be interpreted with caution.