Use of implementation mapping in the planning of a hybrid type 1 pragmatic clinical trial: the BeatPain Utah study.

BACKGROUND: Considerable disparities in chronic pain management have been identified. Persons in rural, lower income, and minoritized communities are less likely to receive evidence-based, nonpharmacologic care. Telehealth delivery of nonpharmacologic, evidence-based interventions for persons with chronic pain is a promising strategy to lessen disparities, but implementation comes with many challenges. The BeatPain Utah study is a hybrid type 1 effectiveness-implementation pragmatic clinical trial investigating telehealth strategies to provide nonpharmacologic care from physical therapists to persons with chronic back pain receiving care in ommunity health centers (CHCs). CHCs provide primary care to all persons regardless of ability to pay. This paper outlines the use of implementation mapping to develop a multifaceted implementation plan for the BeatPain study. METHODS: During a planning year for the BeatPain trial, we developed a comprehensive logic model including the five-step implementation mapping process informed by additional frameworks and theories. The five iterative implementation mapping steps were addressed in the planning year: (1) conduct needs assessments for involved groups; (2) identify implementation outcomes, performance objectives, and determinants; (3) select implementation strategies; (4) produce implementation protocols and materials; and (5) evaluate implementation outcomes. RESULTS: CHC leadership/providers, patients, and physical therapists were identified as involved groups. Barriers and assets were identified across groups which informed identification of performance objectives necessary to implement two key processes: (1) electronic referral of patients with back pain in CHC clinics to the BeatPain team and (2) connecting patients with physical therapists providing telehealth. Determinants of the performance objectives for each group informed our choice of implementation strategies which focused on training, education, clinician support, and tailoring physical therapy interventions for telehealth delivery and cultural competency. We selected implementation outcomes for the BeatPain trial to evaluate the success of our implementation strategies. CONCLUSIONS: Implementation mapping provided a comprehensive and systematic approach to develop an implementation plan during the planning phase for our ongoing hybrid effectiveness-implementation trial. We will be able to evaluate the implementation strategies used in the BeatPain Utah study to inform future efforts to implement telehealth delivery of evidence-based pain care in CHCs and other settings. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04923334 . Registered June 11, 2021.

Use of implementation mapping in the planning of a hybrid type 1 pragmatic clinical trial: the BeatPain Utah study.

Background: Considerable disparities in chronic pain management have been identified. Persons in rural, lower income and minoritized communities are less likely to receive evidence-based, nonpharmacologic care. Telehealth delivery of nonpharmacologic, evidence-based interventions for persons with chronic pain is a promising strategy to lessen disparities, but implementation comes with many challenges. The BeatPain Utah study is a hybrid type I effectiveness-implementation pragmatic clinical trial investigating telehealth strategies to provide nonpharmacologic care from physical therapists to persons with chronic back pain receiving care in Community Health Centers (CHCs). CHCs provide primary care to all persons regardless of ability to pay. This paper outlines the use of implementation mapping to develop a multifaceted implementation plan for the BeatPain study. Methods: During a planning year for the BeatPain trial we developed a comprehensive logic model including the 5-step implementation mapping process informed by additional frameworks and theories. The five iterative implementation mapping steps were addressed in the planning year; 1) conduct needs assessments for involved groups; 2) identify implementation outcomes, performance objectives and determinants; 3) select implementation strategies; 4) produce implementation protocols and materials; and 5) evaluate implementation outcomes. Results: CHC leadership/providers, patients and physical therapists were identified as involved groups. Barriers and assets were identified across groups which informed identification of performance objectives necessary to implement two key processes; 1) electronic referral of patients with back pain in CHC clinics to the BeatPain team; and 2) connecting patients with physical therapists providing telehealth. Determinants of the performance objectives for each group informed our choice of implementation strategies which focused on training, education, clinician support and tailoring physical therapy interventions for telehealth delivery and cultural competency. We selected implementation outcomes for the BeatPain trial to evaluate the success of our implementation strategies. Conclusions: Implementation mapping provided a comprehensive and systematic approach to develop an implementation plan during the planning phase for our ongoing hybrid effectiveness-implementation trial. We will be able to evaluate the implementation strategies used in the BeatPain Utah study to inform future efforts to implement telehealth delivery of evidence-based pain care in CHCs and other settings. Trial registration: Clinicaltrials.gov Identifier: NCT04923334. Registered June 11, 2021 (https://clinicaltrials.gov/study/NCT04923334.

BeatPain Utah: study protocol for a pragmatic randomised trial examining telehealth strategies to provide non-pharmacologic pain care for persons with chronic low back pain receiving care in federally qualified health centers.

INTRODUCTION: Although evidence-based guidelines recommend non-pharmacologic treatments as first-line care for chronic low back pain (LBP), uptake has been limited, particularly in rural, low-income and ethnically diverse communities. The BeatPain study will evaluate the implementation and compare the effectiveness of two strategies to provide non-pharmacologic treatment for chronic LBP. The study will use telehealth to overcome access barriers for persons receiving care in federally qualified health centres (FQHCs) in the state of Utah. METHODS AND ANALYSIS: BeatPain Utah is a pragmatic randomised clinical trial with a hybrid type I design investigating different strategies to provide non-pharmacologic care for adults with chronic LBP seen in Utah FQHCs. The intervention strategies include a brief pain consult (BPC) and telehealth physical therapy (PT) component provided using either an adaptive or sequenced delivery strategy across two 12-week treatment phases. Interventions are provided via telehealth by centrally located physical therapists. The sequenced delivery strategy provides the BPC, followed by telehealth PT in the first 12 weeks for all patients. The adaptive strategy uses a stepped care approach and provides the BPC in the first 12 weeks and telehealth PT to patients who are non-responders to the BPC component. We will recruit 500 English-speaking or Spanish-speaking participants who will be individually randomised with 1:1 allocation. The primary outcome is the Pain, Enjoyment and General Activity measure of pain impact with secondary outcomes including the additional pain assessment domains specified by the National Institutes (NIH) of Health Helping to End Addiction Long Initiative and implementation measures. Analyses of primary and secondary measures of effectiveness will be performed under longitudinal mixed effect models across assessments at baseline, and at 12, 26 and 52 weeks follow-ups. ETHICS AND DISSEMINATION: Ethics approval for the study was obtained from the University of Utah Institutional Review Board. On completion, study data will be made available in compliance with NIH data sharing policies. TRIAL REGISTRATION NUMBER: NCT04923334.

Motivation and Problem Solving Versus Mobile 360° Videos to Promote Enrollment in the National Diabetes Prevention Program's Lifestyle Change Program Among People With Prediabetes: Protocol for a Randomized Trial.

BACKGROUND: More than 88 million Americans are at risk of developing type 2 diabetes mellitus (T2DM). The National Diabetes Prevention Program's Lifestyle Change Program (DPP LCP) has been shown to be effective in reducing the risk of progressing from prediabetes to T2DM. However, most individuals who could benefit from the program do not enroll. OBJECTIVE: The aim of this trial is to test the real-world efficacy of 3 mobile phone-based approaches to increasing enrollment in the DPP LCP including a best-practice condition and 2 novel approaches. METHODS: We will conduct a 3-armed randomized clinical trial comparing enrollment and 1-month engagement in the DPP LCP among adults with prediabetes from 2 health care settings. Participants in the best-practice condition will receive SMS-based notifications that they have prediabetes and a link to a website that explains prediabetes, T2DM, and the DPP LCP. This will be followed by a single question survey, "Would you like the DPP LCP to call you to enroll?" Participants in the 2 intervention arms will receive the same best-practice intervention plus either 2 mobile 360° videos or up to 5 brief phone calls from a health coach trained in a motivational coaching approach known as Motivation and Problem Solving (MAPS). We will collect measures of diabetes-related knowledge, beliefs in the controllability of risk for T2DM, risk perceptions for T2DM, and self-efficacy for lifestyle change pre-intervention and 4 weeks later. The primary outcomes of the study are enrollment in the DPP LCP and 4-week engagement in the DPP LCP. In addition, data on the person-hours needed to deliver the interventions as well as participant feedback about the interventions and their acceptability will be collected. Our primary hypotheses are that the 2 novel interventions will lead to higher enrollment and engagement in the DPP LCP than the best-practice intervention. Secondary hypotheses concern the mechanisms of action of the 2 intervention arms: (1) whether changes in risk perception are associated with program enrollment among participants in the mobile 360° video group and (2) whether changes in self-efficacy for lifestyle change are associated with program enrollment among participants in the MAPS coaching group. Finally, exploratory analyses will examine the cost effectiveness and acceptability of the interventions. RESULTS: The project was funded in September 2020; enrollment began in February 2021 and is expected to continue through July 2022. CONCLUSIONS: We are conducting a test of 2 novel, scalable, mobile phone-based interventions to increase enrollment in the DPP LCP. If effective, they have tremendous potential to be scaled up to help prevent T2DM nationwide. TRIAL REGISTRATION: ClinicalTrials.gov NCT04746781; https://clinicaltrials.gov/ct2/show/NCT04746781. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/28884.

Precision-Exercise-Prescription in patients with lung cancer undergoing surgery: rationale and design of the PEP study trial.

INTRODUCTION: Lung cancer is a significant burden on societies worldwide, and the most common cause of death in patients with cancer overall. Exercise intervention studies in patients with lung cancer have consistently shown benefits with respect to physical and emotional functioning. However, to date, exercise training has not been consistently implemented into clinical practice given that interventions have been costly and not aligned with clinical care. METHODS/DESIGN: The Precision-Exercise-Prescription (PEP) study is a prospective randomised controlled trial comparing the effectiveness and feasibility of a personalised intervention exercise programme among patients with lung cancer undergoing surgery. Two-hundred patients who are diagnosed with stage primary or secondary lung cancer and are eligible to undergo surgical treatment at Huntsman Cancer Institute comprise the target population. Patients are randomised to either the (1) outpatient precision-exercise intervention group or (2) delayed intervention group. The intervention approach uses Motivation and Problem Solving, a hybrid behavioural treatment based on motivational interviewing and practical problem solving. The dosage of the exercise intervention is personalised based on the individual's Activity Measure for Post-Acute-Care outpatient basic mobility score, and incorporates four exercise modes: mobility, callisthenics, aerobic and resistance. Exercise is implemented by physical therapists at study visits from presurgery until 6 months postsurgery. The primary endpoint is the level of physical function assessed by 6 min walk distance at 2 months postsurgery. Secondary outcomes include patient-reported outcomes (eg, quality of life, fatigue and self-efficacy) and other clinical outcomes, including length of stay, complications, readmission, pulmonary function and treatment-related costs up to 6 months postsurgery. ETHICS/DISSEMINATION: The PEP study will test the clinical effectiveness and feasibility of a personalised exercise intervention in patients with lung cancer undergoing surgery. Outcomes of this clinical trial will be presented at national and international conferences and symposia and will be published in international, peer-reviewed journals. Ethics approval was obtained at the University of Utah (IRB 00104671). TRIAL REGISTRATION NUMBER: NCT03306992.

Creatine as a Novel Treatment for Depression in Females Using Methamphetamine: A Pilot Study.

OBJECTIVE: Depression among methamphetamine users is more prevalent in females than males, but gender-specific treatment options for this comorbidity have not been described. Reduced brain phosphocreatine levels have been shown to be lower in female methamphetamine users compared to males, and, of relevance, studies have demonstrated an association between treatment-resistant depression and reduced brain phosphocreatine concentrations. The nutritional supplement creatine monohydrate has been reported to reduce symptoms of depression in female adolescents and adults taking antidepressants, as well as to increase brain phosphocreatine in healthy volunteers. Therefore, the purpose of this pilot study was to investigate creatine monohydrate as a treatment for depression in female methamphetamine users. METHODS: Fourteen females with depression and comorbid methamphetamine dependence were enrolled in an 8-week open label trial of 5 g of daily creatine monohydrate and of these 14, 11 females completed the study. Depression was measured using the Hamilton Depression Rating Scale (HAMD) and brain phosphocreatine levels were measured using phosphorus magnetic resonance spectroscopy pre- and post-creatine treatment. Secondary outcome measures included anxiety symptoms, measured with the Beck Anxiety Inventory (BAI), as well as methamphetamine use, monitored by twice weekly urine drug screens and self-reported use. RESULTS: The results of a linear mixed effects repeated measures model showed significantly reduced HAMD and BAI scores as early as week 2 when compared to baseline scores. This improvement was maintained through study completion. Brain phosphocreatine concentrations were higher at the second phosphorus magnetic resonance spectroscopy scan compared to the baseline scan; Mbaseline = 0.223 (SD = 0.013) vs. Mpost-treatment = 0.233 (SD = 0.009), t (9) = 2.905, p <.01, suggesting that creatine increased phosphocreatine levels. Also, a reduction in methamphetamine positive urine drug screens of greater than 50% was observed by week 6. Finally, creatine was well tolerated and adverse events that were related to gastrointestinal symptoms and muscle cramping were determined as possibly related to creatine. CONCLUSIONS: The current study suggests that creatine treatment may be a promising therapeutic approach for females with depression and comorbid methamphetamine dependence. This study is registered on clinicaltrials.gov (NCT01514630).

Gender differences in the effect of tobacco use on brain phosphocreatine levels in methamphetamine-dependent subjects.

BACKGROUND: A high prevalence of tobacco smoking has been observed in methamphetamine users, but there have been no in vivo brain neurochemistry studies addressing gender effects of tobacco smoking in methamphetamine users. Methamphetamine addiction is associated with increased risk of depression and anxiety in females. There is increasing evidence that selective analogues of nicotine, a principal active component of tobacco smoking, may ease depression and improve cognitive performance in animals and humans. OBJECTIVES: To investigate the effects of tobacco smoking and gender on brain phosphocreatine (PCr) levels, a marker of brain energy metabolism reported to be reduced in methamphetamine-dependent subjects. METHODS: Thirty female and 27 male methamphetamine-dependent subjects were evaluated with phosphorus-31 magnetic resonance spectroscopy ((31)P-MRS) to measure PCr levels within the pregenual anterior cingulate, which has been implicated in methamphetamine neurotoxicity. RESULTS: Analysis of covariance revealed that there were statistically significant slope (PCr versus lifetime amount of tobacco smoking) differences between female and male methamphetamine-dependent subjects (p = 0.03). In females, there was also a statistically significant interaction between lifetime amounts of tobacco smoking and methamphetamine in regard to PCr levels (p = 0.01), which suggests that tobacco smoking may have a more significant positive impact on brain PCr levels in heavy, as opposed to light to moderate, methamphetamine-dependent females. CONCLUSION: These results indicate that tobacco smoking has gender-specific effects in terms of increased anterior cingulate high energy PCr levels in methamphetamine-dependent subjects. Cigarette smoking in methamphetamine-dependent women, particularly those with heavy methamphetamine use, may have a potentially protective effect upon neuronal metabolism.

A review of treatment options for co-occurring methamphetamine use disorders and depression.

Co-occurring methamphetamine use and depression interferes with treatment outcomes. Female methamphetamine users are known to have higher rates of depression than male methamphetamine users, although this is also true for the general population. There are limited treatment options for the management of depression among methamphetamine users. In this integrative review, we summarize data on treatment strategies for co-occurring depression and methamphetamine use disorders. English-language articles were identified from PsychINFO, CINAHL, PubMed, and Medline as well as from reference lists of key articles. Search terms included "methamphetamine," "depression," and "treatment." Research articles describing psychological (n = 3), pharmacological (n = 6), nutritional supplement (n = 1), and psychological combined with pharmacological (n = 3) approaches for the treatment of methamphetamine use or withdrawal and/or depression are included in this review. Psychological and combination of psychological with pharmacological approaches have not been shown to be effective in treating these co-occurring conditions. Antidepressants have been determined to be ineffective and/or to introduce side effects. Gender differences with response to treatment were examined in only one of the published studies. There is a large gap in knowledge regarding treatment of co-occurring methamphetamine use disorders and depression. Considering that female methamphetamine users experience higher rates of depression than men, a focus on gender-specific treatment approaches is warranted.

Decreased frontal lobe phosphocreatine levels in methamphetamine users.

BACKGROUND: Mitochondria-related mechanisms have been suggested to mediate methamphetamine (METH) toxicity. However, changes in brain energetics associated with high-energy phosphate metabolism have not been investigated in METH users. Phosphorus-31 ((31)P) magnetic resonance spectroscopy (MRS) was used to evaluate changes in mitochondrial high energy phosphates, including phosphocreatine (PCr) and ß-nucleoside triphosphate (ß-NTP, primarily ATP in brain) levels. We hypothesized that METH users would have decreased high-energy PCr levels in the frontal gray matter. METHODS: Study participants consisted of 51 METH (age=32.8±6.7) and 23 healthy comparison (age=31.1±7.5) subjects. High-energy phosphate metabolite levels were compared between the groups and potential gender differences were explored. RESULTS: METH users had lower ratios of PCr to total pool of exchangeable phosphate (PCr/TPP) in the frontal lobe as compared to the healthy subjects (p=.001). The lower PCr levels in METH subjects were significantly associated with lifetime amount of METH use (p=.003). A sub-analysis for gender differences revealed that female METH users, who had lower daily amounts (1.1±1.0g) of METH use than males (1.4±1.7g), had significantly lower PCr/TPP ratios than male METH users, controlling for the amount of METH use (p=.02). CONCLUSIONS: The present findings suggest that METH compromises frontal lobe high-energy phosphate metabolism in a dose-responsive manner. Our findings also suggest that the abnormality in frontal lobe high-energy phosphate metabolism might be more prominent in female than in male METH users. This is significant as decreased PCr levels have been associated with depressive symptoms, and poor responses to antidepressant treatment have been reported in those with decreased PCr levels.

Effectiveness of pretreatment interim support group attendance in facilitating treatment enrollment among methamphetamine abusers.

Decreasing state and federal budgets have led to shortages in public health funding for treatment programs to aid long-term users in recovery from methamphetamine abuse. These shortages have led to client "waiting lists" for government-subsidized treatment. Many of these "waiting list" individuals fail to show up for treatment when it is scheduled. The current study investigates the efficacy of "interim support groups" as a means of encouraging methamphetamine abusers to begin treatment programs (defined as attendance on the first day of treatment). A logistic regression revealed that interim group attendance predicted whether a methamphetamine abuser would show up for treatment. These results are discussed in terms of both the value of interim groups in facilitating treatment adherence and the role pretreatment support groups can play in facilitating a methamphetamine abuser's determination to engage in treatment.

Readiness to change in adults waiting for publicly funded substance abuse treatment.

The primary objective of this study was to evaluate the factor structure of a modified version of the Stages of Change Readiness and Treatment Eagerness Scale (SOCRATES) for a sample of indigent adults with alcohol and other drug problems. A community sample of 338 adults on waiting lists for entrance into publicly funded substance abuse treatment completed a 19-item modified version of the SOCRATES. Confirmatory factor analyses were conducted on two structural models of the SOCRATES based on prior literature. The results indicated that a two-factor model of the SOCRATES provided the best fit for the data in this study. Suggestions for future research using a modified version of this measure are discussed.