Stepped implementation-to-target: a study protocol of an adaptive trial to expand access to addiction medications.

BACKGROUND: In response to the US opioid epidemic, significant national campaigns have been launched to expand access to `opioid use disorder (MOUD). While adoption has increased in general medical care settings, specialty addiction programs have lagged in both reach and adoption. Elevating the quality of implementation strategy, research requires more precise methods in tailoring strategies rather than a one-size-fits-all-approach, documenting participant engagement and fidelity to the delivery of the strategy, and conducting an economic analysis to inform decision making and policy. Research has yet to incorporate all three of these recommendations to address the challenges of implementing and sustaining MOUD in specialty addiction programs. METHODS: This project seeks to recruit 72 specialty addiction programs in partnership with the Washington State Health Care Authority and employs a measurement-based stepped implementation-to-target approach within an adaptive trial design. Programs will be exposed to a sequence of implementation strategies of increasing intensity and cost: (1) enhanced monitoring and feedback (EMF), (2) 2-day workshop, and then, if outcome targets are not achieved, randomization to either internal facilitation or external facilitation. The study has three aims: (1) evaluate the sequential impact of implementation strategies on target outcomes, (2) examine contextual moderators and mediators of outcomes in response to the strategies, and (3) document and model costs per implementation strategy. Target outcomes are organized by the RE-AIM framework and the Addiction Care Cascade. DISCUSSION: This implementation project includes elements of a sequential multiple assignment randomized trial (SMART) design and a criterion-based design. An innovative and efficient approach, participating programs only receive the implementation strategies they need to achieve target outcomes. Findings have the potential to inform implementation research and provide key decision-makers with evidence on how to address the opioid epidemic at a systems level. TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov (NCT05343793) on April 25, 2022.

Expanding access to medications for opioid use disorder in primary care clinics: an evaluation of common implementation strategies and outcomes.

BACKGROUND: To combat the opioid epidemic in the USA, unprecedented federal funding has been directed to states and territories to expand access to prevention, overdose rescue, and medications for opioid use disorder (MOUD). Similar to other states, California rapidly allocated these funds to increase reach and adoption of MOUD in safety-net, primary care settings such as Federally Qualified Health Centers. Typical of current real-world implementation endeavors, a package of four implementation strategies was offered to all clinics. The present study examines (i) the pre-post effect of the package of strategies, (ii) whether/how this effect differed between new (start-up) versus more established (scale-up) MOUD practices, and (iii) the effect of clinic engagement with each of the four implementation strategies. METHODS: Forty-one primary care clinics were offered access to four implementation strategies: (1) Enhanced Monitoring and Feedback, (2) Learning Collaboratives, (3) External Facilitation, and (4) Didactic Webinars. Using linear mixed effects models, RE-AIM guided outcomes of reach, adoption, and implementation quality were assessed at baseline and at 9 months follow-up. RESULTS: Of the 41 clinics, 25 (61%) were at MOUD start-up and 16 (39%) were at scale-up phases. Pre-post difference was observed for the primary outcome of percent of patient prescribed MOUD (reach) (ßtime = 3.99; 0.73 to 7.26; p = 0.02). The largest magnitude of change occurred in implementation quality (ES = 0.68; 95% CI = 0.66 to 0.70). Baseline MOUD capability moderated the change in reach (start-ups 22.60%, 95% CI = 16.05 to 29.15; scale-ups -4.63%, 95% CI = -7.87 to -1.38). Improvement in adoption and implementation quality were moderately associated with early prescriber engagement in Learning Collaboratives (adoption: ES = 0.61; 95% CI = 0.25 to 0.96; implementation quality: ES = 0.55; 95% CI = 0.41 to 0.69). Improvement in adoption was also associated with early prescriber engagement in Didactic Webinars (adoption: ES = 0.61; 95% CI = 0.20 to 1.05). CONCLUSIONS: Rather than providing an all-clinics-get-all-components package of implementation strategies, these data suggest that it may be more efficient and effective to tailor the provision of implementation strategies based on the needs of clinic. Future implementation endeavors could benefit from (i) greater precision in the provision of implementation strategies based on contextual determinants, and (ii) the inclusion of strategies targeting engagement.

Promising outcomes from a cognitive behavioral therapy text-messaging intervention targeting drug use, antiretroviral therapy adherence, and HIV risk behaviors among adults living with HIV and substance use disorders.

BACKGROUND: To date, no studies have reported the use of text messaging to deliver cognitive behavioral therapy (CBT) to people living with HIV and substance use disorders. OBJECTIVE: We developed and evaluated a 12-week, CBT-based text-messaging intervention (TXT-CBT) targeting drug use and adherence to antiretroviral therapy (ART) for adults with HIV and comorbid opioid and stimulant use disorders. MATERIALS AND METHODS: Participants were randomly assigned to receive either TXT-CBT (n = 25) or an informational pamphlet (INFO) discussing substance use and medication adherence (n = 25). ART adherence, drug use, and HIV-risk behaviors were assessed at baseline, monthly during treatment, and treatment-end, and were compared between groups using a mixed-model repeated-measures analysis. Injection drug use was examined as a moderator of outcomes. RESULTS: Relative to the INFO group, TXT-CBT participants evidenced increased ART adherence, measured by phone-based unannounced pill counts and biochemically by viral load and CD4 count. TXT-CBT participation was also associated with reductions in opioid use and HIV risk behaviors. While reductions in cocaine use were observed in the TXT-CBT group, relative to the INFO group, other stimulant use did not change. Among people who inject drugs, TXT-CBT produced increases in ART adherence and corresponding changes in viral load, relative to injection drug users in the control condition. CONCLUSIONS: Findings demonstrated promising preliminary evidence for the efficacy of TXT-CBT in improving ART adherence and reducing drug use and HIV-risk behaviors among people with HIV infection and comorbid opioid and stimulant use disorders.

COVID-19 Adaptations in the Care of Patients with Opioid Use Disorder: a Survey of California Primary Care Clinics.

BACKGROUND: With the onset of the COVID-19 crisis, many federal agencies relaxed policies regulating opioid use disorder treatment. The impact of these changes has been minimally documented. The abrupt nature of these shifts provides a naturalistic opportunity to examine adaptations for opioid use disorder treatment in primary care. OBJECTIVE: To examine change in medical and behavioral health appointment frequency, visit type, and management of patients with opioid use disorder in response to COVID-19. DESIGN: A 14-item survey queried primary care practices that were enrolled in a medications for opioid use disorder statewide expansion project. Survey content focused on changes in service delivery because of COVID-19. The survey was open for 18 days. PARTICIPANTS: We surveyed 338 clinicians from 57 primary care clinics located in California, including federally qualified health centers and look-alikes. A representative from all 57 clinics (100%) and 118 staff (34.8% of all staff clinicians) participated in the survey. MAIN MEASURES: The survey consisted of seven dimensions of practice: medical visits, behavioral health visits, medication management, urine drug screenings, workflow, perceived patient demand, and staff experience. KEY RESULTS: A total of 52 of 57 (91.2%) primary care clinics reported practice adaptations in response to COVID-19 regulatory changes. Many clinics indicated that both medical (40.4%) and behavioral health visits (53.8%) were now exclusively virtual. Two-thirds (65.4%) of clinics reported increased duration of buprenorphine prescriptions and reduced urine drug screenings (67.3%). The majority (56.1%) of clinics experienced an increase in patient demand for behavioral health services. Over half (56.2%) of clinics described having an easier or unchanged experience retaining patients in care. CONCLUSIONS: Many adaptations in the primary care approach to patients with opioid use disorder may be temporary reactions to COVID-19. Further evaluation of the impact of these adaptations on patient outcomes is needed to determine whether changes should be maintained post-COVID-19.

Improving Medication Access within Integrated Treatment for Individuals with Co-Occurring Disorders in Substance Use Treatment Agencies.

BACKGROUND: The best approach to provide comprehensive care for individuals with co-occurring disorders (CODs) related to substance use and mental health is to address both disorders through an integrated treatment approach. However, only 25% of behavioral health agencies offer integrated care and less than 7% of individuals who need integrated treatment receive it. A project used a cluster-randomized waitlist control group design to evaluate the effectiveness of Network for the Improvement of Addiction Treatment (NIATx) implementation strategies to improve access to addiction and psychotropic medications. METHODS: This study represents a secondary analysis of data from the NIATx project. Forty-nine agencies were randomized to Cohort1 (active implementation group, receiving the NIATx strategy [n=25]) or Cohort2 (waitlist control group [n=24]). Data were collected at three time points (Baseline, Year1 and Year2). A two-level (patient within agency) multinomial logistic regression model investigated the effects of implementation strategy condition on one of four medication outcomes: both medication types, only psychotropic medication, only addiction medication, or neither medication type. A per-protocol analysis included time, NIATx fidelity, and agency focus as predictors. RESULTS: The intent-to-treat analysis found a statistically significant change in access to addiction versus neither medication, but Cohort1 compared to Cohort2 at Year1 showed no differences. Changes were associated with the experimental intervention and occurred in the transition from Year 1 to Year 2, where greater increases were seen for agencies in Cohort2 versus Cohort1. The per-protocol analysis showed increased access to both medications and addiction medications from pre- to post-intervention for agencies in both cohorts; however, differences in change between high- and low-implementation agencies were not significant. CONCLUSIONS: Access to integrated services for people with CODs is a long-standing problem. NIATx implementation strategies had limited effectiveness in improving medication access for individuals with CODs. Implementation strategy adherence is associated with increased medication access.

Mindfulness Based Relapse Prevention for Stimulant Dependent Adults: A Pilot Randomized Clinical Trial.

In light of the known associations between stress, negative affect, and relapse, mindfulness strategies hold promise as a means of reducing relapse susceptibility. In a pilot randomized clinical trial, we evaluated the effects of Mindfulness Based Relapse Prevention (MBRP), relative to a health education control condition (HE) among stimulant dependent adults receiving contingency management. All participants received a 12-week contingency management (CM) intervention. Following a 4-week CM-only lead in phase, participants were randomly assigned to concurrently receive MBRP (n=31) or HE (n=32). Stimulant dependent adults age 18 and over. A university based clinical research center. The primary outcomes were stimulant use, measured by urine drug screens weekly during the intervention and at 1-month post-treatment, negative affect, measured by the Beck Depression Inventory and Beck Anxiety Inventory, and psychiatric severity, measured by the Addiction Severity Index. Medium effect sizes favoring MBRP were observed for negative affect and overall psychiatric severity outcomes. Depression severity changed differentially over time as a function of group, with MBRP participants reporting greater reductions through follow-up (p=0.03; Effect Size=0.58). Likewise, the MBRP group evidenced greater declines in psychiatric severity, (p=0.01; Effect Size=0.61 at follow-up). Among those with depressive and anxiety disorders, MBRP was associated with lower odds of stimulant use relative to the control condition (Odds Ratio= 0.78, p=0.03 and OR=0.68, p=0.04). MBRP effectively reduces negative affect and psychiatric impairment, and is particularly effective in reducing stimulant use among stimulant dependent adults with mood and anxiety disorders.

Characterization and outcomes of repeat orbital decompression for thyroid-associated orbitopathy.

Orbital decompression for thyroid-associated orbitopathy (TAO) is commonly performed for disfiguring proptosis, congestion, and optic neuropathy. Although one decompression typically achieves goals, a small percentage requires repeat decompression. We performed a 10-year retrospective chart review of all orbital decompressions for TAO at a single tertiary referral institution. Four-hundred and ninety-five orbits (330 patients) were decompressed for TAO, with 45 orbits (37 patients) requiring repeat decompression. We reviewed the repeat cases for indications, clinical activity scores, approach, walls decompressed, and outcomes. Nine percent of orbits required repeat decompression for proptosis (70%), optic neuropathy (25%) or congestion (45%). Sixty-four percent were for recurrence of disease, 36% were for suboptimal decompression. Three incisional approaches were used: lateral upper eyelid crease, inferior transconjunctival, and transcaruncular, with inferior transconjunctival being most common. Of the three walls removed, deep lateral, inferior, and medial, the deep lateral wall was most common (51%). A repeat lateral decompression was the most frequent pattern. Of 37 patients requiring repeat decompression, 40% had diplopia prior to repeat, and an additional 24% developed diplopia after the repeat. Whereas previous studies published by our group cited only 2.6% of deep lateral wall orbital decompressions leading to new-onset primary gaze diplopia, repeat orbital decompressions have a much higher rate of post-operative diplopia. The new onset primary gaze diplopia after repeat decompression group had a higher average preoperative CAS (3.3 vs. 2.4, p < 0.01), higher mean blood loss (56 vs. 19 mL, p = 0.04), more frequent medial wall decompressions (47% vs. 29%, p = 0.33), and greater proptosis reduction (2.4 vs. 1.7 mm, p = 0.24).

A three-dimensional construct of the aging eyebrow: the illusion of volume loss.

BACKGROUND: The eyebrows and eyebrow fat pads, key structures in upper facial aesthetics, are particularly vulnerable to age-related changes. OBJECTIVES: In this study, the authors compare the impact of aging on the eyebrows and eyebrow fat pad volume in men and women through three-dimensional (3D) volumetric analysis. METHODS: Electronic medical records of patients seen at the Jules Stein Eye Institute in the Division of Orbital and Ophthalmic Plastic Surgery between 2005 and 2010 were reviewed. Patients were included if they had undergone investigative imaging of the orbit for unilateral pathology. Computed tomography (CT) scans of patients with Graves disease diagnosis, extensive orbital trauma, and/or previous eyebrow surgery were excluded. A total of 52 CT scans (24 men and 28 women) were retained for analysis. A 3D reconstruction software was used to analyze the scans and calculate volumes of the retroorbicularis oculi fat (ROOF), galeal fat (ROOF and subcutaneous fat), and soft tissue muscles. RESULTS: Galeal and brow fat volumes showed a significant positive trend toward enlargement in women (P values of .01 and .05, respectively). Although men showed a tendency toward fat enlargement with age, this was not statistically significant. Soft tissue-muscle volume decreased significantly in aging women (9.32 mm(3)/y) (P = .02). Data indicated that soft tissue volume in men tended to increase with age (3.92 mm(3)/y) but not significantly (P = .36). Neither total volume nor brow thickness appeared to change significantly in women (P = .56, P = .73). In men, total volume and brow thickness showed weak evidence of increasing with age (P = .12, P = .22). Linear regressions of Hertel measurements with and without sex interaction showed no statistically significant trend between the amount of proptosis and the galeal or brow fat. CONCLUSIONS: Although overall eyebrow volume does not change with age, the relative contribution of fat and soft tissue to the total volume does seem to change. This pattern also differs between males and females. As women age, the fat volume increases and the soft tissue volume decreases. In men, the shift from soft tissue volume to fat volume is less pronounced. Although many clinicians have been drawn to the concept of fat volume deflation as a key element of facial aging, this study does not support this perspective in the eyebrow fat pad. An increasingly refined understanding of the dynamics of facial aging is mandatory for clinical diagnosis and will likely provide the framework from which to develop more innovative treatment options.

Rituximab treatment of patients with severe, corticosteroid-resistant thyroid-associated ophthalmopathy.

PURPOSE: To study the effectiveness of anti-CD20 (rituximab [RTX]; Rituxan; Genentech, Inc., South San Francisco, CA) therapy in patients with severe, corticosteroid (CS)-resistant thyroid-associated ophthalmopathy (TAO). DESIGN: Retrospective, interventional case series. PARTICIPANTS: Six consecutive subjects with severe, progressive TAO unresponsive to CS. METHODS: Electronic medical record review of consecutive patients receiving RTX during the previous 18 months. Responses to therapy were graded using standard clinical assessment and flow cytometric analysis of peripheral lymphocytes. MAIN OUTCOME MEASURES: Clinical activity score (CAS), proptosis, strabismus, treatment side effects, and quantification of regulatory T cells. RESULTS: Six patients were studied. Systemic CS failed to alter clinical activity in all patients (mean CAS+/-standard deviation, 5.3+/-1.0 before vs. 5.5+/-0.8 during therapy for 7.5+/-6.4 months; P = 1.0). However, after RTX treatment, CAS improved from 5.5+/-0.8 to 1.3+/-0.5 at 2 months after treatment (P<0.03) and remained quiescent in all patients (CAS, 0.7+/-0.8; P<0.0001) at a mean follow-up of 6.2+/-4.5 months. Vision improved bilaterally in all 4 patients with dysthyroid optic neuropathy (DON). None of the 6 patients experienced disease relapse after RTX infusion, and proptosis remained stable (Hertel measurement, 24+/-3.7 mm before therapy and 23.6+/-3.7 mm after therapy; P = 0.17). The abundance of T regulatory cells, assessed in 1 patient, increased within 1 week of RTX and remained elevated at 18 months of follow-up. CONCLUSIONS: In progressive, CS-resistant TAO, rapid and sustained resolution of orbital inflammation and DON followed treatment with RTX. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Development of criteria for evaluating clinical response in thyroid eye disease using a modified Delphi technique.

OBJECTIVE: To identify components of a provisional clinical response index for thyroid eye disease using a modified Delphi technique. METHODS: The International Thyroid Eye Disease Society conducted a structured, 3-round Delphi exercise establishing consensus for a core set of measures for clinical trials in thyroid eye disease. The steering committee discussed the results in a face-to-face meeting (nominal group technique) and evaluated each criterion with respect to its feasibility, reliability, redundancy, and validity. Redundant measures were consolidated or excluded. RESULTS: Criteria were parsed into 11 domains for the Delphi surveys. Eighty-four respondents participated in the Delphi 1 survey, providing 220 unique items. Ninety-two members (100% of the respondents from Delphi 1 plus 8 new participants) responded in Delphi 2 and rated the same 220 items. Sixty-four members (76% of participants) rated 153 criteria in Delphi 3 (67 criteria were excluded because of redundancy). Criteria with a mean greater than 6 (1 = least appropriate to 9 = most appropriate) were further evaluated by the nominal group technique and provisional core measures were chosen. CONCLUSIONS: Using a Delphi exercise, we developed provisional core measures for assessing disease activity and severity in clinical trials of therapies for thyroid eye disease. These measures will be iteratively refined for use in multicenter clinical trials.