Improving access to buprenorphine for rural veterans in a learning health care system.

OBJECTIVE: To describe a learning health care system research process designed to increase buprenorphine prescribing for the treatment of opioid use disorder (OUD) in rural primary care settings within U.S. Department of Veterans Affairs (VA) treatment facilities. DATA SOURCES AND STUDY SETTING: Using national administrative data from the VA Corporate Data Warehouse, we identified six rural VA health care systems that had improved their rate of buprenorphine prescribing within primary care from 2015 to 2020 (positive deviants). We conducted qualitative interviews with leaders, clinicians, and staff involved in buprenorphine prescribing within primary care from these sites to inform the design of an implementation strategy. STUDY DESIGN: Qualitative interviews to inform implementation strategy development. DATA COLLECTION/EXTRACTION METHODS: Interviews were audio-recorded, transcribed verbatim, and coded by a primary coder and secondary reviewer. Analysis utilized a mixed inductive/deductive approach. To develop an implementation strategy, we matched clinical needs identified within interviews with resources and strategies participants had utilized to address these needs in their own sites. PRINCIPAL FINDINGS: Interview participants (n = 30) identified key clinical needs and strategies for implementing buprenorphine in rural, primary care settings. Common suggestions included the need for clinical mentorship or a consult service, buprenorphine training, and educational resources. Building upon interview findings and in partnership with a clinical team, we developed an implementation strategy composed of an engaging case-based training, an audit and feedback process, and educational resources (e.g., Buprenorphine Frequently Asked Questions, Rural Care Model Infographic). CONCLUSIONS: We describe a learning health care system research process that leveraged national administrative data, health care provider interviews, and clinical partnership to develop an implementation strategy to encourage buprenorphine prescribing in rural primary care settings.

Patients' Perspectives on Discontinuing Buprenorphine for the Treatment of Opioid Use Disorder.

OBJECTIVES: Buprenorphine and other medications for opioid use disorder (OUD) are recommended as standard of care in the treatment of OUD and are associated with positive health and addiction-related outcomes. Despite benefits, discontinuation is common, with half of patients discontinuing in the first year of treatment. Addressing OUD is a major clinical priority, yet little is known about the causes of medication discontinuation from the patient perspective. METHODS: From March 2021 to April 2022, we conducted qualitative interviews with patients who had discontinued buprenorphine for the treatment of OUD within the past 12 months. Eligible participants were selected from 2 Veterans Health Administration Health Care Systems in Oregon. Coding and analysis were guided by conventional qualitative content analysis. RESULTS: Twenty participants completed an interview; 90% were White and 90% were male, and the mean age was 54.2 years. Before discontinuation, participants had received buprenorphine for 8.3 months on average (range, 1-40 months); 80% had received buprenorphine for less than 12 months. Qualitative analysis identified the following themes relating to discontinuation: health system barriers (eg, logistical hurdles, rules and policy violations), medication effects (adverse effects; attributed adverse effects, lack of efficacy in treating chronic pain) and desire for opioid use. Patient description of decisions to discontinue buprenorphine could be multicausal, reflecting provider or system-level barriers in interaction with patient complexity or medication ambivalence. CONCLUSIONS: Study results identify several actionable ways OUD treatment could be modified to enhance patient retention.

"I'm Clean and Sober, But Not Necessarily Free": Perceptions of Buprenorphine Among Patients in Long-Term Treatment.

BACKGROUND: Patients receiving buprenorphine for the treatment of opioid use disorder (OUD) experience a roughly 50% reduction in mortality risk relative to those not receiving medication. Longer periods of treatment are also associated with improved clinical outcomes. Despite this, patients often express desires to discontinue treatment and some view taper as treatment success. Little is known about the beliefs and medication perspectives of patients engaged in long-term buprenorphine treatment that may underlie motivations to discontinue. METHODS: This study was conducted at the VA Portland Health Care System (2019-2020). Qualitative interviews were conducted with participants prescribed buprenorphine for ≥2 years. Coding and analysis were guided by directed qualitative content analysis. RESULTS: Fourteen patients engaged in office-based buprenorphine treatment completed interviews. While patients expressed strong enthusiasm for buprenorphine as a medication, the majority expressed the desire to discontinue, including patients actively tapering. Motivations to discontinue fell into 4 categories. First, patients were troubled by perceived side effects of the medication, including effects on sleep, emotion, and memory. Second, patients expressed unhappiness with being "dependent" on buprenorphine, framed in opposition to personal strength/independence. Third, patients expressed stigmatized beliefs about buprenorphine, describing it as "illicit," and associated with past drug use. Finally, patients expressed fears about buprenorphine unknowns, including potential long-term health effects and interactions with medications required for surgery. CONCLUSIONS: Despite recognizing benefits, many patients engaged in long-term buprenorphine treatment express a desire to discontinue. Findings from this study may help clinicians anticipate patient concerns and can be used to inform shared decision-making conversations regarding buprenorphine treatment duration.

Major Update 2: Antibody Response and Risk for Reinfection After SARS-CoV-2 Infection-Final Update of a Living, Rapid Review.

BACKGROUND: The durability of the antibody response after SARS-CoV-2 infection and the role of antibodies in protection against reinfection are unclear. PURPOSE: To synthesize evidence on the SARS-CoV-2 antibody response and reinfection risk with a focus on gaps identified in our prior reports. DATA SOURCES: MEDLINE (Ovid), EMBASE, CINAHL, World Health Organization Research Database, and reference lists from 16 December 2021 through 8 July 2022, with surveillance through 22 August 2022. STUDY SELECTION: English-language, cohort studies evaluating IgG antibody duration at least 12 months after SARS-CoV-2 infection, the antibody response among immunocompromised adults, predictors of nonseroconversion, and reinfection risk. DATA EXTRACTION: Two investigators sequentially extracted study data and rated quality. DATA SYNTHESIS: Most adults had IgG antibodies after SARS-CoV-2 infection at time points greater than 12 months (low strength of evidence [SoE]). Although most immunocompromised adults develop antibodies, the overall proportion with antibodies is lower compared with immunocompetent adults (moderate SoE for organ transplant patients and low SoE for patients with cancer or HIV). Prior infection provided substantial, sustained protection against symptomatic reinfection with the Delta variant (high SoE) and reduced the risk for severe disease due to Omicron variants (moderate SoE). Prior infection was less protective against reinfection with Omicron overall (moderate SoE), but protection from earlier variants waned rapidly (low SoE). LIMITATION: Single review for abstract screening and sequential review for study selection, data abstraction, and quality assessment. CONCLUSION: Evidence for a sustained antibody response to SARS-CoV-2 infection is considerable for both Delta and Omicron variants. Prior infection protected against reinfection with both variants, but, for Omicron, protection was weaker and waned rapidly. This information may have limited clinical applicability as new variants emerge. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality. (PROSPERO: CRD42020207098).

Expanding access to medications for opioid use disorder through locally-initiated implementation.

BACKGROUND: Despite demonstrated efficacy, medication treatment for opioid use disorder (MOUD) remain inaccessible to many patients, with barriers identified at the individual, clinic and system level. A wide array of implementation strategies have guided efforts to expand access to MOUD, with most centered around externally-facilitated approaches to practice change. While effective, such approaches may be inaccessible to those clinics and systems that lack the resources necessary to partner with an external team, suggesting a need to identify and describe change-processes that are internally developed and promoted. METHODS: Guided by the Consolidated Framework for Implementation Research (CFIR), we utilized qualitative interviews and ethnographic observation to investigate the planning, design and implementation of a locally-initiated process to expand access to MOUD within one health care system. All study documents were coded by a primary coder and secondary reviewer using a codebook designed for use with the CFIR. To analyze data, we reviewed text tagged by key codes, compared these textual excerpts both across and within documents, and organized findings into themes. Processes identified were mapped to established implementation science constructs and strategies. RESULTS: Interviews with clinicians and administrators (n = 9) and ethnographic observation of planning meetings (n = 3) revealed how a self-appointed local team developed, established broad support for, and successfully implemented a Primary Care-based Buprenorphine Clinic and E-Consult Service to expand access to MOUD to patients across the health care system. First, national and local policy changes-including altered clinical practice guidelines, performance pay incentives regarding opioid prescribing, and a directive from VA Central Office increased individual staff and administrators' perception of the need for change and willingness to invest time and resources. Then, a self-appointed interdisciplinary team utilized cross-clinic meetings and information gathering to identify appropriate, and widely supported, models of care delivery and care consultation. Finally, the team increased staff investment in these change efforts by bringing them into the planning process and encouraging collaborative problem solving. CONCLUSIONS: This study reveals how a local team developed and built widespread support for new processes of care that were tailored to local needs and well-positioned for sustainability over time.

Perioperative Management of Buprenorphine/Naloxone in a Large, National Health Care System: a Retrospective Cohort Study.

BACKGROUND: Medication for opioid use disorder, including buprenorphine and methadone, is considered the gold standard treatment for opioid use disorder (OUD). As the number of patients receiving buprenorphine has grown, clinicians increasingly care for patients prescribed buprenorphine who present for surgery and require management of perioperative pain. OBJECTIVE: To describe practice patterns of perioperative and post-surgical use of buprenorphine among patients prescribed buprenorphine for OUD who experience major surgery. DESIGN: Retrospective cohort study utilizing data from the VA Corporate Data Warehouse (CDW), a national repository of patient-level data. Data not accessible in CDW, including clinical instructions to patients to modify buprenorphine dose, were accessed via chart review. PARTICIPANTS: National sample of patients receiving care through the Veterans Health Administration. MAIN MEASURES: We report descriptive statistics on the incidence of buprenorphine dose hold prior to, during, and immediately following surgery, as well as post-surgical outcomes. Multivariable logistic regression identified socio-demographic and clinical characteristics associated with perioperative hold. KEY RESULTS: Our final sample comprised 183 patients, the majority of whom were white and male. Most patients (66%) experienced a perioperative buprenorphine dose hold: during the pre-operative, day of surgery, and post-operative periods, 40%, 62%, and 55% of patients had buprenorphine held. Buprenorphine dose hold was less likely for patients who had experienced homelessness/housing insecurity in the year prior to surgery (aOR = 0.25; 95% CI 0.10-0.61) as well as patients residing in rural areas (aOR=0.29; 0.12-0.68). Within the 12-month period following surgery, 122 patients (67%) were retained on buprenorphine, 10 patients (5.5%) had experienced an overdose, and 15 (8.2%) had died. CONCLUSIONS: We identified high rates of perioperative buprenorphine dose holds. As holding buprenorphine perioperatively does not align with emerging clinical recommendations and carries significant risks, educational campaigns or other provider-targeted interventions may be needed to ensure patients with OUD receive recommended care.

Adjunct interventions to standard medical management of buprenorphine in outpatient settings: A systematic review of the evidence.

BACKGROUND: A growing body of research has examined adjunctive interventions supportive of engagement and retention in treatment among patients receiving buprenorphine for opioid use disorder (OUD). We conducted a systematic review of the literature addressing the effect on key outcomes of adjunctive interventions provided alongside standard medical management of buprenorphine in outpatient settings. METHODS: We included prospective studies examining adults receiving buprenorphine paired with an adjunctive intervention for the treatment of OUD in an outpatient setting. Data sources included Medline, Cochrane Central Register of Controlled Trials, CINAHL and PsycINFO from inception through January 2020. Two raters independently reviewed full-text articles, abstracted data and appraised risk of bias. Outcomes examined included abstinence, retention in treatment and non-addiction-related health outcomes. RESULTS: The final review includes 20 manuscripts, 11 randomized control trials (RCTs), three secondary analyses of RCTs and six observational studies. Most studies examined psychosocial interventions (n = 14). Few examined complementary therapies (e.g., yoga; n = 2) or technological interventions (e.g., electronic pill dispensation; n = 3); one study examined an intervention addressing structural barriers to care (patient navigators; n = 1). Low risk of bias RCTs found no evidence that adding psychosocial interventions to buprenorphine treatment improves substance use outcomes. CONCLUSIONS: Research is needed to identify adjunctive interventions with potential to support medication adherence and addiction-related outcomes for patients engaged in buprenorphine treatment. Data from clinical trials suggest that lack of ready access to psychosocial treatments should not discourage clinicians from prescribing buprenorphine.

Antibody Response After SARS-CoV-2 Infection and Implications for Immunity : A Rapid Living Review.

BACKGROUND: The clinical significance of the antibody response after SARS-CoV-2 infection remains unclear. PURPOSE: To synthesize evidence on the prevalence, levels, and durability of detectable antibodies after SARS-CoV-2 infection and whether antibodies to SARS-CoV-2 confer natural immunity. DATA SOURCES: MEDLINE (Ovid), Embase, CINAHL, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, World Health Organization global literature database, and Covid19reviews.org from 1 January through 15 December 2020, limited to peer-reviewed publications available in English. STUDY SELECTION: Primary studies characterizing the prevalence, levels, and duration of antibodies in adults with SARS-CoV-2 infection confirmed by reverse transcriptase polymerase chain reaction (RT-PCR); reinfection incidence; and unintended consequences of antibody testing. DATA EXTRACTION: Two investigators sequentially extracted study data and rated quality. DATA SYNTHESIS: Moderate-strength evidence suggests that most adults develop detectable levels of IgM and IgG antibodies after infection with SARS-CoV-2 and that IgG levels peak approximately 25 days after symptom onset and may remain detectable for at least 120 days. Moderate-strength evidence suggests that IgM levels peak at approximately 20 days and then decline. Low-strength evidence suggests that most adults generate neutralizing antibodies, which may persist for several months like IgG. Low-strength evidence also suggests that older age, greater disease severity, and presence of symptoms may be associated with higher antibody levels. Some adults do not develop antibodies after SARS-CoV-2 infection for reasons that are unclear. LIMITATIONS: Most studies were small and had methodological limitations; studies used immunoassays of variable accuracy. CONCLUSION: Most adults with SARS-CoV-2 infection confirmed by RT-PCR develop antibodies. Levels of IgM peak early in the disease course and then decline, whereas IgG peaks later and may remain detectable for at least 120 days. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality. (PROSPERO: CRD42020207098).

Racial and Ethnic Disparities in COVID-19-Related Infections, Hospitalizations, and Deaths : A Systematic Review.

BACKGROUND: Data suggest that the effects of coronavirus disease 2019 (COVID-19) differ among U.S. racial/ethnic groups. PURPOSE: To evaluate racial/ethnic disparities in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection rates and COVID-19 outcomes, factors contributing to disparities, and interventions to reduce them. DATA SOURCES: English-language articles in MEDLINE, PsycINFO, CINAHL, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus, searched from inception through 31 August 2020. Gray literature sources were searched through 2 November 2020. STUDY SELECTION: Observational studies examining SARS-CoV-2 infections, hospitalizations, or deaths by race/ethnicity in U.S. settings. DATA EXTRACTION: Single-reviewer abstraction confirmed by a second reviewer; independent dual-reviewer assessment of quality and strength of evidence. DATA SYNTHESIS: 37 mostly fair-quality cohort and cross-sectional studies, 15 mostly good-quality ecological studies, and data from the Centers for Disease Control and Prevention and APM Research Lab were included. African American/Black and Hispanic populations experience disproportionately higher rates of SARS-CoV-2 infection, hospitalization, and COVID-19-related mortality compared with non-Hispanic White populations, but not higher case-fatality rates (mostly reported as in-hospital mortality) (moderate- to high-strength evidence). Asian populations experience similar outcomes to non-Hispanic White populations (low-strength evidence). Outcomes for other racial/ethnic groups have been insufficiently studied. Health care access and exposure factors may underlie the observed disparities more than susceptibility due to comorbid conditions (low-strength evidence). LIMITATIONS: Selection bias, missing race/ethnicity data, and incomplete outcome assessments in cohort and cross-sectional studies must be considered. In addition, adjustment for key demographic covariates was lacking in ecological studies. CONCLUSION: African American/Black and Hispanic populations experience disproportionately higher rates of SARS-CoV-2 infection and COVID-19-related mortality but similar rates of case fatality. Differences in health care access and exposure risk may be driving higher infection and mortality rates. PRIMARY FUNDING SOURCE: Department of Veterans Affairs, Veterans Health Administration, Health Services Research & Development. (PROSPERO: CRD42020187078).

Barriers and Facilitators to the Use of Medications for Opioid Use Disorder: a Rapid Review.

BACKGROUND: Despite evidence that medications to treat opioid use disorder (OUD) are effective, most people who could benefit from this treatment do not receive it. This rapid review synthesizes evidence on current barriers and facilitators to buprenorphine/naloxone and naltrexone at the patient, provider, and system levels to inform future interventions aimed at expanding treatment. METHODS: We systematically searched numerous bibliographic databases through May 2020 and selected studies published since 2014. Study selection, data abstraction, coding of barriers and facilitators, and quality assessment were first completed by one reviewer and checked by a second. RESULTS: We included 40 studies of buprenorphine (5 also discussed naltrexone). Four types of patient and provider-level barriers to OUD medication use emerged-stigma related to OUD medications, treatment experiences and beliefs (positive or negative), logistical issues (time and costs as well as insurance and regulatory requirements), and knowledge (high or low) of OUD and the role of medications. Stigma was the most common barrier among patients, while logistical issues were the most common barriers among providers. Facilitators for both patients and providers included peer supports. Most administrator-identified or system-level barriers and facilitators fit into the category of logistical issues. We have moderate confidence in buprenorphine findings but low confidence in naltrexone findings due to the small number of studies. DISCUSSION: Stigma, treatment experiences, logistical issues, and knowledge gaps are the main barriers associated with low utilization of OUD medications. These barriers can overlap and mutually reinforce each other, but given that, it is plausible that reducing one barrier may lead to reductions in others. The highest priority for future research is to evaluate interventions to reduce stigma. Other priorities for future research include better identification of barriers and facilitators for specific populations, such as those with OUD related to prescription opioids, and for naltrexone use. PROTOCOL REGISTRATION: PROSPERO; CRD42019133394.

Managing Acute Pain in Patients Taking Medication for Opioid Use Disorder: a Rapid Review.

BACKGROUND: Managing acute pain in patients with opioid use disorder (OUD) on medication (methadone, buprenorphine, or naltrexone) can be complicated by patients' higher baseline pain sensitivity and need for higher opioid doses to achieve pain relief. This review aims to evaluate the benefits and harms of acute pain management strategies for patients taking OUD medications and whether strategies vary by OUD medication type or cause of acute pain. METHODS: We systematically searched multiple bibliographic sources until April 2020. One reviewer used prespecified criteria to assess articles for inclusion, extract data, rate study quality, and grade our confidence in the body of evidence, all with second reviewer checking. RESULTS: We identified 12 observational studies-3 with control groups and 9 without. Two of the studies with control groups suggest that continuing buprenorphine and methadone in OUD patients after surgery may reduce the need for additional opioids and that ineffective pain management in patients taking methadone can result in disengagement in care. A third controlled study found that patients taking OUD medications may need higher doses of additional opioids for pain control, but provided insufficient detail to apply results to clinic practice. The only case study examining naltrexone reported that postoperative pain was managed using tramadol. We have low confidence in these findings as no studies directly addressed our question by comparing pain management strategies and few provided adequate descriptions of the dosage, timing, or rationale for clinical decisions. DISCUSSION: We lack rigorous evidence on acute pain management in patients taking medication for OUD; however, evidence supports the practice of continuing methadone or buprenorphine for most patients during acute pain episodes. Well-described, prospective studies of adjuvant pain management strategies when OUD medications are continued would add to the existing literature base. Studies on nonopioid treatments are also needed for patients taking naltrexone. PROTOCOL REGISTRATION: PROSPERO; CRD42019132924.

Benefits and Harms of Long-term Opioid Dose Reduction or Discontinuation in Patients with Chronic Pain: a Rapid Review.

BACKGROUND: Many clinicians are reevaluating the use of long-term opioid therapy (LTOT) for chronic pain in response to the opioid crisis and calls from organizations including the Centers for Disease Control & Prevention to limit prescribing of high-dose opioids. However, this practice change is occurring largely in the absence of data regarding patient outcomes. A 2017 systematic review found inconclusive evidence on the impact of LTOT dose reduction and discontinuation on pain severity and function, quality of life, withdrawal symptoms, substance abuse, and adverse effects. This rapid systematic review provides an updated evidence synthesis of patient outcomes following LTOT dose reduction including serious harms such as overdose and suicide. METHODS: We systematically searched numerous bibliographic databases from January 2017 (the end search date of the 2017 systematic review) through May 2020. One reviewer used prespecified criteria to assess articles for inclusion, evaluate study quality, abstract data, and grade strength of evidence, with a second reviewer checking. RESULTS: We included 49 studies-1 systematic review, 34 studies included in that systematic review, and 14 new studies. We prioritized evidence synthesis of 19 studies with the most applicability to the Veteran population and outpatient settings. Among these studies, improvements in mean pain scores were common among patients tapering opioids while participating in intensive multimodal pain interventions and mostly unchanged with less intensive or nonspecific co-interventions. Our confidence in these findings is low due to methodological limitations of the studies. Observational data suggests that serious harms such as opioid overdose and suicidal ideation can occur following opioid dose reduction or discontinuation, but the incidence of these harms at the population level is unknown. DISCUSSION: The net balance of benefits and harms of LTOT dose reduction for patients with chronic pain is unclear. Clinicians should closely monitor patients during the tapering process given the potential for harm.