Study Protocol for Pain Self-Management and Patient-Oriented Buprenorphine Dosing for Pain and Retention in Office-Based Opioid Treatment: A Hybrid Type 1, 2 × 2 Factorial Randomized Controlled Trial.

Chronic pain is a significant factor for patients with opioid use disorder (OUD) contributing to suboptimal retention in buprenorphine treatment, which is a crucial predictor of long-term health outcomes. This study aims to address the critical need for effective interventions targeting chronic pain management within office-based opioid treatment (OBOT) programs. We are conducting a multisite, hybrid type 1, 2 × 2 factorial randomized clinical trial to determine the effectiveness of 2 novel interventions, pain self-management (PSM) and patient-oriented buprenorphine dosing (POD), to decrease pain interference and improve retention in buprenorphine treatment. PSM, a manualized and customizable approach delivered through individual and peer-led group sessions, aims to decrease pain-related symptoms and quality of life. POD involves split dosing of buprenorphine to extend the duration of analgesia to better match its duration of efficacy at managing OUD symptoms, leading to improved retention in buprenorphine treatment. Eligible participants will be randomized into 1 of 4 groups: (1) PSM + POD, (2) PSM + Standard Buprenorphine Dosing, (3) Usual Care + POD, or (4) Usual Care + Standard Buprenorphine Dosing. Usual Care refers to usual care for chronic pain and Standard Buprenorphine Dosing refers to the participant's current dosing regimen. Secondary objectives encompass overall pain reduction, decreased opioid use, improved pain symptom management, and exploration of implementation strategies. The supplemental approved protocol provides comprehensive insights into the procedures and variables being investigated. As part of the HEAL Initiative®-funded Integrative Management of Chronic Pain and OUD for Whole Recovery (IMPOWR) network, this study aims to fill gaps in behavioral and medication treatments for individuals with co-occurring chronic pain and OUDs, improving pain management and retention in care. Successful outcomes from this trial may inform future larger trials, offering essential evidence for implementation considerations and reimbursement decisions.

Is There an Association Between Lateralization of Chronic Pain in the Body and Depression?

Depression commonly co-occurs with chronic pain and can worsen pain outcomes. Recent theoretical work has hypothesized that pain localized to the left hemibody is a risk factor for worse depression due to overlap in underlying neural substrates. This hypothesis has not been tested a priori. Using a large sample of treatment-seeking adults with mixed-etiology chronic pain (N = 1,185), our cross-sectional study tested whether patients with left-sided pain endorse worse depressive symptoms. We also examined differences in other pain-related functioning measures. We tested 4 comparisons based on painful body areas using the CHOIR body map: 1) only left-sided (OL) versus any right-sided pain; 2) only right-sided (OR) versus any left-sided pain; 3) OL versus OR versus bilateral pain; and 4) more left-sided versus more right-sided versus equal-sided pain. Analysis of variance models showed OL pain was not associated with worse depression (F = 5.50, P = .019). Any left-sided pain was associated with worse depression, though the effect was small (F = 8.58, P = .003, Cohens d = .29). Bilateral pain was associated with worse depression (F = 8.05, P < .001, Cohens d = .24-.33). Regardless of pain location, more body areas endorsed was associated with greater depression. Although a more rigorous assessment of pain laterality is needed, our findings do not support the hypothesis that left-lateralized pain is associated with worse depression. PERSPECTIVE: Pain lateralized to the left side of the body has been hypothesized as a risk factor for worse depression in chronic pain, despite never being tested in a large, real-world sample of patients with chronic pain. Findings showed that more widespread pain, not pain laterality, was associated with worse depression.

Trends in Patient Representation in Low Back Pain Pharmacological Randomized Clinical Trials, 2011 to 2020: A Systematic Review.

Low back pain (LBP) significantly affects global health, with associated detrimental outcomes such as physical impairment, emotional distress, and exacerbated mental health symptoms. This study evaluated the representation of marginalized groups, including racialized, gender minority, pregnant/lactating, and elderly individuals in randomized controlled trials for pharmacological interventions treating LBP from 2011 to 2020. We searched Embase, MEDLINE, and CINAHL in December 2021, and 139 studies were eligible. Most trials (n = 113, 81%) reported participant sex; however, no study collected data on sexual and gender minorities, and the majority (n = 99, 71%) excluded pregnant/lactating individuals. Most trials (n = 105, 76%) reported no data on participant race or ethnicity. We limited within-country analyses of race and ethnicity to US-based trials because US-based trials were more likely to report race and/or ethnicity (48%) compared to non-US-based trials (8%). Black participants were the only racialized group whose composition was comparable to US Census estimates. About half (n = 73, 53%) of all trials had an upper age limit for eligibility (range: 40-85 years old) and 24% (n = 33) excluded adults aged >65 years. Our findings confirm that trials for pharmacological LBP interventions underreport demographic data, and the trials that include this data have unrepresentative samples. There is an urgent need for more inclusive and representative patient samples to ensure generalizability and equitable benefits. Standardizing demographic data reporting and integrating community-based participatory research methods can help foster inclusive research practices. This review was registered with prospective register of systematic reviews (PROSPERO), ID 296017. PERSPECTIVE: This systematic review investigates patient representation in pharmacological-based clinical trials for low back pain, LBP, the most prevalent pain condition worldwide. Improvements in reporting demographic data and recruiting diverse participant populations-across different racialized, gender and sexual minority, and age groups-will help clinical research generalizability and provide equitable benefits.

When Direct Oral Anticoagulants Should Not Be Standard Treatment: JACC State-of-the-Art Review.

For most patients, direct oral anticoagulants (DOACs) are preferred over vitamin K antagonists for stroke prevention in atrial fibrillation and for venous thromboembolism treatment. However, randomized controlled trials suggest that DOACs may not be as efficacious or as safe as the current standard of care in conditions such as mechanical heart valves, thrombotic antiphospholipid syndrome, and atrial fibrillation associated with rheumatic heart disease. DOACs do not provide a net benefit in conditions such as embolic stroke of undetermined source. Their efficacy is uncertain for conditions such as left ventricular thrombus, catheter-associated deep vein thrombosis, cerebral venous sinus thrombosis, and for patients with atrial fibrillation or venous thrombosis who have end-stage renal disease. This paper provides an evidence-based review of randomized controlled trials on DOACs, detailing when they have demonstrated efficacy and safety, when DOACs should not be the standard of care, where their safety and efficacy are uncertain, and areas requiring further research.

Rural-urban differences in pulmonary embolism mortality by race-ethnicity and sex in the United States, 1999-2020.

INTRODUCTION: Racial and ethnic differences in pulmonary embolism (PE) mortality within rural and urban regions in the U.S. have not previously been described. PE mortality may vary across regions and urbanization given disparities in social and structural determinants and comorbid disease. METHODS: Using surveillance data from the Centers for Disease Control and Prevention, age-adjusted mortality rates (AAMR) related to PE were calculated for rural and urban regions in the U.S., in non-Hispanic Black and White women and men, between 1999 and 2020. RESULTS: Among 137,946 deaths in urban regions and 41,333 deaths in rural regions due to PE during this period, AAMR decreased 1.8% per year in urban regions from 3.1 to 100,000 in 1999 to 2.2 per 100,000 in 2020, and decreased 1% per year in rural regions from 4.3 to 100,000 in 1999 to 3.3 per 100,000 in 2020. Since 2008, AAMR from PE increased in non-Hispanic White males in rural and urban regions, decreased in non-Hispanic Black females in rural regions, and otherwise remained stagnant in all other race-sex groups. CONCLUSIONS: AAMR from PE was higher in rural compared with urban individuals, with differences by race and sex. Mortality rates remained stagnant over the last decade in non-Hispanic Black adults and non-Hispanic White females and increased in non-Hispanic White males.

Venous thromboembolism prevention in cancer care: implementation strategies to address underuse.

Background: Evidenced-based interventions have been developed to prevent venous thromboembolism (VTE) in ambulatory patients with cancer, including VTE-risk assessment for all patients and targeted primary thromboprophylaxis for high-risk patients. Despite supportive evidence and recommendations, oncologists rarely assess VTE risk or provide primary prophylaxis. Our previous work identified barriers and facilitators to using VTE prevention interventions in oncology practice. Objectives: To identify potential strategies that address the identified barriers and leverage facilitators to achieve successful implementation of evidence-based interventions for VTE prevention in oncology practice. Methods: We used the Implementation Research Logic Model, an implementation science framework, to map the relationships among barriers and facilitators, feasible and effective implementation strategies, and implementation and clinical outcomes that will be used to evaluate the implementation strategies. Results: We identified 12 discrete implementation strategies (eg, conducting clinician education and training and staged implementation scale-up) that address barriers and leverage facilitators through their mechanisms of action (eg, increased clinician awareness of evidence and targeting the highest effectiveness). We identified key implementation (eg, penetration, adoption, acceptability, fidelity, appropriateness, and sustainability), system (eg, integration of VTE-risk assessment into clinical workflow), and clinical (eg, lower VTE rates) outcomes targeted by the selected strategies. Conclusion: Using the Implementation Research Logic Model framework and building on our knowledge of barriers and facilitators, we identified implementation strategies and important outcomes to evaluate these strategies. We will use these results to test and measure the strategies to improve the uptake of evidence-based recommendations for VTE prevention in oncology practice.

Innovative treatment formats, technologies, and clinician trainings that improve access to behavioral pain treatment for youth and adults.

Chronic pain is prevalent across the life span and associated with significant individual and societal costs. Behavioral interventions are recommended as the gold-standard, evidence-based interventions for chronic pain, but barriers, such as lack of pain-trained clinicians, poor insurance coverage, and high treatment burden, limit patients' ability to access evidenced-based pain education and treatment resources. Recent advances in technology offer new opportunities to leverage innovative digital formats to overcome these barriers and dramatically increase access to high-quality, evidenced-based pain treatments for youth and adults. This scoping review highlights new advances. First, we describe system-level barriers to the broad dissemination of behavioral pain treatment. Next, we review several promising new pediatric and adult pain education and treatment technology innovations to improve access and scalability of evidence-based behavioral pain treatments. Current challenges and future research and clinical recommendations are offered.

Improving Judicious Use of Heparin-Induced Thrombocytopenia Testing Through Electronic Health Record-Based Intervention.

BACKGROUND: Heparin-induced thrombocytopenia (HIT) is an immune-mediated drug reaction that can cause thromboembolism in the setting of thrombocytopenia. An enzyme-linked immunosorbent assay (ELISA)-based assay to screen for HIT antibodies (HAb) is available but has relatively low specificity and a correspondingly high false positive rate. The 4Ts score has been validated to determine the pretest probability of HIT. The authors hypothesized that an electronic health record (EHR)-based clinical decision support (CDS) tool incorporating the 4Ts score would reduce the volume of HAb orders. METHODS: After implementing a CDS tool into the EHR, the researchers retrospectively evaluated the impact from November 2019 to October 2021, compared to a preintervention period (January to October 2019). The primary outcome was average tests per month. Secondary outcomes included rates of tests ordered per total inpatient encounters and proportion of HAb sent despite low 4Ts score in the postintervention study period. RESULTS: Of 1,833 HAb sent during the study period, 1,217 occurred in the postintervention period. In the postintervention period compared with the preintervention period, the average orders per month was 50.5 (standard deviation [SD] 9.7) vs. 61.6 (SD 7.2) (p = 0.003), and the order incidence rate was 8.0 per 1,000 patient encounters postintervention vs. 9.2 per 1,000 patient encounters preintervention (rate ratio [RR] 0.87, 95% confidence interval [CI] 0.79-0.96, p = 0.002). Postintervention, 252 (20.7%) had a 4Ts score calculated as low probability, 759 (62.4%) as intermediate probability, and 131 (10.8%) as high probability, and 75 had no associated 4Ts score. CONCLUSION: Implementation of a simple CDS tool reduced the rate of HAb orders, reducing unnecessary HAb testing.

Effects of hypnosis, mindfulness meditation, and education for chronic pain on substance use in veterans: A supplementary analysis of a randomized clinical trial.

PURPOSE/OBJECTIVE: To examine the impact of three behavioral interventions for chronic pain on substance use. RESEARCH METHOD/DESIGN: Participants were 328 Veterans with chronic pain receiving care at one of two Veterans Affairs Medical Centers in the northwest United States. Participants were randomly assigned to one of three 8-week manualized in-person group treatments: (a) hypnosis (HYP), (b) mindfulness meditation (MM), or (c) active education control (ED). Substance use frequency was assessed using 10 individual items from the WHO-ASSIST, administered at baseline prior to randomization and at 3- and 6-month posttreatment. RESULTS: Baseline substance use (i.e., any use) in the past 3 months was reported by 22% (tobacco), 27% (cannabis), and 61% (alcohol) of participants. Use of all other substances assessed was reported by < 7% of participants. Results showed that MM, as compared to ED, significantly reduced risk of daily cannabis use by 85% and 81% at the 3- and 6-month posttreatment follow-ups, respectively, after adjusting for baseline use. HYP, as compared to ED, significantly reduced risk of daily cannabis use by 82% at the 6-month posttreatment follow-up after adjusting for baseline use. There was no intervention effect on tobacco or alcohol use at either posttreatment follow-up. CONCLUSIONS/IMPLICATIONS: HYP and MM for chronic pain may facilitate reductions in cannabis use, even when reducing such use is not a focus of treatment. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

A safe and effective use of caplacizumab in pregnancy-related acquired thrombotic thrombocytopenic purpura.

Thrombotic thrombocytopenic purpura (TTP) is not uncommonly seen in pregnancy, either with the first episode or with the exacerbation of known disease. The management of TTP in pregnancy can be challenging if there is refractoriness to the use of therapeutic plasma exchange (TPE) and high-dose corticosteroids. Caplacizumab, a vWF-directed humanized antibody fragment, is approved for the treatment of acquired TTP but there is sparse data on its use in pregnant patients. Antenatal and peripartum haemorrhage is a theoretical concern with the use of the medication in the obstetric population. However, as options for treatment of TTP in the patients who have refractory disease are significantly limited, off-label use of caplacizumab to achieve disease control and prevent maternofetal morbidity and mortality is a reasonable consideration. This article described the successful use of caplacizumab in a pregnant patient with acquired TTP and the associated favourable outcome. The patient suffered an exacerbation following initial TPE and became refractory to both plasma exchange and high-dose corticosteroids. Off-label use of caplacizumab resulted in hematologic recovery and successful delivery of a healthy neonate. This case represents a contribution to the sparse literature on the use of this effective medication in an often-challenging clinical situation.

DOAC compared with warfarin for VTE in patients with obesity: a retrospective cohort study conducted through the VENUS network.

The effectiveness and safety of direct oral anticoagulants (DOAC) compared with warfarin remains uncertain in obese patients. We assessed the comparative effectiveness and safety of DOACs with warfarin for the treatment of VTE among obese patients. This multi-center retrospective cohort study included adults with a BMI ≥ 35 kg/m2 or weight ≥ 120 kg prescribed either DOAC (apixaban, dabigatran, edoxaban, rivaroxaban) or warfarin for a VTE diagnosis. The primary outcome was the 12-month rate of recurrent VTE. The secondary outcome was the 12-month rate of major bleeding. Among 5626 patients, 67% were prescribed warfarin and 33% were prescribed a DOAC. The 12-month VTE recurrence rate was 3.6% (67/1823) for patients treated with DOAC compared with 3.8% (143/3664) for patients treated with warfarin [odds ratio for recurrent VTE on warfarin versus DOAC (OR) (95% CI).07 (0.80, 1.45)]. The 12-month major bleeding rate was 0.5% (10/1868) for patients on DOAC versus 2.4% (89/3758) on warfarin [OR 4.25 (2.19, 8.22)]. Similar proportions of recurrent VTE occurred across BMI thresholds on DOAC and warfarin: for BMI ≥ 35 kg/m2 (N = 5412), 3.6% versus 3.8%, respectively [OR 1.08 (0.80, 1.46)]; for BMI ≥ 40 kg/m2 (N = 2321), 4.4% versus 3.5%, respectively [OR 0.80 (0.51, 1.26)]; and for BMI ≥ 50 kg/m2 (N = 560), 3.1% versus 3.7%, respectively [OR 1.18 (0.39, 3.56)]. Similar proportions of recurrent VTE occurred in patients with obesity treated for VTE with DOACs and warfarin. DOACs were associated with lower major bleeding compared to warfarin in patients with obesity and VTE.

Hereditary thrombotic thrombocytopenic purpura acquired through liver transplantation: A case report.

A 62-year-old received orthotopic liver transplantation. Three weeks later, thrombotic microangiopathy developed. Testing revealed thrombotic thrombocytopenic purpura (TTP) characterized by low ADAMTS13 (A Disintegrin-like Metallopeptidase with ThromboSpondin type 1 motif 13) activity and no inhibitor of ADAMTS13 protein. Retrospective attainment of donor records revealed a TTP diagnosis, presumably hereditary TTP (hTTP), as an ADAMTS13 protein inhibitor was not mentioned. As the grafted liver does not produce ADAMTS13 protein, the recipient now functionally has hTTP and will likely need plasma transfusions indefinitely. While hTTP is extremely rare, it should be considered a contraindication to liver donation outside of exceptional circumstances. If a potential liver donor has TTP listed on medical history, attempts should be made to determine whether it is autoimmune or hereditary. An accurate medical history is critical as it is the only reliable way to identify hTTP, as outside of acute exacerbations of TTP, donors with hTTP can have normal laboratory values, including normal hemoglobin, platelets, and renal function.

Primary Care Clinicians' Prescribing Patterns of Reduced-Dose Direct Oral Anticoagulants for Extended-Phase Venous Thromboembolism Treatment.

The direct anticoagulants (DOACs), apixaban and rivaroxaban, are used for extended-phase treatment of venous thromboembolism (VTE) and have labeling for dose reduction for this indication. The objective of this study was to better understand primary care clinician prescribing patterns of apixaban and rivaroxaban for extended-phase anticoagulation. We conducted a 21-question survey targeting members of the American College of Physicians and United States Veterans Administration anticoagulation management services. Survey questions covered prescribing behaviors for dose reduction of apixaban and rivaroxaban for extended VTE treatment, as well as questions related to the respondent's practice setting. We used logistic regression to assess associations between demographics and prescribing behaviors. We used k-means clustering to identify distinct groups of prescribing patterns. Among 227 respondents, most were attending physicians (60%) and one-third (34%) practiced in internal medicine or primary care. Most (59%) indicated they dose-reduced DOACs. Hospitalists (no outpatient care) were least likely to dose-reduce (OR 0.09 [95% CI 0.03-0.22]), as well as early-career clinicians (0.53 [0.30-0.91]). Pharmacists and clinicians who treat over 500 VTE patients annually were most likely to dose reduce (6.4 [2.9-16.3]), (2.9 [1.5-6.0]), respectively. We identified five clusters of dosing behaviors and characterized clinician makeup. Clusters were primarily differentiated by frequency of dose reduction, DOAC preference, and temporary re-escalation of doses. We identified clinician characteristics that are associated with dose-reduction prescribing behaviors; these analyses provide insight into where targeted interventions, such as protocolization and education, would be most beneficial.