A programmable dual-targeting siRNA scaffold supports potent two-gene modulation in the central nervous system.

Divalent short-interfering RNA (siRNA) holds promise as a therapeutic approach allowing for the sequence-specific modulation of a target gene within the central nervous system (CNS). However, an siRNA modality capable of simultaneously modulating gene pairs would be invaluable for treating complex neurodegenerative disorders, where more than one pathway contributes to pathogenesis. Currently, the parameters and scaffold considerations for multi-targeting nucleic acid modalities in the CNS are undefined. Here, we propose a framework for designing unimolecular 'dual-targeting' divalent siRNAs capable of co-silencing two genes in the CNS. We systematically adjusted the original CNS-active divalent siRNA and identified that connecting two sense strands 3' and 5' through an intra-strand linker enabled a functional dual-targeting scaffold, greatly simplifying the synthetic process. Our findings demonstrate that the dual-targeting siRNA supports at least two months of maximal distribution and target silencing in the mouse CNS. The dual-targeting divalent siRNA is highly programmable, enabling simultaneous modulation of two different disease-relevant gene pairs (e.g. Huntington's disease: MSH3 and HTT; Alzheimer's disease: APOE and JAK1) with similar potency to a mixture of single-targeting divalent siRNAs against each gene. This work enhances the potential for CNS modulation of disease-related gene pairs using a unimolecular siRNA.

Eukaryotic release factor 1 from Euplotes promotes frameshifting at premature stop codons in human cells.

Human physiology is highly susceptible to frameshift mutations within coding regions, and many hereditary diseases and cancers are caused by such indels. Presently, therapeutic options to counteract them are limited and, in the case of direct genome editing, risky. Here, we show that release factor 1 (eRF1) from Euplotes, an aquatic protist known for frequent +1 frameshifts in its coding regions, can enhance +1 ribosomal frameshifting at slippery heptameric sequences in human cells without an apparent requirement for an mRNA secondary structure. We further show an increase in frameshifting rate at the premature termination sequence found in the HEXA gene of Tay-Sachs disease patients, or a breast cancer cell line that harbors a tumor-driving frameshift mutation in GATA3. Although the overall increase in frameshifting would need further improvement for clinical applications, our results underscore the potential of exogenous factors, such as Eu eRF1, to increase frameshifting in human cells.

The Báa nnilah Program: Results of a Chronic-Illness Self-Management Cluster Randomized Trial with the Apsáalooke Nation.

Indigenous people in Montana are disproportionately affected by chronic illness (CI), a legacy of settler colonialism. Existing programs addressing CI self-management are not appropriate because they are not consonant with Indigenous cultures in general and the Apsáalooke culture specifically. A research partnership between the Apsáalooke (Crow Nation) non-profit organization Messengers for Health and Montana State University co-developed, implemented, and evaluated a CI self-management program for community members. This article examines qualitative and quantitative program impacts using a pragmatic cluster randomized clinical trial design with intervention and waitlist control arms. The quantitative and qualitative data resulted in different stories on the impact of the Báa nnilah program. Neither of the quantitative hypotheses were supported with one exception. The qualitative data showed substantial positive outcomes across multiple areas. We examine why the data sets led to two very different stories, and provide study strengths and limitations, recommendations, and future directions.

Developing and Implementing a Culturally Consonant Treatment Fidelity Support Plan with the Apsáalooke Nation.

Treatment fidelity remains underreported in health intervention research, particularly among Indigenous communities. One explanation for this gap is the lack of culturally consonant strategies listed in the National Institutes of Health (NIH) Behavior Change Consortium (BCC) treatment fidelity framework, the gold standard for understanding and measuring fidelity. This paper focuses on the development and implementation of a culturally consonant treatment fidelity support plan across two of the five BCC fidelity areas, provider training and treatment delivery, within a chronic illness self-management program for the Apsáalooke (Crow) Nation. Our team selected and adapted strategies from, and added strategies to, the BCC framework, that centered on relational accountability and the Apsáalooke culture. To be culturally consonant, we approached treatment fidelity as supporting Aakbaabaaniilea (Apsáalooke program facilitators) rather than monitoring them. This resulted in the development of a fifth treatment fidelity area: building and fostering relationships. We propose that fidelity to relational accountability is the foundation of successful programs in Indigenous communities. This suggests an important shift from tracking what was conducted in an intervention to prioritizing how things were conducted. We encourage others to view the BCC framework as a starting point in developing fidelity strategies that are consonant with local cultures.

A study of the impact of the COVID-19 pandemic on equine veterinary care in the UK.

Background: During the COVID-19 pandemic, equine health care in the UK may have been adversely affected due to mandated changes in the delivery of veterinary healthcare and the potential for reduced health-seeking behaviour. Methods: Electronic patient records (EPRs) were analysed to describe veterinary activity for all equids under the active care of 20 veterinary practices in the UK in the 12 months before and after the introduction of the first UK lockdown. Pre-pandemic and pandemic levels of clinical activity were compared. Further comparisons of care, including immediate management and treatment, were made following a detailed review of EPRs from randomly selected subsets of equids under care in four time periods. Results: All measures of activity and face-to-face interaction were lower in the early pandemic period than in the equivalent pre-pandemic period. Compared to pre-pandemic, the early pandemic was associated with a decrease in prophylactic care and non-urgent diagnostic imaging and an increase in systemic non-steroid anti-inflammatory prescription. Convenience sampling of veterinary practices may have limited the generalisability of the findings. The quality of EPRs was variable. Conclusions: While equine veterinary activity was significantly disrupted in the early pandemic period, there was a rapid return to pre-pandemic levels of activity. Subsequent lockdowns appeared to have had little effect on veterinary care.

Setting sail: Maneuvering SHP2 activity and its effects in cancer.

Since the discovery of tyrosine phosphorylation being a critical modulator of cancer signaling, proteins regulating phosphotyrosine levels in cells have fast become targets of therapeutic intervention. The nonreceptor protein tyrosine phosphatase (PTP) coded by the PTPN11 gene "SHP2" integrates phosphotyrosine signaling from growth factor receptors into the RAS/RAF/ERK pathway and is centrally positioned in processes regulating cell development and oncogenic transformation. Dysregulation of SHP2 expression or activity is linked to tumorigenesis and developmental defects. Even as a compelling anti-cancer target, SHP2 was considered "undruggable" for a long time owing to its conserved catalytic PTP domain that evaded drug development. Recently, SHP2 has risen from the "undruggable curse" with the discovery of small molecules that manipulate its intrinsic allostery for effective inhibition. SHP2's unique domain arrangement and conformation(s) allow for a truly novel paradigm of inhibitor development relying on skillful targeting of noncatalytic sites on proteins. In this review we summarize the biological functions, signaling properties, structural attributes, allostery and inhibitors of SHP2.

Personality and insomnia: A systematic review and narrative synthesis.

The inherent nature of personality serves as a predisposing, and possible maintaining, factor of insomnia. However, methodological differences limit the ability to draw causal conclusions regarding the specific traits involved in the aetiology of the disorder. This systematic review of the relationship between insomnia and personality provides a narrative synthesis of the literature to date. Here, we identified N = 76 studies meeting the inclusion/exclusion criteria. The outcomes reliably evidenced the experience of insomnia to be associated with personality traits that are typically considered to be negative or maladaptive in nature. More specifically, insomnia was related to neuroticism, introversion, perfectionistic doubts and concerns, elevated personal standards, negative affect, social inhibition and avoidance, hysteria, hypochondriasis, psychasthenia, impulsive behaviour, anger, hostility, and psychopathic tendencies, schizotypal and borderline traits, reduced conscientiousness and self-directedness, and negatively perceived perception of the self. Several studies examined the role that personality plays in predicting the treatment efficacy and adherence of CBTi. Moving forward, longitudinal research, methodological consistency, the mediating role of treatment outcomes and adherence, and clinical and population representative samples should be prioritised. Methodological strengths and limitations of the literature are discussed alongside the next steps that should be taken to advance our understanding of the literature.

Prevalence of anxiety, depression, mania, insomnia, stress, suicidal ideation, psychotic experiences, & loneliness in UK university students.

Despite existing wellbeing services, university students remain particularly vulnerable to mental health difficulties. Therefore, this study was designed to provide a comprehensive assessment of the prevalence of psychiatric symptoms by using well validated scales with robust psychometric properties. More specifically, the current data provides crucial information concerning the prevalence of anxiety, depression, mania, insomnia, stress, suicidal ideation, psychotic experiences and loneliness amongst a sample of N = 1408 UK university students. A cross-sectional online questionnaire-based study was implemented. Online recruitment for this dataset began on September 17th, 2018, and ended on the 30th July 2019. Eight validated measures were used: Generalized Anxiety Disorder Scale; Patient Health Questionnaire; The Mood Disorder Questionnaire; The Sleep Condition Indicator; The Perceived Stress Scale; Suicidal Behaviours Questionnaire-Revised; The Prodromal Questionnaire 16 (PQ-16); and the University of California Loneliness Scale. The dataset is available to other researchers and is provided on figshare. Information concerning the data records, usage notes, code availability and technical validation are presented. Finally, we present demographic information concerning psychiatric symptom prevalence.

Intratumoral pan-ErbB targeted CAR-T for head and neck squamous cell carcinoma: interim analysis of the T4 immunotherapy study.

BACKGROUND: Locally advanced/recurrent head and neck squamous cell carcinoma (HNSCC) is associated with significant morbidity and mortality. To target upregulated ErbB dimer expression in this cancer, we developed an autologous CD28-based chimeric antigen receptor T-cell (CAR-T) approach named T4 immunotherapy. Patient-derived T-cells are engineered by retroviral transduction to coexpress a panErbB-specific CAR called T1E28ζ and an IL-4-responsive chimeric cytokine receptor, 4αß, which allows IL-4-mediated enrichment of transduced cells during manufacture. These cells elicit preclinical antitumor activity against HNSCC and other carcinomas. In this trial, we used intratumoral delivery to mitigate significant clinical risk of on-target off-tumor toxicity owing to low-level ErbB expression in healthy tissues. METHODS: We undertook a phase 1 dose-escalation 3+3 trial of intratumoral T4 immunotherapy in HNSCC (NCT01818323). CAR T-cell batches were manufactured from 40 to 130 mL of whole blood using a 2-week semiclosed process. A single CAR T-cell treatment, formulated as a fresh product in 1-4 mL of medium, was injected into one or more target lesions. Dose of CAR T-cells was escalated in 5 cohorts from 1×107-1×109 T4+ T-cells, administered without prior lymphodepletion. RESULTS: Despite baseline lymphopenia in most enrolled subjects, the target cell dose was successfully manufactured in all cases, yielding up to 7.5 billion T-cells (67.5±11.8% transduced), without any batch failures. Treatment-related adverse events were all grade 2 or less, with no dose-limiting toxicities (Common Terminology Criteria for Adverse Events V.4.0). Frequent treatment-related adverse events were tumor swelling, pain, pyrexias, chills, and fatigue. There was no evidence of leakage of T4+ T-cells into the circulation following intratumoral delivery, and injection of radiolabeled cells demonstrated intratumoral persistence. Despite rapid progression at trial entry, stabilization of disease (Response Evaluation Criteria in Solid Tumors V.1.1) was observed in 9 of 15 subjects (60%) at 6 weeks post-CAR T-cell administration. Subsequent treatment with pembrolizumab and T-VEC oncolytic virus achieved a rapid complete clinical response in one subject, which was durable for over 3 years. Median overall survival was greater than for historical controls. Disease stabilization was associated with the administration of an immunophenotypically fitter, less exhausted, T4 CAR T-cell product. CONCLUSIONS: These data demonstrate the safe intratumoral administration of T4 immunotherapy in advanced HNSCC.

Choosing wisely: Enteral feeding tube selection, placement, and considerations before and beyond the procedure room.

When an enteral feeding tube (EFT) is placed, it is not always known how long this nutrition support intervention will be needed. As a result, the type of device the patient originally has placed may not match the function it is required to serve or the lifestyle needs of the patient throughout their enteral nutrition journey. Medicare considers an EFT a prosthetic device, as it is replacing a permanently inoperable or nonfunctioning organ. If we think about an EFT the same way we think about a prosthetic limb, one that needs to be customized to meet all of the patient's functional and lifestyle needs, we can also begin to think beyond the procedure room and carefully consider a variety of factors that impact the patient at home receiving enteral nutrition. Proper fit, function, and style is essential in order for the patient to have a positive relationship with their EFT, contributing to their successful home enteral nutrition experience. Clinicians who care for these patients in any setting and in any capacity would benefit from enhancing their understanding of available EFT options, their design components, and available methods of placement. Many home care and outpatient clinicians adopt the role of patient advocate as it relates to a patient's enteral nutrition journey, and this expanded knowledge could be used to benefit the patient by improving their overall enteral nutrition experience and ultimately their relationship with their "prosthetic."

The associations among childhood trauma, loneliness, mental health symptoms, and indicators of social exclusion in adulthood: A UK Biobank study.

AIMS: Childhood trauma has been associated with adult psychosocial outcomes linked to social exclusion. However, the strength of these associations in the general population is unknown. The emergence of the UK Biobank, with rich phenotypic characterization of the adult population, affords the exploration of the childhood determinants of adult psychopathology with greater statistical power. The current study aims to explore (1) the associations between childhood trauma and social exclusion in adulthood and (2) the role that self-reported loneliness and symptoms of distress play in the associations. METHODS: This study was an analysis of 87,545 participants (mean [± SD] age = 55.68 [7.78], 55.0% female, 97.4% White) enrolled in the UK Biobank. Childhood trauma was determined by the five-item Childhood Trauma Screener. Current loneliness and symptoms of anxiety (Generalized Anxiety Disorder Scale-7) and depression (Patient Health Questionnaire-9) were also entered in analyses. Outcomes were "limited social participation," "area deprivation," "individual deprivation," and "social exclusion" from a previously determined dimensional measure of social exclusion in the UK Biobank. RESULTS: Hierarchical multiple regression models indicated small associations between childhood trauma and social exclusion outcomes, explaining between 1.5% and 5.0% of the variance. Associations weakened but remained significant when loneliness, anxiety, and depression were entered in the models; however, anxiety symptoms demonstrated a negative association with "individual deprivation" and "social exclusion" in the final models. Depression was most strongly associated with "individual deprivation," "area deprivation," and "social exclusion" followed by childhood trauma. Loneliness was most strongly associated with "limited social participation." CONCLUSIONS: Experiences of childhood trauma can increase the propensity for adulthood social exclusion. Loneliness and symptoms of depression attenuate but do not eliminate these associations. Anxiety symptoms have a potentially protective effect on the development of "individual deprivation." Findings add to the growing body of literature advocating for trauma-informed approaches in a variety of settings to help ameliorate the effects of childhood trauma on adult psychosocial outcomes. Further research, however, is required.

Use of antimicrobials licensed for systemic administration in UK equine practice.

BACKGROUND: Judicious antimicrobial use (AMU) is important for preserving therapeutic effectiveness. Large-scale studies of antimicrobial prescribing can provide clinical benchmarks and help identify opportunities for improved stewardship. OBJECTIVES: To describe systemic AMU in UK equine practice and identify factors associated with systemic and Category B (third and fourth generation cephalosporins, quinolones and polymixins) AMU. STUDY DESIGN: Retrospective cohort. METHODS: Anonymised electronic patient records (EPRs) for all equids attended by 39 UK veterinary practices between 1 January and 31 December 2018 were collected via the VetCompass programme. Systemic antimicrobial prescriptions were identified using electronic keyword searches. Indications for AMU were determined through manual review of a randomly selected subset of EPRs. The types and frequency of systemic antimicrobials prescribed and indications were summarised using descriptive statistics. Mixed-effects logistic regression was used to evaluate practice- and horse-related risk factors. RESULTS: Systemic antimicrobials were prescribed to 12 538 (19.5%, 95% confidence interval [CI]: 19.2%-19.8%) of 64 322 equids attended in 2018. Category B antimicrobials were prescribed to 1.9% (95% CI: 1.8%-2.0%) of attended equids and in 8.9% (95% CI: 8.5%-9.4%) of antimicrobial courses. Bacteriological culture was performed in 19.1% (95% CI: 17.1%-21.3%) of Category B antimicrobial courses. The most commonly prescribed antimicrobial classes were potentiated sulphonamides (50.2% of equids receiving antimicrobials) and tetracyclines (33.5% of equids receiving antimicrobials). Integumentary disorders were the most common reason for systemic AMU (40.5% of courses). Urogenital disorders were the most common reason for Category B AMU (31.1% of courses). Increased odds of systemic and Category B AMU were observed in equids <1 year compared with those aged 5-14 years. Breed was associated with AMU, with odds of systemic and Category B AMU highest in Thoroughbreds and Thoroughbred crosses. MAIN LIMITATIONS: Convenience sample of practices may limit generalisability. CONCLUSIONS: Empirical use of Category B antimicrobials remains commonplace.

A programmable dual-targeting di-valent siRNA scaffold supports potent multi-gene modulation in the central nervous system.

Di-valent short interfering RNA (siRNA) is a promising therapeutic modality that enables sequence-specific modulation of a single target gene in the central nervous system (CNS). To treat complex neurodegenerative disorders, where pathogenesis is driven by multiple genes or pathways, di-valent siRNA must be able to silence multiple target genes simultaneously. Here we present a framework for designing unimolecular "dual-targeting" di-valent siRNAs capable of co-silencing two genes in the CNS. We reconfigured di-valent siRNA - in which two identical, linked siRNAs are made concurrently - to create linear di-valent siRNA - where two siRNAs are made sequentially attached by a covalent linker. This linear configuration, synthesized using commercially available reagents, enables incorporation of two different siRNAs to silence two different targets. We demonstrate that this dual-targeting di-valent siRNA is fully functional in the CNS of mice, supporting at least two months of maximal target silencing. Dual-targeting di-valent siRNA is highly programmable, enabling simultaneous modulation of two different disease-relevant gene pairs (e.g., Huntington's disease: MSH3 and HTT; Alzheimer's disease: APOE and JAK1) with similar potency to a mixture of single-targeting di-valent siRNAs against each gene. This work potentiates CNS modulation of virtually any pair of disease-related targets using a simple unimolecular siRNA.

Comparison of the pharmacokinetics of continuous and intermittent infusions of ampicillin-sulbactam in dogs with septic peritonitis.

OBJECTIVE: To evaluate the time-course of ampicillin-sulbactam and percentage of time that its concentration is above a given MIC (T% > MIC) in dogs with septic peritonitis when delivered as either a continuous infusion (CI) or intermittent infusion (II). ANIMALS: 11 dogs with septic peritonitis. PROCEDURES: Dogs were randomized to receive ampicillin-sulbactam as either CI or II. Continuous infusions were delivered as a 50 mg/kg bolus IV followed by a rate of 0.1 mg/kg/min. Intermittent infusions were administered as 50 mg/kg IV q8h. Serum ampicillin-sulbactam concentrations were measured at hours 0, 1, 6, and every 12 hours after until patients were transitioned to an oral antimicrobial equivalent. All other care was at the discretion of the attending clinician. Statistical analysis was used to determine each patient's percentage of time T% > MIC for 4 MIC breakpoints (0.25, 1.25, 8, and 16 µg/mL). RESULTS: No dogs experienced adverse events related to ampicillin-sulbactam administration. Both CI and II maintained a T% > MIC of 100% of MIC 0.25 µg/mL and MIC 1.25 µg/mL. The CI group maintained a higher T% > MIC for MIC 8 µg/mL and MIC 16 µg/mL; however, these differences did not reach statistical significance (P = .15 and P = .12, respectively). CLINICAL RELEVANCE: This study could not demonstrate that ampicillin-sulbactam CI maintains a greater T% > MIC in dogs with septic peritonitis than II; however, marginal differences were noted at higher antimicrobial breakpoints. While these data support the use of antimicrobial CI in septic and critically ill patients, additional prospective trials are needed to fully define the optimal doses and the associated clinical responses.

Long-Term Hearing Results of Endoskeletal Ossicular Reconstruction in Chronic Ears Using Titanium Prostheses Having a Helical Coil: Part 1-Kraus K-Helix Crown, Incus to Stapes.

OBJECTIVES: 1) To assess long-term hearing results after endoskeletal ossicular chain reconstruction (eOCR) using the titanium Kraus K-Helix Crown prosthesis, implanted incus to stapes, with glass-ionomer cement (GIC) in chronic ears and 2) to determine safety of the prosthesis and cement. STUDY DESIGN: Prospective, nonrandomized, sequential, single center, single surgeon. SETTING: Private practice, ambulatory surgical center. PATIENTS: N = 15 males (42%) and 21 females (58%). Mean age was 40.4 years (range, 6-81 years); 38 ears (22 right ears [58%] and 16 left ears [42%]). INTERVENTIONS: eOCR in chronic ears. Comprehensive preoperative and postoperative hearing measurements were performed for up to 9 years. MAIN OUTCOME MEASURES: Postoperative hearing results at 1 year showed statistically significant improvement as compared with preoperative hearing. Long-term hearing results remained stable and showed no statistically significant change over 9 years. RESULTS: Estimated mean pure-tone air conduction average improved by 14.5 dB (95% confidence interval = 10.3-18.7). Estimated mean speech reception thresholds improved by 15.5 dB (10.8-20.2). Word recognition scores improved by -2.2% (-5.3 to 1.0). The estimated mean postoperative air-bone gap was 10.5 dB (7.2-13.8). The estimated mean calculated air-bone gap was 11.3 dB (8.0-14.5). The estimated mean change in high-tone bone conduction (HTBC) average was +3.5 dB (0.9-6.0). Two prostheses extruded (5%). No patients experienced any unanticipated serious adverse effects or events. CONCLUSION: eOCR using the K-Helix Crown prosthesis, incus to stapes, and GIC can significantly improve hearing at 1 year and maintain stable hearing over 9 years. Both prosthesis and cement are safe.

Diurnal Preference and Correlates of Multidimensional Perfectionism, Type-D Personality, and Big Five Personality Traits.

This study examined the extent to which the dimensions of the five-factor model, Type-D personality, and multidimensional perfectionism were associated with a diurnal preference in the general population. A sample of (N = 864) individuals completed the measures of diurnal preference, multidimensional perfectionism, Type-D personality, and the Big Five traits. A correlational analysis determined that agreeableness, conscientiousness, emotional stability, organization, and personal standards were independently related to morningness. In contrast, negative affect, social inhibition, Type-D personality, and perfectionistic doubts and concerns, as well as an increased perception of critical parental evaluation, were independently related to eveningness. After accounting for the shared variance amongst the personality traits, only negative affect, conscientiousness, organization, personal standards, and parental perception were significantly associated with diurnal preference. The current outcomes offer further insight into the relationship between personality and diurnal preference. Here, we observed greater reports of adaptive personality traits in relation to morningness, whereas negative affect and perceived parental evaluation and criticism were related to eveningness. As the first study to examine the relationship between Type-D personality, multidimensional perfectionism, and diurnal preference, the current outcomes should be considered preliminary.

Opioid Use After Laparoscopic Surgery for Endometriosis and Pelvic Pain.

STUDY OBJECTIVE: The primary objective was to quantify postoperative opioid use after laparoscopic surgery for endometriosis or pelvic pain. The secondary objective was to identify patient characteristics associated with greater postoperative opioid requirements. DESIGN: Prospective, survey-based study in which subjects completed 1 preoperative and 7 postoperative surveys within 28 days of surgery regarding medication usage and pain control. SETTING: Tertiary care, academic center. PATIENTS: A total of 100 women with endometriosis or pelvic pain. INTERVENTIONS: Laparoscopic same-day discharge surgery by fellowship-trained minimally invasive gynecologists. MEASUREMENTS AND MAIN RESULTS: A total of 100 patients were recruited and 8 excluded, for a final sample size of 92 patients. All patients completed the preoperative survey. Postoperative response rates ranged from 70.7% to 80%. The mean number of pills (5 mg oxycodone tablets) taken by day 28 was 6.8. The average number of pills prescribed was 10.2, with a minimum of 4 (n = 1) and maximum of 20 (n = 3). Previous laparoscopy for pelvic pain was associated with a significant increase in postoperative narcotic use (8.2 vs 5.6; p = .044). Hysterectomy was the only surgical procedure associated with a significant increase in postoperative narcotic use (9.7 vs 5.4; p = .013). There were no difference in number of pills taken by presence of deep endometriosis or pathology-confirmed endometriosis (all p >.36). There was a trend of greater opioid use in patients with diagnoses of self-reported chronic pelvic pain, anxiety, and depression (7.9 vs 5.7, p = .051; 7.7 vs 5.2, p = .155; 8.1 vs 5.6, p = .118). CONCLUSION: Most patients undergoing laparoscopic surgery for endometriosis and pelvic pain had a lower postoperative opioid requirement than prescribed, suggesting surgeons can prescribe fewer postoperative narcotics in this population. Patients with a previous surgery for pelvic pain, self-reported chronic pelvic pain syndrome, anxiety, and depression may represent a subset of patients with increased postoperative opioid requirements.

Improving Chronic Illness Self-Management with the Apsáalooke Nation: The Báa nnilah Project, a cluster randomized trial protocol.

Chronic illness (CI) is a major cause of morbidity and mortality for Indigenous people. In Montana, Indigenous communities disproportionately experience CI, a legacy of settler colonialism. For over two decades, Messengers for Health, an Apsáalooke (Crow Indian) non-profit, and Montana State University have partnered to improve community health using a community-based participatory research (CBPR) approach. We developed Báa nnilah, an intervention utilizing community strengths, to improve CI self-management. This manuscript describes the protocol for a cluster randomized trial with two arms: an intervention group and a wait list control group, who both participated in the Báa nnilah program. Enrollment occurred through family/clan networks and community outreach and attended to limitations of existing CI self-management interventions by using an approach and content that were culturally consonant. Participants received program materials, attended seven gatherings focused on improving CI management, and received and shared health information through storytelling based on a conceptual framework from the Apsáalooke culture and incorporating CI self-management strategies. Participant support occurred within partnership dyads during and between gatherings, from community mentors, and by program staff. The study used mixed methods to evaluate the intervention, with qualitative measures including the Short Form Health Survey (SF-12), Patient Health Questionnaire (PHQ-9), Patient Activation Measure (PAM), and a suite of PROMIS measures, various physical tests and qualitative survey responses, semi-structured interviews, and outcomes shared by participants with program staff. We hypothesized that Báa nnilah would significantly improve participant health outcome measures across multiple dimensions with quality of life (QoL) as the primary outcome. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03036189. Registered on 30 January 2017. (From https://clinicaltrials.gov/ct2/show/NCT03036189).