Stakeholder Engagement to Identify Implementation Strategies to Overcome Barriers to Delivering Chronic Pain Treatments: A NIDILRR and VA TBI Model Systems Collaborative Project.

OBJECTIVE: The purpose of this article is to illustrate the process of stakeholder-engaged intervention mapping approach to identify implementation strategies to overcome data-driven prioritized barriers to receiving chronic pain services for persons with traumatic brain injury (TBI). SETTING: Community. PARTICIPANTS: Healthcare providers (n = 63) with 2 or more years' experience treating persons with TBI, interviewed between October 2020 and November 2021 provided data for identification of barriers. TBI, chronic pain, and qualitative research subject matter experts (SMEs) participated in the mapping approach. DESIGN: Participatory-based research design, using descriptive and intervention mapping approaches. RESULTS: Four barriers to accessing chronic pain treatment by persons with TBI which emerged from provider interviews were prioritized for intervention mapping: cognitive deficits of patients (67%); patient comorbidities (63%); mental health and/or substance abuse issues (59%); and patient participation (62%). SMEs used prioritized barriers to develop 4 primary objectives and implementation strategies designed to: (1) engage consumers to validate and identify strategies; (2) tailor pain treatment and delivery to overcome barriers; (3) develop and disseminate guidelines and best practices when delivering care to persons with TBI to support spread; and (4) increase awareness, skills, and readiness of workforce to deliver pain treatment to persons with TBI. SMEs used an evidence-based approach to develop a mapping matrix of the prioritized barriers, implementation objectives, and aligned implementation strategies to impact change. CONCLUSION: Implementation science is needed to facilitate knowledge translation into practice for this complex population to overcome barriers to care. Implementation strategies to address barriers to accessing chronic pain care for individuals with TBI were chosen through a participatory approach to engaging SMEs to support these rehabilitation implementation efforts. Future work includes gathering input from individuals with TBI and chronic pain and to move the intervention (implementation) mapping matrix forward to inform future implementation research, policy, and practice.

Associations between early sleep-disordered breathing following moderate-to-severe traumatic brain injury and long-term chronic pain status: a Traumatic Brain Injury Model Systems study.

STUDY OBJECTIVES: To explore the relationship between polysomnography-derived respiratory indices and chronic pain status among individuals following traumatic brain injury (TBI). METHODS: Participants (n = 66) with moderate to severe TBI underwent polysomnography during inpatient acute rehabilitation and their chronic pain status was assessed at 1- to 2-year follow-up as part of the TBI Model Systems Pain Collaborative Study. Pairwise comparisons across pain cohorts (ie, chronic pain, no history of pain) were made to explore differences on polysomnography indices. RESULTS: Among our total sample, approximately three-quarters (74.2%) received sleep apnea diagnoses utilizing American Academy of Sleep Medicine criteria, with 61.9% of those endorsing a history of chronic pain. Of those endorsing chronic pain, the average pain score was 4.8 (standard deviation = 2.1), with a mean interference score of 5.3 (2.7). Pairwise comparisons revealed that those endorsing a chronic pain experience at follow-up experienced categorically worse indicators of sleep-related breathing disorders during acute rehabilitation relative to those who did not endorse chronic pain. Important differences were observed with elevations on central (chronic pain: 2.6; no pain: 0.8 per hour) and obstructive apnea (chronic pain: 15.7; no pain: 11.1 per hour) events, as well as oxygen desaturation indices (chronic pain: 19.6; no pain: 7.9 per hour). CONCLUSIONS: Sleep-disordered breathing appears worse among those who endorse chronic pain following moderate-to-severe TBI, but additional research is needed to understand its relation to postinjury pain. Prospective investigation is necessary to determine how clinical decisions (eg, opioid therapy) and intervention (eg, positive airway pressure) may mutually influence outcomes. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Comparison of Sleep Apnea Assessment Strategies to Maximize TBI Rehabilitation Participation and Outcome (C-SAS); URL: https://clinicaltrials.gov/ct2/show/NCT03033901; Identifier: NCT03033901. CITATION: Martin AM, Pinto SM, Tang X, et al. Associations between early sleep-disordered breathing following moderate-to-severe traumatic brain injury and long-term chronic pain status: a Traumatic Brain Injury Model Systems study. J Clin Sleep Med. 2023;19(1):135-143.

Obstructive sleep apnea is associated with worse cognitive outcomes in acute moderate-to-severe traumatic brain injury: A TBI Model Systems study.

OBJECTIVE: To examine the relationship between polysomnography-classified obstructive sleep apnea (OSA) severity and cognitive performance in acute moderate-to-severe traumatic brain injury (TBI). METHOD: This was a cross-sectional, secondary analysis leveraging data from a clinical trial (NCT03033901) and TBI Model Systems. Sixty participants (mean age = 50 ± 18y, 72% male, 67% white) with moderate-to-severe TBI from five civilian rehabilitation hospitals were assessed at one-month post-injury. Participants underwent Level 1 polysomnography. OSA severity was classified as mild, moderate, and severe using the Apnea-Hypopnea Index (AHI). Associations between OSA metrics of hypoxemia (nadir and total time spent below 90%) and AHI with cognition were examined. Cognition was assessed with the Brief Test of Adult Cognition by Telephone (BTACT), which is comprised of six subtests assessing verbal memory, attention/working memory, processing speed, language, and executive function. RESULTS: Over three-quarters of this acute TBI sample (76.7%) were diagnosed with OSA (no OSA n = 14; mild OSA n = 19; moderate/severe OSA n = 27). After adjustment for age, gender, and education, those with OSA had worse processing speed, working memory, and executive functioning compared to those without OSA. Compared to those with moderate/severe OSA, those with mild OSA had worse working memory and executive function. CONCLUSIONS: OSA is highly prevalent during acute stages of TBI recovery, and even in mild cases is related to poorer cognitive performance, particularly in the domains of attention/working memory and executive functioning. Our results support the incorporation of OSA diagnostic tools and interventions into routine clinical care in rehabilitation settings.

Practical Evaluation and Management of Insomnia in Parkinson's Disease: A Review.

BACKGROUND: Insomnia is one of the most common nonmotor features of Parkinson's disease (PD). However, there are few practical guidelines for providers on how to best evaluate and treat this problem. METHODS AND FINDINGS: This review was developed to provide clinicians with a pragmatic approach to assessing and managing insomnia in PD. Recommendations were based on literature review and expert opinion. We addressed the following topics in this review: prevalence of insomnia in PD, sleep-wake mechanisms, theoretical models of insomnia, risk factors, assessment, pharmacologic and nonpharmacologic treatments. Insomnia treatment choices may be guided by PD severity, comorbidities, and patient preference. However, there is limited evidence supporting pharmacotherapy and nonpharmacologic treatments of insomnia in PD. CONCLUSIONS: We provide a pragmatic algorithm for evaluating and treating insomnia in PD based on the literature and our clinical experience. We propose personalized insomnia treatment approaches based on age and other issues. Gaps in the existing literature and future directions in the treatment of insomnia in PD are also highlighted.

Coherence Between Sleep Detection by Actigraphy and Polysomnography in a Multi-Center, Inpatient Cohort of Individuals with Traumatic Brain Injury.

BACKGROUND: Sleep is increasingly recognized as a crucial component to rapid and successful rehabilitation, especially from traumatic brain injuries (TBIs). Assessment of longitudinal patterns of sleep in a hospital setting, however, are difficult and often the expertise or equipment to conduct such studies is not available. Actigraphy (wrist-worn accelerometry) has been used for many years as a simple proxy measurement of sleep patterns, but its use has not been thoroughly validated in individuals with TBI. OBJECTIVE: To determine the validity of different sensitivity settings of actigraphy analysis to optimize its use as a proxy for recording sleep patterns in individuals with a TBI. DESIGN: Comparison of actigraphy to criterion standard polysomnographic (PSG)-determination of sleep on a single overnight study. SETTING: Six rehabilitation hospitals in the TBI Model System. PARTICIPANTS: Two hundred twenty-seven consecutive, medically stable individuals with a TBI. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Concordance between PSG- and actigraphy-determined sleep using different sensitivity threshold settings (low, medium, high, automated). RESULTS: Bland-Altman plots revealed increasing error with increasing amounts of wake during the sleep episode. Precision-recall statistics indicate that with less sensitive actigraphy thresholds, episodes identified as "wake" are usually "wake," but many true episodes of "wake" are missed. With more sensitive actigraphy thresholds, more episodes of "wake" are identified, but only some of these are true episodes of "wake." CONCLUSIONS: In hospitalized patients with TBI and poor sleep, actigraphy underestimates the level of sleep disruption and has poor concordance with PSG-determined sleep. Alternate methods of scoring sleep from actigraphy data are necessary in this population.

Effect of recording duration on the diagnostic accuracy of out-of-center sleep testing for obstructive sleep apnea.

STUDY OBJECTIVES: This study investigated the minimum recording time needed during out-of-center sleep testing (OCST) to accurately diagnose the presence and severity of obstructive sleep apnea (OSA). DESIGN AND SETTING: A retrospective analysis was conducted of OCSTs performed from October 2009 to May 2012 at the Mayo Clinic Center of Sleep Medicine using the portable Embletta™ system. PATIENTS OR PARTICIPANTS: Demographic information was collected for patients who underwent OCSTs during the study period, including presenting symptoms, examination findings, and comorbidities. INTERVENTION: Each study was divided into 60-, 120-, 180-, 240-, 300-, 360-, and 420-min intervals beginning at the recording start time to determine the respiratory event index (REI) for each of these time intervals. These interval values were then compared to the original REI derived from the total recording time (REITRT) by a paired t-test and concordance correlation coefficient (CCC). MEASUREMENTS AND RESULTS: There were significant differences between the REITRT and the REI from the 60-min (P < 0.0001), 120-min (0.0001), 180-min (0.003) and 240-min (0.006) intervals with a lack of concordance, suggesting these intervals are poor diagnostic correlates for the REITRT. REIs determined at 300, 360, and 420 min were not significantly different from the REITRT and had highly significant CCCs, 0.963, 0.987, and 0.995, respectively. CONCLUSIONS: The results suggest that at least 300 min recording time during out-of-center sleep testing is needed for accurate diagnosis of obstructive sleep apnea and determination of obstructive sleep apnea severity.

Chronic thromboembolic pulmonary hypertension in pediatric patients.

OBJECTIVE: Chronic thromboembolic pulmonary hypertension is a rare form of pulmonary hypertension that can lead to progressive right heart failure and death. Pulmonary thromboendarterectomy surgery is the treatment of choice resulting in significant improvements in functional status, cardiopulmonary hemodynamics, and survival. This study reports the largest case series of pediatric patients with chronic thromboembolic pulmonary hypertension who underwent pulmonary thromboendarterectomy surgery at one institution. PATIENT AND METHODS: The University of California, San Diego, chronic thromboembolic pulmonary hypertension database identified patients 18 years or younger at the time of pulmonary thromboendarterectomy surgery (n = 17). Medical charts were reviewed for hemodynamics, thromboembolic risk factors, and postoperative outcomes. RESULTS: Pulmonary thromboendarterectomy surgery in pediatric patients resulted in improved functional status and significantly improved cardiopulmonary hemodynamics: mean arterial pressure decreased from 45.5 mm Hg ± 20.7 to 27.3 ± 13.0 mm Hg (P = .00073), pulmonary vascular resistance decreased from 929 ± dynes · s · cm(-5) to 299 ± 307 dynes · s · cm(-5) (P = .0012), and cardiac output improved from 3.8 ± 1.1 L/min to 5.6 ± 1.6 L/min (P = .0061). There were no deaths during surgery or 30 days after surgery, and long-term survival (5+ years) was achieved in 87.5%. As compared to adults with chronic thromboembolic pulmonary hypertension, there was a higher rate of rethrombosis in pediatric patients (38% vs 1%-4%). CONCLUSIONS: This study demonstrates that pulmonary thromboendarterectomy surgery in pediatric patients with chronic thromboembolic pulmonary hypertension is well tolerated with improved postoperative hemodynamics, functional status, minimal postoperative complications, and low perioperative mortality, similar to that reported for adults with chronic thromboembolic pulmonary hypertension, with the notable exception being a higher rate of rethrombosis in pediatric patients.

Chronic thromboembolic pulmonary hypertension.

The pulmonary hypertension (PH) and right heart dysfunction that results from chronic thromboembolic involvement of the pulmonary vascular bed is potentially curable with surgical endarterectomy. Over the past several decades, growing clinical experience has brought about increased recognition of this treatable form of PH. Moreover, advances in cardiothoracic surgical techniques have given an increasing number of patients with chronic thromboembolic PH (CTEPH) a surgical remedy with decreasing perioperative morbidity and mortality risks. The availability of pulmonary hypertensive-specific medical therapy for CTEPH patients with surgically inaccessible disease also has been a positive therapeutic advance over the past several years. However, despite this progress, chronic thromboembolic disease as a sequela of acute pulmonary emboli continues to be underappreciated. Furthermore, even if CTEPH has been appropriately diagnosed, misinterpretation of diagnostic information may lead to the inappropriate exclusion of patients from surgical consideration. This may result in the prescription of pulmonary hypertensive medical therapy in CTEPH patients with potentially surgically correctable disease. This difficulty arises from a lack of objective criteria as to what constitutes surgical chronic thromboembolic disease, which primarily is a result of the variability in surgical experience in specialty centers in the United States. Consequently, clinicians must be wary about using pulmonary hypertensive medications in CTEPH patients. Before prescription, it is important to exclude patients from surgical consideration by consulting a specialized center with expertise in this discipline.

Phosphoinositide3-kinase regulates actin polymerization during delayed phagocytosis of Helicobacter pylori.

We have shown previously that ulcerogenic (type I) strains of Helicobacter pylori (Hp) retard their entry into macrophages. However, the signaling pathways that regulate Hp phagocytosis are largely undefined. We show here that Hp strongly activated class IA phosphoinositide3-kinases (PI3Ks) in macrophages, coincident with phagocytosis, and endogenous p85 and active protein kinase Balpha accumulated on forming phagosomes. PI3K inhibitors, wortmannin and LY294002, inhibited phagocytosis of Hp in a dose-dependent manner, and blockade of engulfment correlated directly with loss of 3'-phosphoinositides in the membrane subjacent to attached bacteria. During uptake of large immunoglobulin G (IgG)-coated particles, PI3Ks regulate pseudopod extension and phagosome closure. In marked contrast, we show here that 3'-phosphoinositides regulated actin polymerization at sites of Hp uptake. Moreover, Hp and IgG beads activated distinct PI3K isoforms. Phagosomes containing IgG-coated particles accumulated 3'-phosphatase and tensin homologue deleted on chromosome 10 and Src homology 2 domain-containing inositol 5'-phosphatase, yet Hp phagosomes did not. Finally, rapid uptake of IgG-opsonized Hp or a less-virulent type II Hp was PI3K-independent. We conclude that Hp and IgG beads are ingested by distinct mechanisms and that PI3Ks regulate the actin cytoskeleton during slow phagocytosis of ulcerogenic Hp.

Helicobacter pylori disrupts NADPH oxidase targeting in human neutrophils to induce extracellular superoxide release.

Helicobacter pylori (Hp) infection triggers a chronic influx of polymorphonuclear leukocyte neutrophils (PMNs) into the gastric mucosa. Although Hp reside in a neutrophil-rich environment, how these organisms evade phagocytic killing is largely unexplored. We now show that live Hp (strains 11637, 60190, DT61A, and 11916) are readily ingested by PMNs and induce a rapid and strong respiratory burst that is comparable to PMA. Relative to other particulate stimuli, Hp are more potent activators of PMNs than opsonized zymosan, Staphylococcus aureus, or Salmonella. Strikingly, biochemical and microscopic analyses demonstrate that Hp disrupt NADPH oxidase targeting such that superoxide anions are released into the extracellular milieu and do not accumulate inside Hp phagosomes. Specifically, nascent Hp phagosomes acquire flavocytochrome b558 but do not efficiently recruit or retain p47phox or p67phox. Superoxide release peaks at 16 min coincident with the appearance of assembled oxidase complexes in patches at the cell surface. Oxidant release is regulated by formalin-resistant and heat-sensitive bacterial surface factors distinct from urease and Hp(2-20). Following opsonization with fresh serum, Hp triggers a modest respiratory burst that is confined to the phagosome, and ingested bacteria are eliminated. We conclude that disruption of NADPH oxidase targeting allows unopsonized Hp to escape phagocytic killing, and our findings support the hypothesis that bacteria and PMNs act in concert to damage the gastric mucosa.