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.
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).
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.
Demographic information was collected for patients who underwent OCSTs during the study period, including presenting symptoms, examination findings, and comorbidities.
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).
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.
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.
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.
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 Bα 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.
Chronic Thromboembolic Pulmonary Hypertension Wittine, Lara M.; Auger, William R.
Current treatment options in cardiovascular medicine,
04/2010, Volume:
12, Issue:
2
Journal Article
Peer reviewed
Open access
Opinion statement
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.
Abstract
Introduction
Poor sleep quality and chronic pain are common after moderate-to-severe traumatic brain injury (msTBI). Prior studies have not examined the role of PTSD symptoms in the ...relationship between sleep quality and chronic pain experience (i.e., severity and pain-related interference) in those with msTBI. Yet, PTSD is known to be associated with both sleep and pain. The purpose of this analysis is to determine the role of PTSD symptoms in the sleep-pain relationship among this at-risk clinical population.
Methods
Secondary analyses were performed on data (n=1537) from the TBI Model Systems follow-up study. Participants were an average age of 46.21 years old, predominantly male (72.61%), and followed at an average of 8.5 years post injury. Participants completed measures of sleep quality (Pittsburgh Sleep Quality Index; PSQI), pain severity and interference (Brief Pain Inventory; BPI), depression (Patient Health Questionnaire-9; PHQ-9) and PTSD symptoms (PTSD Checklist, PCL-5). Analysis of covariance (ANCOVA) was used to examine differences in pain outcomes controlling for relevant covariates, adjusting for item redundancy prior to analyses.
Results
Sleep quality and pain interference are associated such that “good sleepers” (PSQI≤8, mean=4.92±2.17) have lower pain interference scores than “poor sleepers” (PSQI>8, mean=12.63±2.87), with a mean pain interference of 3.41±2.32 vs 5.26±2.45 (p< 0.0001). “Good sleepers” also had lower pain severity (4.22±1.78 vs 5.28±1.84, p< 0.0001), lower PTSD symptoms (14.62±13.46 vs 28.35±17.82, p< 0.0001), and less depression symptoms (5.32±4.97 vs 10.57±6.22, p< 0.0001) when compared to “poor sleepers.” Pain interference and severity were significantly related to all covariates at a <.001 level. Further, a significant effect of PSQI score cut-off (“good” v “poor sleeper”) in both pain interference and severity remained after controlling for the effect of age, depression, and PTSD symptom scores.
Conclusion
In patients with msTBI, sleep quality and pain interference are positively associated such that better sleep quality corresponds with lower pain interference, a relationship which remains when controlling for PTSD and multiple covariates. Addressing the sleep needs of patients with msTBI through behavioral intervention (e.g., cognitive behavioral therapy for insomnia), even in the presence of additional psychiatric comorbidities, may assist those who experience chronic pain following injury.
Support (if any)
Abstract
Introduction
Sleep disturbance and chronic pain are very common after moderate to severe traumatic brain injury (msTBI). Despite having a bidirectional and mutually exacerbating ...relationship, there is a dearth of literature examining factors involved in the sleep-pain relationship following msTBI. Psychiatric symptoms (e.g., post-traumatic stress, depression) are also prevalent following injury and know to be related to sleep, as well as poor adjustment to chronic pain. The purpose of this study was to examine associations between sleep, psychiatric symptoms, and pain-beliefs among msTBI survivors who have comorbid chronic pain.
Methods
This is a secondary analysis of TBI Model Systems study data of 1,567 individuals reporting chronic pain after msTBI (M=8.5 years, SD=7.1). Participants were 46.8 years old on average (SD=27.9), predominantly male (72.7%) and completed measures of sleep (Pittsburgh Sleep Quality Index; PSQI), post-traumatic stress disorder (PTSD Checklist; PCL-5), depression (Patient Health Questionnaire; PHQ-9), anxiety (General Anxiety Disorder; GAD-7), pain-related catastrophizing (Coping Strategies Questionnaire; CSQ) and self-efficacy (Pain Self-Efficacy Questionnaire; PSEQ-2). Measures were adjusted for overlapping constructs. Relationships between sleep, psychiatric symptoms and pain beliefs were examined through Pearson correlations.
Results
Average PSQI total score for our sample was 8.78 (SD=4.4), indicating poor sleep quality, with an estimated 6.40 (SD=1.9) hours of sleep on average. Over two-third (68.5%) of our sample attributed some of their sleep disturbance to chronic pain and nearly half (47.4%) met cutoff (>8) for clinically significant poor sleep quality. PSQI scores were positively correlated with PCL (r = .44, p <.0001), PHQ-9 (r = .12, p <.0001), GAD-7 (r = .08, p <.01), CSQ (r = .34, p <.0001) and negatively correlated with PSEQ-2 (r = -0.23, p <.0001).
Conclusion
Poorer sleep quality in individuals with chronic pain after msTBI is associated with more psychiatric symptoms, increased pain-related catastrophizing, and lower pain self-efficacy. Results highlight sleep quality as an important modifiable target for intervention in this at-risk clinical population and suggest that behavioral treatments to improve psychiatric comorbidities and adjustment to pain may be beneficial.
Support (if any)
National Institute on Disability, Independent Living, and Rehabilitation Research (NCT03033901).
ABSTRACT
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.
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).
Community.
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.
Participatory-based research design, using descriptive and intervention mapping approaches.
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.
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.
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