The association of TNF inhibitor use with incident cardiovascular events in radiographic axial spondyloarthritis.

BACKGROUND: Whether tumor necrosis factor inhibitor (TNFi) use is cardioprotective among individuals with radiographic axial spondyloarthritis (r-axSpA), who have heightened cardiovascular (CV) risk, is unclear. We tested the association of TNFi use with incident CV outcomes in r-axSpA. METHODS: We identified a r-axSpA cohort within a Veterans Affairs database between 2002 and 2019 using novel phenotyping methods and secondarily using ICD codes. TNFi use was assessed as a time-varying exposure using pharmacy dispense records. The primary outcome was incident CV disease identified using ICD codes for coronary artery disease, myocardial infarction or stroke. We fit Cox models with inverse probability weights to estimate the risk of each outcome with TNFi use versus non-use. Analyses were performed in the overall cohort, and separately in two periods (2002-2010, 2011-2019) to account for secular trends. RESULTS: Using phenotyping we identified 26,928 individuals with an r-axSpA diagnosis (mean age 63.4 years, 94 % male); at baseline 3633 were TNFi users and 23,295 were non-users. During follow-up of a mean 3.3 ± 4.2 years, 674 (18.6 %) TNFi users had incident CVD versus 11,838 (50.8 %) non-users. In adjusted analyses, TNFi use versus non-use was associated with lower risk of incident CVD (HR 0.34, 95 % CI 0.29-0.40) in the cohort overall, and in the two time periods separately. CONCLUSION: In this r-axSpA cohort identified using phenotyping methods, TNFi use versus non-use had a lower risk of incident CVD. These findings provide reassurance regarding the CV safety of TNFi agents for r-axSpA treatment. Replication of these results in other cohorts is needed.

Pain trajectories after bilateral orthotopic lung transplantation surgery performed via a clamshell incision.

INTRODUCTION: The nature, intensity, and progression of acute pain after bilateral orthotopic lung transplantation (BOLT) performed via a clamshell incision has not been well investigated. We aimed to describe acute pain after clamshell incisions using pain trajectories for the study cohort, in addition to stratifying patients into separate pain trajectory groups and investigating their association with donor and recipient perioperative variables. METHODS: After obtaining IRB approval, we retrospectively included all patients ≥18 years old who underwent primary BOLT via clamshell incision at a single center between January 1, 2017, and June 30, 2022. We modeled the overall pain trajectory using pain scores collected over the first seven postoperative days and identified separate pain trajectory classes via latent class analysis. RESULTS: Three hundred one adult patients were included in the final analysis. Three separate pain trajectory groups were identified, with most patients (72.8%) belonging to a well-controlled, stable pain trajectory. Uncontrolled pain was either observed in the early postoperative period (10%), or in the late postoperative period (17.3%). Late postoperative peaking trajectory patients were younger (p = .008), and sicker with a higher lung allocation score (p = .005), receiving preoperative mechanical ventilation (p < .001), or VV-ECMO support (p < .001). CONCLUSION: Despite the extensive nature of a clamshell incision, most pain trajectories in BOLT patients had a well-controlled stable pain profile. The benign nature of pain profiles in our patient population may be attributed to the routine institutional practice of early thoracic epidural analgesia for BOLT patients unless contraindicated.

Interplay between noxious heat sensitivity and temporal summation magnitude in patients with fibromyalgia and long-term opioid use.

Introduction: In chronic pain conditions such as fibromyalgia (FM), pain amplification within the central nervous system, or "central sensitization," may contribute to the development and maintenance of chronic pain. Chronic pain treatments include opioid therapy, and opioid therapy may maladaptively increase central sensitization, particularly in patients who take opioids long-term. However, it has remained unknown how central sensitization is impacted in patients who use opioids long-term. Methods: To investigate how long-term opioid therapy affects central sensitization, we used the validated measure of temporal summation. The temporal summation measurement consists of applying a series of noxious stimuli to a patient's skin and then calculating changes in the patient's pain rating to each stimulus. Using this measurement, we evaluated temporal summation in study participants with fibromyalgia who take opioids long-term (i.e., greater than 90 days duration; n = 24, opioid-FM). We compared opioid-FM responses to 2 control groups: participants with fibromyalgia who do not take opioids (n = 33, non-opioid FM), and healthy controls (n = 31). For the temporal summation measurement, we applied a series of 10 noxious heat stimuli (sensitivity-adjusted temperatures) to the ventral forearm (2s duration of each stimulus, applied once every 3 s). Additionally, we collected responses to standard pain and cognitive-affective questionnaires to assess pain severity and other factors. Results and discussion: Group differences in sensitivity-adjusted stimulus temperatures were observed, with only the non-opioid FM group requiring significantly lower stimulus temperatures (The opioid-FM group also required lower temperatures, but not significantly different from the control group). However, all 3 groups exhibited similar magnitudes of temporal summation. Across combined FM groups, temporal summation negatively correlated with pain severity (r = -0.31, p = 0.021). Within the opioid-FM group, higher pain sensitivity to heat (i.e., lower sensitivity-adjusted temperatures) showed a trend relationship with higher opioid dosage (r = -0.45, p = 0.036), potentially reflective of opioid-related hyperalgesia. Our findings also indicated that heightened pain severity may skew sensitivity-adjusted temporal summation, thereby limiting its utility for measuring central sensitization. Overall, in participants taking opioids, temporal summation may be influenced by hypersensitivity to heat pain, which appeared to vary with opioid dosage.

An Analysis of Outcomes Following a Central Line Associated Blood Stream Infections (CLABSI) Reduction Quality Improvement Project in a Tertiary Care Center.

Central Line Associated Blood Stream Infections (CLABSI) continue to be a significant complication for hospitalized patients. Hospitals have used various strategies to reduce CLABSI events due to the significant complications and associated costs. In this QI analysis, we examined the impact of a CLABSI reduction quality improvement project within a single ICU at a tertiary care medical center. Absolute CLABSI counts were compared between this ICU and other health system ICUs that did not implement the bundle. A sustained reduction in absolute CLABSI counts to or near zero was observed over 17 months after implementation. ICUs not performing the interventions during this time consistently reported ≥ 2 CLABSI per month. Further analysis is needed to assess causality and the generalizability of bundle components to other ICUs. These findings may provide other health systems with additional strategies to prevent CLABSI and provide consistent, evidence-based supportive care to critically ill patients.

Evaluating the Association Between Fibrinogen and Rotational Thromboelastometry and the Progression to Severe Obstetric Hemorrhage.

AIM: This study aims to investigate the ability of fibrinogen and rotational thromboelastometry (ROTEM) parameters measured at obstetric hemorrhage protocol initiation to predict severe hemorrhage. METHODS: In this retrospective study we included patients whose hemorrhage was managed with an obstetric massive transfusion protocol. Fibrinogen and ROTEM parameters EXTEM clotting time (CT), clot formation time (CFT), alpha angle, A10, A20, lysis index 30 min after CT (LI30), FIBTEM A10, A20, were measured at initiation of the protocol with transfusion based on a predefined algorithm. Patients were grouped into either severe or nonsevere hemorrhage based on: peripartum fall in hemoglobin ≥4 g/dL, transfusion of ≥4 units of blood product, invasive procedures for hemorrhage control, intensive care unit admission, or death. RESULTS: Of the 155 patients included, 108 (70%) progressed to severe hemorrhage. Fibrinogen, EXTEM alpha angle, A10, A20, FIBTEM A10, A20 were significantly lower in the severe hemorrhage group while the CFT was significantly prolonged in the severe hemorrhage group. In univariate analysis, predicted progression to severe hemorrhage yielded areas under the receiver operating characteristic curve (95% confidence interval [CI]) of: fibrinogen: 0.683 (0.591-0.776), CFT: 0.671 (0.553, 0.789), EXTEM alpha angle: 0.690 (0.577-0.803), A10: 0.693 (0.570-0.815), A20: 0.678 (0.563-0.793), FIBTEM A10: 0.726 (0.605-0.847), and A20: 0.709 (0.594-0.824). In a multivariable model, fibrinogen was independently associated with severe hemorrhage (odds ratio [95% CI] = 1.037 [1.009-1.066]) for every 50 mg/dL decrease in fibrinogen drawn at obstetric hemorrhage massive transfusion protocol initiation. CONCLUSION: Both fibrinogen and ROTEM parameters measured at the initiation of an obstetric hemorrhage protocol are useful parameters for predicting severe hemorrhage.

Procalcitonin levels in pregnancy: A systematic review and meta-analysis of observational studies.

BACKGROUND: The utility of procalcitonin to identify obstetric sepsis is unknown. OBJECTIVE: To calculate the mean (range) procalcitonin in pregnancy among healthy women not in labor (group 1), healthy women in labor (group 2), and women with preterm prelabor rupture of membranes (PPROM) without clinical chorioamnionitis (group 3). SEARCH STRATEGY: NLM PubMed, Elsevier Embase, and Wiley Cochrane Central Register of Controlled Trials from inception to February 21, 2022. SELECTION CRITERIA: Ten or more pregnant women with procalcitonin reported at more than 20 weeks of pregnancy, with information on labor, PPROM, and infection. Exclusions were major medical comorbidities. DATA COLLECTION AND ANALYSIS: Each abstract and full-text review was independently reviewed by the same two authors. Quality was reviewed using the Newcastle-Ottawa Scale. A meta-analysis was performed using a random effects model. MAIN RESULTS: The systematic review included 25 studies: 10 (40%) of good quality and 15 (60%) of poor quality. The meta-analysis included 21 studies. Mean procalcitonin in group 1 was 0.092 ng/mL (range 0.036-0.049 ng/mL), in group 2 it was 0.130 ng/mL (range 0.049-0.259 ng/mL), and in group 3 it was 0.345 ng/mL (range 0.005-1.292 ng/mL). CONCLUSIONS: Among healthy pregnant women not in labor, procalcitonin levels are comparable to those in non-pregnant adults and may be useful in identifying infection. Procalcitonin levels in other groups overlap abnormal values of procalcitonin in non-pregnant adults, and may not discriminate infection among women in labor or with obstetric comorbidities. PROSPERO: CRD42020157376, registered 4/28/2020.