Sex differences in pain catastrophizing and its relation to the transition from acute pain to chronic pain.

BACKGROUND AND IMPORTANCE: Differences exist between sexes in pain and pain-related outcomes, such as development of chronic pain. Previous studies suggested a higher risk for pain chronification in female patients. Furthermore, pain catastrophizing is an important risk factor for chronification of pain. However, it is unclear whether sex differences in catastrophic thinking could explain the sex differences in pain chronification. OBJECTIVES: The aim of this study was to examine sex differences in pain catastrophizing. Additionally, we investigated pain catastrophizing as a potential mediator of sex differences in the transition of acute to chronic pain. DESIGN, SETTINGS AND PARTICIPANTS: Adults visiting one of the 15 participating emergency departments in the Netherlands with acute pain-related complaints. Subjects had to meet inclusion criteria and complete questionnaires about their health and pain. OUTCOMES MEASURE AND ANALYSIS: The outcomes in this prospective cohort study were pain catastrophizing (short form pain catastrophizing) and pain chronification at 90 days (Numeric Rating Scale ≥ 1). Data was analysed using univariate and multivariable logistic regression models. Finally, stratified regression analyses were conducted to assess whether differences in pain catastrophizing accounted for observed differences in pain chronification between sexes. MAIN RESULTS: In total 1,906 patients were included. Females catastrophized pain significantly more than males (p < 0.001). Multiple regression analyses suggested that pain catastrophizing is associated with pain chronification in both sexes. CONCLUSIONS: This study reported differences between sexes in catastrophic cognitions in the development of chronic pain. This is possibly of clinical importance to identify high-risk patients and ensure an early intervention to prevent the transition from acute to chronic pain.

Real world impact of added FFR-CT to coronary CT angiography on clinical decision-making and patient prognosis - IMPACT FFR study.

OBJECTIVES: The addition of CT-derived fractional flow reserve (FFR-CT) increases the diagnostic accuracy of coronary CT angiography (CCTA). We assessed the impact of FFR-CT in routine clinical practice on clinical decision-making and patient prognosis in patients suspected of stable coronary artery disease (CAD). METHODS: This retrospective, single-center study compared a cohort that received CCTA with FFR-CT to a historical cohort that received CCTA before FFR-CT was available. We assessed the clinical management decisions after FFR-CT and CCTA and the rate of major adverse cardiac events (MACEs) during the 1-year follow-up using chi-square tests for independence. Kaplan-Meier curves were used to visualize the occurrence of safety outcomes over time. RESULTS: A total of 360 patients at low to intermediate risk of CAD were included, 224 in the CCTA only group, and 136 in the FFR-CT group. During follow-up, 13 MACE occurred in 12 patients, 9 (4.0%) in the CCTA group, and three (2.2%) in the FFR-CT group. Clinical management decisions differed significantly between both groups. After CCTA, 60 patients (26.5%) received optimal medical therapy (OMT) only, 115 (51.3%) invasive coronary angiography (ICA), and 49 (21.9%) single positron emission CT (SPECT). After FFR-CT, 106 patients (77.9%) received OMT only, 27 (19.9%) ICA, and three (2.2%) SPECT (p < 0.001 for all three options). The revascularization rate after ICA was similar between groups (p = 0.15). However, patients in the CCTA group more often underwent revascularization (p = 0.007). CONCLUSION: Addition of FFR-CT to CCTA led to a reduction in (invasive) diagnostic testing and less revascularizations without observed difference in outcomes after 1 year. KEY POINTS: • Previous studies have shown that computed tomography-derived fractional flow reserve improves the accuracy of coronary computed tomography angiography without changes in acquisition protocols. • This study shows that use of computed tomography-derived fractional flow reserve as gatekeeper to invasive coronary angiography in patients suspected of stable coronary artery disease leads to less invasive testing and revascularization without observed difference in outcomes after 1 year. • This could lead to a significant reduction in costs, complications and (retrospectively unnecessary) usage of diagnostic testing capacity, and a significant increase in patient satisfaction.

Time estimation and arousal responses in dopa-responsive dystonia.

Dopa-responsive dystonia (DRD) is caused by an impaired dopamine biosynthesis due to a GTP-cyclohydrolase-1 (GCH1) deficiency, resulting in a combination of dystonia and parkinsonism. However, the effect of GCH1 mutations and levodopa treatment on motor control beyond simple movements, such as timing, action preparation and feedback processing, have not been investigated so far. In an active time estimation task with trial-by-trial feedback, participants indicated a target interval (1200 ms) by a motor response. We compared 12 patients tested (in fixed order) under their current levodopa medication ("ON") and after levodopa withdrawal ("OFF") to matched healthy controls (HC), measured twice to control for repetition effects. We assessed time estimation accuracy, trial-to-trial adjustment, as well as task- and feedback-related pupil-linked arousal responses. Patients showed comparable time estimation accuracy ON medication as HC but reduced performance OFF medication. Task-related pupil responses showed the reverse pattern. Trial-to-trial adjustments of response times were reduced in DRD, particularly OFF medication. Our results indicate differential alterations of time estimation accuracy and task-related arousal dynamics in DRD patients as a function of dopaminergic medication state. A medication-independent alteration of task repetition effects in DRD cannot be ruled out with certainty but is discussed as less likely.

Prevention and Treatment of Neuraxial Morphine-Induced Pruritus: A Scoping Review.

The addition of morphine to neuraxial anaesthesia leads to improved postoperative analgesia and lower opioid consumption, but is often accompanied by pruritus. Studies on preventing or treating pruritus show contradictory results. Our objective was to identify effective drugs for the prevention or treatment of pruritus by a scoping review of clinical trials. A systematic literature search was conducted in PubMed, Embase and Web of Science. We identified clinical trials investigating the prevention or treatment of neuraxial morphine-induced pruritus in adults. Systematic reviews and meta-analyses were screened for eligible studies. One-hundred-and-four articles were included covering 13 pharmacological groups. We conclude that dopamine antagonists, µ-opioid agonist/antagonists and neuraxial or orally administered µ-opioid antagonists prevent pruritus caused by neuraxial morphine regardless of the timing of administration. In the reviewed literature, 5HT3-antagonists prevent neuraxial morphine-induced pruritus when administered before morphine administration. For the treatment of neuraxial morphine-induced pruritus, only nalbuphine appears to be consistently effective. More research is needed to find the most effective doses and the optimal timing of the effective medication.

Diagnostic Performance of CCTA and CT-FFR for the Detection of CAD in TAVR Work-Up.

BACKGROUND: The work-up for transcatheter aortic valve replacement (TAVR) currently uses computed tomography to evaluate the annulus diameter and peripheral vascular access plus invasive coronary angiography (ICA) to assess significant coronary artery disease (CAD). ICA might partially be redundant with the use of coronary computed tomography angiography (CCTA). Prior studies found an improvement of the diagnostic accuracy of CCTA with the use of computed tomography-derived fractional flow reserve (CT-FFR). OBJECTIVES: The aim of this study was to assess the diagnostic performance of CT-FFR for the diagnosis of CAD in the work-up for TAVR. METHODS: Consecutive patients with severe symptomatic aortic valve stenosis who underwent TAVR work-up between 2015 and 2019 were included in this retrospective cross-sectional study. All patients underwent CCTA and ICA within 3 months, and the diagnostic performance of both CCTA and CT-FFR was assessed using ICA as the reference. RESULTS: Seventy-six of the 338 patients included in the analysis had ≥1 significant coronary stenosis on ICA. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy per patient were 76.9%, 64.5%, 34.0%, 92.1%, and 66.9% for CCTA and 84.6%, 88.3%, 63.2%, 96.0%, and 87.6% for CT-FFR. The area under the receiver-operating characteristic curve was significantly different between CCTA and CT-FFR (0.84 vs 0.90, P = 0.02). A CT-FFR-guided approach could avoid ICA in 57.1% versus 43.6% of patients using CCTA. CONCLUSIONS: CT-FFR significantly improves the diagnostic accuracy of CCTA without additional testing and increases the proportion of patients in whom ICA could have been safely avoided. It has the potential to be integrated in the current clinical work-up for TAVR for diagnosing stable CAD requiring treatment.

Fractional Flow Reserve: Patient Selection and Perspectives.

The aim of this review was to discuss the current practice and patient selection for invasive FFR, new techniques to estimate invasive FFR and future of coronary physiology tests. We elaborate on the indication and application of FFR and on the contraindications and concerns in certain patient populations.

Ecotoxicity of boric acid in standard laboratory tests with plants and soil organisms.

To verify the continuous sensitivity of ecotoxicological tests (mainly the test organisms), reference substances with known toxicity are regularly tested. Ideally, this substance(s) would lack specificity in its mode action, be bioavailable and readily attainable with cost-effective means of chemical characterization. Boric acid has satisfied these criteria, but has most recently been characterized as a substance of very high concern, due to reproductive effects in humans, thus limiting its recommendation as an ideal reference toxicant. However, there is probably no other chemical for which ecotoxicity in soil has been so intensively studied; an extensive literature review yielded lethal (including avoidance) and sublethal data for 38 taxa. The ecotoxicity data were evaluated using species sensitivity distributions, collectively across all taxa, and separately according to species type, endpoints, soil type and duration. The lack of specificity in the mode of action yielded broad toxicity among soil taxa and soil types, and provided a collective approach to assessing species sensitivity, while taking into consideration differences in test methodologies and exposure durations. Toxicity was species-specific with Folsomia candida and enchytraied species demonstrating the most sensitivity; among plants, the following trend occurred: dicotyledonous (more sensitive) ≫ monocotyledonous ≫ gymnosperm species. Sensitivity was also time and endpoint specific, with endpoints such as lethality and avoidance being less sensitive than reproduction effects. Furthermore, given the breadth of data and toxicity demonstrated by boric acid, lessons learned from its evaluation are discussed to recommend the properties required by an ideal reference substance for the soil compartment.

Prediction of mortality and the need for neonatal extracorporeal membrane oxygenation therapy by 3-dimensional sonography and magnetic resonance imaging in fetuses with congenital diaphragmatic hernias.

OBJECTIVES: To compare different rotation angles for assessment of fetal lung volume by 3-dimensional (3D) sonography with magnetic resonance imaging (MRI) regarding prediction of mortality and the need for neonatal extracorporeal membrane oxygenation (ECMO) therapy in fetuses with congenital diaphragmatic hernias. METHODS: One hundred patients with fetal congenital diaphragmatic hernias between 22 and 39 weeks' gestation were examined by 3D sonography and MRI. Sonographic contralateral fetal lung volumes were assessed by the rotational technique (virtual organ computer-aided analysis) at 3 different rotation angles: 6°, 15°, and 30°. The MRI fetal lung volumes were calculated based on multiplanar T2-weighted MRI. To eliminate the influence of gestational age, the observed to expected contralateral fetal lung volume on sonography and the observed to expected fetal lung volume on MRI were calculated. Receiver operating characteristic (ROC) curves were calculated for the statistical prediction of survival and need for ECMO therapy by the observed to expected contralateral fetal lung volume (sonography) and observed to expected fetal lung volume (MRI). RESULTS: One hundred cases were assessed for survival and 89 for ECMO necessity (11 neonates were not eligible for ECMO). For prediction of postpartum survival and ECMO necessity, the areas under the ROC curves (AUCs) showed very similar results for MRI and 3D sonography: observed to expected fetal lung volume by MRI, 0.819 (95% confidence interval, 0.730-0.909) and 0.835 (0.748-0.922), respectively; 6° sonography, 0.765 (0.647-0.883) and 0.820 (0.734-0.905); 15° sonography, 0.784 (0.672-0.896) and 0.811 (0.719-0.903); and 30° sonography, 0.732 (0.609-0.855) and 0.772 (0.671-0.872). Comparisons between the AUCs revealed no statistical differences. CONCLUSIONS: We have shown the good prognostic value of 3D sonography in fetuses with congenital diaphragmatic hernias compared with MRI, particularly when using small rotation angles. Therefore, it can be an appropriate diagnostic tool when counseling patients for congenital diaphragmatic hernias.