Characteristics of Coronary Atherosclerosis Related to Plaque Burden Regression During Treatment With Alirocumab: The ARCHITECT Study.

BACKGROUND: Intensive lipid-lowering therapy may induce coronary atherosclerosis regression. Nevertheless, the factors underlying the effect of lipid-lowering therapy on disease regression remain poorly characterized. Our aim was to determine which characteristics of atherosclerotic plaque are associated with a greater reduction in coronary plaque burden (PB) after treatment with alirocumab in patients with familial hypercholesterolemia. METHODS: The ARCHITECT study (Effect of Alirocumab on Atherosclerotic Plaque Volume, Architecture and Composition) is a phase IV, open-label, multicenter, single-arm clinical trial to assess the effect of the treatment with alirocumab for 78 weeks on the coronary atherosclerotic PB and its characteristics in subjects with familial hypercholesterolemia without clinical atherosclerotic cardiovascular disease. Participants underwent a coronary computed tomographic angiography at baseline and a final one at 78 weeks. Every patient received alirocumab 150 mg subcutaneously every 14 days in addition to high-intensity statin therapy. RESULTS: One hundred and four patients were enrolled. Median age was 53.3 (46.2-59.4) years and 54 were women (51.9%). The global coronary PB changed from 34.6% (32.5%-36.8%) at entry to 30.4% (27.4%-33.4%) at follow-up, which is -4.6% (-7.7% to -1.9%; P<0.001) reduction. A decrease in the percentage of unstable core (fibro-fatty+necrotic plaque; from 14.1 [7.9-22.3] to 8.0 [6.4-10.6]; -6.6%; P<0.001) was found. A greater PB (ß, 0.36 [0.13-0.59]; P=0.002) and a higher proportion of unstable core (ß, 0.15 [0.08-0.22]; P<0.001) were significantly related to PB regression. CONCLUSIONS: Treatment with alirocumab in addition to high-intensity statin therapy might produce a greater PB regression in patients with familial hypercholesterolemia with higher baseline PB and in those with larger unstable core. Further studies are needed to corroborate the hypothesis raised by these results. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05465278.

E-learning module for cytopathology education based on virtual microscopy.

INTRODUCTION: In cytopathology education, Virtual Microscopy e-learning modules (VM-eLM) have achieved remarkable results in the improvement and personalization of learning. However, it remains to be determined whether these modules can significantly contribute to improving the accuracy of cytological diagnosis. The aim of this work was to create a VM-eLM for gynecologic cytopathology education designed to improve screening and interpretation skills in two groups of cytologists: experienced and nonexperienced. MATERIALS AND METHODS: The module was designed in Moodle with both Whole Slide Images and Static Images taken from Papanicolaou smears that were diagnosed as: negative for intraepithelial lesion, low-grade squamous intraepithelial lesion, high-grade squamous intraepithelial lesion, squamous cell carcinoma, or adenocarcinoma. We assessed the effectiveness of the module using 1) clinical quality indicators to measure skill development and 2) a user survey. RESULTS: After training, participants significantly improved their cytological screening skills, decreasing their false negative diagnosis by 78% in the non-experienced group and eliminating them entirely in the experienced group. Nonexperienced participants also significantly increased their recognition of low-grade squamous intraepithelial lesion and high-grade squamous intraepithelial lesion by 31% and 50%, respectively. Participants positively evaluated the module, highlighting its novelty, the possibility to train remotely, the immediate feedback and the quality of the Whole Slide Images. CONCLUSIONS: We designed, implemented and tested a VM-eLM for Gynecologic Cytopathology Education that improved cytological screening skills for both non-experienced and experienced cytologists, also increasing the diagnostic accuracy of preinvasive lesions by less experienced cytologists. The module was positively evaluated by participants, who perceived an improvement in their interpretive skills.

Preference for Hedonic Goals in Fibromyalgia; Is It Always an Avoidance Mechanism? Looking the Relationship with Pain Acceptance from a Positive Psychology Perspective.

The aim of this study was to analyze the effect of openness to experience on pain acceptance through positive affect (PA) considering the moderating role of preference for mood management goals in women with fibromyalgia (FM). A cross-sectional study (n = 231) was carried out. A simple mediation model and a moderate mediation model were conducted by SPSS macro-PROCESS. Results showed that PA mediated positively the effect of openness to experience on acceptance (B = 0.46, SE = 0.80, t = 5,59; 95% CI = [0.3016, 0.6298], p < .001) and that the contribution of openness to experience to PA varied at different values of mood management goals (medium: - .04; ß = .40, p < .001; high: .95; ß = .61, p<.001). Findings may serve as a foundation for tailored interventions to promote activity through acceptance focusing on PA and mood management goals among women with medium to high level of hedonic goals.

Gallbladder Cancer Risk and Indigenous South American Mapuche Ancestry: Instrumental Variable Analysis Using Ancestry-Informative Markers.

A strong association between the proportion of indigenous South American Mapuche ancestry and the risk of gallbladder cancer (GBC) has been reported in observational studies. Chileans show the highest incidence of GBC worldwide, and the Mapuche are the largest indigenous people in Chile. We set out to assess the confounding-free effect of the individual proportion of Mapuche ancestry on GBC risk and to investigate the mediating effects of gallstone disease and body mass index (BMI) on this association. Genetic markers of Mapuche ancestry were selected based on the informativeness for assignment measure, and then used as instrumental variables in two-sample Mendelian randomization analyses and complementary sensitivity analyses. Results suggested a putatively causal effect of Mapuche ancestry on GBC risk (inverse variance-weighted (IVW) risk increase of 0.8% per 1% increase in Mapuche ancestry proportion, 95% CI 0.4% to 1.2%, p = 6.7 × 10-5) and also on gallstone disease (3.6% IVW risk increase, 95% CI 3.1% to 4.0%), pointing to a mediating effect of gallstones on the association between Mapuche ancestry and GBC. In contrast, the proportion of Mapuche ancestry showed a negative effect on BMI (IVW estimate -0.006 kg/m2, 95% CI -0.009 to -0.003). The results presented here may have significant implications for GBC prevention and are important for future admixture mapping studies. Given that the association between the individual proportion of Mapuche ancestry and GBC risk previously noted in observational studies appears to be free of confounding, primary and secondary prevention strategies that consider genetic ancestry could be particularly efficient.

Ocular surface disease: a known yet overlooked side effect of topical glaucoma therapy.

Ocular surface disease (OSD), a disorder affecting the lacrimal and meibomian glands and the corneal and conjunctival epithelium, is a well-known complication of topical glaucoma therapy. OSD can present as a new or pre-existing condition that virtually any anti-glaucoma formulation can exacerbate. As such, both glaucoma and OSD frequently coexist. Typical OSD symptoms include ocular discomfort, redness, burning, and dryness, whereas signs include periorbital and eyelid skin pigmentation, conjunctival scarring, and superficial punctate keratitis. Pressure-lowering eyedrops can cause toxic, allergic, and inflammatory reactions on the ocular surface. The latter can result from either preservatives or direct toxicity from the active molecule. Although usually mild, OSD can cause significant symptoms that lead to poor quality of life, decreased compliance to therapy, glaucoma progression, and worse visual outcomes. Given the chronic nature of glaucoma, lack of curative therapy, and subsequent lifelong treatment, addressing OSD is necessary. This manuscript aims to provide an up-to-date overview of OSD's signs, symptoms, and pathogenic mechanisms from glaucoma therapy toxicity.

X-linked juvenile retinoschisis associated with an RS1 in-frame deletion and bilateral central serous chorioretinopathy.

PURPOSE: To report the case of a patient with X-linked juvenile retinoschisis (XLRS), caused by an in-frame deletion of the RS1 gene, who presented visual loss due to bilateral central serous chorioretinopathy (CSC).Methods: Observational case report. RESULTS: A 34-year-old man, with type-A personality, presented with a one-month history of decreased visual acuity and metamorphopsia in his right eye. Funduscopic examination showed a dome-like foveal elevation in both eyes (OU), as well as subtle pigmentary changes of the retinal pigment epithelium with a tapetal reflex in the fovea. Spectral-domain optical coherence tomography revealed intraretinal cystic foveal changes and serous retinal detachment in OU. Fundus fluorescein angiography of OU showed a focal area of intense hyperfluorescence with leakage in late phases. Electroretinogram revealed a markedly attenuated b-wave and a diminished a-wave in photopic and scotopic phases. Genetic testing revealed a hemizygous c.282_284delCTT deletion in the RS1 gene, predicting a p.Ser95del change at the protein level. The patient was diagnosed with XLRS and central serous chorioretinopathy as a coexisting condition. Patient was observed during a 3-month period but showed no improvement. Therefore, subthreshold micropulse laser was applied, achieving complete resolution of signs and symptoms of CSC. CONCLUSION: CSC can be a cause of acute or subacute visual loss in patients with XLRS when other complications such as vitreous hemorrhage and retinal detachment have been excluded.

Biology and therapeutic targeting of vascular endothelial growth factor A.

The formation of new blood vessels, called angiogenesis, is an essential pathophysiological process in which several families of regulators have been implicated. Among these, vascular endothelial growth factor A (VEGFA; also known as VEGF) and its two tyrosine kinase receptors, VEGFR1 and VEGFR2, represent a key signalling pathway mediating physiological angiogenesis and are also major therapeutic targets. VEGFA is a member of the gene family that includes VEGFB, VEGFC, VEGFD and placental growth factor (PLGF). Three decades after its initial isolation and cloning, VEGFA is arguably the most extensively investigated signalling system in angiogenesis. Although many mediators of angiogenesis have been identified, including members of the FGF family, angiopoietins, TGFß and sphingosine 1-phosphate, all current FDA-approved anti-angiogenic drugs target the VEGF pathway. Anti-VEGF agents are widely used in oncology and, in combination with chemotherapy or immunotherapy, are now the standard of care in multiple malignancies. Anti-VEGF drugs have also revolutionized the treatment of neovascular eye disorders such as age-related macular degeneration and ischaemic retinal disorders. In this Review, we emphasize the molecular, structural and cellular basis of VEGFA action as well as recent findings illustrating unexpected interactions with other pathways and provocative reports on the role of VEGFA in regenerative medicine. We also discuss clinical and translational aspects of VEGFA. Given the crucial role that VEGFA plays in regulating angiogenesis in health and disease, this molecule is largely the focus of this Review.

Development and internal validation of a multifactorial risk prediction model for gallbladder cancer in a high-incidence country.

Since 2006, Chile has been implementing a gallbladder cancer (GBC) prevention program based on prophylactic cholecystectomy for gallstone patients aged 35 to 49 years. The effectiveness of this prevention program has not yet been comprehensively evaluated. We conducted a retrospective study of 473 Chilean GBC patients and 2137 population-based controls to develop and internally validate three GBC risk prediction models. The Baseline Model accounted for gallstones while adjusting for sex and birth year. Enhanced Model I also included the non-genetic risk factors: body mass index, educational level, Mapuche surnames, number of children and family history of GBC. Enhanced Model II further included Mapuche ancestry and the genotype for rs17209837. Multiple Cox regression was applied to assess the predictive performance, quantified by the area under the precision-recall curve (AUC-PRC) and the number of cholecystectomies needed (NCN) to prevent one case of GBC at age 70 years. The AUC-PRC for the Baseline Model (0.44%, 95%CI 0.42-0.46) increased by 0.22 (95%CI 0.15-0.29) when non-genetic factors were included, and by 0.25 (95%CI 0.20-0.30) when incorporating non-genetic and genetic factors. The overall NCN for Chileans with gallstones (115, 95%CI 104-131) decreased to 92 (95%CI 60-128) for Chileans with a higher risk than the median according to Enhanced Model I, and to 80 (95%CI 59-110) according to Enhanced Model II. In conclusion, age, sex and gallstones are strong risk factors for GBC, but consideration of other non-genetic factors and individual genotype data improves risk prediction and may optimize allocation of financial resources and surgical capacity.

Circulating miRNA expression in long-standing type 1 diabetes mellitus.

Type 1 diabetes is a chronic autoimmune disease which results in inefficient regulation of glucose homeostasis and can lead to different vascular comorbidities through life. In this study we aimed to analyse the circulating miRNA expression profile of patients with type 1 diabetes, and with no other associated pathology. For this, fasting plasma was obtained from 85 subjects. Next generation sequencing analysis was firstly performed to identify miRNAs that were differentially expressed between groups (20 patients vs. 10 controls). hsa-miR-1-3p, hsa-miR-200b-3p, hsa-miR-9-5p, and hsa-miR-1200 expression was also measured by Taqman RT-PCR to validate the observed changes (34 patients vs. 21 controls). Finally, through a bioinformatic approach, the main pathways affected by the target genes of these miRNAs were studied. Among the studied miRNAs, hsa-miR-1-3p expression was found significantly increased in patients with type 1 diabetes compared to controls, and positively correlated with glycated haemoglobin levels. Additionally, by using a bioinformatic approach, we could observe that changes in hsa-miR-1-3p directly affect genes involved in vascular development and cardiovascular pathologies. Our results suggest that, circulating hsa-miR-1-3p in plasma, together with glycaemic control, could be used as prognostic biomarkers in type 1 diabetes, helping to prevent the development of vascular complications in these patients.

Alirocumab and Coronary Atherosclerosis in Asymptomatic Patients with Familial Hypercholesterolemia: The ARCHITECT Study.

BACKGROUND: The effect of alirocumab, a PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor, on coronary plaque burden in patients with familial hypercholesterolemia has not been addressed. Our aim was to assess changes in coronary plaque burden and its characteristics after treatment with alirocumab by quantification and characterization of atherosclerotic plaque throughout the coronary tree on the basis of a noninvasive analysis of coronary computed tomographic angiography in asymptomatic subjects with familial hypercholesterolemia receiving optimized and stable treatment with maximum tolerated statin dose with or without ezetimibe. METHODS: This study is a phase IV, open-label, multicenter, single-arm clinical trial to assess changes in coronary plaque burden and its characteristics after 78 weeks of treatment with alirocumab in patients with familial hypercholesterolemia without clinical atherosclerotic cardiovascular disease. Participants underwent an initial coronary computed tomographic angiography at baseline and another at 78 weeks. Every patient received 150 mg of alirocumab subcutaneiously every 14 days in addition to high-intensity statin therapy. The main outcome was the change on coronary plaque burden and its characteristics by quantification and characterization of atherosclerotic plaque throughout the coronary tree on the basis of analysis of coronary computed tomographic angiography. RESULTS: The study was completed by 104 patients. The median age was 53.3 (46.2-59.4) years. Of these patients, 54 were women (51.9%). Median low-density lipoprotein cholesterol was 138.9 (117.5-175.3) mg/dL at entry and 45.0 (36.0-65.0) mg/dL at follow-up (P<0.001). Coronary plaque burden changed from 34.6% (32.5%-36.8%) at entry to 30.4% (27.4%-33.4%) at follow-up (P<0.001). A significant change in the characteristics of the coronary atherosclerosis was also found: an increase in the proportion of calcified (+0.3%; P<0.001) and mainly fibrous (+6.2%; P<0.001) plaque, accompanied by a decrease in the percentage of fibro-fatty (-3.9%; P<0.001) and necrotic plaque (-0.6%; P<0.001). CONCLUSIONS: Treatment with alirocumab in addition to high-intensity statin therapy resulted in significant regression of coronary plaque burden and plaque stabilization on coronary computed tomographic angiography over 78 weeks in these groups of patients with familial hypercholesterolemia without clinical atherosclerotic cardiovascular disease. ARCHITECT (Effect of Alirocumab on Atherosclerotic Plaque Volume, Architecture and Composition) could link and explain ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) results. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT05465278.

Apelin Enhances the Effects of Fusobacterium nucleatum on Periodontal Ligament Cells In Vitro.

This study aimed to explore effects of Fusobacterium nucleatum with or without apelin on periodontal ligament (PDL) cells to better understand pathomechanistic links between periodontitis and obesity. First, the actions of F. nucleatum on COX2, CCL2, and MMP1 expressions were assessed. Subsequently, PDL cells were incubated with F. nucleatum in the presence and absence of apelin to study the modulatory effects of this adipokine on molecules related to inflammation and hard and soft tissue turnover. Regulation of apelin and its receptor (APJ) by F. nucleatum was also studied. F. nucleatum resulted in elevated COX2, CCL2, and MMP1 expressions in a dose- and time-dependent manner. Combination of F. nucleatum and apelin led to the highest (p < 0.05) expression levels of COX2, CCL2, CXCL8, TNF-α, and MMP1 at 48 h. The effects of F. nucleatum and/or apelin on CCL2 and MMP1 were MEK1/2- and partially NF-κB-dependent. The combined effects of F. nucleatum and apelin on CCL2 and MMP1 were also observed at protein level. Moreover, F. nucleatum downregulated (p < 0.05) the apelin and APJ expressions. In conclusion, obesity could contribute to periodontitis through apelin. The local production of apelin/APJ in PDL cells also suggests a role of these molecules in the pathogenesis of periodontitis.

Does Pain Acceptance Contribute to Improved Functionality through Walking in Women with Fibromyalgia? Looking at Depressive Comorbidity.

In the last decade, research has pointed to physical exercise as an effective treatment in fibromyalgia patients. Some studies have highlighted the role of acceptance and commitment therapy in optimizing the benefits of exercise in patients. However, given the high comorbidity in fibromyalgia, it is necessary to value its possible influence on the effect of certain variables, such as acceptance, on the benefits of treatments, such as physical exercise. Our aim is to test the role of acceptance in the benefits of walking over functional limitation, further assessing whether this model is equally valid, considering depressive symptomatology as an additional differential diagnosis. A cross-sectional study with a convenience sample through contacting Spanish fibromyalgia associations was carried out. A total of 231 women with fibromyalgia (mean age 56.91 years) participated in the study. Data were analyzed with the Process program (Model 4, Model 58, Model 7). The results highlight the role of acceptance as a mediator between walking and functional limitation (B = -1.86, SE = 0.93, 95% CI = [-3.83, -0.15]). This model, when depression is incorporated as a moderator, is significant only in patients without depression, revealing the need for personalized treatments in fibromyalgia, considering their most prevalent comorbidity.

Clinical Evaluation of Patients with Genetically Confirmed Familial Hypercholesterolemia.

Familial hypercholesterolemia (FH) is the most common genetic disorder associated with premature atherosclerotic cardiovascular (CV) disease (ASCVD). However, it still is severely underdiagnosed. Initiating lipid-lowering therapy (LLT) in FH patients early in life can substantially reduce their ASCVD risk. As a result, identifying FH is of the utmost importance. The increasing availability of genetic testing may be useful in this regard. We aimed to evaluate the genetic profiles, clinical characteristics, and gender differences between the first consecutive patients referred for genetic testing with FH clinical suspicion in our institution (a Spanish cohort). Clinical information was reviewed, and all participants were sequenced for the main known genes related to FH: LDLR, APOB, PCSK9 (heterozygous FH), LDLRAP1 (autosomal recessive FH), and two other genes related to hyperlipidaemia (APOE and LIPA). The genetic yield was 32%. Their highest recorded LDLc levels were 294 ± 65 SD mg. However, most patients (79%) were under > 1 LLT medication, and their last mean LDLc levels were 135 ± 51 SD. LDLR c.2389+4A>G was one of the most frequent pathogenic/likely pathogenic variants and its carriers had significantly worse LDLc highest recorded levels (348 ± 61 SD vs. 282 ± 60 SD mg/dL, p = 0.002). Moreover, we identified an homozygous carrier of the pathogenic variant LDLRAP1 c.207delC (autosomal recessive FH). Both clinical and genetic hypercholesterolemia diagnosis was significantly established earlier in men than in women (25 years old ± 15 SD vs. 35 years old ± 19 SD, p = 0.02; and 43 ± 17 SD vs. 54 ± 19 SD, p = 0.02, respectively). Other important CV risk factors were found in 44% of the cohort. The prevalence of family history of premature ASCVD was high, whereas personal history was exceptional. Our finding reaffirms the importance of early detection of FH to initiate primary prevention strategies from a young age. Genetic testing can be very useful. As it enables familial cascade genetic testing, early prevention strategies can be extended to all available relatives at concealed high CV risk.

Exploring the moderated role of two psychological programs on sexual pleasure from physical symptoms, body image distortion and emotional problems of Hispanic women with breast cancer.

Decreased sexual pleasure is a common problem in women with breast cancer. The aim of this study was to evaluate the effect of psychoeducation vs. acceptance and commitment therapy to improve sexual pleasure according to the predictive role of physical, cognitive and emotional factors. Results of 139 Hispanic women (Mexico and Spain) diagnosed with breast cancer reveal that only the emotional factor of depression predicts decreased sexual pleasure. Although women who participated in the psychoeducation program presented greater physical symptomatology, body image distortions and emotional distress, the results seem to indicate that psychoeducational guidelines are relevant to improve sexual pleasure in those women who manifest higher levels of previous depression. Future research is required to clarify these issues.

The Role of Self-Efficacy and Activity Patterns in the Physical Activity Levels of Women with Fibromyalgia.

Keeping high levels of physical activity is a challenge among chronic patients. In this regard, self-efficacy has been identified as a crucial variable to reduce sedentarism and physical inactivity in women with fibromyalgia. The current study aimed to evaluate the associations among objective physical activity levels, self-efficacy, activity patterns, and the impact of the disease, as well as to compare those variables between women with fibromyalgia with different self-efficacy levels. For this purpose, in this cross-sectional study, the physical activity levels of 123 women with fibromyalgia were assessed by accelerometers, together with self-efficacy, the impact of the disease, and activity patterns. Results revealed that self-efficacy for light or moderate physical activity was directly related to light (p < 0.01), moderate (p < 0.01), and vigorous physical activity (p < 0.05), as well as inversely related to sedentary time (p < 0.01). Moreover, the main differences were observed between those with low self-efficacy levels and the rest of the sample, while there were no differences between the high and the medium self-efficacy groups (p > 0.05). Thus, self-efficacy for walking and light physical activity seems to be more relevant than self-efficacy for moderate and vigorous physical activity to achieve higher levels of physical activity.

Pathological Cycle between Pain, Insomnia, and Anxiety in Women with Fibromyalgia and its Association with Disease Impact.

BACKGROUND: Pain, sleep disturbances, and mood disorders are considered common symptoms of fibromyalgia (FM). However, the interactions that are established between them and the implication that this has in the disease are not clear. The main objective of this study is to clarify the relationships established between insomnia, pain intensity and anxiety in women with FM. Additionally, the effect that the indicated pathological cycle between pain, insomnia and anxiety may have on the impact of the disease in these patients is explored. METHODS: A total of 228 women diagnosed with FM participated in this study (mean age = 56.99 years, SD = 10.35). Measurements were conducted at two time points. Initially, the women completed self-report questionnaires about anxiety (The Hospital Anxiety and Depression Scale; HADS), sleep problems (The Insomnia Severity Index; ISI) and pain intensity (Brief Pain Inventory; BPI), and a week later, they answered questions about the impact of fibromyalgia (Fibromyalgia Impact Questionnaire- Revised; FIQ-R). For data analysis, models 4 and 6 of the Macro Process for SPSS were used. RESULTS: Insomnia predicts higher levels of pain, which in turn predicts higher levels of anxiety, which in turn predicts a higher impact of fibromyalgia (B = 2.76, SE = 1.10, 95% CI = [0.79,5.11]). No significant results were found for the other interactions between the variables. CONCLUSIONS: Due to the clinical and scientific relevance of the insomnia-pain-anxiety pathological cycle and given the impact it has on FM, it is especially relevant to develop programs for patients with fibromyalgia based mainly on improving sleep quality.

Sedentary Behavior and Pain after Physical Activity in Women with Fibromyalgia-The Influence of Pain-Avoidance Goals and Catastrophizing.

BACKGROUND: Fibromyalgia is characterized by chronic pain and fatigue that triggers a functional disability caused by the lack of activity. Pain catastrophizing may contribute to avoiding activity with the intention of managing pain levels. Based on the sedentary behavior with fibromyalgia, the present study assessed the preference of pain-avoidance goals and pain catastrophizing as mediator and moderator variables, respectively, that influence pain perception after a 6-min-walking test. METHODS: The sample was composed of 76 women with fibromyalgia (mean age = 55.05, SD = 7.70). Previous sedentary behavior, preference for pain-avoidance goals, and pain catastrophizing were evaluated before starting the walking-test. Subsequently, pain perception was evaluated. RESULTS: A significant moderated-mediation model was found in which pain-avoidance goals mediated the relationship between sedentarism and pain after a walking-test, and pain catastrophizing moderated the relationship between the preference for pain-avoidance goals and pain perception. Specifically, high levels of pain catastrophizing contributed to increased pain perceptions after completing the test (B = 0.570, p = 0.03, CI 95% (0.09, 0.11)]. CONCLUSIONS: The results suggest that motivational interventions can improve the symptoms because their objectives are focused on managing conflict goals. These interventions should focus on catastrophic cognitions considering that pain catastrophizing is deemed to be one of the major inhibitors of physical activity in fibromyalgia.

The Influence of the Fear of Negative Evaluation on Activity Avoidance in Fibromyalgia: Exploring Pain Acceptance and Positive Affect as Resilience Variables.

To examine the mediating role of pain acceptance (PAcc) between fear of negative evaluation (FNE) and activity avoidance (AV) at different levels of positive affect (PA) (moderator) among women diagnosed with fibromyalgia (FM) (moderate mediation model). This study was cross-sectional in design. A convenience sample of women with FM (n = 231) completed measures of pain severity, FNE, PAcc, AV, and PA. A simple mediation model and a moderate mediation model was constructed and analyzed using the SPSS macro-PROCESS. First, PAcc mediated the effect of FNE on AV (ß = .02, SE = 0.008; [95% CI [0.0075, 0.0394]). Second, a mediated effect of PAcc between FNE and AV moderated by PA at medium and high levels of PA were found (m: 0.23; ß = -.22, p = .0006; h: 9.59; ß = -.34, p = .0002. Future work should seek to validate study findings in diverse samples of FM patients. Additionally, future work should explore how FM self-management interventions that include PAcc can promote increased activity among women suffering from FM with medium to high levels of PA.

Symptoms in women with fibromyalgia after performing physical activity: the role of pain catastrophizing and disease impact.

INTRODUCTION: Walking is an effective treatment for symptoms' management in patients with fibromyalgia. However, despite its benefits, fibromyalgia patients face a variety of obstacles that result in reduced ability to sustain physical exercise. The main goal of the study was to analyze the role of pain catastrophizing and fibromyalgia impact in the relationship between regular walking behavior and pain and fatigue experienced after a laboratory walking test. METHOD: The study has an observational analytical laboratory design. A total of 100 women were contacted by the research team. Seventy-six women diagnosed with fibromyalgia aged 18 years and older (mean age = 55.05, SD = 7.69) participated. RESULTS: Significant correlations were found among regular walking behavior, pain catastrophizing, impact of fibromyalgia, pain intensity after walking, and fatigue intensity after walking. The serial multiple mediation analyses confirmed that pain catastrophizing and impact of fibromyalgia mediated the relationship between regular walking behavior and the level of pain (beta B = 0.044, 95% CI = [0.01-0.012]) and fatigue (beta B = 0.028, 95% CI = [0.01-0.08]) after the laboratory walking test. Also, the participants that walked less regularly experienced more pain and fatigue after the 6-Minute Walk Test. CONCLUSIONS: Considering cognitive variables alongside the impact of fibromyalgia will help understand the inhibitors of engaging in physical activity. Therapeutic walking programs must be tailored to patients with fibromyalgia to reduce pain and fatigue related to physical activity and to promote better functioning and quality of life. Key Points • Regular walking behavior was associated with fibromyalgia impact, pain catastrophizing, and less pain and fatigue after physical activity. • When patients catastrophize pain, they usually interpret physical activity as threatening, which generates more pain and fatigue after doing exercise. • Therapeutic programs should be designed to reduce pain catastrophizing and fibromyalgia impact.

How to Generate Self-Efficacy despite Pain: The Role of Catastrophizing and Avoidance in Women with Fibromyalgia.

BACKGROUND AND OBJECTIVE: Fibromyalgia-related pain is influenced by numerous factors, including severity, as well as cognitive profiles based on pain catastrophizing or activity patterns. In this context, self-efficacy is identified as a potential predictor for explaining certain health outcomes. This study aimed to contribute to exploring the role of pain avoidance (as activity pattern) between pain severity and self-efficacy along pain catastrophizing. METHODS: Through a cross-sectional study, a total of 264 women with fibromyalgia completed self-report measures of pain severity, pain avoidance, pain catastrophizing, and self-efficacy. The severity of the symptoms, the time elapsed since diagnosis, and the time elapsed since the onsets of symptoms were included as covariates to control. Regression-based moderated-mediation analysis was used to test the conditional effect of pain severity on self-efficacy via pain avoidance at varying levels of pain catastrophizing. RESULTS: Pain avoidance mediated the effect of pain severity on self-efficacy. The indirect effects showed a moderated effect when patients scored high on the pain catastrophizing scale. The model evaluated, where catastrophic pain moderates the indirect effect of pain intensity on self-efficacy through pain avoidance, explained 49% of the variance. CONCLUSIONS: Catastrophic beliefs associated with pain as being uncontrollable increase the relationship between pain severity and pain avoidance. In turn, pain avoidance is associated with a low perception of capacity.