Effectiveness, cost-utility and physiological underpinnings of the FIBROWALK multicomponent therapy in online and outdoor format in individuals with fibromyalgia : Study protocol of a randomized, controlled trial (On&Out study)

Introduction: The On&Out study is aimed at assessing the effectiveness, cost-utility and physiological underpinnings of the FIBROWALK multicomponent intervention conducted in two different settings: online (FIBRO-On) or outdoors (FIBRO-Out). Both interventions have proved to be efficacious in the short-term but there is no study assessing their comparative effectiveness nor their long-term effects. For the first time, this study will also evaluate the cost-utility (6-month time-horizon) and the effects on immune-inflammatory biomarkers and Brain-Derived Neurotrophic Factor (BDNF) levels of both interventions. The objectives of this 6-month, randomized, controlled trial (RCT) are 1) to examine the effectiveness and cost-utility of adding FIBRO-On or FIBRO-Out to Treatment-As-Usual (TAU) for individuals with fibromyalgia (FM); 2) to identify pre-post differences in blood biomarker levels in the three study arms and 3) to analyze the role of process variables as mediators of 6-month follow-up clinical outcomes. Methods and analysis: Participants will be 225 individuals with FM recruited at Vall d'Hebron University Hospital (Barcelona, Spain), randomly allocated to one of the three study arms: TAU vs. TAU + FIBRO-On vs. TAU + FIBRO-Out. A comprehensive assessment to collect functional impairment, pain, fatigue, depressive and anxiety symptoms, perceived stress, central sensitization, physical function, sleep quality, perceived cognitive dysfunction, kinesiophobia, pain catastrophizing, psychological inflexibility in pain and pain knowledge will be conducted pre-intervention, at 6 weeks, post-intervention (12 weeks), and at 6-month follow-up. Changes in immune-inflammatory biomarkers [i.e., IL-6, CXCL8, IL-17A, IL-4, IL-10, and high-sensitivity C-reactive protein (hs-CRP)] and Brain-Derived Neurotrophic Factor will be evaluated in 40 participants in each treatment arm (total n = 120) at pre- and post-treatment. Quality of life and direct and indirect costs will be evaluated at baseline and at 6-month follow-up. Linear mixed-effects regression models using restricted maximum likelihood, mediational models and a full economic evaluation applying bootstrapping techniques, acceptability curves and sensitivity analyses will be computed. Ethics and dissemination: This study has been approved by the Ethics Committee of the Vall d'Hebron Institute of Research. The results will be actively disseminated through peer-reviewed journals, conference presentations, social media and various community engagement activities. Trial registration number NCT05377567 ()

Early mobilization after total hip or knee arthroplasty: a substudy of the POWER.2 study

Background Early mobilization after surgery is a cornerstone of the Enhanced Recovery After Surgery (ERAS) programs in total hip arthroplasty (THA) or total knee arthroplasty (TKA). Our goal was to determine the time to mobilization after this surgery and the factors associated with early mobilization. Methods This was a predefined substudy of the POWER.2 study, a prospective cohort study conducted in patients undergoing THA and TKA at 131 Spanish hospitals. The primary outcome was the time until mobilization after surgery as well as determining those perioperative factors associated with early mobilization after surgery. Results A total of 6093 patients were included. The median time to achieve mobilization after the end of the surgery was 24 hours [16–30]. 4,222 (69.3%) patients moved in ≤ 24 hours after surgery. Local anesthesia [OR = 0.80 (95% confidence interval [CI]: 0.72–0.90); p = 0.001], surgery performed in a self-declared ERAS center [OR = 0.57 (95% CI: 0.55–0.60); p < 0.001], mean adherence to ERAS items [OR = 0.93 (95% CI: 0.92–0.93); p < 0.001], and preoperative hemoglobin [OR = 0.97 (95% CI: 0.96–0.98); p < 0.001] were associated with shorter time to mobilization. Conclusions Most THA and TKA patients mobilize in the first postoperative day, early time to mobilization was associated with the compliance with ERAS protocols, preoperative hemoglobin, and local anesthesia, and with the absence of a urinary catheter, surgical drains, epidural analgesia, and postoperative complications. The perioperative elements that are associated with early mobilization are mostly modifiable, so there is room for improvement

Adjuvant dabrafenib and trametinib for patients with resected BRAF-mutated melanoma: DESCRIBE-AD real-world retrospective observational study

BRAF and MEK inhibitor, dabrafenib plus trametinib, adjuvant therapy is effective for high-risk resected melanoma patients with BRAF-V600 mutations. However, real-world evidence is limited. We aimed to determine the feasibility of this therapy in routine clinical practice. DESCRIBE-AD, a retrospective observational study, collected real-world data from 25 hospitals in Spain. Histologically confirmed and resected BRAF-mutated melanoma patients aged & GE;18 years who were previously treated with dabrafenib plus trametinib adjuvant therapy, were included. The primary objectives were treatment discontinuation rate and time to discontinuation. The secondary objectives included safety and efficacy. From October 2020 to March 2021, 65 patients were included. Dabrafenib and trametinib discontinuation rate due to treatment-related adverse events (TRAEs) of any grade was 9%. Other reasons for discontinuation included patients' decisions (6%), physician decisions (6%), unrelated adverse events (3%), disease progression (5%), and others (5%). The median time to treatment discontinuation was 9 months [95% confidence interval (CI), 5-11]. G3-4 TRAEs occurred in 21.5% of patients, the most common being pyrexia (3%), asthenia (3%), and diarrhoea (3%). Unscheduled hospitalisations and clinical tests occurred in 6 and 22% of patients, respectively. After 20-month median follow-up (95% CI, 18-22), 9% of patients had exitus due to disease progression, with a 12-month relapse-free survival and overall survival rates of 95.3% and 100%, respectively. Dabrafenib and trametinib adjuvant therapy proved effective for melanoma patients in a real-world setting, with a manageable toxicity profile. Toxicity frequencies were low leading to low incidence of unscheduled medical visits, tests, and treatment discontinuations

Serum tissue inhibitor of matrix metalloproteinase-1 levels are associated with mortality in patients with malignant middle cerebral artery infarction

Background: In the last years, circulating matrix metalloproteinases (MMP)-9 levels have been associated with functional outcome in ischemic stroke patients. However the prognostic value of circulating levels of tissue inhibitor of matrix metalloproteinases (TIMP)-1 and MMP-10 in functional outcome of ischemic stroke patients has been scarcely studied. In addition, to our knowledge, serum MMP-9, MMP-10 and TIMP-1 levels in patients with malignant middle cerebral artery infarction (MMCAI) for mortality prediction have not been studied, and these were the objectives of this study. Methods: This was a multicenter, observational and prospective study carried out in six Spanish Intensive Care Units. We included patients with severe MMCAI defined as Glasgow Coma Scale (GCS) lower than 9. We measured circulating levels of MMP-9, MMP-10, TIMP-1, in 50 patients with severe MMCAI at diagnosis and in 50 healthy subjects. Endpoint was 30-day mortality. Results: Patients with severe MMCAI showed higher serum levels of MMP-9 (p = 0.001), MMP-10 (p 239 ng/mL are associated with 30-day mortality (OR = 5.82; 95 % CI = 1.37-24.73; P = 0.02) controlling for GCS and age. The area under the curve for TIMP-1 as predictor of 30-day mortality was 0.81 (95 % CI = 0.67-0.91; P < 0.001). We found an association between circulating levels of TIMP-1 and MMP-10 (rho = 0.45; P = 0.001), plasminogen activator inhibitor (PAI)-1 (rho = 0.53; P < 0.001), and tumor necrosis factor (TNF)-alpha (rho = 0.70; P < 0.001). Conclusions: The most relevant and new findings of our study, were that serum TIMP-1 levels in MMCAI patients were associated with mortality, and could be used as a prognostic biomarker of mortality in MMCAI patients

Can serum hyaluronic acid replace simple non-invasive indexes to predict liver fibrosis in HIV/Hepatitis C coinfected patients?

<p>Abstract</p> <p>Background</p> <p>Hyaluronic acid (HA) serum levels correlate with the histological stages of liver fibrosis in hepatitis C virus (HCV) monoinfected patients, and HA alone has shown very good diagnostic accuracy as a non-invasive assessment of fibrosis and cirrhosis. The aim of this study was to evaluate serum HA levels as a simple non-invasive diagnostic test to predict hepatic fibrosis in HIV/HCV-coinfected patients and to compare its diagnostic performance with other previously published simple non-invasive indexes consisting of routine parameters (HGM-1, HGM-2, Forns, APRI, and FIB-4).</p> <p>Methods</p> <p>We carried out a cross-sectional study on 201 patients who all underwent liver biopsies and had not previously received interferon therapy. Liver fibrosis was determined via METAVIR score. The diagnostic accuracy of HA was assessed by area under the receiver operating characteristic curves (AUROCs).</p> <p>Results</p> <p>The distribution of liver fibrosis in our cohort was 58.2% with significant fibrosis (F≥2), 31.8% with advanced fibrosis (F≥3), and 11.4% with cirrhosis (F4). Values for the AUROC of HA levels corresponding to significant fibrosis (F≥2), advanced fibrosis (F≥3) and cirrhosis (F4) were 0.676, 0.772, and 0.863, respectively. The AUROC values for HA were similar to those for HGM-1, HGM-2, FIB-4, APRI, and Forns indexes. The best diagnostic accuracy of HA was found for the diagnosis of cirrhosis (F4): the value of HA at the low cut-off (1182 ng/mL) excluded cirrhosis (F4) with a negative predictive value of 99% and at the high cut-off (2400 ng/mL) confirmed cirrhosis (F4) with a positive predictive value of 55%. By utilizing these low and high cut-off points for cirrhosis, biopsies could have theoretically been avoided in 52.2% (111/201) of the patients.</p> <p>Conclusions</p> <p>The diagnostic accuracy of serum HA levels increases gradually with the hepatic fibrosis stage. However, HA is better than other simple non-invasive indexes using parameters easily available in routine clinical practice only for the diagnosing of cirrhosis.</p

Factors associated with excessive bleeding in cardiopulmonary bypass patients: a nested case-control study

<p>Abstract</p> <p>Introduction</p> <p>Excessive bleeding (EB) after cardiopulmonary bypass (CPB) may lead to increased mortality, morbidity, transfusion requirements and re-intervention. Less than 50% of patients undergoing re-intervention exhibit surgical sources of bleeding. We studied clinical and genetic factors associated with EB.</p> <p>Methods</p> <p>We performed a nested case-control study of 26 patients who did not receive antifibrinolytic prophylaxis. Variables were collected preoperatively, at intensive care unit (ICU) admission, at 4 and 24 hours post-CPB. EB was defined as 24-hour blood loss of >1 l post-CPB. Associations of EB with genetic, demographic, and clinical factors were analyzed, using SPSS-12.2 for statistical purposes.</p> <p>Results</p> <p>EB incidence was 50%, associated with body mass index (BMI)< 26.4 (25–28) Kg/m², (<it>P </it>= 0.03), lower preoperative levels of plasminogen activator inhibitor-1 (PAI-1) (<it>P </it>= 0.01), lower body temperature during CPB (<it>P </it>= 0.037) and at ICU admission (<it>P </it>= 0.029), and internal mammary artery graft (<it>P </it>= 0.03) in bypass surgery. We found a significant association between EB and 5G homozygotes for PAI-1, after adjusting for BMI (F = 6.07; <it>P </it>= 0.02) and temperature during CPB (F = 8.84; <it>P </it>= 0.007). EB patients showed higher consumption of complement, coagulation, fibrinolysis and hemoderivatives, with significantly lower leptin levels at all postoperative time points (<it>P </it>= 0.01, <it>P </it>< 0.01 and <it>P </it>< 0.01).</p> <p>Conclusion</p> <p>Excessive postoperative bleeding in CPB patients was associated with demographics, particularly less pronounced BMI, and surgical factors together with serine protease activation.</p

Bladder cancer index: cross-cultural adaptation into Spanish and psychometric evaluation

BACKGROUND: The Bladder Cancer Index (BCI) is so far the only instrument applicable across all bladder cancer patients, independent of tumor infiltration or treatment applied. We developed a Spanish version of the BCI, and assessed its acceptability and metric properties. METHODS: For the adaptation into Spanish we used the forward and back-translation method, expert panels, and cognitive debriefing patient interviews. For the assessment of metric properties we used data from 197 bladder cancer patients from a multi-center prospective study. The Spanish BCI and the SF-36 Health Survey were self-administered before and 12 months after treatment. Reliability was estimated by Cronbach's alpha. Construct validity was assessed through the multi-trait multi-method matrix. The magnitude of change was quantified by effect sizes to assess responsiveness. RESULTS: Reliability coefficients ranged 0.75-0.97. The validity analysis confirmed moderate associations between the BCI function and bother subscales for urinary (r = 0.61) and bowel (r = 0.53) domains; conceptual independence among all BCI domains (r ≤ 0.3); and low correlation coefficients with the SF-36 scores, ranging 0.14-0.48. Among patients reporting global improvement at follow-up, pre-post treatment changes were statistically significant for the urinary domain and urinary bother subscale, with effect sizes of 0.38 and 0.53. CONCLUSIONS: The Spanish BCI is well accepted, reliable, valid, responsive, and similar in performance compared to the original instrument. These findings support its use, both in Spanish and international studies, as a valuable and comprehensive tool for assessing quality of life across a wide range of bladder cancer patients

Estimation of neutron-equivalent dose in organs of patients undergoing radiotherapy by the use of a novel online digital detector.

Neutron peripheral contamination in patients undergoing high-energy photon radiotherapy is considered as a risk factor for secondary cancer induction. Organ-specific neutron-equivalent dose estimation is therefore essential for a reasonable assessment of these associated risks. This work aimed to develop a method to estimate neutron-equivalent doses in multiple organs of radiotherapy patients. The method involved the convolution, at 16 reference points in an anthropomorphic phantom, of the normalized Monte Carlo neutron fluence energy spectra with the kerma and energy-dependent radiation weighting factor. This was then scaled with the total neutron fluence measured with passive detectors, at the same reference points, in order to obtain the equivalent doses in organs. The latter were correlated with the readings of a neutron digital detector located inside the treatment room during phantom irradiation. This digital detector, designed and developed by our group, integrates the thermal neutron fluence. The correlation model, applied to the digital detector readings during patient irradiation, enables the online estimation of neutron-equivalent doses in organs. The model takes into account the specific irradiation site, the field parameters (energy, field size, angle incidence, etc) and the installation (linac and bunker geometry). This method, which is suitable for routine clinical use, will help to systematically generate the dosimetric data essential for the improvement of current risk-estimation models