Jorge clinical study: 10-year outcomes of risk-adapted radiotherapy defined by multiparametric MRI for prostate cancer.

PURPOSE: To analyze the 10-year biochemical relapse-free survival (BRFS), locoregional relapse-free survival (LRFS), metastasis-free survival (MFS), and overall survival (OS) in patients diagnosed with localized prostate adenocarcinoma treated with radiotherapy (RT) ± androgen deprivation therapy (ADT), according to the risk groups based on multiparametric magnetic resonance imaging (mpMRI) instead of digital rectal exam (DRE). METHODS: We retrospectively evaluated 140 consecutive patients diagnosed with localized prostate adenocarcinoma, stratified into different risk groups-low (LR), intermediate (IR), and high (HR) by mpMRI results. RESULTS: After a median follow-up of 104 months, in LR group (n = 15), 10-year BRFS was 86.7%, 10-year LRFS was 86.7%, 10-year MFS was 93.3%, and 10-year OS was 100%. In IR group (n = 80), 10-year BRFS was 80.5%, 10-year LRFS was 86.1%, 10-year MFS was 92.6%, and 10-year OS was 76%. In HR group (n = 45), 10-year BRFS was 72.8%, 10-year LRFS was 78.7%, 10-year MFS was 82.1%, and 10-year OS was 77% (2 deaths from prostate cancer). According to mpMRI results, 36 (25.7%) patients change the risk group and 125 (89.28%) patients change the TNM stage. There was a trend for higher metastatic relapse in patients who switched from IR to HR (due to mpMRI) versus the patients who remained in the IR (20%, vs. 1.81% p = 0.059). Multivariate analysis showed that locoregional relapse was strongly associated with distant relapse (OR = 9.28; 95%CI: 2.60-33.31). There were no cases of acute grade 3 toxicity. Late grade 3 genitourinary, gastrointestinal, and sexual toxicity were 2.8%, 0.7%, and 1.2%, respectively. CONCLUSION: This is the first study with a 10-year median follow-up of patients diagnosed with localized prostate cancer treated with radiotherapy according to the risk groups established by mpMRI. Our findings show that mpMRI is a key tool to diagnose and establish risk groups in these patients, to optimize their treatment.

Exploring Disparities in Self-Reported Mental Health Symptoms Across Professional Categories in Spain's Emergency Medical Services: A Nationwide Cross-Sectional Study.

OBJECTIVE: This study aimed to analyze stress, anxiety, depression, and self-efficacy levels among Spanish out-of-hospital emergency medical professionals from February 1, 2021, to April 30, 2021. METHODS: A nationwide survey was completed by 1666 Emergency Medical Services (EMS) workers. The Depression, Anxiety, and Stress Scale (DASS-21) and the General Self-Efficacy Scale (GSE) were used. Data analysis used chi-squared, análisis of variance (ANOVA), and logistic regressions. RESULTS: The sample comprised 833 (50%) men, with an average age of 44.3 ± 9.9 y (range: 19-67 y). Occupational distribution included 453 (27.2%) physicians, 474 (28.4%) nurses, and 739 (44.4%) emergency medical technicians (EMTs). EMTs exhibited higher odds of severe or extremely severe depression compared with physicians (odds ratio [OR]: 1.569; 95% confidenceinterval [95% CI]: 1.213-2.030) and nurses (OR: 1.561; 95% CI: 1.211-2.012). EMTs also displayed higher probabilities of severe or extremely severe anxiety compared with nurses (OR: 1.944; 95% CI: 1.529-2.701). Furthermore, EMTs demonstrated elevated probabilities of severe or extremely severe stress compared with physicians (OR: 1.387; 95% CI: 1.088-1.770). However, no significant differences were found in self-efficacy, with a median value of 73 [20]. CONCLUSIONS: Out-of-hospital EMS workers experienced mental health challenges, showing varying levels of depression, stress, and anxiety across different occupational groups. EMTs were particularly affected.

Influence of Previous Mental State on Psychological Outcomes of Spanish Out-of-Hospital Professionals during the COVID-19 Pandemic.

This study aimed to describe factors relating to the psychological distress of healthcare workers (HCWs) in Spanish out-of-hospital emergency medical services (EMS), according to the previous or non-use of psychotropic drugs or psychotherapy. A multicentre, cross-sectional descriptive study was designed. The study population were all physicians, nurses, and emergency medical technicians (EMTs) working in any Spanish out-of-hospital EMS between February and April 2021. The main outcomes were the levels of stress, anxiety, depression, and self-efficacy, assessed by DASS-21 and G-SES. Differences in levels of stress, anxiety, depression, and self-efficacy, according to sex, age, previous use of psychotropic drug or psychotherapy, work experience, professional category, type of work, and modification of working conditions were measured using the Student's t-test for independent samples, one-way ANOVA, Pearson's correlation, or 2-factor analysis of covariance. A total of 1636 HCWs were included, of whom one in three had severe mental disorders because of the pandemic. The interaction of the previous or non-use of psychotropic drugs or psychotherapy with the rest of the factors considered did not modify the levels of stress, anxiety, depression, and self-efficacy. However, HCWs with a history of psychotropic drug or psychotherapy use had a more intense negative emotional response and lower self-efficacy, regardless of their sex, professional category, type of work, or change in the working conditions. These HCWs are considered particularly vulnerable to the development or recurrence of new disorders or other comorbidities; therefore, the implementation of monitoring and follow-up strategies should be a priority.

The effect of age on clinical outcomes in critically ill brain-injured patients.

PURPOSE: We studied the impact of age on survival and functional recovery in brain-injured patients. METHODS: We performed an observational cohort study of all consecutive adult patients with brain injury admitted to ICU in 8 years. To estimate the optimal cut-off point of the age associated with unfavorable outcomes (mRS 3-6), receiver operating characteristic (ROC) curve analyses were used. Multivariate logistic regression analyses were performed to identify prognostic factors for unfavorable outcomes. RESULTS: We included 619 brain-injured patients. We identified 60 years as the cut-off point at which the probability of unfavorable outcomes increases. Patients ≥ 60 years had higher severity scores at ICU admission, longer duration of mechanical ventilation, longer ICU and hospital stays, and higher mortality. Factors identified as associated with unfavorable outcomes (mRS 3-6) were an advanced age (≥ 60 years) [Odds ratio (OR) 4.59, 95% confidence interval (CI) 2.73-7.74, p < 0.001], a low GCS score (≤ 8 points) [OR 3.72, 95% CI 1.95-7.08, p < 0.001], the development of intracranial hypertension [OR 5.52, 95% CI 2.70-11.28, p < 0.001], and intracerebral hemorrhage as the cause of neurologic disease [OR 3.87, 95% CI 2.34-6.42, p < 0.001]. CONCLUSION: Mortality and unfavorable functional outcomes in critically ill brain-injured patients were associated with older age (≥ 60 years), higher clinical severity (determined by a lower GCS score at admission and the development of intracranial hypertension), and an intracerebral hemorrhage as the cause of neurologic disease.

Risk and prognostic factors for SARS-CoV-2 infection in Spanish population with multiple sclerosis during the first five waves.

Background: Data on coronavirus disease 2019 (COVID-19) incidence in patients with multiple sclerosis (MS) during the first wave have been published but are scarce for the remaining waves. Factors associated with COVID-19 infection of any grade are also poorly known. The aim of this study was to analyze the incidence, clinical features, and risk factors for COVID-19 infection of any grade in patients with MS (pwMS) during waves 1-5. Methods: This study prospectively analyzes the cumulative incidence of COVID-19 from the first to the fifth waves by periodic case ascertainment in pwMS followed at the University Hospital of Getafe (UHG). Global and stratified cumulative incidence was calculated. Logistic regression models were used to estimate the weight of selected variables as risk and prognostic factors. Results: We included 431 pwMS, of whom 86 (20%) were infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The overall cumulative incidence of confirmed cases was similar to that of Madrid (13,689 vs. 13,307 per 100,000 habitants) but 3 times higher during the first wave and slightly lower from the second to the fifth waves. The majority (86%) of pwMS developed mild forms of COVID-19. Smoking was the only factor associated with a decreased risk of SARS-CoV2 infection of any grade [odds ratio (OR) 0.491; 95% CI 0.275-0.878; p = 0.017]. Risk factors associated with severe forms were Expanded Disability Severity Scale (EDSS) ≥3.5 (OR 7.569; 95% CI 1.234-46.440) and pulmonary disease (OR 10.763; 95% CI 1.27-91.254). Conclusion: The incidence of COVID-19 was similar in this MS cohort to the general population. Smoking halved the risk of being infected. Higher EDSS and pulmonary comorbidity were associated with an increased risk of severe forms.

Effectiveness of Physical Exercise Interventions on Pulmonary Function and Physical Fitness in Children and Adults with Cystic Fibrosis: A Systematic Review with Meta-Analysis.

Objective: Physical exercise is associated with several benefits in the treatment of cystic fibrosis (CF), associated with a reduction in patient mortality. The aim of this systematic review was to determine the effectiveness of exercise interventions on physical condition and lung function in children and adults with CF to establish the most appropriate type and dose of physical exercise used so far. Methods: The studies included were randomized controlled trials with physical exercise interventions performed with children or adults with CF, analyzing the effects on pulmonary function, cardiorespiratory capacity, and muscle strength. The variables analyzed in at least four studies in the same population (children or adults) with the same measuring test were included in the meta-analysis. Results:Pulmonary function: There were no changes in the forced expiratory volume 1 s, but mouth expiratory/inspiratory pressures were improved in some studies. Physical fitness: In children, the interventions did not manage to improve the VO2peak (SMD = 0.22; 95%CI: -0.25 to 0.68; p = 0.73) but improved muscle strength. In adults, physical exercise interventions based on high-intensity aerobic training showed positive results in the VO2peak, and in some muscle strength outcomes. Conclusions: Exercise interventions in children and adults with CF are effective in improving muscle strength, cardiovascular capacity, and respiratory muscle function. However, they do not achieve improvements in lung function. The most effective programs are those using strength training or cardiovascular high-intensity interval training, although to date there have been few such interventions.

Accuracy, feasibility and predictive ability of different frailty instruments in an acute geriatric setting.

PURPOSE: To analyze the feasibility, accuracy and the ability of different frailty instruments to predict adverse outcomes. METHODS: A prospective cohort study was conducted in patients ≥ 70 years admitted to the acute care setting (ACS). Feasibility and prevalence of frailty were assessed by FRAIL, Clinical Frailty Scale (CFS), hand grip strength (HGS) and the Spanish Frailty-VIG. Receiver operator characteristic (ROC) curves and area under the curve (AUC) were performed to identify frailty according to each instrument, setting VIG as the reference. For each instrument, multiple logistic regressions were used to examine the effect of frailty on primary outcome (i.e., three-month mortality) and secondary outcomes (i.e., in-hospital mortality, length of stay, institutionalization, functional decline and 30-day readmission). RESULTS: A total of 185 patients were included, with a median age of 89 years. The feasibility of the instruments was 100%, except for HGS (67%). The prevalence of frailty varied from 65.2% (FRAIL) to 86.7% (VIG). AUCs against VIG ranged from 0.69 (95% confidence interval [CI] 0.57-0.81: FRAIL) to 0.77 (95% CI 63.5-90.2: CFS). Frail patients defined by FRAIL were 2.7times more likely to have a prolonged length of stay than non-frail patients (95% CI 1.385-5.416). Three-month mortality occurred more among frail patients, either defined by FRAIL (OR 2.5; 95% CI 1.072-5.881) or CFS (OR 3.7; 95% CI 1.255-10.812), than in non-frail patients. CONCLUSION: The four instruments had high feasibility providing variable prevalence of frailty. FRAIL and CFS predicted well for three-month mortality, and FRAIL also for length of stay. However, none of the instruments predicted for the other secondary outcomes of the study.

Influence of the Cumulative Incidence of COVID-19 Cases on the Mental Health of the Spanish Out-of-Hospital Professionals.

This study aimed to analyze the psychological affectation of health professionals (HPs) of Spanish Emergency Medical Services (EMSs) according to the cumulative incidence (CI) of COVID-19 cases in the regions in which they worked. A cross-sectional descriptive study was designed, including all HPs working in any EMS of the Spanish geography between 1 February 2021 and 30 April 2021. Their level of stress, anxiety and depression (DASS-21) and the perception of self-efficacy (G-SES) were the study's main results. A 2-factor analysis of covariance was used to determine if the CI regions of COVID-19 cases determined the psychological impact on each of the studied variables. A total of 1710 HPs were included. A third presented psychological impairment classified as severe. The interaction of CI regions with the studied variables did not influence their levels of stress, anxiety, depression or self-efficacy. Women, younger HPs or those with less EMS work experience, emergency medical technicians (EMT), workers who had to modify their working conditions or those who lived with minors or dependents suffered a greater impact from the COVID-19 pandemic in certain regions. These HPs have shown high levels of stress, anxiety, depression and medium levels of self-efficacy, with similar data in the different geographical areas. Psychological support is essential to mitigate their suffering and teach them to react to adverse events.

In Vivo Complete-Arch Implant Digital Impressions: Comparison of the Precision of Three Optical Impression Systems.

(1) Multiple in vitro studies reported insufficient accuracy of intraoral scanners (IOSs) for complete-arch multiple implant impression. The aim of the study is to analyze the precision of three IOSs, PIC dental (Pic dental, Iditec North West SL), TRIOS 3 (3Shape), and True Definition (Midmark Corporation) and the influence of several factors in the edentulous complete maxillary and mandibular arch. (2) A fully edentulous patient with eight implants in the maxillary and in the mandibular jaw was selected. Five impressions were taken per system and arch. A suprastructure was designed on each digital working cast. The precision was analyzed comparing each of the 28 distances and seven relative angulations of the abutments of all the designed suprastructures. The descriptive statistics, the Student's t-test, and the ANOVA test were used to analyze the data (α = 0.05). (3) Significant differences were observed when comparing the IOSs in some of the distances and angulations. (4) The increase in the distance between implants affected the precision of T and TD but not the PIC system. The type of arch did not affect the PIC precision, but the T and TD systems performed worse in the mandibular arch. The system with the best precision was the PIC, followed by TD, and then T.

Patients' self-assessment of essential tremor severity by a validated scale: A useful tool in telemedicine?

INTRODUCTION: There are some validated rating scales to assess severity of Essential tremor (ET), the most common cause of action tremor. Clinical evaluation through telematic consultations has been expanding in the last decade. Patients' self-assessment of tremor severity at home could constitute a useful tool in telemedicine. This paper aims to assess intrarater and interrater reliability of ET severity using Fahn-Tolosa Marin Tremor Rating Scale (FTMTRS) for patients' and neurologists' ratings. MATERIAL AND METHODS: Patients were instructed on how to perform and rate the FTMTRS tasks. Supervised by neurologists, each patient performed one FTMTRS self-assessment at the hospital, which was rated in a blinded way by two neurologists, and six more self-assessments at home afterwards. Postural, intention and specific-tasks tremor were rated. A cumulative linked mixed model was used to assess intrarater and interrater reliability. RESULTS: A total of 161 self-assessments from 19 patients were analyzed. Intrarater reliability of patients' self-ratings at home showed ICCs between 0.843 and 0.962. Interrater ICCs of neurologists' ratings were also excellent for all tremor types (0.903-0.987). Concordance between neurologists' and patients' assessments showed ICCs ranging from 0.407 to 0.824, with the higher agreement for writing/drawing-related tremor (0.824; CI 95% 0.634-0.989). CONCLUSIONS: The rating of ET severity from FTMTRS self-assessments performed by well-trained patients at home could be a suitable clinical measure to assess tremor in non-face-to-face medical consultations. The assessment of tremor during specific tasks could be the most efficient measure for the patient self-assessment at home. These results could be useful in telemedicine.

Early predictive risk factors for dimethyl fumarate-associated lymphopenia in patients with multiple sclerosis.

BACKGROUND: Lymphopenia is a major concern in MS patients treated with dimethyl-fumarate (DMF) as it increases the risk of progressive multifocal leukoencephalopathy. A pronounced reduction in absolute lymphocyte counts (ALCs) early after treatment initiation has been suggested to be associated with the occurrence of lymphopenia thereafter. OBJECTIVES: To identify risk factors for DMF-induced lymphopenia and evaluate whether the degree of decrease in the ALCs three months after initiation of DMF treatment is a predictor of the subsequent development of lymphopenia. METHODS: In this real-world Spanish prospective multicenter study conducted in MS patients who started DMF between 2014 and 2019, we analyzed the association between DMF-related lymphopenia and the percentage of early ALCs decline using regression models, considering both, significant lymphopenia (grades 2 + 3) and severe lymphopenia (grade 3). The cutoff values of early ALCs declines were obtained using the ROC curve. RESULTS: Among 532 MS patients treated with DMF, 193 (36.3%) developed any grade of lymphopenia. Older age and lower ALCs at treatment onset predicted the risk for lymphopenia but the best predictive risk factor was the reduction of ALCs within the three first months of treatment. Specifically, a reduction in ALCs≥21.2% was associated with a 6.5-fold higher risk of developing significant lymphopenia, and a decrease in ALCs≥40.2% with a 12.7-fold higher risk of developing severe lymphopenia. CONCLUSIONS: A pronounced reduction in ALCs early after initiation of DMF in MS patients is the best predictive risk factor for the subsequent development of significant lymphopenia.

Incidence of COVID-19 in 902 Patients With Immunomediated Inflammatory Diseases Treated With Biologics and Targeted Synthetic Disease-Modifying Antirheumatic Drugs-Findings From the BIOCOVID Study.

OBJECTIVES: The aim of this study was to examine the incidence of coronavirus disease 2019 (COVID-19) among patients with immunomediated inflammatory diseases (IMIDs) treated with biologic or targeted synthetic disease-modifying antirheumatic drugs (bDMARDs and tsDMARDs) and to evaluate the influence of either IMIDs or related therapies on the incidence and evolution of COVID-19. METHODS: This observational, cross-sectional study was conducted from January 31, 2020, to May 15, 2020. Data of 902 patients were obtained from clinical records in hospitals, primary care units, and community pharmacies. Inclusion criteria were adults with IMIDs treated with bDMARDs or tsDMARDs who started therapy 3 months prior to study commencement. Patients with poor adherence to treatments were excluded. COVID-19 was classified as "definitive" (severe acute respiratory syndrome coronavirus 2 polymerase chain reaction [PCR]-positive), "possible" (characteristic symptoms and negative PCR), and "suspected" (characteristic symptoms but PCR not performed). RESULTS: COVID-19 was diagnosed in 70 patients (11 definitive, 19 possible, and 40 suspected). The cumulative incidence of definitive COVID-19 was 1.2%. When considering all cases, the incidence was 7.8%. Patients on biosimilars tumor necrosis factor blockers were more likely to have a diagnosis of COVID-19 (odds ratio, 2.308; p < 0.001). Patients on anti-B-cell therapies had a lower incidence of infections (p = 0.046). Low rates of hospitalization (14.3%), pneumonia (14.3%), death (2.9%), or thrombosis (2.9%) were observed, and 94.3% of patients recovered. CONCLUSIONS: The cumulative incidence of confirmed cases of COVID-19 was similar to the general population, with generally low hospitalization, intensive care management, and mortality rates. COVID-19 incidence was less frequent in patients with more severe immunosuppression.

Effectiveness of Workplace Exercise Interventions on Body Composition: A Systematic Review and Meta-Analysis.

OBJECTIVE: The aim of this review was to analyze the effectiveness of workplace exercise interventions on body composition (BC). DATA SOURCE: Studies published in PubMed, Scopus, SPORTDiscus, Web of Science, CINAHL and PsycINFO, from the earliest time point until 8 July 2020. STUDY INCLUSION AND EXCLUSION CRITERIA: Inclusion criteria were worksite interventions, in adults, Randomized Controlled Trials (RCTs), real exercise practice, and measuring BC outcomes. Exclusion criteria were full-text non-available, abstract not in English, and exercise protocol missing. DATA EXTRACTION: 157 studies were retrieved and assessed for inclusion by 2 independent reviewers, who also used the Cochrane's Collaboration Tool to assess study quality and risk of bias. DATA SYNTHESIS: We performed a meta-analysis to determine the effect size of the interventions on BC outcomes reported in at least 5 studies. RESULTS: Twelve RCTs were included (n = 1270, 66% women), quality of studies being low to high (25% moderate, 67% high). Interventions achieved a statistically significant decrease in waist circumference (SMD = 0.24; 95% confidence interval (CI): 0.06 to 0.41; p = 0.008), total mass fat (SMD = 0.21; 95%CI: 0.00 to 0.41; p = 0.047), and body adiposity index (SMD = 0.20; 95%CI: 0.00 to 0.41; p = 0.049). No changes were observed in body weight (SMD = 0.08 95%CI: -0.02 to 0.18; p = 0.128). Additionally, muscle mass increased in interventions that included strength training. There were no adverse events reported. CONCLUSION: The most effective workplace exercise interventions to improve BC combined supervised, moderate-intensity aerobic and strength training, for at least 4 months.

Clinical Characteristics, Frailty, and Mortality of Residents With COVID-19 in Nursing Homes of a Region of Madrid.

OBJECTIVES: To describe the clinical characteristics, 30-day mortality, and associated factors of patients living in nursing homes (NH) with COVID-19, from March 20 to June 1, 2020. DESIGN: This is a retrospective study. A geriatric hospital-based team acted as a consultant and coordinated the care of older people living in NHs from the hospital. SETTING AND PARTICIPANTS: A total of 630 patients aged 70 and older with Coronavirus Disease 2019 COVID-19 living in 55 NHs. METHODS: A logistic regression was performed to analyze the factors associated with mortality. In addition, Kaplan-Meier curves were applied according to mortality and its associated factors using the log-rank Mantel-Cox test. RESULTS: The diagnosis of COVID-19 was mainly made by clinical compatibility (N = 430). Median age was 87 years, 64.6% were women and 45.9% were transferred to be cared for at the hospital. A total of 282 patients died (44.7%) within the 30 days of first attention by the team. A severe form of COVID-19 occurred in 473 patients, and the most frequent symptoms were dyspnea (n = 332) and altered level of consciousness (n = 301). According to multiple logistic regression, male sex (P = .019), the Clinical Frailty Score (CFS) ≥6 (P = .004), dementia (P = .012), dyspnea (P < .001), and having a severe form of COVID-19 (P = .001), were associated with mortality, whereas age and care setting were not. CONCLUSIONS AND IMPLICATIONS: Mortality of the residents living in NHs with COVID-19 was almost 45%. The altered level of consciousness as an atypical presentation of COVID-19 should be considered in this population. A severe form of the disease, present in more than three-quarters of patients, was associated with mortality, apart from the male sex, CFS ≥6, dementia, and dyspnea, whereas age and care setting were not. These findings may also help to recognize patients in which the Advance Care Planning process is especially urgent to assist in the decisions about their care.

Effect of intravenous iron on functional outcomes in hip fracture: a randomised controlled trial.

OBJECTIVES: to determine the safety and effect of intravenous iron sucrose on functional outcomes, delirium, nosocomial infections and transfusion requirements in older patients with hip fracture. DESIGN: single-centre randomised, double-blind, placebo-controlled clinical trial. SETTING AND PARTICIPANTS: orthogeriatric share care service at an academic tertiary care hospital. A total of 253 patients were recruited: 126 patients were assigned to intravenous iron and 127 to placebo. METHODS: on days 1, 3 and 5 after admission, the iron group received 200 mg Venofer® (iron sucrose) in 100 ml saline and the placebo group 100 ml saline. The primary outcome was absolute functional gain, considered as Barthel index (BI) at discharge minus BI on admission. Secondary outcomes included incidence of postoperative delirium according to the confusion assessment method, proportion of patients recovering prior functional status at 3 months, postoperative transfusion requirements, haemoglobin at 3 months, incidence of nosocomial infections and safety. RESULTS: the median participant age was 87 (interquartile range, 82.5-91.5) years. Most patients were female (72.7%), and the median previous BI was 81(59-95). No significant effect of intravenous iron was observed for the primary outcome: the median AFG score was 17.1 points (4.8-23.3) in the intravenous iron group and 16 points (6-26) in the placebo group (P = 0.369). No significant treatment effects were observed for other functional outcomes or secondary end points. CONCLUSION: while we found no impact of intravenous iron sucrose on functional recovery, incidence of postoperative delirium, transfusion requirements, haemoglobin at 3 months, mortality and nosocomial infections rates in older patients with hip fracture, we did find that the intervention was safe.

Three-Year Effectiveness of Dimethyl Fumarate in Multiple Sclerosis: A Prospective Multicenter Real-World Study.

BACKGROUND: Dimethyl fumarate (DMF) has demonstrated efficacy in phase III studies. However, real-world data are still limited. OBJECTIVE: The objective of this study was to describe the profile of patients who receive DMF and to assess the effectiveness of DMF regarding relapses, disability progression, magnetic resonance imaging activity, and NEDA (No Evidence Disease Activity)-3 status in a Spanish population in a real-world setting. METHODS: We conducted a multicenter prospective study of patients who started DMF between 2014 and 2019 in Spain. Three subgroups were considered: naïve, switch to DMF because of inefficacy, and switch to DMF because of adverse effects. The effects of DMF on clinical and radiological measures were evaluated. RESULTS: Among 886 patients, 25.3% were naïve, 28.8% switched because of adverse effects, and 45.9% because of inefficacy. Median follow-up was 38.9 (interquartile range 22.6-41.8) months. Annualized relapse rates were 0.15, 0.10, and 0.10 at 12, 24, and 36 months respectively, and 77.7% of patients were relapse free at month 42. At 12, 24, and 42 months, 96.1%, 87.4%, and 79.7% of patients were progression free, respectively. The number of T1 gadolinium-enhancement (T1Gd+) lesions was 0.19, 0.14, and 0.18 at 12, 24, and 36 months. NEDA-3 status at month 42 was maintained by 49.8% of patients. Relapsing was associated with higher annualized relapse rates the year before (hazard ratio 1.34, p < 0.001) and to the inefficacy switch vs naïve group (hazard ratio 1.76, p = 0.003). A higher baseline Expanded Disability Status Scale score was associated with disability progression (hazard ratio 1.15, p = 0.003) and more T1Gd+ lesions (hazard ratio 1.07, p < 0.001) with radiological progression. A higher baseline Expanded Disability Status Scale score, a larger number of T1Gd+ lesions, and a switch because of inefficacy (vs adverse events) were all risk factors for losing NEDA-3 status. DMF was discontinued in 29.9% of patients, in 13.5% because of inefficacy. CONCLUSIONS: Our findings confirm the sustained effectiveness of DMF on the clinical and radiological activity of multiple sclerosis in a real-world setting, both in naïve patients and in those switching from other multiple sclerosis therapies.

Impact of 68Ga-PSMA PET/CT in the treatment of prostate cancer: Initial experience in Spain.

AIM: To evaluate whether positron-emission tomography/computed tomography with 68Ga-PSMA (68Ga-PSMA PET/CT) influences the therapeutic management of patients with primary or recurrent prostate cancer (PCa). BACKGROUND: Although 68Ga-PSMA PET/CT is one of the best options for staging or restaging patients with PCa, its availability is still very limited in Spain. The present study reports the results of the first group of patients in Spain who underwent 68Ga-PSMA PET/CT imaging. MATERIALS AND METHODS: All patients (n = 27) with a histological diagnosis of PCa who underwent 68Ga-PSMA PET/CT prior to the definitive treatment decision at the only centre with this technology in Spain during 2017-2018 were included. Two nuclear medicine physicians and a radiologist reviewed the imaging studies. The clinical impact was assessed from a theoretical perspective, based on the treatment that would have been applied if no data from the 68Ga-PSMA PET/CT were available. RESULTS: Most patients (n = 26; 96%) had persistent disease or biochemical recurrence after radical prostatectomy, radiotherapy, or combined treatment. One patient underwent 68Ga-PSMA PET/CT imaging to stage high-risk PCa. Overall, 68Ga-PSMA PET/CT was positive in 19 patients (70.4%). In 68.75% of these patients, none of the other imaging tests-MRI, CT, or bone scans-performed prior to the 68Ga-PSMA PET/CT were able to detect the presence of cancerous lesions. Overall, the findings of the 68Ga-PSMA PET/CT led to a modification of the therapeutic approach in 62.96% of the patients in the study. CONCLUSIONS: 68Ga-PSMA PET/CT alters the therapeutic approach in a substantial proportion of patients with PCa.

Tolerability and safety of dimethyl fumarate in relapsing multiple sclerosis: a prospective observational multicenter study in a real-life Spanish population.

BACKGROUND: Dimethyl fumarate (DMF) tolerability and safety in multiple sclerosis (MS) has been analyzed in randomized clinical trials. Real-life studies are needed to assess possible harms of this therapy in a wider MS population. OBJECTIVE: To evaluate DMF tolerability, safety and persistence in MS in a real-world setting. METHODS: We conducted a multicenter prospective study of patients who started DMF, attended in 16 public hospitals of Spain. A specific database was elaborated to collect data on most frequent adverse events (AE). Regression models were used to analyze the effect of demographic and clinical characteristics on risk of AEs and DMF discontinuation. RESULTS: We collected data of 886 patients (2681 patients/years-exposition) with median 39.5 (IQR 23, 51.5) months on DMF exposure; 25.3% were treatment naïve and 74.7% switched to DMF from other disease-modifying therapies. DMF was discontinued in 29.9% of patients, in 13.2% due to AEs and in 13.5% to inefficacy. AEs were experienced by 71.2%, being flushing the most frequent (44.1%), 5.4% developed grade III lymphopenia, without cases of grade IV. Females showed a higher risk of flushing and gastroenteric symptoms (OR 1.49, p = 0.011; OR 1.69, p = 0.001, respectively); lymphopenia was associated with older age (OR 1.04, p < 0.001), and a higher EDSS with lymphopenia (OR 1.10, p = 0.035) and DMF withdrawal (HR 1.43, p = 0.012). No safety problems were reported. CONCLUSIONS: Our findings confirm good tolerability and safety of DMF in real-world setting and suggest that women have an increased risk of AEs and higher baseline disability involves greater risk of drug discontinuation.

Lipid profile changes during the menopausal transition.

OBJECTIVES: There is evidence that the menopausal transition in women is accompanied by changes in the metabolic profile. We evaluated the lipid profile during the perimenopause to postmenopause transition and its association with menopausal status. METHODS: This is a retrospective observational study of laboratory studies from women presenting to the gynecology unit of Hospital Quirón Salud, Madrid (2007-2018) with irregular menstruation, amenorrhea or menopausal symptoms. Inclusion criteria were one or more blood samples with determinations of fasting glucose and lipids (total cholesterol, low-density lipoprotein cholesterol [LDL-c], high-density lipoprotein cholesterol [HDL-c] and triglycerides [TGs]) from women with a menopause diagnosis recorded in the hospital database. The determinations were classified as perimenopausal or postmenopausal based on the date of last menstruation. RESULTS: In total, 13,517 laboratory studies (3,073 perimenopausal and 10,444 postmenopausal) from 275 women were analyzed. Total cholesterol, LDL-c, and TG levels were significantly higher in postmenopausal women than in perimenopausal women, whereas HDL-c levels were significantly lower (P < 0.05 in all cases). Further adjustment by age showed differences only in LDL-c levels. Menopausal status, TG levels, and the number of pregnancies were independently related with total cholesterol and LDL-c levels. HDL-c levels were independently affected by menopausal age, TG levels, and number of pregnancies. Finally, TG concentration was independently affected by total cholesterol, LDL-c, and HDL-c levels. CONCLUSION: Our study suggests that significant changes in LDL-c levels occur during the menopausal transition. Total cholesterol and LDL-c changes are independently affected by menopausal status and HDL-c is influenced by menopausal age.

Antimicrobial Stewardship Programs Are Required in a Department of Surgery: "How" Is the Question A Quasi-Experimental Study: Results after Three Years.

Objective: Our aim was to describe our antimicrobial stewardship program and the methodology based on the results in a surgical department. Methods: Our study was a quasi-experimental study conducted from January 1, 2009, through September 30, 2017. The site was the General and Digestive Surgery Department in a public primary referral center, the University Hospital of Getafe (Madrid, Spain). We implemented the antimicrobial stewardship program following a prospective audit and feedback model, with a surgeon incorporated into the manaagement group. We studied the deaths and 30-day re-admission rates, length of stay, prevalence of gram-negative bacilli, meropenem resistance, and days of treatment with meropenem. Results: After three years of the program, we recorded a significant decrease in Pseudomonas aeruginosa prevalence, a significant increase in Klebsiella pneumoniae prevalence, a decrease in meropenem resistance, and a reduction in meropenem days of treatment. Conclusions: Antimicrobial stewardship programs have a desirable effect on patients. In our experience, the program team should be led by a staff from the particular department. When human resources are limited, the sustainability, efficiency, and effectiveness of interventions are feasible only with adequate computer support. Finally, but no less important, the necessary feedback between the prescribers and the team must be based on an ad hoc method such as that provided by statistical control charts, a median chart in our study.