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Colchicine is one of the most widely studied and best-known anti-inflammatory treatments. This study aimed to assess the effect of colchicine on risk of hospitalization due to COVID-19; and its effect on susceptibility to and severity of the virus in patients with COVID-19. We carried out a population-based case-control study. The following groups were applied: (1) to assess risk of hospitalization, cases were patients with a positive PCR who were hospitalized due to COVID-19, and controls without a positive PCR; (2) to assess susceptibility to COVID-19, cases were patients with a positive PCR (hospitalized and non-hospitalized), and the same controls; (3) to determine potential severity, cases were subjects with COVID-19 hospitalized, and controls patients with COVID-19 nonhospitalised. Different electronic, linked, administrative health and clinical databases were used to extract data on sociodemographic variables, comorbidities, and medications dispensed. The study covered 3060 subjects with a positive PCR who were hospitalized, 26 757 with a positive PCR who were not hospitalized, and 56 785 healthy controls. After adjustment for sociodemographic variables, comorbidities and other treatments, colchicine did not modify risk of hospitalization due to COVID-19 (adjusted odd ratio [OR] 1.08 [95% confidence interval (CI) 0.76−1.53]), patients' susceptibility to contracting the disease (adjusted OR 1.12 (95% CI 0.91−1.37)) or the severity of the infection (adjusted OR 1.03 [95% CI 0.67−1.59]). Our results would neither support the prophylactic use of colchicine for prevention of the infection or hospitalization in any type of patient, nor justify the withdrawal of colchicine treatment due to a higher risk of contracting COVID-19 Instituto de Salud Carlos III SI

The World Health Organization has proposed that a search be made for alternatives to vaccines for the prevention and treatment of COVID-19, with one such alternative being selective serotonin reuptake inhibitors (SSRIs). This study thus sought to assess: the impact of previous treatment with SSRI antidepressants on the severity of COVID-19 (risk of hospitalisation, admission to an intensive care unit [ICU], and mortality), its influence on susceptibility to SARS-CoV-2 and progression to severe COVID-19. We conducted a population-based multiple case-control study in a region in the north-west of Spain. Data were sourced from electronic health records. Adjusted odds ratios (aORs) and 95%CIs were calculated using multilevel logistic regression. We collected data from a total of 86,602 subjects: 3060 cases PCR+, 26,757 non-hospitalised cases PCR+ and 56,785 controls (without PCR+). Citalopram displayed a statistically significant decrease in the risk of hospitalisation (aOR=0.70; 95% CI 0.49–0.99, p = 0.049) and progression to severe COVID-19 (aOR=0.64; 95% CI 0.43–0.96, p = 0.032). Paroxetine was associated with a statistically significant decrease in risk of mortality (aOR=0.34; 95% CI 0.12 – 0.94, p = 0.039). No class effect was observed for SSRIs overall, nor was any other effect found for the remaining SSRIs. The results of this large-scale, real-world data study indicate that, citalopram, could be a candidate drug for being repurposed as preventive treatment aimed at reducing COVID-19 patients’ risk of progressing to severe stages of the disease. SI

The cardiovascular disease is the first cause of deaths in patients with diabetes mellitus 2. The objective is to evaluate and compare the weight loss in patients with diabetes treated with the different GLP-1 receptor agonists for the first time. Secondary endpoints are glycosylated hemoglobin reduction, changes in quality of life and physical activity and the safety of these drugs.It is a postauthorization, multicenter, non-randomized and prospective study. 360 Patients that will start treatment for the first time with GLP-1 receptor agonists will be recruited in 10 centers in the National Health System for a period of 6 months and 44 weeks of follow-up. The primary endpoint will be weight loss achieved with the different GLP-1 receptor agonists and the secondary endpoint will be glycosylated hemoglobin reduction, changes in the quality of life through the EuroQol‑5D and changes physical activity through the SF-12 questionnaire, and also the safety of these drugs. The estimate recruitment period will be 6 months, from 1 December 2021 to 1 May 2022. The follow up will finish in December 2022.The SEVERAL study will try to provide information about weight loss efficacy, changes in quality of life, physical activity and safety of the GLP-1 receptor agonists in patients with diabetes that start treatment with these drugs in the real life. This study try to compare different GLP-1 receptor gonists in terms of effectiveness and safety for a better posterior election when these drugs are used in patients with diabetes mellitus 2 and obesity.La enfermedad cardiovascular es la causa principal de muerte en pacientes con diabetes mellitus 2. El objetivo principal es evaluar y comparar prospectivamente la pérdida de peso en pacientes con diabetes mellitus 2 tratados por primera vez con los diferentes análogos de la GLP-1. Como variables secundarias se estudiará reducción de la hemoglobina glicosilada, cambios en calidad de vida y actividad física y la seguridad de estos fármacos.Método: Se trata de un estudio postautorización, multicéntrico, no leatorizado de seguimiento prospectivo. Se reclutarán 360 pacientes que inicien tratamiento por primera vez con análogos de la GLP1 en 10 centros del sistema público durante un período de 6 meses y un seguimiento de 44 semanas. La variable principal será la pérdida de peso con los diferentes análogos de la GLP1 y como variable secundaria se valorarán: reducción de hemoglobina glicosilada, cambios en la calidad de vida y actividad física a través del EuroQol-5D y SF-12 y seguridad. Se ha estimadoun período de reclutamiento de 6 meses, desde el 1 de Diciembre 2021 al 1 de Mayo 2022. El seguimiento finalizará en Diciembre de 2022.Discusión: El estudio intentará aportar información sobre la efectividad en pérdida de peso, cambios en calidad de vida, actividad física y seguridad de los análogos de la GLP1 en pacientes con diabetes mellitus 2 que inician tratamiento con estos fármacos en la vida real. Este trabajo pretende comparar los diferentes análogos de la GLP1 en términos de eficacia y eguridad para una posterior mejor elección en la prescripción de estos fármacos en pacientes con diabetes mellitus 2 y obesidad.

Background Silicosis is associated with an increased risk of developing systemic autoimmune rheumatic disease (SARD). The prognostic implications of this association are poorly characterized. The aim of this study was to determine the prevalence of SARD and autoimmune markers in a cohort of patients with exposure to silica and assess their impact on prognosis. Method We performed a prospective observational study of all patients attending the dedicated silicosis clinic of our pulmonology unit between 2009 and December 2017. Diagnosis was confirmed by a rheumatologist according to Spanish Rheumatology Society criteria. Autoimmune markers, pulmonary function tests, radiological progression, visits to the emergency department and primary care center, and hospital admissions for respiratory causes, and mortality were analyzed. Results Overall, 489 cases of silicosis and 95 cases of exposure were studied. In total, 54 (11.0%) patients with silicosis had SARD: 12 (2.4%) rheumatoid arthritis, 10 (2.0%) systemic lupus erythematosus, 10 (2.0%) systemic sclerosis, 3 (0.6%) Sjogren syndrome, 2 (0.4%) vasculitis associated with anti-neutrophil cytoplasmic antibodies (ANCA +), 6 (1.2%) psoriatic arthritis, 3 (0.6%) ankylosing spondylitis, and 8 (1.6%) other autoimmune diseases with no special features. The patients with SARD visited the emergency room more often (63.0% vs. 42.5%; p = 0.004), and progressed more rapidly (22.2 vs. 11.7%; p = 0.030). Conclusions The presence of systemic rheumatic autoimmune diseases involves radiological progression and a higher clinical impact.

Resumen Introduccion La silicosis se asocia con aumento del riesgo de padecer alguna de las enfermedades reumatologicas autoinmunitarias sistemicas (ERAS), aunque no se conocen las implicaciones clinicas de esta asociacion. El objetivo del estudio es determinar la prevalencia de ERAS y de marcadores de autoinmunidad en una cohorte de pacientes con exposicion a inhalacion de polvo de silice y evaluar su impacto clinico. Metodo Estudio observacional prospectivo, en pacientes atendidos en una consulta monografica de silicosis, desde 2009 hasta diciembre 2017. El diagnostico de ERAS se confirmo por un especialista en Reumatologia segun criterios de la Sociedad Espanola de Reumatologia. Se analizaron marcadores de autoinmunidad, pruebas de funcion respiratoria, progresion radiologica e impacto clinico medido por visitas a Atencion Primaria, a Servicio de Urgencias, ingresos hospitalarios por causa respiratoria y mortalidad. Resultados Se estudiaron 489 casos de silicosis y 95 de exposicion a inhalacion de polvo de silice sin silicosis. De los pacientes con silicosis 54 (11,0%) tenian ERAS: 12 (2,4%) artritis reumatoide, 10 (2,0%) lupus eritematoso sistemico, 10 (2,0%) esclerosis sistemica, seis (1,2%) artritis psoriasica, tres (0,6%) sindrome de Sjogren, dos (0,4%) vasculitis asociada con anticuerpos anticitoplasma de neutrofilos, tres (0,6%) espondiloartritis y ocho (1,6%) enfermedad autoinmunitaria sin caracteristicas especificas. Los pacientes con ERAS realizaron mas visitas a urgencias (63,0 vs. 42,5%; p = 0,004), y experimentaron mayor progresion (22,2 vs. 11,7%; p = 0,030). Conclusiones Los pacientes con silicosis presentan una prevalencia de ERAS elevada y su presencia se asocia con una mayor progresion radiologica y un mayor impacto clinico.

Little is known about the role played by anticoagulants in COVID-19.The aim of this study was to assess the impact of previous anticoagulant treatment on risk of hospitalization due to COVID-19, progression to severe COVID-19 and susceptibility to COVID-19 infection.We conducted a multiple population-based case-control study in northwest Spain, in 2020, to assess (1) risk of hospitalization: cases were all patients admitted due to COVID-19 with PCR confirmation, and controls were a random matched sample of subjects without a positive PCR; (2) progression: cases were hospitalized COVID-19 subjects, and controls were all non-hospitalized COVID-19 patients; and (3) susceptibility: cases were patients with a positive PCR (hospitalized and non-hospitalized), and the controls were the same as for the hospitalization model. Adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using a generalized linear mixed model.The consumption of antivitamin K and direct-acting anticoagulants apparently was not associated with the risk of progression to severe COVID-19 (OR 0.93 [95% CI 0.74-1.17] and OR 1.04 [95% CI 0.79-1.36], respectively). Antivitamin K anticoagulants were associated with a significantly lower risk of hospitalization (OR 0.77 [95% CI 0.64-0.93]), which, in part, can be explained by a decreased risk of susceptibility to infection (OR 0.83 [95% CI 0.74-0.92]). The use of direct-acting anticoagulants was not associated with the risk of hospitalization, although it also seems to decrease susceptibility (OR 0.85 [95% CI 0.74-0.98]). It has also been observed that low-molecular-weight heparins were associated with an increased risk of progression to severe COVID-19 (OR 1.25 [95% CI 1.01-1.55]).The results of this study have shown that antivitamin K anticoagulants and direct-acting anticoagulants do not increase the risk of progression to more severe stages. Antivitamin K consumption was associated with a lower risk of hospitalization and susceptibility to infection.

Silicosis is a diffuse interstitial lung disease caused by sustained inhalation of silica and silicates. Several cytokines are activated by their inhalation and can mediate the process of pulmonary fibrosis. The identification of biomarkers could allow an early diagnosis before the development of radiological alterations and help monitor the evolution of patients. The objetive of this study was to determine the clinical significance of specific biomarkers, to estimate their association with the development, severity and/or progression of silicosis, and identify determinants of this evolution. We conducted a prospective observational study in patients attending the pulmonology clinic from 2009 to 2018. Serum levels of the following inflammatory mediators were assessed: interleukin-6 (IL-6), interleukin 2 receptor subunit alpha (IL2R) interleukin 1 beta (IL1B), interleukin-8 (IL-8), tumour necrosis factor-alpha (TNF-α), transforming growth factor-beta1 (TGF-β1), alpha-1 antitrypsin (AAT), C-reactive protein (CRP), lactate dehydrogenase (LDH) and ferritin in subjects exposed to silica, with and without silicosis. Association between those inflammatory mediators with lung function measurements and radiological severity of disease and their impact on prognosis were analysed. 337 exposed to silica (278 with silicosis) and 30 subjects in the control group were included. IL-8, α1AT, ferritin, CRP and LDH levels were higher in silicosis than in those exposed to silica without silicosis. IL-8, LDH and AAT levels were associated with progression of silicosis and IL-6, IL-8, LDH, AAT, ferritin, and CRP with vital status. The results of the ROC analysis indicated the potential of IL-8 as a biomarker in the presence of silicosis and for the prediction of mortality.

Current evidence on the diagnostic yield and safety of pleural cryobiopsy (CB) is based on a series of heterogeneous studies with limited cohorts. A pooled analysis of these studies could improve the evidence and contribute to a better understanding of this new technique.We performed a systematic review and meta-analysis of published studies that included data on the yield and diagnostic safety of pleural CB compared with procedures performed using conventional flexible forceps. The heterogeneity of the analysis was evaluated by determining the I2 index, while study quality was measured with the QUADAS-2 tool.Seven studies involving 356 patients were used for the final evaluation. In 55.6%, the etiology of the pleural effusion was malignant, 61.1% of which were lung cancer. The diagnostic yield of pleural CB was 95% (95% CI 92-97) vs. 91% (95% CI 87-94) with conventional flexible forceps (P = .019). Mild bleeding was reported in 67% of CB procedures (95% CI 62-72) compared with 85% of conventional flexible forceps procedures (95% CI 79-90) (P .001). CB specimens were larger, and fewer artifacts were detected. A pooled analysis of the detection of molecular changes could not be performed. Heterogeneity was moderate to high, although the quality of the studies was acceptable.Pleural CB is a safe technique with a high yield for etiological diagnosis of pleural effusion, and larger specimens with fewer artifacts are obtained. Molecular determinations should be investigated in more depth.

Low-density lipoprotein cholesterol (LDLc) is the lead effector of atherosclerosis and main treatment target. Bempedoic acid is a novel oral drug in the therapeutic armamentarium which is able to reduce LDLc. The objectives of this study were (1) to select the potential patients for administering bempedoic acid such as those with a very high cardiovascular risk in which objectives of LDLc were not achieved despite conventional treatment with PCSK9 inhibitors (PCSK9i) and/or statins and ezetimibe and (2) to estimate the cost-effectiveness of bempedoic acid in different scenarios. The methods used were a multicenter and retrospective study of 652 patients initiating treatment with any PCSK9 inhibitor in 17 different hospitals. Before and on-treatment LDLc cholesterol levels, medical treatments, clinical indication, and baseline characteristics were recorded. The results obtained from 443 subjects in secondary prevention were analyzed. The mean (±) LDLc level at baseline was 142.5 ± 46.4 mg/dL and 61.5 ± 40.5 mg/dL in the follow-up, with a reduction of 55.9% ( P0.0001); 71.6% of the patients reached the target of LDL55 mg/dL or50% reduction. Of those patients treated with medium-intensity and low-intensity statins plus PCSK9 inhibitors (with or without ezetimibe), only 5.7% of them were able to reduce LDL below 55 mg/dL and the main LDLc reduction in this group was the lowest (42.9% on average). Patients with TG values135 mg/dL represented 41.6% of the sample, of which approximately 10% of them were using fibrates. Assuming only LDLc reduction and the UK price, the incremental cost-effectiveness ratio was 88,359€; 83,117€; 82,378€; and 79,015€ for different discount rates. In conclusion, one-third of the patients could achieve the target LDL proposed in the 2019 ESC/EAS guidelines. Approximately 10% of them could also benefit from treating hypertriglyceridemia as indicated in the 2021 ESC guidelines on cardiovascular disease prevention. Patients with medium-intensity and low-intensity statins plus PCSK9i and ezetimibe would be the most benefited. Bempedoic acid could be a not cost-efficacy therapy in all the scenarios, but we need to wait for the CLEAR OUTCOMES Trial results.

Background The role of extracellular vesicles (EVs) in human immunodeficiency virus (HIV) pathogenesis is unknown. We examine the cellular origin of plasma microvesicles (MVs), a type of ectocytosis-derived EV, the presence of mitochondria in MVs, and their relationship to circulating cell-free mitochondrial deoxyribonucleic acid (ccf-mtDNA) in HIV-infected patients and controls. Methods Five participant groups were defined: 30 antiretroviral therapy (ART)-naive; 30 ART-treated with nondetectable viremia; 30 elite controllers; 30 viremic controllers; and 30 HIV-uninfected controls. Microvesicles were quantified and characterized from plasma samples by flow cytometry. MitoTrackerDeepRed identified MVs containing mitochondria and ccf-mtDNA was quantified by real-time polymerase chain reaction. Results Microvesicle numbers were expanded at least 10-fold in all HIV-infected groups compared with controls. More than 79% were platelet-derived MVs. Proportions of MVs containing mitochondria (22.3% vs 41.6%) and MV mitochondrial density (706 vs 1346) were significantly lower among HIV-infected subjects than controls, lowest levels for those on ART. Microvesicle numbers correlated with ccf-mtDNA levels that were higher among HIV-infected patients. Conclusions A massive release of platelet-derived MVs occurs during HIV infection. Some MVs contain mitochondria, but their proportion and mitochondrial densities were lower in HIV infection than in controls. Platelet-derived MVs may be biomarkers of platelet activation, possibly reflecting pathogenesis even in absence of HIV replication.

Background: differences in cell-free DNA (cfDNA) fragments have been described as a valuable tool to distinguish cancer patients from healthy individuals. We aim to investigate the concentration and integrity of cfDNA fragments in saliva from oral squamous cell carcinoma (OSCC) patients and healthy individuals in order to explore their value as diagnostic biomarkers. Methods: saliva samples were collected from a total of 34 subjects (19 OSCC patients and 15 healthy controls). The total concentration of salivary cfDNA (scfDNA) was determined using a fluorometry method and quantitative real-time polymerase chain reaction (qPCR). To evaluate the scfDNA quantity and integrity, qPCR targeting Arthobacter luteus (ALU) sequences at three amplicons of different lengths (60, 115, and 247 bp, respectively) was carried out. ScfDNA integrity indexes (ALU115/ALU60 and ALU247/ALU60) were calculated as the ratio between the absolute concentration of the longer amplicons 115 bp and 247 bp and the total scfDNA amount (amplicon 60 bp).Results: the total scfDNA concentration (ALU60) was higher in OSCC than in healthy donors, but this trend was not statistically significant. The medians of scfDNA integrity indexes, ALU115/ALU60 and ALU247/ALU60, were significantly higher in OSCC, showing area under the curve values of 0.8211 and 0.7018, respectively. Conclusion: our preliminary results suggest that scfDNA integrity indexes (ALU115/ALU60 and ALU247/ALU60) have potential as noninvasive diagnostic biomarkers for OSCC SI

Aims Adalimumab is a biological therapy used to treat different chronic inflammatory diseases. At present, there is an increasing number of adalimumab biosimilars. To assume the acceptability of interchangeability between reference adalimumab and biosimilars, there should be evidence about efficacy and safety of this switching. Regulation of this practice falls under the authority of individual European Union Member States. The aim of this study is to systematically review the evidence on the efficacy, safety and immunogenicity of switching between reference adalimumab and biosimilars in different chronic immune-mediated inflammatory diseases. Methods Studies presenting data about switching between reference adalimumab and biosimilars were identified by sensitive search strategies in Medline and EMBASE from 1 January 2004 to 30 June 2021. Results A total of 471 references were obtained and 21 finally included in the analysis (total number of patients switching: 2802). Eight different adalimumab biosimilars were tested after receiving reference adalimumab. Eight articles included rheumatoid arthritis (RA), one miscellaneous rheumatic disease, six psoriasis (PSO) and six inflammatory bowel disease (IBD) patients. Overall, the efficacy results in the switching groups were comparable to those obtained in the arms of continuous biosimilar and continuous reference adalimumab. There were no significant differences in treatment emergent adverse events, anti-drug or neutralising antibodies among the three groups. Conclusions Switching between reference adalimumab and biosimilars has no impact on efficacy, safety and immunogenicity in patients with RA, PSO and IBD. This finding was consistent for the different adalimumab biosimilars analysed. These conclusions could probably be extended to other rheumatic diseases such as psoriatic arthritis and ankylosing spondylitis.

Aberrant methylation of tumor suppressor genes has been reported as an important epigenetic silencer in head and neck cancer (HNC) pathogenesis. Here, we performed a comprehensive meta-analysis to evaluate the overall and specific impact of salivary gene promoter methylation on HNC risk. The methodological quality was assessed using the Newcastle–Ottawa scale (NOS). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the association and Egger’s and Begg’s tests were applied to detect publication bias. The frequency of salivary DNA promoter methylation was significantly higher in HNC patients than in healthy controls (OR: 8.34 (95% CI = 6.10–11.39; p < 0.01). The pooled ORs showed a significant association between specific tumor-related genes and HNC risk: p16 (3.75; 95% CI = 2.51–5.60), MGMT (5.72; 95% CI = 3.00–10.91), DAPK (5.34; 95% CI = 2.18–13.10), TIMP3 (3.42; 95% CI = 1.99–5.88), and RASSF1A (7.69; 95% CI = 3.88–15.23). Overall, our meta-analysis provides precise evidence on the association between salivary DNA promoter hypermethylation and HNC risk. Thus, detection of promoter DNA methylation in saliva is a potential biomarker for predicting HNC risk.

Aim The aim of this study is to determine the most useful diagnostic tools to differentiate appendicitis from non-specific abdominal pain (NSAP) in pre-school children. Methods We prospectively evaluated all children aged 5 years or younger admitted for suspected appendicitis at a paediatric emergency department during 5 years. Cases of NSAP and appendicitis were enrolled according to inclusion and exclusion criteria. The different variables collected were assessed by statistic and diagnostic accuracy studies. Results A total of 82 patients were studied: 27 cases of NSAP and 55 cases of appendicitis. We found no symptoms or signs with a high power of discrimination between both processes. Complicated cases of appendicitis begin to appear when the duration of symptoms exceeds 12 h. Among laboratory tests, C-reactive protein (CRP) value >34 mg/L was the variable with a greater association to appendicitis (odds ratio 9.8). Abdominal ultrasound (US) had high sensitivity and specificity to differentiate appendicitis, significantly improving its diagnostic accuracy when the duration of symptoms exceeds 12 h. Conclusions A good history and physical examination are important in the diagnostic process, but reliable physical signs can be difficult to elicit in pre-school children. CRP and abdominal US are useful investigations that can improve diagnostic accuracy. According to our results, abdominal pain duration longer than 12 h or CRP value >34 mg/L should be an indication to perform an abdominal US in pre-school children with right lower quadrant tenderness.

To evaluate exercise capacity using the 6-minute walk test (6MWT) in patients with complicated silicosis, and to determine how results shape the prognostic value of 6MWT for hospitalization and mortality.Prospective observational study in 143 patients with complicated silicosis who performed the 6MWT in our outpatient pulmonology clinic between 2009 and the end of 2016. Lung function tests, computed tomography findings and 6MWT parameters (distance walked and oxygen desaturation) were evaluated.Patients with complicated silicosis walked 387±92m. Results deteriorated as silicosis severity increased; category A: 407±97m, B: 370±88m, and C: 357±68m (P=.022). The 6MWT correlated positively with lung function and inversely with dyspnea determined by mMRC (P.001). Patients with moderate/severe emphysema and greater CT90 presented a worse result on 6MWT. Patients who walked350m had more hospitalizations (3.7±4.0) than those who walked350m (1.1±2.9). There was an impact on survival: non-survivors walked 327.9±73.0m, while survivors walked 404.5±89.7m (P.001).Spirometry values and category of complicated silicosis correlated with 6MWT and distance walked was a prognostic factor for hospitalization and mortality. The 6MWT is a useful tool in occupational health for monitoring patients with silicosis.

Resumen Objetivo Evaluar la capacidad de ejercicio, utilizando la prueba de la marcha de 6 minutos (6MWT), en pacientes con silicosis complicada, e identificar factores relacionados con dicho resultado, asi como su valor pronostico de hospitalizacion y mortalidad. Metodo Estudio observacional prospectivo en 143 pacientes diagnosticados de silicosis complicada atendidos en consulta de neumologia desde 2009 hasta diciembre 2016, sin limitacion para hacer la 6MWT. Se evaluaron las pruebas de funcion pulmonar, los hallazgos de la tomografia computarizada y los parametros de la 6MWT (distancia caminada y desaturacion de oxigeno). Resultados Los pacientes con silicosis complicada caminaban una media de 387 ± 92 m. Los resultados fueron peores al aumentar la gravedad de la enfermedad; en silicosis A: 407 ± 97; B: 370 ± 88, y C: 357 ± 68 (p = 0,022). La 6MWT mostraba una correlacion positiva con la funcion pulmonar e inversa con la disnea (p 350 (1,1 ± 2,9). Los fallecidos al final del seguimiento caminaron 327,9 ± 73,0 frente a los que sobreviven, que caminaron 404,5 ± 89,7 m (p Conclusiones Los valores de la espirometria y la categoria de la silicosis se relacionan con el resultado de la 6MWT, que resulto ser factor pronostico para hospitalizacion y mortalidad. La 6MWT se perfila como una herramienta util en salud ocupacional para el seguimiento de pacientes con silicosis.

Gastroenterology; Pharmacogenetics Gastroenterologia; Farmacogenètica Gastroenterología; Farmacogenética Bleeding in non-steroidal anti-inflammatory drug (NSAID) users limited their prescription. This first multicenter full case–control study (325 cases and 744 controls), explored the association of e-NOS intron 4 variable number tandem repeat (VNTR) polymorphism with upper gastrointestinal hemorrhage (UGIH) in NSAID exposed and unexposed populations and assessed any interaction between this polymorphism and NSAIDs. NSAID users carrying e-NOS intron 4 wild type genotype or VNTR polymorphism have higher odds of UGIH than those unexposed to NSAIDs [Odds Ratio (OR): 6.62 (95% Confidence Interval (CI): 4.24, 10.36) and OR: 5.41 (95% CI 2.62, 11.51), respectively], with no effect modification from VNTR polymorphism-NSAIDs interaction [Relative Excess Risk due to Interaction (RERI): −1.35 (95% CI −5.73, 3.03); Synergism Index (S): 0.77 (95% CI 0.31, 1.94)]. Similar findings were obtained for aspirin exposure. Non-aspirin NSAID users who carry e-NOS intron 4 VNTR polymorphism have lower odds of UGIH [OR: 4.02 (95% CI 1.85, 8.75) than those users with wild type genotype [OR: 6.52 (95% CI 4.09, 10.38)]; though the interaction estimates are not statistically significant [RERI: −2.68 (95% CI −6.67, 1.31); S: 0.53 (95% CI 0.18, 1.55)]. This exploratory study suggests that the odds of UGIH in NSAID or aspirin users does not modify according to patient´s e-NOS intron 4 genotype. This work was supported by a grant from Instituto de Salud Carlos III [PI12/02414]/Plan Estatal de I + D + I 2012–2016; Fondo Europeo de Desarrollo Regional (FEDER); the Novartis, Pfizer and Dr Esteve pharmaceutical companies; the Health Research Fund/Fondo de Investigación Sanitaria [PI021512, PI021364, PI020661, PI021572]; Ministry of Health & Consumer Affairs, Spain [SAF2002-04057]; Galician Regional Authority, Spain [PGIDIT03PXIC20806PN]; Department of Health of the Basque Country [03/11092 and 11/111103]; and Fundacion vasca de innovacin e investigacin sanitarias [OSIBG19/002 and OSIBG18/105]. The genotyping service was carried out at CEGEN-PRB3-ISCIII; Instituto de Salud Carlos III and ERDF [PT17/0019, of the PE I + D + I 2013–2016].

DNA hypermethylation is an important epigenetic mechanism for gene expression inactivation in head and neck cancer (HNC). Saliva has emerged as a novel liquid biopsy representing a potential source of biomarkers. We performed a comprehensive meta-analysis to evaluate the overall diagnostic accuracy of salivary DNA methylation for detecting HNC. PubMed EMBASE, Web of Science, LILACS, and the Cochrane Library were searched. Study quality was assessed by the Quality Assessment for Studies of Diagnostic Accuracy-2, and sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (dOR), and their corresponding 95% confidence intervals (CIs) were calculated using a bivariate random-effect meta-analysis model. Meta-regression and subgroup analyses were performed to assess heterogeneity. Eighty-four study units from 18 articles with 8368 subjects were included. The pooled sensitivity and specificity of salivary DNA methylation were 0.39 and 0.87, respectively, while PLR and NLR were 3.68 and 0.63, respectively. The overall area under the curve (AUC) was 0.81 and the dOR was 8.34. The combination of methylated genes showed higher diagnostic accuracy (AUC, 0.92 and dOR, 36.97) than individual gene analysis (AUC, 0.77 and dOR, 6.02). These findings provide evidence regarding the potential clinical application of salivary DNA methylation for HNC diagnosis This work was co-funded by the Instituto de Salud Carlos III (ISCIII) (PI20/01449) and the European Regional Development Fund (FEDER). A.D.-L. is funded by a “Juan Rodés” contract from ISCIII (JR17/00016). L.M.-R. is funded by a “Miguel Servet” contract from ISCIII (CP20/00129) SI

Introduction This study aimed to perform a systematic review and meta-analysis on accessory mental foramen (AMF) research using cone-beam computed tomographic (CBCT) imaging. Methods A systematic review was performed in PubMed, Embase, Thomas Reuter's Web of Science, Scopus, and ScienceDirect databases according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis statement. Articles focusing on AMF prevalence and location using CBCT imaging were selected without language restrictions. Studies reporting pooled results only or presenting any pathology in the area surrounding the mental foramen (MF) were excluded. A meta-analysis using random effects was performed. Results The present meta-analysis included a total of 46 articles involving 21,761 subjects. The overall pooled AMF prevalence was 7.87% (95% confidence interval [CI], 6.69–9.24) in subjects and 4.75% (95% CI, 3.79–5.95) in hemimandibles (n = 31,158). AMF presence was most commonly unilateral, reaching 90.15% (95% CI, 82.98–94.49). AMFs were significantly more frequent in right hemimandibles (χ2 = 5.20, P Conclusions Our meta-analysis demonstrates that AMF prevalence is considerable and should not be underestimated. AMFs are most frequently located in right hemimandibles. The presence of AMFs superior to the MF is frequent. Around 3% of people present superior AMFs. This fact puts those patients at greater risk for injury when performing periapical surgery in this area.

Decision making in hospitals, and especially in their own healthcare services, is hardly referenced in the literature. During the pandemic period, healthcare services have put in place contingency plans to minimize the consequences of the coronavirus on professionals and patients. However, the deployment of contingency plans and results are hardly shared, depriving other services of references to refute, compare or emulate the aforementioned plans. The objective of this work was the description of the implementation and evaluation of Contingency Plans in the Covid-19 pandemic in a unit of inflammatory bowel disease of a Digestive Service in the Sanitary Area of Pontevedra and O Salnés.A team of managers and professionals adapted the 10 measures recommended by Deloitte to face a pandemic to the healthcare environment. The measures were then formulated as a checklist. From the Plan-Do-Check-Act improvement cycle, they were grouped into categories: risk management, organizational management and decision-making. Finally, an external team carried out a qualitative evaluation of the implementation of the contingency plan carried out.The Intestinal Inflammatory Disease Unit of the Digestive Service has obtained an assessment of compliance with the 10 recommended measures to confidently face a pandemic.Sharing the deployment of the contingency plan and its results is useful to identify good practices. This article shows a method to evaluate decision-making in pandemic situations. The outcomes faces the The Intestinal Inflammatory Disease Unit in an excelent position.La toma de decisiones en los hospitales y en sus propios servicios asistenciales apenas está referenciada en la literatura. Durante el período de pandemia por Covid-19, los servicios asistenciales han puesto en marcha planes de contingencia para minimizar las consecuencias del coronavirus en los profesionales y pacientes. Sin embargo, apenas se comparte el despliegue de esos planes de contingencia, ni sus resultados, privando de referencias para refutar, comparar o emular los citados planes a otros servicios asistenciales u hospitales. El objetivo del trabajo fue la descripción de la puesta en marcha de dichos planes ante la pandemia de Covid-19 en la Unidad de Enfermedad Inflamatoria Intestinal de un Servicio de Digestivo en el Área Sanitaria de Pontevedra e O Salnés (Galicia).Un equipo de directivos y profesionales adaptaron al entorno sanitario las 10 medidas recomendadas por Deloitte para afrontar una pandemia. A continuación, se formularon las medidas como listado de comprobación. A partir del ciclo de mejora Plan-Do-Check-Act, se agruparon las 10 medidas en las siguientes categorías: gestión del riesgo, gestión organizacional y toma de decisiones. Por último, un equipo externo realizó una evaluación cualitativa de la puesta en marcha del plan de contingencia realizado.La Unidad de Enfermedad Inflamatoria Intestinal del Servicio de Digestivo realizó un plan de contingencia que presenta un cumplimiento de las 10 medidas recomendadas para hacer frente a la pandemia de Covid-19 con garantías.Compartir el despliegue del plan de contingencia y sus resultados es útil para identificar buenas prácticas. Este trabajo ofrece un método para evaluar las tomas de decisiones en los plantes de contingencia en situaciones de pandemia. Los resultados sitúan a la Unidad de Enfermedad Inflamatoria Intestinal en el rango de la excelencia.

Background. Human papillomavirus (HPV) infection has been recognized as an important risk factor in cancer. The purpose of this systematic review and meta-analysis was to determine the prevalence and effect size of association between salivary HPV DNA and the risk of developing oral and oropharyngeal cancer. Methods. A systematic literature search of PubMed, EMBASE, Web of Science, LILACS, Scopus and the Cochrane Library was performed, without language restrictions or specified start date. Pooled data were analyzed by calculating odds ratios (ORs) and 95% confidence intervals (CIs). Quality assessment was performed using the Newcastle–Ottawa Scale (NOS). Results. A total of 1672 studies were screened and 14 met inclusion criteria for the meta-analysis. The overall prevalence of salivary HPV DNA for oral and oropharyngeal carcinoma was 43.2%, and the prevalence of salivary HPV16 genotype was 27.5%. Pooled results showed a significant association between salivary HPV and oral and oropharyngeal cancer (OR = 4.94; 2.82−8.67), oral cancer (OR = 2.58; 1.67−3.99) and oropharyngeal cancer (OR = 17.71; 6.42−48.84). Significant associations were also found between salivary HPV16 and oral and oropharyngeal cancer (OR = 10.07; 3.65−27.82), oral cancer (OR = 2.95; 1.23−7.08) and oropharyngeal cancer (OR = 38.50; 22.43−66.07). Conclusions. Our meta-analysis demonstrated the association between salivary HPV infection and the incidence of oral and oropharyngeal cancer indicating its value as a predictive indicator.

Background: Saliva represents a promising non-invasive source of novel biomarkers for diagnosis and prognosis cancer. This meta-analysis evaluates the diagnostic value of salivary biomarkers for detection of malignant non-oral tumours to better define the value of saliva as an alternative liquid biopsy. Materials and methods: We performed a systematic review and meta-analysis. PubMed, Embase, LILACS and the Cochrane Library were searched to identify articles that examined the potential of salivary biomarkers for the diagnosis of malignant non-oral tumours. To assess the overall accuracy, we calculated the diagnostic odds ratio (DOR), area under hierarchical summary receiver operating characteristic (AUC) curve, sensitivity, specificity, positive likelihood ratio (PLR) and negative likelihood ratio (NLR) using a random- or fixed-effects model. Heterogeneity and publication bias were assessed. Statistical tests were two-sided. Results: One hundred fifty-five study units from 29 articles with 11,153 subjects were included. The pooled sensitivity, specificity, PLR, NLR, DOR and AUC were 0.76 (95% confidence intervals (CI), 0.74–0.77), 0.76 (95% CI, 0.75–0.77), 3.22 (95% CI, 2.92–3.55), 0.31 (95% CI, 0.28–0.34), 13.42 (95% CI, 12.28–15.96) and 0.85 (95% CI, 0.84–0.87), respectively. Conclusion: Salivary biomarkers may be potentially used for non-invasive diagnosis of malignant non-oral tumours.Key messagesThis meta-analysis evaluates the diagnostic value of salivary biomarkers for detection of malignant non-oral tumours to better define the role of saliva as an alternative liquid biopsy.Salivary biomarkers showed 85% accuracy for cancer distant to the oral cavity.Saliva represents a promising non-invasive source of novel biomarkers in cancer. This meta-analysis evaluates the diagnostic value of salivary biomarkers for detection of malignant non-oral tumours to better define the role of saliva as an alternative liquid biopsy. Salivary biomarkers showed 85% accuracy for cancer distant to the oral cavity. Saliva represents a promising non-invasive source of novel biomarkers in cancer.

Background HIV infection is a growing public health problem in Sierra Leone and the wider West Africa region. The countrywide HIV prevalence was estimated at 1.7% (67,000 people), with less than 30% receiving life-saving ART in 2016. Thus, HIV-infected patients tend to present to health facilities late, with high mortality risk. Methods We conducted a prospective study of HIV inpatients aged ≥15 years at Connaught Hospital in Freetown—the main referral hospital in Sierra Leone—from July through September 2017, to assess associated factors and predictors of HIV-related mortality. Results One hundred seventy-three HIV inpatients were included, accounting for 14.2% (173/1221) of all hospital admissions during the study period. The majority were female (59.5%, 70/173), median age was 34 years, with 51.4% (89/173) of them diagnosed with HIV infection for the first time during the current hospitalization. The most common admitting diagnoses were anemia (48%, 84/173), tuberculosis (24.3%, 42/173), pneumonia (17.3%, 30/173) and diarrheal illness (15.0%, 26/173). CD4 count was obtained in 64.7% (112/173) of patients, with median value of 87 cells/μL (IQR 25–266), and was further staged as severe immunosuppression: CD4 p = 0.04) and focal limb weakness (p = 0.04); alcohol use (p = 0.01); jaundice (p = 0.02); cerebral toxoplasmosis (p = 0.01); and tuberculosis (p = 0.04) were significantly associated with mortality; however, only jaundice (AOR 0.11, 95% CI [0.02–0.65]; p = 0.01) emerged as an independent predictor of mortality. Conclusion HIV-infected patients account for a substantial proportion of admissions at Connaught Hospital, with a high morbidity and in-hospital mortality burden. These findings necessitate the implementation of specific measures to enhance early HIV diagnosis and expand treatment access to all HIV-infected patients in Sierra Leone.

Oral squamous cell carcinoma (OSCC) is often diagnosed at advanced stages and is associated with poor survival rates. Increasing evidence suggests that microRNAs (miRNAs) present in liquid biopsies could be potential biomarkers for non-invasive OSCC diagnosis. Here, we performed a comprehensive meta-analysis to evaluate the overall diagnostic accuracy of blood and salivary miRNAs in detecting OSCC. A literature search using PubMed EMBASE, Web of Science, LILACS, Scopus, and the Cochrane Library was undertaken up to February 2019. Study quality was assessed with the Quality Assessment for Studies of Diagnostic Accuracy-2, and sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and their corresponding 95% confidence intervals (CIs) were calculated using a bivariate random-effect meta-analysis model. Meta-regression and subgroup analyses were performed to assess the heterogeneity. Twenty-five study units from 16 articles with 2562 subjects were included in this meta-analysis. The pooled sensitivity and specificity of blood and salivary miRNAs in the diagnosis of OSCC were 0.78 (95% CI: 0.76-0.80) and 0.82 (95% CI: 0.79-0.84), respectively, and the pooled positive and negative likelihood ratios were 4.31 (95% CI: 3.38-5.51) and 0.25 (95% CI: 0.20-0.32), respectively. The overall area under the curve was 0.91 (95% CI: 0.88-0.93), with a diagnostic odds ratio of 21.46 (95% CI: 13.37-34.45). These findings provide evidence regarding the potential clinical application of blood and salivary miRNAs as a novel, non-invasive, and accurate diagnostic tool for OSCC.

Introduction The aim of this study was to assess the diagnostic value of the biomarker fibrinogen (FB), along with the markers white blood cell (WBC) count, absolute neutrophil count (ANC), and C-reactive protein (CRP), to discriminate appendicitis from nonspecific abdominal pain (NSAP) in preschool children. Materials and Methods We prospectively evaluated all children aged Results A total of 82 patients were enrolled in the study (27 NSAP, 17 uncomplicated, and 38 complicated appendicitides). WBC and ANC had moderate diagnostic accuracy for appendicitis versus NSAP (WBC: AUC 0.66, ANC: AUC 0.67). CRP and FB had good diagnostic accuracy for appendicitis versus NSAP (CRP: AUC 0.78, FB: AUC 0.77). WBC and ANC are not useful to discriminate complicated versus uncomplicated appendicitis (WBC: AUC 0.43, ANC: AUC 0.45). CPR and FB had good diagnostic accuracy for complicated versus uncomplicated appendicitis (CRP: AUC 0.80, FB: AUC 0.73). Conclusion CRP and FB are more useful than WBC and ANC to discriminate appendicitis from NSAP in preschool children. CRP and FB are especially useful to discriminate complicated from uncomplicated appendicitis and NSAP. In a child with suspected appendicitis, a plasma FB level (prothrombin time–derived method) >540 mg/dL is associated with an increased likelihood of complicated appendicitis.

Background Array-based comparative genomic hybridization (aCGH) is a molecular analysis method for identifying chromosomal anomalies or copy number variants (CNVs) correlating with clinical phenotypes. The aim of our study was to identify the most significant clinical variables associated with a positive outcome of aCGH analyses to develop a simple predictive clinical score. Methods We conducted a cross-sectional study in a tertiary center comparing the genotype and phenotype of the cases. A score was developed using multivariate logistic regression. The best score cutoff point, sensitivity, specificity, positive and negative predictive values, and area under the curve were calculated with the receiver operating characteristic curve. Results aCGH identified structural chromosomal alterations responsible for the disorder in 13.7% (95% confidence interval [CI]: 10.9–16.5) of our sample (570 patients analyzed by aCGH). Based on the most frequent phenotypic characteristics among patients with a pathogenic CNV, we have created a checklist with the following items: alteration of the cranial perimeter, stature Conclusion All individuals with a score of 1.5 or higher should be genetically screened by aCGH. This approach can improve clinical indications for aCGH in patients with neurodevelopmental disorders, but the scoring system should be validated in an external group.

The layout of this study, designed as a randomized crossover clinical trial, is to evaluate the efficacy of an intervention with mineral-medicinal water from As Burgas (Ourense) in patients suffering from fibromyalgia. This sample was randomly divided into two groups: group A and group B. In phase 1, group A had 14 baths in thermal water for a month and standard pharmacological treatment; group B, standard pharmacological treatment. Washout period is 3 months. In phase 2, group A had standard treatment and group B had 14 baths in thermal water for a month plus standard treatment. The Fibromyalgia Impact Questionnaire (FIQ) was used; this grades the impact of the illness from 1 (minimum) to 10 (maximum), which was measured in both phases. Twenty-five patients were included in each group and the study was concluded with 20 patients in group A and 20 in group B. The intervention group obtained, once the baths finished, a mean score of 60.3 (± 11.8) and the control group of 70.8 (± 13.0) (p

Introduction: There is debate as to whether lung-ultrasound (LUS) can replace lung-auscultation (LA) in the assessment of respiratory diseases. Methodology: The diagnostic validity, safety, and reliability of LA and LUS were analyzed in patients admitted in a pulmonary ward due to decompensated obstructive airway diseases, decompensated interstitial diseases, and pulmonary infections, in a prospective study. Standard formulas were used to calculate the diagnostic sensitivity, specificity, and accuracy. The interobserver agreement with respect to the LA and LUS findings was evaluated based on the Kappa coefficient (ᴋ). Results: A total of 115 patients were studied. LUS was more sensitive than the LA in evaluating pulmonary infections (93.59% vs. 77.02%, p = 0.001) and more specifically in the case of decompensated obstructive airway diseases (95.6% vs. 19.10%, p = 0.001). The diagnostic accuracy of LUS was also greater in the case of pulmonary infections (75.65% vs. 60.90%, p = 0.02). The sensitivity and specificity of the combination of LA and LUS was 95.95%, 50% in pulmonary infections, 76.19%, 100% in case of decompensated obstructive airway diseases, and (100%, 88.54%) in case of interstitial diseases. (ᴋ) was 0.71 for an A-pattern, 0.73 for pathological B‑lines, 0.94 for condensations, 0.89 for pleural-effusion, 0.63 for wheezes, 0.38 for rhonchi, 0.68 for fine crackles, 0.18 for coarse crackles, and 0.29 for a normal LA. Conclusions: There is a greater interobserver agreement in the interpretation of LUS-findings compared to that of LA-noises, their combined use improves diagnostic performance in all diseases examined.

Resumen Objetivo Describir las diferencias clinicas, funcionales y radiograficas de la enfermedad respiratoria por micobacterias ambientales (MA) en pacientes con silicosis y sin silicosis. Metodo Estudio observacional retrospectivo en pacientes a los que se les habia aislado una micobacteria no tuberculosa en el laboratorio de Microbiologia del hospital de O Meixoeiro (CHU de Vigo) desde enero 2007 hasta diciembre 2013. Se diferencio a los pacientes segun presentaran o no silicosis y enfermedad pulmonar por MA utilizando los criterios de la American Thoracic Society. Resultados Se identificaron 156 casos con aislamiento respiratorio de al menos una especie de MA. El 71% eran varones, de los cuales 40 (25,6%) tenian silicosis. En 60 pacientes (38,5%), el 62,5% del grupo de silicosis y el 30,2% del grupo sin silicosis, se cumplian los criterios microbiologicos recomendados por la American Thoracic Society siendo las especies mas comunes Mycobacterium avium complex, Mycobacterium genavense y Mycobacterium chelonae. En 34 pacientes (22,7%), 14 del grupo de silicosis y 20 del grupo sin silicosis, se cumplian los criterios de la American Thoracic Society de enfermedad pulmonar por MA. Se realizo tratamiento en 24 casos, con mayores niveles de erradicacion bacteriologica en el grupo sin silicosis. Conclusiones En nuestros pacientes el antecedente de silicosis se relaciono con mayor incidencia de enfermedad por MA. La especie causante de la mayor parte de los casos de de enfermedad en nuestro medio por MA es Mycobacterium avium complex, seguido de Mycobacterium genavense. Los pacientes con silicosis presentaron menores niveles de curacion tras el tratamiento.

Objective To describe the clinical, functional and radiographic differences of respiratory disease caused by environmental mycobacteria in patients with and without silicosis. Method Retrospective, observational study in patients with nontuberculous mycobacteria isolated in the Hospital Meixoeiro (University Hospital of Vigo) microbiology laboratory between January 2007 and December 2013. Patients were grouped according to the presence or absence of silicosis and mycobacterial lung disease, using American Thoracic Society criteria. Results In 156 cases, at least one species of environmental mycobacteria had been isolated from the respiratory culture. A total of 71% were identified in men, 40 (25.6%) of whom had silicosis. Sixty patients (38.5%) met American Thoracic Society microbiological criteria: 62.5% of the silicosis group and 30.2% of the non-silicosis group. The most common species were Mycobacterium avium complex, Mycobacterium genavense and Mycobacterium chelonae. American Thoracic Society criteria for environmental mycobacterial disease were met in 34 (22.7%) patients: 14 in the silicosis group and 20 in the non-silicosis group. Treatment was administered in 24 cases, with better bacteriological eradication levels in the non-silicosis group. Conclusions In our series, a history of silicosis was related with a higher incidence of environmental mycobacterial disease. The causative species in the majority of cases in our setting was Mycobacterium avium complex, followed by Mycobacterium genavense. Patients with silicosis showed lower cure rates after treatment.

Dear Editor,We read with interest the comment by Lu and Wang [1] concerning the potential inclusion of duplicate articles in our meta-analysis [2]. The first article by Xie et al.[2] included 32 su...

A high prevalence of late-stage disease (75.4%) and severe immunosuppression (23.3%) was observed in 155 newly diagnosed human immunodeficiency virus patients in Freetown, Sierra Leone during August to November 2017. Within the late-stage diagnosis group, a significantly high proportion of patients reported fever (84.2% vs 65.2%; P = .01), weight loss (82.2% vs 63.5%; P = .01), and malaise (89.7% vs 71.7%; P = .05). Fever was identified as the only independent predictor of late-stage disease in this study.

Las desigualdades socioeconómicas son una causa de mortalidad y morbilidad superior a la mayoría de factores de riesgo, especialmente en el entorno urbano. Se llevó a cabo una revisión sistemática de la evidencia científica, en la que se incluyó artículos en inglés, castellano, portugués e italiano y se excluyeron estudios de baja evidencia, y en los que no se analizaba la relación entre mortalidad y nivel socioeconómico en un entorno urbano. La selección de artículos se llevó a cabo por dos revisores independientes y la extracción de datos se realizó con tablas de evidencia. Se obtuvieron 1.509 registros y se incluyeron 24. En todos los trabajos se observó mayor mortalidad en las áreas con peores indicadores de privación. Se observó asociación con patologías cardiovasculares en seis estudios, en cuatro con patologías pulmonares y en tres con SIDA, infecciones y parasitosis y cirrosis. Los estudios incluidos presentan resultados poco consistentes y limitaciones metodológicas importantes que impiden la comparación entre estudios y la extracción de conclusiones relevantes. Socioeconomic inequalities cause more disease and death than most risk factors, especially in cities. This systematic review of the scientific evidence included articles in English, Spanish, Portuguese, and Italian and excluded studies with low levels of evidence and those that did not analyze associations between mortality and socioeconomic status in urban settings. Articles were selected by two independent reviewers, and data extraction used evidence tables. A total of 1,509 records were obtained, and 24 were included. All the studies showed higher mortality rates in poorer areas. Six studies showed an association with cardiovascular diseases, four with lung diseases, and three with AIDS, infectious and parasitic diseases, and cirrhosis. The selected studies showed low consistency in the results and important methodological limitations that prevented comparisons between studies or the extraction of relevant conclusions. As desigualdades socioeconômicas são uma causa de mortalidade e morbidade superior à maioria dos fatores de risco, especialmente no ambiente urbano. Foi realizada uma revisão sistemática da evidência científica, na qual foram incluídos artigos em inglês, espanhol, português e italiano, e da qual foram excluídos estudos de baixa evidência, onde não constava análise da relação entre mortalidade e nível socioeconômico no ambiente urbano. A seleção de artigos foi efetuada por dois revisores independentes e a extração de dados foi feita através de tabelas de evidência. Foram obtidos 1.509 registros e incluídos 24. Em todos os trabalhos, foi observada maior mortalidade nas áreas com os piores indicadores de privação. Observou-se uma associação com patologias cardiovasculares em seis estudos, com patologias pulmonares, em quatro deles, e com a AIDS, infecções, parasitoses e cirrose em três. Os estudos incluídos apresentam resultados pouco consistentes e importantes limitações metodológicas, impedindo a comparação entre estudos e a inferência de conclusões relevantes. SI

Aim. It has been suggested that the repetitive transcranial magnetic stimulation could be useful as a non-pharmacological treatment for spasticity. The aim of this study was to evaluate the clinical and neurophysiological effects of high-frequency intermittent theta burst stimulation (iTBS) on lower limb spasticity in patients with relapsing multiple sclerosis in a randomized, double-blind placebo controlled trial. Patients and methods. Seventeen patients in the remitting phase of the disease were randomly allocated to sham or magnetic therapy group and underwent iTBS over contralateral motor cortex of the most affected leg once a day for two weeks. Each session consisted of 10 bursts containing three pulses at 50 Hz repeated at 200 ms intervals (5 Hz) every 10 s for a total of 600 stimuli. The iTBS effect was assessed by using clinical (such as the Modified Ashworth Scale) and neurophysiological (H/M amplitude ratio and cortical silent period duration) parameters. Results. Two-week iTBS over motor cortex of the most affected leg did not produce any significant clinical effect on spasticity. However, it decreases the H/M amplitude ratio and increases duration of cortical silent period but not significantly, in patients with relapsing multiple sclerosis. Conclusion. The stimulation protocol used in this study does not have significant therapeutic effect. Therefore, we do recommend further studies as neurophysiological changes were evident.