Persistence, effectiveness and safety of ustekinumab and vedolizumab therapy for complex perianal fistula in Crohn's disease: The HEAL study from GETECCU.

BACKGROUND: The efficacy of ustekinumab and vedolizumab for treating complex perianal fistula in Crohn's disease has been barely studied. We aimed to assess treatment persistence, clinical remission, and safety of these drugs in this context. METHODS: Crohn's disease patients who had received ustekinumab or vedolizumab for the indication of active complex perianal fistula, were included. Clinical remission was defined according to Fistula Drainage Assessment Index (no drainage through the fistula upon gentle pressure) based on physicians' assessment. RESULTS: Of 155 patients, 136 received ustekinumab, and 35 vedolizumab (16 received both). Median follow-up for ustekinumab was 27 months. Among those on ustekinumab, 54 % achieved remission, and within this group, 27 % relapsed during follow-up. The incidence rate of relapse was 11 % per patient-year. Multivariate analysis found no variables associated with treatment discontinuation or relapse. Median follow-up time for patients receiving vedolizumab was 19 months. Remission was achieved in 46 % of the patients receiving vedolizumab, and among them, 20 % relapsed during follow-up. The incidence rate of relapse was 7 % per patient-year. Adverse events were mild in 6 % on ustekinumab and 8 % on vedolizumab. CONCLUSION: Ustekinumab and vedolizumab appear effective, achieving remission in around half of complex perianal fistula patients, with favorable safety profiles.

ffectiveness and safety of ustekinumab dose escalation in Crohn’s disease: a multicenter observational study / Efectividad y seguridad del aumento de dosis de ustekinumab en la enfermedad de Crohn: un estudio observacional multicéntrico

Background: ustekinumab has proven effective in Crohn’s disease (CD). However, some patients will partially respond or lose response over time. Data supporting the effectiveness of dose escalation in this scenario is scarce. Aim: to evaluate the effectiveness of ustekinumab dose escalation in CD. Methods: patients with active CD (Harvey-Bradshaw ≥ 5) who had received intravenous (IV) induction and at least a subcutaneous (SC) dose were included in this retrospective observational study. Ustekinumab dose was escalated, either via shortening of the interval to six or four weeks or IV reinduction plus shortening to every four weeks. Results: ninety-one patients were included, and ustekinumab dose was escalated after a median of 35 weeks of treatment. At week 16 after intensification, steroid-free clinical response and remission were observed in 62.6 % and 25.3 % of patients, respectively. Systemic corticosteroids were discontinued in 46.7 % of patients who were on corticosteroids at baseline. Follow-up data beyond week 16 were available for 78 % of patients; at the last visit, 66.2 % and 43.7 % were in steroid-free clinical response and remission, respectively. After a median follow-up of 64 weeks, 81 % of patients were still treated with ustekinumab. Adverse events were reported in 4.3 % of patients; these were all mild and did not lead to hospitalization or discontinuation of treatment. Five patients (5.5 %) underwent surgical resection, with no immediate postsurgical complications. Conclusion: ustekinumab dose escalation was effective in recapturing response in over half of the patients. These findings suggest that dose escalation should be considered in patients who experience loss or partial response to the standard maintenance.(AU)

Case Report: Hemophagocytic Lymphohistiocytosis Secondary to Plasmodium ovale wallikeri Infection.

We report the first known case of hemophagocytic lymphohistiocytosis (HLH) secondary to imported Plasmodium ovale wallikeri infection in a 58-year-old white woman. A delayed diagnosis of malaria and HLH was made after protracted fever and pancytopenia failed to respond adequately to antimalarial treatment, which required intravenous methylprednisolone and gamma-globulin therapy to resolve.

Significance of Umbilical Cord Leptin Profile during Pregnancy in Gestational Diabetes Mellitus-A Systematic Review and Meta-Analysis.

BACKGROUND: The literature provides limited evidence of cord blood leptin levels in gestational diabetes mellitus (GDM), with contradictory and inconsistent results with respect to their possible implications for maternal, perinatal, and future complications. METHODS: MEDLINE/PubMed, Embase, Scopus, and Web of Science databases were searched in order to investigate the state of evidence on the association of leptin profile in cord blood during perinatal complications in GDM. We critically assessed the risk of bias using the Newcastle-Ottawa scale. Meta-analyses were performed, and heterogeneity and publication bias were analyzed. RESULTS: sixteen primary-level studies were included, recruiting 573 GDM and 1118 control pregnant women. Cord blood leptin levels were significantly higher in GDM participants compared to controls (standardized mean difference [SMD] = 0.59, 95% confidence intervals (CI) = 0.37 to 0.80, p < 0.001). All subgroups also maintained significant differences stratified by continents (Asia: SMD = 0.91, 95% CI = 0.45 to 1.37, p < 0.001; Europe: SMD = 0.38, 95% CI = 0.20 to 0.56, p < 0.001), analysis technique (ELISA: SMD = 0.70, 95% CI = 0.44 to 0.97, p < 0.001; RIA: SMD = 0.30, 95% CI = 0.11 to 0.49, p = 0.002), and sample source (plasma: SMD = 0.71, 95% CI = 0.33 to 1.09, p < 0.001; serum: SMD = 0.55, 95% CI = 0.34 to 0.77, p < 0.001). CONCLUSION: Cord blood leptin levels were significantly higher in GDM compared to controls. Further research is needed to clarify its role as a predictive biomarker of subsequent metabolic diseases in mothers with GDM and offspring.

Significance of cell adhesion molecules profile during pregnancy in gestational diabetes mellitus. A systematic review and meta-analysis.

Endothelial dysfunction has been considered as a key etiological factor contributed to the development of vascular disease in diabetes mellitus. Serum level of endothelial cell adhesion molecules (AMs) were reported to be increased in GDM and pregnant women with normal glucose tolerance when compared with nonpregnant women. The literature provides limited evidence of endothelial dysfunction in GDM with heterogeneous and contradictory results respect to their possible involvement in maternal, perinatal and future complications. Our objective is to evaluate current evidence on the role of AMs in maternal and perinatal complications in women with GDM. PubMed, Embase, Web of Science, and Scopus databases were searched. We evaluated the studies' quality using the Newcastle-Ottawa scale. Meta-analyses were conducted, and heterogeneity and publication bias were examined. Nineteen relevant studies were finally included, recruiting 765 GDM and 2368 control pregnant women. AMs levels were generally higher in GDM participants showing statistical significance maternal ICAM-1 levels (SMD = 0.58, 95% CI = 0.25 to 0.91; p = 0.001). Our meta-analysis did not detect significant differences in subgroups or in meta-regression analyses. Future studies are needed to establish the potential role of these biomarkers in GDM and its complications.

Effectiveness and safety of ustekinumab dose escalation in Crohn's disease: a multicenter observational study.

BACKGROUND: ustekinumab has proven effective in Crohn's disease (CD). However, some patients will partially respond or lose response over time. Data supporting the effectiveness of dose escalation in this scenario is scarce. AIM: to evaluate the effectiveness of ustekinumab dose escalation in CD. METHODS: patients with active CD (Harvey-Bradshaw ≥ 5) who had received intravenous (IV) induction and at least a subcutaneous (SC) dose were included in this retrospective observational study. Ustekinumab dose was escalated, either via shortening of the interval to six or four weeks or IV reinduction plus shortening to every four weeks. RESULTS: ninety-one patients were included, and ustekinumab dose was escalated after a median of 35 weeks of treatment. At week 16 after intensification, steroid-free clinical response and remission were observed in 62.6 % and 25.3 % of patients, respectively. Systemic corticosteroids were discontinued in 46.7 % of patients who were on corticosteroids at baseline. Follow-up data beyond week 16 were available for 78 % of patients; at the last visit, 66.2 % and 43.7 % were in steroid-free clinical response and remission, respectively. After a median follow-up of 64 weeks, 81 % of patients were still treated with ustekinumab. Adverse events were reported in 4.3 % of patients; these were all mild and did not lead to hospitalization or discontinuation of treatment. Five patients (5.5 %) underwent surgical resection, with no immediate postsurgical complications. CONCLUSION: ustekinumab dose escalation was effective in recapturing response in over half of the patients. These findings suggest that dose escalation should be considered in patients who experience loss or partial response to the standard maintenance.

Real-world outcomes of switching from adalimumab originator to adalimumab biosimilar in patients with inflammatory bowel disease: The ADA-SWITCH study.

BACKGROUND AND AIMS: Data on the outcomes after switching from adalimumab (ADA) originator to ADA biosimilar are limited. The aim was to compare the treatment persistence, clinical efficacy, and safety outcomes in inflammatory bowel disease patients who maintained ADA originator vs. those who switched to ADA biosimilar. METHODS: Patients receiving ADA originator who were in clinical remission at standard dose of ADA originator were included. Patients who maintained ADA originator formed the non-switch cohort (NSC), and those who switched to different ADA biosimilars constituted the switch cohort (SC). Clinical remission was defined as a Harvey-Bradshaw index ≤4 in Crohn's disease and a partial Mayo score ≤2 in ulcerative colitis. To control possible confounding effects on treatment discontinuation, an inverse probability treatment weighted proportional hazard Cox regression was performed. RESULTS: Five hundred and twenty-four patients were included: 211 in the SC and 313 in the NSC. The median follow-up was 13 months in the SC and 24 months in the NSC (p < 0.001). The incidence rate of ADA discontinuation was 8% and 7% per patient-year in the SC and in the NSC, respectively (p > 0.05). In the multivariate analysis, switching from ADA originator to ADA biosimilar was not associated with therapy discontinuation. The incidence rate of relapse was 8% per patient-year in the SC and 6% per patient-year in the NSC (p > 0.05). Six percent of the patients had adverse events in the SC vs. 5% in the NSC (p > 0.05). CONCLUSION: Switching to ADA biosimilar did not impair patients' outcomes in comparison with maintaining on the originator.

Using "Diraya" System as a Complementary Tool in Nursing Process Education: A Controlled Clinical Study.

Background: Healthcare has been revolutionized by the application of information and communication technologies. The implementation of electronic health record systems improves the quality and safety of patient healthcare. Nursing students who start learning the nursing process without contact with real patients experience difficulties in its correct application. Purpose: To compare the acquisition of skills and competencies in the nursing process by undergraduate nursing students between conventional learning with books and learning with an academic electronic health record system (Diraya). Methods: A controlled experimental study was conducted and included 379 students with a mean age of 20.54 ± 5.09 years, enrolled in the "Nursing Process and Basic Care" degree course at the School of Health Sciences in Granada. All participants gave their informed consent and were allocated by convenience sampling to a control group (n = 187; 21.20 ± 5.77 years) or an experimental group (n = 192, 19.91 ± 4.24 years). Findings: The experimental and control groups did not differ in sex distribution (p = 0.20), mean age (p = 0.01), or previous knowledge of the nursing process (p = 0.96). The groups did not significantly differ in multi-choice test results on the acquisition of theoretical knowledge (p = 0.13). However, the experimental group scored higher on clinical case planning (9.47 ± 0.80 vs. 8.95 ± 1.17; p < 0.001), took less time to complete it (46.9 ± 8.76 min vs. 82.66 ± 13.14 min; p < 0.001), and needed fewer autonomous learning hours to prepare for the final examination (2.26 ± 2.41 vs. 9.58 ± 3.83; p < 0.001). Satisfaction with the program and the rating of its quality were generally higher in the experimental group, while greater difficulty with most phases of the nursing process was reported by the control group. Conclusions: The academic electronic health record system "Diraya" is a useful tool to improve the learning and implementation of the nursing process by undergraduate nursing students.

Significance of Serum-Plasma Leptin Profile during Pregnancy in Gestational Diabetes Mellitus: A Systematic Review and Meta-Analysis.

Gestational diabetes mellitus (GDM) represents a stage of subclinical inflammation and a risk factor for subsequent future type 2 diabetes and cardiovascular disease development. Leptin has been related with vascular and metabolic changes in GDM with heterogeneous and contradictory results with respect to their possible involvement in maternal, perinatal, and future complications. Our objective is to evaluate current evidence on the role of leptin in maternal and perinatal complications in women with GDM. PubMed, Embase, Web of Science, and Scopus databases were searched. We evaluated the studies' quality using the Newcastle-Ottawa scale. Meta-analyses were conducted, and heterogeneity and publication bias were examined. Thirty-nine relevant studies were finally included, recruiting 2255 GDM and 3846 control pregnant women. Leptin levels were significantly higher in GDM participants than in controls (SMD = 0.57, 95%CI = 0.19 to 0.94; p < 0.001). Subgroup meta-analysis did not evidence significant differences in leptin in the different trimesters of pregnancy. Meta-regression showed a positive significant relationship for HOMA in the GDM group (p = 0.05). According to these results, it seems that high levels of leptin can be used as predictive markers in GDM.

Efficacy and safety of tofacitinib in the treatment of ulcerative colitis: real-life experience in Andalusia.

BACKGROUND: tofacitinib is a Janus kinase inhibitor approved for the treatment of moderate-severe ulcerative colitis (UC). This study aimed to evaluate its efficacy in a real-life setting. METHODS: a retrospective and multicenter observational study was performed with UC patients treated with tofacitinib. Short and long-term treatment effectiveness, treatment survival, need for dose escalation and safety were analyzed. Clinical response and remission were defined in accordance with the partial Mayo score. RESULTS: seventy-four patients were included, 98.3 % had received prior biological treatment, 55.4 % with three or more biologicals and up to 64.9% with two or three different mechanisms of action. Clinical remission and response rates were 37.8 % and 77 % at eight weeks, and 41.8 % and 70.1 % at 16 weeks. With regard to non-responders at eight weeks, 37.5 % achieved a delayed clinical response at 16 weeks. Mean treatment duration was 19 months (95 % CI: 16-22), with a treatment survival of 56 % at 28 months, and remission and response rates at 24 months of 53.8 % and 61.5 %. Twenty-three treatments were withdrawn, most of them (18) during the induction period. There were adverse events in a quarter of the patients; only four were severe and led to treatment discontinuation. CONCLUSION: tofacitinib has a demonstrated efficacy in clinical practice to induce and maintain clinical response in treatment-refractory UC patients, with an acceptable safety profile.

What determines the progress of online information access to banking corporate governance practices? The case of Paraguay.

This paper contributes to the lack of longitudinal studies concerning online information access to corporate governance (CG) practices in the banking sector of Latin American countries. In particular, this study aims to analyze the factors that influence information transparency, both mandatory and voluntary, related to CG practices of banks that operate in Paraguay via their websites from 2016 to 2019. Findings indicate the need to improve the level of information available on websites, with disclosure of voluntary information on CG practices being more prevalent than the disclosure of mandatory information. Likewise, banks that operate in Paraguay have made scant "progress" regarding online access to their governance information over the years analyzed. Moreover, the factors "Bank size" and "listed status" positively influence the information transparency regarding CG practices of Paraguayan banks. In contrast, "leverage," "liquidity," "size of the audit firm," and "credit risk rating" are factors that have a negative relation with the extent of CG disclosure.

A Gastroenterologist' clinical experience in COVID 19 and in-hospital mortality and length of stay analysis.

OBJECTIVES: COVID19 pandemic has forced physicians from different specialties to assist cases overload. Our aim is to assess gastroenterologist's assistance in COVID-19 by assessing mortality, ICU admission, and length of stay, and seek for risk factors for in-hospital mortality and longer hospital stay. METHODS: A total of 41 COVID-19 patients assisted by gastroenterologist (GI cohort) and 137 assisted by pulmonologist, internal medicine practitioners, and infectious disease specialists (COVID expert cohort) during October-November 2020 were prospectively collected. Clinical, demographic, imaging, and laboratory markers were collected and compared between both cohorts. Bivariate analysis and logistic regression were performed to search for risk factors of mortality and longer hospital stays. RESULTS: A total of 27 patients died (15.1%), 11 were admitted to ICU (6.1%). There were no differences between cohorts in mortality (14.6% vs 15.4%;p = 0.90), ICU admission (12.1% vs 4%;p = 0.13), and length of stay (6.67 ± 4 vs 7.15 ± 4.5 days; p = 0.58). PaO2/FiO2 on admission (OR 0.991;CI95% 0.984-0.998) and age > 70 (OR 17.54;CI95% 3.93-78.22) were independently related to mortality. Age > 70, history of malignancy, diabetes, and cardiovascular disease were related to longer hospital stays (p < 0.001, p = 0.03, p = 0.04, p = 0.02 respectively). CONCLUSIONS: COVID-19 assistance was similar between gastroenterologist and COVID experts when assessing mortality, ICU admission, and length of stay. Age>70 and decreased PaO2/FiO2 on admission were independent risk factors of mortality. Age and several comorbidities were related to longer hospital stay.

Hábitos de vida y rendimiento académico en periodo evaluativo en estudiantes de enfermería / Life Habits and Academic Performance during the Examination Period in Nursing Students

Introducción: Los hábitos de vida de los estudiantes universitarios, con poco tiempo para su realización debido al estrés académico, prácticas, horario de clase y estudio, suelen ser poco saludables, por tanto, pueden influir negativamente en el rendimiento académico. Objetivo: Analizar los hábitos de vida en periodo evaluativo y su influencia en el rendimiento académico en estudiantes universitarios del grado en enfermería. Métodos: Estudio observacional descriptivo de tipo transversal realizado en el momento del examen a 488 estudiantes de los cuatro cursos del grado en enfermería de una universidad al sur de España, en el curso académico 2018. Los instrumentos empleados fueron: un cuestionario con datos sociodemográficos y otro cuestionario de hábitos de estilo de vida. El análisis de la información se realizó través de estadísticos descriptivos, pruebas paramétricas y no paramétricas y correlación lineal. Se respetaron las consideraciones éticas para estudios con humanos. Resultados: El 53,30 por ciento de la muestra realizaba ejercicio físico de forma regular, siendo similar en los cuatro cursos evaluados para los hombres mientras que en las mujeres aumentó de 31,11 por ciento en 1º a 61,26 por ciento en 4º curso. No diferencias relevantes en el rendimiento académico según variables de estilo de vida excepto sueño. Conclusiones: Las horas de sueño dormidas, sobre todo la semana previa al examen se relacionan con mayor rendimiento académico. Nuestros resultados sugieren que los estilos de vida menos saludables conllevan a peor rendimiento académico(AU)

Introduction: The life habits of university students, with little time to carry them out due to academic stress, practices, class and study hours, are usually unhealthy; therefore, they can influence academic performance negatively. Objective: To analyze life habits in the evaluation period and their influence on academic performance in university students of the Nursing degree. Methods: Descriptive, cross-sectional and observational study carried out, in the academic year 2018, at the time of examination with 488 students from the four courses of the Nursing degree from a university in southern Spain. The instruments used were a questionnaire with sociodemographic data and another lifestyle habits quiz. Information analysis was carried out through descriptive statistics, parametric and nonparametric tests, and linear correlation. Ethical considerations for human studies were respected. Results: 53.30 percent of the sample did physical exercise on a regular basis, being similar for men in the four courses assessed, while for women it increased from 31.11 percent in first academic year to 61.26 percent in the fourth academic year. There were no relevant differences in academic performance according to lifestyle variables except sleep. Conclusions: The hours of sleep per se, especially during the week before the exam, are related to higher academic performance. Our results suggest that less healthy lifestyles lead to poorer academic performance(AU)

Clinical outcome after anti-tumour necrosis factor therapy discontinuation in 1000 patients with inflammatory bowel disease: the EVODIS long-term study.

BACKGROUND: The long-term outcome of patients after antitumour necrosis factor alpha (anti-TNF) discontinuation is not well known. AIMS: To assess the risk of relapse in the long-term after anti-TNF discontinuation. METHODS: This was an extension of the evolution after anti-TNF discontinuation in patients with inflammatory bowel disease (EVODIS) study (Crohn's disease or ulcerative colitis patients treated with anti-TNFs in whom these drugs were withdrawn after achieving clinical remission) based in the same cohort of patients whose outcome was updated. Clinical remission was defined as a Harvey-Bradshaw index ≤4 points in Crohn's disease, a partial Mayo score ≤2 in ulcerative colitis and the absence of fistula drainage despite gentle finger compression in perianal disease. RESULTS: This was an observational, retrospective, multicenter study. A total of 1055 patients were included. The median follow-up time was 34 months. The incidence rate of relapse was 12% per patient-year (95% confidence interval [CI] = 11-14). The cumulative incidence of relapse was 50% (95% CI = 47-53): 19% at one year, 31% at 2 years, 38% at 3 years, 44% at 4 years and 48% at 5 years of follow-up. Of the 60% patients retreated with the same anti-TNF after relapse, 73% regained remission. Of the 75 patients who did not respond, 48% achieved remission with other therapies. Of the 190 patients who started other therapies after relapse, 62% achieved remission with the new treatment. CONCLUSIONS: A significant proportion of patients who discontinued the anti-TNF remained in remission. In case of relapse, retreatment with the same anti-TNF was usually effective. Approximately half of the patients who did not respond after retreatment achieved remission with other therapies.

Physicians' experiences of providing emergency care to undocumented migrants arriving in Spain by small boats.

INTRODUCTION: Access to emergency care for undocumented migrants (UMs) is a public health problem. Spain receives thousands of UMs who arrive by sea. A multidisciplinary team of the Spanish Red Cross, made up of physicians, nurses, police, and cultural mediators, developed emergency care for UMs. AIM: The aim of our study is to describe and understand the experiences of physicians in emergency care for UMs who arrive in Spain by small boats METHODS: Qualitative study, based on Gadamer's phenomenology. Convenience and purposive sampling was carried out and included sixteen in-depth interviews with physicians, between June 2019 and March 2020 in Spain. RESULTS: Three main themes emerged: 1) Rediscovering humanistic medicine; 2) Leaving the personal and professional comfort zone; 3) Improving medical emergency care. CONCLUSIONS: Triage, pharmacological prescription, and the closure of the emergency care process are the key contributions of medical care. Cultural, language and security barriers make emergency care difficult.

Diabetes mellitus and oral cancer/oral potentially malignant disorders: A systematic review and meta-analysis.

The objective was to evaluate current evidence on the prevalence and risk of oral cancer and potentially malignant oral disorders among patients with diabetes mellitus. We searched PubMed, Embase, Web of Science, and Scopus for observational studies published before November 2019. We evaluated the study quality using GRADE, QUIPS, and a specific method for systematic reviews addressing prevalence questions. Meta-analyses were conducted, and heterogeneity and publication bias were examined. A total of 1,489 studies were found, 116 analyzed in full text, 52 included in qualitative synthesis and 49 meta-analyzed. Pooled prevalence (PP) of oral cancer in patients with diabetic was 0.25% (95% CI = 0.15-0.39)-250 per 100,000 patients with diabetes mellitus -with a greater chance of oral cancer among patients with diabetes mellitus (OR = 1.41 [95% CI = 1.10-1.81], p = .007). Patients with oral cancer and diabetes mellitus had a higher mortality than controls (HR = 2.09 [95%CI = 1.36-3.22], p = .001). Leukoplakia had a PP = 2.49% (95% CI = 1.14-4.29)-2,490 per 100,000 patients with diabetes mellitus -(OR = 4.34 [95% CI = 1.14-16.55], p = .03). A PP of 2.72 (95% CI = 1.64-4.02) was obtained for oral lichen planus among patients with diabetic -2,720 per 100,000 patients with diabetes mellitus (OR = 1.87 [95% CI = 1.37-2.57], p < .001). A low PP was estimated for erythroplakia (0.02%[95%CI = 0.00-0.12]-20 per 100,000 patients with diabetes mellitus. In conclusion, patients with diabetes mellitus have a higher prevalence and greater chance of oral cancer and OPMD development in comparison with non-diabetic patients. In addition, patients with oral cancer suffering from diabetes mellitus have a higher mortality compared to non-diabetic patients with oral cancer.