Effect of essential phospholipids on hepatic steatosis in metabolic dysfunction-associated steatotic liver disease associated with type 2 diabetes mellitus and/or hyperlipidemia and/or obesity: study protocol of a randomized, double-blind, phase IV clinical trial.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a predominant chronic liver condition globally and is strongly associated with obesity, diabetes mellitus, and dyslipidemia. Essential phospholipids (EPL) are recommended as supportive treatment for managing liver conditions, including MASLD or metabolic dysfunction-associated steatohepatitis, cirrhosis, and viral hepatitis. While efficacy of EPL as an adjunctive therapy in MASLD treatment has been established earlier, certain aspects of its usage such as the impact of standard-of-care parameters, effect of EPL on quality of life (QoL) and change in symptoms evaluation in patients with MASLD remain unexplored. The proposed trial aims to assess the efficacy and safety of EPL and the subsequent QoL of patients with MASLD associated with type 2 diabetes mellitus (T2DM) and/or hyperlipidemia and/or obesity. METHODS: This is a multicenter, multinational, double-blind, randomized, two-arm, placebo-controlled, parallel-group, phase IV clinical trial. The trial is being conducted in approximately 190 patients who are randomized on a 1:1 basis either to the EPL arm (Essentiale® 1800 mg/day orally + standard of care) or placebo arm (placebo + standard of care). The primary outcome is to assess the efficacy of EPL on hepatic steatosis, as measured by transient elastography, from baseline to 6 months. The secondary outcomes include change in QoL parameters, as measured by the Chronic Liver Disease Questionnaire-metabolic dysfunction-associated steatotic liver disease/ metabolic dysfunction-associated steatohepatitis and change in symptom evaluation (using the Global Overall Symptom scale) from baseline to 6 months for symptoms, including asthenia, feeling depressed, abdominal pain/discomfort, or fatigue. DISCUSSION: The current protocol design will allow to comprehensively explore the efficacy of EPL added to the standard of care on hepatic steatosis and QoL and its safety in patients with MASLD associated with T2DM and/or hyperlipidemia and/or obesity by assessing various outcome measures. TRIAL REGISTRATION: European Union Clinical Trials Register, EudraCT, 2021-006069-39. Registered on March 13, 2022.

Efficacy and safety of Bacillus clausii (O/C, N/R, SIN, T) probiotic combined with oral rehydration therapy (ORT) and zinc in acute diarrhea in children: a randomized, double-blind, placebo-controlled study in India.

BACKGROUND: Childhood diarrhea remains a major disease burden, particularly in developing countries, and is a leading cause of death in children aged < 5 years, worldwide. Treatment of acute diarrhea now includes probiotics to potentially reduce the duration and severity of the illness. This phase 3, randomized, placebo-controlled, double-blind study assessed the efficacy and safety of four strains (O/C, N/R, SIN, T) of Bacillus clausii probiotic (Enterogermina®) plus oral rehydration therapy (ORT) and zinc, versus placebo plus ORT and zinc, in infants and children in India with acute moderate diarrhea. METHODS: Patients aged 6 months to 5 years with acute moderate diarrhea (WHO 2005 definition) of < 48 h' duration were randomly assigned to receive one mini bottle of either polyantibiotic-resistant B. clausii (oral suspension of 2 billion spores per 5 mL bottle) or matching placebo twice daily (morning and evening) for 5 days. Exclusion criteria included known hypersensitivity to B. clausii or excipients in the study treatment, or to other probiotics. Patients were admitted to hospital from Day 1 and discharged ≥6 h after diarrhea resolution, or a maximum of 5 days. The primary endpoint was duration of acute diarrhea from randomization to recovery. Secondary endpoints included frequency of stools, diapers with stools, or dehydration status. RESULTS: In total, 457 patients were randomized; 454 were treated. Similar proportions of patients showed recovery from diarrhea over the 120 h after randomization (97.0% in the B. clausii group [n = 227]; 98.0% on placebo [n = 227]). Median time to recovery was also similar: 42.83 (95% CI: 40.90-44.90) hours for B. clausii and 42.13 (95% CI: 39.80-43.87) hours for placebo. However, no statistically significant difference was observed between groups (hazard ratio = 0.93 [95% CI: 0.77-1.13]; p = 0.6968); nor were there statistically significant differences between groups for the secondary endpoints. Treatment with B. clausii was well tolerated with incidence of adverse events (9.7%) similar to that for placebo (12.3%). CONCLUSIONS: No significant difference in efficacy between B. clausii and placebo was demonstrated. Sample size may have been inadequate to allow detection of a between-group difference in efficacy, given the mild/moderate severity (only ~ 20% of patients had nausea/vomiting or abdominal pains) and short duration of disease among subjects, the relatively late start of treatment (most were already on Day 2 of their disease episode when study treatment started) and the effectiveness of the standard of care with ORT and zinc in both treatment groups. TRIAL REGISTRATION: CTRI number CTRI/2018/10/016053 . Registered on 17 October 2018. EudraCT number 2016-005165-31 . Registered 14 May 2020 (retrospectively registered).

Efficacy and Safety of Sarilumab for the Treatment of Posterior Segment Noninfectious Uveitis (SARIL-NIU):: The Phase 2 SATURN Study.

PURPOSE: To assess efficacy and safety of sarilumab, a human anti-interleukin-6 receptor antibody, for treatment of posterior segment noninfectious uveitis (NIU). DESIGN: Randomized, double-masked, placebo-controlled, phase 2 study. PARTICIPANTS: Fifty-eight patients (eyes) with noninfectious intermediate, posterior, or panuveitis. METHODS: Eyes received treatment every 2 weeks for 16 weeks with subcutaneous sarilumab 200 mg or placebo. MAIN OUTCOME MEASURES: The primary end point was the proportion of patients with ≥2-step reduction in vitreous haze (VH) on the Miami scale or with a reduction of systemic corticosteroids (prednisolone or equivalent) to a dose of <10 mg/day at week 16. Primary end point was based on VH evaluation by a central reading center. Investigator evaluation of VH was a prespecified, planned secondary analysis. RESULTS: At week 16, proportion of patients taking sarilumab or placebo with ≥2-step reduction in VH or corticosteroid dose <10 mg/day was 46.1% vs. 30.0% (P = 0.2354) based on central reading center assessment of VH and 64.0% vs. 35.0% (P = 0.0372) based on investigator assessment of VH, respectively. In the subgroup of eyes with VH grade ≥2 at baseline, the mean VH reduction from baseline to week 16 was significantly greater with sarilumab vs. placebo regardless of assessment by the central reading center (-2.1 [n = 11] vs. -1.7 [n = 3], respectively; P = 0.0255) or investigator (-2.5 [n = 19] vs. -1.2 [n = 11], respectively; P = 0.0170). The mean best-corrected visual acuity gain from baseline to week 16 was greater with sarilumab vs. placebo in the overall population (8.9 vs. 3.6 letters, respectively; P = 0.0333) and in the subgroup of eyes with central subfield thickness (CST) ≥300 µm at baseline (12.2 [n = 13] vs. 2.1 [n = 7] letters, respectively; P = 0.0517). Corresponding changes in CST were -46.8 vs. +2.6 µm (P = 0.0683) in the overall population and -112.5 [n = 13] vs. -1.8 [n = 6] µm (P = 0.1317) in the subgroup of eyes with CST ≥300 µm at baseline, respectively. The most common ocular adverse events were worsening of uveitis (0 [placebo] and 3 [sarilumab] patients) and retinal infiltrates (1 [placebo] and 2 [sarilumab] patients). CONCLUSIONS: Subcutaneous sarilumab may provide clinical benefits in the management of NIU of the posterior segment, especially in eyes with uveitic macular edema.

Intravitreous injection of AAV2-sFLT01 in patients with advanced neovascular age-related macular degeneration: a phase 1, open-label trial.

BACKGROUND: Long-term intraocular injections of vascular endothelial growth factor (VEGF)-neutralising proteins can preserve central vision in many patients with neovascular age-related macular degeneration. We tested the safety and tolerability of a single intravitreous injection of an AAV2 vector expressing the VEGF-neutralising protein sFLT01 in patients with advanced neovascular age-related macular degeneration. METHODS: This was a phase 1, open-label, dose-escalating study done at four outpatient retina clinics in the USA. Patients were assigned to each cohort in order of enrolment, with the first three patients being assigned to and completing the first cohort before filling positions in the following treatment groups. Patients aged 50 years or older with neovascular age-related macular degeneration and a baseline best-corrected visual acuity score of 20/100 or less in the study eye were enrolled in four dose-ranging cohorts (cohort 1, 2 × 108 vector genomes (vg); cohort 2, 2 × 109 vg; cohort 3, 6 × 109 vg; and cohort 4, 2 × 1010 vg, n=3 per cohort) and one maximum tolerated dose cohort (cohort 5, 2 × 1010 vg, n=7) and followed up for 52 weeks. The primary objective of the study was to assess the safety and tolerability of a single intravitreous injection of AAV2-sFLT01, through the measurement of eye-related adverse events. This trial is registered with ClinicalTrials.gov, number NCT01024998. FINDINGS: 19 patients with advanced neovascular age-related macular degeneration were enrolled in the study between May 18, 2010, and July 14, 2014. All patients completed the 52-week trial period. Two patients in cohort 4 (2 × 1010 vg) experienced adverse events that were possibly study-drug related: pyrexia and intraocular inflammation that resolved with a topical steroid. Five of ten patients who received 2 × 1010 vg had aqueous humour concentrations of sFLT01 that peaked at 32·7-112·0 ng/mL (mean 73·7 ng/mL, SD 30·5) by week 26 with a slight decrease to a mean of 53·2 ng/mL at week 52 (SD 17·1). At baseline, four of these five patients were negative for anti-AAV2 serum antibodies and the fifth had a very low titre (1:100) of anti-AAV2 antibodies, whereas four of the five non-expressers of sFLT01 had titres of 1:400 or greater. In 11 of 19 patients with intraretinal or subretinal fluid at baseline judged to be reversible, six showed substantial fluid reduction and improvement in vision, whereas five showed no fluid reduction. One patient in cohort 5 showed a large decrease in vision between weeks 26 and 52 that was not thought to be vector-related. INTERPRETATION: Intravitreous injection of AAV2-sFLT01 seemed to be safe and well tolerated at all doses. Additional studies are needed to identify sources of variability in expression and anti-permeability activity, including the potential effect of baseline anti-AAV2 serum antibodies. FUNDING: Sanofi Genzyme, Framingham, MA, USA.

Estrategia didáctica para gestionar información en el proceso de formación profesional / Didactic strategy for managing information in the process of professional formation

El trabajo aborda el rol que juega la gestión de información en relación con la infotecnología para los profesionales en formación, así como los elementos esenciales de una propuesta de estrategia didáctica que contribuye al desarrollo de la habilidad profesional gestionar información contentiva de las habilidades investigativas. Por su importancia y universalidad constituye una propuesta válida para la formación profesional en cualquiera de sus dimensiones, en el que se incluye, las Ciencias Médicas que bien pudiera ser aplicada como alternativa para favorecer y perfeccionar el aprendizaje de los futuros egresados (AU)

This work deals with the relation between information management and infotechnology, and its influence on incoming professionals; as well as with the essential elements for a didactic strategy that could contribute to the development of a professional skill that is to manage contentious information of the researching skills. Due to its importance and universal values, it constitutes a valid proposal for the formation of professionals and its different venues in which could be included the Medical Sciences. This proposal could be used to favor and improve the learning process of the incoming graduates (AU)

Estrategia didáctica para gestionar información en el proceso de formación profesional / Didactic strategy for managing information in the process of professional formation

El trabajo aborda el rol que juega la gestión de información en relación con la infotecnología para los profesionales en formación, así como los elementos esenciales de una propuesta de estrategia didáctica que contribuye al desarrollo de la habilidad profesional gestionar información contentiva de las habilidades investigativas. Por su importancia y universalidad constituye una propuesta válida para la formación profesional en cualquiera de sus dimensiones, en el que se incluye, las Ciencias Médicas que bien pudiera ser aplicada como alternativa para favorecer y perfeccionar el aprendizaje de los futuros egresados.

This work deals with the relation between information management and infotechnology, and its influence on incoming professionals; as well as with the essential elements for a didactic strategy that could contribute to the development of a professional skill that is to manage contentious information of the researching skills. Due to its importance and universal values, it constitutes a valid proposal for the formation of professionals and its different venues in which could be included the Medical Sciences. This proposal could be used to favor and improve the learning process of the incoming graduates.

Algunas consideraciones teóricas acerca de la Enseñanza Problémica / Problem Solving teaching: some theoretical considerations

Se realizan algunas consideraciones, filosóficas, pedagógica, metodológicas sobre la Enseñanza Problémica la cual constituye una alternativa que pueden emplear los profesores para activar el proceso de enseñanza-aprendizaje, teniendo en cuenta las condiciones y características de los educandos. Se reflexiona sobre el origen de este tipo de enseñanza, su desarrollo histórico a partir de los autores más representativos que asumen esta forma de enseñar tanto en Cuba como de otras latitudes, así como los fundamentos teóricos, las categorías y, sus métodos. Además, se observan las ventajas y desventajas que a criterio de los autores tiene el referido tipo de enseñanza (AU)

Some philosophical, pedagogic and methodological considerations on problem solving teaching are expressed, which constitutes an alternative that professors can use to activate the teaching-learning process, keeping in mind the conditions and characteristic of their students. It is meditated on the origin of this teaching type, its historical development starting from the most representative authors that assume this form of teaching in Cuba as in other latitudes, as well as its theoretical foundations, categories and methods. The advantages and disadvantages of this approach according to the authors are also mentioned (AU)

Algunas consideraciones teóricas acerca de la Enseñanza Problémica / Problem Solving teaching: some theoretical considerations

Se realizan algunas consideraciones, filosóficas, pedagógica, metodológicas sobre la Enseñanza Problémica la cual constituye una alternativa que pueden emplear los profesores para activar el proceso de enseñanza-aprendizaje, teniendo en cuenta las condiciones y características de los educandos. Se reflexiona sobre el origen de este tipo de enseñanza, su desarrollo histórico a partir de los autores más representativos que asumen esta forma de enseñar tanto en Cuba como de otras latitudes, así como los fundamentos teóricos, las categorías y, sus métodos. Además, se observan las ventajas y desventajas que a criterio de los autores tiene el referido tipo de enseñanza(AU)

Algunas consideraciones teóricas acerca de la Enseñanza Problémica / Problem Solving teaching: some theoretical considerations

Se realizan algunas consideraciones, filosóficas, pedagógica, metodológicas sobre la Enseñanza Problémica la cual constituye una alternativa que pueden emplear los profesores para activar el proceso de enseñanza-aprendizaje, teniendo en cuenta las condiciones y características de los educandos. Se reflexiona sobre el origen de este tipo de enseñanza, su desarrollo histórico a partir de los autores más representativos que asumen esta forma de enseñar tanto en Cuba como de otras latitudes, así como los fundamentos teóricos, las categorías y, sus métodos. Además, se observan las ventajas y desventajas que a criterio de los autores tiene el referido tipo de enseñanza.

Some philosophical, pedagogic and methodological considerations on problem solving teaching are expressed, which constitutes an alternative that professors can use to activate the teaching-learning process, keeping in mind the conditions and characteristic of their students. It is meditated on the origin of this teaching type, its historical development starting from the most representative authors that assume this form of teaching in Cuba as in other latitudes, as well as its theoretical foundations, categories and methods. The advantages and disadvantages of this approach according to the authors are also mentioned.

Efectividad y Continuidad de la anticoncepción en el Municpio Diez de Octubre / Effectiveness and continuity of contraception at the municipality of diez de octubre

Una de las formas de valorar el uso adecuado de la anticoncepción y la eficacia de la planificación familiar es conociendo la efectividad y continuidad de los métodos anticonceptivos. El objetivos de este trabajo es mostrar las tasas de efectividad, abandono y fallo de la anticoncepción en mujeres del municipio Diez de Octubre. La información proviene de un proyecto financiado por el Programa de Reproducción Humana de la Organización Mundial de la Salud 'Contracepción y Factores Asociados'. Se utilizó la historia de uso de anticonceptivos de 876 mujeres. Mediante la tabla de vida se obtuvieron todos los indicadores. Las tasas de fallo encontradas van desde 12,67 por cien episodios para los métodos tradicionales, a 5,26 para los DIU tuvo una tasa de fallo de 18,01 por cien episodios. Se encontró diferencia significativa al 0,0001 (con la prueba de Lee-Disu) para el comportamiento del fallo y del abandono en relación con los antecedentes de hijos y abortos previos al inicio del uso. Se concluye que las tasas de fallo del DIU es una de las más altas en comparación con países con información y que tanto el fallo como el abandono de los DIU es elevado. Se recomienda que en el municipio se revisen las orientaciones del uso del DIU para beneficio de la salud reproductiva de las mujeres y aumento de la efectividad de los métodos(AU)

Efectividad y Continuidad de la anticoncepción en el Municpio Diez de Octubre / Effectiveness and continuity of contraception at the municipality of diez de octubre

Una de las formas de valorar el uso adecuado de la anticoncepción y la eficacia de la planificación familiar es conociendo la efectividad y continuidad de los métodos anticonceptivos. El objetivos de este trabajo es mostrar las tasas de efectividad, abandono y fallo de la anticoncepción en mujeres del municipio Diez de Octubre. La información proviene de un proyecto financiado por el Programa de Reproducción Humana de la Organización Mundial de la Salud 'Contracepción y Factores Asociados'. Se utilizó la historia de uso de anticonceptivos de 876 mujeres. Mediante la tabla de vida se obtuvieron todos los indicadores. Las tasas de fallo encontradas van desde 12,67 por cien episodios para los métodos tradicionales, a 5,26 para los DIU tuvo una tasa de fallo de 18,01 por cien episodios. Se encontró diferencia significativa al 0,0001 (con la prueba de Lee-Disu) para el comportamiento del fallo y del abandono en relación con los antecedentes de hijos y abortos previos al inicio del uso. Se concluye que las tasas de fallo del DIU es una de las más altas en comparación con países con información y que tanto el fallo como el abandono de los DIU es elevado. Se recomienda que en el municipio se revisen las orientaciones del uso del DIU para beneficio de la salud reproductiva de las mujeres y aumento de la efectividad de los métodos