Fezolinetant for the treatment of vasomotor symptoms associated with menopause: a meta-analysis.

This systematic review and meta-analysis investigated the efficacy and safety of fezolinetant for the treatment of moderate-to-severe vasomotor symptoms (VMS) associated with menopause. PubMed, Cochrane Library, Embase and Web of Science were searched for randomized controlled trials (RCTs) published from inception to June 2023, comparing fezolinetant to placebo in postmenopausal women suffering from moderate-to-severe VMS. The mean difference and risk ratio were calculated for continuous and binary outcomes, respectively. R software was used for the statistical analysis, and RoB-2 (Cochrane) to assess the risk of bias. We performed subgroup analysis based on different dosing regimens. Five RCTs comprising 3302 patients were included. Compared with placebo, at 12-week follow-up, fezolinetant significantly reduced the daily frequency of moderate-to-severe VMS (weighted mean difference [WMD] - 2.36; 95% confidence interval [CI] - 2.92, -1.81) and daily severity of moderate-to-severe VMS (WMD -0.22; 95% CI -0.31, -0.13). Also, fezolinetant significantly improved the quality of life (WMD -0.42; 95% CI -0.58, -0.26) and sleep disturbance (WMD -1.10; 95% CI -1.96, -0.24). There were no significant differences between groups in adverse events. These findings support the efficacy and safety of fezolinetant for the treatment of VMS related to menopause.

Precision and accuracy of common coral reef sampling protocols revisited with photogrammetry.

The rapid decline of coral reefs calls for cost-effective benthic cover data to improve reef health forecasts, policy building, management responses and evaluation. Reef monitoring has been largely based on divers' observations along transects, and secondarily on quadrat-based protocols, video and photographic records. However, the accuracy and precision of the most common sampling approaches are not yet fully understood. Here, we compared benthic cover estimates from three common sampling protocols: Reef Check (RC), Atlantic and Gulf Rapid Reef Assessment (AGRRA) and photoquadrats (PQ). The reef cover of two contrasting sites was reconstructed with ∼450 m2 orthomosaics built with high resolution Structure-from-Motion (SfM) photogrammetry, which were used as references for comparisons among protocols. In addition, we explored sample size requirements for each protocol and provided cost-effectiveness comparisons. Our results evidenced between-reef differences in the accuracy and precision of estimates with the different protocols. The three protocols performed similarly in the reef with low macroalgal cover (<0.5%), but PQ were more accurate and precise in the reef with relatively high (∼20%) macroalgal cover. The sample size for estimating coral cover with a 20% error margin and a 0.05 significance level was lower for PQ, followed by AGRRA and RC. Considering performance, cost surrogates and equipment needs, cost-effectiveness was higher for PQ. We also discuss costs, limitations and advantages/disadvantages of SfM photogrammetry as a sampling approach for coral reef monitoring.

Comorbid autoimmune disorders in people with multiple sclerosis: A retrospective cohort study.

Most autoimmune disorders, including multiple sclerosis (MS), are influenced by shared genetic and environmental factors. We conducted a cohort study of people with MS to calculate the frequency of comorbid autoimmune disorders and characterize this cohort. Autoimmune diseases were present in 30 (8.6%) of 349 patients. The most prevalent diagnoses were autoimmune thyroiditis, type 1 diabetes mellitus, psoriasis, and inflammatory bowel disease. We found no association with demographic or clinical factors. In our cohort, autoimmune disorders were not uncommon. Identifying such comorbidities in people with MS can be determinant for understanding disease mechanisms, treatment decisions and disease management.

Glucose control and psychosocial outcomes with use of automated insulin delivery for 12 to 96 weeks in type 1 diabetes: a meta-analysis of randomised controlled trials.

BACKGROUND: Glycaemic control of Type 1 Diabetes Mellitus (T1DM) remains a challenge due to hypoglycaemic episodes and the burden of insulin self-management. Advancements have been made with the development of automated insulin delivery (AID) devices, yet, previous reviews have only assessed the use of AID over days or weeks, and potential benefits with longer time of AID use in this population remain unclear. METHODS:  We performed a systematic review and meta-analysis of randomised controlled trials comparing AID (hybrid and fully closed-loop systems) to usual care (sensor augmented pumps, multiple daily insulin injections, continuous glucose monitoring and predictive low-glucose suspend) for adults and children with T1DM with a minimum duration of 3 months. We searched PubMed, Embase, Cochrane Central, and Clinicaltrials.gov for studies published up until April 4, 2023. Main outcomes included time in range 70-180 mg/dL as the primary outcome, and change in HbA1c (%, mmol/mol), glucose variability, and psychosocial impact (diabetes distress, treatment satisfaction and fear of hypoglycaemia) as secondary outcomes. Adverse events included diabetic ketoacidosis (DKA) and severe hypoglycaemia. Statistical analyses were conducted using mean differences and odds ratios. Sensitivity analyses were performed according to age, study duration and type of AID device. The protocol was registered in PROSPERO, CRD42022366710. RESULTS: We identified 25 comparisons from 22 studies (six crossover and 16 parallel designs) including a total of 2376 participants (721 in adult studies, 621 in paediatric studies, and 1034 in combined studies) which were eligible for analysis. Use of AID devices ranged from 12 to 96 weeks. Patients using AID had 10.87% higher time in range [95% CI 9.38 to 12.37; p < 0.0001, I2 = 87%) and 0.37% (4.77 mmol/mol) lower HbA1c (95% CI - 0.49% (- 6.39 mmol/mol) to - 0.26 (- 3.14 mmol/mol); p < 0·0001, I2 = 77%]. AID systems decreased night hypoglycaemia, time in hypoglycaemia and hyperglycaemia and improved patient distress, with no increase in the risk of DKA or severe hypoglycaemia. No difference was found regarding treatment satisfaction or fear of hypoglycaemia. Among children, there was no difference in glucose variability or time spent in hypoglycaemia between the use of AID systems or usual care. In sensitivity analyses, results remained consistent with the overall analysis favouring AID. CONCLUSION: The use of AID systems over 12 weeks, regardless of technical or clinical differences, improved glycaemic outcomes and diabetes distress without increasing the risk of adverse events in adults and children with T1DM.

2023 UPDATE: Luso-Brazilian evidence-based guideline for the management of antidiabetic therapy in type 2 diabetes.

BACKGROUND: The management of antidiabetic therapy in people with type 2 diabetes (T2D) has evolved beyond glycemic control. In this context, Brazil and Portugal defined a joint panel of four leading diabetes societies to update the guideline published in 2020. METHODS: The panelists searched MEDLINE (via PubMed) for the best evidence from clinical studies on treating T2D and its cardiorenal complications. The panel searched for evidence on antidiabetic therapy in people with T2D without cardiorenal disease and in patients with T2D and atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), or diabetic kidney disease (DKD). The degree of recommendation and the level of evidence were determined using predefined criteria. RESULTS AND CONCLUSIONS: All people with T2D need to have their cardiovascular (CV) risk status stratified and HbA1c, BMI, and eGFR assessed before defining therapy. An HbA1c target of less than 7% is adequate for most adults, and a more flexible target (up to 8%) should be considered in frail older people. Non-pharmacological approaches are recommended during all phases of treatment. In treatment naïve T2D individuals without cardiorenal complications, metformin is the agent of choice when HbA1c is 7.5% or below. When HbA1c is above 7.5% to 9%, starting with dual therapy is recommended, and triple therapy may be considered. When HbA1c is above 9%, starting with dual therapyt is recommended, and triple therapy should be considered. Antidiabetic drugs with proven CV benefit (AD1) are recommended to reduce CV events if the patient is at high or very high CV risk, and antidiabetic agents with proven efficacy in weight reduction should be considered when obesity is present. If HbA1c remains above target, intensification is recommended with triple, quadruple therapy, or even insulin-based therapy. In people with T2D and established ASCVD, AD1 agents (SGLT2 inhibitors or GLP-1 RA with proven CV benefit) are initially recommended to reduce CV outcomes, and metformin or a second AD1 may be necessary to improve glycemic control if HbA1c is above the target. In T2D with HF, SGLT2 inhibitors are recommended to reduce HF hospitalizations and mortality and to improve HbA1c. In patients with DKD, SGLT2 inhibitors in combination with metformin are recommended when eGFR is above 30 mL/min/1.73 m2. SGLT2 inhibitors can be continued until end-stage kidney disease.

Safety and Effectiveness of Cladribine in Multiple Sclerosis: Real-World Clinical Experience From 5 Tertiary Hospitals in Portugal.

OBJECTIVES: Cladribine is a selective and oral immunological reconstitution treatment, approved in Europe for very active multiple sclerosis (MS) with relapses. Aims were to assess the safety and effectiveness of cladribine in real-world setting, during treatment follow-up. METHODS: This was a multicentric, longitudinal, observational study with retrospective and prospective data collection of clinical, laboratory, and imaging data. This interim analysis reports data from July 1, 2018 (study onset), to March 31, 2021. RESULTS: A total of 182 patients were enrolled: 68.7% were female; mean age at onset was 30.1 ± 10.0 years, and mean age at first cycle of cladribine treatment was 41.1 ± 12.1; 88.5% were diagnosed with relapse-remitting MS and 11.5% with secondary progressive MS. Mean disease duration at cladribine start was 8.9 ± 7.7 years. Most patients (86.1%) were not naive, and median number of previous disease-modifying therapies was 2 (interquartile range, 1-3). At 12 months, we observed no significant Expanded Disability Status Scale score worsening ( P = 0.843, Mann-Whitney U test) and a significantly lower annualized relapse rate (0.9 at baseline to 0.2; 78% reduction). Cladribine treatment discontinuation was registered in 8% of patients, mainly (69.2%) due to disease activity persistence. Most frequent adverse reactions were lymphocytopenia (55%), infections (25.2%), and fatigue (10.7%). Serious adverse effects were reported in 3.3%. No patient has discontinued cladribine treatment because of adverse effects. CONCLUSION: Our study confirms the clinical efficacy and the safety profile of cladribine for treating MS patients with a long-term active disease in the real-world setting. Our data contribute to the body of knowledge of the clinical management of MS patients and the improvement of related clinical outcomes.

Increased risk of death following recurrent ketoacidosis admissions: a Brazilian cohort study of young adults with type 1 diabetes.

BACKGROUND: Recurrent DKA (rDKA) remains an acute type 1 diabetes complication even in post-insulin era. This study aimed to analyze the predictors and effects of rDKA on the mortality of patients with type 1 diabetes. METHODS: Patients hospitalized (n = 231) wih diabetic ketoacidosis (between 2007 and 2018) were included. Laboratorial and clinical variables were collected. Mortality curves were compared in four groups: diabetic ketoacidosis as a new-onset type 1 diabetes (group A), single diabetic ketoacidosis episode after diagnosis of type 1 diabetes (group B), 2-5 diabetic ketoacidosis events (group C), and > 5 diabetic ketoacidosis events during follow-up period (group D). RESULTS: During the follow-up period (approximately 1823 days), the mortality rate was 16.02% (37/231). The median age at death was 38.7 years. In the survival curve analysis, at 1926 days (5 years), the probabilities of death were indicated by ratios of 7.78%, 4.58%, 24.40%, and 26.63% in groups A, B, C, and D, respectively. One diabetic ketoacidosis episode compared with ≥ 2 events had a relative risk of 4.49 (p = 0.004) of death and > 5 events had 5.81 (p = 0.04). Neuropathy (RR 10.04; p < 0.001), retinopathy (relative risk 7.94; p < 0.01), nephropathy (RR 7.10; p < 0.001), mood disorders (RR 3.57; p = 0.002), antidepressant use (RR 3.09; p = 0.004), and statin use (RR 2.81; p = 0.0024) increased the risk of death. CONCLUSIONS: Patients with type 1 diabetes with > 2 diabetic ketoacidosis episodes have four times greater risk of death in 5 years. Microangiopathies, mood disorders, and use of antidepressants and statins were important risk factors for short-term mortality.

Consensus for the Early Identification of Secondary Progressive Multiple Sclerosis in Portugal: a Delphi Panel.

INTRODUCTION: Multiple sclerosis is a disease with a heterogeneous evolution. The early identification of secondary progressive multiple sclerosis is a clinical challenge, which would benefit from the definition of biomarkers and diagnostic tools applicable in the transition phase from relapsing-remitting multiple sclerosis to secondary progressive multiple sclerosis. We aimed to reach a Portuguese national consensus on the monitoring of patients with multiple sclerosis and on the more relevant clinical variables for the early identification of its progression. MATERIAL AND METHODS: A Delphi panel which included eleven Portuguese Neurologists participated in two rounds of questions between July and August of 2021. In the first round, 39 questions which belonged to the functional, cognitive, imaging, biomarkers and additional evaluations were included. Questions for which no consensus was obtained in the first round (less than 80% of agreement), were appraised by the panel during the second round. RESULTS: The response rate was 100% in both rounds and consensus was reached for a total of 33 questions (84.6%). Consensus was reached for monitoring time, evaluation scales and clinical variables such as the degree of brain atrophy and mobility reduction, changes suggestive of secondary progressive multiple sclerosis. Additionally, digital devices were considered tools with potential to identify disease progression. Most questions for which no consensus was obtained referred to the cognitive assessment and the remaining referred to both functional and imaging domains. CONCLUSION: Consensus was obtained for the determination of the monitorization interval and for most of the clinical variables. Most questions that did not reach consensus were related with the confirmation of progression taking into account only one test/domain, reinforcing the multifactorial nature of multiple sclerosis.

Association of parental cardiovascular risk factors with offspring type 1 diabetes mellitus insulin sensitivity.

AIM: This study aimed to determine whether the insulin resistance (IR) and lipid profiles in Type 1 Diabetes (T1D) offspring are associated with IR and other cardiovascular risk factors in their parents. METHODS: This study included 99 T1D patients (19.6 ± 4.0 yrs.), 85 mothers and 60 fathers. Parents' IR was assessed by HOMA-IR, and the insulin sensitivity in T1D patients was assessed by the estimated Glucose Disposal Rate (eGDR). RESULTS: The eGDR in the T1D offspring was negatively related to age (p = 0.023), weight (p = 0.004), LDL (p = 0.026), and microalbuminuria (p = 0.019). Maternal Type 2 Diabetes (p < 0.001) and HOMA-IR (p = 0.029) were negatively related to eGDR in their T1D offspring. The maternal HOMA-IR and the proband's eGDR were positively (p = 0.012) and negatively (p = 0.042) associated with the birth weight of the T1D offspring, respectively. We didn't find an association with the fathers' profiles. CONCLUSIONS: In a cohort of offspring with T1D the insulin sensitivity was related to the IR, lipid profile, and the presence of T2D only in their mothers. Precocious screening and treatment of these risk factors beyond glycemic control will benefit T1D with this background.

Spray Freeze Drying of Biologics: A Review and Applications for Inhalation Delivery.

Biopharmaceuticals have established an indisputable presence in the pharmaceutical pipeline, enabling highly specific new therapies. However, manufacturing, isolating, and delivering these highly complex molecules to patients present multiple challenges, including the short shelf-life of biologically derived products. Administration of biopharmaceuticals through inhalation has been gaining attention as an alternative to overcome the burdens associated with intravenous administration. Although most of the inhaled biopharmaceuticals in clinical trials are being administered through nebulization, dry powder inhalers (DPIs) are considered a viable alternative to liquid solutions due to enhanced stability. While freeze drying (FD) and spray drying (SD) are currently seen as the most viable solutions for drying biopharmaceuticals, spray freeze drying (SFD) has recently started gaining attention as an alternative to these technologies as it enables unique powder properties which favor this family of drug products. The present review focus on the application of SFD to produce dry powders of biopharmaceuticals, with special focus on inhalation delivery. Thus, it provides an overview of the critical quality attributes (CQAs) of these dry powders. Then, a detailed explanation of the SFD fundamental principles as well as the different existing variants is presented, together with a discussion regarding the opportunities and challenges of SFD as an enabling technology for inhalation-based biopharmaceuticals. Finally, a review of the main formulation strategies and their impact on the stability and performance of inhalable biopharmaceuticals produced via SDF is performed. Overall, this review presents a comprehensive assessment of the current and future applications of SFD in biopharmaceuticals for inhalation delivery.

Diabetes tipo 2 e transplante renal: estudo comparativo sobre adesão medicamentosa / Diabetes tipo 2 y trasplante renal: estudio comparativo sobre la adhesión farmacológica / Type 2 diabetes and kidney transplant: comparative study on medication adherence

Resumo Objetivo Investigar a adesão medicamentosa no Diabetes Mellitus tipo 2 entre transplantados renais e não transplantados. Métodos Estudo comparativo entre pacientes assistidos no Centro de Diabetes (Grupo 1 sem transplante renal) e no Ambulatório de Pós-Transplante Renal do Hospital do Rim e da Hipertensão (Grupo 2 com transplante renal), ambos na cidade de São Paulo. A amostra foi composta por maiores de 18 anos, com diagnóstico de diabete tipo 2 prévio e em uso de medicamentos para o controle glicêmico. A coleta de dados ocorreu de outubro de 2017 a outubro de 2018. Aplicou-se aos participantes: formulário sócio clínico, instrumento de Medida de Adesão ao Tratamento Medicamentoso no Diabetes Mellitus (antidiabéticos orais e insulina) e a escala de Ansiedade e Depressão. O projeto foi aprovado no Comitê de Ética e Pesquisa como 0712/2017. Resultados Amostra composta de 107 pacientes (Grupo 1: 56 e Grupo 2: 51), maior porcentagem de homens, média de idade de 63,3 anos, provenientes da região metropolitana de São Paulo, aposentados, casados, com sobrepeso, sem sintomas de ansiedade e depressão. Os pacientes autorreferiram ter adesão aos medicamentos para o controle do diabetes, porém os resultados da hemoglobina glicada variaram entre 8,3 e 8,7% entre os grupos, ambos acima de 7%. Conclusão Ao analisar a relação entre a adesão autorreferida, hemoglobina glicada, ansiedade e depressão não foi possível evidenciar correlação estatisticamente significante. Os parâmetros avaliados neste estudo não permitiram estabelecer a relação de causa e efeito.

Resumen Objetivo Investigar la adhesión farmacológica en la Diabetes mellitus tipo 2 en trasplantados renales y no trasplantados. Métodos Estudio comparativo entre pacientes atendidos en el Centro de Diabetes (Grupo 1 sin trasplante renal) y en los Consultorios Externos de Postrasplante Renal del Hospital del Riñón y de la Hipertensión (Grupo 2 con trasplante renal), ambos en la ciudad de São Paulo. La muestra fue formada por mayores de 18 años, con diagnóstico previo de diabetes tipo 2 y en uso de medicamentos para control glucémico. La recopilación de datos se realizó de octubre de 2017 a octubre de 2018. Se aplicaron los siguientes instrumentos a los participantes: formulario socio-clínico, instrumento de Medida de Adhesión al Tratamiento Farmacológico (antidiabéticos orales e insulina) y escala de Ansiedad y Depresión. El proyecto fue aprobado por el Comité de Ética e Investigación con el número 0712/2017. Resultados Muestra formada por 107 pacientes (Grupo 1: 56 y Grupo 2: 51), mayor porcentaje de hombres, promedio de edad 63,3 años, provenientes de la región metropolitana de São Paulo, jubilados, casados, con sobrepeso, sin síntomas de ansiedad y depresión. Los pacientes autodeclararon adherir a los medicamentos para el control de la diabetes, pero los resultados de la hemoglobina glicosilada variaron entre 8,3 y 8,7 % entre los grupos, más de 7 % en ambos. Conclusión Al analizar la relación entre la adhesión autodeclarada, la hemoglobina glicosilada, la ansiedad y la depresión, no se observó correlación estadísticamente significativa. Los parámetros evaluados en este estudio no permitieron establecer una relación de causa y efecto.

Abstract Objective To investigate medication adherence in type 2 Diabetes Mellitus among kidney transplant recipients and non-transplant recipients. Methods Comparative study between patients assisted at the Diabetes Center (Group 1 without kidney transplant) and at the Post-Renal Transplant Outpatient Clinic of the Hospital do Rim e da Hipertensão (Group 2 with kidney transplant), both in the city of São Paulo. The sample consisted of people over 18 years of age with a previous diagnosis of type 2 diabetes using medication for glycemic control. The data collection period was from October 2017 to October 2018. The following was applied to participants: socio-clinical form, instrument for Measuring Adherence to Medication Treatment in Diabetes Mellitus (oral antidiabetics and insulin) and the Anxiety and Depression scale. The project was approved by the Research Ethics Committee as 0712/2017. Results Sample composed of 107 patients (Group 1: 56 and Group 2: 51), higher percentage of men, mean age of 63.3 years, from the metropolitan region of São Paulo, retired, married, overweight, without symptoms of anxiety and depression. Even though patients self-reported adherence to medication for diabetes control, results of glycated hemoglobin ranged between 8.3 and 8.7% between groups, both above 7%. Conclusion When analyzing the relationship between self-reported adherence, glycated hemoglobin, anxiety and depression, a statistically significant correlation could not be found. The parameters evaluated in this study did not allow establishing a cause and effect relationship.

Virtual Reality-Induced Dissociative Symptoms: A Retrospective Study.

Objective: The use of virtual reality (VR) has been increasing worldwide, as devices are becoming more sophisticated and provide an escape from reality during the COVID-19 lockdown. This recent rise in the use of VR leads to new side effects being reported, such as dissociative symptoms that may or may not constitute a mental health concern. This retrospective study investigated the prevalence and intensity of dissociative symptoms in VR users, as well as some potential predisposing conditions that may trigger them, and their impact on the subjects' wellbeing. Materials and Methods: We conducted a survey (n = 358) that was posted on VR Facebook groups. This survey was approved by the University of Lisbon Medical Faculty's IRB, and comprised a modified version of the Clinician-Administered Dissociative State Scale (CADSS) and questions regarding potential risk factors known to induce dissociative disorders or experiences. Results: Data analysis revealed that 83.9% participants reported dissociative symptoms, with varying intensity according to CADSS (X̄=7.62;s=7.89). Significant correlations were found between CADSS score and the time spent playing, the use of software applications (apps) that involve virtual hands or hand tracking, history of previous dissociative experiences, traumatic childhood events, avoidant coping strategies, and psychiatric disorders. Nonetheless, most participants categorized the symptoms as nonanxiogenic (85.8%) and minute lasting (77.4%). Conclusion: In conclusion, this study revealed that although VR can induce dissociative experiences, they seem to be short lasting and nonthreatening to the individual's wellbeing and might be predicted or attenuated by managing other known risk factors for dissociative phenomena.

The 2021-2022 position of Brazilian Diabetes Society on diabetic kidney disease (DKD) management: an evidence-based guideline to clinical practice. Screening and treatment of hyperglycemia, arterial hypertension, and dyslipidemia in the patient with DKD.

BACKGROUND: Diabetic kidney disease is the leading cause of end-stage renal disease and is associated with increased morbidity and mortality. This review is an authorized literal translation of part of the Brazilian Diabetes Society (SBD) Guidelines 2021-2022. This evidence-based guideline provides guidance on the correct management of Diabetic Kidney Disease (DKD) in clinical practice. METHODS: The methodology was published elsewhere in previous SBD guidelines and was approved by the internal institutional Steering Committee for publication. Briefly, the Brazilian Diabetes Society indicated 14 experts to constitute the Central Committee, designed to regulate methodology, review the manuscripts, and make judgments on degrees of recommendations and levels of evidence. SBD Renal Disease Department drafted the manuscript selecting key clinical questions to make a narrative review using MEDLINE via PubMed, with the best evidence available including high-quality clinical trials, metanalysis, and large observational studies related to DKD diagnosis and treatment, by using the MeSH terms [diabetes], [type 2 diabetes], [type 1 diabetes] and [chronic kidney disease]. RESULTS: The extensive review of the literature made by the 14 members of the Central Committee defined 24 recommendations. Three levels of evidence were considered: A. Data from more than 1 randomized clinical trial or 1 metanalysis of randomized clinical trials with low heterogeneity (I2 < 40%). B. Data from metanalysis, including large observational studies, a single randomized clinical trial, or a pre-specified subgroup analysis. C: Data from small or non-randomized studies, exploratory analyses, or consensus of expert opinion. The degree of recommendation was obtained based on a poll sent to the panelists, using the following criteria: Grade I: when more than 90% of agreement; Grade IIa 75-89% of agreement; IIb 50-74% of agreement, and III, when most of the panelist recommends against a defined treatment. CONCLUSIONS: To prevent or at least postpone the advanced stages of DKD with the associated cardiovascular complications, intensive glycemic and blood pressure control are required, as well as the use of renin-angiotensin-aldosterone system blocker agents such as ARB, ACEI, and MRA. Recently, SGLT2 inhibitors and GLP1 receptor agonists have been added to the therapeutic arsenal, with well-proven benefits regarding kidney protection and patients' survival.

Late onset neuromyelitis optica spectrum disorders (LONMOSD) from a nationwide Portuguese study: Anti-AQP4 positive, anti-MOG positive and seronegative subgroups.

INTRODUCTION: Several neuroimmunological disorders have distinct phenotypes according to the age of onset, as in multiple sclerosis or myasthenia gravis. It is also described that late onset NMOSD (LONMOSD) has a different phenotype. OBJECTIVE: To describe the clinical/demographic characteristics of the LONMOSD and distinguish them from those with early onset (EONMOSD). METHODS: From a nationwide Portuguese NMOSD study we analyzed the clinical/demographic characteristics of the LONMOSD. RESULTS: From the 180 Portuguese patients 45 had disease onset after 50 years old, 80% were female. 23 had anti-AQP4 antibodies (51.1%), 13 anti-MOG antibodies (28.9%) and 9 were double seronegative (20.0%). The most common presenting phenotypes in LONMOSD were transverse myelitis (53.3%) and optic neuritis (26.7%), without difference from EONMOSD (p = 0.074). The mean EDSS for LONMOSD was 6.0 (SD=2.8), after a mean follow-up time of 4.58 (SD=4.47) years, which was significantly greater than the mean EDSS of EONMOSD (3.25, SD=1.80)(p = 0.022). Anti-AQP4 antibodies positive LONMOSD patients had increased disability compared to anti-MOG antibodies positive LONMOSD (p = 0.022). The survival analysis showed a reduced time to use a cane for LONMOSD, irrespective of serostatus (p<0.001). CONCLUSIONS: LONMOSD has increased disability and faster progression, despite no differences in the presenting clinical phenotype were seen in our cohort.

Can C-budget of natural capital be restored through conservation agriculture in a tropical and subtropical environment?

Conservation agriculture through no-till based on cropping systems with high biomass-C input, is a strategy to restoring the carbon (C) lost from natural capital by conversion to agricultural land. We hypothesize that cropping systems based on quantity, diversity and frequency of biomass-C input above soil C dynamic equilibrium level can recover the natural capital. The objectives of this study were to: i) assess the C-budget of land use change for two contrasting climatic environments, ii) estimate the C turnover time of the natural capital through no-till cropping systems, and iii) determine the C pathway since soil under native vegetation to no-till cropping systems. In a subtropical and tropical environment, three types of land use were used: a) undisturbed soil under native vegetation as the reference of pristine level; b) degraded soil through continuous tillage; and c) soil under continuous no-till cropping system with high biomass-C input. At the subtropical environment, the soil under continuous tillage caused loss of 25.4 Mg C ha-1 in the 0-40 cm layer over 29 years. Of this, 17 Mg C ha-1 was transferred into the 40-100 cm layers, resulting in the net negative C balance for 0-100 cm layer of 8.4 Mg C ha-1 with an environmental cost of USD 1968 ha-1. The 0.59 Mg C ha-1 yr-1 sequestration rate by no-till cropping system promote the C turnover time (soil and vegetation) of 77 years. For tropical environment, the soil C losses reached 27.0 Mg C ha-1 in the 0-100 cm layer over 8 years, with the environmental cost of USD 6155 ha-1, and the natural capital turnover time through C sequestration rate of 2.15 Mg C ha-1 yr-1 was 49 years. The results indicated that the particulate organic C and mineral associate organic C fractions are the indicators of losses and restoration of C and leading C pathway to recover natural capital through no-till cropping systems.

[Development and Implementation of a Patient Registry: The Experience of a Multiple Sclerosis Center in Portugal]. / Desenvolvimento e Implementação de um Registo de Doentes: Experiência de um Centro de Esclerose Múltipla em Portugal.

INTRODUCTION: Patient registries allow better evaluations of therapeutic outcomes and support personalized health care in several conditions. This study aimed to implement a local registry in a multiple sclerosis center in Portugal, in order to carry out a critical analysis of its development stages, and to perform an initial analysis of the included patients. MATERIAL AND METHODS: The establishment of the registry was divided in two phases - development (creation of the online platform for data entry) and implementation (recruitment of patients and retrospective and prospective collection of available information). A demographic and clinical analysis of patients was performed. RESULTS: Neurologists and study coordinators participated in the project, accounting for a total of 1050 hours of work in the implementation phase. Amongst the 498 multiple sclerosis patients included, 72.9% were female and relapsing-remitting multiple sclerosis was the most common subtype of the disease. The most frequently prescribed drugs at diagnosis were beta interferons. Missing data in electronic health records were detected concerning the progression of disability and diagnostic tests. DISCUSSION: The difficulties encountered could be mitigated by defining minimum elements to be included in patient records and by implementing more minimalist registries. This could reduce the time spent by healthcare professionals in collecting information, thus optimizing costs, and allowing the focus to be placed on personalized healthcare by taking advantage of the registry and its associated tools. CONCLUSION: Despite the amount of data collected within the scope of this study, several difficulties affected the implementation and maintenance of the registry, which could be overcome by improving future strategies.

Introdução: Registos de doentes permitem avaliar melhor resultados terapêuticos e suportar a personalização de cuidados de saúde em diversas patologias. Este trabalho teve como objetivos: implementar um registo local num centro de esclerose múltipla em Portugal; proceder a uma análise crítica das suas etapas de desenvolvimento; e realizar uma primeira análise dos doentes incluídos.Material e Métodos: A criação do registo dividiu-se em duas fases: desenvolvimento (construção da plataforma online) e implementação (recrutamento de doentes e recolha retrospetiva e prospetiva da informação disponível). Realizou-se uma análise demográfica e clínica dos doentes incluídos.Resultados: Especialistas em Neurologia e coordenadores de estudo participaram no projeto, num total de 1050 horas de trabalho na fase de implementação. Dos 498 doentes com esclerose múltipla incluídos no estudo, 72,9% eram do género feminino, tendo sido identificada como subtipo de doença mais comum a esclerose múltipla surto remissão. Os fármacos mais frequentemente prescritos após diagnóstico foram interferões beta. Detetaram-se lacunas no processo clínico dos doentes relativamente à progressão da incapacidade e a exames complementares de diagnóstico.Discussão: As dificuldades encontradas poderão ser mitigadas através da definição de elementos obrigatórios nos processos clínicos dos doentes e da implementação de registos mais minimalistas. Este procedimento possibilitaria reduzir o tempo despendido por profissionais de saúde na recolha de informação, otimizar custos, e permitir o foco na utilização do registo e ferramentas associadas ao mesmo para personalização de cuidados de saúde.Conclusão: Apesar do volume de dados recolhidos no âmbito deste estudo, foram encontradas dificuldades que comprometeram a implementação e manutenção do registo, que poderão ser ultrapassadas com a otimização de estratégias futuras.

Parents' cardiovascular risk factors are related to overweight and obesity in young Brazilians with type 1 diabetes.

AIM: To identify family background characteristics and cardiovascular disease (CVD) risk factors linked to overweight and obesity in Brazilian with type 1 diabetes (T1D). METHODS: We performed cross-sectional anthropometric and laboratory analyses in young individuals with T1D. RESULTS: Among 181 participants, 87 were women and 94 were men (64%/78% normal weight, 27%/15% overweight and 9%/7% obese). Obese men were older; were more likely to be Black; had higher triglyceride levels and diastolic blood pressure (BP), lower estimated glucose disposal rate (eGDR) and higher prevalence of first-degree relatives (FDR) with hypertension and early CVD. Overweight and obese women were more likely to have lower eGDR, and obese women were more likely to have FDR with obesity. CONCLUSION: One third of young people with T1D were overweight or obese. Excess weight was associated with family history (FH) of obesity for women and FH of early CVD or hypertension for men. BMI was related to decreased insulin sensitivity in both genders, but only men with T1D had metabolic impairment. Our data highlight the importance of considering family background in individuals with T1D.

Neuromyelitis optica spectrum disorders: A nationwide Portuguese clinical epidemiological study.

INTRODUCTION: Neuromyelitis optica spectrum disorder (NMOSD) is a rare disorder in which astrocyte damage and/or demyelination often cause severe neurological deficits. OBJECTIVE: To identify Portuguese patients with NMOSD and assess their epidemiological/clinical characteristics. METHODS: This was a nationwide multicenter study. Twenty-four Portuguese adult and 3 neuropediatric centers following NMOSD patients were included. RESULTS: A total of 180 patients met the 2015 Wingerchuk NMOSD criteria, 77 were AQP4-antibody positive (Abs+), 67 MOG-Abs+, and 36 seronegative. Point prevalence on December 31, 2018 was 1.71/100,000 for NMOSD, 0.71/100,000 for AQP4-Abs+, 0.65/100,000 for MOG-Abs+, and 0.35/100,000 for seronegative NMOSD. A total of 44 new NMOSD cases were identified during the two-year study period (11 AQP4-Abs+, 27 MOG-Abs+, and 6 seronegative). The annual incidence rate in that period was 0.21/100,000 person-years for NMOSD, 0.05/100,000 for AQP4-Abs+, 0.13/100,000 for MOG-Abs+, and 0.03/100,000 for seronegative NMOSD. AQP4-Abs+ predominated in females and was associated with autoimmune disorders. Frequently presented with myelitis. Area postrema syndrome was exclusive of this subtype, and associated with higher morbidity/mortality than other forms of NMOSD. MOG-Ab+ more often presented with optic neuritis, required less immunosuppression, and had better outcome. CONCLUSION: Epidemiological/clinical NMOSD profiles in the Portuguese population are similar to other European countries.

Defining the prodromal phase of multiple sclerosis based on healthcare access in a Portuguese population - ProdMS study.

BACKGROUND: Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system. Prodromal symptoms and higher healthcare use have been suggested in patients who later develop MS. OBJECTIVES: Assess the healthcare utilization pattern of relapsing-remitting MS (RRMS) patients in the five years prior to MS diagnosis. METHODS: Retrospective, multicentric study. Demographic and clinical data, drug prescriptions and diagnostic tests were collected from electronic health records five-years previous to MS diagnosis and compared with national data. RESULTS: Included 168 patients, 112 (66.7%) female, median age 34±11 years. The mean number of healthcare use per patient per year was 3.14±2,69, most of them in primary healthcare (47%). Most frequent symptoms were musculoskeletal (22%), gastrointestinal (17%), sensitive (14%) and sensory organs (14%). Median number of diagnostic tests per patient was 6 (IQR 7), and drug prescriptions per patient was 6 (IQR 9). Most frequently prescribed drugs were analgesic/anti-inflammatories, antibiotics and anxiolytics and there was a high request rate of MRIs. CONCLUSION: RRMS patients had a high frequency of healthcare utilization when compared to national data. This supports the current evidence showing a prodromal phase in MS.

Development and validation of a pocket guide for the prevention of diabetic foot ulcers.

OBJECTIVE: Diabetic foot ulcers can have serious consequences, including amputation. This project aimed to develop and validate a diabetes care management model-a pocket guide on the prevention of foot ulceration to assist health professionals and scientific societies. METHODS: An adaptation of the Iowa method of evidence-based practice to promote high-quality care was employed. After problems are identified, the Iowa method supports the development of an action plan for addressing them. An evidence-based protocol based on the five cornerstones of the 2015 guidance on the diabetic foot by the International Working Group on the Diabetic Foot was developed in two phases and validated using the Delphi technique. RESULTS: A model was developed to promote these five cornerstones, which are the main recommendations for managing the diabetic foot. These are: foot examination; risk assessment for ulceration; education in diabetes; appropriate footwear; and treatment of pre-ulcerative lesions. To adapt this into a health information document, the management model was synthesised and designed as a pocket guide. The model's individual and global content validity indices surpass 0.78 and 0.90 respectively. CONCLUSION: A management model was created and validated, and produced as a pocket guide to deliver instructions on the care and prevention of diabetic foot problems in people with diabetes.