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.

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.

Incidence of multiple sclerosis in Northern Lisbon, Portugal: 1998-2007.

BACKGROUND: There are few, recent, well assessed, multiple sclerosis (MS) incidence surveys on European populations. This study sought to measure MS incidence in a Northern Lisbon population and assess it using capture-recapture methods (CRMs). METHODS: Among the population residing in the Northern Lisbon Health Area, registered MS diagnoses were obtained from general practitioners in three primary-care districts covering a population of 196,300, and a neurology unit at the main referral hospital. Cases with onset during the periods 1978-1997 and 2008-2012 were excluded due to perceived poor access to image-supported neurological diagnosis and administrative changes in patient referral respectively. Age- and sex-specific incidences for the period 1998-2007 were calculated using McDonald diagnostic criteria, and CRMs were used to correct age-specific incidence rates. The corrected figures were also adjusted for age using the European Standard Population as reference. RESULTS: When applied to 62 MS patients with onset in the period 1998-2007, the rates per 100,000 population were as follows for both sexes: crude, 3.16; age-adjusted, 3.09 (95% CI 2.32 to 3.87); CRM-adjusted, 4.53 (95% CI 3.13 to 5.94); and age- and CRM-adjusted, 4.48 (3.54-5.41). In general, the rates were 3-fold higher among women than among men. Negative source dependency and CRM impact were highest at ages 35-44 years, where a 60% rise led to a peak incidence. CONCLUSIONS: MS incidence in Northern Lisbon, Portugal, is moderately lower than that yielded by surveys on European populations. CRMs, which in this instance suggest undercounts, are a potentially useful tool for case-finding assessment but their application may introduce bias.

Modification of polysulfone membrane used in the water filtration process to reduce biofouling.

Polysulfone membranes (PSF) were modified with silver nanoparticles obtained by new synthesis (nAgNS), silver nanoparticles obtained commercially (nAgC), silver sulfadiazine (SP), dodecyltrimethylammonium bromide (DOTAB), benzalkonium chloride (CB) or sodium dodecylbenzene sulfonate (DBSS) to improve the efficiency of the water filtration process by reducing biofouling. All membranes had lower hydrophobicity compared with PSF. The zeta potentials of all membranes were negative at pH 7.0, except for CB 10%. In the agar diffusion test, E. coli was considered to be sensitive to the antimicrobial effect of the nAgNS 1%, 3%, 6%, 10% and DOTAB 10%, whereas S. aureus was sensitive to the nAgNS 1%, 3%, 6%, 10%, DOTAB 10%, CB 0.22%, 2% and 10%. The lowest adhesion of E. coli was found in the nAgNS 6% and 10%. In the evaluation of the loss of flow rate during filtration of the E. coli suspension and pure water, nAgNS showed higher flow rate values when compared with PSF. The nAgNS did not release quantities of silver (0.1 mg/l) above the amount considered safe by the World Health Organization. Membranes nAgNS 6% and 10% showed the best anti-biofouling characteristic.

Once-weekly insulin icodec versus once-daily long-acting insulins for type 2 diabetes mellitus: Systematic review and meta-analysis.

Background: Insulin icodec is a novel, long-acting, once-weekly basal insulin analog. Its comparative efficacy and safety with basal once-daily insulins in type 2 diabetes mellittus is uncertain. Objective: Evaluate potential efficacy, benefits and risks associated with icodec compared to once-daily basal insulin analogs (degludec or glargine). Methods: We systematically searched PubMed, Cochrane, and Embase for randomized controlled trials (RCTs) published until June 2023 comparing icodec versus long-acting insulin analogs (degludec and glargine) in type 2 diabetes mellitus (T2DM) with at least 12 weeks of follow-up. Binary endpoints were assessed with risk ratios (RRs) and continuous endpoints were compared using mean differences (MDs), with 95% confidence intervals (CIs). The protocol was registered in PROSPERO (CRD42023452468). Results: A total of seven RCTs and 3286 patients with T2DM were included, of whom 1509 (60.6%) received icodec treatment. The follow-up period ranged from 16 to 78 weeks. Compared with once-daily basal insulin analogs, icodec led to a greater improvement in HbA1c (MD -0.15%; 95% CI -0.21, -0.10; p < 0.0001; I2 = 0%) and time in range (TIR) (MD 2.83%; 95%CI 0.94; 4.71; p = 0.003; I2 = 22%). Body weight was increased with icodec treatment (MD 0.78 Kg; 95%CI 0.42, 1.15; p < 0.01; I2 = 86%). There was also a higher rate of injection site reactions (RR 1.89; 95%CI 1.12, 3.18; p = 0.016; I2 = 0%) and nasopharyngitis (RR 1.94; 95%CI 1.11, 3.38; p = 0.020; I2 = 0%) in the icodec group, compared with once-daily regimens. There was no significant difference between groups in fasting plasma glucose. Conclusions: In this meta-analysis of RCTs, insulin icodec led to better control of HbA1c and TIR as compared with once-daily insulin regimens, albeit with increased weight gain and a higher rate of injection site reaction in the Icodec group.

Incidence of multiple sclerosis among European Economic Area populations, 1985-2009: the framework for monitoring.

BACKGROUND: A debate surrounding multiple sclerosis epidemiology has centred on time-related incidence increases and the need of monitoring. The purpose of this study is to reassess multiple sclerosis incidence in the European Economic Area. METHODS: We conducted a systematic review of literature from 1965 onwards and integrated elements of original research, including requested or completed data by surveys authors and specific analyses. RESULTS: The review of 5323 documents yielded ten studies for age- and sex-specific analyses, and 21 studies for time-trend analysis of single data sets. After 1985, the incidence of multiple sclerosis ranged from 1.12 to 6.96 per 100,000 population, was higher in females, tripled with latitude, and doubled with study midpoint year. The north registered increasing trends from the 1960s and 1970s, with a historic drop in the Faroe Islands, and fairly stable data in the period 1980-2000; incidence rose in Italian and French populations in the period 1970-2000, in Evros (Greece) in the 1980s, and in the French West Indies in around 2000. CONCLUSIONS: We conclude that the increase in multiple sclerosis incidence is only apparent, and that it is not specific to women. Monitoring of multiple sclerosis incidence might be appropriate for the European Economic Area.

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.

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.

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.

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.

[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.

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.

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.

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.

The first series of cases of ketosis-prone type 2 diabetes (flatbush diabetes) in Brazilian adults.

Ketosis-prone type 2 diabetes (KPD) is an emerging form of diabetes mellitus characterized by unprovoked ketoacidosis, absence of autoimmunity and beta-cell dysfunction. The KPD may improve after initial glycemic compensation and evolve to exogenous insulin independence, most cases were observed in populations with African or Hispanic backgrounds. We reviewed the literature on KPD and, to date, only one case of KPD has been described in Brazil's multi-ethnic population. A group of adult Brazilian KPD patients without autoimmunity and insulinopenia was identified for this study. We report a retrospective study of four KPD cases (3 males) evaluated in southeast Brazil, the patients were overweight or obese, age between the third and fifth decades of life, had a family history of type 2 diabetes, hyperglycemia (809.5 ± 344.2 mg/dL), acidosis (pH 7.21 ± 0.07; normal range (nr): 7.35-7.45 and bicarbonate 9.1 ± 6.2; nr: 22-26 mEq/mL), ketonuria (142.5 ± 114.4 mg/dL; nr: absence), absence of glutamic acid decarboxylase antibodies (GAD-65), and beta-cell function reserve (C-peptide 1.19 ± 0.53 ng/mL - nr: 1.1-4.4 ng/mL) on diagnosis. After glycemic compensation, there was increase of C-peptide (2.21 ± 0.41) indicating the recovery of beta-cell function and the time to insulin independence was 7.7 ± 3.5 months. They evolved after the period of glucotoxicity with insulin withdrawal and could be treated with oral antidiabetic therapy. This is the first case series of KPD described in Brazil being characterized by ketoacidosis at diagnosis, absence of autoimmunity, recovery of beta-cell function and insulin independence.

Multiple Sclerosis Patient Management During the COVID-19 Pandemic: Practical Recommendations From the Portuguese Multiple Sclerosis Study Group (GEEM).

The spread of the COVID-19 pandemic has imposed significant challenges on healthcare provision, requiring changes in the conventional patient management, particularly in chronic diseases like multiple sclerosis (MS). To increase patient safety and reduce the risk of infection, while ensuring an appropriate and regular follow-up, tele-medicine gained prominence as a valid alternative to face-to-face appointments. However, the urgency of the implementation and the lack of experience in most MS centers led to "ad hoc" and extremely diverse approaches, which now merit to be standardized and refined. Indeed, while tele-consultation cannot fully replace face-to-face visits, it certainly can, and will, be incorporated as part of the routine care of MS patients in the near future. Bearing this in mind, the Portuguese Multiple Sclerosis Study Group (GEEM) has developed a set of recommendations for the usage of tele-medicine in the management of MS patients, both during the pandemic and in the future. The consensus was obtained through a two-step modified Delphi methodology, resulting in 15 recommendations, which are detailed in the manuscript.

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.