Natalizumab extended interval dosing: what about wearing-off effect?

BACKGROUND: Up to two thirds of patients with multiple sclerosis (MS) under natalizumab report a resurgence of symptoms at the end of the natalizumab cycle (wearing-off (WO) effect). At the outbreak of COVID-19, in line with the international recommendations for MS management, our centre switched all clinically stable patients on natalizumab therapy for more than one year from standard interval dosing (SID) to extended interval dosing (EID) with every six weeks infusions. This study aimed to evaluate the impact of EID in WO in MS patients under natalizumab. METHODS: An observational retrospective study in patients with MS under natalizumab on EID was conducted. A questionnaire regarding current (on EID) and past (on SID) experience of WO effect was applied. RESULTS: Seventy-six patients were included. No significant differences were found in the annual relapse rate after the switch to EID (p = 0.083). However, there was a significant increase in the proportion of patients complaining of WO from 38.2% to 56.6% (p = 0.001). Moreover, patients with WO on SID, referred a significant increase in severity (p = 0.019) and duration of WO symptoms (p = 0.029), due to an anticipation of the symptoms relative to the day of natalizumab infusion (p = 0.019), when switching to EID. Symptoms improved with treatment maintenance in 23.3% of patients; instead, a reduction in interval dosing was needed in 54.8% with symptom improvement. CONCLUSION: WO affects a significant proportion of MS patients under natalizumab. Its prevalence, severity, and duration increase on EID, therefore despite clinical effectiveness maintenance of this posology should be individualized.

Prevalence, Incidence, and Mortality of Multiple Sclerosis in Coimbra, Portugal.

Multiple sclerosis (MS) is the most common chronic inflammatory, demyelinating, and neurodegenerative disease of the central nervous system in young adults, representing the leading cause of nontraumatic disability in this population. The rising prevalence of MS worldwide makes it critical to recognize the absolute number of patients with MS, demanding the execution of a sustainable healthcare policy. In Portugal, only six studies evaluating MS rates were published, disclosing a prevalence of 64 cases per 100,000 persons and an incidence of 3.1 cases per 100,000 persons/year, but the mortality rates have not been reported. Thus, this observational, cross-sectional study aimed to assess MS prevalence, incidence, and mortality in the city of Coimbra, a region in the center of Portugal. Patients who fulfilled McDonald's Diagnosis Criteria (2017) for MS were recruited. Inclusion criteria were defined according to prevalence, incidence, and mortality studies. The baseline demographic and clinical characterization of the prevalence study population was performed. The MS prevalence rate in Coimbra was 143.45 cases per 100,000 inhabitants. Between 2018 and 2021, the cumulative incidence was 8.52 new cases per 100,000 persons/year. The mortality rate between 2018 and 2021 was 2.84 deaths per 100,000 inhabitants. MS prevalence and incidence in Coimbra are higher than reported in previous similar studies and comparable to Europe's mean prevalence and incidence.

Difference in determinants of ICU admission and death among COVID-19 hospitalized patients in two epidemic waves in Portugal: possible impact of healthcare burden and hospital bed occupancy on clinical management and outcomes, March-December 2020.

Aim: Identify factors associated with COVID-19 intensive care unit (ICU) admission and death among hospitalized cases in Portugal, and variations from the first to the second wave in Portugal, March-December 2020. Introduction: Determinants of ICU admission and death for COVID-19 need further understanding and may change over time. We used hospital discharge data (ICD-10 diagnosis-related groups) to identify factors associated with COVID-19 outcomes in two epidemic periods with different hospital burdens to inform policy and practice. Methods: We conducted a retrospective cohort study including all hospitalized cases of laboratory-confirmed COVID-19 in the Portuguese NHS hospitals, discharged from March to December 2020. We calculated sex, age, comorbidities, attack rates by period, and calculated adjusted relative risks (aRR) for the outcomes of admission to ICU and death, using Poisson regressions. We tested effect modification between two distinct pandemic periods (March-September/October-December) with lower and higher hospital burden, in other determinants. Results: Of 18,105 COVID-19 hospitalized cases, 10.22% were admitted to the ICU and 20.28% died in hospital before discharge. Being aged 60-69 years (when compared with those aged 0-49) was the strongest independent risk factor for ICU admission (aRR 1.91, 95%CI 1.62-2.26). Unlike ICU admission, risk of death increased continuously with age and in the presence of specific comorbidities. Overall, the probability of ICU admission was reduced in the second period but the risk of death did not change. Risk factors for ICU admission and death differed by epidemic period. Testing interactions, in the period with high hospital burden, those aged 80-89, women, and those with specific comorbidities had a significantly lower aRR for ICU admission. Risk of death increased in the second period for those with dementia and diabetes. Discussion and conclusions: The probability of ICU admission was reduced in the second period. Different patient profiles were identified for ICU and deaths among COVID-19-hospitalized patients in different pandemic periods with lower and higher hospital burden, possibly implying changes in clinical practice, priority setting, or clinical presentation that should be further investigated and discussed considering impacts of higher burden on services in health outcomes, to inform preparedness, healthcare workforce planning, and pandemic prevention measures.

HBM4EU-MOM: Prenatal methylmercury-exposure control in five countries through suitable dietary advice for pregnancy - Study design and characteristics of participants.

BACKGROUND: Seafood is a major source of vital nutrients for optimal fetal growth, but at the same time is the main source of exposure to methylmercury (MeHg), an established neurodevelopmental toxicant. Pregnant women must be provided with dietary advice so as to include safely fish in their diet for nutrition and mercury control. The aim of this work is to present the design of a multicentre randomized control trial (RCT), which combines human biomonitoring (HBM) with dietary interventions using seafood consumption advice to pregnant women for MeHg control, and to collect information about other possible sources of exposure to mercury. It also presents the materials developed for the implementation of the study and the characteristics of the study participants, which were self-reported in the first trimester of pregnancy. METHODS: The "HBM4EU-MOM" RCT was performed in the frame of the European Human Biomonitoring Initiative (HBM4EU) in five coastal, high fish-consuming European countries (Cyprus, Greece, Spain, Portugal and Iceland). According to the study design, pregnant women (≥120/country, ≤20 weeks gestational age) provided a hair sample for total mercury assessment (THg) and personal information relevant to the study (e.g., lifestyle, pregnancy status, diet before and during the pregnancy, information on seafood and factors related to possible non-dietary exposures to mercury) during the first trimester of pregnancy. After sampling, participants were randomly assigned to "control" (habitual practices) or "intervention" (received the harmonized HBM4EU-MOM dietary advice for fish consumption during the pregnancy and were encouraged to follow it). Around child delivery, participants provided a second hair sample and completed another tailored questionnaire. RESULTS: A total of 654 women aged 18-45 years were recruited in 2021 in the five countries, primarily through their health-care providers. The pre-pregnancy BMI of the participants ranged from underweight to obese, but was on average within the healthy range. For 73% of the women, the pregnancy was planned. 26% of the women were active smokers before the pregnancy and 8% continued to smoke during the pregnancy, while 33% were passive smokers before pregnancy and 23% remained passively exposed during the pregnancy. 53% of the women self-reported making dietary changes for their pregnancy, with 74% of these women reporting making the changes upon learning of their pregnancy. Of the 43% who did not change their diet for the pregnancy, 74% reported that their diet was already balanced, 6% found it difficult to make changes and 2% were unsure of what changes to make. Seafood consumption did not change significantly before and during the first trimester of pregnancy (overall average ∼8 times per month), with the highest frequency reported in Portugal (≥15 times per month), followed by Spain (≥7 times per month). During the first-trimester of pregnancy, 89% of the Portuguese women, 85% of the Spanish women and <50% of Greek, Cypriot and Icelandic women reported that they had consumed big oily fish. Relevant to non-dietary exposure sources, most participants (>90%) were unaware of safe procedures for handling spillage from broken thermometers and energy-saving lamps, though >22% experienced such an incident (>1 year ago). 26% of the women had dental amalgams. ∼1% had amalgams placed and ∼2% had amalgams removed during peri-pregnancy. 28% had their hair dyed in the past 3 months and 40% had body tattoos. 8% engaged with gardening involving fertilizers/pesticides and 19% with hobbies involving paints/pigments/dyes. CONCLUSIONS: The study design materials were fit for the purposes of harmonization and quality-assurance. The harmonized information collected from pregnant women suggests that it is important to raise the awareness of women of reproductive age and pregnant women about how to safely include fish in their diet and to empower them to make proper decisions for nutrition and control of MeHg, as well as other chemical exposures.

Teriflunomide treatment outcomes in multiple sclerosis: A Portuguese real-life experience.

Teriflunomide is an oral disease-modifying therapy for relapsing-remitting multiple sclerosis patients. A decline in physical and cognitive functions, which negatively impacts their quality of life (QoL), is observed in relapsing-remitting multiple sclerosis patients. The aim of this study was to characterise adult Portuguese relapsing-remitting multiple sclerosis patients treated with teriflunomide in routine clinical practice concerning their quality of life, comorbidities, treatment effectiveness, satisfaction, compliance and safety. TeriLIVE-QoL was a multicentre, non-interventional, prospective cohort study that collected demographic and clinical characteristics, patient-reported outcomes and adverse events from patients treated with teriflunomide of 14 mg over 2 years. Notably, around 18 months of this period occurred during the COVID-19 pandemic. Of the 99 participants, 25% were treatment-naïve. Annualised relapse rate and the score for the Hospital Anxiety and Depression Scale decreased after 1 (p = 0.01) and 2 years of treatment (p < 0.001), respectively. Convenience (p = 0.001), effectiveness (p = 0.002) and global satisfaction scores (p < 0.001) presented high values (up to 95.6) and continued to improve along the study. Treatment persistence was 77%, and compliance reached 82% 2 years after initiation. Three patients experienced serious adverse events. TeriLIVE-QoL provides real-world evidence of clinical effectiveness, high treatment satisfaction, consistent safety and improved psychiatric outcomes, associated with elevated treatment persistence and compliance in patients treated with teriflunomide.iance reached 82% 2 years after initiation. Three patients experienced serious adverse events.

The Effect of Timeliness of Care on Lung Cancer Survival - A Population-Based Approach.

Background: Timeliness of care is an important dimension of healthcare quality but it's unclear whether it improves clinical outcomes in lung cancer (LC) patients. Objectives: This study aims to analyze treatment patterns, time-to-treatment (TTT) and the impact of treatment timeliness (TT) in overall survival (OS) of patients diagnosed with LC in 2009-2014 in a population-based registry from Southern Portugal. Materials and Methods: We estimated median TTT for overall population, treatment type and stage. The impact of treatment and TT on five-year OS was analyzed using the Kaplan-Meier method and Cox regression modelling to determine the hazard ratio (HR) of death associated with treatment and TT. Results: From the 11,308 cases diagnosed, 61.7% received treatment. Treatment rate decreased with increasing stage from 88% in stage I to 66.1% in stage IV. Overall median TTT was 49 days (IQR: 28-88) and 43.3% received TT. Surgery had a longer TTT than radiotherapy and systemic treatment. Patients in earlier stages had lower TT rates and longer TTT compared to more advanced, 24.7% and 80 days in stage I versus 51.3% and 42 days in stage IV (p < 0.0001). OS was 14.9% for total population and 19.6% and 7.1% for patients with and without treatment registered, respectively. TT had no observed impact on OS for stages I/II but a negative effect for stages III/IV. Relative to treated, the adjusted mortality risk was higher in untreated patients (HR = 2.240; 95%CI: 2.293-2.553). Contrary to treatment, TT had a negative impact on survival, with 11.3% in timely vs. 21.5% in untimely treated. Compared to untimely treated, the risk of death in TT patients was 46.6% higher (HR = 1.465; 95%CI: 1.381-1.555). Conclusions: LC survival is highly dependent on early diagnosis and adequate treatment. Time-to-treatment was longer than recommended for all treatment types but particularly for surgery. Overall TT results were paradoxical, as better survival was observed in patients untimely treated. The factors associated with TT were not possible to analyze and its impact on patient outcomes remains unclear. However, it is important to assess quality-of-care to improved LC management.

LOCUS (LOng Covid-Understanding Symptoms, events and use of services in Portugal): A three-component study protocol.

Approximately 10% of patients experience symptoms of Post COVID-19 Condition (PCC) after a SARS-CoV-2 infection. Akin acute COVID-19, PCC may impact a multitude of organs and systems, such as the cardiovascular, respiratory, musculoskeletal, and neurological systems. The frequency and associated risk factors of PCC are still unclear among both community and hospital settings in individuals with a history of COVID-19. The LOCUS study was designed to clarify the PCC's burden and associated risk factors. LOCUS is a multi-component study that encompasses three complementary building blocks. The "Cardiovascular and respiratory events following COVID-19" component is set to estimate the incidence of cardiovascular and respiratory events after COVID-19 in eight Portuguese hospitals via electronic health records consultation. The "Physical and mental symptoms following COVID-19" component aims to address the community prevalence of self-reported PCC symptoms through a questionnaire-based approach. Finally, the "Treating and living with Post COVID-19 Condition" component will employ semi-structured interviews and focus groups to characterise reported experiences of using or working in healthcare and community services for the treatment of PCC symptoms. This multi-component study represents an innovative approach to exploring the health consequences of PCC. Its results are expected to provide a key contribution to the optimisation of healthcare services design.

COVID-19 surveillance: Large decrease in clinical notifications and epidemiological investigation questionnaires for laboratory-confirmed cases after the 2nd epidemic wave, Portugal March 2020-July 2021.

Introduction: In Portugal, COVID-19 laboratory notifications, clinical notifications (CNs), and epidemiological investigation questionnaires (EI) were electronically submitted by laboratories, clinicians, and public health professionals, respectively, to the Portuguese National Epidemiological Surveillance System (SINAVE), as mandated by law. We described CN and EI completeness in SINAVE to inform pandemic surveillance efforts. Methods: We calculated the proportion of COVID-19 laboratory-notified cases without CN nor EI, and without EI by region and age group, in each month, from March 2020 to July 2021. We tested the correlation between those proportions and monthly case counts in two epidemic periods and used Poisson regression to identify factors associated with the outcomes. Results: The analysis included 909,720 laboratory-notified cases. After October 2020, an increase in the number of COVID-19 cases was associated with a decrease in the submissions of CN and EI. By July 2021, 68.57% of cases had no associated CN nor EI, and 96.26% had no EI. Until January 2021, there was a positive correlation between monthly case counts and the monthly proportion of cases without CN nor EI and without EI, but not afterward. Cases aged 75 years or older had a lower proportion without CN nor EI (aRR: 0.842 CI95% 0.839-0.845). When compared to the Norte region, cases from Alentejo, Algarve, and Madeira had a lower probability of having no EI (aRR;0.659 CI 95%0.654-0.664; aRR 0.705 CI 95% 0.7-0.711; and aRR 0.363 CI 95% 0.354-0.373, respectively). Discussion: After January 2021, CN and EI were submitted in a small proportion of laboratory-confirmed cases, varying by age and region. Facing the large number of COVID-19 cases, public health services may have adopted other registry strategies including new surveillance and management tools to respond to operational needs. This may have contributed to the abandonment of official CN and EI submission. Useful knowledge on the context of infection, symptom profile, and other knowledge gaps was no longer adequately supported by SINAVE. Regular evaluation of pandemic surveillance systems' completeness is necessary to inform surveillance improvements and procedures considering dynamic objectives, usefulness, acceptability, and simplicity.

Tuberculin skin test and interferon-γ release assays: Can they agree?

INTRODUCTION: The diagnosis of latent tuberculosis infection (LTBI) relies largely on the tuberculin skin test (TST) or, more recently, on interferon-gamma release assays (IGRA). Knowledge regarding these tests is essential to improve their usefulness in combating the tuberculosis epidemic. OBJECTIVES: To characterize the agreement between the IGRA and TST tests by determining the kappa coefficient (K) and agreement rate between these two tests in patients with active tuberculosis (TB). METHODS: Retrospective cohort study conducted with data from active TB patients notified in the Portuguese Tuberculosis Surveillance System (SVIG-TB), from 2008 to 2015. TST results were interpreted using a 5 mm (TST-5 mm) and 10 mm (TST-10 mm) cutoff. Kappa coefficient and agreement rate were calculated in order to evaluate the agreement between IGRA and TST (both cutoffs) test results. RESULTS: A total of 727 patients with results for both tests were included in the study, of which 3.4% (n = 25) had HIV infection, 5.6% (n = 41) diabetes, 5.0% (n = 36) oncological diseases and 4.4% (n = 32) inflammatory diseases. Of the 727 patients, 16.5% (n = 120) presented different outcomes between IGRA and TST-5 mm, and 20.5% (n = 149) presented different outcomes between IGRA and TST-10 mm. Kappa coefficient between IGRA and TST-5 mm was 0.402 (p < 0.001) with an agreement rate of 83.5%. Between IGRA and TST-10 mm, the kappa coefficient was 0.351 (p < 0.001), with an agreement rate of 79.5%. Patients with HIV infection, diabetes, oncologic diseases and inflammatory diseases presented a substantial agreement between IGRA and TST-5 mm, while inflammatory diseases was the only variable that presented a substantial agreement between IGRA and TST-10 mm. CONCLUSION: As both tests can present false-negative results, the low level of agreement between the tests can potentially help identify more cases of LTBI if the two tests are used in parallel, with infections not detected by IGRA possibly being detected by the TST and vice versa.

Motivação para a prática de atividade física em estudantes de enfermagem / Motivation for physical activity among nursing students / Motivación para la práctica de actividad física en estudiantes de enfermería

Resumo Enquadramento: A motivação para a prática de atividade física condiciona a adesão à atividade a realizar e o envolvimento a longo prazo. Objetivos: Analisar a motivação dos estudantes de enfermagem para a prática de atividade física. Identificar as variáveis sociodemográficas e académicas que interferem na prática de atividade física. Metodologia: Estudo descritivo, analítico, com 372 estudantes de enfermagem. Aplicou-se um questionário de caracterização sociodemográfica, o Questionário de Motivação para o Exercício e o Questionário Internacional de Avaliação da Atividade Física. Resultados: Motivos relacionados com a condição física, de saúde e relacionados com o corpo foram os mais indicados pelos estudantes para a prática de atividade física. Os estudantes do sexo masculino (OM = 227,67) e dos 2º e 3º anos apresentam maior índice de atividade física. Quanto mais idade, menor a atividade física. Conclusão: Motivos psicológicos estabelecem relação direta e os motivos de saúde relação inversa com a prática de atividade física, sugerindo que maior motivação psicológica e melhores níveis de saúde conduzem a uma maior prática de atividade física.

Abstract Background: Long-term involvement and adherence to physical activity are conditioned by motivation. Objectives: To analyze nursing students' motivation to engage in physical activity and to identify the sociodemographic and academic variables that interfere with the practice of physical activity. Methodology: This is a descriptive and analytical study involving 372 nursing students. A sociodemographic characterization questionnaire, the Exercise Motivations Inventory (EMI-2), and the International Physical Activity Questionnaire (IPAQ) were administered. Results: The students' most frequent motives for physical activity were physical fitness, health, and body-related motives. Male students (MR = 227.67) and 2nd and 3rd-year students had the highest physical activity levels. This study also observed that the older the students, the lower the physical activity levels. Conclusion: The psychological motives are directly related to physical activity, whereas health motives are inversely related to physical activity, which suggests that higher psychological motivation and better levels of health lead to higher levels of physical activity.

Resumen Marco contextual: La motivación para la práctica de la actividad física condiciona la adherencia a la actividad que se va a realizar y la implicación a largo plazo. Objetivos: Analizar la motivación de los estudiantes de enfermería para realizar actividad física. Identificar las variables sociodemográficas y académicas que interfieren en la práctica de actividad física. Metodología: Estudio descriptivo y analítico, con 372 estudiantes de enfermería. Se aplicó un cuestionario de caracterización sociodemográfica, el Cuestionario de Motivación para el Ejercicio y el Cuestionario Internacional de Evaluación de la Actividad Física. Resultados: Los motivos relacionados con la condición física, la salud y el cuerpo fueron los más indicados por los estudiantes para practicar actividad física. Los estudiantes del sexo masculino (OM = 227,67) y los de 2.º y 3.er año presentan mayor índice de actividad física. Cuanto mayor es la edad, menor es su actividad física. Conclusión: Los motivos psicológicos establecen una relación directa y los motivos de salud una relación inversa con la práctica de actividad física, lo que sugiere que una mayor motivación psicológica y mejores niveles de salud conducen a una mayor práctica de actividad física.

Comprehensive geriatric assessment of older patients and associated factors of admission to Emergency Departments in pre-covid 19 Era - A Portuguese study.

OBJECTIVES: Identifying frequent users' (≥3admissions/year) associated factors in an emergency department (ED), using a comprehensive geriatric assessment (CGA), describing the characteristics of patients over 65 years of age. METHODS: A cross-sectional study was performed between August 2017 and June 2018 in an ED in Lisbon, Portugal. CGA was applied and completed with clinical records. Clinical, functional, mental and social scores were created based in Portuguese Society of Internal Medicine, and a statistical model was developed. RESULTS: CGA was applied to 426 patients over 64 years old in an ED. The mean age was 79.3, 84.7% had multimorbidity. 51.2%, 75.6%, and 40% had dependence on basic, instrumental, and walking activities, respectively. 52% had depressive symptoms, 65.7% had cognitive impairment, 63% were undernourished/at risk for malnutrition. 33.1% were socially at risk. Polypharmacy was present with a use on average of 6.5 drugs daily. Social, clinical, functional, and mental scores were unfavourable in 48.6%, 79.6%, 54.9% and 83.1% of the population, respectively. There were 2.7 hospital admissions/year and 39.9% were frequent ED users (≥3/year). The logistic regression model was weak, but showed that patients with polypharmacy, elevated Charlson Comorbidity index and an impairment nutritional status presented higher risk of being frequent users. CONCLUSIONS: This study showed that 97.1% of patients had needs that would justify an interventional care plan. This intervention should be extended to primary care and nursing homes. While not providing a robust model, our study has indicated nutritional problems, polypharmacy, and an elevated Charlson index as the features with more weight in frequent users' admissions.

A temporal analysis on patient and health service delays in pulmonary tuberculosis in Portugal: inter and intra­regional differences and in(equalities) between gender and age.

BACKGROUND: Tuberculosis (TB) diagnosis and treatment delays increase the period of infectiousness, making TB control difficult and increasing the fatality rates. This study aimed to determine the evolution of health care service delay (time between the patient's first contact with the health service and the diagnosis/start of treatment) and patient delay (time between onset symptoms date and the date of first contact with health services) for Pulmonary Tuberculosis (PTB) in Portugal between 2008 and 2017 across different regions, age groups and gender. METHODS: An exploratory analysis was performed, trends of both delays were studied, and 36 months forecasts were generated. We used the permutation test to test differences between groups and the Seasonal and Trend decomposition using Loess (STL) method and Autoregressive Integrated Moving Average (ARIMA) models for forecasting for both Health and Patient delays. We used data from notified PTB cases in mainland Portugal between 2008 and 2017, provided by the national surveillance system. RESULTS: Health delays remained relatively constant while patient delays increased. Females had significantly higher health delays in some regions. Individuals older than 64 had higher health delays than younger individuals, while patient delay for working-age individuals between 15 and 64 years old, presents higher patient delay. CONCLUSIONS: Forecasts presage that the upward trend of the delays is unlikely to fall in the coming years. It is important to understand the evolution of the delays and predict how these will evolve. Our understanding of the delays behaviours will contribute to better health policies and resources allocation.

Comprehensive geriatric assessment of older patients and associated factors of admission to Emergency Departments in pre-covid 19 Era – A Portuguese study / Valoración geriátrica integral de pacientes mayores y factores asociados de frecuentación en servicios de urgencias en la era pre-COVID-19 – Un estudio portugués

Objectives: Identifying frequent users’ (≥3admissions/year) associated factors in an emergency department (ED), using a comprehensive geriatric assessment (CGA), describing the characteristics of patients over 65 years of age. Methods: A cross-sectional study was performed between August 2017 and June 2018 in an ED in Lisbon, Portugal. CGA was applied and completed with clinical records. Clinical, functional, mental and social scores were created based in Portuguese Society of Internal Medicine, and a statistical model was developed. Results: CGA was applied to 426 patients over 64 years old in an ED. The mean age was 79.3, 84.7% had multimorbidity. 51.2%, 75.6%, and 40% had dependence on basic, instrumental, and walking activities, respectively. 52% had depressive symptoms, 65.7% had cognitive impairment, 63% were undernourished/at risk for malnutrition. 33.1% were socially at risk. Polypharmacy was present with a use on average of 6.5 drugs daily. Social, clinical, functional, and mental scores were unfavourable in 48.6%, 79.6%, 54.9% and 83.1% of the population, respectively. There were 2.7 hospital admissions/year and 39.9% were frequent ED users (≥3/year). The logistic regression model was weak, but showed that patients with polypharmacy, elevated Charlson Comorbidity index and an impairment nutritional status presented higher risk of being frequent users. (AU)

Objetivos: Identificar factores asociados con usuarios frecuentadores (≥ 3 ingresos/año) en un departamento de urgencias (DU), mediante valoración geriátrica integral (VGI) y describir las características de los pacientes mayores de 65 años que acuden a urgencias.Métodos: El estudio transversal se realizó entre agosto del 2017 y junio del 2018 en un DU de Lisboa, Portugal. Se realizó una VGI además de la historia clínica. Se crearon scores clínicos, funcionales, mentales, sociales, basándose en el protocolo de cuestionario del grupo de geriatría de la Sociedad Portuguesa de Medicina Interna y se desarrolló un modelo estadístico para identificar los factores asociados con la alta frecuentación.Resultados: Se realizó una VGI a 426 usuarios mayores de un DU. La edad media fue de 79,3 años, siendo 53,8% mujeres con un 84,7% de multimorbilidad, 51,2% de dependencia de las actividades básicas (Katz), 75,6% instrumentales (Lawton < 5 en mujeres, < 3 hombres y 40% de dependencia de la marcha (Holden). El 52% tenían síntomas depresivos (Yesavage), 65,7% tenían deterioro cognitivo (MMSE < 24), 63% estaban desnutridos/en riesgo de desnutrición (MNA < 23,5). El 33,1% estaba en riesgo social (Gijón, APGAR familiar). La polifarmacia con el uso de un promedio de 6,5 medicamentos al día. Los scores sociales, clínicos, funcionales y mentales fueron adversos en el 48,6, 79,6, 54,9 y 83,1%, respectivamente. Hubo 2,7 admisiones/año y el 39,9% eran usuarios frecuentes de DU (≥ 3/año). Un modelo de regresión logística fue débil, pero mostró que los pacientes con polifarmacia, índice de comorbilidad de Charlson elevado y un estado nutricional adverso presentaban mayor riesgo de ser usuarios frecuentes. (AU)

CD8 T cell function and cross-reactivity explored by stepwise increased peptide-HLA versus TCR affinity.

Recruitment and activation of CD8 T cells occur through specific triggering of T cell receptor (TCR) by peptide-bound human leucocyte antigen (HLA) ligands. Within the generated trimeric TCR-peptide:HLA complex, the molecular binding affinities between peptide and HLA, and between TCR and peptide:HLA both impact T cell functional outcomes. However, how their individual and combined effects modulate immunogenicity and overall T cell responsiveness has not been investigated systematically. Here, we established two panels of human tumor peptide variants differing in their affinity to HLA. For precise characterization, we developed the "blue peptide assay", an upgraded cell-based approach to measure the peptide:HLA affinity. These peptide variants were then used to investigate the cross-reactivity of tumor antigen-specific CD8 T cell clonotypes derived from blood of cancer patients after vaccination with either the native or an affinity-optimized Melan-A/MART-1 epitope, or isolated from tumor infiltrated lymph nodes (TILNs). Vaccines containing the native tumor epitope generated T cells with better functionality, and superior cross-reactivity against potential low affinity escape epitopes, as compared to T cells induced by vaccines containing an HLA affinity-optimized epitope. Comparatively, Melan-A/MART-1-specific TILN cells displayed functional and cross-reactive profiles that were heterogeneous and clonotype-dependent. Finally, we took advantage of a collection of T cells expressing affinity-optimized NY-ESO-1-specific TCRs to interrogate the individual and combined impact of peptide:HLA and TCR-pHLA affinities on overall CD8 T cell responses. We found profound and distinct effects of both biophysical parameters, with additive contributions and absence of hierarchical dominance. Altogether, the biological impact of peptide:HLA and TCR-pHLA affinities on T cell responses was carefully dissected in two antigenic systems, frequently targeted in human cancer immunotherapy. Our technology and stepwise comparison open new insights into the rational design and selection of vaccine-associated tumor-specific epitopes and highlight the functional and cross-reactivity profiles that endow T cells with best tumor control capacity.

Association between perception of COVID-19 risk, confidence in health services and avoidance of emergency department visits: results from a community-based survey in Portugal.

OBJECTIVES: To examine the association between the perception of COVID-19 risk, confidence in health services and avoidance of emergency department (ED) visits in Portugal during the COVID-19 pandemic. DESIGN: Community-based, cross-sectional survey. SETTING: Volunteer sample that completed the online survey between April 2020 and May 2021. PARTICIPANTS: 987 participants who perceived needing ED care. Of those, 242 reported avoiding ED visits. OUTCOME MEASURES: Logistic regression models for ED avoidance were conducted to estimate the effect of risk perception and confidence in health services, adjusted for sociodemographics, health status and time. RESULTS: The adjusted odds for ED avoidance were higher for participants lacking confidence in health service response to non-COVID-19 conditions (adjusted OR: 6.39; 95% CI 3.19 to 12.82) and COVID-19 (1.81; 1.19 to 2.77) and lower for those perceiving a low risk of being infected at a health provider (0.16; 0.07 to 0.38). CONCLUSION: In our sample, confidence in health services and risk perception of infection at a health provider were associated with the decision to avoid the ED. These results suggest that policymakers and care providers need to mitigate the negative consequences of delayed healthcare; be aware of the implications of distrust and fear from those in need of healthcare and provide equally distributed safe alternatives to ED care.

earlyMYCO: A Pilot Mother-Child Cohort Study to Assess Early-Life Exposure to Mycotoxins-Challenges and Lessons Learned.

Early-life exposure occurs during gestation through transfer to the fetus and later, during lactation. Recent monitoring data revealed that the Portuguese population is exposed to mycotoxins, including young children. This study aimed to develop a pilot study to assess the early-life exposure to mycotoxins through a mother-child cohort, and to identify the associated challenges. Participants were recruited during pregnancy (1st trimester) and followed-up in three moments of observation: 2nd trimester of pregnancy (mother), and 1st and 6th month of the child's life (mother and child), with the collection of biological samples and sociodemographic and food consumption data. The earlyMYCO pilot study enrolled 19 mother-child pairs. The analysis of biological samples from participants revealed the presence of 4 out of 15 and 5 out of 18 mycotoxins' biomarkers of exposure in urine and breast milk samples, respectively. The main aspects identified as contributors for the successful development of the cohort were the multidisciplinary and dedicated team members in healthcare units, reduced burden of participation, and the availability of healthcare units for the implementation of the fieldwork. Challenges faced, lessons learned, and suggestions were discussed as a contribution for the development of further studies in this area.

Models of care for low back pain patients in primary healthcare: a scoping review protocol.

INTRODUCTION: Low back pain (LBP) is the most prevalent musculoskeletal condition worldwide and it is responsible for high healthcare costs and resources consumption. It represents a challenge for primary care services that struggle to implement evidence-based practice. Models of care (MoCs) are arising as effective solutions to overcome this problem, leading to better health outcomes. Although there is growing evidence regarding MoCs for the management of LBP patients, an analysis of the existing body of evidence has not yet been carried out. Therefore, this scoping review aims to identify and map the current evidence about the implementation of MoCs for LBP in primary healthcare. Findings from this study will inform policy makers, health professionals and researchers about their characteristics and outcomes, guiding future research and best practice models. METHODS AND ANALYSIS: This protocol will follow the Joanna Briggs Institute methodological guidelines for scoping reviews. Studies that implemented an MoC for LBP patients in primary healthcare will be included. Searches will be conducted on PubMed, EMBASE, Cochrane Central Register of Controlled Trials, PEDro, Scopus, Web of Science, grey literature databases and relevant organisations websites. This review will consider records from 2000, written in English, Portuguese or Spanish. Two researchers will independently screen all citations and full-text articles and abstract data. Data extracted will include the identification of the MoC, key elements of the intervention, organisational components, context-specific factors and patient-related, system-related and implementation-related outcomes. ETHICS AND DISSEMINATION: As a secondary analysis, this study does not require ethical approval. It will provide a comprehensive understanding on existing MoCs for LBP, outcomes and context-related challenges that may influence implementation in primary healthcare, which is meaningful knowledge to inform future research in this field. Findings will be disseminated through research papers in peer-reviewed journals, presentations at relevant conferences and documentation for professional organisations and stakeholders.

Distribuição e dependência espacial da mortalidade por tuberculose em um município da região amazônica / Spatial distribution and dependence of mortality due to tuberculosis in a city in the Amazon region

Resumo Introdução A mortalidade por tuberculose é um indicador sensível às desigualdades em saúde, considerando-se que o risco para sua ocorrência está relacionado à vulnerabilidade dos territórios. Objetivo Investigar se as variações espaciais dos determinantes sociais afetam as mortes por tuberculose em um município da região amazônica. Método Estudo ecológico com medidas múltiplas de análise, composto por óbitos por tuberculose como causa básica em Manaus, Amazonas, Brasil, notificados no Sistema de Informação sobre Mortalidade (2006-2015). Nas análises, foram calculadas as taxas bruta e padronizada, e usado o Índice de Moran para verificar a autocorrelação espacial da mortalidade e, posteriormente, foi aplicada a regressão geograficamente ponderada para aferir a relação da desigualdade com as mortes por tuberculose. Resultados Foram identificados 731 óbitos pela doença. A distribuição da mortalidade ocorreu de forma heterogênea, sendo que as altas taxas de óbito por tuberculose estavam em áreas mais socialmente vulneráveis. Foram confirmadas a autocorrelação e a dependência espacial. O modelo final apresentou as variáveis indicadoras de iniquidades (baixa renda, pobreza e escolaridade), mostrando relação destas com a mortalidade. Conclusão Ficou evidente que os determinantes sociais no espaço urbano influenciam a mortalidade por tuberculose na região. Portanto, avançar em políticas públicas para corrigir as iniquidades em saúde pode influenciar positivamente esse cenário.

Abstract Background Mortality from tuberculosis is a sensitive indicator of health inequalities, given that the risk for its occurrence is related to the vulnerability of the territories. Objective To investigate whether the spatial variations of social determinants affect deaths from tuberculosis in a municipality in the Amazon region. Method Ecological study with multiple measures of analysis. The study was composed of deaths from tuberculosis as a basic cause in Manaus, Amazonas, Brazil, reported in the Brazilian Mortality Information System (2006-2015). In the analyzes, the crude and standardized rate was calculated, Moran Index was used to verify the spatial autocorrelation of mortality, and subsequently, the geographically weighted regression was applied to assess the inequality relationship of deaths from tuberculosis. Results 731 deaths from the disease were identified. The distribution of mortality was heterogeneous, with high rates of death from tuberculosis in more socially vulnerable areas. The autocorrelation and spatial dependence was confirmed. The final model presented variables that indicate inequities: low income, poverty and education, showing their relationship with mortality. Conclusion It was evident that social determinants in the urban space influence mortality from tuberculosis in the region. Therefore, advancing public policies to correct health inequities can positively impact this scenario.

Monitoring of SARS-CoV-2 Specific Antibodies after Vaccination.

Vaccination is considered the most important measure to control the COVID-19 pandemic. Extensive follow-up studies with distinct vaccines and populations are able to promote robust and reliable data to better understand the effectiveness of this pharmacologic strategy. In this sense, we present data regarding binding and neutralizing (achieved by surrogate ELISA assay) antibodies throughout time, from vaccinated and previously infected (PI) health care workers (HCW) in Portugal. We analyzed serum samples of 132 HCW, who were vaccinated and with previous SARS-CoV-2 infection. Samples were collected before vaccination (baseline, M1), at second dose vaccine uptake (M2), and 25-70 days (M3) and 150-210 days (M4) after the second dose for vaccinated individuals. The IgG (anti-RBD/S) antibody geometric mean titers found on vaccinated HCW at M2 (GM = 116.1 BAU/mL; CI: 92.3-146.1) were significantly higher than those found on PI HCW at recruitment (M1) (GM = 35.9 BAU/mL; CI:15.4-83.4), and the neutralizing antibodies (nAb) were similar between these groups, of 93.2 UI/mL (95% CI 73.2-118.5) vs. 84.1 UI/mL (95% CI 40.4-155.9), respectively. We detected around 10-fold higher IgG (anti-RBD/S) antibodies titers in M3 when compared with M2, with a slight but significant decrease in titers from 36 days after the second dose vaccine uptake. The increase of nAb titers was correlated with IgG (anti-RBD/S) antibodies titers; however, in contrast to IgG (anti-RBD/S) antibodies titers, we did not detect a decrease in the nAb titer 36 days after a second vaccine dose uptake. At M4, a decrease of 8-fold in binding IgG (anti-RBD/S) and nAb was observed. No significant differences in antibody titers were observed by sex, age or chronic diseases. Our results suggest that IgG (anti-RBD/S) antibodies titers and nAb titers could be correlated, but an ongoing follow up of the cohort is required to better understand this correlation, and the duration of the immune response.