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Background: Communities and local governments invest in compassionate communities (CCs) a great deal of time, money, effort, and work. However, it is not known whether the CCs are having the effect they are expected to have, so the value of continuing with these initiatives is unknown, and there is a need for a model for evaluating CCs to solve the question. Objectives: To identify a set of core outcomes or benefits that should be measured to assess the impact of the CCs. Design: Multiple-methods study involving three communities, each in a different country (Argentina, Colombia, and Switzerland). Methods and analysis: To identifying the set of core outcomes, which is the first step in developing the CC evaluation model, five phases will follow: online meetings, literature review, fieldwork, Delphi survey, and social transfer. We will involve members of the local communities of Bern, Buenos Aires, and Medellin at three different levels: (1) citizens (e.g. patients, caregivers, and family members), (2) organizations and institutions involved in the program implementation (e.g. health care organizations, churches, non-governmental organizations, and schools), and (3) political and governmental sectors. Ethics: The study will be conducted following existing international regulations and guidance such as the Declaration of Helsinki. The ethics committee of Pallium Latin America and the ethics committee of the canton of Bern considered our application exempt from the need for approval. Ethics approval in Bern and Buenos Aires is in the process of being obtained. The ethics committee of the Pontifical Bolivarian University approved this protocol. Discussion: We expect that this project will help bridge the gap in knowledge regarding the measurable impact of the CCs and enhance more CC development.

ObjectiveTo identify risk factors for SARS-CoV-2 infection and for severe/critical COVID-19, and to assess the humoral response after COVID-19 in these patients.MethodsNationwide study of adult patients with inflammatory RMDs prospectively followed in the Rheumatic Diseases Portuguese Register—Reuma.pt—during the first 6 months of the pandemic. We compared patients with COVID-19 with those who did not develop the disease and patients with mild/moderate disease with those exhibiting severe/critical COVID-19. IgG antibodies against SARS-CoV-2 were measured ≥3 months after infection and results were compared with matched controls.Results162 cases of COVID-19 were registered in a total of 6,363 appointments. Patients treated with TNF inhibitors (TNFi; OR = 0.160, 95% CI 0.099–0.260, P < 0.001) and tocilizumab (OR 0.147, 95% CI 0.053–0.408, P < 0.001) had reduced odds of infection. Further, TNFi tended to be protective of severe and critical disease. Older age, major comorbidities, and rituximab were associated with an increased risk of infection and worse prognosis. Most patients with inflammatory RMDs (86.2%) developed a robust antibody response. Seroconversion was associated with symptomatic disease (OR 13.46, 95% CI 2.21–81.85, P = 0.005) and tended to be blunted by TNFi (OR 0.17, 95% CI 0.03–1.05; P = 0.057).ConclusionsTNFi and tocilizumab reduced the risk of infection by SARS-CoV-2. Treatment with TNFi also tended to reduce rates of severe disease and seroconversion. Older age, general comorbidities and rituximab were associated with increased risk for infection and worse prognosis, in line with previous reports. Most patients with RMDs developed a proper antibody response after COVID-19, particularly if they had symptomatic disease.

Background: Wound infections continue to be a cause of concern as they can delay healing and cause wound breakdown. Their effective treatment demands quick isolation and identification of causative organisms with appropriate antibiotic sensitivity pattern. Material and Methods: Wound swab and pus samples received from inpatient as well as outpatient department of all age groups and both genders were processed using conventional media as well as chromogenic medium (HiCrome UTI) and results of both were compared. Antibiotic sensitivity testing was done on Vitek 2 Compact automated system. Results: Among 342 samples, 77% showed growth. Fifty eight percentage were Gram negative and 42% were Gram positive organisms. Polymicrobial growth was seen in 11% of samples. HiCrome UTI isolated all organisms in culture. Colony characteristics and colour of all isolates on HiCrome UTI were comparable to their identification on Vitek 2 Compact. Among the Gram positive organisms, commonest was Methicillin Sensitive Staphylococcus aureus (MSSA 42%) followed by Methicillin Resistant Staphylococcus aureus (MRSA 33%), Enterococcus faecalis (10%), Staphylococcus epidermidis (8%), Staphylococcus haemolyticus (3%), Streptococcus pyogenes (2%) and Streptococcus agalactiae (2%). Most of the Gram positive organisms were sensitive to vancomycin, teicoplanin, linezolid and clindamycin The common Gram negative organisms were E. coli (36%), Klebsiella pneumoniae (20%), Pseudomonas aeruginosa (18%), Proteus mirabilis (7%), Enterobacter cloacae (6%) and Acinetobacter baumannii (4%). Most of the Gram negative organisms were sensitive to cefepime, beta lactams-beta lactamase inhibitors, aminoglycosides and fluoroquinolones. Conclusion: Gram-negative organisms predominated in our study. HiCrome UTI agar can be used as a cost-effective approach for rapid isolation of all organisms. It gives definite identification of common organisms and thus reduces turn-around-time for the same. It provides presumptive identification of infrequent organisms which can be further confirmed by simple biochemical tests. Hence these properties of HiCrome UTI agar help serve the purpose especially from mixed cultures and in resource constraint settings.

Objectives: To identify ultrasound (US) features associated with the presence of shoulder complaints.Methods: This observational, case-control study, compared US findings between participants with and without shoulder complaints, matched for age, sex, and dominancy. Data was collected from February 2018 to June 2020. Two-tailed Fisher's and Mann-Whitney U-tests were used, with p-values < 0.05 considered significant.Results: A total of 202 participants were enrolled (median age 56 years, range 18–70, 155 women), comprising 140 cases and 62 controls. A calcification size ≥6 mm, when age < 56 (p = 0.02), and a distance to tendon insertion ≥6 mm, when age ≥56 (p = 0.009), were only found in symptomatic shoulders. Color Doppler in rotator cuff (RC) tendons predominated in the presence of symptoms (26/140 vs. 2/62, p = 0.003). An algorithm also combining the number of calcifications, tendon echotexture and insertional thickening, osseous irregularity, cuff tears, and subacromial effusion showed a 92% (57/62) specificity for shoulder pain on this study sample.Conclusion: Calcification diameter of 6 mm or more is associated with shoulder pain in patients younger than 56 years. A distance from calcification to tendon insertion of 6 mm or more is related to pain in older patients. Doppler signal also is associated with shoulder pain. An algorithm based on a set of specific ultrasonographic criteria have a strong association with the presence of symptoms.

Background: The public’s view of palliative care often involves its potential to improve of quality-of-life as well as its use as a last resource prior to death. Objective: To obtain an idea of the image of palliative care held by the public in the German-speaking part of Switzerland, the authors sought to understand (1) the perceptions of palliative care and the (2) elements important when thinking about their own end of life. Methods and Sample: A qualitative design with an inductive reasoning approach based on Mayring (2014) was chosen. Visitors at an exhibition about palliative care in six locations provided hand-written answers on provided cards to two statements: (1) if I hear the term ‘Palliative Care’ I think of … and (2) when thinking about my own end of life, the following is important to me … Results: Answers of 199 visitors (mean age 52, mostly in a good/very good health status) were analysed. In response to hearing the term palliative care, six areas were categorized: (1) the main focus; (2) ways of providing palliative care; (3) the best timing; (4) places where palliative care is provided; (5) who is seen as provider and (6) outcomes of palliative care. Five categories to the statement about their own end-of-life were identified: (1) the ability to look back on a fulfilled life and being satisfied; (2) maintaining trusting relationships until the end; (3) organizing affairs and having everything settled; (4) having their family being cared for and (5) relief of suffering with the support of knowledgeable people. Conclusion: Palliative care was mostly associated with positive terms acknowledging an interprofessional approach. Maintaining one’s dignity as well as dying without suffering pointed at the persisting stigma that palliative care is mainly limited to end-of-life care. The results may help healthcare professionals to better understand how the public view palliative care.

Background and Aims: Atherosclerosis and osteoporosis share common risk factors, as well as inflammatory mechanisms. Our aim was to understand how atherosclerotic lesions are related with disturbances in bone.Methods: Gene expression of pro-inflammatory and bone metabolism related proteins (IL-1β, IL-6, IL-17A, TNF, RANKL, OPG, COL1, CTSK, OCL, TRAP, CBFA1, DKK1, SOST, ADIPOQ, and ADIPOR1) were analyzed in arteries and bones from 45 deceased donors and adipose tissue was used as control. Additionally, in 139 patients with advanced atherosclerosis submitted to carotid endarterectomy we compared calcium content (Alizarin red) and plaque inflammatory scores (CD3+, CD68+, and adiponectin) of patients with normal bone mineral density (BMD) with those with low BMD and explored the associations between gene expression in atherosclerotic plaques and BMD. Serum levels of pro-inflammatory and bone related proteins were measured both in donors and patients. Associations were investigated by the Pearson or Spearman correlation tests, and multivariate regression analyzes were performed when justified.Results: Gene expression of bone remodeling and pro-inflammatory proteins correlated positively in bone and aorta, independently of age and sex of donors, but not in adipose tissue. The expression of bone formation genes was significantly higher in atheroma plaques from endarterectomized patients with normal vs. low BMD as well as inflammatory CD68+ scores, regardless of patients' age and sex, but not of body mass index. No relationship was observed between serum levels and gene expression levels of pro-inflammatory or bone remodeling proteins.Conclusions: Our results suggest that the relationship between bones and vessels in the context of atherosclerotic disease and osteoporosis may rely on the intrinsic connection between the tissues involved, independently of disease stage. Serum measurements of pro-inflammatory and bone-remodeling proteins do not accurately translate tissue pathologic processes.

Salmonellosis is a global disease caused by bacteria belonging to the genus Salmonella. It is the most important food-borne pathogen which is transmitted usually through contaminated food and water and is responsible for illnesses, hospitalisations and deaths worldwide. We present two cases of Salmonellosis caused by two unusual serotypes of Salmonella. Also, highlighted is the role of automation in bacterial identification and significance of serotyping of the bacterium.

Psoas abscess is a rare medical disease. Streptococcus intermedius is a commensal of the mouth and the upper respiratory tract but can cause various pyogenic infections especially liver and brain abscesses but rarely muscular abscess even in an immunocompromised host. We report a case of primary psoas abscess in a HIV positive patient caused by Streptococcus intermedius along with Escherichia coli. The patient responded well to antibiotic treatment along with percutaneous abscess drainage.

Streptococcus agalactiae, Group B Streptococcus (GBS) has been considered to be a major pathogen in neonates and pregnant women.GBS disease in nonpregnant adults is increasing, particularly in elderly persons and those with significant underlying diseases.We report a case of balanitis and urinary tract infection caused by Group B Streptococcus (Streptococcus agalactiae) in an adult male with multiple underlying diseases.The patient was successfully treated with antibiotics.

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É central e inquestionável a importância de um acesso justo e digno à saúde Os direitos e a autonomia do utente, sendo um pilar central da ética médica, permite a escolha livre entre serviços de saúde públicos e privados. Contudo, esta autonomia traz consigo desafios, especialmente quando se trata de equilibrar a liberdade de escolha do utente com a necessidade de manter a coerência na prestação de serviços de saúde. A esta consideração surge associada a questão da multipatologia e da complexidade de pacientes que são seguidos em várias especialidades e instituições, diluindo o papel tradicional do médico de família. Em simultâneo, a modernização dos serviços de saúde proporcionou uma maior flexibilidade e conveniência aos utentes, permitindo-lhes optar por horários mais convenientes e acesso mais rápido a consultas. No entanto, tudo isto resulta em desafios logísticos, como a coordenação eficaz entre diferentes instituições de saúde, essencial para manter a qualidade e a continuidade dos cuidados. A utilização de múltiplos serviços pode levar à repetição desnecessária de exames, sobrecarga nos serviços de saúde e riscos para a relação médico-doente. Apesar da informatização dos processos clínicos dos utentes e a rápida evolução da tecnologia médica têm vindo a contribuir significativamente para uma maior coerência dos cuidados prestados aos utentes, trazem também desafios como a falta de integração entre os sistemas de informação de diferentes instituições de saúde. Como consequência, apesar da maior facilidade que o utente tem no acesso a diversas instituições e serviços clínicos, da modernização e informatização dos sistemas de saúde que facilitam a agregação e partilha de informação clínica, dificuldades relacionadas com a eficácia e coordenação de todos os atores envolvidos e de todas estas ferramentas conduzem à falta de confiança em todo o processo de tratamento do utente.

Stroke is the leading cause of disability and the second cause of death worldwide. The increasing burden of stroke underscores the importance of optimising rehabilitation protocols. Virtual reality (VR) can improve poststroke prognosis. A VR software combining gamification, full immersion and stroke specificity (ie, the Development and validation of a novel viRtual rEality software for improving diSability and quality of lifE in patients with sTroke (RESET) software) might substantially improve disability and quality of life (QoL). However, this technology is still very scarce. The RESET trial aims to assess the effects of an early 10-week gamified, fully immersive and stroke-specific VR intervention (ie, starting at week 3 poststroke) on disability and QoL in people with stroke in the subacute phase. People with ischaemic or haemorrhagic stroke (n=94) aged ≥18 years will be randomised to receive (1) usual care (UC), (2) commercial VR or (3) gamified, fully immersive and stroke-specific VR (RESET). The three groups will receive UC (ie, three sessions/week of 90 min of standard rehabilitation). The VR groups will additionally receive three VR sessions of 20 min per week. The outcome measures will be assessed at baseline (week 2 from stroke occurrence), week 13 (approximately 90 days from the event) and week 26 (approximately 6 months from the event). The primary outcome is disability measured with the Barthel Index. Secondary outcomes include QoL, upper-extremity and lower-extremity motor function, gross manual dexterity, handgrip strength and cognitive function. This study will unravel the effects of a gamified, fully immersive and stroke-specific VR software on disability and QoL in patients with stroke in the early subacute phase.NCT06132399.

Introduction: Stress factors influence surgical procedures. This study aims to assess the impact of stress factors on surgical performance in ophthalmology simulation. Specifically, the study aims to identify which exercises are most affected by stress and to examine the relationship between stress levels, surgical complexity, and technical skills. Material and methods: A prospective study of a cohort of 13 ophthalmology residents, at Vall Hebron University Hospital. All study participants received basic training before the study to become familiar with the simulator and surgical maneuvers. Once completed, the participants were invited to perform 3 defined exercises (E1, E2, and E3, increasing difficulty level from 1 to 3) in relaxed conditions. Afterwards, the same exercises were performed again under a stressful environment. The stress was created introducing physical, auditory, and interruptions factors. The results in technical skills were evaluated through the relaxation and stress scores, as well as the time required to complete the exercises under relaxation and stress conditions. A detailed metric was used to assess the variables in relation to stress situations, including physical stress, haste, the presence of background music, and scheduled interruptions.The results are expressed by median and interquartile range. To compare them, Wilcoxon test for paired samples and the Whitney U Test were performed. The results were stratified by year of residence (1–2 years vs 3–4 years). Results: The stress score was significantly lower in the 3 exercises compared to the relax score (75 vs 86, 52 vs 90, 55 vs 61, respectively, p>.05). Time to perform the exercises was less predictable and was even lower in stressful situations with no statistical differences. Under stress, both younger and older residents scored worse on the more complex exercises. Conclusion: Stress affects surgery with simulators. The most difficult exercises are the most likely to be affected by stress. These results suggest that through ophthalmic simulators ophthalmologists have the opportunity to train surgical stress and therefore improving patient safety. Resumen: Introducción: Los factores de estrés influyen en los procedimientos quirúrgicos. Este estudio tiene como objetivo evaluar el impacto de los factores de estrés en el desempeño quirúrgico en simulaciones oftalmológicas. Específicamente, el estudio busca identificar qué ejercicios se ven más afectados por el estrés y examinar la relación entre los niveles de estrés, la complejidad quirúrgica y las habilidades técnicas Materiales y métodos: Estudio prospectivo de una cohorte de 13 residentes de oftalmología en el Hospital Universitario Vall Hebron. Todos los participantes del estudio recibieron entrenamiento básico antes del estudio para familiarizarse con el simulador y las maniobras quirúrgicas. Una vez completado, se invitó a los participantes a realizar tres ejercicios definidos (E1, E2, E3, aumentando el nivel de dificultad de 1 a 3) en condiciones relajadas. Posteriormente, los mismos ejercicios se realizaron nuevamente bajo un entorno estresante. El estrés se creó introduciendo factores físicos, auditivos e interrupciones.Los resultados en habilidades técnicas fueron evaluados mediante la puntuación de relajación y estrés, así como el tiempo requerido para completar los ejercicios bajo condiciones de relajación y estrés. Se utilizó una métrica detallada para evaluar las variables en relación con las situaciones de estrés, incluyendo el estrés físico, la prisa, la presencia de música ambiental e interrupciones programadas.Los resultados se expresan mediante la mediana y el rango intercuartílico. Para compararlos, se realizaron la prueba de Wilcoxon para muestras pareadas y la prueba U de Whitney. Los resultados se estratificaron por año de residencia (1-2 años vs. 3-4 años). Resultados: La puntuación de estrés fue significativamente menor en los tres ejercicios en comparación con la puntuación de relajación (75 vs. 86, 52 vs. 90, 55 vs. 61 respectivamente, p>0.05). El tiempo para realizar los ejercicios fue menos predecible y fue aún menor en situaciones estresantes sin diferencias estadísticas. Bajo estrés, tanto los residentes más jóvenes como los más avanzados obtuvieron peores puntuaciones en los ejercicios más complejos. Conclusión: El estrés afecta a la cirugía con simuladores. Los ejercicios más difíciles son los más propensos a ser afectados por el estrés. Estos resultados sugieren que a través de simuladores oftálmicos, los oftalmólogos tienen la oportunidad de entrenar el estrés quirúrgico y por lo tanto mejorar la seguridad del paciente.

Background: Family is a crucial social institution in end-of-life care. Family caregivers are encouraged to take on more responsibility at different times during the illness, providing personal and medical care. Unpaid work can be overburdening, with women often spending more time in care work than men. Objectives: This study explored multiple views on the family’s role in end-of-life care from a critical perspective and a relational autonomy lens, considering gender in a socio-cultural context and applying a relational autonomy framework. It explored patients, relatives and healthcare providers’ points of view. Design: This qualitative study was part of the iLIVE project, involving patients with incurable diseases, their relatives and health carers from hospital and non-hospital sites. Methods: Individual interviews of at least five patients, five relatives and five healthcare providers in each of the 10 participating countries using a semi-structured interview guide based on Giger–Davidhizar–Haff’s model for cultural assessment in end-of-life care. Thematic analysis was performed initially within each country and across the complete dataset. Data sources, including researchers’ field notes, were translated into English for international collaborative analysis. Results: We conducted 158 interviews (57 patients, 48 relatives and 53 healthcare providers). After collaborative analysis, five themes were identified across the countries: family as a finite care resource, families’ active role in decision-making, open communication with the family, care burden and socio-cultural mandates. Families were crucial for providing informal care during severe illness, often acting as the only resource. Patients acknowledged the strain on carers, leading to a conceptual model highlighting socio-cultural influences, relational autonomy, care burden and feminisation of care. Conclusion: Society, health teams and family systems still need to better support the role of family caregivers described across countries. The model implies that family roles in end-of-life care balance relational autonomy with socio-cultural values. Real-world end-of-life scenarios do not occur in a wholly individualistic, closed-off atmosphere but in an interpersonal setting. Gender is often prominent, but normative ideas influence the decisions and actions of all involved.

Mujer de 85 años con múltiples comorbilidades: Enfermedad pulmonar obstructiva crónica (EPOC) y falla cardiaca. Hospitalización hace 1 mes por tromboembolismo pulmonar (TEP) manejado con rivaroxaban 20 mg/día; delirium mixto y demencia en tratamiento con risperidona inicialmente 0.5 mg/día y luego 1 mg/día al egreso. Reingreso hospitalario por choque séptico urinario por Klebsiella Pneumoniae (KPC), tratado con ceftazidime/avibactam 2.5 gr c/8h. Cuadro hemático (CH) de ingreso con 770 leucocitos/mm3, hemoglobina 6,3 gr/dl, hematocrito 18,9% y plaquetas 61.000/mm3. Se suspende risperidona e inicia haloperidol, se transfundieron 2 unidades de glóbulos rojos, presentando mejoría al cuarto día, CH muestra leucocitos 1.840, neutrófilos 740/mm3, hemoglobina 9,8 gr/dl, hematocrito 29,3% y plaquetas 227.000/mm3. La causalidad de la reacción adversa al medicamento (RAM) evaluada con algoritmo de la Organización Mundial de la Salud (OMS) fue clasificada como “posible”.

A infeção por SARS-CoV-2 pode acompanhar-se de diversas complicações cardiovasculares, como tromboembolismo pulmonar, lesão miocárdica e pericardite. Este caso refere-se a um homem de 48 anos com história de angina instável, que recorreu ao serviço de urgência por dor torácica, dispneia, tosse e febre. Ficou internado no serviço de medicina interna por tromboembolismo pulmonar associado a enfarte pulmonar e pneumonia. Durante o internamento desenvolveu quadro de precordialgia, tendo realizado eletrocardiograma que mostrou ligeiro supradesnivelamento do segmento ST com concavidade superior nas derivações inferiores e laterais e infradesnivelamento do intervalo PR. Associadamente, verificou-se aumento dos marcadores de necrose miocárdica, levantando a suspeita de miopericardite. Perante história de síndrome gripal nas 3 semanas que antecederam o internamento, colheu serologia para SARS-CoV-2 com valor de IgG >100 u/mL. Iniciou tratamento com acetilsalicilato de lisina com resolução da toracalgia. Três meses depois, o doente encontrava-se assintomático, com reversão dos achados eletrocardiográficos.

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Bone Strain Index (BSI), based on dual-energy X-ray absorptiometry (DXA), is a densitometric index of bone strength of the femur and lumbar spine. Higher BSI values indicate a higher strain applied to bone, predisposing to higher fracture risk. This retrospective, multicentric study on Italian women reports the BSI normative age-specific reference curves. A cohort of Caucasian Italian women aged 20 to 90 years was selected from three different clinical centres. Bone mineral density (BMD) and BSI measurements were obtained for the lumbar spine vertebrae (L1–L4) and for the femur (neck, trochanter and intertrochanter) using Hologic densitometers scans. The data were compared with BMD normative values provided by the densitometer manufacturer. Then, the age-specific BSI curve for the femur and lumbar spine was generated. No significant difference was found between the BMD of the subjects in this study and BMD reference data provided by Hologic (p = 0.68 for femur and p = 0.90 for lumbar spine). Spine BSI values (L1–L4) increase by 84% between 20 and 90 years of age. The mean BSI of the total femur increases about 38% in the same age range. The BSI age-specific reference curve could help clinicians improve osteoporosis patient management, allowing an appropriate patient classification according to the bone resistance to the applied loads and fragility fracture risk assessment.

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Summary: Background: Patients with chronic lymphocytic leukemia (CLL) have a higher risk of developing other malignancies (OMs) compared to the general population. However, the impact of CLL-related risk factors and CLL-directed treatment is still unclear and represents the focus of this work. Methods: We conducted a retrospective international multicenter study to assess the incidence of OMs and detect potential risk factors in 19,705 patients with CLL, small lymphocytic lymphoma, or high-count CLL-like monoclonal B-cell lymphocytosis, diagnosed between 2000 and 2016. Data collection took place between October 2020 and March 2022. Findings: In 129,254 years of follow-up after CLL diagnosis, 3513 OMs were diagnosed (27.2 OMs/1000 person-years). The most common hematological OMs were Richter transformation, myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Non-melanoma skin (NMSC) and prostate cancers were the most common solid tumors (STs).The only predictor for MDS and AML development was treatment with fludarabine and cyclophosphamide with/without rituximab (FC ± R) (OR = 3.7; 95% CI = 2.79–4.91; p

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Introduction: The International Health Regulations (IHR) were developed to prepare countries to deal with public health emergencies. The spread of SARS-CoV-2 underlined the need for international coordination, although few attempts were made to evaluate the integrated implementation of the IHR’s core capacities in response to the COVID-19 pandemic. The aim of this study was to evaluate whether IHR shortcomings stem from non-compliance or regulatory issues, using Portugal as a European case study due to its size, organization, and previous discrepancies between self-reporting and peer assessment of the IHR’s core capacities. Methods: Fifteen public health medical residents involved in contact tracing in mainland Portugal interpreted the effectiveness of the IHR’s core capabilities by reviewing the publicly available evidence and reflecting on their own field experience, then grading each core capability according to the IHR Monitoring Framework. The assessment of IHR enforcement considered efforts made before and after the onset of the pandemic, covering the period up to July 2021. Results: Four out of nine core IHR capacities (surveillance; response; risk communication; and human resource capacity) were classified as level 1, the lowest. Only two were graded level 3 (preparedness; and laboratory), the highest. The remaining three) (national legislation, policy & financing; coordination and national focal point communication; and points of entry) were classified as level 2. Conclusion: Portugal exemplifies the extent to which implementation of the IHR was not fully achieved, which has resulted in the underperformance of several core capacities. There is a need to improve preparedness and international cooperation in order to harmonize and strengthen the global response to public health emergencies, with better political, institutional, and financial support.

Abstract Background The Portuguese National Health System (NHS) provides universal coverage and near-free health care, but the population has high out-of-pocket expenses and unmet care needs. This suggests impaired accessibility, a key dimension of primary care. The COVID-19 pandemic has further affected access to health care. Understanding General Practitioners’ (GP) experiences during the pandemic is necessary to reconfigure post-pandemic service delivery and to plan for future emergencies. This study aimed to assess accessibility to GPs, from their perspective, evaluating determinants of accessibility during the second pandemic year in Portugal. Methods All GPs working in NHS Family Practices in continental Portugal were invited to participate in a survey in 2021. A structured online self-administered anonymous questionnaire was used. Accessibility was assessed through waiting times for consultations and remote contacts and provision of remote access. NHS standards were used to assess waiting times. Descriptive statistics were used to characterize the study sample. Associations between categorical variables were tested using the χ2 statistic and the Student t-test was used to compare means of continuous variables. Results A total of 420 GPs were included (7% of the target population). Median weekly working hours was 49.0 h (interquartile range 42.0–56.8), although only 14% reported a contracted weekly schedule over 40 h. Access to in-person consultations and remote contacts was reported by most GPs to occur within NHS time standards. Younger GPs more often reported waiting times over these standards. Most GPs considered that they do not have enough time for non-urgent consultations or for remote contacts with patients. Conclusions Most GPs reported compliance with standards for waiting times for most in-person consultations and remote contacts, but they do so at the expense of work overload. A persistent excess of regular and unpaid working hours by GPs needs confirmation. If unpaid overtime is necessary to meet the regular demands of work, then workload and specific allocated tasks warrant review. Future research should focus on younger GPs, as they seem vulnerable to restricted accessibility. GPs’ preferences for more in-person care than was feasible during the pandemic must be considered when planning for the post-pandemic reconfiguration of service delivery.

Summary: Background: While a low CD4/CD8 ratio during HIV treatment correlates with immunosenescence, its value in identifying patients at an increased risk for clinical events remains unclear. Methods: We analyzed data from the CoRIS cohort to determine whether CD4 count, CD8 count, and CD4/CD8 ratio at year two of antiretroviral therapy (ART) could predict the risk of serious non-AIDS events (SNAEs) during the next five years. These included major adverse cardiovascular events, non-AIDS-defining malignancies, and non-accidental deaths. We used pooled logistic regression with inverse probability weighting to estimate the survival curves and cumulative risk of clinical events. Findings: The study included 4625 participants, 83% male, of whom 200 (4.3%) experienced an SNAE during the follow-up period. A CD4/CD8 ratio

today, in the conditions of military operations on the territory of Ukraine, the need for training cadets of higher military educational institutions (MEIs) for the successful performance of various combat tasks. The readiness of cadets to perform these tasks in conditions of significant psycho-emotional, nervous and physical stress is growing. The best way to achieve the maximum level of willingness of cadets of MEIs is to conduct a training simulation of the performance of a combat mission. However, the analysis of the technical and special training of the combat vehicle teams indicates an insufficient level of training for the crews, which does not ensure the full performance of combat tasks. During the educational process, not enough time is devoted to training on training equipment. We regarded it relevant to consider the issue of assessing the cardiological indicators of cadets when performing training simulations of a combat task for a better selection of people. This category of human has to carry out their professional activities in conditions of chronic stress and constant risk to their lives and health. The purpose of our work is to obtain and analyze the monitoring data of the basic parameters of the heart in the category of healthy men aged 18-21 years who are studying at the National Academy of the National Guard of Ukraine (NANGU). Also, we need to evaluate the cardiological parameters of tolerance during a training simulation of the performance of a combat task. 88 cadets of the 3rd and 4th years of NANGU were examined. The study did not include cadets with existing chronic diseases in the exacerbation phase, who had acute respiratory infections, signs of psycho-emotional overload, aged less than 18 years, and those who refused the examination. We used the BTR-4E training complex equipped with the Parus combat module to simulate a combat mission. The response of the cardiovascular system of cadets to the training load is characterized by a statistically significant (p=0.025) increase in the amplitude of T peaks, a decrease in the amplitude of P peaks (p

Sarcoidosis is an inflammatory granulomatous disease of unknown etiology involving any organ or tissue along with any combination of active sites, even the most silent ones clinically. The unpredictable nature of the sites involved in sarcoidosis dictates the highly variable natural history of the disease and the necessity to cluster cases at diagnosis based on clinical and/or imaging common characteristics in an attempt to classify patients based on their more homogeneous phenotypes, possibly with similar clinical behavior, prognosis, outcome, and therefore with therapeutic requirements. In the course of the disease's history, this attempt relates to the availability of a means of detection of the sites involved, from the Karl Wurm and Guy Scadding's chest x-ray staging through the ACCESS, the WASOG Sarcoidosis Organ Assessment Instruments, and the GenPhenReSa study to the 18F-FDG PET/CT scan phenotyping and far beyond to new technologies and/or the current “omics.” The hybrid molecular imaging of the 18F-FDG PET/CT scan, by unveiling the glucose metabolism of inflammatory cells, can identify high sensitivity inflammatory active granulomas, the hallmark of sarcoidosis—even in clinically and physiologically silent sites—and, as recently shown, is successful in identifying an unexpected ordered stratification into four phenotypes: (I) hilar–mediastinal nodal, (II) lungs and hilar–mediastinal nodal, (III) an extended nodal supraclavicular, thoracic, abdominal, inguinal, and (IV) all the above in addition to systemic organs and tissues, which is therefore the ideal phenotyping instrument. During the “omics era,” studies could provide significant, distinct, and exclusive insights into sarcoidosis phenotypes linking clinical, laboratory, imaging, and histologic characteristics with molecular signatures. In this context, the personalization of treatment for sarcoidosis patients might have reached its goal.

Introduction: Genomic assays are useful tools for tailoring adjuvant treatment in early breast cancer. We aimed to analyse the role of an institutional protocol of a genomic assay for chemotherapy de-escalation. Material and Methods: Prospective cohort study of all consecutive women diagnosed with hormone receptor-positive and human epidermal growth factor receptor 2-negative early breast cancer, tested with the 21-gene Recurrence Score (RS) assay from August 2015 to July 2018 at a Portuguese cancer centre. For being tested, patients should meet at least one of the pre-defined inclusion criteria: i) luminal A-like, pT2pN0; ii) luminal A-like, 1 – 3 positive nodes and comorbidities with higher risk of chemotherapy-induced toxicity; iii) pT1-2pN0, progesterone receptor ≤ 20% and/or Ki67 14% – 40%. Adjuvant treatment was de-escalated to isolated endocrine therapy if RS was less than 18. We measured the reduction in chemotherapy prescribing and its clinical impact, the RS association with pathologic features, and the protocol feasibility. Results: We tested 154 women with a median age of 61 years old (range: 25 – 79), 69% postmenopausal. Tumours were mainly pT1 (55%), pN0 (82%), invasive ductal (73%), G2 (86%), luminal B-like (69%) and stage IA (85%). We obtained a RS less than 18 in 60% of women, with an overall adjuvant chemotherapy reduction of 65%. Seven (95% confidence interval: 5 – 10) patients needed to be screened with the 21-gene RS assay to prevent one clinically relevant adverse event during the first six months of adjuvant treatment. Considering the currently used RS cut-off, only 9% of node-negative and 11% of node-positive patients had RS over 25. We found no relevant associations between RS and pathologic features. The protocol was feasible and did not compromise the adequate timing for adjuvant treatment. Conclusion: These criteria allowed the de-escalation of adjuvant systemic treatment in at least six out of ten women.

Introducción: en diciembre del año 2019 surgió en China una neumonía viral; el virus fue identificado como un coronavirus SARS-CoV-2, que se propagó rápidamente de tal manera que se convirtió en pandemia. La alta contagiosidad y la presencia de portadores asintomáticos dificultaron el diagnóstico de la infección y la toma de decisiones sanitarias. Objetivo: el objetivo de esta revisión bibliográfica es presentar y describir las principales técnicas utilizadas actualmente para el diagnóstico de COVID-19 y establecer su relación con los conocimientos de distintas disciplinas y tecnologías emergentes que confluyen en la Biotecnología bioquímico-farmacéutica orientada a la Salud humana. Metodología: se realizó una revisión de la bibliografía disponible en PubMed a partir de enero de 2020 sobre las pruebas diagnósticas que se encuentran actualmente en uso, en el ámbito sanitario, para la detección y seguimiento de la enfermedad COVID-19. También se realizaron búsquedas a través de Google y Google Académico para publicaciones de organismos de Salud en referencia a métodos diagnósticos. Resultados: se presenta una importante cantidad de pruebas diagnósticas, basadas en diferentes tecnologías, que desempeñan un papel clave en la pandemia de COVID-19. Algunas de ellas muy sofisticadas, como la secuenciación genómica de próxima generación, otras más estándar, pero igualmente robustas, como la reacción en cadena de la polimerasa (PCR). También otras adaptadas para el brote pandémico, como la amplificación isotérmica de ácidos nucleicos mediada por bucle. Todas las mencionadas se consideran de tipo molecular, pero también existen las pruebas serológicas, como ELISA, que incluyen ensayos en plasma o de tipo inmunológico. Estas sirven para detectar anticuerpos frente a la exposición al virus o antígenos en personas potencialmente infectadas. Conclusiones: los procesos de investigación y desarrollo biotecnológicos aplicados al diagnóstico y los conocimientos científicos previos permitieron una respuesta tanto nacional como internacional rápida y eficaz en medio de una inédita pandemia global. En esta revisión destacamos las principales técnicas, en qué estadio se deben usar y qué información nos aportan.

ObjectiveTo assess usability and acceptability of iSupport-Brasil (iSupport-BR) to virtually support family caregivers of people who have dementia.Materials and methodsIn the first stage, nine caregivers/former caregivers assessed the interface of the platform that hosts iSupport-BR. In the second stage, 10 caregivers assessed acceptability of the platform and answered the System Usability Scale (SUS), which varies from 0 to 100 points. A descriptive analysis of the quantitative data was performed, as well as a thematic analysis on the open questions. All the ethical aspects were respected.ResultsThe results of the first stage indicated a user-friendly interface of the system and relevant content of the program, with 55.6 and 77.8% of the participants assigning the maximum grade to these questions, respectively. Of the five possible points, the system’s mean score was 3.7. In Stage 2, 80% of the caregivers rated the program as very useful and 100% would recommend it to other caregivers. Perception of the program’s usability by the SUS scale was excellent (M = 86.5 ± 11.5).ConclusionThis research allowed elaborating the final version of iSupport-BR, considering usability and acceptability of the platform and the program for computers/notebooks, being a pioneer in evaluating it for use in smartphones. Future research studies will have to assess the effects of iSupport-BR on the caregivers’ mental health.

Introdução: Os doentes assintomáticos ou com sintomatologia ligeira a moderada representam 80-85% dos doentes infetados com SARS-CoV-2. Um melhor conhecimento sobre o curso da doença, os sinais de agravamento, podem ser de grande importância para uma otimização do seguimento destes doentes e antecipação de complicações. Objetivo: Estudar as características e evolução da doença por SARS-CoV-2 pelos cuidados de saúde primários, em indivíduos com critério para vigilância domiciliária. Métodos: Identificados doentes com infeção confirmada, inscritos na plataforma Trace COVID-19 e atribuídos à USF, de 26/Mar a 30/Jun de 2020. Os dados foram recolhidos através de contacto telefónico, tendo sido estudadas as variáveis: número de casos; caracterização demográfica, clínica e laboratorial, assim como evolução da doença. A análise dos dados foi efetuada no programa Microsoft® Excel. Resultados: Dos 41 indivíduos estudados, 53,7% era do sexo feminino e a média de idades foi de 44,9 anos. A duração média dos sintomas foi de 15,9 dias, sendo a mialgia o sintoma mais prevalente (61%). Em relação às comorbilidades, a patologia mais frequentemente encontrada foi a hipertensão arterial (22%). De acordo com a evolução clínica apenas 14,6% teve necessidade de observação em áreas dedicadas à COVID-19 na comunidade ou no serviço de urgência hospitalar. Conclusões: Os sintomas gripais, como mialgias (61%), cefaleias (58,5%), cansaço (56,1%) e tosse (48,8%), foram os mais frequentes. O único doente com necessidade de internamento apresentava como única comorbilidade a obesidade. Este é hoje reconhecido como um fator de risco para complicações associadas à COVID-19, a par da idade (acima dos 65 anos), das doenças cardiovasculares, da doença pulmonar crónica e da diabetes. Este estudo constitui um contributo para uma melhor caracterização desta patologia conhecida apenas há cerca de dois anos e reforça a importância do médico de família no seguimento dos doentes e integração de cuidados.

Abstract Background Aging is marked by a progressive rise in chronic diseases with an impact on social and healthcare costs. Physical activity (PA) may soothe the inconveniences related to chronic diseases, has positive effects on the quality of life and biological rhythms, and can prevent the decline in motor functions and the consequent falls, which are associated with early death and disability in older adults. Methods We randomized 120 over-65 males and females into groups of similar size and timing and will give each either moderate physical activity or cultural and recreational activities. Being younger than 65 years, inability to participate in physical activity for any medical reason, and involvement in a massive program of physical exercise are the exclusion criteria. The primary outcome measures are: quality of life, walking speed, and postural sway. Participants are tested at baseline, post-treatment, and 6-month (24 weeks) and 12-month (48 weeks) follow-ups. Discussion This study aims at improving the quality of life, wellness, and cognitive functioning in the elderly through a low-cost affordable program of moderate physical activity. Given the growing aging of the world population and the social and economic burden of disability in the elderly, our results might have a major impact on future practices. Trial registration ClinicalTrials.gov NCT03858114 . Registered on 28 February 2019.

Abiotrophia defectiva is a rare agent of endocarditis and subacute presentation may delay the diagnosis. We present the case of a 41-year-old male who was admitted to the hospital for further investigation regarding a consumptive syndrome with microcytic anaemia. Past medical history included new-onset mitral insufficiency followed by an ischaemic stroke due to small vessel disease. Thoraco-abdominal computed tomography revealed a splenic infarction. In the presence of two ischaemic events associated with mitral valve disease of unknown aetiology, we considered the possibility of subacute endocarditis. Blood cultures were positive for Abiotrophia defectiva, and transoesophageal echocardiography confirmed the diagnosis. As a subacute presentation of endocarditis, the paucity of symptoms caused a five-month delay in diagnosis. New-onset valvular disease and a stroke in an otherwise healthy young patient should always prompt proper investigation. This case highlights several complications caused by septic emboli of undiagnosed and untreated endocarditis.

ObjectiveTo evaluate the role of cognitive frailty and its components as risk factors of mortality in older adults of the Centro Médico Naval (CEMENA) in Callao, Peru during 2010-2015.MethodsWe performed a secondary analysis of data from a prospective cohort that included older adults (60 years and older) treated at the CEMENA Geriatrics service between 2010–2015. Frailty was defined as the presence of three or more criteria of the modified Fried Phenotype. Cognitive impairment was assessed using the Peruvian version of the Mini Mental State Examination (MMSE), considering a score

Introduction: Since the publication of endovascular treatment trials and European Stroke Guidelines, Portugal has re-organized stroke healthcare. The nine centers performing endovascular treatment are not equally distributed within the country, which may lead to differential access to endovascular treatment. Our main aim was to perform a descriptive analysis of the main treatment metrics regarding endovascular treatment in mainland Portugal and its administrative districts. Material and Methods: A retrospective national multicentric cohort study was conducted, including all ischemic stroke patients treated with endovascular treatment in mainland Portugal over two years (July 2015 to June 2017). All endovascular treatment centers contributed to an anonymized database. Demographic, stroke-related and procedure-related variables were collected. Crude endovascular treatment rates were calculated per 100 000 inhabitants for mainland Portugal, and each district and endovascular treatment standardized ratios (indirect age-sex standardization) were also calculated. Patient time metrics were computed as the median time between stroke onset, first-door, and puncture. Results: A total of 1625 endovascular treatment procedures were registered. The endovascular treatment rate was 8.27/100 000 inhabitants/year. We found regional heterogeneity in endovascular treatment rates (1.58 to 16.53/100 000/year), with higher rates in districts closer to endovascular treatment centers. When analyzed by district, the median time from stroke onset to puncture ranged from 212 to 432 minutes, reflecting regional heterogeneity. Conclusion: The overall national rate of EVT in the first two years after the organization of EVT-capable centers is one of the highest among European countries, however, significant regional disparities were documented. Moreover, stroke-onset-to-first-door times and in-hospital procedural times in the EVT centers were comparable to those reported in the randomized controlled trials performed in high-volume tertiary hospitals.

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Background: Numerous dietary components have been linked to the development of islet autoimmunity (IA) and type 1 diabetes (T1D); however, no associations are firmly established. This systematic review and meta-analysis aimed to synthesize current knowledge on diet and incidence of IA and T1D. Methods: Literature search was performed in Medline, Embase, and Cochrane Library, from inception until October 2020. Eligible studies had IA or T1D as outcome; any dietary exposure; case-control, cohort, or randomized controlled trial design; and hazard, risk, or odds ratios as measures of association. Summary relative risks (RR) and 95% confidence intervals (CI) were estimated with random-effects models. Certainty of evidence was assessed with GRADE. PROSPERO registration number: CRD42020212505. Findings: Among 5935 identified records, 96 were eligible, and pooled estimates could be produced for 26 dietary factors. Evidence with moderate/high certainty indicated lower risk of T1D in relation to longer (≥6-12 vs

The impact of hematopoietic stem cell transplantation (HSCT) on growth in patients diagnosed with mucopolysaccharidosis I Hurler (MPS-IH) has been historically regarded as unsatisfactory. Nevertheless, the growth patterns recorded in transplanted patients have always been compared to those of healthy children.The objective of this study was to verify the impact of HSCT on MPS-IH long term growth achievements. The auxological data of 15 patients were assessed longitudinally and compared both to the WHO growth centiles for healthy individuals and to recently published curves of untreated MPS-IH children. Despite a progressive decrease after HSCT when estimated with reference to the WHO growth charts, median height SDS showed a progressive and statistically significant increase when comparing the stature recorded at each timepoint in our population to the curves of untreated MPS-IH individuals (from ‐0.39 SDS at t0 to +1.35 SDS 5 years after HSCT, p value

Introducción: la parálisis cerebral (PC) es la causa más frecuente de discapacidad motriz en niños y adolescentes. En el 85% de los casos, la manifestación motora predominante es la espasticidad. Las inyecciones de toxina botulínica tipo A (TB-A) se han usado para reducir la espasticidad en niños con PC. No existen investigaciones a nivel nacional que comprueben si los resultados son comparables a los reportados en la literatura. Objetivo: determinar el efecto del tratamiento con TB-A en el tríceps sural en conjunto con la rehabilitación física en niños con PC espástica durante los años 2017-2018 en el Centro de Rehabilitación Infantil Teletón, Uruguay. Métodos: se realizó un estudio descriptivo, retrospectivo, de cohorte histórica única con seguimiento longitudinal, mediante la revisión de historias clínicas de los pacientes con PC con marcha independiente o asistida que recibieron tratamiento con TB-A para el tratamiento de la espasticidad del tríceps sural durante el período 2017-2018. Resultados: se analizaron 40 procedimientos de inyección de TB-A. Se observó una buena respuesta al mes y a los 3 meses del tratamiento con TB-A, con mejoría del ángulo de dorsiflexión del pie con la rodilla en flexión y en extensión, mejoría del puntaje de la escala de espasticidad de Ashworth modificada y, en el 95% de los procedimientos, de la percepción subjetiva de los padres. Se observó una disminución del efecto hacia los 6 meses de la aplicación. Conclusión: la aplicación de TB-A en el Centro Teletón muestra resultados positivos, comparables con los reportados en la bibliografía internacional.

El Ministerio de Salud del Perú se enfoca en el logro de la cuádruple meta para su sistema sanitario; buscando mejorar la salud de la población, una mejor experiencia del usuario cuando utiliza los servicios sanitarios, mejor uso de los recursos públicos que se vienen inyectando en la última década y una mejor satisfacción laboral de los trabajadores de salud. La promulgación de la Ley 30885 de Redes Integradas de Salud, marca un hito en el esfuerzo del país de lograr resolver las necesidades de atención de los ciudadanos en una red y es la apuesta del sector salud para mejorar el desempeño del sistema sanitario. Para ello se plantean elementos clave para la organización y funcionamiento: Identificación de población y familias, asignación de responsabilidad del cuidado, fortalecimiento de las puertas de entrada al sistema de salud, estratificación de riesgos individuales y familiares, coordinación para facilitar el acceso y utilización de servicios de salud, continuidad y complementariedad del cuidado, y gobernanza en la red. Esta nueva propuesta política implica ajustes en la red de servicios de salud: establecimientos de salud (clínicas de familia) de 12 y 24 horas para el cuidado individual, familiar, manejo de los determinantes de la salud y hospitales para complementar el cuidado. El modelo de cuidado será más complejo y de avance difícil si no está unido a ajustes en el financiamiento, aseguramiento y en la gestión del cambio cultural de los trabajadores, usuarios del sistema y del sistema de gobernanza en salud.

Background: Acute T-cell mediated rejection (TCMR) is usually indicated by alteration in serum-creatinine measurements when considerable transplant damage has already occurred. There is, therefore, a need for non-invasive early detection of immune signals that would precede the onset of rejection, prior to transplant damage. Methods: We examined the RT-qPCR expression of 22 literature-based genes in peripheral blood samples from 248 patients in the Kidney Allograft Immune Biomarkers of Rejection Episodes (KALIBRE) study. To account for post-transplantation changes unrelated to rejection, we generated time-adjusted gene-expression residuals from linear mixed-effects models in stable patients. To select genes, we used penalised logistic regression based on 27 stable patients and 27 rejectors with biopsy-proven T-cell-mediated rejection, fulfilling strict inclusion/exclusion criteria. We validated this signature in i) an independent group of stable patients and patients with concomitant T-cell and antibody-mediated-rejection, ii) patients from an independent study, iii) cross-sectional pre-biopsy samples from non-rejectors and iv) longitudinal follow-up samples covering the first post-transplant year from rejectors, non-rejectors and stable patients. Findings: A parsimonious TCMR-signature (IFNG, IP-10, ITGA4, MARCH8, RORc, SEMA7A, WDR40A) showed cross-validated area-under-ROC curve 0.84 (0.77–0.88) (median, 2.5th–97.5th centile of fifty cross-validation cycles), sensitivity 0.67 (0.59–0.74) and specificity 0.85 (0.75–0.89). The estimated probability of TCMR increased seven weeks prior to the diagnostic biopsy and decreased after treatment. Gene expression in all patients showed pronounced variability, with up to 24% of the longitudinal samples in stable patients being TCMR-signature positive. In patients with borderline changes, up to 40% of pre-biopsy samples were TCMR-signature positive. Interpretation: Molecular marker alterations in blood emerge well ahead of the time of clinically overt TCMR. Monitoring a TCMR-signature in peripheral blood could unravel T-cell-related pro-inflammatory activity and hidden immunological processes. This additional information could support clinical management decisions in cases of patients with stable but poor kidney function or with inconclusive biopsy results.

Introducción: Dentro del marco de su actividad profesional el estomatólogo se enfrenta a diversas afecciones como la reabsorción radicular interna, cuyos casos avanzados pueden complicar el pronóstico del tratamiento endodóntico, debido al debilitamiento de la estructura dental remanente y las posibles afectaciones periodontales. Debido a que la boca está localizada en uno de los puntos focales de la cara, cualquier alteración en la apariencia estética puede provocar implicaciones psicológicas que pueden ir desde una simple forma de esconder el defecto hasta la más grande introversión. Objetivo: Presentar un caso clínico de reabsorción dentaria interna resuelto con implante postextractivo de carga inmediata. Presentación de caso: Paciente femenina de 31 años con reabsorción dental interna de incisivo central superior. Se llevó a cabo un adecuado diagnóstico y plan de tratamiento del caso, colocándose un implante transalveolar cargado de forma inmediata y la rehabilitación definitiva metalcerámica una vez concluida la fase de osteointegración. Conclusiones: Se consiguió una rehabilitación estética, funcional y biomecánicamente estable a largo plazo, que coincide con las expectativas del paciente, lo cual demuestra que cuando se cumplan los requisitos adecuados y la planificación sea exhaustiva, la implantología ofrece el tratamiento más avanzado en casos en que es inminente la extracción dental. Palabras clave: implante postextractivo; reabsorción dentinaria interna; carga inmediata.

Abstract Surgery in COVID‐19 disease complicated by APF represents the last life‐saving treatment option. The choice of the therapeutic period to indicate this approach is fundamental. In fact, the clinical stability of patient is necessary in order to allow single‐lung ventilation and to minimize postoperative sequelae.

Background: The role of the gut microbiome in the biotransformation of drugs has recently come under scrutiny. It remains unclear whether the gut microbiome directly influences the extent of drug absorbed after oral administration and thus potentially alters clinical pharmacokinetics. Methods: In this study, we evaluated whether changes in the gut microbiota of male Sprague Dawley rats, as a result of either antibiotic or probiotic administration, influenced the oral bioavailability of two commonly prescribed antipsychotics, olanzapine and risperidone. Findings: The bioavailability of olanzapine, was significantly increased (1.8-fold) in rats that had undergone antibiotic-induced depletion of gut microbiota, whereas the bioavailability of risperidone was unchanged. There was no direct effect of microbiota depletion on the expression of major CYP450 enzymes involved in the metabolism of either drug. However, the expression of UGT1A3 in the duodenum was significantly downregulated. The reduction in faecal enzymatic activity, observed during and after antibiotic administration, did not alter the ex vivo metabolism of olanzapine or risperidone. The relative abundance of Alistipes significantly correlated with the AUC of olanzapine but not risperidone. Interpretation: Alistipes may play a role in the observed alterations in olanzapine pharmacokinetics. The gut microbiome might be an important variable determining the systemic bioavailability of orally administered olanzapine. Additional research exploring the potential implication of the gut microbiota on the clinical pharmacokinetics of olanzapine in humans is warranted. Funding: This research is supported by APC Microbiome Ireland, a research centre funded by Science Foundation Ireland (SFI), through the Irish Government's National Development Plan (grant no. 12/RC/2273 P2) and by Nature Research-Yakult (The Global Grants for Gut Health; Ref No. 626891).

Objetivos: As infeções do trato urinário (ITU) são das infeções bacterianas mais frequentes em pediatria. O exame bacteriológico da urina (EBU) é o teste referência para o diagnóstico de ITU. Sendo um exame moroso, a decisão de iniciar antibioterapia baseia-se na clínica e na urinálise (ASU). A suspeita de ITU na criança e adolescente poderá ser orientada pelo médico de família. O objetivo deste estudo foi avaliar a eficácia da ASU no diagnóstico precoce da ITU em idade pediátrica. Métodos: Efetuou-se um estudo observacional que incluiu doentes (0-18 anos) que recorreram à urgência pediátrica entre 01/01/2015 e 31/12/2016 e que realizaram colheita de urina para ASU e EBU. Foram analisados os resultados da ASU e comparados com os resultados do EBU. Atribuiu-se diagnóstico definitivo de ITU a todos os doentes com EBU positivo. Determinou-se a sensibilidade, especificidade, valor preditivo positivo (VPP), valor preditivo negativo (VPN) e odds ratio (OR) dos parâmetros nitritos e esterase leucocitária (EL) para o diagnóstico de ITU. Resultados: Das 3.400 amostras incluídas, 21,2% tiveram resultado bacteriológico positivo. O microrganismo mais frequente foi Escherichia coli. Os nitritos demonstraram sensibilidade de 28% e especificidade de 99% para o diagnóstico. A EL revelou sensibilidade de 90% e especificidade de 63%. Para o conjunto dos dois, a sensibilidade foi de 27% e a especificidade de 99%, com VPP 91% e VPN 83%. Para EL superior a 500 células/mcl verificou-se especificidade de 93%. No grupo etário 0-12 meses verifica-se um VPP 93% e VPN 82% para os dois em conjunto. Conclusões: Os resultados são concordantes com a literatura: a EL é sensível para o diagnóstico de ITU e os nitritos são específicos. O melhor indicador para exclusão de ITU foi a EL. Estes resultados poderão ser aplicados na consulta aberta de saúde infantil e juvenil ao nível dos cuidados de saúde primários.