Relatório de estágio em farmácia comunitária

Relatório de estágio realizado no âmbito do Mestrado Integrado em Ciências Farmacêuticas, apresentado à Faculdade de Farmácia da Universidade de Coimbr

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Music therapy versus treatment as usual for refugees diagnosed with posttraumatic stress disorder (PTSD): study protocol for a randomized controlled trial

Abstract Background Meta-analyses of studies on psychological treatment of refugees describe highly varying outcomes, and research on multi-facetted and personalized treatment of refugees with post-traumatic stress disorder (PTSD) is needed. Music therapy has been found to affect arousal regulation and emotional processing, and a pilot study on the music therapy method Trauma-focused Music and Imagery (TMI) with traumatized refugees resulted in significant changes of trauma symptoms, well-being and sleep quality. The aim of the trial is to test the efficacy of TMI compared to verbal psychotherapy. Methods A randomized controlled study with a non-inferiority design is carried out in three locations of a regional outpatient psychiatric clinic for refugees. Seventy Arabic-, English- or Danish-speaking adult refugees (aged 18–67 years) diagnosed with PTSD are randomized to 16 sessions of either music therapy or verbal therapy (standard treatment). All participants are offered medical treatment, psychoeducation by nurses, physiotherapy or body therapy and social counseling as needed. Outcome measures are performed at baseline, post therapy and at 6 months’ follow-up. A blind assessor measures outcomes post treatment and at follow-up. Questionnaires measuring trauma symptoms (HTQ), quality of life (WHO-5), dissociative symptoms (SDQ-20, DSS-20) and adult attachment (RAAS) are applied, as well as physiological measures (salivary oxytocin, beta-endorphin and substance P) and participant evaluation of each session. Discussion The effect of music therapy can be explained by theories on affect regulation and social engagement, and the impact of music on brain regions affected by PTSD. The study will shed light on the role of therapy for the attainment of a safe attachment style, which recently has been shown to be impaired in traumatized refugees. The inclusion of music and imagery in the treatment of traumatized refugees hopefully will inform the choice of treatment method and expand the possibilities for improving refugee health and integration. Trial registration ClinicalTrials.gov ID number NCT03574228, registered retrospectively on 28 June 2016

Clearance of defective muscle stem cells by senolytics restores myogenesis in myotonic dystrophy type 1

Abstract Muscle stem cells, the engine of muscle repair, are affected in myotonic dystrophy type 1 (DM1); however, the underlying molecular mechanism and the impact on the disease severity are still elusive. Here, we show using patients’ samples that muscle stem cells/myoblasts exhibit signs of cellular senescence in vitro and in situ. Single cell RNAseq uncovers a subset of senescent myoblasts expressing high levels of genes related to the senescence-associated secretory phenotype (SASP). We show that the levels of interleukin-6, a prominent SASP cytokine, in the serum of DM1 patients correlate with muscle weakness and functional capacity limitations. Drug screening revealed that the senolytic BCL-XL inhibitor (A1155463) can specifically remove senescent DM1 myoblasts by inducing their apoptosis. Clearance of senescent cells reduced the expression of SASP, which rescued the proliferation and differentiation capacity of DM1 myoblasts in vitro and enhanced their engraftment following transplantation in vivo. Altogether, this study identifies the pathogenic mechanism associated with muscle stem cell defects in DM1 and opens a therapeutic avenue that targets these defective cells to restore myogenesis

Mutant Ras and inflammation-driven skin tumorigenesis is suppressed via a JNK-iASPP-AP1 axis.

Concurrent mutation of a RAS oncogene and the tumor suppressor p53 is common in tumorigenesis, and inflammation can promote RAS-driven tumorigenesis without the need to mutate p53. Here, we show, using a well-established mutant RAS and an inflammation-driven mouse skin tumor model, that loss of the p53 inhibitor iASPP facilitates tumorigenesis. Specifically, iASPP regulates expression of a subset of p63 and AP1 targets, including genes involved in skin differentiation and inflammation, suggesting that loss of iASPP in keratinocytes supports a tumor-promoting inflammatory microenvironment. Mechanistically, JNK-mediated phosphorylation regulates iASPP function and inhibits iASPP binding with AP1 components, such as JUND, via PXXP/SH3 domain-mediated interaction. Our results uncover a JNK-iASPP-AP1 regulatory axis that is crucial for tissue homeostasis. We show that iASPP is a tumor suppressor and an AP1 coregulator

Additional file 2: of Music therapy versus treatment as usual for refugees diagnosed with posttraumatic stress disorder (PTSD): study protocol for a randomized controlled trial

Informed consent (English version). (DOCX 167 kb

Additional file 1: of Music therapy versus treatment as usual for refugees diagnosed with posttraumatic stress disorder (PTSD): study protocol for a randomized controlled trial

Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2013 Checklist: recommended items to address in a clinical trial protocol and related documents*. (DOCX 45 kb

Music therapy versus treatment as usual for refugees diagnosed with posttraumatic stress disorder (PTSD): study protocol for a randomized controlled trial

Abstract Background Meta-analyses of studies on psychological treatment of refugees describe highly varying outcomes, and research on multi-facetted and personalized treatment of refugees with post-traumatic stress disorder (PTSD) is needed. Music therapy has been found to affect arousal regulation and emotional processing, and a pilot study on the music therapy method Trauma-focused Music and Imagery (TMI) with traumatized refugees resulted in significant changes of trauma symptoms, well-being and sleep quality. The aim of the trial is to test the efficacy of TMI compared to verbal psychotherapy. Methods A randomized controlled study with a non-inferiority design is carried out in three locations of a regional outpatient psychiatric clinic for refugees. Seventy Arabic-, English- or Danish-speaking adult refugees (aged 18–67 years) diagnosed with PTSD are randomized to 16 sessions of either music therapy or verbal therapy (standard treatment). All participants are offered medical treatment, psychoeducation by nurses, physiotherapy or body therapy and social counseling as needed. Outcome measures are performed at baseline, post therapy and at 6 months’ follow-up. A blind assessor measures outcomes post treatment and at follow-up. Questionnaires measuring trauma symptoms (HTQ), quality of life (WHO-5), dissociative symptoms (SDQ-20, DSS-20) and adult attachment (RAAS) are applied, as well as physiological measures (salivary oxytocin, beta-endorphin and substance P) and participant evaluation of each session. Discussion The effect of music therapy can be explained by theories on affect regulation and social engagement, and the impact of music on brain regions affected by PTSD. The study will shed light on the role of therapy for the attainment of a safe attachment style, which recently has been shown to be impaired in traumatized refugees. The inclusion of music and imagery in the treatment of traumatized refugees hopefully will inform the choice of treatment method and expand the possibilities for improving refugee health and integration. Trial registration ClinicalTrials.gov ID number NCT03574228, registered retrospectively on 28 June 2016

Music therapy versus treatment as usual for refugees diagnosed with posttraumatic stress disorder (PTSD): study protocol for a randomized controlled trial

Abstract Background Meta-analyses of studies on psychological treatment of refugees describe highly varying outcomes, and research on multi-facetted and personalized treatment of refugees with post-traumatic stress disorder (PTSD) is needed. Music therapy has been found to affect arousal regulation and emotional processing, and a pilot study on the music therapy method Trauma-focused Music and Imagery (TMI) with traumatized refugees resulted in significant changes of trauma symptoms, well-being and sleep quality. The aim of the trial is to test the efficacy of TMI compared to verbal psychotherapy. Methods A randomized controlled study with a non-inferiority design is carried out in three locations of a regional outpatient psychiatric clinic for refugees. Seventy Arabic-, English- or Danish-speaking adult refugees (aged 18–67 years) diagnosed with PTSD are randomized to 16 sessions of either music therapy or verbal therapy (standard treatment). All participants are offered medical treatment, psychoeducation by nurses, physiotherapy or body therapy and social counseling as needed. Outcome measures are performed at baseline, post therapy and at 6 months’ follow-up. A blind assessor measures outcomes post treatment and at follow-up. Questionnaires measuring trauma symptoms (HTQ), quality of life (WHO-5), dissociative symptoms (SDQ-20, DSS-20) and adult attachment (RAAS) are applied, as well as physiological measures (salivary oxytocin, beta-endorphin and substance P) and participant evaluation of each session. Discussion The effect of music therapy can be explained by theories on affect regulation and social engagement, and the impact of music on brain regions affected by PTSD. The study will shed light on the role of therapy for the attainment of a safe attachment style, which recently has been shown to be impaired in traumatized refugees. The inclusion of music and imagery in the treatment of traumatized refugees hopefully will inform the choice of treatment method and expand the possibilities for improving refugee health and integration. Trial registration ClinicalTrials.gov ID number NCT03574228, registered retrospectively on 28 June 2016