Hospital admissions of adults with community-acquired pneumonia in Portugal between 2000 and 2009.

Recent studies in the USA and northern Europe have shown an increase in community-acquired pneumonia (CAP). In southern Europe, this increase has not yet been documented. We carried out a retrospective analysis from encoded information from the Portuguese database for hospital admissions that included all individuals aged ≥18 years, with a primary diagnosis of pneumonia, who were discharged between 2000 and 2009. We excluded patients infected with HIV, individuals immunocompromised as a result of anti-cancer or immunosuppressive treatment, and transplant recipients. Of the 294 027 admissions for CAP, 56% were male. The mean age was 73.1 years and the median age 77 years. Between 2000 and 2009, there was a 5% increase in the average age of patients admitted with CAP. Admissions for CAP represented 3.7% of total admissions of adult patients. The average annual rate of hospital admissions for adults with CAP was 3.61 per 1000 total population, rising to 13.4 for those aged ≥65 years. Between 2000-2004 and 2005-2009 the average annual rate of hospital admission for CAP per 1000 population increased by 28.2%. Hospital admissions for CAP in Portugal increased between 2000 and 2009. It has grown consistently over time, varying according to age with males over-represented.

Safety and immunogenicity of an mRNA-lipid nanoparticle vaccine candidate against SARS-CoV-2 : A phase 1 randomized clinical trial.

BACKGROUND: We used the RNActive® technology platform (CureVac N.V., Tübingen, Germany) to prepare CVnCoV, a COVID-19 vaccine containing sequence-optimized mRNA coding for a stabilized form of SARS-CoV­2 spike (S) protein encapsulated in lipid nanoparticles (LNP). METHODS: This is an interim analysis of a dosage escalation phase 1 study in healthy 18-60-year-old volunteers in Hannover, Munich and Tübingen, Germany, and Ghent, Belgium. After giving 2 intramuscular doses of CVnCoV or placebo 28 days apart we assessed solicited local and systemic adverse events (AE) for 7 days and unsolicited AEs for 28 days after each vaccination. Immunogenicity was measured as enzyme-linked immunosorbent assay (ELISA) IgG antibodies to SARS-CoV­2 S­protein and receptor binding domain (RBD), and SARS-CoV­2 neutralizing titers (MN50). RESULTS: In 245 volunteers who received 2 CVnCoV vaccinations (2 µg, n = 47, 4 µg, n = 48, 6 µg, n = 46, 8 µg, n = 44, 12 µg, n = 28) or placebo (n = 32) there were no vaccine-related serious AEs. Dosage-dependent increases in frequency and severity of solicited systemic AEs, and to a lesser extent local AEs, were mainly mild or moderate and transient in duration. Dosage-dependent increases in IgG antibodies to S­protein and RBD and MN50 were evident in all groups 2 weeks after the second dose when 100% (23/23) seroconverted to S­protein or RBD, and 83% (19/23) seroconverted for MN50 in the 12 µg group. Responses to 12 µg were comparable to those observed in convalescent sera from known COVID-19 patients. CONCLUSION: In this study 2 CVnCoV doses were safe, with acceptable reactogenicity and 12 µg dosages elicited levels of immune responses that overlapped those observed in convalescent sera.

Pharmacokinetics of Ambroxol Sustained Release (Mucosolvan® Retard) Compared with Other Formulations in Healthy Volunteers.

INTRODUCTION: Ambroxol is used in the treatment of acute and chronic respiratory conditions characterized by abnormal mucus secretion and impaired mucus transport and is available in a variety of formulations. This study aimed to compare the steady-state (SS) pharmacokinetic characteristics of extended-release (ER) 75-mg retard capsules with two immediate-release (IR) formulations (60-mg effervescent tablets and 30-mg tablets) over a 24-h period. METHODS: An open-label, randomized, three-period, six-sequence crossover study was conducted in healthy volunteers aged 18-45 years who had a normal body mass index. The test (ER 75-mg retard capsule once daily) and reference treatments (half of IR 60-mg effervescent tablet twice daily or 30-mg IR tablet twice daily) were administered on days 1-5 of each treatment period. Meals were standardized and concomitant therapy was prohibited. Blood samples for pharmacokinetic assessment were collected on day 5 (SS) of each treatment period. The co-primary endpoints were exposure (AUCSS 0-24) and maximum plasma level (Cmax SS). RESULTS: Twenty-four participants received ambroxol (male n = 13, 54.2%; mean ± standard deviation [SD] age 25.0 ± 6.4 years) and 23 completed the study. ER retard capsules provided similar AUCSS 0-24 compared to IR tablets (geometric means ratio [GMR] 110.7%; 90% confidence interval [CI] 99.8%, 122.7%) and effervescent tablets (GMR 106.9%; 90% CI 100.3%, 114.0%). ER retard capsules provided similar Cmax SS compared to IR tablets (GMR 84.7%, 90% CI 77.0%, 93.3%), and lower Cmax SS compared to effervescent tablets (GMR 80.9%, 90% CI 73.9%, 88.6%). Time to Cmax SS (tmax SS) was longer with ER retard capsules (6.0 h) than with IR tablets (2.0 h) or effervescent tablets (1.0 h). CONCLUSIONS: ER ambroxol 75-mg retard capsules given once daily showed a similar pharmacokinetic profile to IR ambroxol formulations and therefore can be used instead of these in the treatment of respiratory conditions. CLINICALTRIALS. GOV IDENTIFIER: NCT02036775.

Ambroxol is used to relieve the symptoms of respiratory conditions in which abnormal mucus secretion is a problem, including the common cold, acute and chronic bronchitis, and chronic obstructive pulmonary disease. Different formulations of ambroxol are available, including tablets and effervescent tablets that release the drug as soon as they are digested, but need to be taken twice a day, or extended release (retard) capsules that release the drug slowly over 24 h and can be taken once a day. This randomized, three-period, six-sequence crossover study in 24 healthy volunteers compared the pharmacokinetics of three formulations of ambroxol: tablets, effervescent tablets, and retard capsules. The amount of drug in the bloodstream over 24 h was similar with all three formulations, but (as expected) the time to reach peak plasma concentration was longer with the retard capsules than both forms of tablet. These results show that people who take ambroxol for respiratory conditions will receive the same amount of ambroxol whether they take retard capsules, standard tablets, or effervescent tablets.

An overview of efficacy and safety of ambroxol for the treatment of acute and chronic respiratory diseases with a special regard to children.

Introduction: Ambroxol (2-amino-3,5-dibromo-N-[trans-4-hydroxycyclohexyl]benzylamine), an over-the-counter product, is a mucoactive agent and has been used widely to treat both acute and chronic respiratory diseases since 1978. This review aims to provide an overview of the clinical evidence available on the use of ambroxol in children with acute and chronic respiratory diseases. Data for this review were obtained from both published and unpublished clinical studies, and real-world evidence studies. Although conducted prior to the introduction of Good Clinical Practice (GCP), these studies, representing almost 1,300 pediatric patients, report strong clinical outcomes following the use of ambroxol in pediatric patients. Furthermore, efficacy findings were consistent irrespective of age, including for patients as young as 1 month old. Additionally, the majority of studies found ambroxol to be well tolerated in children. Taken together, the clinical evidence for ambroxol shows treatment effects that offer significant benefits to pediatric patients for its licensed use as a secretolytic therapy in acute and chronic bronchopulmonary disorders associated with abnormal mucus secretion and impaired mucus transport. The findings from this review indicate that ambroxol, for its intended over-the-counter indications, is both efficacious and well tolerated in children and that the favorable benefit/risk profile of ambroxol reported in adults extends to the pediatric population, starting from early infancy, with acute and chronic respiratory diseases.

Bronchogenic cyst of the neck in an elder patient: A case report.

INTRODUCTION: Bronchogenic cysts are rare malformations, mostly diagnosed in children. We report the rare case of a neck bronchogenic cyst diagnosed in an elderly patient. PRESENTATION OF CASE: The patient complained of a long-standing submental mass. The diagnostic work-up resulted in a thyroglossal duct cyst diagnosis for which the patient underwent a Sistrunk procedure. However, the histological analysis of the lesion ultimately revealed a bronchogenic cyst. DISCUSSION: Neck bronchogenic cysts are rare and, in adults, normally asymptomatic. Imaging exams can suggest the diagnosis but they are most important for surgical planning. Surgery is the elected treatment for bronchogenic cysts and the histopathologic exam of the specimen provides definitive diagnosis. CONCLUSION: This case demonstrates than even though they are a rare diagnosis, bronchogenic cysts should be considered in the diagnostic work-up of neck cysts, even in elderly patients.

Parotid metastasis of an amelanotic melanoma of the scalp: The great masquerader.

BACKGROUND: Cutaneous melanoma is often characterized by its pigmented appearance; however, up to 8.1% of such lesions contain little or no pigmentation. Amelanotic melanomas, lesions devoid of visible pigment, present a diagnostic quandary because they can masquerade as many other skin pathologies. Recognizing amelanotic melanoma is even more clinically challenging when it is first detected as a metastasis to the secondary tissue. METHODS: We report a rare case of metastasis of an amelanotic melanoma to the parotid gland. RESULTS: A 75-year-old man presented with an 8-month history of a painless, mobile, hardened mass in the right parotid region. Histopathological analysis of a fine-needle aspiration biopsy of the parotid mass indicated that the mass was melanoma. Careful clinical and radiological examination revealed an 8 mm erythematous papule in the right temporal scalp, initially diagnosed by visual examination as basal cell carcinoma. After right superficial parotidectomy, neck dissection, and excision of the temporal scalp lesion, histological examination revealed the scalp lesion to be amelanotic melanoma. CONCLUSION: Although metastatic amelanotic melanoma to the parotid gland is a rare diagnosis, the clinician should be familiar with this presentation to increase the likelihood of making the correct diagnosis and delivering prompt treatment.

WT1, MSH6, GATA5 and PAX5 as epigenetic oral squamous cell carcinoma biomarkers - a short report.

PURPOSE: Oral squamous cell carcinoma (OSCC) is a frequently occurring aggressive malignancy with a heterogeneous clinical behavior. Based on the paucity of specific early diagnostic and prognostic biomarkers, which hampers the appropriate treatment and, ultimately the development of novel targeted therapies, we aimed at identifying such biomarkers through a genetic and epigenetic analysis of these tumors. METHODS: 93 primary OSCCs were subjected to DNA copy number alteration (CNA) and methylation status analyses using methylation-specific multiplex ligation-dependent probe amplification (MS-MPLA). The genetic and epigenetic OSCC profiles obtained were associated with the patients' clinic-pathological features. RESULTS: We found that WT1 gene promoter methylation is a predictor of a better prognosis and that MSH6 and GATA5 gene promoter methylation serve as predictors of a worse prognosis. GATA5 gene promoter methylation was found to be significantly associated with a shorter survival rate. In addition, we found that PAX5 gene promoter methylation was significantly associated with tongue tumors. To the best of our knowledge, this is the first study that highlights this specific set of genes as epigenetic diagnostic and prognostic biomarkers in OSCC. CONCLUSIONS: Our data highlight the importance of epigenetically assessing OSCCs to identify key genes that may serve as diagnostic and prognostic biomarkers and, potentially, as candidate therapeutic targets.

Hospital admissions for herpes zoster in Portugal between 2000 and 2010.

INTRODUCTION AND OBJECTIVES: Herpes zoster and post-herpetic neuralgia increasing incidence is related to ageing. These conditions can be very debilitating and have an important impact in patients' quality of life. In an ageing population like the Portuguese, is expected that the burden of herpes zoster and post-herpetic neuralgia rises, nevertheless, a specific surveillance system for zoster does not exist in the country, and data regarding the incidence of herpes zoster and the burden of the disease in Portugal in the last decades was not found. In Portugal, the vaccine is still not available. Scaling the burden of disease is important to support public health policies regarding zoster vaccination. MATERIAL AND METHODS: We carried out a retrospective analysis from encoded information from the Portuguese Ministery of Health database for hospital admissions which included all individuals with a primary diagnosis of Herpes Zoster (IDC-9-CM 053), who were discharged between 2000 and 2010. RESULTS: In Portugal, between 2000 and 2010, 1 706 hospital admissions with primary diagnosis of herpes zoster occurred. The majority of the patients were elderly. Eleven percent of the patients had potentially severe immunocompromise. The predominant disease was uncomplicated herpes zoster, followed by nervous system and ophthalmic herpes zoster. Mean hospital stay length was 9.3 days, increasing with age. There was a 1% case fatality rate. Considering the 2000-2009 period and the adult population only, the average annual incidence rate of hospitalization with primary diagnosis of herpes zoster in Portugal was 1.9/100 000 inhabitants, increasing with age. CONCLUSION: This study confirms that, in Portugal, severe herpes zoster is related to ageing and associated with significant morbidity, mortality and health resources allocation.

Introdução e Objectivos: O aumento da incidência de herpes zoster e da nevralgia pós-herpética estão associados ao envelhecimento da população. Estas patologias podem ser francamente debilitantes e ter um grande impacto na qualidade de vida dos doentes. Numa população envelhecida como a portuguesa, é esperado que o impacto do herpes zoster e da post-herpetic neuralgia aumentem. No entanto, não existe no país nenhum sistema específico de monitorização da doença e não foram encontrados dados epidemiológicos portugueses nas últimas décadas. A vacina contra o herpes zoster, já recomendada noutros países europeus, ainda não se encontra disponível em Portugal. Conhecer o impacto do herpes zoster é importante para fundamentar medidas de saúde pública relacionadas com a vacinação.Material e Métodos: Procedeu-se a uma análise retrospetiva da base de dados da Administração Central dos Sistemas de Saúde com a informação clínica codificada dos internamentos hospitalares de todos os indivíduos com o diagnóstico principal de herpes zoster (ICD-9-CM 053) e que tiveram alta entre 2000 e 2010.Resultados: Em Portugal, entre 2000 e 2010, ocorreram 1 706 internamentos hospitalares com o diagnóstico principal de herpes zoster. A maioria dos doentes era idosa. Do total de internados, 10,6% tinham formas potencialmente graves de imunocompromisso. A doença predominante de herpes zoster sem complicações, seguido de herpes zoster do sistema nervoso e oftálmico. A duração média dos internamentos foi de 9,3 dias, aumentando com a idade. A letalidade intra-hospitalar foi de 1%. Considerando o período de 2000-2009 e apenas a população adulta, a média anual da incidência dos internamentos hospitalares com o diagnóstico principal deherpes zoster foi de 1,9 por 100 000 habitantes, aumentando com a idade.Conclusão: Este estudo confirma que, em Portugal, as formas graves de herpes zoster estão relacionadas com a idade e associadas a significativa morbilidade, mortalidade e utilização de recursos em saúde.