Survival Analysis of COPD Patients in a 13-Year Nationwide Cohort Study of the Brazilian National Health System

Background: Chronic obstructive pulmonary disease (COPD) has an appreciable socioeconomical impact in low- and middle-income countries, but most epidemiological data originate from high-income countries. For this reason, it is especially important to understand survival and factors associated with survival in COPD patients in these countries. Objective: To assess survival of COPD patients in Brazil, to identify risk factors associated with overall survival, including treatment options funded by the Brazilian National Health System (SUS). Methodology: We built a retrospective cohort study of patients dispensed COPD treatment in SUS, from 2003 to 2015 using a National Database created from the record linkage of administrative databases. We further matched patients 1:1 based on sex, age and year of entry to assess the effect of the medicines on patient survival. We used the Kaplan-Meier method to estimate overall survival of patients, and Cox's model of proportional risks to assess risk factors. Result: Thirty seven thousand and nine hundred and thirty eight patients were included. Patient's survival rates at 1 and 10 years were 97.6% (CI 95% 97.4–97.8) and 83.1% (CI 95% 81.9–84.3), respectively. The multivariate analysis showed that male patients, over 65 years old and underweight had an increased risk of death. Therapeutic regimens containing a bronchodilator in a free dose along with a fixed-dose combination of corticosteroid and bronchodilator seem to be a protective factor when compared to other regimens. Conclusion: Our findings contribute to the knowledge of COPD patients' profile, survival rate and related risk factors, providing new evidence that supports the debate about pharmacological therapy and healthcare of these patients

Microrreservas marinas artificiales en la línea de costa. Hacia un nuevo modelo de gestión de la biodiversidad en áreas litorales

Recientemente se ha propuesto a la comunidad científica la nueva figura de protección MRMA (Microrreserva Marina Artificial; AMMR en inglés) la cual también ha sido formalmente solicitada a la UNESCO para que esta institución considere reconocerla y consecuentemente, validarla. Se expone la contribución de las MRMAs a la preservación de especies protegidas, particularmente a las consideradas en peligro de extinción que propendan, de forma natural, a establecerse en escolleras y diques de abrigo de instalaciones costeras. Se mencionan las especies protegidas localizadas en las MRMAs, así como sus figuras de protección y disposiciones oficiales que les conciernen. Se exponen criterios generales de designación de MRMAs, posibles vías de solución ante problemas previsibles que puedan surgir (entendimiento entre administraciones, calidad de aguas, medidas de contingencia ante vertidos accidentales, etc.) y se deja entrever las potencialidades de las MRMAs como activo ecológico, medioambiental, urbanístico y educativo, así como el futuro papel que desempeñarán las MRMAs en la gestión del medio litoral y en el campo de la biología de la conservación. Finalmente, se establece una revisión de la legislación actual que más pudiera concernirles, destacándose los aspectos más importantes que en ellas pudieran influir. Al respecto, se destaca que ley 41/2010 de Protección del Medio Marino (Artº 26) establece que podrán formar parte de la red de Áreas Marinas Protegidas “ las áreas protegidas por instrumentos internacionales, sin perjuicio de que su declaración y gestión se ajustará a lo dispuesto en su correspondiente normativa internacional ” por lo que, si la nueva figura de protección “Microrreserva Marina Artificial” consiguiera marchamo UNESCO, aquélla podría incorporarse a la legislación española sin ninguna dificultad especial

Immune-based therapies for hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the third most frequent cause of cancer-related death. The immune-rich contexture of the HCC microenvironment makes this tumour an appealing target for immune-based therapies. Here, we discuss how the functional characteristics of the liver microenvironment can potentially be harnessed for the treatment of HCC. We will review the evidence supporting a therapeutic role for vaccines, cell-based therapies and immune-checkpoint inhibitors and discuss the potential for patient stratification in an attempt to overcome the series of failures that has characterised drug development in this disease area

Cyclooxygenase 2-dependent and independent activation of Akt through casein kinase 2α contributes to human bladder cancer cell survival

<p>Abstract</p> <p>Background</p> <p>Survival rate for patients presenting muscle invasive bladder cancer is very low, and useful therapeutic target has not been identified yet. In the present study, new COX2 downstream signals involved in urothelial carcinoma cell survival were investigated <it>in vitro </it>and <it>in vivo</it>.</p> <p>Methods</p> <p>COX2 gene was silenced by siRNA transfection. Orthotopic implantation animal model and transurethral instillation of siRNA with atelocollagen was constructed to examine the effects of COX2 knockdown <it>in vivo</it>. Cell cycle was examined by flowcytoketry. Surgical specimens derived from patients with urinary bladder cancer (all were initially diagnosed cases) were used for immunohistochemical analysis of the indicated protein expression in urothelial carcinoma cells.</p> <p>Results</p> <p>Treatment with the COX2 inhibitor or knockdown of COX2 reduced expression of casein kinase (CK) 2 α, a phophorylated Akt and urokinase type plasminogen activator (uPA), resulting in p27 induction, cell cycle arrest at G1 phase and cell growth suppression in human urothelial carcinoma cell lines expressing COX2. Silencing of CK2α exhibited the similar effects. Even in UMUC3 cells lacking the COX2 gene, COX2 inhibition also inhibited cell growth through down-regulation of the CK2α-Akt/uPA axis. The mouse orthotropic bladder cancer model demonstrated that the COX2 inhibitor, meloxicam significantly reduced CK2α, phosphorylated Akt and uPA expression, whereas induced p27 by which growth and invasiveness of bladder cancer cells were strongly inhibited. Immunohistochemically, high expression of COX2, CK2α and phosphorylated form of Akt was found in high-grade, invasive carcinomas as well as carcinoma <it>in situ</it>, but not in low-grade and noninvasive phenotypes.</p> <p>Conclusions</p> <p>COX2-dependent and independent activation of CK2α-Akt/uPA signal is mainly involved in urothelial carcinoma cell survival, moreover, not only COX2 but also CK2α could be direct targets of COX2 inhibitors.</p

Factors affecting compliance with the measles vaccination schedule in a Brazilian city

CONTEXT AND OBJECTIVE: The success of vaccination campaigns depends on the degree of adherence to immunization initiatives and schedules. Risk factors associated with children's failure to receive the measles vaccine at the correct age were studied in the city of São Paulo, Brazil. DESIGN AND SETTING: Case-control and exploratory study, in the metropolitan area of São Paulo. METHODS: The caregivers of 122 children were interviewed regarding their perceptions and understanding about the measles vaccination and the disease. RESULTS: The results showed that age, region of residence, marital status and education level were unrelated to taking measles vaccines adequately. Most individuals remembered being informed about the last annual vaccination campaign by television, but no communication channel was significantly associated with vaccination status. The answers to questions about knowledge of the disease or the vaccine, when analyzed alone, were not associated with taking measles vaccinations at the time indicated by health agencies. The results showed that, when parents felt sorry for their children who were going to receive shots, they delayed the vaccination. Most of the children did not take the measles vaccination on the exactly recommended date, but delayed or anticipated the shots. CONCLUSION: It is clear that there is no compliance with the government's recommended measles vaccination schedule (i.e. first dose at nine and second at 15 months of age, as recommended in 1999 and 2000). Feeling sorry for the children receiving shots can delay vaccination taking

Density functional theory study of the multimode Jahn-Teller effect – ground state distortion of benzene cation

The multideterminental-DFT approach performed to analyze Jahn-Teller (JT) active molecules is described. Extension of this method for the analysis of the adiabatic potential energy surfaces and the multimode JT effect is presented. Conceptually a simple model, based on the analogy between the JT distortion and reaction coordinates gives further information about microscopic origin of the JT effect. Within the harmonic approximation the JT distortion can be expressed as a linear combination of all totally symmetric normal modes in the low symmetry minimum energy conformation, which allows calculating the Intrinsic Distortion Path, IDP, exactly from the high symmetry nuclear configuration to the low symmetry energy minimum. It is possible to quantify the contribution of different normal modes to the distortion, their energy contribution to the total stabilization energy and how their contribution changes along the IDP. It is noteworthy that the results obtained by both multideterminental-DFT and IDP methods for different classes of JT active molecules are consistent and in agreement with available theoretical and experimental values. As an example, detailed description of the ground state distortion of benzene cation is given

Pattern and determinants of BCG immunisation delays in a sub-Saharan African community

<p>Abstract</p> <p>Background</p> <p>Childhood immunisation is recognised worldwide as an essential component of health systems and an indispensable indicator of quality of care for vaccine-preventable diseases. While performance of immunisation programmes is more commonly measured by coverage, ensuring that every child is immunised at the earliest/appropriate age is an important public health goal. This study therefore set out to determine the pattern and predictors of Bacille de Calmette-Guérin (BCG) immunisation delays in the first three months of life in a Sub-Saharan African community where BCG is scheduled at birth in order to facilitate necessary changes in current policy and practices for improved services.</p> <p>Methods</p> <p>A cross-sectional study in which immunisation delays among infants aged 0-3 months attending community-based BCG clinics in Lagos, Nigeria over a 2-year period from July 2005 to June 2007 were assessed by survival analysis and associated factors determined by multivariable logistic regression. Population attributable risk (PAR) was computed for the predictors of delays.</p> <p>Results</p> <p>BCG was delayed beyond three months in 31.6% of all eligible infants. Of 5171 infants enrolled, 3380 (65.4%) were immunised within two weeks and a further 1265 (24.5%) by six weeks. A significantly higher proportion of infants born in hospitals were vaccinated in the first six weeks compared to those born outside hospitals. Undernourishment was predictive of delays beyond 2 and 6 weeks while treated hyperbilirubinaemia was associated with decreased odds for any delays. Lack of antenatal care and multiple gestations were also predictive of delays beyond 6 weeks. Undernourishment was associated with the highest PAR for delays beyond 2 weeks (18.7%) and 6 weeks (20.8%).</p> <p>Conclusions</p> <p>BCG immunisation is associated with significant delays in this setting and infants at increased risk of delays can be identified and supported early possibly through improved maternal uptake of antenatal care. Combining BCG with subsequent immunisation(s) at 6 weeks for infants who missed the BCG may be considered.</p