Incidence and Predictors of Adverse Drug Reactions Caused by Drug-Drug Interactions in Elderly Outpatients: A Prospective Cohort Study

Purpose. The primary objective of this study was to investigate the incidence of drug-drug interactions (DDIs) related to adverse drug reactions (ADRs) in elderly outpatients who attended public primary healthcare units in a southeastern region of Brazil. The secondary objective was to investigate the possible predictors of DDI-related ADRs. Methods. A prospective cohort study was conducted between November 1, 2010, and November 31, 2011, in the primary public healthcare system in the Ourinhos micro-region in Brazil. Patients who were at least 60 years old, with at least one potential DDI, were eligible for inclusion in the study. Eligible patients were assessed by clinical pharmacists for DDI-related ADRs for 4 months. The causality of DDI-related ADRs was assessed independently by four clinicians using three decisional algorithms. The incidence of DDI-related ADRs during the study period was calculated. Logistic regression analysis was used to study DDI-related ADR predictors. Results. A total of 433 patients completed the study. The incidence of DDI-related ADRs was 6.5%. A multivariate analysis indicated that the adjusted odds ratios (ORs) rose from 0.91 (95% confidence interval [CI] = 0.75-1.12, p = 0.06) in patients aged 65-69 years to 4.40 (95% CI = 3.00-6.12, p < 0.01) in patients aged 80 years or older. Patients who presented two to three diagnosed diseases presented lower adjusted ORs (OR = 0.93 [95% CI = 0.68-1.18, p = 0.08]) than patients who presented six or more diseases (OR = 1.12 [95% CI = 1.02-2.01, p < 0.01]). Elderly patients who took five or more drugs had a significantly higher risk of DDI-related ADRs (OR = 2.72 [95% CI = 1.92-3.12, p < 0.01]) than patients who took three to four drugs (OR = 0.93 [95% CI = 0.74-1.11, p = 0.06]). No significant difference was found with regard to sex (OR = 1.08 [95% CI 0.48-2.02, p = 0.44]). Conclusion. The incidence of DDI-related ADRs in elderly outpatients was significant, and most of the events presented important clinical consequences. Because clinicians still have difficulty managing this problem, highlighting the factors that increase the risk of DDI-related ADRs is essential. Polypharmacy was found to be a significant predictor of DDI-related ADRs in our sample.

Incomplete fissures in severe emphysematous patients evaluated with MDCT: Incidence and interobserver agreement among radiologists and pneumologists

Objective: Pulmonary fissures completeness predicts efficacy in endobronchial valves (EBV) implantation, a new lobar volume reduction therapy for severe emphysematous patients. We assessed the incidence of incomplete fissures and the interobserver agreement in its evaluation with MDCT, in severe emphysematous patients prior to EBV implantation. Materials and Methods: Volumetric thin-section CT scans of 35 patients (CODP GOLD 3/4, heterogeneous emphysema) were retrospectively reviewed by 2 pneumologists, 1 general and 2 experienced chest radiologists, independently and blinded for treatment outcome, and the pulmonary fissures were classified as either complete or incomplete. Interobserver agreement was assessed with Kappa index (KI). Results: Agreement between all readers for the left oblique, right oblique and horizontal fissure was, respectively, moderate (KI = 0.53), fair (KI = 0.37) and moderate (KI = 0.42). Highest agreement (99/105 fissures) was observed among experienced radiologists, being for left oblique, right oblique and horizontal, respectively, almost perfect (KI = 0.79), perfect (KI = 1.0) and moderate (KI = 0.52). These 2 reviewers found that all of 35 patients had at least one incomplete fissure, with a proportion of incomplete fissures assigned as 74/65%, 85/85% and 91/88%, respectively for the left oblique, right oblique and horizontal fissures. Conclusions: Pneumologists and radiologists agreed fairly to moderately in fissures analysis, while the experienced chest radiologists reached the highest clinically adequate agreement of 94%. We believe that clinical routine visual analysis of the fissures integrity can be done with a good degree of confidence in MDCT images, and experienced readers might be required. Also, a higher than expected incidence of incomplete fissures was described in our studied population. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

Models of passive and active dendrite motoneuron pools and their differences in muscle force control

Motoneuron (MN) dendrites may be changed from a passive to an active state by increasing the levels of spinal cord neuromodulators, which activate persistent inward currents (PICs). These exert a powerful influence on MN behavior and modify the motor control both in normal and pathological conditions. Motoneuronal PICs are believed to induce nonlinear phenomena such as the genesis of extra torque and torque hysteresis in response to percutaneous electrical stimulation or tendon vibration in humans. An existing large-scale neuromuscular simulator was expanded to include MN models that have a capability to change their dynamic behaviors depending on the neuromodulation level. The simulation results indicated that the variability (standard deviation) of a maintained force depended on the level of neuromodulatory activity. A force with lower variability was obtained when the motoneuronal network was under a strong influence of PICs, suggesting a functional role in postural and precision tasks. In an additional set of simulations when PICs were active in the dendrites of the MN models, the results successfully reproduced experimental results reported from humans. Extra torque was evoked by the self-sustained discharge of spinal MNs, whereas differences in recruitment and de-recruitment levels of the MNs were the main reason behind torque and electromyogram (EMG) hysteresis. Finally, simulations were also used to study the influence of inhibitory inputs on a MN pool that was under the effect of PICs. The results showed that inhibition was of great importance in the production of a phasic force, requiring a reduced co-contraction of agonist and antagonist muscles. These results show the richness of functionally relevant behaviors that can arise from a MN pool under the action of PICs.

Spatial analysis of leprosy incidence and associated socioeconomic factors

OBJECTIVE: To identify clusters of the major occurrences of leprosy and their associated socioeconomic and demographic factors. METHODS: Cases of leprosy that occurred between 1998 and 2007 in Sao Jose do Rio Preto (southeastern Brazil) were geocodified and the incidence rates were calculated by census tract. A socioeconomic classification score was obtained using principal component analysis of socioeconomic variables. Thematic maps to visualize the spatial distribution of the incidence of leprosy with respect to socioeconomic levels and demographic density were constructed using geostatistics. RESULTS: While the incidence rate for the entire city was 10.4 cases per 100,000 inhabitants annually between 1998 and 2007, the incidence rates of individual census tracts were heterogeneous, with values that ranged from 0 to 26.9 cases per 100,000 inhabitants per year. Areas with a high leprosy incidence were associated with lower socioeconomic levels. There were identified clusters of leprosy cases, however there was no association between disease incidence and demographic density. There was a disparity between the places where the majority of ill people lived and the location of healthcare services. CONCLUSIONS: The spatial analysis techniques utilized identified the poorer neighborhoods of the city as the areas with the highest risk for the disease. These data show that health departments must prioritize politico-administrative policies to minimize the effects of social inequality and improve the standards of living, hygiene, and education of the population in order to reduce the incidence of leprosy.

The impact of atmospheric particulate matter on cancer incidence and mortality in the city of São Paulo, Brazil

This study aimed to verify the impact of inhalable particulate matter (PM10) on cancer incidence and mortality in the city of São Paulo, Brazil. Statistical techniques were used to investigate the relationship between PM10 on cancer incidence and mortality in selected districts. For some types of cancer (skin, lung, thyroid, larynx, and bladder) and some periods, the correlation coefficients ranged from 0.60 to 0.80 for incidence. Lung cancer mortality showed more correlations during the overall period. Spatial analysis showed that districts distant from the city center showed higher than expected relative risk, depending on the type of cancer. According to the study, urban PM10 can contribute to increased incidence of some cancers and may also contribute to increased cancer mortality. The results highlight the need to adopt measures to reduce atmospheric PM10 levels and the importance of their continuous monitoring.

Effect of rearing technique over skeletal deformities incidence and osteological development in red porgy Pagrus pagrus (Linnaeus, 1758) larvae

[EN]Red porgy is a candidate species for marine aquaculture diversification.The objective of the present study was to describe the osteological development and the occurrence of skeletal deformities in Pagrus pagrus larvae in relation to the intensification of the rearing system. Fish samples were periodically collected along the development from hatching to juveniles (95days after hatching). Osteological development and the presence of skeleton abnormalities were evaluated. X-ray studies revealed a high number of fish (Semi-intensive:38.8%; Intensive:46.5 %) with skeletal deformities. No significant interaction was found on the incidence of lordosis and fused vertebrae with the rearing tecnique. However, cranial abnormalities and kyphosis incidences were significantly higher in intensive system cultured red porgy. Also, the position of fused vertebrae in this fish was located mainly in the caudal area instead of pre-hemal area for semi-intensive system reared red porgy. Present results, suggest a relationship among feeding sequence, osteological development and deformity incidence and location in red porgy larvae

Statistical Mechanics of Monomer-Dimer Models on Complete and Erdös-Rényi Graphs

Nella tesi sono trattate due famiglie di modelli meccanico statistici su vari grafi: i modelli di spin ferromagnetici (o di Ising) e i modelli di monomero-dimero. Il primo capitolo è dedicato principalmente allo studio del lavoro di Dembo e Montanari, in cui viene risolto il modello di Ising su grafi aleatori. Nel secondo capitolo vengono studiati i modelli di monomero-dimero, a partire dal lavoro di Heilemann e Lieb,con l'intento di dare contributi nuovi alla teoria. I principali temi trattati sono disuguaglianze di correlazione, soluzioni esatte su alcuni grafi ad albero e sul grafo completo, la concentrazione dell'energia libera intorno al proprio valor medio sul grafo aleatorio diluito di Erdös-Rényi.

Essays on the Empirical Analysis of Economic and Political Development in Sub-Saharan Africa

In Sub-Saharan Africa, non-democratic events, like civil wars and coup d'etat, destroy economic development. This study investigates both domestic and spatial effects on the likelihood of civil wars and coup d'etat. To civil wars, an increase of income growth is one of common research conclusions to stop wars. This study adds a concern on ethnic fractionalization. IV-2SLS is applied to overcome causality problem. The findings document that income growth is significant to reduce number and degree of violence in high ethnic fractionalized countries, otherwise they are trade-off. Income growth reduces amount of wars, but increases its violent level, in the countries with few large ethnic groups. Promoting growth should consider ethnic composition. This study also investigates the clustering and contagion of civil wars using spatial panel data models. Onset, incidence and end of civil conflicts spread across the network of neighboring countries while peace, the end of conflicts, diffuse only with the nearest neighbor. There is an evidence of indirect links from neighboring income growth, without too much inequality, to reduce the likelihood of civil wars. To coup d'etat, this study revisits its diffusion for both all types of coups and only successful ones. The results find an existence of both domestic and spatial determinants in different periods. Domestic income growth plays major role to reduce the likelihood of coup before cold war ends, while spatial effects do negative afterward. Results on probability to succeed coup are similar. After cold war ends, international organisations seriously promote democracy with pressure against coup d'etat, and it seems to be effective. In sum, this study indicates the role of domestic ethnic fractionalization and the spread of neighboring effects to the likelihood of non-democratic events in a country. Policy implementation should concern these factors.

Multidimensional item response theory models with general and specific latent traits for ordinal data

The aim of the thesis is to propose a Bayesian estimation through Markov chain Monte Carlo of multidimensional item response theory models for graded responses with complex structures and correlated traits. In particular, this work focuses on the multiunidimensional and the additive underlying latent structures, considering that the first one is widely used and represents a classical approach in multidimensional item response analysis, while the second one is able to reflect the complexity of real interactions between items and respondents. A simulation study is conducted to evaluate the parameter recovery for the proposed models under different conditions (sample size, test and subtest length, number of response categories, and correlation structure). The results show that the parameter recovery is particularly sensitive to the sample size, due to the model complexity and the high number of parameters to be estimated. For a sufficiently large sample size the parameters of the multiunidimensional and additive graded response models are well reproduced. The results are also affected by the trade-off between the number of items constituting the test and the number of item categories. An application of the proposed models on response data collected to investigate Romagna and San Marino residents' perceptions and attitudes towards the tourism industry is also presented.

Statistical mechanics of polymer models: rigorous results and applications

Monomer-dimer models are amongst the models in statistical mechanics which found application in many areas of science, ranging from biology to social sciences. This model describes a many-body system in which monoatomic and diatomic particles subject to hard-core interactions get deposited on a graph. In our work we provide an extension of this model to higher-order particles. The aim of our work is threefold: first we study the thermodynamic properties of the newly introduced model. We solve analytically some regular cases and find that, differently from the original, our extension admits phase transitions. Then we tackle the inverse problem, both from an analytical and numerical perspective. Finally we propose an application to aggregation phenomena in virtual messaging services.

Injection drug use before and after liver transplantation: a retrospective multicenter analysis on incidence and outcome

Injecting drug use (IDU) before and after liver transplantation (LT) is poorly described. The aim of this study was to quantify relapse and survival in this population and to describe the causes of mortality after LT.