Promoting adverse drug reaction reporting: comparison of different approaches

ABSTRACT OBJECTIVE To describe different approaches to promote adverse drug reaction reporting among health care professionals, determining their cost-effectiveness. METHODS We analyzed and compared several approaches taken by the Northern Pharmacovigilance Centre (Portugal) to promote adverse drug reaction reporting. Approaches were compared regarding the number and relevance of adverse drug reaction reports obtained and costs involved. Costs by report were estimated by adding the initial costs and the running costs of each intervention. These costs were divided by the number of reports obtained with each intervention, to assess its cost-effectiveness. RESULTS All the approaches seem to have increased the number of adverse drug reaction reports. We noted the biggest increase with protocols (321 reports, costing 1.96 € each), followed by first educational approach (265 reports, 20.31 €/report) and by the hyperlink approach (136 reports, 15.59 €/report). Regarding the severity of adverse drug reactions, protocols were the most efficient approach, costing 2.29 €/report, followed by hyperlinks (30.28 €/report, having no running costs). Concerning unexpected adverse drug reactions, the best result was obtained with protocols (5.12 €/report), followed by first educational approach (38.79 €/report). CONCLUSIONS We recommend implementing protocols in other pharmacovigilance centers. They seem to be the most efficient intervention, allowing receiving adverse drug reactions reports at lower costs. The increase applied not only to the total number of reports, but also to the severity, unexpectedness and high degree of causality attributed to the adverse drug reactions. Still, hyperlinks have the advantage of not involving running costs, showing the second best performance in cost per adverse drug reactions report.

Plasmodium falciparum drug resistance in Angola

Facing chloroquine drug resistance, Angola promptly adopted artemisinin-based combination therapy as the first-line to treat malaria. Currently, the country aims to consolidate malaria control, while preparing for the elimination of the disease, along with others African countries in the region. However, the remarkable capacity of Plasmodium to develop drug resistance represents an alarming threat for those achievements. Herein, the available, but relatively scarce and dispersed, information on malaria drug resistance in Angola, is reviewed and discussed. The review aims to inform but also to encourage future research studies that monitor and update the information on anti-malarial drug efficacy and prevalence of molecular markers of drug resistance, key fields in the context and objectives of elimination.

Nonlinear dynamics of the patient’s response to drug effect during general anesthesia

In today’s healthcare paradigm, optimal sedation during anesthesia plays an important role both in patient welfare and in the socio-economic context. For the closed-loop control of general anesthesia, two drugs have proven to have stable, rapid onset times: propofol and remifentanil. These drugs are related to their effect in the bispectral index, a measure of EEG signal. In this paper wavelet time–frequency analysis is used to extract useful information from the clinical signals, since they are time-varying and mark important changes in patient’s response to drug dose. Model based predictive control algorithms are employed to regulate the depth of sedation by manipulating these two drugs. The results of identification from real data and the simulation of the closed loop control performance suggest that the proposed approach can bring an improvement of 9% in overall robustness and may be suitable for clinical practice.

Optimizing potentiometric ionophore and electrode design for environmental on-site control of antibiotic drugs: Application to sulfamethoxazole

Potentiometric sensors are typically unable to carry out on-site monitoring of environmental drug contaminants because of their high limits of detection (LODs). Designing a novel ligand material for the target analyte and managing the composition of the internal reference solution have been the strategies employed here to produce for the first time a potentiometric-based direct reading method for an environmental drug contaminant. This concept has been applied to sulfamethoxazole (SMX), one of the many antibiotics used in aquaculture practices that may occur in environmental waters. The novel ligand has been produced by imprinting SMX on the surface of graphitic carbon nanostructures (CN) < 500 nm. The imprinted carbon nanostructures (ICN) were dispersed in plasticizer and entrapped in a PVC matrix that included (or not) a small amount of a lipophilic additive. The membrane composition was optimized on solid-contact electrodes, allowing near-Nernstian responses down to 5.2 μg/mL and detecting 1.6 μg/mL. The membranes offered good selectivity against most of the ionic compounds in environmental water. The best membrane cocktail was applied on the smaller end of a 1000 μL micropipette tip made of polypropylene. The tip was then filled with inner reference solution containing SMX and chlorate (as interfering compound). The corresponding concentrations were studied for 1 × 10−5 to 1 × 10−10 and 1 × 10−3 to 1 × 10−8 mol/L. The best condition allowed the detection of 5.92 ng/L (or 2.3 × 10−8 mol/L) SMX for a sub-Nernstian slope of −40.3 mV/decade from 5.0 × 10−8 to 2.4 × 10−5 mol/L.

Nonlinear dynamics of the patient’s response to drug effect during general anesthesia

In today’s healthcare paradigm, optimal sedation during anesthesia plays an important role both in patient welfare and in the socio-economic context. For the closed-loop control of general anesthesia, two drugs have proven to have stable, rapid onset times: propofol and remifentanil. These drugs are related to their effect in the bispectral index, a measure of EEG signal. In this paper wavelet time–frequency analysis is used to extract useful information from the clinical signals, since they are time-varying and mark important changes in patient’s response to drug dose. Model based predictive control algorithms are employed to regulate the depth of sedation by manipulating these two drugs. The results of identification from real data and the simulation of the closed loop control performance suggest that the proposed approach can bring an improvement of 9% in overall robustness and may be suitable for clinical practice.

Physical therapy with drug treatment in bell palsy: a focused review

ABSTRACT: The physical therapy (PT) associated with standard drug treatment (SDT) in Bell palsy has never been investigated. Randomized controlled trials or quasirandomized controlled trials have compared facial PT (except treatments such as acupuncture and osteopathic) combined with SDT against a control group with SDT alone. Participants included those older than 15 yrs with a clinical diagnosis of Bell palsy, and the primary outcome measure was motor function recovery by the House-Brackmann scale. The methodologic quality of each study was also independently assessed by two reviewers using the PEDro scale. Four studies met the inclusion criteria. Three trials indicate that PT in association with SDT supports higher motor function recovery than SDT alone between 15 days and 1 yr of follow-up. On the other hand, one trial showed that electrical stimulation added to conventional PT with SDT did not influence treatment outcomes. The present review suggests that the current practice of Bell palsy treatment by PT associated with SDT seems to have a positive effect on grade and time recovery compared with SDT alone. However, there is very little quality evidence from randomized controlled trials, and such evidence is insufficient to decide whether combined treatment is beneficial in the management of Bell palsy.

Anti-Tumor Necrosis Factor Alpha-Induced Drug Eruptions: One Patient, More Than a Pattern

Background: Tumor necrosis factor alpha (TNFα) antagonists are effective in treating several immune-inflammatory diseases, including psoriasis and inflammatory bowel disease. The paradoxical and unpredictable induction of psoriasis and psoriasiform skin lesions is a recognized adverse event, although of unclear aetiology. However, histological analysis of these eruptions remains insufficient, yet suggesting that some might constitute a new pattern of adverse drug reaction, rather than true psoriasis. Case report: The authors report the case of a 43-year-old woman with severe recalcitrant Crohn disease who started treatment with infliximab. There was also a personal history of mild plaque psoriasis without clinical expression for the past eight years. She developed a heterogeneous cutaneous eruption of psoriasiform morphology with pustules and crusts after the third infliximab infusion. The histopathological diagnosis was of a Sweet-like dermatosis. The patient was successfully treated with cyclosporine in association with both topical corticosteroid and vitamin D3 analogue. Three weeks after switching to adalimumab a new psoriasiform eruption was observed, histologically compatible with a psoriasiform drug eruption. Despite this, and considering the beneficial effect on the inflammatory bowel disease, it was decided to maintain treatment with adalimumab and to treat through with topicals, with progressive control of skin disease. Discussion: Not much is known about the pathogenesis of psoriasiform eruptions induced by biological therapies, but genetic predisposition and Koebner phenomenon may contribute to it. Histopathology can add new facets to the comprehension of psoriasiform reactions. In fact, histopathologic patterns of such skin lesions appear to be varied, in a clear asymmetry with clinical findings. Conclusion: The sequential identification in the same patient of two clinical and histopathologic patterns of drug reaction to TNFα antagonists is rare. Additionally, to the authors’ knowledge, there is only one other description in literature of a TNFα antagonist-induced Sweet-like dermatosis, emphasizing the singularity of this case report.

CHEMOPROPHYLAXIS TO CONTROL LEPROSY AND THE PERSPECTIVE OF ITS IMPLEMENTATION IN BRAZIL: A PRIMER FOR NON-EPIDEMIOLOGISTS

The occurrence of leprosy has decreased in the world but the perspective of its elimination has been questioned. A proposed control measure is the use of post-exposure chemoprophylaxis (PEP) among contacts, but there are still questions about its operational aspects. In this text we discuss the evidence available in literature, explain some concepts in epidemiology commonly used in the research on this topic, analyze the appropriateness of implementing PEP in the context of Brazil, and answer a set of key questions. We argue some points: (1) the number of contacts that need to receive PEP in order to prevent one additional case of disease is not easy to be generalized from the studies; (2) areas covered by the family health program are the priority settings where PEP could be implemented; (3) there is no need for a second dose; (4) risk for drug resistance seems to be very small; (5) the usefulness of a serological test to identify a higher risk group of individuals among contacts is questionable. Given that, we recommend that, if it is decided to start PEP in Brazil, it should start on a small scale and, as new evidence can be generated in terms of feasibility, sustainability and impact, it could move up a scale, or not, for a wider intervention.

Nevirapine in an animal model of pre-diabetes: study of drug pharmacokinetic and its effects on fasting glycemia and insulin resistance

Dissertação para obtenção do Grau de Mestre em Biotecnologia

Risky behavior regarding drug use and HIV infection: an Internet questionnaire coupled with short education texts for Portuguese speakers

Surveys of risky behavior relating to HIV/AIDS are generally made for groups at risk of infection, for which HIV/AIDS prevalence is usually expected to be higher than in the general population. Therefore, an educational homepage in Portuguese was created on the Internet to inform/ask internauts regarding knowledge and behavior. The internauts were classified as adolescents (13 to 25 years) and adults (>25 years). The number of STDs was reported as 1. 8 ± 2. 6 infections (range: 1 to 20 infections); 43% used condoms during sexual intercourse. Alcohol consumption was reported by 63% and illicit drug use by 32% (marijuana 24% and inhalants 15%). Among the adolescents, 31% did not classified alcohol as a drug. The adults more frequently reported homosexuality, anal intercourse and STDs, although the adolescents also presented high rates of risky behavior. These results show the need to reach out to internauts through better control strategies. Different types of strategies must be encouraged, in order to reach people that use this means of communication and entertainment.

Drug resistance of Mycobacterium tuberculosis strains in southern Brazil

INTRODUCTION: The aim of this work was to evaluate the prevalence of Mycobacterium tuberculosis (MT) strains with mutations that could result in resistance to the main drugs used in treatment in a region with one of the highest numbers of tuberculosis (TB) cases in southern Brazil. METHODS: Deoxyribonucleic acid (DNA) from 120 sputum samples from different patients suspicious of pulmonary tuberculosis who attended the Municipal Public Laboratory for Mycobacterium sp. diagnosis was directly amplified and analyzed by PCR-SSCP. The DNA was amplified in known hotspot mutation regions of the genes rpoB, ahpC, embB, katG, inhA, and pncA. RESULTS: The percentage of samples positive by culture was 9.2% (11/120); 5% (6/120) were positive by bacilloscopy and MT-PCR, and DNA fragments of the aforementioned resistance genes could be amplified from seven (7) of the eleven (11) samples with positive results, either by culture or PCR/bacilloscopy. All presented a SSCP pattern similar to a native, nonresistant genotype, with the ATCC strain 25177 as control, except for one sample (0.01%), which presented a SSCP profile demonstrating mutation at the embB gene. CONCLUSIONS: These results are consistent with the empirical observations by physicians treating TB patients in our region of a low occurrence of cases that are refractory to conventional treatment schemes, in contrast to other parts of the country. Continued surveillance, especially molecular, is essential to detect and monitor the outbreak of MT-resistant strains.

Improving tuberculosis control through the partnership between university and the health system

INTRODUCTION: Tuberculosis (TB) control is linked to the availability of qualified methods for microbiological diagnostics; however, microscopy with limited sensitivity is the only method available in many locations. The objective of this study was to evaluate the introduction of culture, drug susceptibility testing (DST), and genotyping in the routine of a Municipal Program of Tuberculosis Control. METHODS: Direct microscopy of sputum and culture in Ogawa-Kudoh were performed on 1,636 samples from 787 patients. DST of positive cultures was performed by resazurin microtiter assay and genotyping by mycobacterial interspersed repetitive units-variable number tandem repeat. RESULTS: A total 91 patients with TB were identified. The culture increased case detection by 32% compared with the microscopy; acquired resistance was 3.3% and the genotyping showed high genetic diversity. CONCLUSIONS: Ogawa-Kudoh contributed significantly to the increase in case detection and is suitable for implementation in poor-resource locations. The acquired resistance rate was lower than that reported in a recent Brazilian survey. The high genetic diversity is possibly related to the high TB prevalence in the population, as well as to early detection and suitable treatment of patients. The interaction between research and health care is important for reorienting the practice, transferring technology, and improving TB control.

Primary multidrug-resistant tuberculosis and its control implications in the State of Amazonas, Brazil: report of 3 cases

The occurrence of tuberculosis with first-line multidrug resistance leads to the use of alternative medications, often at higher costs, longer treatment periods, and greater clinical complexity. Here, we report 3 patients with multidrug-resistant tuberculosis. One patient with human immunodeficiency virus died before the sensitivity test was performed. The early diagnosis of multidrug-resistant tuberculosis and appropriate treatment should be priorities of the National Tuberculosis Control Program in order to break the chain of transmission. In addition, the possibility of substituting the proportion method with more modern and faster techniques should be urgently evaluated.

Environmental isolation, biochemical identification, and antifungal drug susceptibility of Cryptococcus species

Introduction The incidence of opportunistic fungal infections has increased in recent years and is considered an important public health problem. Among systemic and opportunistic mycoses, cryptococcosis is distinguished by its clinical importance due to the increased risk of infection in individuals infected by human immunodeficiency virus. Methods To determine the occurrence of pathogenic Cryptococcus in pigeon excrement in the City of Araraquara, samples were collected from nine environments, including state and municipal schools, abandoned buildings, parks, and a hospital. The isolates were identified using classical tests, and susceptibility testing for the antifungal drugs (fluconazole, itraconazole, voriconazole, and amphotericin B) independently was also performed. After collection, the excrement samples were plated on Niger agar and incubated at room temperature. Results A total of 87 bird dropping samples were collected, and 66.6% were positive for the genus Cryptococcus. The following species were identified: Cryptococcus neoformans (17.2%), Cryptococcus gattii (5.2%), Cryptococcus ater (3.5%), Cryptococcus laurentti (1.7%), and Cryptococcus luteolus (1.7%). A total of 70.7% of the isolates were not identified to the species level and are referred to as Cryptococcus spp. throughout the manuscript. Conclusions Although none of the isolates demonstrated resistance to antifungal drugs, the identification of infested areas, the proper control of birds, and the disinfection of these environments are essential for the epidemiological control of cryptococcosis.

A novel hanging spherical drop system for the generation of cellular spheroids and high throughput combinatorial drug screening

We propose a novel hanging spherical drop system for anchoring arrays of droplets of cell suspension based on the use of biomimetic superhydrophobic flat substrates, with controlled positional adhesion and minimum contact with a solid substrate. By facing down the platform, it was possible to generate independent spheroid bodies in a high throughput manner, in order to mimic in vivo tumour models on the lab-on-chip scale. To validate this system for drug screening purposes, the toxicity of the anti-cancer drug doxorubicin in cell spheroids was tested and compared to cells in 2D culture. The advantages presented by this platform, such as feasibility of the system and the ability to control the size uniformity of the spheroid, emphasize its potential to be used as a new low cost toolbox for high-throughput drug screening and in cell or tissue engineering.