Interventions to Reduce Problems Related to the Readability and Comprehensibility of Drug Packages and Labels: A Systematic Review.

OBJECTIVE: The aim of the study was to evaluate the effectiveness of interventions designed to reduce problems with readability and comprehensibility in drug labels. METHODS: A systematic review of observational and experimental studies was conducted using MEDLINE (via PubMed), Embase, and Scopus databases. Two independent reviewers selected articles and collected data about study design, interventions, and outcomes. RESULTS: Of 1786 studies screened, 17 were included in this systematic review. The main findings were described according to the type of intervention in the drug package or label: color-coded labels (7 studies); changes in information layout (5 studies); changes in font size (3 studies); and interventions involving look-alike/sound-alike (LASA) drugs (3 studies). Color changes were important both for healthcare professionals to improve safety in hospital practice and for medication users to differentiate between the types of insulin. Layout changes were effective and included highlighting key information, such as medication name, dose, and instructions. Increased font size yielded good results in the recognition and identification of medications mainly for the population with impaired vision. This review was limited by the heterogeneity of interventions and populations studied, as well as the small number of high-quality studies, which prevented meta-analysis across any one intervention or outcome. CONCLUSIONS: All studies reported positive results for the proposed interventions. In the case of LASA drug names, the use of resources beyond Tall Man lettering (such as color and highlighting) reduced recognition errors, which may contribute to the development of new strategies to improve safety in the use of LASA drugs.

Users' preferences and perceptions of the comprehensibility and readability of medication labels.

OBJECTIVE: To evaluate the labeling preferences of medication users and characterize their perceptions of the comprehensibility and readability of medication labels. METHODS: We conducted a population-based cross-sectional study of medication users aged 18 years or older in 10 Brazilian capital cities. Perceptions of the comprehensibility and readability of medication labels in relation to sociodemographic characteristics were evaluated by Poisson regression models with robust variance. Labeling preferences were assessed through questions addressing possible improvements and through the use of digitally simulated packages. RESULTS: Of 6,255 medication users interviewed, more than half found it difficult or very difficult to read (50.8%) and/or understand (52.0%) medication labels. Difficulties were more pronounced for participants aged 40 years or older, with lower levels of education, and non-whites. Increasing the font size (93.7%), describing the indications for use (95.9%) and contraindications (95.6%) on the label, and highlighting the expiration date (96.3%) were the most widely accepted improvements. In the evaluation of simulated packages, users preferred factors that improved readability, such as increased font size, use of graphic elements and color to highlight the concentration of the active ingredient, and contrast between the font color and background. The new simulated package design, with increased font size, color to highlight the concentration and contrast between the font color and background, was preferred over the standard design by 77.0% of participants. CONCLUSION: Based on users' perceptions, increased font size and use of graphic elements and color to emphasize critical information, such as expiration date and concentration, are factors that contribute to making medication labels clearer to users. Pharmaceutical industries and policy makers should consider these items when developing labels and defining policies on this issue.

Mode of action of antimicrobial peptide P45 on Listeria monocytogenes.

The mode of action of an antimicrobial peptide produced by Bacillus sp. P45 isolated from the intestine of the Amazonian basin fish Piaractus mesopotamicus was investigated. The antimicrobial peptide was purified from culture supernatants by precipitation with ammonium sulfate and gel filtration chromatography. The peptide has an EC(50) of 300 AU (activity units) ml(-1) and kills all viable cells of Listeria monocytogenes with a concentration of 800 AU ml(-1). A decrease in OD was observed when L. monocytogenes cultures were treated with the peptide, suggesting that cells were lysed. Transmission electron microscopy showed damage of the cell envelope and loss of protoplasmic material. The peptide P45 was bactericidal and bacteriolytic to L. monocytogenes. There is evidence that the mode of action is interfering at cell membranes and the cell wall. The knowledge of the mode of action of antimicrobial peptides is an essential step to consider their utilization in food or clinic.

The effect of Lorenzo's oil on oxidative stress in X-linked adrenoleukodystrophy.

X-linked adrenoleukodystrophy (X-ALD) is a peroxisomal disorder biochemically characterized by the accumulation of very long chain fatty acids (VLCFA), particularly hexacosanoic acid (C(26:0)) and tetracosanoic acid (C(24:0)), in tissues and biological fluids. Although patients affected by this disorder predominantly present central and peripheral demyelination as well as adrenal insufficiency, the mechanisms underlying the brain damage in X-ALD are poorly known. The current treatment of X-ALD with glyceroltrioleate (C(18:1))/glyceroltrierucate (C(22:1)) (Lorenzo's oil, LO) combined with a VLCFA-poor diet normalizes VLCFA concentrations, but the neurological symptoms persist or even progress in symptomatic patients. Considering that free radical generation is involved in various neurodegenerative disorders and that in a previous study we showed evidence that oxidative stress is probably involved in the pathophysiology of X-ALD symptomatic patients, in the present study we evaluated various oxidative stress parameters, namely thiobarbituric acid reactive species (TBA-RS) and total antioxidant reactivity (TAR) in plasma, as well as the activities of the antioxidant enzymes catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) in erythrocytes from symptomatic and asymptomatic X-ALD patients and verified whether LO treatment and a VLCFA restricted diet could change these parameters. We observed a significant increase of plasma TBA-RS in symptomatic and asymptomatic X-ALD patients, reflecting induction of lipid peroxidation even before the disease was manifested. In addition, LO treatment did not alter this profile. Furthermore, plasma TAR measurement of X-ALD patients was not different from that of controls. Similarly, the antioxidant enzyme activities CAT, SOD and GPx were not altered in erythrocyte from X-ALD patients as compared to controls. We also examined the in vitro effects of hexacosanoic acid (C(26:0)) and tetracosanoic acid (C(24:0)) alone or combined with oleic (C(18:1))/erucic (C(22:1)) acids on various oxidative stress parameters in cerebral cortex of young rats, namely chemiluminescence, TBA-RS, TAR, CAT, SOD and GPx in order to investigate whether those fatty acids were able to induce oxidative stress. We found that there was a significant increase of TBARS and of chemiluminescence in rat cerebral cortex exposed to C(26:0)/C(24:0), and that the addition of C(18:1)and C(22:1) to the assays did not prevent this effect. Furthermore, TAR measurement was not altered by C(26:0) and C(24:0) acids in rat cerebral cortex. Taken together, our results indicate that lipid peroxidation occurs in X-ALD and that LO treatment does not attenuate or prevent free radical generation in these patients. Therefore, it may be presumed that antioxidants should be considered as an adjuvant therapy for X-ALD patients.

Detection of organic acidemias in Brazil.

BACKGROUND: Organic acidurias or organic acidemias are inherited metabolic disorders in which organic acids (carboxylic acids) accumulate in tissues and physiologic fluids of affected individuals. They are considered the most frequent metabolic disorders among severely ill children. Patients frequently present acute symptoms in early life. Metabolic acidosis and neurologic symptoms are the most common signs. METHODS: Urine specimens obtained from 1,926 children from January 1994 to July 2001 were used in analyses. Venous blood specimens were also collected from some patients. Samples were initially submitted to screening tests for detection of inborn errors of metabolism. Identification and semi-quantitation of organic acids in urine were performed by gas chromatography or gas chromatography coupled to mass spectrometry using capillary column (DB-5) and flame ionization detection. RESULTS: Ninety three (4.8%) cases of organic acidemias were diagnosed among 1,926 patients investigated from January 1994 to July 2001. Prompt therapy was instituted after diagnosis in a considerable number of patients and resulted in rapid improvement in their symptomatology, distinct from our previous cases diagnosed abroad where patients representing index cases died before any measure could be taken. CONCLUSIONS: Results demonstrate the importance of diagnosing organic acidurias in loco in developing countries despite implied extra costs.