Off-label drug use in an adult intensive care unit of a Brazilian hospital

Abstract The objective of this study was to determine the prevalence and describe the factors associated with off-label drug use in an adult intensive care unit (ICU) of a Brazilian hospital. An analytical, cross-sectional, prospective study was conducted in the adult ICU population from March 2018 to May 2018. Off-label use of medication was classified by indication, dosage, route of administration, type and volume of diluent, and duration of administration. Most patients were female (57.89%), non-elderly (56.14%), and had a mean age of 54.44 ± 17.15 years. The prevalence of off-label drug use was 70.31%, but was not associated with the clinical severity of the patients. A statistically significant association was observed between label use of drugs and prescribing potentially inappropriate medicines (PIM). The most common reasons for off-label drug use were therapeutic indication (19.58%) and volume of diluent (23.30%). Drug administration by enteral tubes accounted for the largest number of off-label uses due to route of administration (90.85%). There was a higher prevalence of off-label use of systemic antimicrobials (14.44%) and norepinephrine (9.28%). Our study provided a broad characterization of off-label drug use in an adult ICU and showed why it is important for health professionals to evaluate the specific risks and benefits of this practice

Potentially inappropriate medications in older kidney transplant recipients: a Brazilian prevalence study.

Background Older kidney transplant recipients take a larger number of medications than younger patients, but there is currently no evidence that this affects health outcomes or that is it associated with potentia medicine-related problems. Objective To evaluate the prevalence and number of potentially inappropriate medications in older kidney transplant recipients and also the possible associated factors (sex, age, comorbidities, number of medications, etc.). Setting A renal post-transplant ambulatory outpatient clinic of a university hospital in Fortaleza, Brazil. Method PIMs were defined according to the Beers criteria, version 2015. Medications were classified following the Anatomical Therapeutic Chemical Classification System. Chi squared tests and analysis of variance were used for the analyses. Main outcome measure Prevalence of potentially inappropriate medications and medication groups with higher prevalence rates of PIMs, including associated factors. Results Among 143 kidney transplant recipients, 77.6% had at least one potentially inappropriate medication as part of their prescription regime. Medication groups that were most implicated in PIM are medicines that act on the alimentary tract and metabolism (55.9%), cardiovascular system (32.2%) and nervous system (21.7%). We detected a high prevalence (63.6%) of self-medication (use of OTC medicines without indication of a healthcare professional) among the population studied. There was a statistically significant association between the number of prescribed medications and the presence of potentially inappropriate medication in the prescription regime (P < 0.01). Conclusion Our data draw attention to the need of medicine therapy management by clinical pharmacists and clinicians in this group of patients and also assessing the real clinical impacts of these medications in the prescription regimes of elderly renal transplant patients.

Molecular characterization of virulence and antimicrobial resistance profile of Shigella species isolated from children with moderate to severe diarrhea in northeastern Brazil.

Molecular characterization of virulence and antimicrobial resistance profiles were determined for Shigella species isolated from children with diarrhea in Fortaleza, Brazil. Fecal specimens were collected along with socioeconomic and clinical data from children with moderate to severe diarrhea requiring emergency care. Shigella spp. were isolated by standard microbiological techniques, and we developed 4 multiplex polymerase chain reaction assays to detect 16 virulence-related genes (VRGs). Antimicrobial susceptibility tests were performed using disk diffusion assays. S. flexneri and S. sonnei were the predominant serogroups. S. flexneri was associated with low monthly incomes; more severe disease; higher number of VRGs; and presence of pic, set, and sepA genes. The SepA gene was associated with more intense abdominal pain. S. flexneri was correlated with resistance to ampicillin and chloramphenicol, whereas S. sonnei was associated with resistance to azithromycin. Strains harboring higher numbers of VRGs were associated with resistance to more antimicrobials. We highlight the correlation between presence of S. flexneri and sepA, and increased virulence and suggest a link to socioeconomic change in northeastern Brazil. Additionally, antimicrobial resistance was associated with serogroup specificity in Shigella spp. and increased bacterial VRGs.

Vitamin E ameliorates high dose trans-dehydrocrotonin-associated hepatic damage in mice.

trans-Dehydrocrotonin (t-DCTN), the diterpenoid from Croton cajucara Bentham, exhibits hypoglycemic and hypolipidemic activities, but in high doses is associated with a discrete hepatotoxicity. In the search for measures to mitigate this, pretreatment with the antioxidants N-acetylcysteine and vitamin E has been examined. Mice that received a high dose t-DCTN (100 mg/kg) manifested hepatic damage, as evidenced by significant elevations in serum ALT and AST, and hepatic GSH, and histological alterations, which could be obliterated by pretreatment with vitamin E, but not with N-acetylcysteine, possibly by creating an effective antioxidant balance.

Investigação farmacológica dos mecanismos de ação gastroenteroprotetors do ácido centipédico, um diterpeno de Egletes viscosa Less., em modelos experimentais [manuscrito] / Pharmacological investigation of the mechanisms of action of gastroenteroprotetors centipédico acid, a diterpene Egletes viscous Less., in experimental models [manuscript]

Ácido Centipédico (AC), um diterpeno isolado Egletes viscosa Less. (Asteraceae) foi avaliado em modelos experimentais de lesão gástrica aguda e crônica, e, em modelo de lesão intestinal. AC (50 e 100 mg/kg, v.o.) atenuou significativamente as lesões gástricas induzidas por etanol (53 e 79% de inibição). Na dose de 50 mg/kg mostrou envolvimento do óxido nítrico, prostaglandinas, canais de potássio ATP-dependente, mas de receptores TRPV1. O diterpeno diminuiu significativamente a depleção dos grupos sulfidrilas não-proteicos e SOD e diminuiu a formação de MDA, associados à administração de etanol. AC aumentou ainda os níveis de muco gástrico. No modelo de etanol acidificado AC (50 e 100 mg/kg, v.o.) e lansoprazol (30 mg/kg, v.o.) atenuaram significativamente as lesões gástricas...

Gastroprotective mechanisms of centipedic acid, a natural diterpene from Egletes viscosa LESS.

This study was aimed to clarify the mechanisms of gastroprotection by centipedic acid (CPA), a natural diterpene from Egletes viscosa LESS. (Asteraceae) using ethanol-induced gastric mucosal damage in mice and gastric secretion in 4-h pylorus-ligated rats as model systems. In mice, intragastrically administered CPA (25, 50, 100 mg/kg) greatly reduced the mucosal lesions induced by 96% ethanol (0.2 ml, p.o.) by 18, 53, and 79%, respectively, whereas N-acetylcysteine (NAC, 300 mg/kg, i.p.), the reference compound produced a 50% inhibition. In 4-h pylorus-ligated rats, CPA (50 mg/kg) applied intraduodenally decreased both gastric secretory volume and total acidity. Similar to NAC, the plant diterpene effectively prevented the ethanol associated decrease in non-proteic sulfhydryls (NP-SH) and the elevated thiobarbituric acid-reactive substances (TBARS) in gastric tissue, suggesting that these compounds exert an antioxidant effect. Pretreatment of mice with indomethacin, the cyclooxygenase inhibitor but not with capsazepine, the transient receptor potential vanilloid-1 (TRPV1)-receptor antagonist greatly suppressed the gastroprotective effect of CPA. Furthermore, CPA gastroprotection was significantly attenuated in mice pretreated with L-NAME or glibenclamide the respective inhibitors of nitric oxide synthase and K(+)(ATP) channel activation. These data suggest that CPA affords gastroprotection by different and complementary mechanisms, which include a sparing effect on NP-SH reserve, and roles for endogenous prostaglandins, nitric oxide, and TRPV1-receptor and K(+)(ATP) channel activation.