Correction: Risk factors for drug-related problems in a general hospital: A large prospective cohort.

[This corrects the article DOI: 10.1371/journal.pone.0230215.].

Nonadherence to Immunosuppressant Therapy of Kidney Transplant Candidate Patients: External Validation of the KATITA-25 Scale.

BACKGROUND: The self-administered Kidney AlloTransplant Immunosuppressive Therapy Adherence (KATITA-25) questionnaire is a multidimensional scale for use in the pretransplant setting that evaluates the predisposition to nonadherence of patients who are candidates to kidney transplant. The scale has shown adequate internal consistency and test-retest reliability. This study presents the results of an external validation study of the KATITA-25 scale. METHODS: Patients >18 y old scheduled for kidney transplant were included in this multicenter study. The KATITA-25 scale was administered before surgery and then at 3-mo posttransplantation for evaluation of scale sensitivity to change. At this time, 2 validated medication adherence scales were applied for assessment of concurrent validity. For evaluation of predictive validity, nonadherence to immunosuppressive medication was assessed at 6 and 12 mo after transplantation by 3 independent methods: patient self-report of nonadherence using the Morisky-Green-Levine Medication Assessment Questionnaire scale, serum trough levels of immunosuppressants, and pharmacy refills. RESULTS: Three twenty-two patients were available for evaluation of concurrent validity and 311 patients of predictive validity. After kidney transplant, the median KATITA-25 score decreased from 20 to 8 (P < 0.001), demonstrating scale sensitivity to change, and the KATITA-25 score showed correlation with the Basel Assessment of Adherence to Immunosuppressive Medication Scale score (Spearman's ρ 0.18, P = 0.002) and the Cuestionario para la Evaluación de la Adhesión al Tratamiento Antiretroviral scores (ρ -0.17, P = 0.002), confirming concurrent validity. The nonadherence rate was 57.6%. The scale predictive validity was demonstrated by the area under the receiver operating characteristics curve (0.68), sensitivity (59.8%), specificity (68.2%), and positive predictive value (71.8%). CONCLUSIONS: This external validation study of KATITA-25 scale provided evidence of sensitivity to change, and structural, criterion, and predictive validity.

Development and Internal Validation of a Questionnaire Assessing Predisposition to Nonadherence to Immunosuppressive Medication in Kidney Pretransplant Patients.

BACKGROUND: After kidney transplant, nonadherence to immunosuppressive therapy is the main cause of impaired kidney function and graft loss. The objective of this study was the development and internal validation of a clinical questionnaire for assessing the predisposition to adherence to immunosuppressive therapy in kidney pretransplant patients. METHODS: Multicenter prospective study conducted in 7 kidney hemodialysis and 6 kidney transplant centers of 3 Brazilian state capitals. Kidney transplant candidate patients of both sexes and >18-y-old were included. Retransplanted patients were excluded. A 72-item pilot version of the questionnaire, created through literature review complemented with a focus group of 8 kidney pretransplant patients, was administered to 541 kidney transplant candidate patients. Factor analysis with varimax rotation was used for questionnaire development. Internal validity evaluation used Cronbach's alpha and test-retest reliability. Construct validity was assessed by differentiation by known groups. RESULTS: The final questionnaire, named Kidney AlloTransplant Immunosuppressive Therapy Adherence (KATITA) Questionnaire, consisting of 25 items in 3 dimensions, presented good internal consistency reliability (Cronbach's alpha 0.81). The 3 dimensions and respective Cronbach's alpha were "Carelessness" (14 items, 0.81), "Skepticism" (6 items, 0.57), and "Concern" (5 items, 0.62). The interdimension correlation matrix showed low correlation coefficients (<0.35). Test-retest reliability, evaluated with 154 patients, showed an intraclass correlation coefficient of 0.62 (moderate agreement). The scale showed construct validity. CONCLUSIONS: The KATITA-25 questionnaire is the first psychometric instrument for evaluation of predisposition to nonadherence to immunosuppressive medication in candidate patients for kidney transplant in the pretransplant setting.

Development and validation of a predictive tool for adverse drug reactions in neonates under intensive care.

AIMS: Neonates hospitalized in neonatal intensive care units (NICUs) commonly experience adverse drug reactions (ADRs). Thus, we aimed to develop and validate a tool for predicting ADRs in neonates hospitalized in NICUs. METHODS: A nested case-control study in an open cohort with neonates admitted to the NICU of a maternity hospital in Natal, Brazil was conducted from January 2019 to January 2022 [Correction added on 4 December 2023, after first online publication: 2023 has been changed to 2019 in the preceding sentence.]. Neonates with ADR were randomly paired with 2 controls. For the development of the tool, a multivariate logistic regression was applied on 2/3 of the sample (cases with respective controls). The model's fit was evaluated using the Hosmer-Lemeshow test for calibration and the Brier score for performance assessment. Validation of the tool was performed by determining the area under the receiver operating characteristic curve with bootstrap adjusted c-statistics. RESULTS: In all, 450 neonates (150 cases and 300 controls) were included in the study. We identified 5 independent risk factors for ADR, 4 related to the neonate (current mechanical ventilation, heart rate ≥178 beats/min, intravenous medications, ≥5 prescription medications) and 1 to the mother (gestational hypertension). The tool had a classification cut-off point of ≥15, and its total score ranged from 0 to 34. In validation, the tool had an area under the receiver operating characteristic curve of 0.74 (95% confidence interval [CI] 0.66-0.81) with sensitivity of 52.02% (95% CI 47.40-56.64) and specificity of 81.35% (95% CI 77.75-84.95). CONCLUSION: The tool demonstrated adequate discriminative ability and utilized 5 commonly monitored variables in the NICU.

Um raro caso de vasculite leucocitoclástica induzida por oxacilina / A rare case of oxacillin-induced leukocytoclastic vasculitis

A vasculite leucocitoclástica é uma patologia cujos mecanismos estão associados ao processo de inflamação vascular. Estima-se que até 24% dos casos de vasculite estão relacionados ao uso de fármacos, sendo os antimicrobianos beta-lactâmicos um dos grupos farmacológicos comumente associados a este desfecho adverso. A oxacilina, uma penicilina semissintética, possui um anel beta-lactâmico que confere atividade biológica e está associada com maior frequência a relatos de vasculite leucocitoclástica. No entanto, casos semelhantes relacionados a esse antimicrobiano são raros, sendo identificados apenas três casos na literatura. Diante desse contexto, relatamos um quarto caso de vasculite leucocitoclástica em um homem de 56 anos, em tratamento com oxacilina, que desenvolveu a vasculite no 3º dia de uso do antimicrobiano. Além da suspensão da oxacilina, ele foi tratado com 125 mg/dia de metilprednisolona endovenosa por sete dias, seguido de 20 mg/dia de prednisona oral por quatro dias, resultan-do em remissão satisfatória das lesões cutâneas e ausência de novos desfechos adversos. Este caso corrobora a possível relação causal entre o uso de oxacilina e o desenvolvimento da vasculite leucocitoclástica, apesar de sua ocorrência ser rara. A resposta favorável às intervenções terapêuticas, incluindo a suspensão da oxacilina e o uso de corticosteroides, destaca a eficácia dessas abordagens no tratamento dessa complicação (AU).

Leukocytoclastic vasculitis is a pathology whose mechanisms are associated with the process of vascular inflammation. It is estimated that up to 24% of the cases of vasculitis are drug-related, with beta-lactam antimicrobials be-ing one of the pharmacological groups commonly associated with this adverse outcome. Oxacillin, a semisynthetic penicillin, has a beta-lactam ring that confers biological activity and is most frequently associated with reports of leukocytoclastic vasculitis. However, similar cases related to this antimicrobial are rare, with only three cases identified in the literature. Against this background, we report a fourth case of leukocytoclastic vasculitis in a 56-year-old man, on oxacillin treatment, who developed the vasculitis on the 3rd day of antimicrobial use. In addition to oxacillin suspension, he was treated with 125 mg/day of intravenous methylprednisolone for seven days, followed by 20 mg/day of oral prednisone for four days, resulting in satisfactory remission of the skin lesions and no new adverse outcomes. This case provides further evidence supporting the potential causal relationship between the use of oxacillin and the development of leukocytoclastic vasculitis, albeit a rare occurrence. The positive response to therapeutic interventions, such as oxacillin suspension and corticosteroid treatment, underscores the effectiveness of these approaches in addressing this complication (AU),

Polypharmacy, physical activity, and sedentary time in older adults: A scoping review.

OBJECTIVE: To map out the studies that have investigated the associations of polypharmacy and/or potentially inappropriate medication (PIM) use with physical activity and sedentary time in older adults. METHODS: We conducted a literature search from inception to December 2022 in PubMed, Embase, Web of Science, and Scopus. INCLUSION CRITERIA: observational studies including older adults (≥60 years); English, Portuguese, and Spanish languages; any definition of polypharmacy; implicit and explicit criteria of PIM use; physical activity and/or sedentary time data. RESULTS: Fourteen cross-sectional studies were included; 11 defined polypharmacy as ≥5 medications (prevalence ranging from 9.5 % to 57 %). No study reported information on PIM use. Most studies included participants aged <80 years. Twelve studies included self-reported measures of physical activity, while two studies used accelerometer-measured physical activity. Ten studies included analyses adjusted for confounders, and nine considered polypharmacy as an outcome. All of them demonstrated an inverse association between physical activity and polypharmacy, irrespective of the definition of polypharmacy and the assessment method employed (self-reported or accelerometry). One study reported an inverse association between polypharmacy (as the exposure) and physical activity (as the outcome). None of the studies investigated the association between sedentary time and polypharmacy. CONCLUSIONS: Limited evidence suggests an inverse association between physical activity and polypharmacy in older adults. However, the relationship between PIM use, physical activity, and sedentary time remains unknown. Longitudinal studies utilizing objectively-measured physical activity and sedentary time are needed to better clarify the relationship between these movement behaviors and polypharmacy and/or PIM use in older adults.

Temporal profile of adverse drug reactions and associated clinical factors: a prospective observational study in a neonatal intensive care unit.

OBJECTIVE: Although adverse drug reactions (ADRs) are quite common in hospitalised neonates, pharmacovigilance activities in this public are still incipient. This study aims to characterise ADRs in neonates in a neonatal intensive care unit (NICU), identifying causative drugs, temporal profile and associated factors. DESIGN: Prospective observational study. SETTING: NICU of a public maternity hospital in Natal/Brazil. PARTICIPANTS: All neonates admitted to the NICU for more than 24 hours and using at least one medication were followed up during the time of hospitalisation. PRIMARY OUTCOME MEASURES: Incidence rate and risk factors for ADRs. The ADRs were detected by an active search in electronic medical records and analysis of spontaneous reports in the hospital pharmacovigilance system. RESULTS: Six hundred neonates were included in the study, where 118 neonates had a total of 186 ADRs. The prevalence of ADRs at the NICU was 19.7% (95% CI 16.7% to 23.0%). The most common ADRs were tachycardia (30.6%), polyuria (9.1%) and hypokalaemia (8.6%). Tachycardia (peak incidence rate: 57.1 ADR/1000 neonates) and hyperthermia (19.1 ADR/1000 neonates) predominated during the first 5 days of hospitalisation. The incidence rate of polyuria and hypokalaemia increased markedly after the 20th day, with both reaching a peak of 120.0 ADR/1000 neonates. Longer hospitalisation time (OR 0.018, 95% CI 0.007 to 0.029; p<0.01) and number of prescribed drugs (OR 0.127, 95% CI 0.075 to 0.178; p<0.01) were factors associated with ADRs. CONCLUSION: ADRs are very common in NICU, with tachycardia and hyperthermia predominant in the first week of hospitalisation and polyuria and hypokalaemia from the third week onwards.

Temporal assessment of entomological surveillance of Trypanosoma cruzi vectors in an endemic area of northeastern Brazil.

Entomological surveillance is essential for the control of triatomines and the prevention of Trypanosoma cruzi infection in humans and domestic animals. Thus, the objective of this study was to evaluate entomological indicators and triatomine control during the period from 2005 to 2015 in an endemic area in the state of Rio Grande do Norte, Brazil. This observational and retrospective study was developed based on data analysis related to active entomological surveillance activities and chemical control of infested housing units (HU) in the Agreste mesoregion of the state of Rio Grande do Norte, Brazil, in the period between 2005 to 2015. The quantitative analysis of housing units surveyed for entomological indicators was performed by linear regression of random effects (p < 0.05). The effect of the number of HU surveyed on the entomological indicators was analyzed by fitting a linear random effects regression model and an increasing intradomiciliary colonization rate was significant. In the period evaluated 92,156 housing units were investigated and the presence of triatomines was reported in 4,639 (5.0%). A total of 4,653 specimens of triatomines were captured and the species recorded were Triatoma pseudomaculata (n = 1,775), Triatoma brasiliensis (n = 1,569), Rhodnius nasutus (n = 741) and Panstrongylus lutzi (n = 568), with an index of natural infection by T. cruzi of 2.2%. Only 53.1% of the infested HU were subjected to chemical control. Moreover, there was a decrease in the total number of HU surveyed over time associated with an increase in the index of intradomiciliary colonization (p = 0.004). These data demonstrated that entomological surveillance and control of vectors in the Agreste mesoregion of the state has been discontinued, emphasizing the need for more effective public policies to effectively control the vectors, in order to avoid the exposure of humans and domestic animals to the risk of T. cruzi infection.

Causality assessment of adverse drug reactions in neonates: a comparative study between Naranjo's algorithm and Du's tool.

BACKGROUND: Algorithms for causality assessment of adverse drug reactions (ADRs) in a neonatal intensive care unit (NICU) are important in the management of adverse events, however, it is inconclusive which tool best suits pharmacovigilance in neonates. AIM: To compare the performance of the algorithms of Du and Naranjo in determining causality in cases of ADRs in neonates in a NICU. METHOD: This observational and prospective study was conducted in a NICU of a Brazilian maternity school between January 2019 and December 2020. Independently, three clinical pharmacists used the algorithms of Naranjo and Du in 79 cases of ADRs in 57 neonates. The algorithms were evaluated for inter-rater and inter-tool agreement using Cohen's kappa coefficient (k). RESULTS: The Du algorithm showed greater ability to identify definite ADRs (≈ 60%), but had low reproducibility (overall k = 0.108; 95% CI 0.064-0.149). In contrast, the Naranjo algorithm showed a lower proportion of definite ADRs (< 4%), but had good reproducibility (overall k = 0.402; 95% CI 0.379-0.429). The tools showed no significant correlation regarding ADR causality classification (overall k = - 0.031; 95% CI - 0.049 to 0.065). CONCLUSION: Although the Du algorithm has a lower reproducibility compared to the Naranjo, this tool showed good sensitivity for classifying ADRs as definite, proving to be a more suitable tool for neonatal clinical routine.

Drug-related problems in hypertension and gestational diabetes mellitus: A hospital cohort.

OBJECTIVE: To characterize the drug-related problems (DRPs) in high-risk pregnant women with hypertension and gestational diabetes mellitus according to frequency, type, cause, and factors associated with their occurrence in the hospital setting. METHODOLOGY: This is an observational, longitudinal, prospective study that included 571 hospitalized pregnant women with hypertension and gestational diabetes mellitus using at least one medication. DRPs were classified according to the Classification for Drug-Related Problems (PCNE V9.00). In addition to descriptive statistics, a univariate and multivariate logistic regression model was employed to determine the factors associated with the DRPs. RESULTS: A total of 873 DRPs were identified. The most frequent DRPs were related to therapeutic ineffectiveness (72.2%) and occurrence of adverse events (27.0%) and the main drugs involved were insulins and methyldopa. These were followed in the first five days of treatment by: the ineffectiveness of insulin (24.6%), associated with underdosage (12.9%) or insufficient frequency of administration (9.5%) and methyldopa associated with the occurrence of adverse reactions (40.2%) in the first 48h. Lower maternal age (OR 0.966, 95% CI 0.938-0.995, p = 0.022), lower gestational age (OR 0.966, 95% CI 0.938-0.996, p = 0.026), report of drug hypersensitivity (OR 2.295, 95% CI 1.220-4.317, p = 0.010), longer treatment time (OR 1.237, 95% CI: 1.147-1.333, p = 0.001) and number of prescribed medications (OR 1.211, 95% CI: 0.240-5.476, p = 0.001) were risk factors for occurrence of DRPs. CONCLUSION: DRPs are frequent in pregnant women with hypertension and gestational diabetes mellitus, and they are mainly related to therapeutic ineffectiveness and the occurrence of adverse events.

Effectiveness and safety of ivermectin in the treatment of COVID-19: protocol for a systematic review and meta-analysis.

INTRODUCTION: Ivermectin is a drug with antiviral properties and has been proposed as an alternative treatment for patients with COVID-19, in some countries; however, there is limited evidence to support its clinical use. Accordingly, the aim of this review and meta-analysis is to obtain superior evidence on the effectiveness and safety of ivermectin in treatment of COVID-19. METHODS AND ANALYSIS: We will search in the medical databases and International Clinical Trials Registry Platform databases for randomised clinical trials and quasi-randomised trials published from December 2019. The criteria for inclusion are that infection needs to be confirmed by a real-time PCR or serology test, and the effect of ivermectin has been compared with placebo, symptomatic treatment or no treatment. We will exclude observational studies and clinical trials that involved patients with symptoms suggestive of COVID-19, but without a laboratorial diagnosis. Outcomes of interest include mortality, time to symptom resolution, time of hospitalisation, frequency of invasive mechanical ventilation and extracorporeal membrane oxygenation, incidence of severe acute respiratory syndrome, admission to intensive care unit, viral load, PCR-negative status, percentage of infection after prophylactic use, and total incidence of adverse and side effects. Study selection will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Two reviewers will independently select the studies and assess their eligibility. Two other reviewers will independently extract data from each study. Meta-analysis will then be carried out using fixed-effects or random-effects model, using the mean difference for continuous outcomes and the relative risk for dichotomous outcomes. Bias risk will be assessed using the Cochrane risk-of-bias tool. The quality of evidence for each outcome will be assessed using GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology. Review Manager V.5.3.5 will be used for synthesis and subgroup analysis. ETHICS AND DISSEMINATION: Owing to the nature of the review, ethical approval is not required. The results will be disseminated through peer-reviewed publications. PROSPERO REGISTRATION NUMBER: CRD42020197395.

Proton pump inhibitor and community pharmacies: Usage profile and factors associated with long-term use.

AIM: To characterize the usage profile and the factors associated with the prolonged use of proton pump inhibitor drugs in a community pharmacy. METHODOLOGY: This is a cross-sectional, prospective and observational study involving interviews with 410 patients who acquired PPI for their own use from community pharmacies. To characterize the factors associated with the prolonged use of PPI, a multivariate logistic regression model was used. RESULTS: Pantoprazole (42.7%) and omeprazole (31%) were the most acquired PPIs, prescribed mainly by gastroenterologists (49.5%). They are used in the morning, especially for gastrointestinal symptoms, however, they had been consumed for more than 5 years in 30% of cases. The factors associated with prolonged use are old age (OR 1.03 CI95% 1.01-1.05), body mass index (OR 1.07 CI95% 1.01-1.12), use of non-steroidal anti-inflammatories (OR 3.18 CI95% 1.20-8.43) and selective serotonin reuptake inhibitors (OR 3.5 95% CI 1.39-8.88). CONCLUSION: PPIs are adequate in terms of indication and form of use, however, prolonged use associated with old age, being overweight and use of anti-inflammatories and antidepressants is frequent.

[Prescription of potentially inappropriate medications for the elderly: a study in Primary Health Care]. / Prescrição de medicamentos potencialmente inapropriados para idosos: um estudo na Atenção Primária à Saúde.

The elderly population is vulnerable to the risks of the use of medications, especially those considered potentially inappropriate medications (PIMs), in which the risks outweigh the benefits. The study sought to evaluate the PIMs prescribed in Primary Health Care (PHC) and associated factors. A cross-sectional, analytical study was carried out from March to December 2019 in PHC in Campina Grande, Paraíba, through interviews with 458 elderly individuals. The independent variables included socioeconomic characteristics, health status and the use of medications, and the outcome was classified as PIM by the Brazilian Consensus on Potentially Inappropriate Medications. There was a prescription of at least one PIM for 44.8% of the elderly and the majority affecting the Central Nervous System (54.4%). In the adjusted model, depression (PR=2.01; 95%CI 1.59-2.55), using other medications in addition to those prescribed (PR=1.36; 95%CI 1.08-1.72) and polypharmacy (PR=1.80; 95%CI 1.40-2.33) remained an associated factor, and self-reporting systemic arterial hypertension became a protective factor (PR=0.65; 95%CI 0.49-0.87). This reveals the need for actions to monitor closely the use of PIMs by the elderly to ensure access in conjunction with safety.

Os idosos são vulneráveis aos riscos do uso de medicamentos, principalmente daqueles considerados potencialmente inapropriados (MPI) em que os riscos superam os benefícios. O estudo buscou avaliar os MPI prescritos na Atenção Primária à Saúde (APS) e seus fatores associados. Realizou-se um estudo transversal, analítico, de março a dezembro de 2019, na APS em Campina Grande, Paraíba, através de entrevistas com 458 idosos. As variáveis independentes abrangeram características socioeconômicas, condição de saúde e utilização de medicamentos e o desfecho foi medicamento classificado como MPI pelo Consenso Brasileiro de Medicamentos Potencialmente Inapropriados. Verificou-se a prescrição de pelo menos um MPI para 44,8% dos idosos e a maioria de atuação no Sistema Nervoso Central (54,4%). No modelo ajustado, depressão (RP=2,01; IC95% 1,59-2,55), utilizar outros medicamentos além dos prescritos (RP=1,36; IC95% 1,08-1,72) e polifarmácia (RP=1,80; IC95% 1,40-2,33) permaneceram como fator associado e autorreferir ser portador de hipertensão arterial sistêmica tornou-se fator de proteção (RP=0,65; IC95% 0,49-0,87). Evidencia-se necessidade de ações que qualifiquem o uso de medicamentos por idosos, de modo a garantir acesso aliado à segurança.

Prescrição de medicamentos potencialmente inapropriados para idosos: um estudo na Atenção Primária à Saúde / Prescription of potentially inappropriate medications for the elderly: a study in Primary Health Care

Resumo Os idosos são vulneráveis aos riscos do uso de medicamentos, principalmente daqueles considerados potencialmente inapropriados (MPI) em que os riscos superam os benefícios. O estudo buscou avaliar os MPI prescritos na Atenção Primária à Saúde (APS) e seus fatores associados. Realizou-se um estudo transversal, analítico, de março a dezembro de 2019, na APS em Campina Grande, Paraíba, através de entrevistas com 458 idosos. As variáveis independentes abrangeram características socioeconômicas, condição de saúde e utilização de medicamentos e o desfecho foi medicamento classificado como MPI pelo Consenso Brasileiro de Medicamentos Potencialmente Inapropriados. Verificou-se a prescrição de pelo menos um MPI para 44,8% dos idosos e a maioria de atuação no Sistema Nervoso Central (54,4%). No modelo ajustado, depressão (RP=2,01; IC95% 1,59-2,55), utilizar outros medicamentos além dos prescritos (RP=1,36; IC95% 1,08-1,72) e polifarmácia (RP=1,80; IC95% 1,40-2,33) permaneceram como fator associado e autorreferir ser portador de hipertensão arterial sistêmica tornou-se fator de proteção (RP=0,65; IC95% 0,49-0,87). Evidencia-se necessidade de ações que qualifiquem o uso de medicamentos por idosos, de modo a garantir acesso aliado à segurança.

Abstract The elderly population is vulnerable to the risks of the use of medications, especially those considered potentially inappropriate medications (PIMs), in which the risks outweigh the benefits. The study sought to evaluate the PIMs prescribed in Primary Health Care (PHC) and associated factors. A cross-sectional, analytical study was carried out from March to December 2019 in PHC in Campina Grande, Paraíba, through interviews with 458 elderly individuals. The independent variables included socioeconomic characteristics, health status and the use of medications, and the outcome was classified as PIM by the Brazilian Consensus on Potentially Inappropriate Medications. There was a prescription of at least one PIM for 44.8% of the elderly and the majority affecting the Central Nervous System (54.4%). In the adjusted model, depression (PR=2.01; 95%CI 1.59-2.55), using other medications in addition to those prescribed (PR=1.36; 95%CI 1.08-1.72) and polypharmacy (PR=1.80; 95%CI 1.40-2.33) remained an associated factor, and self-reporting systemic arterial hypertension became a protective factor (PR=0.65; 95%CI 0.49-0.87). This reveals the need for actions to monitor closely the use of PIMs by the elderly to ensure access in conjunction with safety.

[Comparative assessment of off-label and unlicensed drug prescription in neonatal intensive care: FDA versus Brazilian guidelines]. / Evaluación comparativa de la prescripción off-label y unlicensed de fármacos en cuidados intensivos neonatales: Guías de la FDA versus guías brasileñas.

INTRODUCTION: Regulatory agencies are responsible for defining the use of off-label (OL) and unlicensed (UL) drug prescription in neonatal intensive care. However, these regulatory criteria may differ between agencies in different countries. The aim of this study was to establish the frequency of OL and UL drug prescription in a sample of patients in a neonatal intensive care unit applying the criteria of the Food and Drug Administration (FDA) of the United States and the Agência Nacional de Vigilância Sanitária (ANVISA) of Brazil, analysing the differences observed in the results based on the applied criteria. METHODS: Prospective cohort study in neonates admitted for more than 24hours to the neonatal intensive care unit (NICU) of a teaching maternity hospital between August 2017 and July 2018. We obtained information concerning the drugs included in the analysis of OL and UL prescriptions from the DrugDex-Micromedex® and official information on pharmaceutical products in Brazil. We used the kappa correlation coefficient to assess the agreement between the FDA and ANVISA criteria. We defined disagreement as a kappa value of less than 0.200. RESULTS: We evaluated 220 neonates admitted to the NICU and 17,421 items prescribed during the study period. We did not find a difference in the proportion of neonates in which at least 1 drug was prescribed under OL conditions applying the FDA versus the ANVISA criteria (96.4% vs. 98.6%). We found differences between the FDA and ANVISA in the OL classification based on the authorised age of use and indications for prescription, mainly in systemic antimicrobials and cardiovascular drugs. When we compared the prescribing information provided by the FDA and the ANVISA, we found that the criteria of the ANVISA were less specific. CONCLUSIONS: OL and UL drug prescription are frequent in neonatal intensive care applying the criteria of either agency, although the FDA has established more detailed criteria in terms of the ages and indications for which prescription is authorised.

Drug-drug interactions in neonatal intensive care: A prospective cohort study.

BACKGROUND: To characterize the prevalence and profile of drug-drug interactions (DDIs), the drugs most related to major DDIs and risk factors of their prescription in a neonatal intensive care unit (NICU). METHODS: Neonates admitted to a NICU who had at least one medication prescribed and a hospital stay >24 h were included in a prospective cohort study (August 2017 to July 2018). All medications prescribed during the hospitalization were collected from all neonates (n = 220), with the screening for DDIs. Prevalence and type of DDIs was identified. Network analysis was used to identify the drugs more implicated with DDIs. Logistic regression was used for the analysis of risk factors (p < 0.05). RESULTS: Over 70% of neonates were exposed to DDIs and 29% were exposed to major DDIs. The network analysis identified furosemide, fentanyl, aminophylline and fluconazole as most implicated with DDI, fentanyl was especially associated with major DDIs. The number of drugs (OR 1.60, p < 0.01), caesarean delivery (OR 2.68, p < 0.05), gestational age (OR 1.03, p < 0.01) and APGAR score (OR 0.78, p < 0.01) were identified as risk factors for exposure to DDI. CONCLUSION: Neonates in intensive care have a high exposure to DDIs and the occurrence of major DDIs is related specifically to the prescription of fentanyl. The number of prescribed drugs, gestational age, cesarean delivery and low APGAR score in the first minute were identified as risk factors for DDIs in NICU.

Manejo e Prevenção de Reações Adversas da Quimioterapia Antineoplásica com Platinas em Pacientes com Cânceres Esofágico e Gástrico: Revisão Sistemática da Literatura / Management and Prevention of Adverse Reactions to Platinum Antineoplastic Chemotherapy in Patients with Esophageal and Gastric Cancer: Systematic Literature Review / Manejo y Prevención de Reacciones Adversas a la Quimioterapia Antineoplásica con Platino en Pacientes con Cánceres de Esófago y Gástrico: Revisión Sistemática de la Literatura

Introdução: O câncer gástrico é a quinta doença maligna mais comum em todo o mundo. Trata-se do tumor maligno mais incidente na Ásia, especialmente na China. O carcinoma esofágico é um dos tipos mais agressivos de tumor maligno. Os tratamentos multimodais, incluindo quimioterapia neoadjuvante e quimiorradioterapia, são utilizados e podem causar fadiga, vômito, diarreia, alterações cutâneas, caquexia e neuropatia periférica, que podem ser efeitos colaterais importantes para muitos pacientes que realizam seus tratamentos. Objetivo: Realizar uma revisão sistemática sobre o manejo e a prevenção de reações adversas da quimioterapia antineoplásica com platinas em pacientes com câncer esofágico e tumor gástrico. Método: Para seleção dos artigos, foi realizada a busca em três bases de dados: MEDLINE/PubMed, Cochrane e Embase, com a estratégia PICO, variando os descritores MeSH/DeCs e operadores booleanos. Resultados: Foram encontrados 455 títulos, dos quais, após utilizar a diretriz PRISMA, restaram 15 artigos para a revisão sistemática, que abordavam o manejo e a prevenção de náusea e vômitos, neuropatia periférica, caquexia, suplementação de magnésio, tratamento de depressão e toxicidade geral. Conclusão: Verificou-se que náuseas, vômitos, neuropatia e hipomagnesemia tiveram maior número de estudos relacionados ao manejo e à prevenção desses sintomas, nos quais identificaram-se algumas sugestões de condutas com maior evidência para essas reações. As demais reações encontradas ainda carecem de mais estudos, principalmente nos casos de cânceres gástrico e esofágico

Introduction: Gastric cancer is the fifth most common malignancy worldwide. It is the most frequent malignant tumor in Asia, especially in China. Esophageal carcinoma is one of the more aggressive types of malignant tumor. Multimodal treatments, including neoadjuvant chemotherapy and chemoradiotherapy are utilized and can cause fatigue, vomiting, diarrhea, skin changes, cachexia, and peripheral neuropathy, which can be important side effects for many patients undergoing their treatments. Objective: Carry out a systematic review on the management and prevention of adverse reactions of antineoplastic chemotherapy with platinum in patients with esophageal cancer and gastric tumor. Method: To select the articles, a search was conducted in three databases: MEDLINE/PubMed, Cochrane and Embase, with the PICO strategy, alternating between MeSH/DeCs descriptors and Boolean operators. Results: 455 titles were found, of which, after using the PRISMA guideline, 15 articles remained for systematic review, addressing the management and prevention of nausea and vomiting, peripheral neuropathy, cachexia, magnesium supplementation, treatment of depression and general toxicity. Conclusion: The greatest number of studies addressing the management and prevention of the symptoms of nausea, vomits, neuropathy and hypomagnesemia were found, and it was possible to identify some suggestions of conducts to treat these reactions. More studies are necessary for the other reactions encountered, mainly in the cases of gastric and esophageal cancer

Introducción: El cáncer gástrico es la quinta neoplasia maligna más común en todo el mundo. Es el tumor maligno más común en Asia, especialmente en China. El carcinoma de esófago es uno de los tipos de tumores malignos más agresivos. Se utilizan tratamientos multimodales, que incluyen quimioterapia neoadyuvante y quimiorradioterapia que pueden provocar: fatiga, vómitos, diarrea, alteraciones cutáneas, caquexia y neuropatía periférica, que pueden ser efectos secundarios importantes para muchos pacientes sometidos a sus tratamientos. Objetivo: Realizar una revisión sistemática sobre el manejo y prevención de reacciones adversas de la quimioterapia antineoplásica con platino en pacientes con cáncer de esófago y tumor gástrico. Método: Para la selección de los artículos se realizó una búsqueda en tres bases de datos: MEDLINE/PubMed, Cochrane y Embase, con la estrategia PICO, variando los descriptores MeSH/DeCs y operadores booleanos. Resultados: Se encontraron 455 títulos, de los cuales, luego de utilizar la guía PRISMA, quedaron 15 artículos para revisión sistemática, que abordaron el manejo y prevención de náuseas y vómitos, neuropatía periférica, caquexia, suplementación con magnesio, tratamiento de la depresión y toxicidad general. Conclusión: Se verifico que náuseas, vómitos, neuropatía e hipomagnesemia tuvieron un mayor número de estudios relacionados con el manejo y prevención de los síntomas, en los cuales fue posible identificar algunas sugerencias de conducta con mayor evidencia de estas reacciones. Las otras reacciones encontradas aún necesitan más estudios, especialmente en casos de cánceres gástrico y de esófago

Development and validation of a clinical instrument to predict risk of an adverse drug reactions in hospitalized patients.

OBJECTIVE: Development and internal validation of a clinical tool for assessment of the risk of adverse drug reactions (ADR) in hospitalized patients. METHODOLOGY: Nested case-control study in an open cohort of all patients admitted to a general hospital. Cases of ADR were matched to two controls. Eighty four patient variables collected at the time of the ADR were analyzed by conditional logistic regression. Multivariate logistic regression with clustering of cases in a random sample of 2/3 of the cases and respective controls, with baseline odds-ratio corrected with an estimate of ADR incidence, was used to obtain regression coefficients for each risk factor and to develop a risk score. The clinical tool was validated in the remaining 1/3 observations. The study was approved by the institution's research ethics committee. RESULTS: In the 8060 hospitalized patients, ADR occurred in 343 (5.31%), who were matched to 686 controls. Fourteen variables were identified as independent risk factors of ADR: female, past history of ADR, heart rate ≥72 bpm, systolic blood pressure≥148 mmHg, diastolic blood pressure <79 mmHg, diabetes mellitus, serum urea ≥ 67 mg/dL, serum sodium ≥141 mmol/L, serum potassium ≥4.9 mmol/L, main diagnosis of neoplasia, prescription of ≥3 ATC class B drugs, prescription of ATC class R drugs, prescription of intravenous drugs and ≥ 6 oral drugs. In the validation sample, the ADR risk tool based on those variables showed sensitivity 61%, specificity 73% and area under the ROC curve 0.73. CONCLUSION: We report a clinical tool for ADR risk stratification in patients hospitalized in general wards based on 14 variables.

Comparison of phenol-chloroform and a commercial deoxyribonucleic acid extraction kit for identification of bloodmeal sources from triatomines (Hemiptera: Reduviidae).

INTRODUCTION: Knowledge of triatomine bloodmeal sources is essential for understanding vector-host interactions in Trypanosoma cruzi transmission cycles. Expensive commercial deoxyribonucleic acid (DNA) extraction kits are widely used for bloodmeal identification. This study assessed the performance of an inexpensive phenol-chloroform DNA extraction protocol for identification of triatomine bloodmeal sources, comparing it with a commercially available kit. METHODS: Both methods were used to obtain DNA from the intestinal contents of Triatoma brasiliensis blood-fed on either Columba sp., Mus musculus, or Gallus gallus. Subsequently, the mitochondrial 12S ribosomal ribonucleic acid (rRNA) gene was amplified by polymerase chain reaction, sequenced, and compared with GenBank data. RESULTS: Twelve (80%) samples extracted with the commercial kit and four (26.7%) with phenol-chloroform were pure (according to the A260/A280 ratio). Samples extracted with phenol-chloroform, except for Columba sp. samples, had higher DNA concentration than those extracted with the commercial kit. Samples extracted using phenol-chloroform and blood-fed on G. gallus had significantly higher DNA concentration than those blood-fed on Columba sp. (p-value <0.001) and M. musculus (p-value <0.001). The 215-base-pair 12S rRNA fragment was amplified from all samples and produced reliable sequences, enabling the identification of the bloodmeal source, most of which showed identity and coverage above 95%. The phenol-chloroform method was much less expensive than the commercial kit but took considerably more time to perform. CONCLUSIONS: Our data showed that both DNA extraction methods produced reliable sequences enabling identification of triatomine bloodmeal sources but differed greatly in cost and time required.

Population Pharmacokinetics of Magnesium Sulfate in Preeclampsia and Associated Factors.

BACKGROUND AND OBJECTIVE: The pharmacokinetic basis of magnesium sulphate (MgSO4) dosing regimens for preeclampsia (PE) prophylaxis and treatment is not clearly established. The aim of study is to develop a population pharmacokinetic (PK) model of MgSO4 in PE, and to determine key covariates having an effect in MgSO4 pharmacokinetics in preeclampsia (PE) and to determine key covariates having an effect in MgSO4 PK. METHODS: A prospective cohort study was conducted from June 2016 to February 2018 in patients with PE administered MgSO4 as a 4-g bolus followed by continuous infusion at a rate of 1 g/h. Serum magnesium concentrations were obtained before treatment administration and 2, 6, 12, and 18 h after the initial dose. The software Monolix was used to estimate population PK parameters of MgSO4 [clearance (CL), volume of distribution (V), half-life] and to develop a PK model with baseline patient demographic, clinical, and laboratory covariates. RESULTS: The study population consisted of 109 patients. The PK profile of MgSO4 was adequately described by a one-compartment PK model. The model estimate of the population CL was 1.38 L/h; for V, it was 13.3 L; and the baseline magnesium concentration was 0.77 mmol/L (1.87 mg/dL). The baseline body weight and serum creatinine statistically influenced MgSO4 CL and V, respectively. The model was parameterized as CL and V. CONCLUSION: The PK of MgSO4 in pregnant women with PE is significantly affected by creatinine and body weight. Pregnant women with PE and higher body weight have a higher V and, consequently, a lower elimination rate of MgSO4. Pregnant women with PE and a higher serum creatinine value show lower CL and, therefore, lower MgSO4 elimination rate.