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.

Assessment of severity and avoidability of adverse drug reactions in neonates: a reproducibility study of the Hartwig tool and LAAT.

OBJECTIVE: Tools for classifying adverse drug reactions (ADRs) have not yet been validated in the context of the neonatal intensive care unit (NICU). The study aims to investigate the inter-rater reliability of the Hartwig tool and the Liverpool avoidability assessment tool (LAAT) in assessing the severity and avoidability of ADR cases in hospitalized neonates. METHODS: An observational and prospective study was conducted in the NICU of a maternity hospital in Natal, Brazil. The Hartwig tool and LAAT were employed to assess the severity and avoidability of ADRs, respectively. Three experienced clinical pharmacists independently assessed all ADR cases. Inter-rater reliability was measured using Cohen's kappa coefficient (k) with corresponding 95% confidence intervals (CI). RESULTS: Among 79 ADR cases, the mean gestational age was 29.7 ± 4.4 weeks, and the birth weight averaged 1446.0 ± 1179.3 g. The assessment of ADR severity using the Hartwig tool revealed a significant overall correlation (overall k = 0.573; 95% CI 0.395 to 0.753) with exact agreement (EA) and extreme disagreement (ED) rates between evaluators of 86.5% and 2.5%, respectively. However, no statistically significant correlation was observed for determining avoidability using the LAAT (overall k = 0.017; 95% CI - 0.048 to 0.082), with an EA rate of 83.6% and ED rate of 10.1%. CONCLUSION: The Hartwig tool demonstrates good reproducibility among different evaluators in determining the severity of ADRs, unlike the LAAT for assessing avoidability.

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.

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-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.

DRUG-RELATED PROBLEMS IN CARDIAC NEONATES UNDER INTENSIVE CARE.

OBJECTIVE: To determine the frequency and nature of the Drug Related Problems (DRP) in neonates with cardiac diseases admitted to an Intensive Care Unit. METHODS: This prospective cross-sectional study was developed at the Neonatal Intensive Care Unit (NICU) of a teaching maternity hospital in Brazil from January 2014 to December 2016. All neonates diagnosed with any heart disease (congenital heart disease, cardiomyopathy, arrhythmias, etc.) and who were admitted to the NICU for more than 24 hours with at least one prescribed drug were included in the study. Demographic and clinical data were collected from the records of the institution's clinical pharmacy service. DRP and their respective interventions were independently reviewed and classified by two pharmacists. DRP classification was performed through the Pharmaceutical Care Network Europe v6.2 system. RESULTS: 122 neonates were included in the study. The frequency of neonates exposed to DRP was 76.4% (confidence interval of 95% [95%CI] 65.9-82.0), with a mean of 3.2±3.8 cases/patient. In total, 390 DRP were identified, of which 49.0% were related to "treatment effectiveness", 46.7% to "adverse reactions" and 1.0% to "treatment costs". The medicines most involved in DRP were Vancomycin (10.2%; n=46), Meropenem (8.0%; n=36) and Furosemide (7.1%; n=32). Pharmacists performed 331 interventions, of which 92.1% were accepted by physicians and nurses. CONCLUSIONS: The study showed that DRP are very frequent in patients with cardiac diseases hospitalized in the NICU, predominating problems related to the effectiveness and safety of the drug treatment.

Potential drug incompatibilities in the neonatal intensive care unit: a network analysis approach.

BACKGROUND: There is little information on the frequency of drug incompatibilities in neonatal intensive care units (NICU) and the agents most commonly involved in them. The objective of the study was to characterize potential Drug Incompatibilities (DI) in the NICU by frequency, type and combination of drugs. METHODS: Between August 2015 and December 2016, all neonates admitted for more than 24 h and who received any drug treatment were included in this cohort study conducted in the NICU of a teaching maternity hospital in Brazil. Patient data were collected from patient records and prescription orders, and the compatibilities of all drug pairs were classified using the Trissel's™ 2 IV Compatibility tool. Network analysis was performed in order to visualize the drug pairs commonly involved in potential DI. RESULTS: The study population consisted of 281 neonates with a median NICU length of stay of 11 days (range 2-184) and received 1343 intravenous medications. A total of 1114 potential DI were identified, 469 (42.1%) were restricted compatibilities, 348 (31.2%) unknown compatibilities and 297 (26.7%) documented incompatibilities. The incidence of documented incompatibilities in the NICU was 25.0% patient-days (95% confidence interval (CI) 19.4-30.7% patient-days). Incompatible potential DI affected 46.3% (95%CI 40.3-52.3%) of the neonates. Ampicillin (408 of 1114 pairs), gentamicin (216 of 1114 pairs) and aminophylline (197 of 1114 pairs) were the main medicines involved in potential DI. CONCLUSION: Potential DI are extremely common in NICU, with half of the population susceptible to simultaneous administration of incompatible medications. More research is needed to understand the actual drug incompatibilities and their clinical outcomes.

Potential intravenous drug incompatibilities in a pediatric unit.

OBJECTIVE: To investigate potential intravenous drug incompatibilities and related risk factors in a pediatric unit. METHODS: A cross-sectional analytical study conducted in the pediatric unit of a university hospital in Brazil. Data on prescriptions given to children aged 0-15 years from June to October 2014 were collected. Prescriptions that did not include intravenous drugs and prescriptions with incomplete dosage regimen or written in poor handwriting were excluded. Associations between variables and the risk of potential incompatibility were investigated using the Student's t test and ANOVA; the level of significance was set at 5% (p<0.05). Relative risks were calculated for each drug involved in potential incompatibility with 95% confidence interval. RESULTS: A total of 222 children participated in the study; 132 (59.5%) children were male and 118 (53.2%) were aged between 0 and 2 years. The mean length of stay was 7.7±2.3 days. Dipyrone, penicillin G and ceftriaxona were the most commonly prescribed drugs. At least one potential incompatibility was detected in about 85% of children (1.2 incompatibility/patient ratio). Most incompatibilities detected fell into the non-tested (93.4%), precipitation (5.5%), turbidity (0.7%) or chemical decomposition (0.4%) categories. The number of drugs and prescription of diazepam, phenytoin, phenobarbital or metronidazole were risk factors for potential incompatibility. CONCLUSION: Most pediatric prescriptions involved potential incompatibilities, with higher prevalence of non-tested incompatibilities. The number of drugs and prescription of diazepam, phenobarbital, phenytoin or metronidazole were risk factors for potential incompatibilities. OBJETIVO: Avaliar o potencial de incompatibilidade dos medicamentos intravenosos, identificando possíveis fatores de risco em uma unidade pediátrica. MÉTODOS: Trata-se de um estudo observacional analítico do tipo transversal realizado na unidade de pediatria de um hospital de ensino no Brasil. Os dados foram coletados de junho a outubro de 2014 a partir da análise das prescrições de crianças (0 a 15 anos) hospitalizadas. Foram excluídas prescrições sem medicamento intravenoso e com posologia incompletas ou grafia inadequada. A associação entre as variáveis e o risco de potenciais incompatibilidades foi determinada pelo teste t de Student e ANOVA, considerando significativo para p<0,05. Calculou-se o risco relativo com intervalo de confiança de 95% de cada medicamento envolvido. RESULTADOS: Duzentos e vinte e duas crianças participaram do estudo, 132 (59,5%) eram do gênero masculino, 118 (53,2%) tinham idade entre 0 a 2 anos e estiveram internados em média 7,7±2,3 dias. Os medicamentos mais prescritos foram dipirona, penicilina G e ceftriaxona. Quase 85% das crianças apresentaram ao menos uma potencial incompatibilidade, razão de 1,2 incompatibilidades/paciente. Os tipos de incompatibilidades mais comuns foram: não testada (93,4%), precipitação (5,5%), turbidez (0,7%) e decomposição química (0,4%). Os fatores associados a potenciais incompatibilidades foram: número de medicamentos e a prescrição dos medicamentos diazepam, fenitoína, fenobarbital e metronidazol. CONCLUSÃO: A maioria das prescrições pediátricas apresentou potenciais incompatibilidades e a incompatibilidade não testada foi o tipo mais comum. O número de medicamentos e a prescrição dos medicamentos diazepam, fenobarbital, fenitoína e metronidazol foram fatores de risco para potenciais incompatibilidades.

Drug-related problems in cardiac neonates under intensive care / Problemas relacionados a medicamentos em neonatos cardiopatas sob terapia intensiva

ABSTRACT Objective: To determine the frequency and nature of the Drug Related Problems (DRP) in neonates with cardiac diseases admitted to an Intensive Care Unit. Methods: This prospective cross-sectional study was developed at the Neonatal Intensive Care Unit (NICU) of a teaching maternity hospital in Brazil from January 2014 to December 2016. All neonates diagnosed with any heart disease (congenital heart disease, cardiomyopathy, arrhythmias, etc.) and who were admitted to the NICU for more than 24 hours with at least one prescribed drug were included in the study. Demographic and clinical data were collected from the records of the institution's clinical pharmacy service. DRP and their respective interventions were independently reviewed and classified by two pharmacists. DRP classification was performed through the Pharmaceutical Care Network Europe v6.2 system. Results: 122 neonates were included in the study. The frequency of neonates exposed to DRP was 76.4% (confidence interval of 95% [95%CI] 65.9-82.0), with a mean of 3.2±3.8 cases/patient. In total, 390 DRP were identified, of which 49.0% were related to "treatment effectiveness", 46.7% to "adverse reactions" and 1.0% to "treatment costs". The medicines most involved in DRP were Vancomycin (10.2%; n=46), Meropenem (8.0%; n=36) and Furosemide (7.1%; n=32). Pharmacists performed 331 interventions, of which 92.1% were accepted by physicians and nurses. Conclusions: The study showed that DRP are very frequent in patients with cardiac diseases hospitalized in the NICU, predominating problems related to the effectiveness and safety of the drug treatment.

RESUMO Objetivo: Determinar a frequência e a natureza dos problemas relacionados a medicamentos (PRMs) em neonatos cardiopatas internados em uma unidade de terapia intensiva. Métodos: Trata-se de um estudo transversal prospectivo desenvolvido na Unidade de Terapia Intensiva Neonatal (UTIN) de uma maternidade de ensino do Brasil, de janeiro de 2014 a dezembro de 2016. Todos os neonatos diagnosticados com alguma doença cardíaca (cardiopatias congênitas, cardiomiopatias, arritmias etc.) e internados na UTIN por período superior a 24 horas, com pelo menos um medicamento prescrito, foram incluídos no estudo. Dados demográficos e clínicos foram coletados a partir dos registros do serviço de farmácia clínica da instituição. Os PRMs e suas respectivas intervenções foram revisadas e classificadas independentemente por dois farmacêuticos. A classificação dos PRMs foi realizada por meio do sistema Pharmaceutical Care Network Europe versão 6.2. Resultados: Cento e vinte e dois neonatos foram incluídos no estudo. A frequência de neonatos expostos a PRM foi de 76,4% (intervalo de confiança de 95% [IC95%] 65,9-82,0), com média de 3,2±3,8 casos por paciente. Ao todo, 390 PRM foram identificados, sendo que 49,0% estiveram relacionados à "efetividade do tratamento", 46,7% a "reações adversas" e 1,0% a "custos do tratamento". Os medicamentos mais envolvidos em PRM foram: vancomicina (10,2%; n=46), meropenem (8,0%; n=36) e furosemida (7,1%; n=32). Os farmacêuticos realizaram 331 intervenções, sendo 92,1% aceitas por médicos e enfermeiros. Conclusões: O estudo mostrou que PRMs são muito frequentes em pacientes cardiopatas internados em UTIN, predominando problemas relacionados à efetividade e segurança do tratamento medicamentoso.

[Adherence to drug treatment among registered users in the "HIPERDIA" Program in Teresina in the State of Piauí]. / Adesão ao tratamento medicamentoso em usuários cadastrados no Programa Hiperdia no município de Teresina (PI).

Arterial hypertension and diabetes mellitus are among the most chronic diseases prevalent in Brazil. The study sought to evaluate the socioeconomic profile and the therapeutic adherence of users registered in the HIPERDIA Program in Teresina in the State of Piauí. This research was conducted in the Primary Healthcare Units, where a questionnaire was given to four hundred people evaluating their adherence based on the Batalla and Morisky-Green tests. The socioeconomic profile of interviewees was as follows: senior citizens, women, married with 1 to 4 years of study, pensioners and salaried employees. Only 22.5% of hypertensive and 30.7% of diabetic interviewees were considered adherents according to Batalla, and among all of them only 26.75% were adherents according to Morisky-Green. There was no association between sociodemographic and clinical variables and adherence according to Morisky-Green, however there was an association with the type of morbidity presented. In light of these results, health education is the main strategy to improve adherence of users as well as the participation of professionals in the Family Healthcare Team, including the pharmacist, the nutritionist and the physical trainer.

Potential intravenous drug incompatibilities in a pediatric unit / Potencial de incompatibilidade de medicamentos intravenosos em uma unidade pediátrica

ABSTRACT Objective To investigate potential intravenous drug incompatibilities and related risk factors in a pediatric unit. Methods A cross-sectional analytical study conducted in the pediatric unit of a university hospital in Brazil. Data on prescriptions given to children aged 0-15 years from June to October 2014 were collected. Prescriptions that did not include intravenous drugs and prescriptions with incomplete dosage regimen or written in poor handwriting were excluded. Associations between variables and the risk of potential incompatibility were investigated using the Student’s t test and ANOVA; the level of significance was set at 5% (p<0.05). Relative risks were calculated for each drug involved in potential incompatibility with 95% confidence interval. Results A total of 222 children participated in the study; 132 (59.5%) children were male and 118 (53.2%) were aged between 0 and 2 years. The mean length of stay was 7.7±2.3 days. Dipyrone, penicillin G and ceftriaxona were the most commonly prescribed drugs. At least one potential incompatibility was detected in about 85% of children (1.2 incompatibility/patient ratio). Most incompatibilities detected fell into the non-tested (93.4%), precipitation (5.5%), turbidity (0.7%) or chemical decomposition (0.4%) categories. The number of drugs and prescription of diazepam, phenytoin, phenobarbital or metronidazole were risk factors for potential incompatibility. Conclusion Most pediatric prescriptions involved potential incompatibilities, with higher prevalence of non-tested incompatibilities. The number of drugs and prescription of diazepam, phenobarbital, phenytoin or metronidazole were risk factors for potential incompatibilities.

RESUMO Objetivo Avaliar o potencial de incompatibilidade dos medicamentos intravenosos, identificando possíveis fatores de risco em uma unidade pediátrica. Métodos Trata-se de um estudo observacional analítico do tipo transversal realizado na unidade de pediatria de um hospital de ensino no Brasil. Os dados foram coletados de junho a outubro de 2014 a partir da análise das prescrições de crianças (0 a 15 anos) hospitalizadas. Foram excluídas prescrições sem medicamento intravenoso e com posologia incompletas ou grafia inadequada. A associação entre as variáveis e o risco de potenciais incompatibilidades foi determinada pelo teste t de Student e ANOVA, considerando significativo para p<0,05. Calculou-se o risco relativo com intervalo de confiança de 95% de cada medicamento envolvido. Resultados Duzentos e vinte e duas crianças participaram do estudo, 132 (59,5%) eram do gênero masculino, 118 (53,2%) tinham idade entre 0 a 2 anos e estiveram internados em média 7,7±2,3 dias. Os medicamentos mais prescritos foram dipirona, penicilina G e ceftriaxona. Quase 85% das crianças apresentaram ao menos uma potencial incompatibilidade, razão de 1,2 incompatibilidades/paciente. Os tipos de incompatibilidades mais comuns foram: não testada (93,4%), precipitação (5,5%), turbidez (0,7%) e decomposição química (0,4%). Os fatores associados a potenciais incompatibilidades foram: número de medicamentos e a prescrição dos medicamentos diazepam, fenitoína, fenobarbital e metronidazol. Conclusão A maioria das prescrições pediátricas apresentou potenciais incompatibilidades e a incompatibilidade não testada foi o tipo mais comum. O número de medicamentos e a prescrição dos medicamentos diazepam, fenobarbital, fenitoína e metronidazol foram fatores de risco para potenciais incompatibilidades.

Adesão ao tratamento medicamentoso em usuários cadastrados no Programa Hiperdia no município de Teresina (PI) / Adherence to Drug Treatment among registered users in the "HIPERDIA" Program in Teresina in the State of Piauí

A hipertensão arterial e o diabetes mellitus estão entre as doenças crônicas mais prevalentes no Brasil. Em decorrência disso, em 2002, foi criado o Plano de Reorganização da Atenção à Hipertensão Arterial e Diabetes Mellitus. O presente estudo objetivou avaliar o perfil socioeconômico e a adesão terapêutica dos usuários cadastrados no Programa Hiperdia no município de Teresina (PI). Esta pesquisa foi desenvolvida nas Unidades Básicas de Saúde, onde foi aplicado um questionário a 400 pessoas, avaliando-se sua adesão através dos testes de Batalla e Morisky-Green. O perfil socioeconômico dos entrevistados foi o seguinte: idosos, mulheres, casados, com 1 a 4 anos de estudo, aposentados e assalariados; destes, a maioria são hipertensos. Apenas 22,50% dos hipertensos e 30,70% dos diabéticos foram consideradas aderentes segundo Batalla e de todos apenas 26,75% foram aderentes, segundo Morisky-Green. Não houve associação entre as variáveis sociodemográficas-clínicas e a adesão segundo Morisky-Green, no entanto houve associação com o tipo de morbidade apresentada. Diante desses resultados, a educação em saúde torna-se a principal estratégia para melhorar a adesão dos usuários, como também a participação de profissionais na Equipe Saúde da Família, como: o farmacêutico, o nutricionista e o educador físico.

Arterial hypertension and diabetes mellitus are among the most chronic diseases prevalent in Brazil. The study sought to evaluate the socioeconomic profile and the therapeutic adherence of users registered in the HIPERDIA Program in Teresina in the State of Piauí. This research was conducted in the Primary Healthcare Units, where a questionnaire was given to four hundred people evaluating their adherence based on the Batalla and Morisky-Green tests. The socioeconomic profile of interviewees was as follows: senior citizens, women, married with 1 to 4 years of study, pensioners and salaried employees. Only 22.5% of hypertensive and 30.7% of diabetic interviewees were considered adherents according to Batalla, and among all of them only 26.75% were adherents according to Morisky-Green. There was no association between sociodemographic and clinical variables and adherence according to Morisky-Green, however there was an association with the type of morbidity presented. In light of these results, health education is the main strategy to improve adherence of users as well as the participation of professionals in the Family Healthcare Team, including the pharmacist, the nutritionist and the physical trainer.