Adverse drug reactions in hospitals: population estimates for Portugal and the ICD-9-CM to ICD-10-CM crosswalk.

BACKGROUND: Adverse drug reactions (ADR), both preventable and non-preventable, are frequent and pose a significant burden. This study aimed to produce up-to-date estimates for ADR rates in hospitals, in Portugal, from 2010 to 2018. In addition, it explores possible pitfalls when crosswalking between ICD-9-CM and ICD-10-CM code sets for ADR identification. METHODS: The Portuguese Hospital Morbidity Database was used to identify hospital episodes (outpatient or inpatient) with at least one ICD code of ADR. Since the study period spanned from 2010 to 2018, both ICD-9-CM and ICD-10-CM codes based on previously published studies were used to define episodes. This was an exploratory study, and descriptive statistics were used to provide ADR rates and summarise episode features for the full period (2010-2018) as well as for the ICD-9-CM (2010-2016) and ICD -10-CM (2017-2018) eras. RESULTS: Between 2010 and 2018, ADR occurred in 162,985 hospital episodes, corresponding to 1.00% of the total number of episodes during the same period. Higher rates were seen in the oldest age groups. In the same period, the mean annual rate of episodes related to ADR was 174.2/100,000 population. The episode rate (per 100,000 population) was generally higher in males, except in young adults (aged '15-20', '25-30' and '30-35' years), although the overall frequency of ADR in hospital episodes was higher in females. CONCLUSIONS: Despite the ICD-10-CM transition, administrative health data in Portugal remain a feasible source for producing up-to-date estimates on ADR in hospitals. There is a need for future research to identify target recipients for preventive interventions and improve medication safety practices in Portugal.

[Oral Anticoagulation and the Incidence of Stroke Associated with Atrial Fibrillation in Mainland Portugal: A Modelling Study]. / Anticoagulação Oral e Incidência de Acidente Vascular Cerebral Associado a Fibrilhação Auricular em Portugal Continental: Um Estudo de Modelação.

INTRODUCTION: Atrial fibrillation is the most prevalent persistent dysrhythmia, contributing to a significant social and economic burden. The main objective of this study was to evaluate the association between oral anticoagulant use and the incidence of stroke associated with atrial fibrillation, in mainland Portugal. METHODS: The number of episodes of inpatient care with a main diagnosis of stroke and an additional diagnosis of atrial fibrillation, occurring monthly between January 2012 and December 2018, in individuals aged 18 years or over, was extracted from the hospital morbidity database. The number of patients with an atrial fibrillation code documented in this database was used as a proxy for the prevalence of known atrial fibrillation. The number of anticoagulated patients was estimated from total medicine sales of vitamin K antagonists and novel oral anticoagulants (apixaban, dabigatran, edoxaban and rivaroxaban) in mainland Portugal. Descriptive analyses were performed, and seasonal autoregressive integrated moving average (SARIMA) models were built using the R software. RESULTS: The mean number of episodes of stroke per month was 522 (± 57). The number of anticoagulated patients increased gradually from 68 943 to 180 389 per month. The decreasing trend in the number of episodes has been observed since 2016, along with the increased use of new oral anticoagulants compared to vitamin K antagonists. The final model indicated that the increase in oral anticoagulation use between 2012 and 2018, in mainland Portugal, was associated with a decrease in the number of episodes of stroke associated with atrial fibrillation. It was estimated that the shift in the type of anticoagulation used, between 2016 and 2018, was associated with a reduction of 833 episodes of stroke in patients with atrial fibrillation (4.2%). CONCLUSION: The use of oral anticoagulation was associated with a reduced incidence of stroke in patients with atrial fibrillation in mainland Portugal. This reduction was more relevant in the period between 2016 and 2018, and is probably related with the introduction of the novel oral anticoagulants.

Introdução: A fibrilhação auricular é a disritmia persistente mais prevalente, tendo um importante impacto social e económico. O objetivo principal deste estudo foi avaliar a associação entre a utilização de anticoagulantes orais e a incidência de acidente vascular cerebral associado a fibrilhação auricular, em Portugal continental. Métodos: A base de dados de morbilidade hospitalar foi utilizada para a contabilização dos episódios de internamento com um diagnóstico principal de acidente vascular cerebral e um diagnóstico adicional de fibrilhação auricular, ocorridos durante cada mês do período em análise (janeiro de 2012 a dezembro de 2018), em indivíduos com idade igual ou superior a 18 anos. O número de doentes com registo de fibrilhação auricular presentes nesta base de dados foi utilizado como um proxy da prevalência de fibrilhação auricular conhecida. O número de doentes anticoagulados foi estimado a partir das estatísticas das vendas de antagonistas da vitamina K e novos anticoagulantes orais (apixabano, dabigatrano, edoxabano e rivaroxabano) em Portugal continental. Foi realizada uma análise descritiva das variáveis, construindo-se depois modelos auto-regressivos integrados de médias móveis sazonais (seasonal autoregressive integrated moving average, SARIMA), com recurso ao software R. Resultados: Ocorreram, em média, 522 (± 57) episódios de acidente vascular cerebral por mês. Verificou-se um aumento gradual do número de doentes anticoagulados, passando de 68 943 para 180 389, por mês. A tendência decrescente no número de episódios verificou-se a partir de 2016, a par da maior utilização dos novos anticoagulantes orais, comparativamente aos antagonistas da vitamina K. O modelo final estimado indicou que o aumento do consumo de anticoagulação oral entre 2012 e 2018 em Portugal continental foi associado a um decréscimo do número de acidentes vasculares cerebrais associados a fibrilhação auricular. Estimou-se que, entre 2016 e 2018, a mudança no tipo de anticoagulação se associou a uma redução de 833 episódios de acidentes vascular cerebrais em doentes com fibrilhação auricular (4,2%). Conclusão: A anticoagulação oral associou-se à redução da incidência de acidente vascular cerebral em doentes com fibrilhação auricular, em Portugal continental. Esta redução foi mais relevante no período 2016 a 2018, em provável relação com a introdução dos novos anticoagulantes orais.

Screening strategies for atrial fibrillation in the elderly population: a systematic review and network meta-analysis.

Opportunistic screening for atrial fibrillation (AF) is currently recommended for patients aged 65 years and older. However, this has recently been called into question by two studies that report that opportunistic screening is no more effective than usual care. Furthermore, there seems to be no consensus on which is the most effective screening strategy (opportunistic or systematic). Thus, we aimed to compare the different AF detection strategies with each other using the methodology of systematic review with network meta-analysis. An electronic database search of MEDLINE, CENTRAL, and EMBASE was performed. In addition, we also searched OpenGrey, experts' knowledge and screened the reference list of included studies or other relevant publications. The search was performed on the 2nd of November of 2020 and updated on the 20th of September of 2021. We performed a random-effects pairwise meta-analysis and a random-effects network meta-analysis within a frequentist framework in an intention to screen analysis. We reported the results as relative risk (RR) with 95% confidence intervals (CI). We assessed the confidence in the evidence using the GRADE framework. Nine studies were included, enrolling 80,665 participants. Pooled effect sizes suggested that systematic screening was effective when compared with usual care (RR 2.11; 95% CI 1.48-3.02; high GRADE confidence) and when compared with opportunistic screening (RR 1.86; CI 1.23-2.82; high GRADE confidence) but no significant difference was found between opportunistic screening and usual care (RR 1.13; 95% CI 0.79-1.63; low GRADE confidence). Systematic screening was the most effective strategy for detecting atrial fibrillation in individuals aged 65 years or older. Opportunistic screening was no more effective than usual care, but the results were weakened by a low quality of evidence due to risk of bias of the included studies and imprecision in the results. PROSPERO registration number: CRD42020218672.

Atherosclerosis in the primary health care setting: A real-word data study.

INTRODUCTION AND OBJECTIVES: To characterize patients with atherosclerosis, a disease with a high socioeconomic impact, in the Lisbon and Tagus Valley Health Region. METHODS: A cross-sectional observational study was carried out through the Lisbon and Tagus Valley Regional Health Administration primary health care database, extracting data on the clinical and demographic characteristics and resource use of adult primary health care users with atherosclerosis during 2016. Different criteria were used to define atherosclerosis (presence of clinical manifestations, atherothrombotic risk factors and/or consumption of drugs related to atherosclerosis). Comparisons between different subpopulations were performed using parametric tests. RESULTS: A total of 318 692 users were identified, most of whom (n=224 845 users; 71%) had no recorded clinical manifestations. The subpopulation with clinical manifestations were older (72.0±11.5 vs. 71.3±11.0 years), with a higher proportion of men (58.0% vs. 45.9%), recorded hypertension (78.3% vs. 73.5%) and dyslipidemia (55.8% vs. 53.5%), and a lower proportion of recorded obesity (18.2% vs. 20.8%), compared to those without clinical manifestations (p<0.001). Mean blood pressure, LDL-C and glycated hemoglobin values were lower in the subpopulation with manifestations (142/74 vs. 146/76 mmHg, 101 vs. 108 mg/dl, and 6.80 vs. 6.84%, respectively; p<0.001). Each user with atherosclerosis attended 4.1±2.9 face-to-face medical consultations and underwent 8.6±10.0 laboratory test panels, with differences in subpopulations with and without clinical manifestations (4.4±3.2 vs. 4.0±2.8 and 8.3±10.3 vs. 8.7±9.8, respectively; p<0.001). CONCLUSIONS: About one in three adult primary health care users with atherosclerosis have clinical manifestations. The results suggest that control of cardiovascular risk factors is suboptimal in patients with atherosclerosis.

The epidemiology of falls in Portugal: An analysis of hospital admission data.

BACKGROUND: Falls are a common cause of injury and pose an increased risk of morbidity, mortality, and lifelong disability. Falls encompass a troublesome definition and can pose challenges in epidemiological studies. Data on fall-related hospital admissions in Portugal remain unpublished. This study aimed to examine the epidemiology of fall-related hospital admissions in the Portuguese population between 2010 and 2018. It also aimed to examine annual rates of fall-related hospital admissions using three methodological approaches. METHODS: The Portuguese Hospital Morbidity Database was used to identify all cases resulting in one or more inpatient admission in public hospitals related to falls from 2010 to 2018. Fall-related hospital admissions were described by age groups, sex, geographical area of residence, and type of fall. Annual rates were computed using three approaches: i) based on the number of inpatient admissions with an ICD code of fall, ii) based on the number of patients admitted to inpatient care with an ICD code of fall, and iii) based on the number of inpatient admissions with a principal diagnosis of injury. RESULTS: Between 2010 and 2018, 383,016 fall-related admissions occurred in 344,728 patients, corresponding to 2.1% of the total number of hospitalizations during the same period. Higher rates were seen among the younger (20-25) and the oldest age groups (+85), males until the age of 60, females from the age of 60, and areas of residence with a higher aging index. An overall rate of falls per 100,000 population was estimated at 414 (based on number of admissions), 373 (based on number of patients) and 353 (based on number of admissions with a principal diagnosis of injury). CONCLUSIONS: This study provides an overall picture of the landscape of falls in a scarcely explored setting. The results aim to contribute to identifying appropriate preventive interventions and policies for these populations.

Atherosclerosis: The cost of illness in Portugal.

INTRODUCTION AND OBJECTIVES: Cardiovascular disease is the leading cause of death in Portugal and atherosclerosis is the most common underlying pathophysiological process. The aim of this study was to quantify the economic impact of atherosclerosis in Portugal by estimating disease-related costs. METHODS: Costs were estimated based on a prevalence approach and following a societal perspective. Three national epidemiological sources were used to estimate the prevalence of the main clinical manifestations of atherosclerosis. The annual costs of atherosclerosis included both direct costs (resource consumption) and indirect costs (impact on population productivity). These costs were estimated for 2016, based on data from the Hospital Morbidity Database, the health care database (SIARS) of the Regional Health Administration of Lisbon and Tagus Valley including real-world data from primary care, the 2014 National Health Interview Survey, and expert opinion. RESULTS: The total cost of atherosclerosis in 2016 reached 1.9 billion euros (58% and 42% of which was direct and indirect costs, respectively). Most of the direct costs were associated with primary care (55%), followed by hospital outpatient care (27%) and hospitalizations (18%). Indirect costs were mainly driven by early exit from the labor force (91%). CONCLUSIONS: Atherosclerosis has a major economic impact, being responsible for health expenditure equivalent to 1% of Portuguese gross domestic product and 11% of current health expenditure in 2016.

The burden of atherosclerosis in Portugal.

AIMS: This article sought to estimate the burden of disease attributable to atherosclerosis in mainland Portugal in 2016. METHODS AND RESULTS: The burden of atherosclerosis was measured in disability-adjusted life years following the latest 2010 Global Burden of Disease (GBD) methodology. Disability-adjusted life years were estimated as the sum of years of life lost (YLL) with years lived with disability (YLD). The following clinical manifestations of atherosclerosis were included: ischaemic heart disease (IHD) (including acute myocardial infarction, stable angina, and ischaemic heart failure), ischaemic cerebrovascular disease (ICVD), and peripheral arterial disease (PAD). Years of life lost were estimated based on all-cause mortality data for the Portuguese population and mortality due to IHD, ICVD, and PAD for the year 2016 sourced from national statistics. Standard life expectancy was sourced from the GBD study. Years lived with disability corresponded to the product of the number of prevalent cases by an average disability weight for all possible combinations of disease. Prevalence data for the different clinical manifestations of atherosclerosis were sourced from epidemiological studies. Disability weights were sourced from the published literature. In 2016, 15 123 deaths were attributable to atherosclerosis, which corresponded to 14.3% of overall mortality in mainland Portugal. Disability-adjusted life years totalled 260 943, 75% due to premature death (196 438 YLL) and 25% due to disability (64 505 YLD). CONCLUSION: Atherosclerosis entails a high disease burden to society. A large part of this burden would be avoidable if evidence-based effective and cost-effective interventions targeting known risk factors, from prevention to treatment, were implemented.

Current costs of heart failure in Portugal and expected increases due to population aging. / Os custos da insuficiência cardíaca em Portugal e a sua evolução previsível com o envelhecimento da população.

INTRODUCTION AND OBJECTIVES: Heart failure (HF) is a growing public health problem. This study estimates the current and future costs of HF in mainland Portugal. METHODS: Costs were estimated based on prevalence and from a societal perspective. The annual costs of HF included direct costs (resource consumption) and indirect costs (productivity losses). Estimates were mostly based on data from the Diagnosis-Related Groups database, real-world data from primary care, and the opinions of an expert panel. Costs were estimated for 2014 and, taking population aging into account, changes were forecast up to 2036. RESULTS: Direct costs in 2014 were €299 million (39% for hospitalizations, 24% for medicines, 17% for exams and tests, 16% for consultations, and the rest for other needs, including emergencies and long-term care). Indirect costs were €106 million (16% for absenteeism and 84% for reduced employment). Between 2014 and 2036, due to demographic dynamics, total costs will increase from €405 to €503 million. Per capita costs are estimated to rise by 34%, which is higher than the increase in total costs (+24%), due to the expected reduction in the resident population. CONCLUSIONS: HF currently has a significant economic impact, representing around 2.6% of total public health expenditure, and this is expected to increase in the future. This should be taken into account by health policy makers, alerting them to the need for resource management in order to mitigate the impact of this disease.

Cost-effectiveness of sacubitril/valsartan for the treatment of patients with heart failure with reduced ejection fraction in Portugal.

Objectives: This study assesses the cost-effectiveness of sacubitril/valsartan versus enalapril in patients with symptomatic heart failure with reduced ejection fraction (HFrEF).Methods: We used a previously developed Markov model calibrated with patient-level data from the PARADIGM-HF trial, adapted to the Portuguese setting. The model considers two health states (alive or dead) and uses regression analyzes to estimate hospitalizations and deaths over time. A panel of experts estimated resource consumption in the outpatient setting. To estimate resource consumption with hospitalizations, the National Health Service Diagnosis Related Groups database was used. Unit costs were based on national legislation, and on the Infomed database. The model considers a societal perspective, a time horizon of 30-years, and a 5% annual discount rate. Sensitivity analyses assessed the robustness of results.Results: Sacubitril/valsartan increases life expectancy by 0.5 life-years, corresponding to 0.4 incremental quality adjusted life-years (QALY) versus enalapril. The estimated incremental cost-effectiveness ratio (ICER) is 22,702€/QALY. Sensitivity analysis shows that results are robust, but sensitive to the parameter estimates of the cardiovascular survival curve.Conclusion: Sacubitril/valsartan is a cost-effective therapeutic option in the treatment of Portuguese patients with HFrEF and translate into significant health gains and increased life expectancy versus the current standard of care.

The current and future burden of heart failure in Portugal.

AIMS: Heart failure (HF) is a clinical syndrome with significant social and economic burden. We aimed to estimate the burden of HF in mainland Portugal over a 22-year time horizon, between 2014 and 2036. METHODS AND RESULTS: Heart failure burden was measured in disability-adjusted life years (DALYs), resulting from the sum of years of life lost (YLL) due to premature death and years lost due to disability (YLD). YLL were estimated based on the Portuguese mortality rates reported by the European Detailed Mortality Database. For YLD, disease duration and the overall incidence were estimated using an epidemiological model developed by the World Health Organization (DISMOD II). Disability weights were retrieved from published literature. The impact of ageing was estimated with a shift-share analysis using official demographic projections. In 2014, 4688 deaths were attributed to HF, corresponding to 4.7% of the total deaths in mainland Portugal. DALYs totalled 21 162, 53.9% due to premature death (YLL: 11 398) and 46.1% due to disability (YLD: 9765). Considering only population ageing over a 22-year horizon, the deaths and burden of HF are expected to increase by 73.0% and 27.9%, respectively, reaching 8112 deaths and 27 059 DALYs lost due to HF in 2036. DALY's growth is mainly driven by the increase of YLL, whose contribution to overall burden will increase to 62.0%. CONCLUSIONS: Heart failure is an emerging and growing health problem where significant health gains may be obtained. The projected significant increase of HF burden highlights the need to set HF as a priority for healthcare system.

Does acute myocardial infarction kill more people on weekends? Analysis of in-hospital mortality rates for weekend admissions in Portugal.

Objectives To investigate a possible weekend effect in the in-hospital mortality rate for acute myocardial infarction in Portugal, and whether the delay in invasive intervention contributes to this effect. Methods Data from the National 2011-2015 Diagnostic-Related-Group databases were analysed. The focus was on adult patients admitted via the emergency department and with the primary diagnosis of acute myocardial infarction. Patients were grouped according to ST-elevation myocardial infarction and non-ST-elevation myocardial infarction episodes. We employed multivariable logistic regressions to determine the association between weekend admission and in-hospital mortality, controlling for episode complexity (through a severity index and acute comorbidities), demographic characteristics and hospital identifications. The association between the probability of a prompt surgery (within one day) and the day of admission was investigated to explore the possible delay of care delivery for patients admitted during weekends. Results Our results indicate that in-hospital mortality rates were not significantly higher for weekend admissions than for weekday admissions in both ST-elevation myocardial infarction (STEMI) and non-STEMI episodes. This result is robust to the inclusion of a number of potential confounding mechanisms. Patients admitted on weekends had lower probabilities of undergoing invasive cardiac surgery within the day after admission, but delay in care delivery during the weekend was not associated with worse outcomes in terms of in-hospital mortality. Conclusions There is no evidence for the existence of a weekend effect due to admission for acute myocardial infarction in Portugal, in both STEMI and non-STEMI episodes.

Clinical comparability of the new antiepileptic drugs in refractory partial epilepsy: a systematic review and meta-analysis.

PURPOSE: Evaluate the clinical comparability of new antiepileptic drugs (AEDs) in partial refractory epilepsy. METHODS: Systematic review of randomized trials (RCTs) comparing a new AED (add-on treatment) with placebo or another AED. PRIMARY OUTCOMES: responder (≥50% seizure reduction) and withdrawal (tolerability) rates. Pooled estimates of odds ratios (ORs) and number needed treat/harm (NNT/NNH) taking into account baseline risk were derived by random-effects meta-analysis. Adjusted frequentist indirect comparisons between AEDs were estimated. KEY FINDINGS: Sixty-two placebo-controlled (12,902 patients) and eight head-to-head RCTs (1,370 patients) were included. Pooled ORs for responder and withdrawal rates (vs. placebo) were 3.00 [95% confidence interval (CI) 2.63-3.41] and 1.48 (1.30-1.68), respectively. Indirect comparisons of responder rate based on relative measurements of treatment effect (ORs) favored topiramate (1.52; 1.06-2.20) in comparison to all other AEDs, whereas gabapentin (0.67; 0.46-0.97) and lacosamide (0.66; 0.48-0.92) were less efficacious, without significant heterogeneity. When analyses were based on absolute estimates (NNTs), topiramate and levetiracetam were more efficacious, whereas gabapentin and tiagabine were less efficacious. Withdrawal rate was higher with oxcarbazepine (OR 1.60; 1.12-2.29) and topiramate (OR 1.68; 1.07-2.63), and lower with gabapentin (OR 0.65; 0.42-1.00) and levetiracetam (OR 0.62; 0.43-0.89). SIGNIFICANCE: The differences found are of relatively small magnitude to allow a definitive conclusion about which new AED(s) has superior effectiveness. This uncertainty probably reflects the limitations of conclusions based on indirect evidence. The process of pharmacologic clinical decision making in partial refractory epilepsy probably depends more on other aspects, such as individual patient characteristics and pharmacoeconomics, than on available controlled randomized evidence.

Drug therapy for chronic heart failure due to left ventricular systolic dysfunction: a review. III. Angiotensin-converting enzyme inhibitors.

The role of angiotensin-converting enzyme inhibitors (ACEIs) in heart failure (HF), which act primarily by inhibiting the renin-angiotensin-aldosterone system, has been thoroughly studied in different subgroups. This article reviews the most valid and recent evidence available concerning the use of ACEIs in HF due to left ventricular systolic dysfunction. The administration of ACEIs leads to statistically and clinically significant reductions in mortality (20 to 23%), risk of myocardial infarction (20 to 21%), hospitalization for heart failure (33%) and symptoms (as measured by NYHA classification). The existence of a class effect has been suggested for ACEIs. However, it has not been possible to demonstrate a significant effect on mortality in subgroup analysis for females or blacks. Higher doses of ACEIs are associated with a significant reduction in the combined endpoint of death or hospitalization for any reason and fewer hospitalizations for heart failure, but not in mortality risk or improvement as measured by NYHA class. All patients with HF should be prescribed an ACEI except in cases of contraindication or adverse reactions.

Drug therapy for chronic heart failure due to left ventricular systolic dysfunction. II. Diuretics.

Diuretics (particularly loop diuretics) are usually considered the first-line treatment for patients with chronic heart failure (CHF). The aldosterone antagonists, spironolactone and eplerenone, which are not unanimously classified as diuretics, have recently been included in therapy for CHF. Diuretics are the only drugs able to reduce fluid retention in CHF, although they are unable to maintain clinical stability for long periods of time when used in isolation. This article reviews the most valid and recent evidence available, based exclusively on large randomized controlled trials and systematic reviews and meta-analyses selected from secondary sources, on the use of diuretics in CHF with left ventricular systolic dysfunction.