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BACKGROUND: Respiratory syncytial virus (RSV) infection in children under 5 years have a significant clinical burden, also in primary care settings. This study investigates the epidemiology and burden of RSV in Italian children during the 2019/20 pre-pandemic winter season. METHODS: A prospective cohort study was conducted in two Italian regions. Children with Acute Respiratory Infection (ARI) visiting pediatricians were eligible. Nasopharyngeal swabs were collected and analyzed via multiplex PCR for RSV detection. A follow-up questionnaire after 14 days assessed disease burden, encompassing healthcare utilization and illness duration. Statistical analyses, including regression models, explored associations between variables such as RSV subtype and regional variations. RESULTS: Of 293 children with ARI, 41% (119) tested positive for RSV. Median illness duration for RSV-positive cases was 7 days; 6% required hospitalization (median stay: 7 days). Medication was prescribed to 95% (110/116) of RSV cases, with 31% (34/116) receiving antibiotics. RSV subtype B and regional factors predicted increased healthcare utilization. Children with shortness of breath experienced a 36% longer illness duration. CONCLUSIONS: This study highlights a significant clinical burden and healthcare utilization associated with RSV in pre-pandemic Italian primary care settings. Identified predictors, including RSV subtype and symptomatology, indicate the need for targeted interventions and resource allocation strategies. RSV epidemiology can guide public health strategies for the implementation of preventive measures.
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COVID-19 , Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Infecções Respiratórias , Criança , Humanos , Lactente , Pré-Escolar , Vírus Sincicial Respiratório Humano/genética , Hospitalização , Estações do Ano , Estudos Prospectivos , Pandemias , COVID-19/epidemiologia , Infecções por Vírus Respiratório Sincicial/epidemiologia , Infecções Respiratórias/epidemiologia , Itália/epidemiologia , Atenção Primária à SaúdeRESUMO
BACKGROUND: As of 2024, vaccination remains the main mitigation measure against COVID-19, but there are contradictory results on whether people living with HIV (PLWH) are less protected by vaccines than people living without HIV (PLWoH). In this study we compared the risk of SARS-CoV-2 infection and COVID-19 hospitalisation following full vaccination in PLWH and PLWoH. METHODS: We linked data from the vaccination registry, the COVID-19 surveillance system and from healthcare/pharmacological registries in four Italian regions. We identified PLWH fully vaccinated (14 days post completion of the primary cycle) and matched them at a ratio of 1:4 with PLWoH by week of vaccine administration, age, sex, region of residence and comorbidities. Follow-up started on January 24, 2021, and lasted for a maximum of 234 days. We used the Kaplan-Meier estimator to calculate the cumulative incidence of infection and COVID-19 hospitalisation in both groups, and we compared risks using risk differences and ratios taking PLWoH as the reference group. RESULTS: We matched 42,771 PLWH with 171,084 PLWoH. The overall risk of breakthrough infection was similar in both groups with a rate ratio (RR) of 1.10 (95% confidence interval (CI):0.80-1.53). The absolute difference between groups at the end of the study period was 8.28 events per 10,000 person-days in the PLWH group (95%CI:-18.43-40.29). There was a non-significant increase the risk of COVID-19 hospitalisation among PLWH (RR:1.90; 95%CI:0.93-3.32) which corresponds to 6.73 hospitalisations per 10,000 individuals (95%CI: -0.57 to 14.87 per 10,000). CONCLUSIONS: Our findings suggest PLWH were not at increased risk of breakthrough SARS-CoV-2 infection or COVID-19 hospitalisation following a primary cycle of mRNA vaccination.
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Vacinas contra COVID-19 , COVID-19 , Infecções por HIV , Hospitalização , Humanos , Hospitalização/estatística & dados numéricos , Itália/epidemiologia , COVID-19/prevenção & controle , COVID-19/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Infecções por HIV/epidemiologia , Adulto , Vacinas contra COVID-19/administração & dosagem , Idoso , SARS-CoV-2 , Sistema de Registros , Adulto Jovem , Fatores de Risco , Vacinação/estatística & dados numéricos , Incidência , Infecções IrruptivasRESUMO
INTRODUCTION: This study investigates the association between parental attitudes towards mandatory and recommended vaccines in the National Immunization Plan (NIP) of Italy and their acceptance of the COVID-19 vaccine in children aged 5-11 years. METHODS: Using data from approximately 42,000 children in Southern Italy, parental attitudes towards previous vaccinations were examined. Mandatory and recommended vaccinations were considered for the analysis, with the first shot of each schedule being considered relevant, regardless of when it was administered or whether the recommended number of doses was administered. A multivariate logistic regression was performed to analyze associations between the covariates of age, sex, adherence to mandatory vaccinations, number of recommended vaccinations, and COVID-19 vaccination. RESULTS: The COVID-19 vaccine acceptance rate was 50.7% in our sample. We revealed a strong association between parental attitudes towards previous vaccinations and the acceptance of the COVID-19 vaccine. Mandatory vaccinations under the NIP showed the highest acceptance rates, and among non-mandatory vaccines, the pneumococcal conjugate vaccine had the highest acceptance rate, potentially due to its co-administration with the hexavalent vaccine. The study identified a trend of lower COVID-19 vaccine coverage in younger children. CONCLUSIONS: The study underscores the importance of co-administration approaches and well-planned vaccination schedules in enhancing vaccine coverage. It suggests that integrating newer vaccines, like the COVID-19 vaccine, into established vaccination schedules could potentially increase acceptance and coverage. The findings highlight the urgency of addressing vaccine hesitancy, particularly in the pediatric population, to ensure high vaccination coverage and effective disease control. Further research is needed to explore the potential strategies to increase vaccine acceptance.
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Vacinas contra COVID-19 , COVID-19 , Pais , Vacinação , Humanos , Itália , Masculino , Feminino , Pais/psicologia , Criança , Pré-Escolar , COVID-19/prevenção & controle , Vacinas contra COVID-19/administração & dosagem , Vacinação/psicologia , Vacinação/estatística & dados numéricos , Programas de Imunização/estatística & dados numéricos , SARS-CoV-2/imunologia , Programas Obrigatórios , Hesitação Vacinal/estatística & dados numéricos , Hesitação Vacinal/psicologia , Cobertura Vacinal/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Conhecimentos, Atitudes e Prática em SaúdeRESUMO
INTRODUCTION: Human respiratory syncytial virus (RSV) is one of the most frequent causes of respiratory infections in children under 5 years of age, but its socioeconomic impact and burden in primary care settings is still little studied. METHODS: During the 2022/2023 winter season, 55 pediatricians from five Italian regions participated in our community-based study. They collected a nasal swab for RSV molecular test from 650 patients under the age of 5 with acute respiratory infections (ARIs) and performed a baseline questionnaire. The clinical and socioeconomic burden of RSV disease in primary care was evaluated by two follow-up questionnaires completed by the parents of positive children on Days 14 and 30. RESULTS: RSV laboratory-confirmed cases were 37.8% of the total recruited ARI cases, with RSV subtype B accounting for the majority (65.4%) of RSV-positive swabs. RSV-positive children were younger than RSV-negative ones (median 12.5 vs. 16.5 months). The mean duration of symptoms for all children infected by RSV was 11.47 ± 6.27 days. We did not observe substantial differences in clinical severity between the two RSV subtypes, but RSV-A positive patients required more additional pediatric examinations than RSV-B cases. The socioeconomic impact of RSV infection was considerable, causing 53% of children to be absent from school, 46% of parents to lose working days, and 25% of families to incur extra costs. CONCLUSIONS: Our findings describe a baseline of the RSV disease burden in primary care in Italy before the introduction of upcoming immunization strategies.
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Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Infecções Respiratórias , Humanos , Criança , Lactente , Pré-Escolar , Infecções por Vírus Respiratório Sincicial/epidemiologia , Estações do Ano , Itália/epidemiologia , Efeitos Psicossociais da Doença , Atenção Primária à Saúde , HospitalizaçãoRESUMO
BACKGROUND: Artificial intelligence (AI) is a rapidly developing field with the potential to transform various aspects of health care and public health, including medical training. During the "Hygiene and Public Health" course for fifth-year medical students, a practical training session was conducted on vaccination using AI chatbots as an educational supportive tool. Before receiving specific training on vaccination, the students were given a web-based test extracted from the Italian National Medical Residency Test. After completing the test, a critical correction of each question was performed assisted by AI chatbots. OBJECTIVE: The main aim of this study was to identify whether AI chatbots can be considered educational support tools for training in public health. The secondary objective was to assess the performance of different AI chatbots on complex multiple-choice medical questions in the Italian language. METHODS: A test composed of 15 multiple-choice questions on vaccination was extracted from the Italian National Medical Residency Test using targeted keywords and administered to medical students via Google Forms and to different AI chatbot models (Bing Chat, ChatGPT, Chatsonic, Google Bard, and YouChat). The correction of the test was conducted in the classroom, focusing on the critical evaluation of the explanations provided by the chatbot. A Mann-Whitney U test was conducted to compare the performances of medical students and AI chatbots. Student feedback was collected anonymously at the end of the training experience. RESULTS: In total, 36 medical students and 5 AI chatbot models completed the test. The students achieved an average score of 8.22 (SD 2.65) out of 15, while the AI chatbots scored an average of 12.22 (SD 2.77). The results indicated a statistically significant difference in performance between the 2 groups (U=49.5, P<.001), with a large effect size (r=0.69). When divided by question type (direct, scenario-based, and negative), significant differences were observed in direct (P<.001) and scenario-based (P<.001) questions, but not in negative questions (P=.48). The students reported a high level of satisfaction (7.9/10) with the educational experience, expressing a strong desire to repeat the experience (7.6/10). CONCLUSIONS: This study demonstrated the efficacy of AI chatbots in answering complex medical questions related to vaccination and providing valuable educational support. Their performance significantly surpassed that of medical students in direct and scenario-based questions. The responsible and critical use of AI chatbots can enhance medical education, making it an essential aspect to integrate into the educational system.
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Large Language Models (LLMs) have recently gathered attention with the release of ChatGPT, a user-centered chatbot released by OpenAI. In this perspective article, we retrace the evolution of LLMs to understand the revolution brought by ChatGPT in the artificial intelligence (AI) field. The opportunities offered by LLMs in supporting scientific research are multiple and various models have already been tested in Natural Language Processing (NLP) tasks in this domain. The impact of ChatGPT has been huge for the general public and the research community, with many authors using the chatbot to write part of their articles and some papers even listing ChatGPT as an author. Alarming ethical and practical challenges emerge from the use of LLMs, particularly in the medical field for the potential impact on public health. Infodemic is a trending topic in public health and the ability of LLMs to rapidly produce vast amounts of text could leverage misinformation spread at an unprecedented scale, this could create an "AI-driven infodemic," a novel public health threat. Policies to contrast this phenomenon need to be rapidly elaborated, the inability to accurately detect artificial-intelligence-produced text is an unresolved issue.
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Inteligência Artificial , Infodemia , Saúde Pública , Idioma , Processamento de Linguagem NaturalRESUMO
Antimicrobial resistance (AMR) presents a growing threat to global healthcare. This descriptive epidemiological study investigates the prevalence and characteristics of Enterobacterales with AMR factors in a tertiary teaching hospital in Italy over the course of the year 2021. In 2021, the prevalence of colonisation by Enterobacterales with AMR factors in patients was 1.08%. During the observation period, a total of 8834 rectal swabs were performed, with 1453 testing positive. A total of 5639 rectal swabs were performed according to a hospital procedure for the active screening of MDRO colonisation at the time of admission. Of these, 679 were positive for microorganisms under surveillance, and 74 patients were colonised with Enterobacterales, predominantly Klebsiella pneumoniae and Escherichia coli. Antibiotic resistance factors were observed in 61 of these 74 patients (82.43%) of these patients, with NDM and KPC being the most frequent resistance factors. A statistically significant trend in positive swabs was observed across different ward categories (surgery, ICUs, and medical wards). Regarding specific trends, the rate of positive admission screening in medical and surgical wards was higher than in ICU wards. The results highlight the ease with which Enterobacterales develops resistance across different ward categories. The findings underscore the need for adjusted screening protocols and tailored infection prevention strategies in various care settings.
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Background: Vaccination in pregnancy offers protection to the mother and the newborn. In Italy, influenza, pertussis, and COVID-19 vaccinations are recommended in pregnancy, but vaccination coverage is still far from the National Immunization Plan goals. We aimed to assess knowledge and attitude on maternal immunization in two groups of Italian women, in pregnancy and in reproductive age (non pregnant). Methods: A cross sectional study on Italian childbearing age women gathering information on their knowledge on maternal immunization and attitudes to receiving influenza and pertussis vaccines in pregnancy was carried out at the University of Rome Tor Vergata, between September 2019 and February 2020. Logistic and multinomial regressions were chosen as statistical tests for our analysis. Results: 1,031 women participated in the survey by answering the questionnaire. Out of these, 553 (53.6%) women were pregnant, and 478 (46.4%) were in the reproductive age. 37% (204/553) of pregnant women and 41% (198/476) of non pregnant women are aware of the existence of an immunization plan for pregnant women in Italy. The group with age between 20 and 30, for both pregnant women and women in the reproductive age, has a better knowledge of vaccination in pregnancy. Working status is a variable associated with more awareness about vaccination during pregnancy only for pregnant women (OR = 2.34, p < 0.00001). Educational status, trimester of pregnancy and knowledge on the topic are associated with vaccine hesitancy in our multivariate analysis for pregnant women. In the reproductive age group women who had a previous pregnancy are more likely to be hesitant towards vaccination in pregnancy, on the other hand the one with a higher knowledge and educational status are more likely to get vaccinated. Conclusions: The study highlights the persistent vaccine hesitancy among Italian women of reproductive age and pregnant women. Despite healthcare providers being identified as a reliable source of information, their recommendations alone are insufficient to overcome vaccine hesitancy. Factors such as employment status, educational level, pregnancy trimester, and knowledge about vaccinations during pregnancy influence vaccine hesitancy. Tailored educational interventions and communication campaigns targeting these areas can help reduce vaccine hesitancy and promote maternal immunization.
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As the COVID19 pandemic progresses, there is an increasing need to evaluate the performance of vaccine strategies. This study investigated the vaccine schedule performance of heterologous vaccination compared to homologous vaccination in preventing Omicron SARS-CoV2 infection in the adult population. This retrospective cohort study utilized data from the Infections Regional Information System and the Apulia Regional Vaccine Registry to identify individuals who received a booster dose of one of 14 different COVID19 vaccination schedules between September 2021 and August 2022 in the province of Lecce, Southern Italy. The standardized cumulative incidence of SARS-CoV2 infection after the booster dose was assessed and the risk of infection between subgroups of heterologous and homologous vaccination schedules was compared using the Cochran-Mantel-Haenszel test. A total of 469,069 subjects were included in the study. The standardized incidence of SARS-CoV2 infection varied greatly among different vaccine schedules, with the highest and lowest being AZ-AZ-BNT (34.7 %) and MOD-MOD-BNT (18.9 %), respectively, and some heterologous schedules performing better than homologous ones. The risk of SARS-CoV2 infection was significantly lower in individuals who received specific heterologous vaccination schedules compared to homologous vaccination schedules, the best performing being MOD-MOD-BNT with a common odd ratio of 0.661 (IC. 95 % [0.620-0.704]). This study provides evidence that heterologous vaccination schedules may be more effective in preventing Omicron SARS-CoV2 infection compared to homologous vaccination schedules, highlighting how the vaccine product, rather than the platform, is involved in the different protection provided by heterologous vaccination.
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Vacinas contra COVID-19 , COVID-19 , Adulto , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , RNA Viral , Estudos Retrospectivos , SARS-CoV-2 , Itália/epidemiologia , Vacinação , Anticorpos AntiviraisRESUMO
INTRODUCTION: Healthcare-associated infections (HAIs) and antimicrobial resistance (AMR) are major public health threats in upper- and lower-middle-income countries. Electronic health records (EHRs) are an invaluable source of data for achieving different goals, including the early detection of HAIs and AMR clusters within healthcare settings; evaluation of attributable incidence, mortality, and disability-adjusted life years (DALYs); and implementation of governance policies. In Italy, the burden of HAIs is estimated to be 702.53 DALYs per 100,000 population, which has the same magnitude as the burden of ischemic heart disease. However, data in EHRs are usually not homogeneous, not properly linked and engineered, or not easily compared with other data. Moreover, without a proper epidemiological approach, the relevant information may not be detected. In this retrospective observational study, we established and engineered a new management system on the basis of the integration of microbiology laboratory data from the university hospital "Policlinico Tor Vergata" (PTV) in Italy with hospital discharge forms (HDFs) and clinical record data. All data are currently available in separate EHRs. We propose an original approach for monitoring alert microorganisms and for consequently estimating HAIs for the entire period of 2018. METHODS: Data extraction was performed by analyzing HDFs in the databases of the Hospital Information System. Data were compiled using the AREAS-ADT information system and ICD-9-CM codes. Quantitative and qualitative variables and diagnostic-related groups were produced by processing the resulting integrated databases. The results of research requests for HAI microorganisms and AMR profiles sent by the departments of PTV from 01/01/2018 to 31/12/2018 and the date of collection were extracted from the database of the Complex Operational Unit of Microbiology and then integrated. RESULTS: We were able to provide a complete and richly detailed profile of the estimated HAIs and to correlate them with the information contained in the HDFs and those available from the microbiology laboratory. We also identified the infection profile of the investigated hospital and estimated the distribution of coinfections by two or more microorganisms of concern. Our data were consistent with those in the literature, particularly the increase in mortality, length of stay, and risk of death associated with infections with Staphylococcus spp, Pseudomonas aeruginosa, Klebsiella pneumoniae, Clostridioides difficile, Candida spp., and Acinetobacter baumannii. Even though less than 10% of the detected HAIs showed at least one infection caused by an antimicrobial resistant bacterium, the contribution of AMR to the overall risk of increased mortality was extremely high. CONCLUSIONS: The increasing availability of health data stored in EHRs represents a unique opportunity for the accurate identification of any factor that contributes to the diffusion of HAIs and AMR and for the prompt implementation of effective corrective measures. That said, artificial intelligence might be the future of health data analysis because it may allow for the early identification of patients who are more exposed to the risk of HAIs and for a more efficient monitoring of HAI sources and outbreaks. However, challenges concerning codification, integration, and standardization of health data recording and analysis still need to be addressed.
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Anti-Infecciosos , Infecção Hospitalar , Humanos , Inteligência Artificial , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologia , Hospitais Universitários , Fatores de RiscoRESUMO
BACKGROUND: Stroke is a dangerous long-term complication of kidney failure, yet its occurrence early in disease is poorly characterized. Our aim was to investigate the association of reduced kidney function, hypertension and diabetes with acute ischaemic stroke and the outcome thereof. METHODS: In this prospective cohort study, the association of reduced kidney function, hypertension and diabetes with stroke and 2-year all-cause mortality was investigated. Glomerular filtration rate (eGFR) was estimated by the simplified Modification of Diet in Renal Disease formula in 13 365 consecutive patients (671 with acute ischaemic stroke) admitted to our clinical facility over a 12-month period. RESULTS: Ischaemic stroke, after adjustment for age and gender, was significantly associated with eGFR <60 mL/min/1.73m(2) [odds ratio (OR) 1.53, 95% confidence interval (CI) 1.30-1.81], hypertension (2.77, 95% CI 2.33-3.28) and diabetes (1.30, 95% CI 1.04-1.63). Multivariate analysis of interaction indicated the absence of an additive effect between eGFR, hypertension and diabetes, on the risk of stroke. Age and gender-adjusted survival analysis by Cox regression showed an association of mortality with reduced eGFR alone (HR = 4.29, 95% CI 1.02-19.60). CONCLUSIONS: In patients acutely admitted to hospital, reduced kidney function, hypertension and diabetes are independently associated with ischaemic stroke, but do not exert a synergic effect. After hospital discharge, mortality is strongly associated with reduced eGFR but with neither hypertension nor diabetes.
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Diabetes Mellitus/etiologia , Hipertensão/etiologia , Isquemia/complicações , Nefropatias/etiologia , Acidente Vascular Cerebral/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Taxa de Filtração Glomerular , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores de Risco , Taxa de Sobrevida , Adulto JovemRESUMO
BACKGROUND: Chronic kidney disease (CKD) is an emerging worldwide problem. The lack of attention paid to kidney disease is well known and has been described in previous publications. However, little is known about the magnitude of the problem in highly specialized hospitals where serum creatinine values are used to estimate GFR values. METHODS: We performed a cross-sectional evaluation of hospitalized adult patients who were admitted to the medical or surgical department of Santa Maria della Misericordia Hospital in 2007. Information regarding admissions was derived from a database. Our goal was to assess the prevalence of CKD (defined as an estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73 m2) and detection of CKD using diagnostic codes (Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM]). To reduce the impact of acute renal failure on the study, the last eGFR obtained during hospitalization was the value used for analysis, and intensive care and nephrology unit admissions were excluded. We also excluded patients who had ICD-9-CM codes for renal replacement therapy, acute renal failure, and contrast administration listed as discharge diagnoses. RESULTS: Of the 18,412 patients included in the study, 4,748 (25.8%) had reduced eGFRs, falling into the category of Kidney Disease Outcomes Quality Initiative (KDOQI) stage 3 (or higher) CKD. However, the diagnosis of CKD was only reported in 19% of these patients (904/4,748). It is therefore evident that there was a "gray area" corresponding to stage 3 CKD (eGFR 30-59 ml/min), in which most CKD diagnoses are missed. The ICD-9 code sensitivity for detecting CKD was significantly higher in patients with diabetes, hypertension, and cardiovascular disease (26.8%, 22.2%, and 23.7%, respectively) than in subjects without diabetes, hypertension, or cardiovascular disease (p < 0.001), but these values are low when the widely described relationship between such comorbidities and CKD is considered. CONCLUSION: Although CKD was common in this patient population at a large inpatient regional hospital, the low rates of CKD detection emphasize the primary role nephrologists must play in continued medical education, and the need for ongoing efforts to train physicians (particularly primary care providers) regarding eGFR interpretation and systematic screening for CKD in high-risk patients (i.e., the elderly, diabetics, hypertensives, and patients with CV disease).
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Taxa de Filtração Glomerular , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Creatinina/sangue , Reações Falso-Negativas , Feminino , Humanos , Incidência , Itália/epidemiologia , Falência Renal Crônica/sangue , Masculino , Pessoa de Meia-Idade , Programas Médicos Regionais/estatística & dados numéricos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Adulto JovemAssuntos
Inteligência Artificial , Medicina de Viagem , Humanos , Medicina de Viagem/métodos , ViagemRESUMO
BACKGROUND: The aim of this study was to investigate the association of reduced kidney function, diabetes and arterial hypertension with mortality in cardiovascular disease patients admitted to hospital. METHODS: This was a prospective cohort study. The setting was the reference hospital for the population area. Unselected consecutive patients (n=7,487) admitted to the hospital over 12 months were enrolled. In all subjects, the estimated glomerular filtration rate (eGFR) was determined, and the association of acute and 36-month mortality with kidney function impairment, diabetes and arterial hypertension was assessed. RESULTS: Short-term mortality (314 deaths) was significantly associated with reduced eGFR only in patients with chronic ischemic heart disease. The study of 36-month survival in the whole cohort showed that mortality (918 deaths) was significantly associated with age, male sex and reduced eGFR. The study repeated for the individual CV conditions showed that reduced eGFR was associated with mortality only in chronic ischemic heart disease. No association with sex of patient, diabetes or arterial hypertension was found. CONCLUSIONS: Although the association between reduced kidney function and CV diseases was confirmed, the analysis of survival in the individual conditions shows that only in chronic ischemic disease is mortality associated with reduced eGFR. Any interaction with 2 major predisposing diseases - diabetes and arterial hypertension - has not been shown.