RESUMO
Approximately half of individuals with hypophosphatasemia (low levels of serum alkaline phosphatase) have hypophosphatasia, a rare genetic disease in which patients may have stress fractures, bone and joint pain, or premature tooth loss. We developed a predictive model based on specific biomarkers of this disease to better diagnose this condition. INTRODUCTION: Hypophosphatasemia is a condition in which low levels of alkaline phosphatase (ALP) are detected in the serum. Some individuals presenting with this condition may have a rare genetic disease called hypophosphatasia (HPP), which involves mineralization of the bone and teeth. Lack of awareness of HPP and its nonspecific symptoms make this genetic disease difficult to diagnose. We developed a predictive model based on biomarkers of HPP such as ALP and pyridoxal 5'-phosphate (PLP), because clinical manifestations sometimes are not recognized as symptoms of HPP. METHODS: We assessed 325,000 ALP results between 2010 and 2015 to identify individuals suspected of having HPP. We performed univariate and multivariate analyses to characterize the relationship between hypophosphatasemia and HPP. Using several machine learning algorithms, we developed several models based on biomarkers and compared their performance to determine the best model. RESULTS: The final cohort included 45 patients who underwent a genetic test. Half (23 patients) showed a mutation of the ALPL gene that encodes the tissue-nonspecific ALP enzyme. ALP (odds ratio [OR] 0.61, 95% confidence interval [CI] 0.3-0.8, p = 0.01) and PLP (OR 1.06, 95% CI 1.01-1.15, p = 0.04) were the only variables significantly associated with the presence of HPP. Support vector machines and logistic regression were the machine learning algorithms that provided the best predictive models in terms of classification (area under the curve 0.936 and 0.844, respectively). CONCLUSIONS: Given the high probability of a misdiagnosis, its nonspecific symptoms, and a lack of awareness of serum ALP levels, it is difficult to make a clinical diagnosis of HPP. Predictive models based on biomarkers are necessary to achieve a proper diagnosis. Our proposed machine learning approaches achieved reasonable performance compared to traditional statistical methods used in biomedicine, increasing the likelihood of properly diagnosing such a rare disease as HPP.
Assuntos
Hipofosfatasia , Adulto , Osso e Ossos , Testes Genéticos , Humanos , Hipofosfatasia/diagnóstico , Hipofosfatasia/genética , Mutação , Fosfato de PiridoxalRESUMO
OBJECTIVE: VEIA study is an evolutional registry of acute poisonings (AP) attended in the Emergency Room of the Doce de Octubre Hospital in Madrid (Spain) in a whole year (1979,1985, 1990, 1994,1997 and 2000). We present the 2004 study and compare the results with the previous years. METHODS AND RESULTS: Methodology has been identical across VEIA study. Of 1508 AP, 610 are suicide attempts (IAVIS), 319 ethylic, (IAVE), and 218 by illicit drugs (IAVD). Of the 2,259 toxics involved, 48% are medications (50% benzodiacepines) alcohol 25% and illicit drugs 13%. CONCLUSIONS: There is an important increase (34%) of cases and the incidence surpasses all published in our country. There are no gender differences nor in the whole neither the Health Area Census, but there are differences in IAVIS, IAVE and IAVD. IAVIS increase in 35%. Benzodiacepines poisoning increases two-fold as well as antidepressive drugs do in women. In men also increase, but in a minor extent. Acetaminophen remains the same in 23%. NSAID's, adjuvants and myorelaxants increase in women as do also alcohol and other poisons that almost equal men's. There are 13 cases of IAVIS in patients with alimentary disorders. Among men, a quarter are illicit drug abusers. In IAVE, the group without alcoholism grows and the total decreases. Illicit drugs duplicate the number of the former year. Cocaine supposes already 2/3 of the cases, MDMA ascends to 22 cases and they appear new substances as glue, without doubt as an effect of immigration and ketamine. Finally 205 household accidents and 57 industrial injuries complete the series.
Assuntos
Intoxicação/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Espanha , População UrbanaRESUMO
OBJECTIVE: VEIA study is an evolutional registry of acute poisonings (AP) attended in the Emergency Room of the Doce de Octubre Hospital in Madrid (Spain) in a whole year (1979, 1985, 1990, 1994,1997 and 2000). We present the 2004 study and compare the results with the previous years. METHODS AND RESULTS: Methodology has been identical across VEIA STUDY. Of 1508 AP, 610 are suicide attempts (IAVIS), 319 ethylic, (IAVE), and 218 by illicit drugs (IAVD). Of the 2,259 toxics involved, 48% are medications (50% benzodiacepines) alcohol 25% and illicit drugs 13%. CONCLUSIONS: There is an important increase (34%) of cases and the incidence surpasses all published in our country. There are no gender differences nor in the whole neither the Health Area Census, but there are differences in IAVIS, IAVE and IAVD. IAVIS increase in 35%. Benzodiacepines poisoning increases two-fold as well as antidepressive drugs do in women. In men also increase, but in a minor extent. Acetaminophen remains the same in 23%. NSAID's, adjuvants and myorelaxants increase in women as do also alcohol and other poisons that almost equal men's. There are 13 cases of IAVIS in patients with alimentary disorders. Among men, a quarter are illicit drug abusers. In IAVE, the group without alcoholism grows and the total decreases. Illicit drugs duplicate the number of the former year. Cocaine supposes already 2/3 of the cases, MDMA ascends to 22 cases and they appear new substances as glue, without doubt as an effect of immigration and ketamine. Finally 205 household accidents and 57 industrial injuries complete the series.