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Abstract Objective To present the different aspects that may be involved in the genesis and maintenance of obesity in children and adolescents. Data source Narrative review of articles published in the PubMed, Scielo, Lilacs, Scopus and Google Scholar databases, using the search terms: overweight, obesity, pre-conception, prenatal, infants, schoolchildren, children, and adolescents. The search was conducted in studies written in Portuguese, English and Spanish, including narrative, integrative or systematic reviews, meta-analyses, cross-sectional, case-control and cohort studies, published between 2003 and 2023. Data synthesis A total of 598 studies were initially screened and 60 of them, which showed the main biopsychosocial aspects related to greater risks of excessive adiposity in the pediatric age, were included in the review. The data were presented taking into account the incidence of risk factors and their consequences in six periods: pre-conception, pre-natal, infant, preschool, school age, and adolescence. Conclusions The causal factors described in the scientific literature that have been shown to be related to obesity in childhood and adolescence are presented.
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RESUMEN Introducción: Las reacciones adversas a medicamentos (RAM) son manifestaciones clínicas o de laboratorio no deseadas que se relacionan con el consumo de medicamentos. Las RAM se asocian con un riesgo significativo de morbimortalidad e ingresos hospitalarios. Los antipsicóticos poseen una reducida ventana terapéutica y se han relacionado con la manifestación de una diversidad de RAM. Objetivo: Evaluar el patrón de las RAM debido a fármacos antipsicóticos, detectadas en pacientes atendidos en el Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz entre diciembre de 2021 y mayo de 2022. Métodos: Estudio observacional, descriptivo, prospectivo y transversal de una serie de casos. La gravedad, la severidad y la calidad de la información de la notificación de las RAM se definieron conforme a la NOM-220-SSA1-2016, instalación y operación de la farmacovigilancia, mientras que la causalidad se determinó mediante el algoritmo de Naranjo. Resultados: La incidencia de las RAM fue del 59% y se detectó una o más RAM en 52 de los 88 pacientes que estaban en tratamiento antipsicótico durante el periodo de estudio. El 45% de las RAM tuvo una causalidad probable y el 55%, posible; únicamente tres RAM se clasificaron como graves, debido a que prolongaron la estancia hospitalaria y pusieron en peligro la vida del paciente. Conclusiones: Las RAM de los sistemas gastrointestinal y endocrino fueron las más incidentes, y la hiperprolactinemia fue la más frecuente. La olanzapina y clozapina fueron los medicamentos que más RAM provocaron. Se recomienda fomentar la cultura de notificación y seguimiento de RAM causadas por fármacos antipsicóticos.
ABSTRACT Introduction: Adverse Drug Reactions (ADR) are unwanted clinical or laboratory manifestations that are related to drug use. ADR are common and are associated with significant risk of morbidity, mortality and hospital admissions. Antipsychotics have a reduced therapeutic window, and have been related to the manifestation of a variety of ADR. Objetive: To evaluate the pattern of ADRs due to antipsychotic drugs detected in patients treated at the Ramón de la Fuente Muñiz National Institute of Psychiatry between December 2021 and May 2022. Methods: Observational, descriptive, prospective and cross-sectional study of a series of cases. The seriousness, severity, and quality of the information in the notification of the ADR were defined in accordance with NOM-220-SSA1-2016, Installation and Operation of Pharmacovigilance, while causality was determined using the Naranjo algorithm. Results: The incidence of ADRs was 59%, with one or more ADR detected in 52 of the 88 patients who were receiving antipsychotic treatment during the study period. Forty-five percent of the ADR had probable causality and 55% possible; only three ADR were classified as serious as they prolonged the hospital stay and endangered the patient's life. Conclusions: The ADR of the gastrointestinal and endocrine systems were the most incidental, with hyperprolactinemia being the most frequent. Olanzapine and clozapine were the medications that caused the most ADR. It is recommended to promote the culture of notification and follow-up of ADR caused by antipsychotic drugs.
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Nonalcoholic fatty liver disease （NAFLD） is an abnormal lipid metabolic disorder of the liver characterized by accumulation of a large amount of lipids in the liver， and it is currently the most common liver disease around the world. Mendelian randomization （MR） incorporates genomic data into traditional epidemiological study designs to infer the causal relationship between exposure factors and disease risk. In recent years， MR has been widely used in studies on inference of the etiology of NAFLD. This article systematically summarizes the advances in the application of MR in NAFLD research， so as to provide new ideas for understanding the nature of the disease and scientific interventions.
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Objective At present, the grading evaluation of patients with disorders of consciousness (DOC) is still a focus and difficulty in related fields. Electroencephalogram (EEG) can directly read and continuously reflect scalp electrical activity generated by brain tissue structure, with high temporal resolution. Auditory stimulation is easy to operate and has broad application prospects in clinical detection of DOC. The causal network can intuitively reflect the direction of information transmission through the causal relationship between time series, helping us better understand the information interaction between different regions of the brain of patients. This paper combines EEG and causal networks to explore the differences in brain functional connectivity between patients with unresponsive arousal syndrome (VS) and those with minimum state of consciousness (MCS) under auditory stimulation. MethodsA total of 23 DOC patients were included, including 11 MCS patients and 12 VS patients. Based on the Oddball paradigm, auditory naming stimulation was performed on DOC patients and EEG signals of DOC patients were synchronously collected. The brain functional networks were constructed using multivariate Granger causality method, and the differences in node degree, clustering coefficient, global efficiency, and causal flow of the brain networks between MCS patients and VS patients were calculated. The differences in network characteristics of patients with different levels of consciousness under auditory stimulation were compared from the perspective of cooperation between brain regions. ResultsThe causal connectivity between most brain regions in MCS patients was stronger than that in VS patients, and MCS patients had more brain network connectivity edges than VS patients. The average degree (P<0.05), average clustering coefficient, and global efficiency (P<0.05) of MCS patients under naming stimulation were higher than those of VS patients. The difference in out-degree between each node of VS patients was larger, and the difference in in-degree between each node of MCS patients was smaller. The difference in in-degree of MCS patients was more significant than that of VS patients, and the inflow and outflow of information in the brain functional network of MCS patients were stronger than those of VS patients. MCS and VS patients had differences of causal flow in the frontal and temporal lobes, the direction of information transmission in the parietal lobe and central region was not the same, and MCS patients had more electrodes as causal sources than VS patients. ConclusionThe information transmission ability of MCS patients is stronger than that of VS patients under auditory naming stimulation. Compared with VS patients, MCS patients have an increase in the number of electrode channels as the causal source, an increase in information output to other brain regions, and also an increase in the information output within brain regions, which may indicate a better state of consciousness in patients. MCS patients have more electrode channels for information output in the frontal lobe than VS patients, and the number of electrode channels for changing the direction of information transmission in the frontal lobe is the highest. The frontal lobe is closely related to the level of consciousness in patients with consciousness disorders. This study can provide a theoretical basis for the grading evaluation of consciousness levels in DOC patients.
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Objective @#To examine the causal relationship between ulcerative colitis (UC) and pancreatitis, to provide basis for early screening of pancreatitis among UC patients.@*Methods@#Genomic data of UC were obtained from 47 745 European individuals pooled by the International Inflammatory Bowel Disease Genetics Consortium, including 156 116 single nucleotide polymorphism (SNP), and genomic data of pancreatitis were obtained from 198 166 European individuals pooled from FinnGen, including 16 380 428 SNPs. Mendelian randomization (MR) analysis was performed using the inverse variance weighted (IVW) method with 72 UC-associated SNPs as instrumental variables and pancreatitis as the study outcome. The heterogeneity was assessed using Cochran Q test, the horizontal pleiotropy was assessed using MR-Egger regression, MR-PRESSO was performed with the exclusion of outliers, and effect of individual SNP on the results was tested with the leave-one-out method. @*Results@#MR analysis results showed that patients with genetically predicted UC had an increased risk of pancreatitis relative to those without UC (OR=1.076, 95%CI: 1.019-1.136, P<0.05). Cochran Q test showed no heterogeneity (P>0.05), and MR-Egger regression did not reveal horizontal pleiotropy of instrumental variables (P>0.05). The MR analysis results were robust after removing SNP one by one.@*Conclusions@#Genetically predicted UC is associated with an increased risk of pancreatitis. The screening for pancreatitis risk should be enhanced in patients with UC.
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Etiological research is necessary for understanding the occurrence and epidemiological patterns of diseases, and is also a prerequisite for the diagnosis, prevention and treatment of clinical diseases. Mendelian randomization(MR), a method of research that combines genetics and epidemiology, has the advantage of exploring the causal relationship between exposure and disease genetically as well as avoiding confounding factors and reverse causation. Thus, it has been extensively utilized in the etiological study of diseases. This paper reviews the implementation of MR in the research of ocular diseases and provides ideas and approaches for the investigation of related mechanisms as well as the development of intervention strategies.
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Objective:To investigate the changes of abnormal spontaneous brain activity and whole-brain effector connectivity in patients with obsessive-compulsive disorder (OCD) by combining low frequency amplitude (ALFF) and Granger causality analysis (GCA), and explore their relations with clinical symptoms.Methods:Forty-nine patients with OCD admitted to Department of Psychiatry, Second Affiliated Hospital of Xinxiang Medical College from January 2020 to September 2023 were selected as OCD group; 50 healthy volunteers matched with gender, age and years of education were enrolled as healthy control (HC) group. Obsessive-compulsive symptoms and severities in the OCD group were assessed by Yale Brown obsessive-compulsive scale (Y-BOCS). All subjects underwent whole-brain resting-state functional magnetic resonance imaging scanning (rs-fMRI). ALFF differences between the 2 groups were compared. Brain regions with ALFF differences were used as seed points, and effector connectivity changes in seed points were compared with those in whole-brain by GCA. Correlations of ALFF and effector connectivity in brain regions with ALFF differences with total scores, obsession scores and compulsion scores of Y-BOCS were analyzed by partial correlation analysis.Results:(1) Compared with that in the HC group, ALFF was significantly enhanced in the right supplementary motor area, right hippocampus, left caudate nucleus, and right fusiform gyrus, and statistically attenuated in the left suboccipital gyrus in the OCD group ( P<0.05). (2) Compared with that in the HC group, effector connectivity from the right dorsolateral superior frontal gyrus to right supplementary motor area was significantly attenuated, and effector connectivity from the left superior occipital gyrus to right supplementary motor area was significantly enhanced in the OCD group ( P<0.05); compared with that in the HC group, effector connectivity from the right fusiform gyrus to right precentral gyrus was significantly attenuated, and effector connectivity from the right hippocampus to left mesial temporal gyrus was significantly enhanced in the OCD group ( P<0.05). (3) In OCD patients, altered ALFF in the left caudate nucleus was positively correlated with obsession scores ( r=0.357, P=0.027), and altered effector connectivity from the right dorsolateral superior frontal gyrus to right supplementary motor area was negatively correlated with obsession scores ( r=-0.312, P=0.029). Conclusion:Abnormalities in sensorimotor network function are closely related to clinical symptoms in patients with OCD.
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Resumo A esfera das perícias comumente reduz a questão do estabelecimento do nexo de causalidade entre trabalho e saúde/doença apenas ao binômio trabalho/vida pessoal. Partindo dos pressupostos dos campos Saúde do Trabalhador (ST) e Saúde Mental Relacionada ao Trabalho (SMRT), este ensaio visa problematizar o resultado da questão, que reside na existência de dificuldades enfrentadas por trabalhadores na obtenção do nexo causal entre seus agravos/adoecimentos, cuja causalidade mais complexa se explica a partir de várias mediações pouco consideradas nos atos periciais circunscritos apenas às anamneses clínicas de cunho biomédicas pautadas nos pressupostos da Medicina do Trabalho, Higiene e Saúde Ocupacional. As formas de superação à ideia de causa-efeito passam pelo entendimento de que o processo de adoecimento é social e histórico e de que é preciso buscar mediações entre trabalho e adoecimento para elucidar sintomatologias singulares a partir da experiência do desgaste coletivo. Tal averiguação deve, ao mesmo tempo, problematizar os próprios processos de trabalho dos atores sociais envolvidos nas investigações periciais e partir das prioridades definidas pelos próprios trabalhadores que atuam como sujeitos da análise da nocividade do trabalho para a saúde.
Abstract Expert testimonies commonly reduce the establishment of causal links between work and health/illness solely to the dichotomy of work/personal life. Based on the assumptions from the fields of Workers Health and Work-Related Mental Health, this essay problematizes the results of this issue, namely the difficulties faced by workers in establishing the causal link between their ailments/illnesses, whose more complex causality is explained through several mediations that are often overlooked by the limited expert acts restricted only to clinical anamneses based on Occupational Medicine, Hygiene, and Occupational Health. Overcoming the idea of cause and effect involves understanding that the process of falling ill is social and historical, and requires exploring the mediations between work and illness to elucidate singular symptomatology based on the collective wear and tear experience. Such an investigation should simultaneously problematize the very work processes of the social actors involved in the expert investigations, starting from the priorities defined by the workers themselves who act as subjects in the analysis of work-related harm to health.
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Mental Health , Occupational Health , Delivery of Health Careالملخص
Abstract This paper examines the causal effect of the levels of democracy in countries on the levels of corruption. Research shows that the levels of corruption in countries decrease when they reach higher levels of democracy. However, most of the evidence has been obtained through correlational or regression studies that do not make clear the causal connection between the variables. The research applied a robust estimator (IPWRA) to a database of 161 countries with average data from 2010-2019, assessing a causality model within the counterfactual framework. The results indicate that a causal relationship does exist; that is, a higher level of democracy in the countries reduces the levels of corruption.
Resumo Este artigo examina o efeito causal dos níveis de democracia dos países sobre seus níveis de corrupção. As pesquisas mostram que os níveis de corrupção nos países diminuem quando atingem níveis mais altos de democracia. No entanto, a maior parte da evidência foi obtida através de estudos correlacionais ou de regressão que não esclarecem a conexão causal entre as variáveis. O presente estudo utilizou dados médios de 161 países correspondentes ao período de 2010-2019 para estimar um modelo de causalidade usando um estimador robusto (IPWRA), seguindo o referencial teórico da análise contrafactual. Os resultados indicam que existe uma relação causal, ou seja, maiores níveis de democracia nos países resultam em reduções nos níveis de corrupção.
Resumen Este artículo examina el efecto causal de los niveles de democracia de los países sobre sus niveles de corrupción. Las investigaciones muestran que los niveles de corrupción en los países disminuyen cuando alcanzan niveles más altos de democracia. Sin embargo, la mayor parte de la evidencia se ha obtenido a través de estudios correlacionales o de regresión que no aclaran la conexión causal entre las variables. El presente estudio utilizó datos promedio de 161 países correspondientes al período 2010-2019 para estimar un modelo de causalidad mediante un estimador robusto (IPWRA), siguiendo el marco teórico del análisis contrafactual. Los resultados indican que sí existe una relación causal, es decir, mayores niveles de democracia en los países producen reducciones en los niveles de corrupción.
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The prefrontal cortex and hippocampus may support sequential working memory beyond episodic memory and spatial navigation. This stereoelectroencephalography (SEEG) study investigated how the dorsolateral prefrontal cortex (DLPFC) interacts with the hippocampus in the online processing of sequential information. Twenty patients with epilepsy (eight women, age 27.6 ± 8.2 years) completed a line ordering task with SEEG recordings over the DLPFC and the hippocampus. Participants showed longer thinking times and more recall errors when asked to arrange random lines clockwise (random trials) than to maintain ordered lines (ordered trials) before recalling the orientation of a particular line. First, the ordering-related increase in thinking time and recall error was associated with a transient theta power increase in the hippocampus and a sustained theta power increase in the DLPFC (3-10 Hz). In particular, the hippocampal theta power increase correlated with the memory precision of line orientation. Second, theta phase coherences between the DLPFC and hippocampus were enhanced for ordering, especially for more precisely memorized lines. Third, the theta band DLPFC → hippocampus influence was selectively enhanced for ordering, especially for more precisely memorized lines. This study suggests that theta oscillations may support DLPFC-hippocampal interactions in the online processing of sequential information.
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Adult , Female , Humans , Young Adult , Male , Epilepsy , Hippocampus , Memory, Short-Term , Mental Recall , Prefrontal Cortex , Theta Rhythmالملخص
Objective To investigate whether chemokine CCL2(also known as monocyte chemotactic protein 1 or MCP-1)has a causal relationship with lung cancer.Methods Genetic data of chemokine CCL2 and different pathological subtypes of lung cancer were extracted from genome-wide association studies(GWAS),and inverse-variance weighted(IVW)analysis was used as main analysis,while weighted median,simple model,MR-Egger regression,and weighted model were chosen as supplementary analyses.Sensitivity analyses were performed to verify the reliability of the data.Results The result of IVW analysis on chemokine CCL2 to lung adenocarcinoma was OR = 1.065,95%CI(0.919～1.234),P = 0.401.The result of IVW analysis on chemokine CCL2 to squamous cell lung carcinoma was OR = 1.059,95%CI(0.931～1.205),P = 0.381.The result of IVW analysis on chemokine CCL2 to small cell lung carcinoma was OR = 0.959,95%CI(0.760～1.208),P = 0.720.Conclusions There is no direct causal relationship between chemokine CCL2 and lung cancer.
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BACKGROUND:Osteonecrosis due to drugs is a serious adverse reaction occurring after the application of such drugs.Increasing evidence suggests that the gut microbiota composition is associated with osteonecrosis due to drugs.However,the causal relationship of the gut microbiota to osteonecrosis due to drugs is still unclear. OBJECTIVE:To evaluate the potential causal relationship between the gut microbiota and the risk of osteonecrosis due to drugs using the Mendelian randomization method. METHODS:A two-sample Mendelian randomization study was performed using the summary statistics of gut microbiota from the largest available genome-wide association study meta-analysis(n=13 266)conducted by the MiBioGen consortium as well as the summary statistics of osteonecrosis due to drugs obtained from the FinnGen consortium R9 release data(264 cases and 377 013 controls).Inverse variance weighted,MR-Egger,weighted median,weighted model and simple model were used to examine the causal association between gut microbiota and osteonecrosis due to drugs.Sensitivity analysis was used to test whether the results of the Mendelian randomization analysis were reliable.Reverse Mendelian randomization analysis was performed on all the bacteria as an outcome for effect analysis and sensitivity analysis. RESULTS AND CONCLUSION:Inverse variance weighted estimates suggested that Lentisphaerae(phylum),Lentisphaeria(class),Melainabacteria(class),Gastranaerophilales(order),Rhodospirillales(order),Victivallales(order)and Bifidobacterium(genus)had protective causal effects on osteonecrosis due to drugs.Methanobacteria(class),Bacillales(order),Methanobacteriaceae(family),Lachnospiraceae(family),Methanobacteriales(order),Holdemania(genus),Holdemania(UCG010 group)(genus),Odoribacter(genus)and Tyzzerella3(genus)had negative causal effects on osteonecrosis due to drugs.According to the results of reverse Mendelian randomization analysis,Clostridiaceae1(family),Peptostreptococcaceae(family),Streptococcaceae(family),Clostridiumsensustricto1(genus)and Streptococcus(genus)showed negative causal effects on osteonecrosis due to drugs.However,Eisenbergiella(genus)showed protective causal effects on osteonecrosis due to drugs.None of the bidirectional sensitivity analysis revealed heterogeneity or horizontal pleiotropy.When gut microbiota were used as exposure and osteonecrosis due to drugs as the outcome,Mendelian randomization analysis found that seven bacterial traits were positively correlated to osteonecrosis due to drugs,nine bacterial traits were negatively related to osteonecrosis due to drugs.When osteonecrosis due to drugs were used as exposure and gut microbiota as the outcome,reverse Mendelian randomization analysis found a negative correlated relationship with five bacterial traits and a positive causal relationship with one bacterial trait.By changing the diversity and composition of gut microbiota,it is expected to improve the incidence and prognosis of osteonecrosis due to drugs,providing new ideas for the study of orthopedic diseases.
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BACKGROUND:Osteonecrosis is a common refractory disease in clinical practice,and observational studies have suggested that micronutrients may have a prognostic role in osteonecrosis.However,the specific causal association between micronutrients and osteonecrosis is not known. OBJECTIVE:To explore the causal association between micronutrients and osteonecrosis by Mendelian randomization using summary data from a large population-based genome-wide association study(GWAS)for clinical diagnosis and treatment. METHODS:The required exposure and outcome data(calcium,magnesium,iron,vitamin E,carotenoids,retinol&osteonecrosis)were extracted from the IEU OpenGWAS database,GWAS catalog database,and FinnGen database.Data were analyzed by bidirectional Mendelian randomization with inverse-variance weighted as the primary study method,and weighted median method,simple mode method,weighted mode method,and MR-Egger regression to complement the results.The reliability of the data was then verified through sensitivity analyses. RESULTS AND CONCLUSION:(1)The results found a positive correlation between serum iron concentration and osteonecrosis,while no correlation was found for other micronutrients.There was no reverse causality in all the data.(2)The results of sensitivity analysis showed a robust causality.(3)By Mendelian randomization method,this study provided evidence of causality between serum iron concentration and osteonecrosis,and understanding the causality of micronutrient elements on osteonecrosis can help in the clinical diagnosis and treatment of osteonecrosis,which is of great clinical significance.
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BACKGROUND:It has been found in recent observational studies that assessing localized fat mass is crucial in the evaluation of disc degeneration.Although obesity has been recognized as a risk factor for disc degeneration,the causal relationship between fat mass,which is a key factor in obesity,and intervertebral disc degeneration has been unclear in previous studies. OBJECTIVE:To investigate the causal risk factors of intervertebral disc degeneration associated with different distributions of fat mass,thereby enhancing the understanding of the pathogenesis of intervertebral disc degeneration and contributing to the development of preventive,therapeutic,and prognostic strategies. METHODS:Genetic markers associated with trunk and lower limb fat mass were extracted as instrumental variables from the publicly available IEU Open GWAS under the conditions of strong correlation and fulfillment of linkage disequilibrium.These markers were combined with the Mendelian randomization analysis to investigate the relationship between body fat and intervertebral disc degeneration.We used the latest version 9 database of FinnGen and assessed the results using several regression models,including inverse variance weighting,MR-Egger regression,simple mode,weighted mode,and weighted median estimator.We also assessed the heterogeneity of the genetic markers using Cochran's Q test,and multiplicity was assessed using the MR-Egger intercept test.Additionally,we used the leave-one-out method to determine the sensitivity of individual genetic markers to the causal effect of the exposure and outcome.The results were presented as odds ratios(OR)and 95%confidence intervals(CI). RESULTS AND CONCLUSION:The results from the inverse variance weighting method revealed that there was a positive causal relationship between trunk fat mass and the risk of developing intervertebral disc degeneration(OR=1.25,95%CI:1.15-1.35,P＜0.001).Additionally,there was an inverse causal relationship between bilateral lower limb fat mass and the risk of developing intervertebral disc degeneration(OR=0.7,95%CI:0.63-0.78,P＜0.001;OR=0.69,95%CI:0.62-0.76,P＜0.001).Furthermore,the MR-Egger intercept analysis did not detect any potential horizontal pleiotropy.No bias single nucleotide polymorphisms were detected,while heterogeneity tests were present,and the leave-one-out sensitivity analysis suggested reliable results.The results above demonstrate a positive causal relationship between trunk fat mass and intervertebral disc degeneration.As trunk fat mass increases,the risk of intervertebral disc degeneration rises.With an increase in both lower limb fat mass,the risk of intervertebral disc degeneration decreases.Fat content and distribution affects the risk of developing intervertebral disc degeneration and should be given more attention.
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Purpose/Significance The relative positions of causality words are utilized to assist deep learning models to improve cau-sality prediction and mine medical text gain information.Method/Process The relative position information of causality words in medical texts is represented as a relational feature layer embedded in a pre-trained language model,and the baseline model is integrated for enti-ty recognition and relationship extraction.Result/Conclusion The F1 value of the model embedded in the relational feature layer is im-proved by 2.92 percentage points and 6.41 percentage points compared with the baseline models BERT-BiLSTM-CRF and CasRel,re-spectively,with better causal prediction capacity.
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Background: Cutaneous adverse drug reactions (CADRs) range from mild-to-severe types and occasionally can become fatal. Hence, these incur additional financial burden both to patients and community. Aim and Objective: The aim of the study was to describe the characteristics of CADRs reported to ADR monitoring center (AMC) of a tertiary care center. Materials and Methods: CADRs reported to the AMC over a period of 2 ½ years were retrospectively studied. This study mainly focused on affected age group, gender, various pattern of CADRs, the group and name of drugs causing CADRs, and severity and causality assessment. Results: CADRs contributed 31.6% of the total ADRs reported to the AMC. Among these, 51.7% were females and 40% were of 51–60 years age group. About 37.9% of CADRs were pruritus. Antibacterial drugs were the most common cause of CADRs and beta-lactam antibiotics were responsible for 30% of CADRs. Stevens Johnson syndrome (SJS) constituted 4.9% of CADRs and 20% of this was due to Paracetamol. Drugs were withdrawn in 89% of cases and 85% cases recovered. On causality assessment, 94% were of probable category. Conclusion: Pruritus was the most commonly observed CADR and antibacterial drugs were the most common cause. Beta lactam antibiotic was the most frequent antibacterial drug to cause CADRs. The most common serious CADR was SJS and Paracetamol was the most frequent culprit drug.
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Resumen Este ensayo cuestiona las verdades matemáticas como principio explicativo del conocimiento científico médico. Se analiza, en primer término, el concepto de normalidad actual basado en una distribución de valores probabilísticos, y se destacan sus limitaciones y equívocos para captar la complejidad de la condición humana. Los sistemas cerrados (juegos de azar), origen de la teoría de las probabilidades y del binomio causalidad-azar, se comparan con los sistemas abiertos propios del proceso vital y se argumentan sus diferencias extremas. Se destaca el despropósito de depositar en el binomio causalidad-azar el significado de asociaciones entre sucesos propios de la complejidad de la vida humana en salud y enfermedad. Se confrontan las características de la causalidad mecanicista (puntual, lineal, unidireccional, homogénea y fija), que equipara al organismo con una máquina y es la única explicación científica aceptada del acontecer de la vida humana, con las de la causalidad contextual (difusa, heterogénea, jerárquica, multidireccional y cambiante), que especifica diversos órdenes causales interactuantes que dan forma a la condición humana: el histórico, el social, el político, el económico, el cultural o el biológico, que representa una mirada escrutadora y penetrante de la complejidad de los seres humanos. Se concluye la superioridad de la causalidad contextual sobre la mecanicista, que abre posibilidades explicativas de sucesos vitales que suelen arrumbarse como «efectos del azar¼. Esta aproximación integradora a la complejidad humana puede enriquecer y fortalecer el método clínico, hoy degradado y en riesgo de extinción.
Abstract This essay questions mathematical truths as an explanatory principle of the medical scientific knowledge. It analyzes, in the first place, the current concept of normality based on a distribution of probabilistic values and its limitations and mistakes to capture the complexity of the human condition are highlighted. The closed systems (gambling) origin of the theory of probabilities and the binomial causality-chance are compared with open systems typical of the complexity of the vital process, and their extreme differences are argued. The nonsense of depositing in the causality-chance binomial the meaning of associations between events typical of the complexity of human life in health and disease is highlighted. The characteristics of mechanistic causality (punctual, homogeneous, linear, unidirectional and fixed), which equates the organism with a machine and is the only accepted scientific explanation of events of human life, are confronted with those of contextual causality (diffuse, heterogeneous, hierarchical, multidirectional and changing), which specifies various interacting causal orders that shape of human condition: the historical, the social, the political, the economical, the cultural or the biological that represents a scrutinizing and penetrating look at the complexity of human beings. It concludes the superiority of contextual causality over mechanistic causality that opens up explanatory possibilities of the vital events that are usually put away as "effects of chance". This integrative approach to the human complexity can enrich and strengthen the clinical method that is now degraded and at risk of extinction.
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Background: Adverse drug reactions (ADRs) to antiretroviral drugs have a varied pattern and wide spectrum of severity from mild to very serious. The lack of a pre-established time-reaction sequence hampers the causality assessment of ADRs. Recognition of pattern of ADRs to antiretroviral drugs in a particular setup might sensitize the reporters to report ADRs, especially in setups dependent on spontaneous reporting. Aim and Objectives: The study of pattern and time-reaction sequence for ADRs reported to antiretroviral drugs. Materials and Methods: Retrospective study was conducted at a first-line antiretroviral therapy (ART) center after obtaining approval from the Institutional Ethics Committee. Pattern of ADRs associated with ART was done by analyzing the type of ADRs, severity, and outcome of ADRs reported to antiretroviral drugs. Mean duration of time lapse between administration of drug to onset of adverse drug reaction was calculated. Descriptive statistics was used for data analysis. Results: There were 73 adverse reactions reported. Most common type of adverse reaction was cutaneous (53.42%) followed by anemia (31%). Causality assessment of most ADRs was concluded as possible (60.27%). Most ADRs were of moderate severity and 12% were severe reactions. Reactions such as anemia and neuropsychiatric ADRs often occurred late, while maculopapular rash usually occurred within 30 days of drug administration. Conclusions: ADRs to ART include an array of reactions ranging from mild rash to psychosis or severe anemia. Most of these reactions are of moderate severity and have a favorable outcome. Many of these reactions actually occur almost a month after initiating a drug regime suggesting the need for intensive monitoring around this time.
الملخص
Objective:To explore the causal relationship between body mass index (BMI) and hypothyroidism using the two-sample Mendelian randomization model.Methods:A large-scale anthropometric genome-wide association study published in the GIANT database was used to select single nucleotide polymorphisms (SNPs) which were statistically significantly associated with BMI as an instrumental variable ( P<5×10 -8, linkage disequilibrium r 2<0.1). The causal relationship between BMI and hypothyroidism was determined by the inverse variance weighted (IVW), weighted median method and the MR-Egger method, respectively. A heterogeneity test, gene pleiotropy test, and sensitivity analysis were performed to evaluate the stability and reliability of the results. Results:A total of 89 SNPs related to BMI were screened out as instrumental variables. IVW analysis suggested that for every standard deviation increase in BMI, the risk of hypothyroidism increased by 0.9% (odd ratio ( OR)=1.009, 95% confidence interval ( CI): 1.006-1.012, P<0.001). Similar results were obtained with the weighted median method ( OR=1.007, 95% CI: 1.002-1.011, P=0.003) and the MR-Egger method ( OR=1.008, 95% CI: 1.001-1.015, P=0.006). The MR-Egger analysis showed that genetic pleiotropy did not bias the results (intercept=0.000 1, P=0.776), the one-by-one exclusion method did not show that a single instrumental variable SNP had a significant impact on the results, and the difference was not statistically significant ( P>0.05). Conclusion:Mendelian randomized analysis showed a positive causal relationship between BMI and hypothyroidism.
الملخص
Objective:The present study delves into the realm of scientific unknowns, which serve as the primary representation of major scientific challenges and often give rise to subversive, non-consensus, and high-risk scientific problems. Addressing this pivotal aspect, we focus on the development of scientific unknown identification methods and tool platforms to provide essential data support for priority setting of basic research through a problem-oriented approach. Such efforts are imperative for managing the scientific and technological innovation system within the context of demands and problem-solving.Methods:While numerous knowledge bases have been established in the medical field, there remains a notable lack of focus on the unknown base. The paper synthesizes relevant literature and existing research, amalgamating the methodological paradigm of scientific big data research with text mining. This integration facilitates comprehensive interpretations and enlightening insights concerning the concept, identification methods, and construction of an unknown-base.Results:By systematically analyzing the concept of scientific unknowns, we present a recognition method based on cognitive state and logical rules. Furthermore, we discuss a classification framework and realization path for scientific unknowns from the dimensions of attribute, relationship, and disease, thereby providing foundational insights for the construction of a medical unknown database.Conclusions:Notably, the research on unknowns in medical science transcends disciplinary boundaries, encompassing the confluence of information science, data science, medical informatics, and science and technology management. As such, this paper seeks to expound upon the significance and application scenarios of unknown research in science, furnishing valuable ideas and references for scholars in the field.