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HIV estimation using data from the demographic and health surveys (DHS) is limited by the presence of non-response and test refusals. Conventional adjustments such as imputation require the data to be missing at random. Methods that use instrumental variables allow the possibility that prevalence is different between the respondents and non-respondents, but their performance depends critically on the validity of the instrument. Using Manski's partial identification approach, we form instrumental variable bounds for HIV prevalence from a pool of candidate instruments. Our method does not require all candidate instruments to be valid. We use a simulation study to evaluate and compare our method against its competitors. We illustrate the proposed method using DHS data from Zambia, Malawi and Kenya. Our simulations show that imputation leads to seriously biased results even under mild violations of non-random missingness. Using worst case identification bounds that do not make assumptions about the non-response mechanism is robust but not informative. By taking the union of instrumental variable bounds balances informativeness of the bounds and robustness to inclusion of some invalid instruments. Non-response and refusals are ubiquitous in population based HIV data such as those collected under the DHS. Partial identification bounds provide a robust solution to HIV prevalence estimation without strong assumptions. Union bounds are significantly more informative than the worst case bounds without sacrificing credibility.
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Simulación por Computador , Infecciones por VIH , Encuestas Epidemiológicas , Humanos , Infecciones por VIH/epidemiología , Kenia/epidemiología , Prevalencia , Malaui/epidemiología , Modelos Estadísticos , Zambia/epidemiología , Masculino , Femenino , Sesgo , Interpretación Estadística de DatosRESUMEN
BACKGROUND: Surveys have been used worldwide to provide information on the COVID-19 pandemic impact so as to prepare and deliver an effective Public Health response. Overlapping panel surveys allow longitudinal estimates and more accurate cross-sectional estimates to be obtained thanks to the larger sample size. However, the problem of non-response is particularly aggravated in the case of panel surveys due to population fatigue with repeated surveys. OBJECTIVE: To develop a new reweighting method for overlapping panel surveys affected by non-response. METHODS: We chose the Healthcare and Social Survey which has an overlapping panel survey design with measurements throughout 2020 and 2021, and random samplings stratified by province and degree of urbanization. Each measurement comprises two samples: a longitudinal sample taken from previous measurements and a new sample taken at each measurement. RESULTS: Our reweighting methodological approach is the result of a two-step process: the original sampling design weights are corrected by modelling non-response with respect to the longitudinal sample obtained in a previous measurement using machine learning techniques, followed by calibration using the auxiliary information available at the population level. It is applied to the estimation of totals, proportions, ratios, and differences between measurements, and to gender gaps in the variable of self-perceived general health. CONCLUSION: The proposed method produces suitable estimators for both cross-sectional and longitudinal samples. For addressing future health crises such as COVID-19, it is therefore necessary to reduce potential coverage and non-response biases in surveys by means of utilizing reweighting techniques as proposed in this study.
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COVID-19 , Pandemias , Humanos , Estudios Transversales , Calibración , Encuestas y Cuestionarios , COVID-19/epidemiología , COVID-19/prevención & control , Sesgo , Atención a la SaludRESUMEN
Suicidal ideation and depression are common in people living with HIV (PLWH) in sub-Saharan Africa, but longitudinal data on their persistence in the modern antiretroviral therapy era are lacking. We examined the prevalence of persistent suicidal ideation and depression symptoms using the PHQ-9 in a well-characterized cohort of PLWH and HIV-uninfected community controls. Multivariable logistic regression models were used to determine the relationship between HIV and persistent depression and suicidal ideation. Persistent suicidal ideation was more common in PLWH but there was no difference in persistent depression by HIV status. Approximately one out of five participants with depression at baseline had persistent depression after 12-24 months and only about one out of four participants reporting suicidal ideation at baseline had persistent suicidal ideation after 12-24 months. HIV was associated with suicidal ideation at baseline. Persistent suicidal ideation was significantly associated with HIV immune non-response (p = 0.022). These findings highlight the need for integration of mental health services into HIV care in sub-Saharan Africa with a focus on suicide prevention.
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BACKGROUND: PIENTER 3 (P3), conducted in 2016/17, is the most recent of three nationwide serological surveys in the Netherlands. The surveys aim to monitor the effects of the National Immunisation Programme (NIP) by assessing population seroprevalence of included vaccine preventable diseases (VPDs). The response rate to the main sample was 15.7% (n = 4,983), following a decreasing trend in response compared to the previous two PIENTER studies (P1, 55.0%; 1995/1996 [n = 8,356] and P2, 33.0%; 2006/2007 [n = 5,834]). Non-responders to the main P3 survey were followed-up to complete a "non-response" questionnaire, an abridged 9-question version of the main survey covering demographics, health, and vaccination status. We assess P3 representativeness and potential sources of non-response bias, and trends in decreasing participation rates across all PIENTER studies. METHODS: P3 invitees were classified into survey response types: Full Participants (FP), Questionnaire Only (QO), Non-Response Questionnaire (NRQ) and Absolute Non-Responders (ANR). FP demographic and health indicator data were compared with Dutch national statistics, and then the response types were compared to each other. Random forest algorithms were used to predict response type. Finally, FPs from all three PIENTERs were compared to investigate the profile of survey participants through time. RESULTS: P3 FPs were in general healthier, younger and higher educated than the Dutch population. Random forest was not able to differentiate between FPs and ANRs, but when predicting FPs from NRQs we found evidence of healthy-responder bias. Participants of the three PIENTERs were found to be similar and are therefore comparable through time, but in line with national trends we found P3 participants were less inclined to vaccinate than previous cohorts. DISCUSSION: The PIENTER biobank is a powerful tool to monitor population-level protection against VPDs across 30 years in The Netherlands. However, future PIENTER studies should continue to focus on improving recruitment from under-represented groups, potentially by considering alternative and mixed survey modes to improve both overall and subgroup-specific response. Whilst non-responder bias is unlikely to affect seroprevalence estimates of high-coverage vaccines, the primary aim of the PIENTER biobank, other studies with varied vaccination/disease exposures should consider the influence of bias carefully.
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Enfermedades Prevenibles por Vacunación , Humanos , Países Bajos/epidemiología , Estudios Seroepidemiológicos , Vacunación , Programas de InmunizaciónRESUMEN
Treatments for anorexia nervosa (AN) remain ineffective for many patients. Processes that can account for differential treatment outcomes remain mostly unknown. We propose that the field test the role of associative learning in current psychological treatments. We hold that this line of research could yield actionable information for understanding non-response and improving long-term outcomes. To make this argument, we define associative learning and outline its proposed role in understanding psychiatric disorders and their treatment. We then briefly review data exploring associative learning in AN. We argue that associative learning processes are implicitly implicated in existing treatments; by this rationale, baseline differences in learning may interfere with treatment response. Finally, we outline future research to test our hypotheses. Altogether, future research aimed at better understanding how associative learning may contribute to AN symptom persistence has the potential to inform novel directions in intervention research. PUBLIC SIGNIFICANCE: There is a pressing need to improve outcomes in treatments for anorexia nervosa (AN). We propose that individual differences in associative learning-the ability to form and update associations between cues, contexts, behaviors, and outcomes-may account for differential response to existing treatments. Undertaking this research could provide an understanding of how current treatments work and inform new approaches for those who may be at risk of poor outcomes.
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Anorexia Nerviosa , Aprendizaje por Asociación , Anorexia Nerviosa/terapia , HumanosRESUMEN
BACKGROUND: Owing to the evidence that as many as 30-40% of patients with vulvar lichen sclerosus (VLS) fail to report a remission of symptoms with first-line corticosteroid treatment (TCS), especially as what regards dyspareunia, we aimed to analyze patients' satisfaction following vulvar injection of autologous platelet-rich plasma (PRP). This is intended as an adjunctive treatment, to be used following TCS, and appears to promote tissue repair. It may also possibly have immunomodulatory proprieties. MATERIALS AND METHODS: Patients with VLS were considered eligible for this pilot study if, despite having been treated with a 3-month TCS regimen, they reported a persistence of symptoms. PRP was produced in a referral center using a manual method and a standardized protocol. Each patient received three treatments 4 to 6 weeks apart. RESULTS: A total of 50 patients with a median age of 53 years [IQR 38-59 years] were included in the study. 6 months after the last injection of PRP all patients were either satisfied or very satisfied with the treatment (100%; 95% CI 93-100%). Median NRS scores for itching, burning, dyspareunia and dysuria were significantly reduced (p < 0.05) and FSFI, HADS and SF-12 questionnaires revealed a significant improvement in sexual function, psychological wellbeing and quality of life (p < 0.05). The number of patients reporting the need for maintenance TCS treatment was reduced by 42% (p < 0.001) and an improvement in vulvar elasticity and color was reported in all patients. CONCLUSION: Following standard medical therapy, PRP may be effective not only in improving symptoms, but also in restoring function.
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Dispareunia , Satisfacción del Paciente , Plasma Rico en Plaquetas , Liquen Escleroso Vulvar , Humanos , Femenino , Proyectos Piloto , Liquen Escleroso Vulvar/terapia , Liquen Escleroso Vulvar/tratamiento farmacológico , Persona de Mediana Edad , Adulto , Dispareunia/terapia , Dispareunia/etiología , Resultado del Tratamiento , InyeccionesRESUMEN
OBJECTIVES: To identify associations between frailty and non-response to follow-up questionnaires, in a longitudinal head and neck cancer (HNC) study with patient-reported outcome measures (PROMs). MATERIALS AND METHODS: Patients referred with HNC were included in OncoLifeS, a prospective data-biobank, underwent Geriatric Assessment (GA) and frailty screening ahead of treatment, and were followed up at 3, 6, 12 and 24 months after treatment using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and Head and Neck 35. Statistical analysis for factors associated with non-response was done using Generalized Linear Mixed Models. RESULTS: 289 patients were eligible for analysis. Mean age was 68.4 years and 68.5% were male. Restrictions in Activities of Daily Living [OR 4.46 (2.04-9.78)] and Instrumental Activities of Daily Living [OR 4.33 (2.27-8.24)], impaired mobility on Timed Up and Go test [OR 3.95 (1.85-8.45)], cognitive decline [OR 4.85 (2.28-10.35)] and assisted living (OR 5.54 (2.63-11.67)] were significantly associated with non-response. Frailty screening, with Geriatric 8 and Groningen Frailty Indicator, was also associated with non-response [OR, respectively, 2.64 (1.51-4.59) and 2.52 (1.44-4.44)]. All findings remained significant when adjusted for other factors that were significantly associated with non-response, such as higher age, longer study duration and subsequent death. CONCLUSION: Frail HNC patients respond significantly worse to follow-up PROMs. The drop-out and underrepresentation of frail patients in studies may lead to attrition bias, and as a result underestimating the effect sizes of associations. This is of importance when handling and interpreting such data.
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Fragilidad , Neoplasias de Cabeza y Cuello , Humanos , Masculino , Anciano , Femenino , Fragilidad/complicaciones , Fragilidad/diagnóstico , Anciano Frágil , Calidad de Vida , Estudios de Seguimiento , Estudios Prospectivos , Actividades Cotidianas , Equilibrio Postural , Estudios de Tiempo y Movimiento , Neoplasias de Cabeza y Cuello/complicaciones , Neoplasias de Cabeza y Cuello/terapia , Evaluación GeriátricaRESUMEN
The advent of biologic drugs has revolutionized the treatment of Inflammatory Bowel Disease, increasing rates of response and mucosal healing in comparison to conventional therapies by allowing the treatment of corticosteroid-refractory cases and reducing corticosteroid-related side effects. However, biologic therapies (anti-TNFα inhibitors, anti-α4ß7 integrin and anti-IL12/23) are still burdened by rates of response that hover around 40% (in biologic-naïve patients) or lower (for biologic-experienced patients). Moreover, knowledge of the mechanisms underlying drug resistance or loss of response is still scarce. Several cellular and molecular determinants are implied in therapeutic failure; genetic predispositions, in the form of single nucleotide polymorphisms in the sequence of cytokines or Human Leukocyte Antigen, or an altered expression of cytokines and other molecules involved in the inflammation cascade, play the most important role. Accessory mechanisms include gut microbiota dysregulation. In this narrative review of the current and most recent literature, we shed light on the mentioned determinants of therapeutic failure in order to pave the way for a more personalized approach that could help avoid unnecessary treatments and toxicities.
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Productos Biológicos , Enfermedades Inflamatorias del Intestino , Humanos , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Citocinas/metabolismo , Factor de Necrosis Tumoral alfa/uso terapéutico , Corticoesteroides/uso terapéutico , Productos Biológicos/uso terapéuticoRESUMEN
BACKGROUND: Prospective cohorts may be vulnerable to bias due to attrition. Inverse probability weights have been proposed as a method to help mitigate this bias. The current study used the "All Our Families" longitudinal pregnancy cohort of 3351 maternal-infant pairs and aimed to develop inverse probability weights using logistic regression models to predict study continuation versus drop-out from baseline to the three-year data collection wave. METHODS: Two methods of variable selection took place. One method was a knowledge-based a priori variable selection approach, while the second used Least Absolute Shrinkage and Selection Operator (LASSO). The ability of each model to predict continuing participation through discrimination and calibration for both approaches were evaluated by examining area under the receiver operating curve (AUROC) and calibration plots, respectively. Stabilized inverse probability weights were generated using predicted probabilities. Weight performance was assessed using standardized differences of baseline characteristics for those who continue in study and those that do not, with and without weights (unadjusted estimates). RESULTS: The a priori and LASSO variable selection method prediction models had good and fair discrimination with AUROC of 0.69 (95% Confidence Interval [CI]: 0.67-0.71) and 0.73 (95% CI: 0.71-0.75), respectively. Calibration plots and non-significant Hosmer-Lemeshow Goodness of Fit Tests indicated that both the a priori (p = 0.329) and LASSO model (p = 0.242) were well-calibrated. Unweighted results indicated large (> 10%) standardized differences in 15 demographic variables (range: 11 - 29%), when comparing those who continued in the study with those that did not. Weights derived from the a priori and LASSO models reduced standardized differences relative to unadjusted estimates, with the largest differences of 13% and 5%, respectively. Additionally, when applying the same LASSO variable selection method to develop weights in future data collection waves, standardized differences remained below 10% for each demographic variable. CONCLUSION: The LASSO variable selection approach produced robust weights that addressed non-response bias more than the knowledge-driven approach. These weights can be applied to analyses across multiple longitudinal waves of data collection to reduce bias.
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Estudios Prospectivos , Embarazo , Femenino , Humanos , Modelos Logísticos , Probabilidad , Recolección de DatosRESUMEN
This paper addresses new exponential estimators for population mean in case of non-response on both the study and the concomitant variables using simple random sampling. The expressions for theoretical bias and mean square error of new estimators are derived up to first-order approximation and comparisons are made with the existing estimators. The proposed estimators are observed more efficient as compared to the considered estimators in the literature. For instance, the classical [4] unbiased estimator, the estimator of [9], and other existing estimators under the explained conditions. The theoretical results are supported numerically by using real-life data sets, under the criteria of bias, mean square error, percent relative efficiency and mathematical conditions. It is also clear from the numerical results that the suggested exponential estimators performed better than the estimators in the literature.
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Background: Adverse childhood experiences (ACE) encompass traumatic events occurring before age 18, with lasting impacts on health. While ACE disclosure is important for understanding these effects, some individuals decline to respond to ACE-related survey items due to sensitivity, privacy concerns, or psychological distress. This study explores the relationship between non-response to ACE items and health outcomes, shedding light on the implications for those who choose not to disclose. Methods: We performed a secondary analysis of the 2021 Behavioral Risk Factor Surveillance System (BRFSS)-a national telephone survey querying health behaviors and conditions. Sociodemographic factors, ACE exposure, and non-response to ACE items were analyzed. Results: Individuals who decline to respond to ACE items exhibit similar patterns of health behaviors and conditions as those reporting ACE exposure. Non-response is linked to both healthier behaviors (lifetime HIV testing) and riskier behaviors (higher odds of smoking and e-cigarette use). Moreover, non-responders have higher odds of being underweight or obese, experiencing concentration difficulties, reporting poor self-rated health, and reporting multiple health diagnoses including depression, diabetes, high blood pressure, heart attack, and stroke. Conclusions: The study underscores the need to address health disparities associated with ACE, regardless of disclosure status. Healthcare interventions should target respondents and non-respondents of ACE screeners, tailoring strategies to promote healthier coping mechanisms and mitigate maladaptive behaviors. These results emphasize the importance of trauma-informed care, early intervention, and targeted public health initiatives for individuals affected by ACE, irrespective of their disclosure choices.
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BACKGROUND: The advent of the hepatitis B vaccine has achieved tremendous success in eradicating and reducing the burden of hepatitis B infection, which is the main culprit for hepatocellular carcinoma-one of the most fatal malignancies globally. Response to the vaccine is achieved in about 90-95% of healthy individuals and up to only 50% in immunocompromised patients. This review aimed to provide an overview of hepatitis B vaccine non-response, the mechanisms involved, B cell amnesia, and strategies to overcome it. METHODS: Databases, including Google Scholar, PubMed, Scopus, Cochrane, and ClinicalTrials.org, were used to search and retrieve articles using keywords on hepatitis B vaccine non-response and B cell amnesia. The PRISMA guideline was followed in identifying studies, screening, selection, and reporting of findings. RESULTS: A total of 133 studies on hepatitis B vaccine non-response, mechanisms, and prevention/management strategies were included in the review after screening and final selection. Factors responsible for hepatitis B vaccine non-response were found to include genetic, immunological factors, and B cell amnesia in healthy individuals. The genetic factors were sex, HLA haplotypes, and genetic polymorphisms in immune response markers (cytokines). Non-response was common in conditions of immunodeficiency, such as renal failure, haemodialysis, celiac disease, inflammatory bowel disease, hepatitis C co-infection, and latent hepatitis B infection. Others included diabetes mellitus and HIV infection. The mechanisms involved were impaired immune response by suppression of response (T helper cells) or induced suppression of response (through regulatory B and T cells). DISCUSSION: A comprehensive and careful understanding of the patient factors and the nature of the vaccine contributes to developing effective preventive measures. These include revaccination or booster dose, vaccine administration through the intradermal route, and the use of adjuvants in the vaccine.
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In the real-world, there are various situations when all units are not accessible of the respondent called unit non-response. The effect of unit non-response is a tricky matter for estimating the total number of unit. The present work highlights the interest about subpopulations (domains) in two affairs: i. if domains total of the supportive information is accessible ii. if domains total of the supportive variable does not access. The government needs to be introducing the actual facilities in these small domains. The supportive information is used to find out the estimate of the non respondent information and to apply this information for desired domains. Sometimes, it has been found that the accessible auxiliary variable for the domains might be positive shape. Therefore, it develops an appropriate model that has positive skewness. The present context highlighted the indirect method using a power-based estimation with calibration approach. By combining power based estimation and calibration technique, it is possible to obtain more accurate estimates for intended small domains. Even the supportive information is positively biased. This approach helps us in mitigating the effect of non-respondent and improving the overall reliability of the estimators. The simulation was conducted for different sizes 70 and 90 when nonresponse variable in the study variable. The results show that investigated power-based estimate provides better option over relevant exponential, ratio, and generalized regression estimators for intended domains.
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This paper considers the problem of estimation of the population total under probability proportional to size (PPS) sampling scheme when complete data is not available due to the presence of missing observations or non-response. The suggested estimators are developed based on available multi-auxiliary information for the response group and non-response group utilizing the calibration approach. The variances of the suggested estimators have been derived up to the first order of approximation. A simulation study done on a real dataset using R software also supports the performance of the suggested estimators. The empirical percentage absolute relative biases (%ARB) and percentage relative root mean squared errors (%RRMSE) are computed for the suggested estimators. The developed estimators are compared with the estimators of the population total due to the design-based Horvitz and Thompson (HT) estimator and calibration HT type estimator obtained on the available complete response units along with the design-based Hansen and Hurwitz (HH) estimator in the presence of non-response.
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This paper introduces a new method to estimate the population variance of a study variable in stratified successive sampling over two occasions, while accounting for random non-response. The method uses a logarithmic type estimator and leverages information from a highly positively correlated auxiliary variable. The paper also presents calibrated weights for the new estimator and examines its properties through numerical and simulation studies. The results indicate that the suggested estimator is more effective than the standard estimator for estimating the population variance.
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BACKGROUND: Bipolar disorder is a broad diagnostic construct associated with significant phenotypic and genetic heterogeneity challenging progress in clinical practice and discovery research. Prospective studies of well-characterized patients and their family members have identified lithium responsive (LiR) and lithium non-responsive (LiNR) subtypes that hold promise for advancement. METHOD: In this narrative review, relevant observations from published longitudinal studies of well-characterized bipolar patients and their families spanning six decades are highlighted. DSM diagnoses based on SADS-L interviews were decided in blind consensus reviews by expert clinicians. Genetic, neurobiological, and psychosocial factors were investigated in subsets of well-characterized probands and adult relatives. Systematic maintenance trials of lithium, antipsychotics, and lamotrigine were carried out. Clinical profiles that included detailed histories of the clinical course, symptom sets and disorders segregating in families were documented. Offspring of LiR and LiNR families were repeatedly assessed up to 20 years using KSADS-PL format interviews and DSM diagnoses and sub-threshold symptoms were decided by expert clinicians in blind consensus reviews using all available clinical and research data. RESULTS: A characteristic clinical profile differentiated bipolar patients who responded to lithium stabilization from those who did not. The LiR subtype was characterized by a recurrent fully remitting course predominated by depressive episodes and a positive family history of episodic remitting mood disorders, and not schizophrenia. Response to lithium clustered in families and the characteristic clinical profile predicted lithium response, with the episodic remitting course being a strong correlate. There is accumulating evidence that genetic and neurobiological markers differ between LiR and LiNR subtypes. Further, offspring of bipolar parents subdivided by lithium response differed in developmental history, clinical antecedents and early course of mood disorders. Moreover, the nature of the emergent course bred true from parent to offspring, independent of the nature of emergent psychopathology. CONCLUSIONS: Bipolar disorders are heterogeneous and response to long-term lithium is associated with a familial subtype with characteristic course, treatment response, family history and likely pathogenesis. Incorporating distinctive clinical profiles that index valid bipolar subtypes into routine practice and research will improve patient outcomes and advance the development and translation of novel treatment targets to improve prevention and early intervention.
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Ongoing extensive research in the field of gut microbiota (GM) has highlighted the crucial role of gut-dwelling microbes in human health. These microbes possess 100 times more genes than the human genome and offer significant biochemical advantages to the host in nutrient and drug absorption, metabolism, and excretion. It is increasingly clear that GM modulates the efficacy and toxicity of drugs, especially those taken orally. In addition, intra-individual variability of GM has been shown to contribute to drug response biases for certain therapeutics. For instance, the efficacy of cyclophosphamide depends on the presence of Enterococcus hirae and Barnesiella intestinihominis in the host intestine. Conversely, the presence of inappropriate or unwanted gut bacteria can inactivate a drug. For example, dehydroxylase of Enterococcus faecalis and Eggerthella lenta A2 can metabolize L-dopa before it converts into the active form (dopamine) and crosses the blood-brain barrier to treat Parkinson's disease patients. Moreover, GM is emerging as a new player in personalized medicine, and various methods are being developed to treat diseases by remodeling patients' GM composition, such as prebiotic and probiotic interventions, microbiota transplants, and the introduction of synthetic GM. This review aims to highlight how the host's GM can improve drug efficacy and discuss how an unwanted bug can cause the inactivation of medicine.
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Intravenous immunoglobulin(IVIG)is internationally recognized as the main treatment for Kawasaki disease(KD)in the acute phase, and its application can effectively reduce the incidence of coronary artery disease(CAL).However, in clinical practice, up to 26.8% of KD children do not respond to IVIG treatment, and their risk of CAL is higher and the degree of CAL is more severe.Early adjustment of treatment, such as early combined use of glucocorticoids, may play an important role in improving the prognosis and shortening the course of IVIG non-responsive KD.Therefore, early identification of IVIG non-response KD is of great significance to clinicians.In the past 20 years, domestic and foreign scholars have successively established predictive scoring system to predict the possibility of IVIG non-response in children with KD and optimize the early treatment.This article reviews the domestic and foreign research on the score system for predicting IVIG non-response in KD, in order to provide reference for clinical diagnosis and treatment.
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Inflammatory bowel disease(IBD)is a group chronic inflammatory gastrointestinal diseases with unknown etiology, which includes Crohn′s disease, ulcerative colitis and indeterminate colitis.The number of pediatric IBD patients increases year by year and the disease causes a huge burden on patients, families and society.Infliximab(IFX) is an effective and important drug, but more and more patients don′t respense to it.The reason for non-respense is complex and unclear.This review discussed the factors that may cause failure to respond to IFX, in order to find a suitable method to improve the therapeutic effect of IFX on children with IBD.