Persistent Depression and Suicidal Ideation in People Living with HIV in Tanzania: A Longitudinal Cohort Study.

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.

Factors associated with non-response and nutrional status of non-responders at 6-month post-discharge: a cohort study nested in a MUAC-based nutrition programme for acutely malnourished children in Mirriah, Niger.

Background: In the treatment of acute malnutrition (AM), non-response is considered a treatment failure for not meeting recovery criteria within a therapeutic window of 12-16 weeks, but this category of children is misunderstood. As current research emphasizes ways to simplify and optimize treatment protocols, non-response emerges as a new issue to enhance program efficiency. Methods: A prospective cohort study was conducted from 2019 to 2020 at two health centres in Mirriah, Niger among children aged 6-59 months with uncomplicated AM treated under the Optimising treatment for Acute MAlnutrition (OptiMA) protocol. Children who did not meet recovery criteria by 12 weeks (mid-upper arm circumference (MUAC) ≥125 mm without oedema for two consecutive weeks) were classified as non-responders. Non-responders received a home visit six-months post-discharge. Logistic regression was used to analyze factors associated with non-responders compared with children who recovered. Results: Of the 1,112 children enrolled, 909 recovered and 139 were non-responders, of which 127 (80.6%) had significant MUAC gain (mean: +9.6 mm, sd = 5.1) at discharge. Girls (adjusted hazard ratio (aHR) = 2.07, 95% CI 1.33-3.25), children <12 months of age (aHr = 4.23, 95% CI 2.02-9.67), those with a MUAC <115 mm (aHR = 11.1, 95% CI 7.23-17.4) or severe stunting (aHR = 2.5, 1.38-4.83) at admission and a negative or flat MUAC trajectory between admission and week 4 (aHR = 4.66, 95% CI 2.54-9.13) were more likely to be non-responders. The nutritional status of non-responders had generally improved 6 months after discharge, but only 40% had achieved MUAC ≥125 mm. Conclusion: Non-responders are not a homogeneous group; while most children ultimately show significant nutritional improvement, rapid hospital referral is crucial for those not gaining MUAC early in treatment. As efforts to expand MUAC-based programming progress, adapting exit criterion and/or providing additional food supplementation with smaller daily ration for children with risk factors discussed here may help improve programme efficiency without adding to the cost of treatment.

Older adults' compliance with mobile ecological momentary assessments in behavioral nutrition and physical activity research: pooled results of four intensive longitudinal studies and recommendations for future research.

BACKGROUND: Mobile Ecological Momentary Assessment (EMA) is increasingly used to gather intensive, longitudinal data on behavioral nutrition, physical activity and sedentary behavior and their underlying determinants. However, a relevant concern is the risk of non-random non-compliance with mobile EMA protocols, especially in older adults. This study aimed to examine older adults' compliance with mobile EMA in health behavior studies according to participant characteristics, and prompt timing, and to provide recommendations for future EMA research. METHODS: Data of four intensive longitudinal observational studies employing mobile EMA to understand health behavior, involving 271 community-dwelling older adults (M = 71.8 years, SD = 6.8; 52% female) in Flanders, were pooled. EMA questionnaires were prompted by a smartphone application during specific time slots or events. Data on compliance (i.e. information whether a participant answered at least one item following the prompt), time slot (morning, afternoon or evening) and day (week or weekend day) of each prompt were extracted from the EMA applications. Participant characteristics, including demographics, body mass index, and smartphone ownership, were collected via self-report. Descriptive statistics of compliance were computed, and logistic mixed models were run to examine inter- and intrapersonal variability in compliance. RESULTS: EMA compliance averaged 77.5%, varying from 70.0 to 86.1% across studies. Compliance differed among subgroups and throughout the day. Age was associated with lower compliance (OR = 0.96, 95%CI = 0.93-0.99), while marital/cohabiting status and smartphone ownership were associated with higher compliance (OR = 1.83, 95%CI = 1.21-2.77, and OR = 4.43, 95%CI = 2.22-8.83, respectively). Compliance was lower in the evening than in the morning (OR = 0.82, 95%CI = 0.69-0.97), indicating non-random patterns that could impact study validity. CONCLUSIONS: The findings of this study shed light on the complexities surrounding compliance with mobile EMA protocols among older adults in health behavior studies. Our analysis revealed that non-compliance within our pooled dataset was not completely random. This non-randomness could introduce bias into study findings, potentially compromising the validity of research findings. To address these challenges, we recommend adopting tailored approaches that take into account individual characteristics and temporal dynamics. Additionally, the utilization of Directed Acyclic Graphs, and advanced statistical techniques can help mitigate the impact of non-compliance on study validity.

Calibration estimation of population total using multi-auxiliary information in the presence of non-response.

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.

Overview of Hepatitis B Vaccine Non-Response and Associated B Cell Amnesia: A Scoping Review.

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.

HIV estimation using population-based surveys with non-response: A partial identification approach.

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.

Non-response to ACE items is associated with demographic variables and health indicators in the 2021 Behavioral Risk Factor Surveillance System.

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.

Longitudinal studies of bipolar patients and their families: translating findings to advance individualized risk prediction, treatment and research.

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.

Is there a role for platelet rich plasma injection in vulvar lichen sclerosus? A self-controlled pilot study.

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.

Improved estimation of population variance in stratified successive sampling using calibrated weights under non-response.

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.

Cellular and Molecular Determinants of Biologic Drugs Resistance and Therapeutic Failure in Inflammatory Bowel Disease.

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.

Head and neck cancer patients with geriatric deficits are more often non-responders and lost from follow-up in quality of life studies.

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.

Improved exponential type mean estimators for non-response case using two concomitant variables in simple random sampling.

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.

Simulation analysis of non-respondent information in context of small domain.

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.

Investigating sources of non-response bias in a population-based seroprevalence study of vaccine-preventable diseases in the Netherlands.

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.

Calibration and XGBoost reweighting to reduce coverage and non-response biases in overlapping panel surveys: application to the Healthcare and Social Survey.

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.

Testing the role of associative learning in evidence-based treatments for anorexia nervosa.

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.

Development and validation of a nomogram to predict non-response to 5-aminosalicylic acid in patients with ulcerative colitis

Background: there are some patients with ulcerative colitis (UC) who have non-response (NR) to 5-aminosalicylic acid (5-ASA). To promote individualized treatment in UC patients, it is crucial to identify valid predictors to estimate NR to 5-ASA. Therefore, this study aimed to identify the predictive value of clinical and biochemical markers and to construct a nomogram model predicting NR to 5-ASA in patients with UC. Methods: data of patients diagnosed with UC in the First Hospital of China Medical University between January 2012 and December 2020 were retrospectively analyzed. Primary outcome was the proportion of NR to 5-ASA. Multivariable logistic regression was used to construct prediction models. Area under the curve (AUC), calibration and decision curve analyses (DCA) were assessed in the validation cohort. Results: of 284 UC patients who were treatment-naive, 86 (30.3 %) had NR to 5-ASA. Univariate regression analysis showed that disease classification (DC) (p = 0.008), monocytes (MONO) (p = 0.041), platelet distribution width (PDW) (p = 0.027), serum total cholesterol (TC) (p = 0.031) and α1 globulin (p < 0.001) were strongly associated with NR to 5-ASA. Receiver operating characteristics (ROC) analysis indicated the AUC was 0.852, it showed that this model has a good degree of discrimination. The DCA curve showed that the predicted probability is 0.0-96.0 %. Conclusion: this study developed a predictive model with good discrimination and calibration, and high clinical validity, which can effectively estimate the risk of NR to 5-ASA. DC, MONO, PDW, TC and α1 globulin can be used as predictors for NR to 5-ASA in UC patients. (AU)

Long-term effectiveness and safety of anti-TNF in pediatric-onset inflammatory bowel diseases: A population-based study.

BACKGROUND: Anti-TNF agents are the first biologic treatment option in inflammatory bowel disease (IBD). The long-term effectiveness of this strategy at the population level is poorly known, particularly in pediatric-onset IBD. METHODS: All patients diagnosed with Crohn's disease (CD) or ulcerative colitis (UC) before the age of 17 between 1988 and 2011 in the EPIMAD population-based registry were followed retrospectively until 2013. Among patients treated with anti-TNF, the cumulative probabilities of anti-TNF failure defined by primary failure, loss of response (LOR) or intolerance were evaluated. Factors associated with anti-TNF failure were investigated by a Cox model. RESULTS: Among a total of 1,007 patients with CD and 337 patients with UC, respectively 481 (48%) and 81 (24%) were treated with anti-TNF. Median age at anti-TNF initiation was 17.4 years (IQR, 15.1-20.9). Median duration of anti-TNF therapy was 20.4 months (IQR, 6.0-59.9). In CD, the probability of failure of 1st line anti-TNF at 1, 3 and 5 years was respectively 30.7%, 51.3% and 61.9% for infliximab and 25.9%, 49.3% and 57.7% for adalimumab (p = 0.740). In UC, the probability of failure of 1st line anti-TNF therapy was respectively 38.4%, 52.3% and 72.7% for infliximab and 12.5% for these 3 timepoints for adalimumab (p = 0.091). The risk of failure was maximal in the first year of treatment and LOR was the main reason for discontinuation. Female gender was associated with LOR (HR, 1.48; 95%CI 1.02-2.14) and with anti-TNF withdrawal for intolerance in CD (HR, 2.31; 95%CI 1.30-4.11) and disease duration (≥ 2 y vs. < 2 y) was associated with LOR in UC (HR, 0.37; 95%CI 0.15-0.94) in multivariate analysis. Sixty-three (13.5%) patients observed adverse events leading to termination of treatment (p = 0.57). No death, cancer or tuberculosis was observed while the patients were under anti-TNF treatment. CONCLUSION: In a population-based study of pediatric-onset IBD, about 60% in CD and 70% in UC experienced anti-TNF failure within 5 years. Loss of response account for around two-thirds of failure, both for CD and UC.