Negative Binomial Regression Models Research Articles

Early warning and predicting of COVID-19 using zero-inflated negative binomial regression model and negative binomial regression model

BackgroundIt is difficult to detect the outbreak of emergency infectious disease based on the exiting surveillance system. Here we investigate the utility of the Baidu Search Index, an indicator of how large of a keyword is in Baidu’s search volume, in the early warning and predicting the epidemic trend of COVID-19.MethodsThe daily number of cases and the Baidu Search Index of 8 keywords (weighted by population) from December 1, 2019 to March 15, 2020 were collected and analyzed with times series and Spearman correlation with different time lag. To predict the daily number of COVID-19 cases using the Baidu Search Index, Zero-inflated negative binomial regression was used in phase 1 and negative binomial regression model was used in phase 2 and phase 3 based on the characteristic of independent variable.ResultsThe Baidu Search Index of all keywords in Wuhan was significantly higher than Hubei (excluded Wuhan) and China (excluded Hubei). Before the causative pathogen was identified, the search volume of “Influenza” and “Pneumonia” in Wuhan increased with the number of new onset cases, their correlation coefficient was 0.69 and 0.59, respectively. After the pathogen was public but before COVID-19 was classified as a notifiable disease, the search volume of “SARS”, “Pneumonia”, “Coronavirus” in all study areas increased with the number of new onset cases with the correlation coefficient was 0.69 ~ 0.89, while “Influenza” changed to negative correlated (rs: -0.56 ~ -0.64). After COVID-19 was closely monitored, the Baidu Search Index of “COVID-19”, “Pneumonia”, “Coronavirus”, “SARS” and “Mask” could predict the epidemic trend with 15 days, 5 days and 6 days lead time, respectively in Wuhan, Hubei (excluded Wuhan) and China (excluded Hubei). The predicted number of cases would increase 1.84 and 4.81 folds, respectively than the actual number of cases in Wuhan and Hubei (excluded Wuhan) from 21 January to 9 February.ConclusionThe Baidu Search Index could be used in the early warning and predicting the epidemic trend of COVID-19, but the search keywords changed in different period. Considering the time lag from onset to diagnosis, especially in the areas with medical resources shortage, internet search data can be a highly effective supplement of the existing surveillance system.

The Robust Negative Binomial Regression Model on Under-five Mortality due to Pneumonia in the Province of East Java

Robust Negative Binomial regression model (RNBR) is a modelling method to overcome a problem if there are outliers and overdispersion in the data. Outliers are data points that are significantly different from other data. Outliers have a significant effect on modelling to the resulting model. Furthermore, overdispersion is indicated by the presence of too large values of Pearson statistics. In this study, the RNBR model was used to determine the factors of the toddler immune variable at post neonatal age that significantly influenced the number of under-five deaths caused by pneumonia in East Java Province. Based on the modelling obtained, it shows that the RNBR model provides more robust results in handling outlier and overdispersion problems. This can be seen from the AIC value of the RNBR model is smaller than the AIC of the Poisson regression model. In addition, and which are measures of the influence of outliers on the model, decreased from 1 for the Poisson regression model to around 0.42 for the RNBR model.

Impacts of government social media on public engagement in low-carbon practices focusing on Japan

This study investigates the role of Government Social Media (GSM) in enhancing public engagement with Low-Carbon Practices (LCP) in Japan. Motivated by the need to foster sustainable development and mitigate climate change impacts, this research utilizes negative binomial regression model analyzing 1022 posts from nine Japanese government social media accounts. Our findings reveal that increased media richness negatively correlates with engagement, suggesting that content depth over visual appeal is more effective for LCP-related communication. Surprisingly, the dialogic loop reduces engagement, indicating complex public reactions to governmental initiatives. Content themes related to governmental actions and LCP information significantly enhance engagement, while emotional valence shows minimal impact. The study introduces 'social media capital' as a moderating factor, which mitigates the negative effects of dialogic loops and media richness on engagement, and influences the impact of content themes. These insights provide a foundation for future research and guide the development of effective public engagement strategies in environmental policy. The study highlights the need for nuanced GSM strategies that prioritize information quality and relevance to increase public participation in low-carbon initiatives.

Hospital admissions among adolescents in out-of-home care or special educational needs in England: insights from the ECHILD database of linked health, education and social care records

ObjectiveWe quantified planned and unplanned hospital admissions during adolescence for children with special educational needs (SEN) or placed into the care of the local authority (child looked after in out-of-home care; CLA). ApproachWe analysed linked hospital, education and social care records with whole nation coverage of England (ECHILD). Our cohort comprised pupils who started secondary school between 2007/8 and 2011/12 (aged 11), with follow-up until 2018/19 (up to 17-22 years old). Hospital admission rates were examined by sex across distinct groups with varying levels of support: i) no support, ii) school-based SEN only, iii) higher SEN (an Education and Health Care Plan) only, iv) CLA only, v) SEN and CLA, and vi) higher SEN and CLA. Negative binomial regression models were used to estimate rate ratios (RR) for each group relative to no support. Results The study population totalled 2,827,464 children; 65% (1,835,404) had no support, 30% (848,620) SEN only, 3% (93,620) higher SEN only, 1% (30,880) SEN and CLA, with the remaining groups accounting for <1%. Planned and unplanned hospital admission rates were higher for girls than boys. Planned admission rates were highest among younger children in both higher SEN groups. CLA groups had the highest rates of unplanned hospital admissions, especially girls aged 13-15 years with higher SEN (RR: 7.69, 95% CI: 6.86-8.65). A significant proportion of all unplanned admissions in adolescence were mental health-related. ImplicationsOur findings highlight significant unmet health needs, particularly in mental health, among care-experienced adolescent girls with SEN in their mid-teens.

Differences in Musculoskeletal Injury and Disability Rates in U.S. Navy Sailors Aboard Aircraft Carrier and Amphibious Assault Ships.

Musculoskeletal injuries (MSKI) are the most common clinical condition in the military that affect medical readiness. Evaluation of MSKI burden and the effects of these injuries on readiness in large deck Navy ships is warranted. A retrospective cohort study assessing population-level MSKI rates, short-term disability (restricted duty), and long-term disability episode counts of all Sailors assigned to U.S. Navy Aircraft Carriers (CVNs) and Amphibious Assault Ships (LHA/LHD) from November 2016 to February 2023 was extracted from the Musculoskeletal Naval Epidemiological Surveillance Tool. A negative binomial regression and general additive (Gaussian) models evaluate the association of ship platform, deployment status, days underway, and sex with MSKI rates and the proportion of cases that resulted in short-term disability, returned-to-duty following restricted duty, or progressed to long-term disability. Sailors attached to CVNs contributed a mean 17,893.8 ± 23,280.6 person-months, with those attached to LHA/LHDs contributing an average 5,981.8 ± 8,432.7 person-months. Aboard CVNs, MSKI occurred at a rate of 0.30 ± 0.16/1,000 person-months while deployed and 0.64 ± 0.31/1,000 person-months in homeport. Aboard LHA/LHDs, Sailors incurred MSKI at a rate of 0.59 ± 0.58/1,000 person-months while on deployment and 1.24 ± 0.68/1,000 person-months in homeport. Among Sailors aboard CVNs, short-term disability occurred in 7.95 ± 7.75% of MSKI cases while deployed and 5.13 ± 5.26% while in homeport. Aboard LHA/LHDs, 8.57 ± 13.42% of MSKI cases were placed on short-term disability while deployed and 4.95 ± 5.27% while in homeport. In the multivariable assessment of short-term disability, being deployed underway was a significant factor (B = 3.62 P = .03, variance explained = 3.86%). Sailors that were female and served aboard LHA/LHDs returned to full duty at a significantly greater frequency compared to their male counterparts and Sailors serving aboard CVNs. None of the independent variables evaluated were associated with long-term disability. The findings in the current study demonstrate the substantial burden of MSKI aboard large deck ships, both in homeport and while deployed. Inclusion of a physical therapist aboard LHA/LHDs, like the CVN, may help to prevent and mitigate the effects of MSKI through early access to specialized care and integral injury prevention and performance optimization methods.

Healthcare use among people using methamphetamine in Winnipeg, Canada

ObjectiveWe examined healthcare use among people using methamphetamine who were connected to a Community Health Centre (CHC) in Winnipeg, Canada. CHCs are primary care clinics designed to provide person-centred, holistic care to people who may be impacted by discrimination and/or oppression. ApproachFrom population-based administrative health data, we identified people with a record of a methamphetamine-related healthcare system encounter from 2013-2020 (cases) and created a comparison group matched on age, sex, and postal code but with no recorded history of using methamphetamine (controls). We narrowed this population to those who visited a CHC at least once. Then, using negative binomial regression models adjusted for sociodemographic characteristics, we produced rate ratios and 95% confidence intervals for primary care visits, CHC visits, emergency service contacts, emergency department (ED) visits, and hospitalizations in the 5 years after the first recorded methamphetamine use. ResultsAdjusted rate ratios showed that healthcare use among CHC-connected people using methamphetamine was higher than among CHC-connected people not using methamphetamine: primary care 1.15 (95% CI 1.07-1.23); CHC 1.17 (95% CI 1.01-1.37); emergency services 6.19 (95% CI 5.46-7.02); ED 3.19 (95% CI 2.92-3.48); hospitalization 2.77 (95% CI 2.46-3.10). Conclusion & ImplicationsBeing connected to a CHC may have facilitated access to other health and social services, but there is still unmet need for high quality, holistic care among people using methamphetamine. This research informs our team’s ongoing efforts to address mental health and addictions concerns across sectors and to promote anti-discriminatory approaches to addictions care in the healthcare system.

Determining the learning curve of minimally invasive antireflux surgery: systematic review, meta-analysis, and meta-regression.

The rapid uptake of minimally invasive antireflux surgery has led to interest in learning curves for this procedure. This study ascertains the learning curve in laparoscopic and robotic-assisted antireflux surgery. A systematic review of the literature pertaining to learning curves in minimally invasive fundoplication with or without hiatal hernia repair was performed using PubMed, Medline, Embase, Web of Science, and Cochrane Library databases. A meta-regression analysis was undertaken to identify the number of cases to achieve surgical proficiency, and a meta-analysis was performed to compare outcomes between cases that were undertaken during a surgeon's learning phase and experienced phase. Twenty-five studies met the eligibility criteria. A meta-regression analysis was performed to quantitatively investigate the trend of number of cases required to achieve surgical proficiency from 1996 to present day. Using a mixed-effects negative binomial regression model, the predicted learning curve for laparoscopic and robotic-assisted antireflux surgery was found to be 24.7 and 31.1 cases, respectively. The meta-analysis determined that surgeons in their learning phase may experience a moderately increased rate of conversion to open procedure (odds ratio [OR] 2.44, 95% confidence interval [CI] 1.28, 4.64), as well as a slightly increased rate of intraoperative complications (OR 1.60; 95% CI 1.08, 2.38), postoperative complications (OR 1.98; 95% CI 1.36, 2.87), and needing reintervention (OR 1.64; 95% CI 1.16, 2.34). This study provides an insight into the expected caseload to be competent in performing antireflux surgery. The discrepancy between outcomes during and after the learning curve for antireflux surgery suggests a need for close proctorship for learning surgeons.

Grossman’s Generalised Health Demand Model: An Application on Türkiye

Health is the main source of economic activity and human capital. Each individual wants to be healthy throughout her life in order to maximize his/her individual benefit and strives for this. In this study, which examined the health demand of individuals, Grossman's health demand (consumption and investment) model, which pioneered research on health demand, was referenced. The demands of 25825 individuals for medical care included in the 2016 and 2019 health research micro datasets in Türkiye were examined using the negative binomial regression model. In addition, the effects of human capital components (education, income, etc.) on the general health status of individuals were analyzed using the ordinal logit model. Health demand is influenced by economic variables as well as social and cultural factors and individuals' life behaviors. Such variables are also included in the analysis. According to the results, it was seen that individuals with chronic diseases are more likely to receive medical care than those who do not have such a disease. Besides, it was concluded that education, income, and sports exercises improve the health status of individuals, whereas aging and an increase in the number of diseases worsen the health status.

The effects of built environments on bicycle accidents around bike-sharing program stations using street view images and deep learning techniques: The moderating role of streetscape features

With the global rise of bike-sharing programs (BSP), planners and traffic experts have raised concerns as to whether the rapid growth of BSP ensures cycling safety. Despite numerous studies on built environments encouraging bike usage, there is limited knowledge whether streetscape environments around BSP stations affect bicycle accidents. We address this gap by investigating the relationships between various built environments and bicycle accidents around BSP stations, with a particular focus on the moderating effects of comprehensive streetscapes. Streetscape environments, estimated through semantic segmentation and k-means clustering, were used in two-level negative binomial regression models to clarify how street- and station-level environments affect different types of bicycle accidents. The findings indicate increased crash likelihoods on higher-speed roads, streets with traffic facilities, in proximity to public transportation infrastructure, and specific streetscape types. In particular, streetscape features like green oasis streets and open-sky roadways positively contribute to mitigating the negative effects of traffic facilities, such as bike networks and crosswalks, on cycling safety. This study aids in developing comprehensive strategies and guidelines to retrofit built environments for better traffic safety and thereby promote urban cycling.

The relationships between the campus built environment and walking activity

Despite the gradual development of students’ sedentary habits and associated health problems, only a few studies have extensively and systematically measured campus built environments (CBE) and their impact on street walking activity. This study explores the association between CBEs and pedestrian volume (PV). Comprehensive questionnaires, field audits, and GIS were used to measure the CBE variables and PV of 892 street segments on eight Chinese campuses in Tianjin. We used negative binomial regression models without spatial autocorrelations to investigate the relationship between the CBEs and PV. The findings indicated that campus Walk Score, facility and residential land ratio, campus design qualities, sidewalk conditions, street amenities, and other streetscape features were positively associated with PV. This study presents implications for campus research and planning practices in designing a pedestrian-friendly, sustainable, and healthy campus.

Multi-Institutional Study of Referral Patterns for Gynecologic Oncology Consultation.

Evaluation by a gynecologic oncologist (GO) is associated with improved clinical outcomes for patients with gynecologic cancers, yet little is known about health care factors that influence patients' referrals to GO. Medical records of 50 consecutive new patients seen in GO clinics at each of six referral centers across the United States were reviewed. Patient and disease characteristics were collected along with referral indication, evaluation and referral dates, diagnostic procedures, provider specialties, and zone improvement plan (ZIP) code of up to three referring providers per patient. The primary outcome was interval between first evaluation and referral. Univariate associations were evaluated with Chi-square and Wilcoxon rank-sum tests and multivariable associations with negative binomial regression models. Secondary outcome was prolonged time to GO referral, defined as greater than the 75th percentile. Logistic regression was used for multivariable modeling. Three hundred patient records were analyzed. The median time from first health care encounter to referral was 15 days (IQR, 5-43). The mean distance from residence to GO was 39.8 miles (standard deviation, 53.8). Seventy-one percent of GO referrals were initiated by obstetrician-gynecologists, 9% by family physicians, and 6% internists. Presentation-to-referral interval was 76% shorter for patients evaluated by an emergency medicine clinician (exp(Beta), 0.24; 95% CI, 0.11 to 0.53; P < .001). Public insurance was associated with 1.47 times longer time to referral compared with private insurance (exp(Beta), 1.47; 95% CI, 1.05 to 2.04; P = .001). Residents of nonmetropolitan ZIP codes were less likely to have prolonged time to referral (odds ratio [OR], 0.288; P = .017). Distance from residence to GO (per 10 miles) increased the likelihood of prolonged time to referral (OR, 1.10; P = .010). Interventions are needed to improve recognition and referral of patients for gynecologic oncology evaluation. Community outreach and engagement with obstetrician-gynecologists should be prioritized to improve times to referral.

Patent output and patent transfer network in China universities: Moderating roles of absorptive capacity and desorptive capacity

Although absorptive capacity and desorptive capacity has been widely present in university-industry relationships, there has been no research on their potential impact on the relationship between university patent output and university patent transfer network. We constructed datasets of patent applications and patent transfers to firms from 383 universities between 2002 and 2021 in China, and empirically demonstrated the effect of the patent output on university patent transfer network using negative binomial regression models. We also examined the moderating effects of absorptive capacity and desorptive capacity. The results reveal that university patent output positively affects the size and the connection strength of the university patent transfer network. Technology transfer offices and satellite institutions, for desorptive capacity in universities, negatively moderate the relationship between the university patent output and the university patent transfer network, respectively. For absorptive capacity in firms, research and development intensity of new products and the level of research and development personnel input, respectively, have a positively moderate effect on the relationship between the university patent output and the university patent transfer network. Our research provides insights into the dynamics of the university patent transfer network; especially against the backdrop of a sharp increase in university patent output and insufficient development of the university patent transfer network, this study provides evidence to the substitution effect of desorptive capacity in universities and the bidirectional effect of absorptive capacity in firms.

Analyzing Fatal Police Shootings: The Roles of Social Vulnerability, Race, and Place in the U.S.

IntroductionSocial vulnerability, race, and place are three important predictors of fatal police shootings. This research offers the first assessment of these factors at the zip code level. MethodsThe 2015-2022 Mapping Police Violence and Washington Post Fatal Force Data (2015-2022) were used and combined with the American Community Survey (2015-2022). The social vulnerability index (SVI) was computed for each zip code by using indicators suggested by CDC, then categorized into low-, medium-, and high-SVI. The analytical file included police officers who fatally shot 6,901 individuals within 32,736 zip codes between 2015-2022. Negative Binomial Regression (NBRG) models were run to estimate the association between number of police shootings and zip code SVI, racial composition, and access to guns using 2015-2022 data. ResultsMoving from low-SVI to high-SVI revealed the number of fatal police shootings increased 8.3 times, with the highest increases in Blacks (20.4 times), and Hispanics (27.1 times). The NBRG showed that moderate-, and high-SVI zip codes experienced higher fatal police shootings by 1.97, and 3.26 times than low-SVI zip codes; zip code racial composition, working age population, number of violent crimes, number of police officers and access to a gun, were other predictors of fatal police shootings. ConclusionsSocial vulnerability and racial composition of a zip code are associated with fatal police shooting, both independently and when considered together. What drives deadly police shootings in the United States is not one single factor, but rather complex interactions between social-vulnerability, race, and place that must be tackled synchronously. Action must be taken to address underlying determinants of disparities in policing.

Visual field loss and falls requiring hospitalisation: results from the eFOVID study.

Visual fields are important for postural stability and ability to manoeuvre around objects. Examine the association between visual field loss and falls requiring hospitalisation in adults aged 50 +. Older adults aged 50+ with and without visual field loss were identified using a fields database obtained from a cross-section of ophthalmologists' practices in Western Australia (WA). Data were linked to the Hospital Morbidity Data Collection and WA Hospital Mortality System to identify participants who experienced falls-related hospitalisations between 1990 and 2019. A generalised linear negative binomial regression model examined the association between falls requiring hospitalisation for those with and without field loss, based on the better eye mean deviation (mild: -2 to -6dB, moderate: -6.01dB to -12dB, severe < -12.01dB) in the most contemporaneous visual field test (3years prior or if not available, 2years after the fall), after adjusting for potential confounders. A total of 31 021 unique individuals of whom 6054 (19.5%) experienced 11 818 falls requiring hospitalisation during a median observation time of 14.1years. Only mean deviation index of <-12.01dB (severe) was significantly associated with an increased rate of falls requiring hospitalisations by 14% (adjusted IRR 1.14, 95% CI 1.0-1.25) compared with no field loss, after adjusting for potential confounders. Other factors included age, with those aged 80+ having an increased rate (IRR 29.16, 95% CI 21.39-39.84), other comorbid conditions (IRR 1.49, 95% CI 1.38-1.60) and diabetes (IRR 1.25, 95% CI 1.14-1.37). Previous cataract surgery was associated with a decreased rate of falls that required hospitalisations by 13% (IRR 0.87, 95% CI 0.81-0.95) compared with those who did not have cataract surgery. The findings highlight the importance of continuous clinical monitoring of visual field loss and injury prevention strategies for older adults with visual field loss.

Impacts of climate change on diarrhoeal disease hospitalisations: How does the global warming targets of 1.5-2°C affect Dhaka, Bangladesh?

Dhaka is one of the world's densely populated cities and faces significant public health challenges including high burden of diarrhoeal diseases. Climate change is intensifying existing environmental problems including urban heat island effect and poor water quality. While numerous epidemiological studies have linked meteorological factors to diarrhoeal diseases in Bangladesh, assessment of the impacts of future climate change on diarrhoeal diseases is scarce. We provide the assessment of climate change impacts on diarrhoeal disease in Dhaka and project future health risks under climate change scenarios. About 3 million acute diarrhoea cases presenting to the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research Bangladesh (icddr,b) during 1981-2010 were linked to daily temperature, rainfall and humidity and association investigated using time series adapted negative binomial regression models employing constrained distributed lag linear models. The findings were applied to climate projections to estimate future risks of diarrhoea under various global warming scenarios. There was a significantly raised risk of diarrhoea hospitalisation in all ages with daily mean temperature (RR: 3.4, 95% CI: 3.0-3.7) after controlling for the confounding effects of heavy rainfall, humidity, autocorrelations, day of the week effect, long-term time, and seasonal trends. Using the incidence rate ratio (IRR) of 1.034, temperature increases based on the global warming targets of 1.5-2°C could result in an increase of diarrhoea hospitalisations by 4.5-7.4% in all age groups by the 2100s. These effects were more pronounced among <5 children where the predicted temperature increases could raise diarrhoea hospitalisation by 5.7% - 9.4%. Diarrhoea hospitalisation will increase significantly in Dhaka even if the global warming targets adopted by the Paris Agreement is reached. This underscores the importance of preparing the city for management and prevention of diarrhoeal diseases.

Quality of Advance Care Planning in Long-Term Care and Transfers to Hospital at the End Of Life

ObjectivesOur primary objective was to determine if more comprehensive advance care planning (ACP) documentation was associated with fewer transfers to hospital in the last year of life. Our secondary objective was to determine the impact of ACP processes and practices on hospital transfers in the last year of life. DesignRetrospective cohort study. Setting and ParticipantsLong-term care (LTC) residents in Ontario, Canada, 65 years and older who died between January 1, 2017, and May 30, 2018, and resided in a participating LTC home. MethodsWe administered a survey to directors of care at LTC homes inquiring about ACP practices. Our exposure of interest was living in a home with comprehensive ACP documentation that includes information beyond preferences for cardiopulmonary resuscitation and hospital transfer. Our primary outcome was the number of transfers to hospital in the last year of life. We fit negative binomial regression models to determine the independent effect of comprehensive ACP and other indicators of ACP quality. ResultsA total of 157 LTC homes with 6637 decedent residents were included in our study; 2942 lived in homes with comprehensive ACP documentation and 3695 had non-comprehensive ACP documents. Comprehensive documentation was not associated with fewer hospital transfers in the final year of life [incidence rat ratio (IRR), 1.00; 95% CI, 0.91–1.09]. ACP documentation update frequency, availability of ACP documents in the electronic medical record, referring to ACP documents during a health crisis, inclusion of resident values in ACP documents, and involvement of a multidisciplinary team were all associated with fewer transfers to hospital during follow-up in the last year of life. Conclusions and ImplicationsACP documents that contain information beyond preferences for cardiopulmonary resuscitation and hospital transfer had no association with transfers to hospital, but high-quality ACP practices and processes were associated with fewer transfers.

Trends in direct healthcare utilization observed for persons with MS among teleneurology users and diverse populations

Background: The impact of teleneurology on healthcare utilization (HCU) in MS is unknown. Objective: Evaluate the association between teleneurology and HCU. Methods: A retrospective longitudinal analysis of HCU among adult MS and clinically isolated syndrome (CIS) patients residing in the Cleveland/Akron area from July 2020 to July 2022. Negative binomial regression models evaluated the association between number of laboratory and MRI orders per visit and number of emergency visits per patient across patient groups with variable proportions of teleneurology visits. Results: A total of 3208 patients completed 15,795 visits. Patients using teleneurology had more visits (rate ratio (RR) 1.707–1.719, p < 0.001). Teleneurology visits had fewer laboratory (RR 0.571) and MRI orders (RR 0.693, p < 0.001). There was no difference in emergency care utilization for teleneurology patients (p ⩾ 0.05). More emergency visits were observed in Black (RR 1.414) and Medicaid (RR 1.893) patients, regardless of visit type (p < 0.001). Conclusion: Teleneurology visits were associated with fewer orders, suggesting teleneurology may be incorporated into healthcare models without increasing utilization related to the visit. Teleneurology was also associated with increased visit volumes but no difference in emergency HCU. More studies are needed to clarify the ultimate impact of teleneurology on overall HCU. More emergency visits, regardless of visit type, were observed among at-risk populations, warranting further investigation.

Associations between Urinary Phthalate Metabolites with BDNF and Behavioral Function among European Children from Five HBM4EU Aligned Studies.

Based on toxicological evidence, children's exposure to phthalates may contribute to altered neurodevelopment and abnormal regulation of brain-derived neurotrophic factor (BDNF). We analyzed data from five aligned studies of the Human Biomonitoring for Europe (HBM4EU) project. Ten phthalate metabolites and protein BDNF levels were measured in the urine samples of 1148 children aged 6-12 years from Italy (NACII-IT cohort), Slovakia (PCB-SK cohort), Hungary (InAirQ-HU cohort) and Norway (NEBII-NO). Serum BDNF was also available in 124 Slovenian children (CRP-SLO cohort). Children's total, externalizing and internalizing behavioral problems were assessed using the Child Behavior Checklist at 7 years of age (only available in the NACII-IT cohort). Adjusted linear and negative binomial regression models were fitted, together with weighted quantile sum (WQS) regression models to assess phthalate mixture associations. Results showed that, in boys but not girls of the NACII-IT cohort, each natural-log-unit increase in mono-n-butyl phthalate (MnBP) and Mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) was cross-sectionally associated with higher externalizing problems [incidence rate ratio (IRR): 1.20; 95% CI: 1.02, 1.42 and 1.26; 95% CI: 1.03, 1.55, respectively]. A suggestive mixture association with externalizing problems was also observed per each tertile mixture increase in the whole population (WQS-IRR = 1.15; 95% CI: 0.97, 1.36) and boys (IRR = 1.20; 95% CI: 0.96, 1.49). In NACII-IT, PCB-SK, InAirQ-HU and NEBII-NO cohorts together, urinary phthalate metabolites were strongly associated with higher urinary BDNF levels, with WQS regression confirming a mixture association in the whole population (percent change (PC) = 25.9%; 95% CI: 17.6, 34.7), in girls (PC = 18.6%; 95% CI: 7.92, 30.5) and mainly among boys (PC = 36.0%; 95% CI: 24.3, 48.9). Among CRP-SLO boys, each natural-log-unit increase in ∑DINCH concentration was associated with lower serum BDNF levels (PC: -8.8%; 95% CI: -16.7, -0.3). In the NACII-IT cohort, each natural-log-unit increase in urinary BDNF levels predicted worse internalizing scores among all children (IRR: 1.15; 95% CI: 1.00, 1.32). Results suggest that (1) children's exposure to di-n-butyl phthalate (DnBP) and di(2-ethylhexyl) phthalate (DEHP) metabolites is associated with more externalizing problems in boys, (2) higher exposure to DINCH may associate with lower systemic BDNF levels in boys, (3) higher phthalate exposure is associated with higher urinary BDNF concentrations (although caution is needed since the possibility of a "urine concentration bias" that could also explain these associations in noncausal terms was identified) and (4) higher urinary BDNF concentrations may predict internalizing problems. Given this is the first study to examine the relationship between phthalate metabolite exposure and BDNF biomarkers, future studies are needed to validate the observed associations.

Trajectories of maternal parenting stress and adolescent behavioral symptoms in unmarried families: The role of family immigration status

BackgroundMaternal parenting stress during childhood may have important influences on offspring internalizing and externalizing behaviors during adolescence in unmarried households, but it is unclear whether effects differ across different trajectory patterns of maternal parenting stress and for native-born vs. immigrant families. MethodsUsing data from the Future of Families and Child Wellbeing Study, we identified trajectory patterns of maternal parenting stress from ages 1–9 years using semi-parametric group-based trajectory modeling. We used negative binomial regression models to estimate associations between maternal parenting stress trajectories and adolescent behavioral symptoms at age fifteen. ResultsFive maternal parenting stress trajectory groups were identified among the 1982 unmarried families included in this study, representing consistently low (9.2 %), consistently mild (54.2 %), moderate and decreasing (14.4 %), moderate and increasing (16.0 %) and consistently high (6.2 %) levels of maternal parenting stress. For adolescent internalizing symptoms, all maternal parenting stress trajectory groups exhibited higher symptoms compared to the consistently low group: IRR for consistently mild: 1.21 (95 % CI: 0.98–1.56); IRR for moderate/decreasing: 1.34 (95 % CI: 1.04–1.74); IRR for moderate/increasing: 1.62 (95 % CI: 1.28–2.13); and IRR for consistently high: 1.74 (95 % CI = 1.29–2.41). Similar results were observed for adolescent externalizing symptoms. Stronger effects of maternal parenting stress trajectories on adolescent externalizing symptoms were observed among native-born vs. immigrant families. LimitationsDifferential attrition and same-source bias may lead to under- or over-estimation of the associations of interest. ConclusionsInterventions targeting unmarried families with elevated maternal parenting stress during childhood may reduce behavioral symptoms in adolescence.

Achievement of Endoscopic Remission After Induction Reduces Hospitalization Burden in Crohn's Disease: Findings From a Pooled Post Hoc Analysis of Risankizumab and Upadacitinib Phase III Trials.

Endoscopic remission has emerged as an important treatment target in Crohn's disease (CD) and has been associated with improvement in long-term outcomes. We examined the relationship between achievement of endoscopic remission and hospitalizations using pooled 52-week Phase III risankizumab and upadacitinib maintenance trials for patients with moderate-to-severely active CD. Included patients received maintenance therapy after achieving a clinical response following a 12-week induction with risankizumab or upadacitinib. Endoscopic remission defined as a Simple Endoscopic Score for CD no greater than 4 with at least a 2-point reduction versus induction baseline and no subscore greater than 1. All subsequent hospitalization events were recorded until completion of the maintenance trial or discontinuation. Exposure-adjusted negative binomial regression models were estimated to assess the relationship between post-induction endoscopic remission and long-term hospitalization, controlling for demographics, clinical variables, and treatment arm. Post-induction hospitalization rates were lower in patients who achieved endoscopic remission at the end of the induction period. In multivariable models, post-induction endoscopic remission was independently associated with an IRR of 0.45 (95% CI [0.22-0.95], p=0.036) and 0.71 (95% CI [0.44-1.14], p=0.156) for long-term disease-related and all-cause hospitalizations, respectively. Week 12 endoscopic remission is independently associated with reducing 52-week disease-related hospitalizations. However, achieving this stringent endpoint within 12 weeks of therapy may be challenging. Endoscopic response may be a more realistic early endoscopic target in the post-induction timeframe. Additional research is needed to evaluate early achievement of alternative endoscopic endpoints in CD.