Negative Binomial Mixed Models Research Articles

Salivary polyreactive antibodies and Haemophilus influenzae are associated with respiratory infection severity in young children with recurrent respiratory infections.

Recurrent respiratory tract infections (rRTIs) are a common reason for immunodiagnostic testing in children, which relies on serum antibody level measurements. However, because RTIs predominantly affect the respiratory mucosa, serum antibodies may inaccurately reflect local immune defences. We investigated antibody responses in saliva and their interplay with the respiratory microbiota in relation to RTI severity and burden in young children with rRTIs. We conducted a prospective cohort study including 100 children aged <10 years with rRTIs, their family members and healthy healthcare professionals. Total and polyreactive antibody concentrations were determined in serum and saliva (ELISA); respiratory microbiota composition (16S rRNA sequencing) and respiratory viruses (quantitative PCR) were characterised in nasopharyngeal swabs. Proteomic analysis (Olink) was performed on saliva and serum samples. RTI symptoms were monitored with a daily mobile phone application and assessed using latent class analysis and negative binomial mixed models. Serum antibody levels were not associated with RTI severity. Strikingly, 28% of salivary antibodies and only 2% of serum antibodies displayed polyreactivity (p<0.001). Salivary polyreactive IgA was negatively associated with recurrent lower RTIs (adjusted OR 0.80, 95% CI 0.67-0.94) and detection of multiple respiratory viruses (adjusted OR 0.76, 95% CI 0.61-0.96). Haemophilus influenzae abundance was positively associated with RTI symptom burden (regression coefficient 0.05, 95% CI 0.02-0.08). These results highlight the importance of mucosal immunity in RTI severity and burden, and suggest that the level of salivary polyreactive IgA and H. influenzae abundance may serve as indicators of infection severity and burden in young children with rRTIs.

326 Relationship between activity and social interactions of beef bulls during the pre-breeding period and siring capacity in multi-sire breeding groups

Abstract It is currently unknown whether the behavior of bulls during pre-breeding is related to their siring capacity. This information could help producers anticipate the reproductive potential of their bulls and include it in their decision-making. This study aimed to investigate the relationship between the activity and characteristics of social interaction of beef bulls expressed in drylot pens during the pre-breeding period and their siring capacity. Collars with 3-axis accelerometers and proximity sensors were placed on bulls for 12 d prior to breeding season in 2020 (n = 11 bulls) and in 2021 (n = 10 bulls). Bulls were satisfactory at the breeding soundness evaluation, and ages ranged from 1.5 to 5.4 yr. Afterward, bulls were exposed to cows in multi-sire groups at a 1:30 ratio for 2 mo, however, some bulls were removed early due to injuries (range = 15 to 62 d). DNA samples were collected from bulls and calves to calculate the number of calves sired per bull (SRC), adjusted to days exposed to cows. Daily proportion of time active (AC) was measured through a machine learning algorithm created in Python for beef bulls to differentiate activity vs. non-activity from accelerometer data every 20 sec (Precision = 95%). Daily non-directional social networks were created from proximity perceived by the sensors (Precision = 91%, &amp;lt;3m) in Python, where nodes represented bulls and a connection represented one second in proximity. Eigencentrality (how well connected a bull is to others, EC) and strength (proportion of connections among overall connections, ST) were calculated for each bull daily, where greater EC and ST values indicated more interactions. The statistical analyses were performed in RStudio. Negative binomial mixed effect models were fitted to AC (mean ± S.E., 26.05 ± 0.31 %), EC (26.50 ± 0.89), and ST (8.90 ± 0.21 %) as repeated measures, age (3.3 ± 0.3 yr), days exposed to cows (54 ± 3.1 d), and year as covariates, identification of bull as a random effect, and SRC as the outcome variable (21 ± 2, 2 to 45 calves). Estimates were transformed into percentage change. Days exposed to cows, year, and interactions were not significant (P &amp;gt; 0.05). Separate models with EC or ST (model-EC and model-ST) were built due to collinearity (r = 0.89, P &amp;lt; 0.001). In model-EC (marginal-R2 = 0.26, conditional-R2 = 0.70) bulls with increased AC (estimate = 2.16±0.67, P = 0.001), increased EC (0.56±0.24, P = 0.019), and younger (-20.75 ± 5.51, P &amp;lt; 0.001) had greater SRC. In model-ST (marginal-R2 = 0.25, conditional-R2 = 0.72) bulls with increased AC (2.29 ± 0.65, P &amp;lt; 0.001), increased ST (3.57 ± 0.98, P &amp;lt; 0.001), and younger (-19.90 ± 5.49, P &amp;lt; 0.001) had greater SRC. These preliminary results suggest that activity and social interactions during pre-breeding of beef bulls are related to SRC when accounted for age. Therefore, the behavior of beef bulls during the pre-breeding period might have the potential to predict their SRC, and future studies could investigate using this information to select bulls and form breeding groups aiming at optimization of the use of the bulls.

The Hispanic paradox in child maltreatment: Does it fade over time?

BackgroundThe “Hispanic Paradox” refers to a commonly noted tendency for Hispanic immigrants to have good health outcomes relative to risks faced. This paper demonstrates the presence of the Hispanic Paradox relative to child maltreatment, with a focus on how it appears to “fade” generationally. ObjectivesTo use national child maltreatment and census data to determine if the protective effects of the Hispanic Paradox are weaker (“fade”) for counties with fewer foreign-born Hispanics. DesignCensus data, including the percentage of Hispanics in a county who were foreign-born, was used to predict child maltreatment rates as observed in the National Child Abuse and Neglect Data System. The analysis was done at a county level and included a number of covariates (e.g. Hispanic Median Income, Rural/Urban status…). Participants and settingWe included national child maltreatment data at the county level. ResultsA negative binomial mixed effects model showed that for each point of increase in the percentage of the Hispanic foreign-born population of a county, the county Hispanic child maltreatment rate was expected to drop by 1 %. Variation in Hispanic national origin (i.e. Puerto Rico) was found to significantly moderate this relationship. ConclusionCounties with higher percentages of foreign-born Hispanics have lower child maltreatment rates after controlling for other factors. This is consistent with emerging findings in the child mortality data and suggests that for child maltreatment, the Hispanic Paradox may fade generationally.

Association of Dialysate Bicarbonate with Arrhythmia in the Monitoring in Dialysis Study.

Sudden death accounts for ∼25% of deaths among maintenance hemodialysis (HD) patients, occurring more frequently on HD days. Higher dialysate bicarbonate (DBIC) may predispose to alkalemia and arrhythmogenesis. We conducted a 12-month analysis of session-level data from 66 patients with implantable loop recorders. We fit logistic regression and negative binomial mixed effects regression models to assess the association of DBIC with clinically significant arrhythmia (CSA - ventricular tachycardia ≥115 beats per minute (BPM) for at least 30 seconds, bradycardia ≤40 BPM for at least 6 seconds, or asystole for at least 3 seconds) and reviewer confirmed arrhythmia (RCA - implantable-loop-recorder-identified or patient-marked event for which a manual review of the stored ECG tracing confirmed the presence of atrial fibrillation, supraventricular tachycardia, sinus tachycardia with rate >130 BPM, ventricular tachycardia, asystole, or bradycardia). Models adjusted for age, sex, race, HD vintage, vascular access, and pre-HD serum bicarbonate and additionally for serum and dialysate potassium levels. Mean age was 56 ± 12 years, 70% were male, 53% were Black, and 35% were Asian. Fewer RCA episodes were associated with DBIC >35 than 35 mEq/L (incidence rate ratio [IRR] 0.45 (0.27, 0.75) and aIRR 0.54 (0.30, 0.97)), but the association was not significant when adjusting for serum and dialysate potassium levels (aIRR 0.60 (0.32, 1.11)). Otherwise, no associations between DBIC and arrhythmia were identified. We observed a lower frequency of RCA with higher DBIC, compared with DBIC of 35 mEql/L, contrary to our original hypothesis, but this association was attenuated in fully adjusted models. Validation of these findings in larger studies is required, with a further need for interventional studies to explore the optimal DBIC concentration.

Impact of four years of annually repeated indoor residual spraying (IRS) with Actellic 300CS on routinely reported malaria cases in an agricultural setting in Malawi.

Indoor residual spraying (IRS) is one of the main vector control tools used in malaria prevention. This study evaluates IRS in the context of a privately run campaign conducted across a low-lying, irrigated, sugarcane estate from Illovo Sugar, in the Chikwawa district of Malawi. The effect of Actellic 300CS annual spraying over four years (2015-2018) was assessed using a negative binomial mixed effects model, in an area where pyrethroid resistance has previously been identified. With an unadjusted incidence rate ratio (IRR) of 0.38 (95% CI: 0.32-0.45) and an adjusted IRR of 0.50 (95% CI: 0.42-0.59), IRS has significantly contributed to a reduction in case incidence rates at Illovo, as compared to control clinics and time points outside of the six month protective period. This study shows how the consistency of a privately run IRS campaign can improve the health of employees. More research is needed on the duration of protection and optimal timing of IRS programmes.

How turtles keep their cool: Seasonal and diel basking patterns in a tropical turtle

Behavioural thermoregulation by ectotherms is an important mechanism for maintaining body temperatures to optimise physiological performance. Experimental studies suggest that nocturnal basking by Krefft's river turtles (Emydura macquarii krefftii) in the tropics may allow them to avoid high water temperatures, however, this hypothesis has yet to be tested in the field. In this study, we examined the influence of environmental temperature on seasonal and diel patterns of basking in E. m. krefftii in tropical north Queensland, Australia. Wildlife cameras were used to document turtle basking events for seven consecutive days and nights for each month over a year (April 2020–March 2021). Air and water temperatures were recorded simultaneously using temperature loggers. We used a negative binomial mixed effects model to compare mean basking durations (min) occurring among four environmental temperature categories based on population thermal preference (26 °C): 1) air temperature above and water temperature below preferred temperature; 2) air temperature below and water temperature above preferred temperature; 3) air and water temperatures both above preferred temperature; and 4) air and water temperatures both below preferred temperature. Basking behaviour was influenced significantly by the relationship between air and water temperature. During the day, turtles spent significantly less time basking when both air and water temperatures were above their preferred temperatures. Conversely, at night, turtles spent significantly more time basking when water temperatures were warm and air temperatures were cool relative to their preferred temperature. This study adds to the growing body of work indicating pronounced heat avoidance as a thermoregulatory strategy among tropical reptile populations.

Subnational inequalities in years of life lost and associations with socioeconomic factors in pre-pandemic Europe, 2009–19: an ecological study

Health inequalities have been associated with shorter lifespans. We aimed to investigate subnational geographical inequalities in all-cause years of life lost (YLLs) and the association between YLLs and socioeconomic factors, such as household income, risk of poverty, and educational attainment, in countries within the European Economic Area (EEA) before the COVID-19 pandemic. In this ecological study, we extracted demographic and socioeconomic data from Eurostat for 1390 small regions and 285 basic regions for 32 countries in the EEA, which was complemented by a time-trend analysis of subnational regions within the EEA. Age-standardised YLL rates per 100 000 population were estimated from 2009 to 2019 based on methods from the Global Burden of Disease study. Geographical inequalities were assessed using the Gini coefficient and slope index of inequality. Socioeconomic inequalities were assessed by investigating the association between socioeconomic factors (educational attainment, household income, and risk of poverty) and YLLs in 2019 using negative binomial mixed models. Between Jan 1, 2009, and Dec 31, 2019, YLLs lowered in almost all subnational regions. The Gini coefficient of YLLs across all EEA regions was 14·2% (95% CI 13·6-14·8) for females and 17·0% (16·3 to 17·7) for males. Relative geographical inequalities in YLLs among women were highest in the UK (Gini coefficient 11·2% [95% CI 10·1-12·3]) and among men were highest in Belgium (10·8% [9·3-12·2]). The highest YLLs were observed in subnational regions with the lowest levels of educational attainment (incident rate ratio [IRR] 1·19 [1·13-1·26] for females; 1·22 [1·16-1·28] for males), household income (1·35 [95% CI 1·19-1·53]), and the highest poverty risk (1·25 [1·18-1·34]). Differences in YLLs remain within, and between, EEA countries and are associated with socioeconomic factors. This evidence can assist stakeholders in addressing health inequities to improve overall disease burden within the EEA. Research Council of Norway; Development, and Innovation Fund of Hungary; Norwegian Institute of Public Medicine; and COST Action 18218 European Burden of Disease Network.

Comparison of factors associated with seasonal influenza and COVID-19 booster vaccination coverage among healthcare personnel working at acute care hospitals during 2021–2022 influenza season, National Healthcare Safety Network, United States

The simultaneous circulation of seasonal influenza virus and SARS-CoV-2 variants will likely pose unique challenges to public health during the future influenza seasons. Persons who are undergoing treatment in healthcare facilities may be particularly at risk. It is important for healthcare personnel to protect themselves and patients by receiving vaccines. The purpose of this study is to assess coverage of the seasonal influenza vaccine and COVID-19 monovalent booster among healthcare personnel working at acute care hospitals in the United States during the 2021–22 influenza season and to examine the demographic and facility characteristics associated with coverage. A total of 3260 acute care hospitals with over 7 million healthcare personnel reported vaccination data to National Healthcare Safety Network (NHSN) during the 2021–22 influenza season. Two separate negative binomial mixed models were developed to explore the factors associated with seasonal influenza coverage and COVID-19 monovalent booster coverage. At the end of the 2021–2022 influenza season, the overall pooled mean seasonal influenza coverage was 80.3%, and the pooled mean COVID-19 booster coverage was 39.5%. Several demographic and facility-level factors, such as employee type, facility ownership, and geographic region, were significantly associated with vaccination against influenza and COVID-19 among healthcare personnel working in acute care hospitals. Our findings highlight the need to increase the uptake of vaccination among healthcare personnel, particularly non-employees, those working in for-profit and non-medical school-affiliated facilities, and those residing in the South.

Single‐cell Transcriptomes Reveal Cell‐type Specific Roles of VEGF Family Genes in the Pathogenesis of Alzheimer’s Disease

AbstractBackgroundThe role of the vascular endothelial growth factors (VEGFs) in the pathogenesis of Alzheimer’s disease (AD) has been recently described, including notable changes along the VEGFB/FLT1 signaling pathway. Yet, cell‐specific alterations are not well characterized. To disentangle VEGFs’ cell‐specific effect on AD‐related traits, we performed association analyses of mRNA expression from 10 VEGF genes with cognitive performance and AD pathology in eight brain cell types using a large single nucleus RNA sequencing dataset from human brain.MethodThis project utilized recently published single‐cell transcriptomes derived from dorsolateral prefrontal cortex tissues of 424 donors collected at Rush Alzheimer’s Disease Center. Processed single cell RNA sequencing data were acquired from AD Knowledge Portal (syn2580853). Mean age at death was 89 years, 68% were females, and 37% were AD cases. Negative binomial lognormal mixed models implemented in the NEBULA R package were used to detect differential expression between AD cases and cognitively normal controls, and to analyze the associations with immunohistochemical amyloid and tangles, and finally to assess cross‐sectional and longitudinal global cognitive scores. Correction for multiple comparisons was completed using the false discovery rate procedure (Pfdr&lt;0.05).ResultPrefrontal cortical FLT1 expression was upregulated in AD participants compared to cognitively normal controls in both endothelial (endo) and microglial (micro) cells. Higher micro‐FLT1, endo‐FLT4, and oligodendrocyte (oligo) VEGFB expression was associated with greater β‐amyloid burden in AD samples, whereas higher VEGFB expression in inhibitory neurons was associated with lower β‐amyloid burden. Higher expression of micro‐FLT1 and oligo‐VEGFB associated with worse cognitive trajectories. Higher micro‐ and endo‐ expression of FLT1 associated with lower cognition scores at the last clinic visit before death. Lastly, higher astrocyte‐expressed NRP1 was associated with lower tangle burden.ConclusionConsistent with our previously reported bulk tissue results, prefrontal cortical expression of FLT1 and FLT4 were associated with global cognition, longitudinal cognitive trajectories, and AD neuropathology, and these associations appear to be limited to endothelial and microglial cells. In contrast, VEGFB expression seems to have opposite effects on amyloid burden depending on the cell types, suggesting its more dynamic role in AD physiopathology.

FoMO predicts alcohol use and harms over and above the big five personality traits among university students

ABSTRACT Background University students are an at-risk group for alcohol use. Fear of Missing Out (FoMO), the feeling that others are having rewarding experiences that one is missing out on, may drive alcohol use and harm. We aimed to investigate whether FoMO could uniquely predict alcohol use over and above known predictors like the big five personality traits. Methods We recruited 392 university students and invited them to take part in a daily diary study where they reported their alcohol use daily over 13 days. Participants also completed a baseline survey and reported personality traits (neuroticism, extraversion, openness, agreeableness, and conscientiousness), and alcohol-related consequences and completed a final follow-up survey where they reported FoMO. Results Using a zero-inflated negative binomial mixed model, we found that those higher in FoMO consumed more alcohol on drinking days (IRR = 1.11) when controlling for personality traits. Similarly, we found that those higher in FoMO experienced more harms (IRR = 1.10), when controlling personality traits. Conclusion We found that FoMO is a distinct construct and not just isomorphic with the big five personality traits. This suggests that reducing FoMO may be a key aim for alcohol interventions and should be considered when aiming to reduce university student alcohol use.

Successful elimination of falciparum malaria following the introduction of community-based health workers in Eastern Myanmar: A retrospective analysis.

Myanmar has a large majority of all malaria in the Greater Mekong Subregion. In the past decade, substantial progress was made in malaria control. The residual burden of malaria is in remote areas where currently recommended malaria elimination approaches are generally not feasible. In such hard-to-reach communities in Mon state, East Myanmar, Medical Action Myanmar introduced community health workers (CHWs) to deliver early diagnosis and treatment for malaria. We conducted a retrospective analysis to assess the impact of this intervention. This retrospective analysis involved data collected routinely from a CHW programme in Mon state conducted between 2011 and 2018. A network of 172 CHWs serving a population of 236,340 was deployed. These CHWs carried out 260,201 malaria rapid diagnostic tests (RDTs) to investigate patients with acute febrile illness. The median blood examination rate was 1.33%; interquartile range (IQR) (0.38 to 3.48%); 95% CI [1.28%, 1.36%] per month. The changes in malaria incidence and prevalence in patients presenting with fever were assessed using negative binomial regression mixed effects models fitted to the observed data. The incidence of Plasmodium falciparum malaria (including mixed infections) declined by 70%; 95% CI [65%, 75%]; p < 0.001 for each year of CHW operation. The incidence of P. vivax malaria declined by 56%; 95% CI [50%, 62%]; p < 0.001 per year. Malaria RDT positivity rates for P. falciparum and P. vivax declined by 69%; 95% CI [62%, 75%]; p < 0.001 and 53%; 95% CI [47%, 59%]; p < 0.001 per year, respectively. Between 2017 and 2018, only 1 imported P. falciparum case was detected in 54,961 RDTs. The main limitations of the study are use of retrospective data with possible unidentified confounders and uncharacterised population movement. The introduction of CHWs providing community-based malaria diagnosis and treatment and basic health care services in remote communities in Mon state was associated with a substantial reduction in malaria. Within 6 years, P. falciparum was eliminated and the incidence of P. vivax fell markedly.

Abstract 18813: Economic Burden of Pregnancy Among Privately Insured Women With Congenital Heart Disease

Background: Women with congenital heart defects (CHD) are increasingly reaching childbearing age. Understanding their healthcare costs in pregnancy may inform resource allocation, financial planning, and pre-conception counseling. Methods: We used 2010-2016 US commercially insured beneficiaries’ data within the IBM ® MarketScan® database to identify pregnancies among 18-55-year-old women with CHD and matched controls without CHD. We assessed baseline characteristics, cardiac and noncardiac conditions, pregnancy related conditions, birth outcomes, and cesarean section. We estimated total and out-of-pocket (OOP) costs, compiled and adjusted to 2016 medical component of the consumer price index. Negative binomial mixed model was used. Results: There were 6385 pregnancies in 5077 women with CHD (672 pregnancies among severe and 5713 among nonsevere) and 9438 pregnancies in 7737 controls. Compared to controls, pregnancies with CHD were more likely to be 35+ years of age at delivery, resided in the Northeast and West regions, had flexible insurance plans, cardiac conditions, noncardiac conditions, birth outcomes, pregnancy related conditions and cesarean sections, while there was no difference in the year of delivery and gestational diabetes rates. After adjusting for all covariates, having CHD was an independent predictor of higher adjusted pregnancy-related cost ratio for total (1.49, 95% confidence interval [CI] 1.40, 1.59) and OOP costs (1.27, 95% CI 1.19, 1.35). The adjusted mean total and OOP cost difference for pregnancy per patient for any CHD, severe CHD, and nonsevere CHD was significantly higher than controls (Figure). Total expenditure and OOP cost of CHD pregnancies during the study period were $162.5 and $15.7 million dollars respectively. Conclusions: We provide novel estimates of economic burden of pregnancy among privately insured CHD patients for clinical and financial counseling and planning for patients, payors and policymakers.

Subnational inequalities in YLLs and associated socioeconomic factors: a disease burden study

Abstract Background Health inequalities are an unjust and avoidable problem. This study examines subnational geographical inequalities in all-cause years of life lost (YLLs) and the association of socioeconomic factors in pre-coronavirus European Economic Area (EEA) countries. Methods In this ecological study complimented with a longitudinal analysis, demographic and socioeconomic data for 1390 small regions and 285 basic regions of 32 EEA countries were extracted from Eurostat. Age-standardised YLL rates per 100,000 population were estimated from 2009 to 2019 based on methods from the Global Burden of Disease Study. Inequalities were assessed using the Gini coefficient (GC) and slope index of inequality (SII). The association between socioeconomic factors by YLLs were assessed using negative binomial mixed models in 2019. Findings Over the period 2009-2019, YLLs have decreased in almost all subnational regions. The GC of YLLs across EEA regions was 14% for females (95% CI = 13·5 to 14·6%) and 17% for males (CI = 16·1 to 17·5%). Greece (GC = 10·1%, CI = 7·8 to 2·5%) and Belgium (GC = 10·8%, CI = 9·5 to 12·0%) had the highest relative inequalities in YLLs for women and men, respectively. Subnational regions with the lowest income (incident rate ratio (IRR)=1·39, CI = 1·23 to 1·58) and levels of educational attainment (IRRfemales=1·19, CI = 1·13 to 1·26; IRRmales=1·22, CI = 1·16 to 1·28), and highest poverty risk (IRR=1·18, CI = 1·12 to 1·25) were associated with increased YLLs, with stronger associations observed in Central and Eastern Europe. Interpretation Differences in YLLs remain within and between EEA countries and are associated with socioeconomic factors. This evidence can assist stakeholders in addressing specific health inequities to improve overall disease burden within the EEA. Key messages • The study highlights the need for public health policies targeted at the subnational level to reduce health inequalities in the EEA. • The study describes the effect of existing public health policies targeting socioeconomic factors.

Longitudinal Microbiome Changes in Supragingival Biofilm Transcriptomes Induced by Orthodontics.

Common oral diseases are known to be associated with dysbiotic shifts in the supragingival microbiome, yet most oral microbiome associations with clinical end points emanate from cross-sectional studies. Orthodontic treatment is an elective procedure that can be exploited to prospectively examine clinically relevant longitudinal changes in the composition and function of the supragingival microbiome. A longitudinal cohort study was conducted among 24 adolescent orthodontic patients who underwent saliva and plaque sampling and clinical examinations at time points: before fixed appliance bonding and at 1, 6, and 12 wk thereafter. Clinical indices included bleeding on probing (BOP), mean gingival index (GI), probing depths (PDs), and plaque index (PI). To study the biologically (i.e., transcriptionally) active microbial communities, RNA was extracted from plaque and saliva for RNA sequencing and microbiome bioinformatics analysis. Longitudinal changes in microbiome beta diversity were examined using PERMANOVA tests, and the relative abundance of microbial taxa was measured using Kruskal-Wallis tests, Wilcoxon rank-sum tests, and negative binomial and zero-inflated mixed models. Clinical measures of oral health deteriorated over time-the proportion of sites with GI and PI ≥1 increased by over 70% between prebonding and 12 wk postbonding while the proportion of sites with PD ≥4 mm increased 2.5-fold. Streptococcus sanguinis, a health-associated species that antagonizes cariogenic pathogens, showed a lasting decrease in relative abundance during orthodontic treatment. Contrarily, caries- and periodontal disease-associated taxa, including Selenomonas sputigena, Leptotrichia wadei, and Lachnoanaerobaculum saburreum, increased in abundance after bonding. Relative abundances of Stomatobaculum longum and Mogibacterium diversum in prebonding saliva predicted elevated BOP 12 wk postbonding, whereas Neisseria subflava was associated with lower BOP. This study offers insights into longitudinal community and species-specific changes in the supragingival microbiome transcriptome during fixed orthodontic treatment, advancing our understanding of microbial dysbioses and identifying targets of future health-promoting clinical investigations. Bonding braces was associated with subsequent changes in the oral microbiome characterized by increases in disease-associated species, decreases in health-associated species, and worsened clinical measures of oral health.

Contact with caregivers is associated with composition of the infant gastrointestinal microbiome in the first 6 months of life.

Little is known about how physical contact at birth and early caregiving environments influence the colonization of the infant gastrointestinal microbiome. We investigated how infant contact with caregivers at birth and within the first 2 weeks of life relates to the composition of the gastrointestinal microbiome in a sample of U.S. infants (n = 60). Skin-to-skin and physical contact with caregivers at birth and early caregiving environments were surveyed at 2 weeks postpartum. Stool samples were collected from infants at 2 weeks, 2, 6, and 12 months of age and underwent 16S rRNA sequencing as a proxy for the gastrointestinal microbiome. Associations between early caregiving environments and alpha and beta diversity, and differential abundance of bacteria at the genus level were assessed using PERMANOVA, and negative binomial mixed models in DEseq2. Time in physical contact with caregivers explained 10% of variation in beta diversity at 2 weeks' age. The number of caregivers in the first few weeks of life explained 9% of variation in beta diversity at 2 weeks and the number of individuals in physical contact at birth explained 11% of variation in beta diversity at 6 months. Skin-to-skin contact on the day of birth was positively associated with the abundance of eight genera. Infants held for by more individuals had greater abundance of eight genera. Results reveal a potential mechanism (skin-to-skin and physical contact) by which caregivers influence the infant gastrointestinal microbiome. Our findings contribute to work exploring the social transmission of microbes.

Comparison of different statistical models for the analysis of fracture events: findings from the Prevention of Falls Injury Trial (PreFIT)

BackgroundFractures are rare events and can occur because of a fall. Fracture counts are distinct from other count data in that these data are positively skewed, inflated by excess zero counts, and events can recur over time. Analytical methods used to assess fracture data and account for these characteristics are limited in the literature.MethodsCommonly used models for count data include Poisson regression, negative binomial regression, hurdle regression, and zero-inflated regression models. In this paper, we compare four alternative statistical models to fit fracture counts using data from a large UK based clinical trial evaluating the clinical and cost-effectiveness of alternative falls prevention interventions in older people (Prevention of Falls Injury Trial; PreFIT).ResultsThe values of Akaike information criterion and Bayesian information criterion, the goodness-of-fit statistics, were the lowest for negative binomial model. The likelihood ratio test of no dispersion in the data showed strong evidence of dispersion (chi-square = 225.68, p-value < 0.001). This indicates that the negative binomial model fits the data better compared to the Poisson regression model. We also compared the standard negative binomial regression and mixed effects negative binomial models. The LR test showed no gain in fitting the data using mixed effects negative binomial model (chi-square = 1.67, p-value = 0.098) compared to standard negative binomial model.ConclusionsThe negative binomial regression model was the most appropriate and optimal fit model for fracture count analyses.Trial registrationThe PreFIT trial was registered as ISRCTN71002650.

Does the built environment influence location- and trip-based sedentary behaviors? Evidence from a GPS-based activity space approach of neighborhood effects on older adults

ObjectiveEvidence on the influence of built environments on sedentary behaviors remains unclear and is often contradictory. The main limitations encompass the use of self-reported proxies of sedentary time (ST), the scarce consideration of the plurality of sedentary behaviors, and environmental exposures limited to the residential neighborhood. We investigated the relationships between GPS-based activity space measures of environmental exposures and accelerometer-based ST measured in total, at the place of residence, at all locations, and during trips. MethodsThis study is part of the CURHA project, based on 471 older adults residing in Luxembourg, who wore a GPS receiver and a tri-axial accelerometer during 7 days. Daily ST was computed in total, at the residence, at all locations and during trips. Environmental exposures included exposure to green spaces, walking, biking, and motorized transportation infrastructures. Associations between environments and ST were examined using linear and negative binomial mixed models, adjusted for demographics, self-rated health, residential self-selection, weather conditions and wear time. ResultsParticipants accumulated, on average, 8 h and 14 min of ST per day excluding sleep time. ST spent at locations accounted for 83 % of the total ST. ST spent at the residence accounted for 87 % of the location-based ST and 71 % of the total ST. Trip-based ST represents 13 % of total ST, and 4 % remained unclassified. Higher street connectivity was negatively associated with total ST, while the density of parking areas correlated positively with total and location-based ST. Stronger associations were observed for sedentary bouts (uninterrupted ST over 20 and 30 min). ConclusionImproving street connectivity and controlling the construction of new parking, while avoiding the spatial segregation of populations with limited access to public transport, may contribute to limit ST. Such urban planning interventions may be especially efficient in limiting the harmful uninterrupted bouts of ST among older adults.

Impact of COVID-19 epidemic on temporal pattern of new HIV diagnoses in Italy, 2021 database.

New HIV diagnoses in Italy decreased drastically in 2020 due to COVID-19 related effects: 50% fewer diagnoses were reported by the National HIV Surveillance System. COVID-19 pandemic impact on HIV surveillance is unclear. We estimated the expected number of new HIV diagnoses in 2020 in order to isolate the impact of the COVID-19 pandemic. We analyzed 29697 new HIV infections diagnosed from 2012 to 2020, reported to the National HIV Surveillance System. We assessed temporal trends of new HIV diagnoses applying negative binomial mixed effects models. We estimated the COVID-19 impact as the difference between the model-estimated slopes from 2012 to 2019 and the change reported in the diagnoses. The expected number of new HIV diagnoses in 2020 was also estimated and compared with the reported count. Based on the historical trend, we expected a 15% (95% CI: 5-25%) decline of new HIV diagnoses in 2020. We reported, however, a 49% decrease, yielding to a 34% net decrease in the number of new diagnoses. The strongest impact was estimated in northern regions (-40%) and MSM (-38%). We estimated 761 (95% prediction interval: 350-1277) missed diagnoses during 2020, the majority of them occurring in the North (465 cases), among MSM (416) and heterosexual males (217). In 2020, when excluding 15% decrease of new diagnoses attributable to the expected reduction, an additional 34% decrease was observed, representing a large decline in new HIV diagnoses associated with the COVID-19 pandemic.

IDESC: identifying differential expression in single-cell RNA sequencing data with multiple subjects

BackgroundSingle-cell RNA sequencing (scRNA-seq) technology has enabled assessment of transcriptome-wide changes at single-cell resolution. Due to the heterogeneity in environmental exposure and genetic background across subjects, subject effect contributes to the major source of variation in scRNA-seq data with multiple subjects, which severely confounds cell type specific differential expression (DE) analysis. Moreover, dropout events are prevalent in scRNA-seq data, leading to excessive number of zeroes in the data, which further aggravates the challenge in DE analysis.ResultsWe developed iDESC to detect cell type specific DE genes between two groups of subjects in scRNA-seq data. iDESC uses a zero-inflated negative binomial mixed model to consider both subject effect and dropouts. The prevalence of dropout events (dropout rate) was demonstrated to be dependent on gene expression level, which is modeled by pooling information across genes. Subject effect is modeled as a random effect in the log-mean of the negative binomial component. We evaluated and compared the performance of iDESC with eleven existing DE analysis methods. Using simulated data, we demonstrated that iDESC had well-controlled type I error and higher power compared to the existing methods. Applications of those methods with well-controlled type I error to three real scRNA-seq datasets from the same tissue and disease showed that the results of iDESC achieved the best consistency between datasets and the best disease relevance.ConclusionsiDESC was able to achieve more accurate and robust DE analysis results by separating subject effect from disease effect with consideration of dropouts to identify DE genes, suggesting the importance of considering subject effect and dropouts in the DE analysis of scRNA-seq data with multiple subjects.

Impact of pharmacist‐provided medication therapy management service on reducing unplanned readmissions in adult patients in Singapore

AbstractIntroductionOlder patients on polypharmacy are predisposed to drug‐related problems (DRPs). While medication therapy management (MTM) with pharmacist involvement can reduce DRP occurrence, few have examined its impact on reducing unplanned admissions. This study was designed to determine whether a pharmacist‐provided MTM service can reduce unplanned admissions through the comparison with patients receiving usual care.MethodsA retrospective case–control study was conducted in Changi General Hospital. Patients enrolled to MTM service from January 2016 to December 2021 were included in the intervention arm (n = 96) while patients who were not enrolled were recruited as control (n = 96). Primary outcome was the incidence rate ratio (IRR) of unplanned admissions within 6 months postindex visit comparing between intervention arm and control arm. Secondary outcomes included number of DRPs identified, types of DRPs, and the potential risks avoided by resolving DRPs. The negative binomial mixed model was used to model the unplanned admissions data.ResultsMTM with pharmacists' involvement was associated with a 39% (IRRs 0.61, 95% confidence interval [CI] 0.37–0.99, p = 0.047) lower rate of admissions in the intervention compared with the control group. There were higher number of DRPs (144 vs. 2) found in the intervention arm compared with control arm, respectively. The most prevalent types of DRPs were “Nonadherence” (80.1%), “Drug omission” (5.6%), and “Inappropriate dose” (2.8%). The most common potential risks avoided were increased cardiovascular risk, n = 29 (22.1%), increased fall risk, n = 18 (13.7%), and increased fracture risk, n = 17 (13.0%).ConclusionThe study suggests that pharmacist‐provided MTM service decreased unplanned admission. It has improved medication safety and quality of care by identifying and resolving more DRPs.