Mixed Linear Regression Models Research Articles

Sinus Bone Graft Stability and Implant Survival Following Transalveolar Sinus Floor Elevation in Severely Atrophic Maxilla: A Retrospective Study With 5-8 Years of Follow-Up.

To evaluate the clinical and radiographic results of transalveolar sinus floor elevation (TSFE) with grafting in cases of severely atrophic maxilla. A retrospective analysis of clinical and radiographic data was conducted. Between 2015 and 2018, a total of 105 implants were placed in 105 patients over a follow-up period of 5-8 years. Implant failures and endo-sinus bone gain (ESBG) were assessed. Statistical models were established to investigate the potential influencing factors of implant survival and ESBG. Six patients with six implants were lost, resulting in cumulative survival rates of 94% for both patient- and implant-based analyses. The 8-year cumulative survival rate was significantly lower for residual bone height (RBH) < 4 mm (88%) compared to RBH 4-6 mm (98%). ESBG ≥ 4 mm and ESBG ≥ 6 mm were observed in 89.90% and 58.59% of implant sites, respectively. According to the log-rank Mantel-Cox analysis results, none of the factors examined were significantly related to implant failure, except for RBH (p = 0.038) at baseline. The linear mixed-model regression results showed that the final ESBG was positively correlated with implant insertion site (p = 0.003), implant length (p < 0.001), sinus floor elevation (SFE) methods (p = 0.010), and RBH (p < 0.001). Within the limitations of this study, it has been established that TSFE with grafting was a reliable method for implant placement in the posterior atrophic maxilla ridges with RBH ranging from 4 to 6 mm. Nevertheless, caution was advised when considering its application in cases where the initial bone height falls below 4 mm.

Early adolescent attitudes toward the police post-Floyd

ABSTRACT The current study assesses the impact of the movement that followed George Floyd’s murder on early adolescent attitudes toward the police (ATP). Using a repeated cross-sectional design, we examine ATP among a Midwestern sample of 5th and 6th grade students before (fall 2018 and fall 2019) and after (fall 2020) Floyd’s murder. Descriptive results reveal that the distributions of ATP were identical during fall 2018 and fall 2019 survey years but shifted during the fall 2020 survey year. Results from mixed effects linear regression models indicate that Black and White girls experienced the largest declines in ATP from fall 2019 to fall 2020. Boys, particularly White boys, were less impacted. While Black boys’ average attitudes did not change in the post-Floyd era, overall, their attitudes were significantly lower than other groups. The findings highlight the need for ongoing measurement of early adolescent perceptions of law enforcement during the post-Floyd era and the current legitimacy crisis.

Driving after Concussion: Symptom Clusters and Neurocognition Uniquely Relate to Post-Concussion Driving Performance.

To identify clinical concussion assessment outcomes that uniquely capture simulated driving performance among acutely concussed individuals, relative to controls. Cross-sectional design. Twenty-eight college students within 72-hours of concussion and 46 non-concussed controls participated in the study. We collected the following clinical concussion assessment outcomes: 4 concussion symptom clusters, 7 computerized neurocognitive domain scores, Standardized Assessment of Concussion (SAC) total score, Balance Error Scoring System total score, and tandem gait completion time. The following simulated driving outcomes were included (count): total collisions, speed exceedances, centerline crossings, and road edge excursions. We used separate generalized linear mixed regression models fit using a Poisson distribution with group, assessment, and interaction effects. Higher migrainous symptoms (p < 0.001), cognitive-fatigue symptoms (p = 0.041), poorer visual memory (p = 0.015), and slower reaction time (p = 0.023) in concussion group were associated with higher risk of committing speed exceedances, relative to controls. Conversely, better performance on the continuous performance test (p = 0.046) and SAC (p = 0.045) in concussion group were associated with higher risk of committing speed exceedances relative to controls. Poorer performance on psychomotor speed (p = 0.001), reaction time (p = 0.031), cognitive flexibility (p = 0.004), and executive function (p = 0.003) were associated with higher risk of committing centerline crossings in concussion group, relative to controls. Conversely, better performance on the continuous performance test (p = 0.035) and higher affective symptoms (p = 0.013) were associated with higher risk of committing centerline crossings and road edge excursions, respectively. relative to controls. Our results highlight key symptom clusters and computerized neurocognitive outcomes that uniquely inform poorer simulated driving performance in acutely concussed individuals. Symptom clusters and computerized neurocognitive function might be helpful when discussing with patients about return to driving decisions post-concussion.

Efficacy of a couple-based intervention addressing sexual concerns for breast cancer survivors: Results of a randomized controlled trial.

Sexual concerns are common and problematic for breast cancer survivors. Partner and relationship factors often play a key role in determining survivors' sexual adjustment, making it likely that couple-based interventions that integrate survivors' partners could be especially promising for addressing survivors' sexual concerns. Yet few such interventions have been tested. The objective of this study was to evaluate the efficacy of the Intimacy Enhancement (IE) intervention, a four-session, couple-based intervention addressing breast cancer survivors' sexual concerns by telephone in a randomized controlled trial. Female posttreatment breast cancer survivors reporting sexual concerns and their intimate partners (N=120 couples; 240 participants) were randomized either to the IE intervention or to Living Healthy Together (LHT), an active control intervention of equivalent length. Outcomes (measured at baseline, postintervention, and at 3 and 6 months postintervention) included breast cancer survivors' sexual function (primary), partners' sexual function (secondary), and survivors' and partners' psychosocial and relationship outcomes (secondary). Mixed linear regression models examined intervention effects on outcomes at all follow-ups. Model-based estimates of intervention effects showed greater improvements in survivors' overall sexual function, sexual satisfaction, arousal, lubrication, and orgasm at postintervention (p<.05). Effects on survivors' 3-month and 6-month sexual functioning or other secondary outcomes were minimal. Most couples completed all IE sessions (97%) and LHT (92%), and satisfaction ratings were high. Compared with an active control intervention, the IE intervention had significant short-term benefits for survivors' sexual function. Efforts may be needed to increase the longevity of the positive effects, such as more frequent or adjunctive treatments.

Associations between blood markers of glucose metabolism and characteristics of circulating lymphocytes

AimsThe pathophysiology of diabetes is not fully understood; recent research indicates close relations with immunological alterations. Therefore, the aim of this study was to investigate the associations between markers of glucose metabolism and characteristics of blood lymphocytes in a population-based cohort. MethodsThe analysis was based on data from 219 non-diabetic participants of the MEGA study in Augsburg, Germany, who were recruited between 2018 and 2021. The majority of participants were examined two different times with a time lag of 9 months. Fasting venous blood samples were taken and oral glucose tolerance tests (OGTT) were performed at both visits. Immune cells were analyzed from fresh blood using flow cytometry. The associations between fasting blood glucose levels, glucose levels at 2 hours after oral glucose bolus and glycated hemoglobin (HbA1c) concentrations and the quantity of different lymphocyte subsets were analyzed using linear mixed regression models with random intercept. P values were FDR-adjusted. ResultsHbA1c was negatively associated with the marginal zone B cells (IgD+ CD27+ B cells). Fasting glucose was positively associated with natural killer (NK) cells and 2-hour OGTT glucose was positively associated with NKT cells. Finally, HbA1c showed significantly negative associations with the CD57-PD1-NKT cell subset. ConclusionMarkers of glucose metabolism showed significant associations with B cell, NK cell and NKT cell subsets, which clearly indicates a relation between glucose metabolism and the adaptive immune system.

Effect of nonsteroidal anti-inflammatory drugs on neonatal calf diarrhea when administered at a disease alert generated by automated milk feeders.

The objective of this randomized clinical trial was to assess whether early intervention with a nonsteroidal anti-inflammatory drug (NSAID) following a disease alert generated by automated milk feeders could reduce diarrhea severity and improve performance in dairy calves. Seventy-one Holstein calves were enrolled on an automated milk feeder (recorded milk intake and drinking speed) at 3 d of age and received up to 15 L/d (150 g/L) of milk replacer until 35 d of age. An alert that was previously validated as diagnostically accurate to identify calves at risk for diarrhea was used using automated milk feeder data (≤60% rolling dividends in milk intake and/or drinking speed over 2 d). At their first alert, calves were randomly allocated to receive a single subcutaneous injection of meloxicam (Metacam, Boehringer Ingelheim) at a rate of 0.5 mg/kg of body weight (NSAID) or an equal volume of a placebo, saline (CON). Fecal consistency was scored daily, and calves were diagnosed with diarrhea when they had loose feces for ≥2 d or watery feces for ≥1 d. Body weight was recorded at birth and weekly thereafter. A subset of calves (n = 32) were fitted with IceQube pedometers at 3 d of age to measure activity behaviors (lying time and step count). Mixed linear regression models were used to assess the association of study treatment with the duration of diarrhea after the alert; and to evaluate the association of study treatment with milk intake, drinking speed, lying time, overall activity for 5 d following the alert, and ADG for 3 wk following the alert. On average calves triggered an alert at (mean ± SD) 9.3 ± 2.3 d of age and were diagnosed with diarrhea at 9.6 ± 2.1 d of age. Diarrhea duration was similar between treatments (NSAID: 2.85 vs. CON: 2.94 ± 0.37 d) as were feeding behaviors [Milk intake (NSAID: 8.2 vs. CON: 8.1 ± 0.4 L/d) and drinking speed (NSAID: 0.38 vs. CON: 0.37 ± 0.02 min/L)]. Treatment was also not associated with ADG for the 3 wk after the alert (NSAID: 0.97 vs. CON: 0.97 ± 0.06 kg/d). However, calves provided an NSAID had reduced odds of being treated with electrolytes (OR = 0.32, 95% CI: 0.10 - 0.98). In addition, calves provided an NSAID spent less time lying (NSAID: 17.64 vs. CON: 18.17 ± 0.19 h/day) and performed more steps over the 5-d following the alert (NSAID: 789.1 vs. CON: 628.0 steps/d), suggesting that CON calves may have been more lethargic. Overall, providing an NSAID at the time of a diarrhea alert did not affect diarrhea duration, feed intake, or growth. However, providing an NSAID increased activity in the 5 d following the alert, which may have reduced pain and symptoms of lethargy, indicating a milder response to the disease. We suggest that providing an NSAID at the time of diarrhea alert had little benefit on the calf; however, further work is needed to understand behaviors associated with malaise and pain in calves with diarrhea, and the efficacy of NSAID under different management conditions.

Get BusActive!: Protocol of a single-blinded randomised controlled trial incentivising public transport use for physical activity gain among young people and adults.

Population level physical activity generally does not meet recommended targets. Compared with private motor vehicle users, public transport users tend to be more physically active and financial incentives may encourage more public transport use, but these relationships are under-investigated. This paper describes the protocol of a randomised controlled trial that aimed to determine the effect of financially incentivising public transport use on physical activity in a regional Australian setting. Get BusActive! is a 9.5-month single-blinded randomised controlled trial. A convenience sample of Tasmanians aged ≥15 years will be randomised to a 14-week incentive-based intervention (bus trip target attainment rewarded by bus trip credits and weekly supportive text messages) or an active control following baseline measures and will be followed up ∼24 weeks later (maintenance phase). Both groups will receive written physical activity guidelines. The primary outcome is change in accelerometer-measured steps/day from baseline to immediately post intervention phase and maintenance phase. Secondary outcomes are change in: smartcard-measured bus trips/week; measured and self-reported minutes/week of physical activity and sitting; transport-related behaviour (using one-week travel diary), perspectives (e.g. enablers/barriers) and costs; health. Linear mixed model regression will determine group differences. Participant-level process evaluation will be conducted and intervention cost to the public transport provider determined. Get BusActive! will fill an important knowledge gap about the causal relationship between financially incentivised public transport use and physical activity-the findings will benefit health and transport-related decision makers. ACTRN12623000613606. U1111-1292-3414.

Mood, Activity, and Instability in Bipolar Disorder and Unipolar Disorder-An Exploratory Post Hoc Study Using Digital Data.

Mood, activity, and instability in symptomatology hold significant roles in bipolar disorder (BD) and unipolar disorder (UD). The objectives were to examine disparities in these symptoms among patients with BD and UD. Data from two studies including patients with BD and UD, respectively, were combined for exploratory analyses. Patients provided daily smartphone-based evaluations of mood and activity/energy for a 6-month period. A total of 47 patients with BD and 59 patients with UD were included in the analyses. The dataset contains more than 13,000 patient-reported evaluations of mood and activity. Daily mood and activity instability measures were calculated using the root squared successive difference method. In linear mixed effect regression models adjusted for age, sex, and work status, there were statistically significant lower levels of activity in patients with BD as compared with patients with UD overall, during euthymic states and during depressive states (B: -0.61, 95% CI: -0.98; -0.24, p = 0.001). There were no statistically significant differences in mood instability and activity instability between patients with BD and patients with UD overall, during euthymic states and during depressive states, when accounting for multiple testing (p > 0.012). Analyses were exploratory and post hoc. Findings should be interpreted with caution. The sample size was modest. Patients with BD presented with lower level of activity as compared with patients with UD. There were no differences in mood and activity instability between these groups. Future studies including larger sample sizes should investigate differences between BD and UD. ClinicalTrials.gov identifier: NCT03033420.

Association of post-stroke delirium with short-term trajectories of cognition.

Delirium could increase the risk of cognitive decline. We aimed to determine if changes in cognitive functions shortly after stroke differ between patients with and patients without delirium. We included patients who participated in the Prospective Observational Polish Study on post-stroke delirium and underwent the Montreal Cognitive Assessment (MoCA) at day 1, day 8 and 3months after stroke. Delirium was diagnosed using DSM-5 criteria. We used mixed linear regression models to characterize changes in mean adjusted MoCA scores over time. We included 402 patients (mean age: 68.9 ± 13.3years; mean NIHSS on admission: 6.2 ± 5.5; 48.8% female). Delirium occurred in 18.9% of them. Mean adjusted MoCA scores increased from day 1 to day 8 (20.48 vs 23.34, P<0.001) and then declined from day 8 to month 3 (23.34 vs 22.21, P<0.001). The rate of change in total MoCA scores from day 1 to day 8 (net effect: 0.65, 95%CI: -1.19; 2.49, P=0.489) and from day 8 to month 3 (net effect: -2.43, 95%CI: -4.84; -0.02, P=0.147) did not differ between patients with and patients without delirium. Compared with patients without delirium, those with delirium showed a greater improvement in naming, orientation and attention, accompanied by a worsening in memory from day 1 to day 8. They also experienced a greater decline in attention and orientation, along with a greater improvement in memory from day 8 to 3months. Post-stroke delirium is associated with short-term trajectories of specific cognitive domains, but not with changes in global cognition.

Global Comparisons of Age, Gender and Socioeconomic Status Differences of Physical Fitness Health Risk in South African Primary School Children: Longitudinal Data from the NW-CHILD Study

Global physical fitness (PF) levels have declined over the past 50 years, contributing to early health risks in children although it is still unclear how age, gender and socioeconomic status (SES) impact PF risk. This study aimed to identify unique health risks related to age, SES and gender that might influence muscular fitness (MF) and cardiorespiratory fitness (CRF) levels of primary school children in South Africa. Children (N = 349, boys = 165; girls = 184) of low (n = 201) and high SES (n = 148) underwent three time point measurements at 6, 9 and 12 years spanning seven primary school years. MF was assessed with the strength sub-test of the Bruininks–Oseretsky Test of Motor Proficiency (BOT-2) and CRF with a 20 m shuttle run. Relationships between biographical data, anthropometric data and PF were analysed using mixed linear regression models. After controlling for covariates, findings from unadjusted interaction models were used, revealing significant (p &lt; 0.05) two-way age and SES interactions in standing long jump (SLJ), push-ups, wall-sit, sit-ups and VO2max and age and gender interactions (p &lt; 0.001) in sit-ups, push-ups and VO2max. Universal cut-points are considered valid monitoring guidelines of PF risk in South African school children. For comparison, standardised global protocols for sit-ups and push-ups should be prioritised and intervention strategies should focus on improving PF in girls, older children from the age of 9 and children from low SES backgrounds.

Clonal hematopoiesis of indeterminate potential: a risk factor for future exacerbation in patients with COPD

BackgroundThere is limited data regarding the clinical significance of clonal hematopoiesis of indeterminate potential (CHIP) in patients with COPD. We aimed to evaluate whether CHIP could serve as a biomarker for the long-term prognosis of patients with COPD.MethodsNext-generation sequencing was used to detect CHIP in peripheral blood mononuclear cell samples. Participants with COPD were enrolled in a prospective observational cohort between January 2013 and December 2023. We investigated the association of CHIP status with the risk of subsequent acute exacerbation and longitudinal changes in lung function, by using negative binomial regression and linear mixed regression models, respectively.ResultsAmong 125 patients with COPD, the CHIP-positive group was 32 (25.6%). Higher smoking intensity and CAT score were significantly associated with increased risk of positive CHIP status, especially in current smokers. Positive CHIP of specific genes was significantly associated with a higher risk of subsequent mild and total acute exacerbation. Positive CHIP of ASXL transcriptional regulator 1 (ASXL1) had a lower risk of subsequent total acute exacerbation (aOR, 0.19; 95% CI, 0.04–0.95). The CHIP status did not show a statistically significant association with longitudinal changes in lung function.ConclusionsIn patients with COPD, CHIP positivity was significantly associated with an increased risk of subsequent acute exacerbations, but not with longitudinal changes in lung function.

Evaluation of digital radiographic measurements for the diagnosis of acute laminitis.

Traditional radiographic measurements of distal phalanx (Pd) displacement based on the outer hoof wall are not useful for diagnosis of acute laminitis. We hypothesised that the distance between the inner hoof wall and Pd ('lamellar lucent zone'; LLZ) measured on lateromedial digital radiographs would be increased in horses with acute and subacute laminitis compared with healthy horses. Retrospective cohort study and in vivo experimental study. Forelimb radiographs from 32 healthy and 18 laminitic mixed-breed horses were analysed retrospectively. Laminitis was defined by at least two clinical signs (acute multi-limb lameness, increased digital pulse amplitude and/or persistently warm hooves) for ≤3 days (acute), or >3 and ≤14 days (subacute) duration, without overt palmar rotation (≥3°), remodelling, or distal displacement of the Pd. Some laminitic limbs initially classified as acute were subsequently radiographed later in hospitalisation and also included as subacute. Twelve measurements including LLZ at proximal, middle, and distal locations were performed on 126 forelimb radiographs that met the criteria for acute laminitis (n = 39), subacute laminitis (n = 23) or healthy control (n = 64). A mixed effects linear regression model was used for comparisons and a receiver-operator characteristic (ROC) curve was created for select measurements. Three horses were serially radiographed to study the impact of magnification and obliquity. The mean [95% confidence interval] LLZ (mm) was increased in acute and subacute laminitis compared with control in the proximal (acute = 8.8 [8.4-9.2]; subacute = 9 [8-9.9]; control = 7.3 [7-7.7]), middle (acute = 8.9 [8.5-9.3]; subacute = 9.1 [8.2-10]; control = 6.9 [6.5-7.2]), and distal (acute = 9.1 [8.5-9.7]; subacute = 10.2 [9.1-11.3]; control = 7.5 [7.2-7.8]) dorsal lamellar regions (p < 0.001). At a cut-off of >7.5 mm for middle LLZ, sensitivity was 87% [73%-94%] and specificity 91% [81%-96%] for diagnosis of acute laminitis. Using the ratio of middle LLZ to distal phalanx cortical length, sensitivity was 95% [81%-99%] and specificity was 95% [87%-99%] (cut-off >0.11). Magnification and obliquity affected absolute LLZ measurements but did not alter LLZ ratios. No histological confirmation of laminitis. LLZ measurements are potentially useful for radiographic diagnosis of acute and subacute laminitis.

Integrating spatial transcriptomics and snRNA-seq data enhances differential gene expression analysis results of AD-related phenotypes.

Spatial transcriptomics ( ST ) data provide spatially-informed gene expression for studying complex diseases such as Alzheimer's disease ( AD ). Existing studies using ST data to identify genes with spatially-informed differential gene expression ( DGE ) of complex diseases have limited power due to small sample sizes. Conversely, single-nucleus RNA sequencing ( snRNA-seq ) data offer larger sample sizes for studying cell-type specific ( CTS ) DGE but lack spatial information. In this study, we integrated ST and snRNA-seq data to enhance the power of spatially-informed CTS DGE analysis of AD-related phenotypes. First, we utilized the recently developed deep learning tool CelEry to infer the spatial location of ∼1.5M cells from snRNA-seq data profiled from dorsolateral prefrontal cortex ( DLPFC ) tissue of 436 postmortem brains in the ROS/MAP cohorts. Spatial locations of six cortical layers that have distinct anatomical structures and biological functions were inferred. Second, we conducted cortical-layer specific ( CLS ) and CTS DGE analyses for three quantitative AD-related phenotypes -- β-amyloid, tangle density, and cognitive decline. CLS-CTS DGE analyses were conducted based on linear mixed regression models with pseudo-bulk scRNA-seq data and inferred cortical layer locations. We identified 450 potential CLS-CTS significant genes with nominal p-values<10 -4 , including 258 for β-amyloid, 122 for tangle density, and 127 for cognitive decline. Majority of these identified genes, including the ones having known associations with AD (e.g., APOE , KCNIP3 , and CTSD ), cannot be detected by traditional CTS DGE analyses without considering spatial information. We also identified 8 genes shared across all three phenotypes, 21 between β-amyloid and tangle density, 10 between cognitive decline and tangle density, and 10 between β-amyloid and cognitive density. Particularly, Gene Set Enrichment Analyses with the CLS-CTS DGE results of microglia in cortical layer-6 of β-amyloid identified 12 significant AD-related pathways. Incorporating spatial information with snRNA-seq data detected significant genes and pathways for AD-related phenotypes that would not be identified by traditional CTS DGE analyses. These identified CLS-CTS significant genes not only help illustrate the pathogenesis of AD, but also provide potential CLS-CTS targets for developing therapeutics of AD.

Does Transforaminal Endoscopic Lumbar Discectomy Provide More Value than Microdiscectomy? An Application of the Operative Value Index.

A few studies have compared the value (outcomes per dollar spent) provided by transforaminal endoscopic discectomy (TED) vs microdiscectomy (MD) for lumbar disc herniations. Here, we attempt to address this gap using a novel Operative Value Index (OVI), which combines a procedure-specific patient-reported outcome with intraoperative cost data based on time-driven activity-based costing. MD (n = 95) and TED (n = 23) performed by neurosurgeons at our institution from 2017 to 2022 were retrospectively identified. Time-driven activity-based costing was applied to identify both direct and indirect costs for all cases. Individual costs were obtained by direct observation, electronic medical records, and through consulting multiple departments (including business operations, sterile processing, plant operations, and pharmacy). Oswestry Disability Index (ODI) scores were prospectively collected at baseline and 3 months after surgery. Our primary outcome of interest was the OVI, defined as the percent change in the ODI per $1000 spent intraoperatively. Generalized linear mixed model regression was performed to assess whether TED was associated with significantly different OVI as compared to MD. Similar analyses were also performed for operative times and length of stay. The average intraoperative cost of a TED was $3698, as compared to $3410 for an MD. For both procedures, this total cost was largely driven by the cost of supplies and personnel. Multivariable regression revealed that MD was associated with significantly higher OVI (β-coefficient: 7.2, P < .05) and lower operative times (β-coefficient: - 34.6 minutes, P < .01) compared with TED, with no significant differences in length of stay (P = .17). When performed by surgeons at our institution from 2017 to 2022, MD was associated with a 7% greater improvement in ODI per $1000 spent intraoperatively. Continual assessment of value over time (both for established procedures and new techniques) will become increasingly important with the emergence of value-based care.

Sex-dependent variability of isoniazid and rifampicin serum levels in patients with tuberculosis.

Drug-sensitive TB (DS-TB) is treated with isoniazid, rifampicin, ethambutol, and pyrazinamide. Factors like fast-metabolizing enzymes, malabsorption, and drug interactions can influence serum drug levels. Current TB treatment guidelines recommend weight-adapted dosing without considering sex differences. This study examines drug levels of isoniazid and rifampicin in TB patients treated between 2019 and 2023 at our center focusing on sex-specific aspects. Patients diagnosed with TB and available serum levels of isoniazid or rifampicin between 2019 and 2023 were retrospectively identified. Serum levels were measured using liquid chromatography-mass spectrometry and high-performance liquid chromatography. Patients were stratified by sex and a linear regression mixed effect model was used to assess predictors for different serum levels. The study included 281 single therapeutic drug monitoring (TDM) measurements from 59 patients (28 women, 47.5%). For isoniazid, no sex-specific differences in serum drug levels were identified. On the other hand, female sex was a significant predictor of higher rifampicin plasma levels (coefficient 4.16, 95% CI 0.74-7.59, p = 0.009). Only 38.2% of rifampicin serum level measurements in male patients were within target range, the majority (40/68, 58.8%) were below range and only 2 (2.9%) TDM-levels were above range. Women displayed higher overall rifampicin serum levels than men (median 13.7mg/l vs. 7.1mg/l, p = 0.04), although weight adjusted doses were not significantly different (median 10.0mg/kg vs. 9.8mg/kg p = 0.56). Adverse effects were noted in 42.9% (42/98) of measurements in women and 29.5% (54/183) of measurements in men (p = 0.03). Rifampicin levels were significantly lower in men compared to women, despite weight-adjusted dosing. Clinicians should consider TDM and potential sex differences when treating patients with TB.

Changes to inflammatory markers during 5 years of viral suppression and during viral blips in people with HIV initiating different integrase inhibitor based regimens.

Heightened levels of inflammatory markers are linked to increased morbidity/mortality in people with HIV (PWH) and often remain elevated after virologic suppression by antiretroviral therapy (ART). As new combinations of ART become available, an evaluation of their effects on immune activation and inflammation is warranted. Additionally, it remains unknown whether transient increases in viral load ("blips") during ART are associated with increases in inflammation. We utilized cryopreserved samples from treatment-naïve PWH enrolled in two Phase 3 clinical trials investigating the efficacy and safety of bictegravir, emtricitabine and tenofovir alafenamide (B/F/TAF) or dolutegravir, abacavir, and lamivudine (DTG/ABC/3TC) or DTG + F/TAF over a 5-year window (GS-US-380-1489/1490). At week 144, participants were offered the option to switch to open label B/F/TAF for an additional 96 weeks. We measured levels of interleukin-6 (IL-6), C-reactive protein (hsCRP), D-dimer, soluble CD14 (sCD14), and tumor necrosis factor-α receptor 1 (TNFR1) from available baseline, week 24, 48, 144, and 240 samples (B/F/TAF, N=123; DTG/ABC/3TC, N=62; DTG+F/TAF, N=58). Additional samples from PWH who experienced a viral blip (n=44, defined as a single HIV-1 RNA >50c/mL) were also analyzed and paired with the most recent available suppressed sample before the blip. Longitudinal biomarker changes were assessed using a constrained mixed effects linear regression model adjusting for covariates. Baseline demographics and selected laboratory characteristics were similar across groups. Levels of D-dimer, sCD14, and TNFR1 decreased significantly from baseline in all treatment arms, with no significant differences between arms at any timepoint. Biomarker levels also remained stable following ART-switch at week 144. No significant changes in hsCRP or IL-6 were observed versus baseline in any arm at any timepoint. A significant association was observed between sCD14 and increasing viral load (p=0.022) in viral blips; D-dimer also increased with blips in the B/F/TAF arm. Viral suppression was associated with reductions in most inflammatory markers in PWH, with no significant differences among the three ART regimens during the 144-week randomized period. These decreases were sustained after the open label switch to B/F/TAF. Viral blips were associated with increases in monocyte activation (sCD14). Further analysis is needed to confirm these findings and determine the potential impact on clinical outcomes.

Association of hypertension defined by the 2017 ACC/AHA guideline and choroidal thickness changes in type 2 diabetes: a 2-year longitudinal study.

This prospective cohort study investigated the longitudinal relationship between hypertension (HTN), defined by the 2017 ACC/AHA guidelines, and changes in choroidal thickness (CT) in patients with type 2 diabetes. Patients aged 30-80 years from the Guangzhou Diabetic Eye Study were categorized into non-HTN, stage 1-HTN, and stage 2-HTN groups based on BP criteria. Macular and parapapillary CT were measured using swept-source optical coherence tomography (SS-OCT). Mixed linear regression models analysed CT decline rates over a median 2.1-year follow-up, adjusting for confounders. 803 diabetes patients were included. Both stage 1-HTN and stage 2-HTN groups showed significantly thinner macular and parapapillary CT compared to non-HTN (all P < 0.05). Stage 2-HTN correlated with reduced macular CT thinning (coef = -11.29 μm/year; 95% CI, -22.36 to -0.22; P = 0.046) after adjustment, but not in the parapapillary area (coef = -4.07 μm/year; 95% CI, -12.89 to 4.74; P = 0.365). Subgroup analyses indicated faster macular CT decline in stage 2-HTN among those <65 years old (coef = -20.31 μm/year; 95% CI, -35.67 to -4.95; P = 0.10), males (coef = -14.1 μm/year; 95% CI, -32.54 to -4.33; P = 0.004), BMI ≥ 25 kg/m2 (coef = -10.24 μm/year; 95% CI, -26.86 to -6.38; P = 0.007), HbA1c > 6.5% (coef = -8.91 μm/year; 95% CI, -13.49 to -4.68; P = 0.001), and diabetes duration <10 years (coef = -12.78 μm/year; 95% CI, -27.48 to -1.91; P = 0.008). Stage 2-HTN is associated with accelerated macular CT loss in diabetic patients, suggesting macular CT measurements could potentially serve as early indicators of systemic hypertension. Further research is needed to establish precise CT cutoff values for clinical use in detecting and monitoring hypertension-related ocular changes.

A novel piglet model of esophageal stricture following variable segmental esophageal resection and re-anastomosis.

Esophageal strictures following esophageal atresia repair are a source of significant morbidity. To test new therapeutic approaches, we designed a piglet model of esophageal stricture by resecting variable lengths of esophagus with subsequent re-anastomosis. This study describes the model and validates its physiologic impact by blinded analysis of the weight gains of the piglets. A total of 24 two-week old Pietrain piglets had esophageal resections performed, ranging from 0 to 5 cm, with the goal of inducing postoperative esophageal strictures. Postoperative body-weights were evaluated by repeated analysis of variance followed by pairwise group-comparisons based on estimated marginal means. In addition, body weight was modeled by linear-mixed model regression. Different resection lengths were compared. The esophagi were evaluated postmortem for stricture. Of 24 operated piglets, 23 reached the endpoint, and 90% developed an esophageal stricture that was radiologically visible in a contrast study, as well as appreciable macroscopically in the necropsy. We found differences in pre- and postoperative body weights for all piglets (F (1, 18) = 298.54, p < 0.001), but no differences between resection lengths (F (4, 18) = 0.36, p = 0.837). Our model of postoperative esophageal stricture offers the opportunity to investigate potential treatments for strictures associated with esophageal atresia, since it reliably induces strictures and results in minimal loss of animals. The similar body weight gain in all groups indicates that stricture is mainly the result of esophageal resection and re-anastomosis, regardless of the length of the resected segment.

Effect of school feeding program on dietary folate intake among school adolescent girls in Sidama region, southern Ethiopia.

Ethiopia recently initiated a school feeding program (SFP) that provides nutritious meals to vulnerable students during school to combat malnutrition and improve their nutrition. However, there is limited evidence regarding the program's impact on dietary folate intake among adolescent girls. Improving folate status in adolescent girls is important to prevent neural tube defect and anemia This study was aimed at assessing the effect of the SFP on dietary folate intake among school adolescent girls in the Sidama Region, Southern Ethiopia. This school-based cross-sectional study compared dietary folate intake among adolescent girls enrolled in schools with (n = 290) and without (n = 290) SFP. Multistage sampling method was used to select adolescent girls from 12 schools. The multiple pass 24-h dietary recall method was used to estimate the dietary intake of adolescent girls. Dietary diversity in the preceding day of the survey was assessed with the standard nine-food group score. Nutrient inadequacy was defined as a proportion of adolescents with dietary value of nutrient intake less than the recommended daily allowance (RDA). The dietary folate intake was compared between two groups using multilevel mixed effects linear regression model adjusted for potential confounders. The result showed significantly higher mean (±SD) dietary folate intake in SFP beneficiaries (421.12 ± 78.60 μg/day) than the non-beneficiaries (393.26 ± 74.57 μg/day; β = 27.19, p < 0.001). SFP beneficiary girls had a significantly higher mean (±SD) dietary diversity score (5.24 ± 1.35) compared to non-beneficiary girls (4.83 ± 1.54; β = 0.40, p = 0.001). The prevalence of inadequate folate intake was significantly higher among no-beneficiaries (47.4%) compared to beneficiaries (36.9%; p = 0.01). The SFP in Sidama region improved folate intake and dietary diversity of adolescent girls. The evidence from this study supports the expansion of the program to enhance dietary intake of nutrients of adolescent girls in the region.

In-utero exposure to tenofovir-containing pre-exposure prophylaxis and bone mineral content in HIV-unexposed infants in South Africa.

Tenofovir disoproxil fumarate (TDF) is a common drug of choice for pre-exposure prophylaxis (PrEP) or as a combination HIV treatment for pregnant women. In-utero exposure to TDF was found to be associated with lower bone mineral content (BMC) in HIV-exposed uninfected neonates. Data for infants born to women taking TDF-PrEP are lacking. The CAP016 randomized control trial was conducted in South Africa between September 2017 and August 2021 and pregnant women either initiated TDF/FTC PrEP in pregnancy (Immediate PrEP arm-IP) or at cessation of breastfeeding (Deferred PrEP arm-DP). In a secondary data analysis, we evaluated BMC in HIV-unexposed infants in the CAP016 trial in the first 18 months of life in association with maternal TDF-PrEP use during pregnancy. Infants born to women randomized to the IP arm or DP arm in the CAP016 clinical trial had BMC measurements of the whole body with head (WBH) and lumbar spine (LS) by dual energy X-ray absorptiometry (DXA) at 6, 26, 50 and 74 weeks. Of 481 infants born to women enrolled in the CAP016 clinical trial, 335 (69.6%) infants had a minimum of one DXA scan of the WBH and LS between 6 and 74 weeks of age (168 IP and 167 DP). Women in the IP arm received TDF-FTC PreP for a median of 19 weeks between initiation in pregnancy and delivery. Using a mixed linear regression model and adjusted for gestational age, sex and ever-breastfed, the mean difference (95% CI) for BMC of the WBH between IP and DP arms were -0.74 (-8.69 to 7.20), -1.26 (-10.75 to 8.23), -9.17 (-20.02 to 1.69) and 5.02 (-6.74 to 16.78) g at 6, 26, 50 and 74 weeks (p = 0.283). Mean differences in BMC of the LS were 0.07 (-0.10 to 0.23), 0.02 (-0.18 to 0.22), -0.14 (-0.36 to 0.09) and 0.14 (-0.11 to 0.38) g at 6, 26, 50 and 74 weeks, respectively (p = 0.329). In a randomized controlled trial, there were no differences in BMC of the WBH and LS between infants exposed to in-utero TDF-FTC PrEP and unexposed infants in the first 18 months of life.