Mixed-effects Models Research Articles

Distinct medical and substance use histories associate with cognitive decline in Alzheimer's Disease.

Phenotype clustering reduces patient heterogeneity and could be useful when designing precision clinical trials. We hypothesized that the onset of early cognitive decline in patients would exhibit variance predicated on the clinical history documented prior to an Alzheimer's Disease (AD) diagnosis. Self-reported medical and substance use history (i.e., problem history) was used to cluster participants from the National Alzheimer's Coordinating Centers (NACC) into distinct subtypes. Linear mixed effects modeling was used to determine the effect of problem history subtype on cognitive decline over two years. 2754 individuals were partitioned into three subtypes: minimal (n = 1380), substance use (n = 1038), and cardiovascular (n = 336) subtypes. The cardiovascular problem history subtype had significantly worse cognitive decline over a two-year follow-up period (p = 0.013). Our study highlights the need to account for problem history to reduce heterogeneity of outcomes in AD clinical trials.

Freshwater fish in mid and northern German rivers – Long-term trends and associated species traits

To understand biodiversity change and support conservation decision-making, estimates of species' long-term population trends at regional and national scales are essential. However, such estimates are missing for many freshwater taxa, despite the diverse range of threats that they face. For this study, we mobilised monitoring data on riverine freshwater fish abundance collected across different regions of Germany. We applied generalized mixed effect models to estimate the population trends for 55 native species and 11 non-native species between 2004 and 2020. In addition, we used boosted regression trees to identify trait-based predictors of species trends and assessed their predictive ability. We found evidence of increasing abundance trends for 14 species and decreasing trends for 15 species; while the remaining species were mostly stable (26 species). Native species were more typically decreasing than increasing (14 vs 10 species); while non-native species were more often increasing (4 vs 1 species). Important traits associated with trends were maximum length, spawning temperature, and water quality tolerance, with small species, those spawning at high temperatures, and those preferring unpolluted waters, being most likely to have positive trends. Despite these associations, overall trait-based models showed limited power to predict trends in terms of direction as well as magnitude. Our results highlight the ongoing change in riverine fish communities and the importance of on-going species-level monitoring. The trait-based associations also indicate climate change and invasive species as important drivers of change in European freshwater rivers.

Patterns of Adherence to Home Blood Pressure Monitoring Among Older Adults With Ischemic Heart Disease: An Analysis From the RESILIENT Trial of Mobile Health Cardiac Rehabilitation.

Hypertension (HTN) is common and represents a major modifiable risk factor for ischemic heart disease in older adults. While home blood pressure monitoring (HBPM) is important in HTN management, patterns of HBPM engagement in older adults undergoing mobile health cardiac rehabilitation (mHealth-CR) are unknown. We aimed to identify patterns of adherence to HBPM in a cohort of older adults undergoing mHealth-CR to optimize HBPM use in the future. We used interim data from the ongoing Rehabilitation using Mobile Health for Older Adults with Ischemic Heart Disease in the Home Setting (RESILIENT) randomized trial, in which intervention arm participants (adults≥65years with ischemic heart disease) were instructed to monitor blood pressure (BP) at least weekly. Engagement groups were determined by latent class analysis and compared using ANOVA or Chi-Square tests. Longitudinal mixed effect modeling determined the associations between weekly HBPM and baseline covariates including uncontrolled HTN, obesity, diabetes, depression, alcohol, and tobacco use. Of the 111 participants, the mean age was 71.9±5.6years, and 83% had HTN. Over the 12-week study, mean HBPM engagement was 2.3±2.3d/wk. We observed 3 distinct patterns of engagement: high engagement (22%), gradual decline (10%), and sustained baseline engagement (68%). HBPM adherence decreased in two of the engagement groups over time. Of the covariates tested, only depression was associated with weekly HBPM after adjusting for relevant covariates (OR 9.09, P =.03). In this older adult cohort undergoing mHealth-CR, we found three main engagement groups with declining engagement over time in two of the three groups. These patterns can inform future mHealth-CR interventions.

Serum folate levels, but not vitamin B12, are associated with slower progression in carotid intima-media thickness in a population exposed to mandatory folic acid fortification

Background&AimsFolate and vitamin B12 are vitamins involved in one carbon metabolism. Carotid intima-media thickness (cIMT) is a non-invasive test and an early atherosclerosis marker. The relationship between these vitamins and cIMT is not well established. This study aimed to investigate the association between baseline vitamins and cIMT changes during a median follow-up of 8 years. MethodsProspective cohort study involving 5,061 ELSA-Brasil participants from São Paulo state aged 35-74 years at baseline. Serum folate and vitamin B12 levels and dietary intake were assessed at baseline. Ultrasound cIMT measurements were performed at baseline and wave 3. Linear mixed-effects models, adjusted for covariables, assessed the association between vitamins at baseline and changes in cIMT. Results4,260 participants were included; mean (SD) age was 51.4 (8.9) years and 54.5% were women. Folate (0.02%) and vitamin B12 (2.6%) deficiencies were almost nonexistent. Participants in the 4th quartile of serum folate had a slower cIMT increase during 8 years of follow-up than those in the 1st quartile (1st vs. 4th quartile comparison: β (95% CI): -0.015 (-0.026; -0.004), P: 0.006 for model 3). These findings remained the same after sensitivity analysis for overall dietary supplements and specifically multivitamins use. No association was found between vitamin B12 biomarker and the outcome. Dietary folate intake was also not associated with cIMT changes. ConclusionIn this population exposed to mandatory folic acid food fortification, prevalence of vitamins deficiencies was very low. Highest quartile of serum folate seemed to slow down the increment of cIMT measurements over time.

Correlations between propofol concentration in exhaled breath and BIS in patients undergoing thyroid surgery

Several clinical studies have reported promising correlations between propofol concentration in exhaled breath (Ce-pro) and the bispectral index (BIS) in patients, suggesting the potential of exhaled propofol measurement as a non-invasive method for adjusting anesthesia depth. However, these studies are still in the validation phase of instrument effectiveness, often limited by small sample sizes or inappropriate instrument selection, and thus lack convincing results regarding these correlations. In this study, one hundred patients aged 18-65, undergoing elective thyroid surgery under general anesthesia were included. The vacuum ultraviolet photoionization and time-of-flight mass spectrometry was employed to monitor Ce-pro at 20 s intervals, alongside continuous BIS measurement. The association between Ce-pro and BIS was analyzed using linear mixed-effects models, with marginalR2used to assess the correlation. The threshold of Ce-pro at awakening was also explored. Additionally, the univariate and multifactorial diagnostic model, including end-of-surgery Ce-pro, were employed to assess the accuracy of predicting delayed recovery. A weak correlation was observed between intraoperative Ce-pro and BIS (marginalR2= 0.348). Predictive models utilizing end-of-surgery Ce-pro levels showed good accuracy (area under the curve (AUC) = 0.75, 95% CI: 0.62-0.89,P= 0.003) in predicting delayed recovery, while the model using end-of-surgery Ce-pro combined with gender, sufentanil dosage, the time from the last administration of sufentanil to the end of surgery, and anesthesia duration demonstrated stronger predicting accuracy (AUC = 0.91, 95% CI: 0.85-0.98,P< 0.001). This study suggests that Ce-pro alone may not reliably predict the depth of anesthesia in clinical practice, but shows promising accuracy in predicting delayed recovery from anesthesia.

Relationship Between Heart Rate and Perceived Stress in Intensive Care Unit Residents: Exploratory Analysis Using Fitbit Data.

Intensive care unit (ICU) residents are exposed to high stress levels due to the intense nature of their work, which can impact their mental health and job performance. Heart rate measured through wearable devices has the potential to provide insights into residents' self-reported stress and aid in developing targeted interventions. This exploratory study aims to analyze continuous heart rate data and self-reported stress levels and stressors in ICU residents to examine correlations between physiological responses, stress levels, and daily stressors reported. A secondary data analysis was conducted on heart rate measurements and stress assessments collected from 57 ICU residents over a 3-week period using Fitbit Charge 3 devices. These devices captured continuous physiological data alongside daily surveys that assessed stress levels and identified stressors. The study used Spearman rank correlation, point-biserial correlation analysis, 2-tailed paired t tests, and mixed-effect models to analyze the relationship between heart rate features and stress indicators. The findings reveal complex interactions between stress levels and heart rate patterns. The correlation analysis between stress levels and median heart rate values across different percentile ranges showed that lower percentile heart rates (bottom 5%, 10%, 25%, and 50%) had modest correlations with stress, whereas higher percentiles (top 50%, 25%, 10%, and 5%) did not correlate significantly (all P>.05). The 2-tailed paired t test indicated significant differences in stress levels reported in midday versus end-of-day surveys (P<.001), although these changes in stress levels were not consistently reflected in heart rate patterns. Additionally, we explored and found that stressors related to "other health" issues had the highest positive correlation with stress level changes from midday to end-of-day surveys. However, the weak effect of these stressors on peak heart rate suggests that their impact on physiological measures like heart rate is not yet clear. According to our mixed-effects model, stress levels significantly influenced heart rate variations when hierarchical data were taken into account (P=.03), meaning that as the stress level increased, there was a significant increase in mean heart rate. This study highlights the complexity of using heart rate as an indicator of stress, particularly in high-stress environments like the ICU. Our findings suggest that while heart rate is found to correlate with self-reported stress in the mixed-effect model, its impact is modest, and it should be combined with other physiological and psychological measures to obtain a more accurate and comprehensive assessment of residents' stress levels.

Relationship between high-resolution computed tomography quantitative imaging analysis and physiological and clinical features in antisynthetase syndrome-related interstitial lung disease

ObjectivesTo explore the association between the extent of CT abnormalities by quantitative imaging analysis (QIA) and clinical/physiological disease parameters in patients with antisynthetase syndrome associated interstitial lung disease (ARS-ILD).MethodsWe analysed...

Applying a transformer architecture to intraoperative temporal dynamics improves the prediction of postoperative delirium

BackgroundPatients who experienced postoperative delirium (POD) are at higher risk of poor outcomes like dementia or death. Previous machine learning models predicting POD mostly relied on time-aggregated features. We aimed to assess the potential of temporal patterns in clinical parameters during surgeries to predict POD.MethodsLong short-term memory (LSTM) and transformer models, directly consuming time series, were compared to multi-layer perceptrons (MLPs) trained on time-aggregated features. We also fitted hybrid models, fusing either LSTM or transformer models with MLPs. Univariate Spearman’s rank correlations and linear mixed-effect models establish the importance of individual features that we compared to transformers’ attention weights.ResultsBest performance is achieved by a transformer architecture ingesting 30 min of intraoperative parameter sequences. Systolic invasive blood pressure and given opioids mark the most important input variables, in line with univariate feature importances.ConclusionsIntraoperative temporal dynamics of clinical parameters, exploited by a transformer architecture named TRAPOD, are critical for the accurate prediction of POD.

The Impact of Blood Lead and Its Interaction with Occupational Factors and Air Pollution on Hypertension Prevalence

Large-scale epidemiological studies on the association of blood lead levels with blood pressure and hypertension prevalence are still limited, particularly among lead-exposed workers. The evidence is even more scarce on the interaction of blood lead levels with occupational variables and ambient air pollution levels. We developed mixed-effect models based on a large group of lead-exposed workers (N = 22,002). The results were also stratified by multiple groupings. Compared to participants with blood lead &lt; 20 μg/L, those with levels &gt; 20 μg/L had a 26–37% higher prevalence of hypertension, as well as a 0.65–13.7mmHg higher systolic and diastolic blood pressure. Workers exposed to high PM10 levels had a 21–28% higher risk. Workers exposed to high temperatures had a 0.41–2.46 mmHg greater increase in blood pressure, and those not exposed to dust had a 1.29–1.65 mmHg greater blood pressure increase. Our findings suggested the negative impact of blood lead on blood pressure and the prevalence of hypertension, with workers exposed to high PM10 concentrations, those exposed to occupational high temperature, and those without dust exposure being more vulnerable.

EGFR slope as predictor of mortality in heart failure patients.

Heart failure (HF) leads to an imbalance between heart and kidney function, resulting in poor outcomes. However, the prognostic significance of the estimated glomerular filtration rate (eGFR) trajectory in HF patients remains unclear. We analysed electronic health records (EHRs) of real-world HF patients, assessing eGFR trajectories and their impact on mortality. Retrospective clinical data of HF patients were processed using natural language processing. Chronic kidney disease (CKD) was evaluated, and eGFR trajectories were analysed using linear mixed-effects models. Cox proportional hazard models were used to evaluate the relationship between baseline variables and mortality, while joint modelling combined eGFR trends and mortality. The dataset comprised 1986 patients, with a mean age of 74.8years (SD±11.7) and 58% male. At the time of HF diagnosis, 58% of patients were diagnosed with CKD, and 39% presented with heart failure with preserved ejection fraction (HFpEF). The median follow-up duration was 3.16years, during which 399 patients (20%) died. Patients with CKD were significantly older and exhibited a higher prevalence of myocardial infarction (P=0.048), coronary revascularization (P=0.004), stroke (P<0.001), atrial fibrillation (P<0.001) and type 2 diabetes (P<0.001). Mortality rates at 1 and 2years were nearly twice as high in CKD patients compared with those without (P<0.001). Notably, CKD was significantly less prevalent among survivors (55% vs. 71%, P<0.001). Key predictors of mortality included older age, beta-blocker use, prior stroke, lower serum haemoglobin levels, and elevated potassium and NT-proBNP levels. Each 10mL/min/1.73m2 decrease in eGFR was associated with a 1.22 (95% CI: 1.10-1.35, P<0.001) increase in mortality hazard. Additionally, a 1-year decline of 10mL/min/1.73m2 in eGFR resulted in a mortality hazard of 1.97 (95% CI: 1.45-2.69, P<0.001). CKD is prevalent in a real-world HF population and is an independent predictor of mortality. The current eGFR value and the eGFR slope from the previous year have the potential to be used for assessing individual mortality risk in the clinical follow-up of HF patients.

Macular Capillary Nonperfusion in Eyes With Stable Laser-Treated Proliferative Diabetic Retinopathy

Some eyes with proliferative diabetic retinopathy (PDR) treated to stability with panretinal photocoagulation (PRP) continue to lose vision without diabetic macular edema. One presumed cause is macular capillary nonperfusion (CNP)-associated ischemia or infarction. Natural history data of macular CNP might guide treatment trials for it. To assess visual function and optical coherence tomography angiography (OCTA) changes over 12 months in PRP-treated stable eyes with PDR and macular CNP. This prospective observational cohort study was conducted in a single center in the United Kingdom. Participants had stable laser-treated PDR in at least 1 eye with macular CNP and a best-corrected visual acuity (BCVA) letter score of at least 54 (Snellen equivalent ≥20/80) using Early Treatment Diabetic Retinopathy Study (ETDRS) chart. Recruitment was from December 2019 to August 2021 and follow-up for 12 months; data were analyzed from May to July 2024. Changes in BCVA, low-luminance visual acuity (LLVA), and OCTA metrics over 12 months using linear mixed-effects models with unstructured variance accounting for within-participant correlation between the eligible study eye and repeated measures across time. The cohort included 63 participants and 88 eyes. The mean (SD) age was 57.4 (11.9) years; 41 were male (65.1%) and 22 female (34.9%). Mean BCVA and LLVA ETDRS letter scores were 77.52 (SD, 8.0; approximate Snellen equivalent, 20/32) and 68.33 (SD, 8.9; Snellen, 20/40) at baseline and 78.76 (SD, 8.3; Snellen 20/25) and 70.20 (SD, 8.1; Snellen, 20/40) at 12 months. However, 7 participants (9.3%) lost at least 5 letters of visual acuity at 12 months. Linear mixed-effects analysis showed the foveal avascular zone (FAZ) area deteriorated over 12 months, with a mean increase of 1.80% (95% CI, 0.01%-3.63%; P = .05) at 6 months and 2.26% (95% CI, 0.29%-4.26%; P = .03) from baseline. Eyes that lost 5 or more letters had lower baseline superficial vascular density in both the 3 × 3-mm scan (mean [SD], 36.7 [4.8] vs 33.5 [2.0]; P = .006) and parafoveal area (38.7 [5.6] vs 34.7 [2.6]; P = .005). No association was found between a loss of 5 or more letters at 12 months and any baseline FAZ parameters. This study found that FAZ area deteriorated over 12 months in eyes with stable laser-treated peripheral retina in eyes and macular CNP. Vision loss was uncommon and more prevalent in eyes with decreased SVD at baseline rather than FAZ parameters. Longer trials may be required to observe more events of change of 5 or more letters.

Avatar Intervention in Virtual Reality for Cannabis Use Disorder in Individuals With Severe Mental Disorders: Results From a 1-Year, Single-Arm Clinical Trial.

The dual diagnosis of cannabis use disorder (CUD) and severe mental disorder (SMD) results in clinically complex individuals. Cannabis use is known to have negative consequences on psychiatric symptoms, medication compliance, and disease prognosis. Moreover, the effectiveness of currently available psychotherapeutic treatments is limited in this population. In this context, our research team developed avatar intervention, an approach using virtual reality as a therapeutic tool to treat CUD in individuals with SMD. This pilot clinical trial aimed to evaluate, until the 1-year follow-up, the efficacy of avatar intervention for CUD among 32 participants with a dual diagnosis of SMD and CUD. Over the course of the 8 intervention sessions, participants were given the opportunity to enter a dialogue in virtual reality with an avatar representing a person with a significant role in their consumption, who was animated in real time by a therapist. The primary outcomes were the quantity of cannabis consumed and the frequency of use. Secondary outcomes included severity of problematic cannabis use, motivation for change, protective strategies for cannabis use, consequences of cannabis use, psychiatric symptoms, and quality of life. Changes in reported outcomes during the assessment periods before the intervention; postintervention; and 3, 6, and 12 months after the end of the intervention were assessed using a linear mixed-effects model. Significant reductions were observed in the quantity of cannabis consumed, and these were maintained until the 12-month follow-up visit (d=0.804; P<.001; confirmed by urine quantification). Frequency of cannabis use showed a small significant reduction at the 3-month follow-up (d=0.384; P=.03). Moreover, improvements were observed in the severity of CUD, cannabis-related negative consequences, the motivation to change cannabis use, and the strategies used to mitigate harms related to cannabis use. Finally, moderate benefits were observed for quality of life and psychiatric symptoms. Overall, this unique intervention shows promising results that seem to be maintained up to 12 months after the end of the intervention. With the aim of overcoming the methodological limitations of a pilot study, a single-blind randomized controlled trial is currently underway to compare the avatar intervention for CUD with a conventional addiction intervention.

Quantitative modelling for dengue and Aedes mosquitoes in Africa: A systematic review of current approaches and future directions for Early Warning System development.

The rapid spread and growing number of dengue cases worldwide, alongside the absence of comprehensive vaccines and medications, highlights the critical need for robust tools to monitor, prevent, and control the disease. This review aims to provide an updated overview of important covariates and quantitative modelling techniques used to predict or forecast dengue and/or its vector Aedes mosquitoes in Africa. A systematic search was conducted across multiple databases, including PubMed, EMBASE, EBSCOhost, and Scopus, restricted to studies conducted in Africa and published in English. Data management and extraction process followed the 'Preferred Reporting Items for Systematic Reviews and Meta-Analyses' (PRISMA) framework. The review identified 30 studies, with the majority (two-thirds) focused on models for predicting Aedes mosquito populations dynamics as a proxy for dengue risk. The remainder of the studies utilized human dengue cases, incidence or prevalence data as an outcome. Input data for mosquito and dengue risk models were mainly obtained from entomological studies and cross-sectional surveys, respectively. More than half of the studies (56.7%) incorporated climatic factors, such as rainfall, humidity, and temperature, alongside environmental, demographic, socio-economic, and larval/pupal abundance factors as covariates in their models. Regarding quantitative modelling techniques, traditional statistical regression methods like logistic and linear regression were preferred (60.0%), followed by machine learning models (16.7%) and mixed effects models (13.3%). Notably, only 36.7% of the models disclosed variable selection techniques, and a mere 20.0% conducted model validation, highlighting a significant gap in reporting methodology and assessing model performance. Overall, this review provides a comprehensive overview of potential covariates and methodological approaches currently applied in the African context for modelling dengue and/or its vector, Aedes mosquito. It also underscores the gaps and challenges posed by limited surveillance data availability, which hinder the development of predictive models to be used as early warning systems in Africa.

Environmental and Atmospheric Influences on Academic Performance: The Role of Green Spaces, Roads, and Wildfires Around Schools and Homes in the Federal District, Brazil

Environmental characteristics, such as proximity to green spaces and exposure to roads, can significantly influence atmospheric factors like air quality. For instance, areas with abundant green spaces typically exhibit better air quality, while high road density often correlates with increased air pollution, both of which can affect students’ cognitive functioning and academic performance. This study aimed to evaluate the association between the environmental and atmospheric conditions—specifically green spaces (measured by the NDVI and green space area), roads (total road length), and wildfires—around students’ schools and homes in the Federal District (FD), Brazil, and their impact on academic performance. We analyzed data from 344,175 public school students across 256 schools in the FD, covering the years 2017 to 2020. Using a mixed-effects regression model, we investigated how neighborhood characteristics such as green spaces, road density, and wildfire frequency influence individual-level academic performance while controlling for temporal, socioeconomic, and school-specific factors. Our findings indicate that the environmental factors around schools, particularly green spaces and road density, have significant associations with academic outcomes. Specifically, a higher road density around schools was linked to lower academic performance, whereas green space presence had a generally positive impact, especially around schools. Wildfires, while negatively associated with performance around homes, had mixed effects around schools. These results underscore the importance of considering environmental and atmospheric factors in urban planning and education policy to enhance student performance.

Coupled aging of cyto- and myeloarchitectonic atlas-informed gray and white matter structural properties.

A key aspect of brain aging that remains poorly understood is its high regional heterogeneity and heterochronicity. A better understanding of how the structural organization of the brain shapes aging trajectories is needed. Neuroimaging tissue "types" are often collected and analyzed as separate acquisitions, an approach that cannot provide a holistic view of age-related change of the related portions of the neurons (cell bodies and axons). Because neuroimaging can only assess indirect features at the gross macrostructural level, incorporating post-mortem histological information may aid in better understanding of structural aging gradients. Longitudinal design, coupling of gray and white matter (GM, WM) properties, and a biologically informed approach to organizing neural properties are needed. Thus, we tested aging of the regional coupling between GM (cortical thickness, surface area, volume) and WM (fractional anisotropy, mean, axial, and radial diffusivities) structural metrics using linear mixed effects modeling in 102 healthy adults aged 20-94 years old, scanned on two occasions over a four-year period. The association between age-related within-person change in GM morphometry and the diffusion properties of the directly neighboring portion of white matter were assessed, capturing both aspects of neuronal health in one model. Additionally, we parcellated the brain utilizing the histological-staining informed von Economo-Koskinas atlas to consider regional cyto- and myelo-architecture. Results demonstrate several gradients of coupled association in the age-related decline of neighboring white and gray matter. Most notably, gradients of coupling along the heteromodal association to sensory axis were found for several areas (e.g., anterior frontal and lateral temporal cortices, vs pre- and post-central gyrus, occipital, and limbic areas), in line with heterochronicity and retrogenesis theories of aging. Further effort to bridge across data and measurement scales will enhance understanding of the mechanisms of the aging brain.

Quality and quantity of carbohydrates, faecal short-chain fatty acids and gastrointestinal symptoms – results from a randomised, controlled trial (CARBFUNC)

Background& aims: Diet is a key determinant of gastrointestinal (GI) health, in part in association with microbiota-derived short-chain fatty acids (SCFAs). However, we need more knowledge of the relative impact of dietary carbohydrate amount and quality on GI symptoms, GI-associated quality of life (QoL) and faecal SCFAs. Methods193 males and females with obesity were randomly allocated to follow one of three isocaloric, iso-proteinic dietary patterns (2,000 kcal/day for females, 2,500 kcal/day for males): a higher-carbohydrate lower-fat diet with refined carbohydrate sources (acellular diet, A-HCLF, comparator arm), a higher-carbohydrate lower-fat diet with minimally refined carbohydrate sources (intact cellular structures, cellular diet, C-HCLF), or a low-carbohydrate high-fat diet (LCHF), all low in added sugars. Secondary outcomes of this randomised controlled trial (CARBFUNC) were assessed, i.e., changes in abdominal symptoms (irritable bowel syndrome severity scoring system (IBS-SSS)), reflux symptoms (gastro-oesophageal reflux disease questionnaire (GerdQ)), GI-related QoL (Short-Form Nepean Dyspepsia Index (SF-NDI)) and fatigue (Fatigue Impact Scale), and faecal SCFAs concentrations after following the diets for 3 and 12 months. Group differences were analysed by constrained linear mixed effect modelling (cLMM). Results118 and 57 participants completed 3 and 12 months of the dietary intervention, respectively, with no significant group differences in weight loss at 12 months (5-7%). At 12 months, the mean daily fibre intake was 34±7 g/day, 41±14.3 g/day, and 18.5±6 g/day on the A-HCLF, C-HCLF and LCHF diet, respectively, compared to 21±7, 21±7 and 20±6 g/day at baseline. We observed no significant between-group difference in IBS-SSS sum score after 3 and 12 months. We found significant improvement in GerdQ score (change score [95% CI]: −0.62 [−1.18, −0.048], p=0.034), and SF-NDI sum score (−1.88 [−3.22, −0.52], p=0.007) after 3 months on the LCHF diet compared to the A-HCLF diet, and GerdQ remained significant at 12 months (−1.03 [−1.88, −0.19], p=0.017). Compared to the A-HCLF diet, the concentration of faecal butyric acid increased significantly more after 3 months on the C-HCLF diet (4.97 [1.71, 8.23] p=0.003) and faecal acetic acid decreased more (−6.41 [−12.8, −0.047]. p=0.048) on the LCHF diet. At 12 months the greater reduction in faecal acetic acid on the LCHF diet remained significant (−9.82 [−19.0, −0.67], p=0.036), along with significantly greater reductions also in total SCFAs (−21.3 [−38.0, −4.56], p=0.013), propionic (−4.42 [−7.79, −1.05], p=0.010), and butyric acid (−5.05 [−9.60, −0.51], p=0.030). ConclusionIn this sample of adults with obesity and mild GI symptoms at baseline, modest improvements were observed only for the LCHF diet in QoL (at 3 months) and reflux symptoms (at 3 and 12 months), which was significantly different from the acellular carbohydrate diet, and independent of total fibre intake. Concomitantly, compared to the acellular carbohydrate diet, the cellular diet significantly increased the faecal concentration of butyric acid, whereas the LCHF diet lowered acetic acid after 3 months and all the major SCFAs after 12 months. Clinical trials identifierNCT03401970. https://clinicaltrials.gov/ct2/show/NCT03401970.

Therapeutic drug monitoring for antimicrobial agents for people living with HIV (TAP)

Background Antimicrobial resistance (AMR) is a growing health concern, particularly in Africa, and is predicted to be the leading cause of death after cancer by 2050. Factors like overuse or inappropriate use of antibiotics, contribute to this crisis. People living with HIV (PLWH) are particularly vulnerable to AMR with potential drug-drug interactions between antiretroviral and antimicrobial agents against common organisms like Mycobacterium tuberculosis. There is limited data on the concentrations of commonly used antimicrobial agents in people living with HIV in resource-limited settings. Therapeutic Drug Monitoring (TDM) offers a promising approach to optimize antibiotic dosing and improve treatment outcomes for those with sub-optimal drug concentrations. TDM has been recommended for PLWH on anti-tuberculosis treatment due to sub-optimal drug concentrations found in a significant proportion of those with TB. Objectives The main objectives of this study are to determine the concentrations of selected antimicrobial agents in people living with HIV requiring antimicrobial therapy and to assess the utility of therapeutic drug monitoring in achieving therapeutic targets for PLWH receiving rifampicin and isoniazid for the treatment of tuberculosis Methods This prospective observational study will enroll adult PLWH receiving amoxicillin, azithromycin, ciprofloxacin, rifampicin, isoniazid, or ceftriaxone. Concentrations of these antibiotics will be measured locally using validated liquid chromatography mass spectrometry methods and high-performance liquid chromatography with ultraviolet detection. TDM with dose adjustment will be performed in a subset of participants on TB treatment. Pharmacokinetic parameters will be estimated using non-linear mixed effects models. Results This study was reviewed and approved by the research and ethics committee in February 2024. Enrolment is projected to begin by August 2024. Conclusions We anticipate that the findings from this research will characterize pharmacokinetic and pharmacodynamics relationships to predict treatment response for optimal antimicrobial therapeutic and anti-tuberculosis dosing among people living with HIV (PLWH). Clinical registration The study is registered with Pan African Clinical Trials Registry, registration number PACTR202409710100607, registration date 07 August 2024, pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=31764

Physical Activity Declines over a 12-Month Period in Parkinson's Disease: Considerations for Longitudinal Activity Monitoring.

The purpose of this project was to evaluate trends in daily steps in individuals with Parkinson's disease (PD) over a 12-month period using continuous activity monitoring. Environmental (temperature) and cultural factors (represented by day of the week) were evaluated as potential external sources of variability. It was hypothesized that participants daily step counts would decline over the course of 12 months. Further, it was hypothesized that participants would take more steps on warmer days and that the day of the week would have minimal impact on step count as many participants were no longer in the workforce. Participants were part of the Usual and Customary Care arm (N = 119) of the CYClical Lower Extremity Exercise Trial for Parkinson's disease - II (CYCLE-II) at the Cleveland Clinic and University of Utah. Participants wore a Garmin Vivofit4® device daily for 12-months. A linear mixed effects model was created to model daily steps over 12-months. Participants wore their activity monitors 93% of study days. Steps per day declined by 6.1% over 12 months (95% CI 12.6% decline, 0.9% increase, p = 0.09). Steps per day were greater with warmer temperatures (p < 0.001), plateauing and declining around 75-85 degrees Fahrenheit (24-29 degrees Celsius). Participants took fewer steps on Sundays; this difference was more pronounced for Utah participants, who took 25% fewer steps on Sundays compared to other weekdays (p < 0.001). Most individuals live with PD for decades, and interventions should address the expected decline of 6% in daily step count. Environmental and cultural factors impact daily step count and should be adjusted for in short- and long-term monitoring of physical activity in individuals with PD.

Longitudinal history of mammographic breast density and breast cancer risk by familial risk, menopausal status, and initial mammographic density level in a high risk cohort: a nested case–control study

BackgroundElevated mammographic density is associated with increased breast cancer risk. However, the contribution of longitudinal changes in mammographic density to breast cancer risk beyond initial mammographic density levels, considering familial breast cancer risk and menopausal status, remains uncertain but holds important clinical implications.MethodsIn a nested case–control study within the Sister Study (323 cases, 899 controls; 12,095 mammograms), a cohort enriched for family history of breast cancer, we examined case–control status in relation to the largest annual change in percent density and dense area using mammograms available spanning 5.4 years, on average, using multivariable logistic regression and to the rate of mammographic density change using linear mixed-effects models. We considered effect modification by: mammographic density level of the earlier mammogram, the extent of family history, Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation (BOADICEA) risk strata, and menopausal status.ResultsCases (diagnosed < 60 years) had greater initial percent density and dense area levels and a slower rate of decline in dense area than controls. Women with stable mammographic density (≤ 10% annual change) had an increased breast cancer risk as compared with women whose largest mammographic density change was > 10% annual decline (e.g., Odds Ratio (OR) 2.34, 95% Confidence Interval (CI) 1.63–3.37 for dense area). Increasing vs. decreasing dense area was also associated with elevated risk, especially in women with the highest dense area levels at the earlier mammogram (OR: 2.56, 95%CI 1.50–4.36). Although generally similar across menopausal and familial risk categories, the associations of MD change with risk appeared stronger in pre-menopausal and lower-risk women.ConclusionsWomen who maintain higher levels of mammographic density (i.e. do not decrease over time) or have increasing mammographic density over time have a higher risk of subsequent breast cancer than women with high mammographic density that decreases over time. These findings suggest potential for incorporating mammographic density trajectories in clinical risk assessment, and the importance of additional breast cancer monitoring in women not experiencing declines in mammographic density over time.

The long-term impact of family economic empowerment on viral suppression and mental health outcomes among adolescents living with HIV in low-income settings: A cluster-randomized controlled trial in Southern Uganda

ObjectivesWe examined the impact of a family-based economic empowerment intervention on viral suppression and mental health among ALHIV. Study designBetween 2013 and 2014, 702 participants aged 10–16, living with HIV, and taking antiretroviral therapy, were recruited from 39 clinics in Uganda. Twenty clinics (n = 358 participants) were randomized to the intervention and 19 clinics (n = 344 participants) were randomized to the control conditions. The intervention comprised a matched savings account, financial literacy training, and microenterprise workshops. The primary outcome was viral suppression, while the secondary outcomes included depression, hopelessness, and self-concept. We ran mixed-effects models to determine the intervention effects. ResultsAt enrollment, participants’ mean age was 12 years. The intervention improved viral suppression, evidenced by significant intervention-by-time interaction effects [χ2(5) = 12·81, p = 0·025], further qualified by increased viral suppression in the intervention group at year two, OR = 1.89 (95% CI: 1.14–3.15), year three, OR = 2.31 (95% CI: 1.05–5.04), and year four, OR = 2.34 (95% CI: 1.03–5.33). Regarding mental health, we did not find significant intervention main effects or intervention-by-time interaction effects for depressive symptoms, hopelessness, or self-concept for the entire sample. However, for participants owning fewer assets, we found significant intervention-by-time interaction effects for hopelessness [χ2(5) = 12·33, p = 0·031], and self-concept [χ2(5) = 27·26, p < 0·001], suggesting beneficial intervention effect for this demographic. ConclusionsFamily EE interventions have the potential to improve viral suppression and mental health outcomes among ALHIV. These findings offer insights in designing programs and policies to improve outcomes among ALHIV.