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PubMed2003

Acetaminophen in cerebrospinal fluid in children.

BACKGROUND: There are few studies describing acetaminophen (APAP) cerebrospinal fluid (CSF) concentrations in children. This current study was undertaken in children--from neonates to adolescents--in order to investigate age-related changes in the plasma to CSF equilibration half-time (Teq) of APAP. METHODS: Children (n=41) 1 week to 18 years of age undergoing (semi) elective surgery for placement or revision of a ventriculo-peritoneal shunt or insertion of a temporary external ventricular drain received a loading dose of 30-40 mg/kg APAP 1 h before scheduled surgery. Blood and CSF samples for APAP concentration analysis were collected during surgery. In those children with a temporary external drain, blood and CSF sampling were extended into the postoperative period. APAP and CSF pharmacokinetics were estimated using non-linear mixed-effects models. Size was standardized to a 70-kg person using allometric "1/4 power models". RESULTS: Median (25-75th percentile) age and weight of the patients included in this study were 12 months (3-62 months) and 10.0 kg (5.8-20.0 kg). Median (25-75th percentile) time between APAP loading dose administration and collection of blood samples and median time (25-75th percentile) between APAP loading dose and collection of CSF were, respectively, 125 min (95-210 min) and 133 min (33-202 min). The population mean Teq, standardized to a 70-kg person, was 1.93 h (CV 43%), an estimate similar to that described in adults (2.1 h). There was no relationship between age and Teq other than that predicted by size. APAP plasma concentrations ranged from 0.0 mg/l to 33.0 mg/l, APAP CSF concentrations ranged from 0.0 mg/l to 21.0 mg/l. CONCLUSION: Size rather than blood-brain-barrier maturation determines Teq changes with age in children. We predict a neonate (3.5 kg), 1-year-old child (10 kg), 5-year-old child (20 kg), 10-year-old child (30 kg) and adult (70 kg) to have Teq values of 0.9, 1, 1.4, 1.6, and 1.93 h, respectively.

Acetaminophen↗

PubMed2004

Population pharmacokinetic analysis of mirtazapine.

OBJECTIVE: Mirtazapine belongs to the new generation of antidepressants that is commonly used in clinical routine. Therefore, we feel it mandatory to control compliance in the context of non-response, adverse events or other clinical situations by means of plasma concentration measurements. While controlled clinical studies have evaluated the effect of individual covariates on the pharmacokinetics of mirtazapine, our analysis aims to identify covariates within a naturalistic clinical setting. METHODS: We performed non-linear mixed-effects modelling with data from 65 depressed inpatients whose plasma concentrations were measured weekly during their stay in hospital. Each patient's age, height, weight, co-medication, alcohol, coffee and cigarette consumption, weekly serum creatinine concentrations, liver enzyme activity, blood pressure and pulse was noted. From 49 patients, the genotype of cytochrome P450 (CYP) isoenzymes 2D6, 2C9 and 2C19 was analysed. RESULTS: The clearance of CYP2D6 intermediate metabolisers was reduced by 26% compared with extensive metabolisers. No other factor significantly influenced the clearance of these patients. CONCLUSION: The variability of mirtazapine plasma concentrations in clinical routine is caused to a relevant degree by CYP2D6. This should be taken into account when therapeutic drug monitoring is carried out to check treatment adherence or when a special clinical situation, such as co-morbidity and add-on medication, demands careful dosing of this drug.

Antidepressive Agents, Tricyclic↗

PubMed2004

Intravenous paracetamol (propacetamol) pharmacokinetics in term and preterm neonates.

BACKGROUND: The aim of this study was to describe propacetamol pharmacokinetics in term and preterm neonates to suggest dosing regimens. METHODS. A population pharmacokinetic analysis of paracetamol (acetaminophen) time-concentration profiles in 48 neonates was undertaken using non-linear mixed-effects models. Neonates were given either single (n=30) or multiple doses (n=18) of propacetamol infusion over 15 min. Neonates had a median postnatal age of 1 day (range, 1-76 days). Median post-conceptual age (PCA) was 35 weeks (range, 27-42 weeks), and median weight was 2.4 kg (range, 0.51-4 kg). RESULTS: The population volume of distribution estimate and between-subject variability (%) for a one-compartment model with zero-order input and first-order elimination was 70.4 l (30.7%)/70 kg. Clearance increased from 2.85 l/70 kg, CV 40.7% at 27 weeks PCA to reach 7.05 l/h per 70 kg by 42 weeks PCA (standardised to a 70-kg person using allometric "1/4-power" models). Between-occasion variability for volume of distribution and clearance were 17.4% and 26%, respectively. CONCLUSIONS: A mean paracetamol steady-state target concentration above 10 mg/l at trough can be achieved using a loading dose of 40 mg/kg and maintenance doses of 20 mg/kg 6 h in 28-week PCA neonates, 25 mg/kg 6 h at 32 weeks, 30 mg/kg 6 h at 36 weeks and 20 mg/kg 4 h at term (propacetamol doses). Since the role of the oxidative enzyme CYP2E1 and production of the hepatotoxic metabolite N-acetyl-p-benzoquinone-imine still is unknown in premature neonates, lower doses scaled by age-related clearance and centred on a daily dose of 60 mg/kg per day in a child of 6-8 years with a clearance of 0.25 l/h per kg (12.5 l/h per 70 kg) may be more appropriate.

Acetaminophen↗

PubMed2004

No relationship between high nevirapine plasma concentration and hepatotoxicity in HIV-1-infected patients naive of antiretroviral treatment or switched from protease inhibitors.

OBJECTIVE: A prospective population pharmacokinetic study of nevirapine (NVP) was performed to test the relationship between hepatotoxicity and NVP trough plasma concentration and to identify which covariates could influence NVP pharmacokinetics. METHODS: All patients [77 HIV-1 (human immunodeficiency virus type 1)-infected patients (128 samples)] were either on first-line antiretroviral therapy or switched from successful therapy containing protease inhibitor. Population pharmacokinetic parameters were estimated by a non-linear mixed-effect modelling method. Hepatotoxicity was evaluated by ASAT (aspartate aminotransferase) plasma level. RESULTS: No correlation was found between high NVP trough plasma concentration and high ASAT level or the increase of ASAT level on NVP therapy. Age and Caucasian race were found to be significant covariates of NVP clearance (Cl/F). Population pharmacokinetic parameters (rate absorption constant=1.04 h(-1); Cl/F=3.31 h(-1); apparent volume of distribution=92 l) are consistent with previous studies. CONCLUSION: High NVP trough plasma concentrations are not correlated with hepatotoxicity in our population. NVP clearance is decreased in the elderly patients, suggesting a potential increase of NVP plasma level and the interest of therapeutic drug monitoring for this population.

Anti-HIV Agents↗

PubMed2005

A population approach to study the influence of nevirapine administration on lopinavir pharmacokinetics in HIV-1 infected patients.

OBJECTIVE: The influence of nevirapine (NVP) on lopinavir (LPV) pharmacokinetics was investigated by a population analysis based on a non-linear mixed-effect modelling method. METHODS: In this analysis, 95 HIV-1 infected patients were studied [52 treated with LPV/ritonavir (400/100 mg twice a day) plus nucleoside reverse transcriptase inhibitors (group A), 22 patients treated with LPV/ritonavir (533.3/133.3 mg twice a day) plus NVP (group B) and 21 patients treated with LPV/ritonavir (400/100 mg twice a day) plus NVP (group C)]. RESULTS: The apparent clearance of LPV [mean+/-SD: 4.56+/-3.94 l h(-1) (group A) versus 7.14+/-1.77 l h(-1) (group B) versus 7.74+/-1.45 l h(-1) (group C)] was significantly (P <0.001) increased by the presence of NVP in the antiretroviral regimen and the mean trough plasma concentration of LPV was reduced in group C relative to group A [mean+/-SD: 2.23+/-1.35 mg/l versus 5.29+/-2.19 mg/l (P < 0.001)]. CONCLUSION: These results suggest an induction of LPV metabolism by NVP.

Adult↗

PubMed2004

Molecular cloning and sequencing of porcine C5 gene and its association with immunological traits.

The complement system helps in the lysis of invading pathogens and modulates the inflammatory as well as the humoral and cellular immune responses. C5 mediates many potent inflammatory and cytolytic events after proteolytic activation by complement convertase enzymes. Hence, to investigate the role of pig C5 ( pC5) as a candidate gene for disease resistance in pigs, the complete cDNA of pC5 was sequenced, screened for single nucleotide polymorphisms (SNPs), and an association analysis with various immunological parameters measured in F2 animals of a pig resource population based on a cross of Duroc and Berlin miniature pigs (DUMI) was carried out. In total, 5,422 bp of pC5 cDNA was sequenced, which codes for the 1,677-amino-acid precursor of C5. Four polymorphic sites were detected, one of which was segregating in the DUMI population in three genotypic patterns: AA, AC and CC. Classical (CH50) and alternative (AH50) complement activities, C3c levels, haptoglobin (HP) acute phase protein levels, and antibody titers against Mycoplasma (Mk) and Aujesky (ADV) vaccines were measured in the resource population. Association analysis between C5 and the immunological parameters was carried out using repeated measures mixed and general linear model analysis. The homozygote AA was found to be significantly different from the other two genotypes with respect to AH50 and CH50, whereas genotype CC was found to be significantly different from the other genotypes for C3c and HP levels. No significant difference could be seen between genotypes for antibody titers against vaccinations. Association of C5 with complement activity traits and acute phase proteins promotes pC5 as a candidate gene for innate disease resistance.

Acute-Phase Proteins↗

PubMed2026

Phase-resolved functional lung MRI detects single-dose and sustained bronchodilator responses in COPD in a randomized crossover trial.

OBJECTIVES: To evaluate the effects of tiotropium/olodaterol (T/O) on phase-resolved functional lung (PREFUL) MRI parameters in hyperinflated chronic obstructive pulmonary disease (COPD) patients and examine correlations with conventional cardiopulmonary and hyperpolarized 129Xe MRI measures. MATERIALS AND METHODS: Retrospective subanalysis of a prospective, randomized, placebo-controlled, crossover trial with open-label extension. Thirty-two patients with moderate-to-severe COPD (61.5 ± 7.7 years; 17 men); 30 completed the MRI extension at 1.5 T. PREFUL analysis yielded regional ventilation (RVent), flow-volume loop correlation metric (FVL-CM), normalized perfusion (QN), ventilation defect percentage (VDP), perfusion defect percentage (QDP), V/Q match metrics (VQM), and pulmonary pulse wave velocity (PWV; post-hoc parameter). Linear mixed-effects models tested treatment effects; correlations were evaluated with Spearman's rank and bootstrap 95% confidence intervals (95% CIs). RESULTS: PREFUL parameters improved after T/O single dose (SD) versus placebo, including improvements in FVL-CM by 4.1 percentage points (pp; 95% CI: 1.0 to 7.3 pp) and QN by 0.4 pp (95% CI: 0.2 to 0.6 pp) and reductions in VDP and QDP, with parallel gains in VQM(Non-Defect) (p < 0.05). PWV decreased after multiple doses (-0.87 m/s, 95% CI: -1.26 to -0.48 m/s). PREFUL MRI baseline values showed significant correlations with pulmonary function tests, cardiac, dynamic contrast-enhanced and 129Xe MRI. SD treatment-induced absolute changes in VDP(FVL-CM) correlated with reductions in residual volume (ρ = 0.41, 95% CI: 0.02 to 0.64). Further correlations were observed between PREFUL MRI and ¹²⁹Xe-derived VDP, apparent diffusion coefficient, and compartment ratios. CONCLUSION: PREFUL MRI sensitively captured immediate SD T/O-induced improvements in V/Q parameters and dose-dependent PWV responses after sustained bronchodilation. KEY POINTS: Question Can phase-resolved functional lung (PREFUL) MRI sensitively capture immediate single-dose and sustain multi-dose effects of tiotropium/olodaterol on ventilation-perfusion and vascular function in COPD patients? Findings Tiotropium/olodaterol improved PREFUL MRI-derived ventilation, perfusion, and V/Q matching parameters after a single dose, with sustained pulmonary vascular improvements after repeated dosing. Clinical relevance PREFUL MRI detected immediate and sustained functional improvements after tiotropium/olodaterol and showed significant correlations with cardiopulmonary tests and hyperpolarized ¹²⁹Xe MRI, supporting its role as a sensitive, radiation-free tool for monitoring COPD treatment response.

Humans↗

PubMed2026

Effects of 12 weeks of resistance and concurrent training with graded protein intakes on lipid profile, kidney and liver biomarkers in middle-aged to older women.

PURPOSE: To examine secondary lipid, kidney-related, and liver-enzyme responses to three protein intakes during resistance training (RT) alone or the same RT plus cycling (CT) in middle-aged to older women. METHODS: In this randomized 2×3 factorial trial, 108 women aged 40-77 years were assigned to RT or CT and 0.8, 1.6, or 2.2 g kg-1 d-1 protein for 12 weeks. This complete-case secondary analysis included 83 participants. Linear mixed-effects models tested Time × Training, Time × Protein, and Time × Training × Protein effects, with false-discovery-rate-adjusted omnibus tests and Holm-adjusted contrasts. RESULTS: Triglycerides, total cholesterol, LDL-C, and apolipoprotein B decreased and HDL-C increased in all conditions. Lipid changes differed by protein condition, and several were more favorable with CT; however, CT comprised RT plus additional cycling and greater exercise exposure. Urea, blood urea nitrogen, creatinine, the blood urea nitrogen-to-creatinine ratio, and cystatin C increased, whereas three eGFR estimates decreased. Responses differed mainly between 0.8 and the two higher protein conditions, with little evidence of differences between 1.6 and 2.2 g kg-1 d-1. ALT, AST, and GGT differed by protein condition; AST and GGT also showed training-dependent responses. CONCLUSIONS: The dietary and exercise interventions modified lipid and clinical-chemistry responses. Because energy and food composition were not fully matched and CT added cycling to RT, the findings do not isolate protein dose or exercise modality. Changes in eGFR estimates and liver enzymes do not establish organ injury or long-term safety.

Humans↗

PubMed2007

Change in quality of life in Chinese women with breast cancer: changes in psychological distress as a predictor.

INTRODUCTION: The effect of fluctuating psychological distress on quality of life (QoL) scores is not well delineated. We examined how changes in psychological distress affected change in QoL over time in 259 Chinese women recovering from breast cancer (BC). PATIENTS AND METHODS: Women were interviewed during their first postoperative outpatient visit for chemotherapy (Baseline), at 3 months (FU1), and at 6 months after Baseline (FU2). Respondents completed the Chinese version of the FACT-G version-3 scale [FACT-G (Ch)]. Psychological distress was assessed using three categorical measures of depression, mood, and boredom. Linear mixed effects (LME) models examined whether changes in psychological distress predicted subsequent changes in QoL. RESULTS: Respondents' mood improved significantly over time from baseline to FU2 (Baseline/FU2: standardized beta = -0.266, p < 0.005; FU1/FU2: standardized beta = -0.243, p < 0.005). Changes in depression scores consistently predicted subsequent changes in overall (standardized beta = 4.96; 95% CI, 3.749, 6.171, p < 0.001), physical (standardized beta = 1.752; 95% CI, 1.209, 2.294, p < 0.001), and functional (standardized beta = 0.872; 95% CI, 0.308, 1.436, p < 0.001) QoL scores. CONCLUSIONS: The magnitude of change in psychological distress significantly impacted physical and functional, but not social QoL in Chinese BC patients. These data highlight the need to address psychological and physical distress as part of the drive to improve physical and functional QoL for women with BC.

Adult↗

PubMed2005

Factors influencing cortisol level and slope among community dwelling older adults in Minnesota.

Cortisol has frequently been used as a stress marker and has been shown to be elevated in response to laboratory stressors, severe real-life stressors, and daily hassles. Furthermore, variation in cortisol rhythms has been observed in some disease states and may be related to health outcomes. The majority of cortisol and stress research has been conducted on young adults. This study examines factors associated with cortisol level and slope in healthy older adults. Forty-eight older adults from the Twin Cities, MN (age = 76.4 +/- 5.8) were interviewed regarding health, stress, affect, and social networks. Participants collected saliva every two hours over a three-day period while keeping a record of their emotions and activities. Cortisol was assayed by radioimmunoassay. Data were analyzed using a random mixed effects model and linear regression. In univariate models cortisol was associated with age (p < 0.0001), time of day (p < 0.001), stress level (p = 0.01), positive affect measured in interview (p = 0.005), positive mood state (p < 0.0001), negative mood state (p = 0.09), and morningness (p = 0.0006). In multivariate models, affect was no longer significantly associated with cortisol. Age (p < 0.001), morningness (p = 0.014), physical activity (p = 0.017), and hours slept (p < 0.001) predicted cortisol slope. These results suggest that while cortisol reactivity to current mood and daily stressors may be diminished in older adults, perception of average stress on a trait level is predictive of cortisol level. As such, salivary cortisol might not be a good marker of acute stress in older adults, while still valuable to measure stress over a longer period of time.

Aged↗

PubMed2006

Do competence skills moderate the impact of social influences to drink and perceived social benefits of drinking on alcohol use among inner-city adolescents?

Only a few studies have found competence skills to be a protective factor against adolescent alcohol use; others did not find a direct effect on alcohol. A possible reason for this is that competence skills may moderate the effects of risk factors for alcohol use and that aspect has not been examined often or in a longitudinal design. This study tested whether several competence skills served either as direct protective factors against alcohol use or moderators of the impact of social risk factors on alcohol use. Participants (N = 1318) completed questionnaires that included measures of decision-making skills, refusal skill techniques, resisting media influences, friends' drinking and perceived social benefits of drinking, as well as current drinking amount and future drinking at baseline, one-year follow-up and two-year follow-up. Data analyses were conducted using multi-level mixed effects generalized linear models with random intercept. All the competence skills and the risk factors predicted current and future drinking. Several significant interactions were found between (1) perceived social benefits of drinking and decision-making skills, (2) perceived social benefits of drinking and refusal skill techniques and (3) friends' drinking and refusal skill techniques. Competence skills served as protective factors, as well as moderators. One possible reason that competence enhancement approaches to alcohol prevention are effective may be due to the inclusion of the competence skills component.

Adolescent↗

PubMed2006

Quality of life and pain in Chinese lung cancer patients: Is optimism a moderator or mediator?

OBJECTIVE: To clarify if optimism exerts a primarily moderating or mediating influence on the pain-QoL association in Chinese lung cancer patients. METHODS: About 334 Chinese lung cancer patients were interviewed at baseline during the first outpatient visit (Baseline), at 4 months after Baseline (FU1), and at 8 months after Baseline (FU2). Respondents completed the Chinese version of the FACT-G version-3 scale (FACT-G (Ch)). Optimism and pain were assessed using two 11-point self-rated items. Linear mixed effects (LME) models tested the moderating and mediating effects of optimism on QoL. RESULTS: Optimism, pain, and QoL were most strongly correlated at FU1. LME models failed to show any moderating effect by optimism on the pain-QoL association (standardized beta = -0.049, 95% CI -0.097 to 0.001). After adjustment for age, cancer stage, and disease recurrence, a modest mediating effect was observed for optimism on the pain-QoL association over the duration of the study (standardized beta = 0.047; Sobel test z = -4.317, p < 0.001). CONCLUSIONS: Optimism qualifies as a mediator between pain and QoL suggesting that pessimistic lung cancer patients are likely to experience greater QoL decrements in response to pain in the early post-diagnostic period. Effective pain control may be enhanced by inclusion of interventions that facilitate optimistic perspectives in patients. This study lends further support to the view that lung cancer patients' psychological needs are important in both pain control and QoL.

Adult↗

PubMed2006

Evaluation of lung MDCT nodule annotation across radiologists and methods.

RATIONALE AND OBJECTIVES: Integral to the mission of the National Institutes of Health-sponsored Lung Imaging Database Consortium is the accurate definition of the spatial location of pulmonary nodules. Because the majority of small lung nodules are not resected, a reference standard from histopathology is generally unavailable. Thus assessing the source of variability in defining the spatial location of lung nodules by expert radiologists using different software tools as an alternative form of truth is necessary. MATERIALS AND METHODS: The relative differences in performance of six radiologists each applying three annotation methods to the task of defining the spatial extent of 23 different lung nodules were evaluated. The variability of radiologists' spatial definitions for a nodule was measured using both volumes and probability maps (p-map). Results were analyzed using a linear mixed-effects model that included nested random effects. RESULTS: Across the combination of all nodules, volume and p-map model parameters were found to be significant at P < .05 for all methods, all radiologists, and all second-order interactions except one. The radiologist and methods variables accounted for 15% and 3.5% of the total p-map variance, respectively, and 40.4% and 31.1% of the total volume variance, respectively. CONCLUSION: Radiologists represent the major source of variance as compared with drawing tools independent of drawing metric used. Although the random noise component is larger for the p-map analysis than for volume estimation, the p-map analysis appears to have more power to detect differences in radiologist-method combinations. The standard deviation of the volume measurement task appears to be proportional to nodule volume.

Artificial Intelligence↗

PubMed2026

Virtual reality physical education and adolescents' exercise interest and physical fitness: An explanatory sequential mixed-methods randomized trial with exploratory pathway analysis.

Traditional physical education (PE) faces declining student interest and limited fitness gains. Virtual reality (VR) offers immersive, gamified experiences, but evidence regarding its effectiveness and explanatory pathways remains limited. This explanatory sequential mixed-methods randomized trial assigned 360 adolescents (aged 13-16) from three middle schools to either VR-supported PE (n = 180) or conventional PE (n = 180) for 12 weeks, with a 4-week follow-up. Outcomes included exercise interest (validated scale), physical fitness (coordination via MABC-2, cardiorespiratory endurance via the 20-m shuttle run, explosive power via the standing long jump, and speed via the 10-m sprint), and accelerometer-measured physical activity. The qualitative component involved 38 unique students: 32 completed individual semi-structured interviews, and six additional students participated only in focus groups. Three-level linear mixed-effects models and exploratory structural equation modeling were used. The VR group showed significantly greater improvements in exercise interest (d = 0.78), coordination (d = 0.62), cardiorespiratory endurance (d = 0.55), and speed (d = 0.48) than the control group (all p < 0.001), but not in explosive power (d = 0.12, p = 0.148). Effects were partially retained at follow-up (interest d = 0.65, coordination d = 0.48, endurance d = 0.42, and speed d = 0.30), a pattern not fully consistent with a purely novelty-driven explanation. Exploratory mediation identified exercise interest as a statistically compatible explanatory pathway (indirect effect = 0.34, 95% CI [0.22, 0.46]), although the timing of measurement precludes causal interpretation. Qualitative findings contextualized these results by highlighting immersion, feedback, self-efficacy, and perceived transfer. VR-supported PE may enhance adolescents' exercise interest and selected fitness dimensions, but its limited effect on explosive power and possible novelty contribution indicate that it should complement, rather than replace, conventional PE. Longer-term studies are needed.

Humans↗

PubMed2026

Source- and Solubility-specific Choline, Gut Microbiota, and Dyslipidemia Risk: Trimethylamine N-oxide-associated and Non-trimethylamine N-oxide-Associated Patterns in a Prospective Cohort Study.

BACKGROUND: Dietary choline, a major precursor of the gut microbial metabolite trimethylamine N-oxide (TMAO), is implicated in dyslipidemia risk; however, source- and form-specific associations and interactions with gut microbiota remain unclear. OBJECTIVES: The aim of this study was to examine longitudinal associations of source- and form-specific dietary choline with plasma TMAO and dyslipidemia and to identify gut microbiota interactions. METHODS: Using data from the China Health and Nutrition Survey (2018-2023), dietary intake was assessed via 3 consecutive 24-h recalls in this prospective cohort study. Two-level generalized linear mixed-effects models were applied in 4828 adults (mean age: 55.9 ± 12.6 y, 56.6% females) to assess choline-dyslipidemia associations. Choline-TMAO and TMAO-dyslipidemia analyses were conducted in 1091 participants free of dyslipidemia at baseline. Among 7169 adults with gut microbiome data, Least Absolute Selection and Shrinkage Operator and logistic regression identified lipid-associated gut genera; TMAO relationships were examined in a subset of 693 participants. RESULTS: Higher intakes of total [Q4 compared with Q1: odds ratio (OR) = 1.261; 95% confidence interval (CI): 1.007, 1.580], red meat-derived (OR: 1.753; 95% CI: 1.196, 2.568), and lipid-soluble choline (OR: 1.304; 95% CI: 1.047, 1.624) were associated with higher risk of elevated low-density lipoprotein cholesterol (LDL cholesterol), whereas vegetable-derived choline was inversely associated. Egg-derived and lipid-soluble choline were positively associated with plasma TMAO, which was prospectively associated with 5-y incident dyslipidemia (Q4 compared with Q1-OR: 1.620; 95% CI: 1.047, 2.509), elevated LDL cholesterol (Q3 compared with Q1-OR: 2.478; 95% CI: 1.187, 5.174), and hypertriglyceridemia (Q4 compared with Q1-OR: 1.829; 95% CI: 1.028, 3.225). Three TMAO-associated genera were identified: Lachnospiraceae and Phascolarctobacterium as pro-risk taxa and Turicibacter as protective. The adverse LDLcholesterol association of egg-derived choline was observed exclusively in Phascolarctobacterium-enriched individuals. CONCLUSIONS: Dietary choline source and solubility differentially associated with dyslipidemia risk through TMAO-associated and non-TMAO-associated patterns, with gut microbiota as key modulators.

Humans↗

PubMed2004

Fibrinolytic administration for acute myocardial infarction in a tertiary ED: factors associated with an increased door-to-needle time.

The purpose of this study was to evaluate the door-to-needle time for fibrinolytic administration for acute myocardial infarction (AMI) at Vancouver General Hospital (VGH) and identify factors associated with time prolongation. A retrospective chart review of all patients fibrinolysed for AMI in the ED at VGH was performed from January 1, 1998, to December 31, 1999, to determine door-to-needle time. A mixed-effects linear regression model was fit to the fibrinolytic data with the door-to-needle time to identify factors associated with prolonged times. One hundred forty patients were included in the final analysis. The mean and median door-to-needle times were 58 and 43 minutes, respectively. A door-to-needle time of under 30 minutes was achieved in 24.3% of patients, 30 to 40 minutes in 24.3%, 40 to 60 minutes in 22.1%, and over 60 minutes in 29.3%. EP prescribers without prior cardiologist consultation resulted in a significantly shorter door-to-needle time compared with requesting a cardiology consult before administration (mean [median] 41 [35] minutes vs. 108 [90] minutes respectively; P <.001). Patients who arrived by ambulance had shorter door-to-needle times than those who did not (mean [median] 50 [38] minutes vs. 71 [57] minutes, respectively; P =.008). Patients who arrived during the night shift (2300-0700 hrs) had significantly shorter door-to-needle times than those patients who arrived during the day (0700-1500 hrs) or afternoon (1500-2300) shifts (P = 0481); and patients who had a longer time from chest pain onset to ED arrival also had longer door-to-needle times (P =.0233). A significant number of AMI patients fibrinolysed at VGH do not meet the national guideline for door-to-needle time less than 30 minutes. Factors associated with this should be addressed to improve the care of patients with AMI.

Aged↗

PubMed2026

Association Between 24-Hour Blood Pressure and Rates of Retinal Nerve Fiber Layer Progression in Glaucoma: The Vascular Imaging in Glaucoma Study.

PURPOSE: Low systemic blood pressure (BP) has been implicated as a risk factor for glaucoma progression. The purpose of this study was to investigate the association between 24-hour BP and rates of retinal nerve fiber layer (RNFL) loss in eyes with primary open-angle glaucoma. DESIGN: Prospective cohort study. PARTICIPANTS: Seventy-nine eyes from 42 subjects with glaucoma (mean age, 68.5 ± 7.6 years) enrolled in the Vascular Imaging in Glaucoma Study at the Bascom Palmer Eye Institute. METHODS: Participants underwent 24-hour ambulatory BP monitoring at baseline. Follow-up evaluations were conducted at 4-month intervals and included ophthalmic examination, BP measurement, and peripapillary RNFL thickness measurement with spectral-domain optical coherence tomography. The association between BP and RNFL loss over time was assessed using linear mixed-effects models adjusted for age, sex, race, baseline RNFL thickness, central corneal thickness, and intraocular pressure. MAIN OUTCOME MEASURES: The effect of baseline 24-hour mean arterial pressure (MAP), systolic BP (SBP), and diastolic BP (DBP) on the rate of average RNFL loss over time. RESULTS: Eyes underwent an average of 13 ± 3 optical coherence tomography exams over 43 ± 10 months of follow-up. The mean rate of RNFL loss was -0.34 ± 0.64 µm/y (median: -0.32; interquartile range: -0.66 to -0.04 µm/y). After adjusting for confounding factors, every 10 mm Hg lower in 24-hour minimum MAP, SBP, and DBP was associated with -0.542 µm/y (P < .001), -0.360 µm/y (P = .003), and -0.458 µm/y (P = .008) faster RNFL loss, respectively. Eyes in the lowest quartile of average 24-hour MAP (81-90 mm Hg) and minimum 24-hour DBP (35-47 mm Hg) experienced significantly faster progression compared to those in the highest quartile, with differences of -0.68 µm/y (P = .017) and -0.63 µm/y (P = .030), respectively. CONCLUSIONS: Lower systemic BP, especially minimum MAP, SBP, and DBP measured by 24-hour ambulatory BP monitoring, is associated with faster rates of RNFL loss in primary open-angle glaucoma eyes. 24-hour BP monitoring may help predict glaucoma patients at greater risk of progression.

Humans↗

PubMedDate not supplied

Relationship of childhood behavior disorders to weight gain from childhood into adulthood.

OBJECTIVE: Obesity and behavior disorders are important conditions that affect the health of children and adolescents; some evidence suggests that they are associated. However, these relationships have not been studied longitudinally from childhood to adulthood. We investigated childhood to adulthood weight change associated with attention-deficit and disruptive behavior disorders. METHODS: We analyzed data from a prospective cohort study in which 655 individuals observed before age 16.6 years, and assessed in 1983 (when aged 9.1 to 16.6 years), 1985-1986 (when 11.1 to 20.8 years), 1991-1994 (when 16.6 to 26.9 years), and 2001-2003 (when 27.7 to 38.3 years). Attention-deficit/hyperactivity disorder, oppositional defiant disorder, and conduct disorder (collectively, "disruptive disorders") were assessed by trained interviewers who used the Diagnostic Interview Schedule for Children. We evaluated the association of disruptive disorders (assessed when youth were <16.6 years) with longitudinal body mass index (BMI) z scores from childhood to adulthood using linear mixed-effects models. RESULTS: Female subjects with disruptive disorders were estimated, at all ages, to have mean BMI z scores 0.23 (95% confidence interval, 0.03-0.44) units higher than female subjects without disruptive disorders. Male subjects with disruptive disorders were estimated, at all ages, to have mean BMI z scores 0.20 (95% confidence interval, 0.00-0.39) units higher than male subjects without disruptive disorders. For male and female subjects, annual BMI z-score change was statistically unrelated to disruptive disorder history. CONCLUSIONS: Disruptive disorders were associated with elevated weight status that was maintained from childhood into adulthood. These findings suggest that associations between behavior disorders and increased weight begin early in childhood and may have lifelong health effects.

Adolescent↗