SEARCH · Search PubMed

Results for “linear mixed model”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 415 records · Page 23Linked to original sources

PubMed1995

The Working Well Trial: baseline dietary and smoking behaviors of employees and related worksite characteristics. The Working Well Research Group.

BACKGROUND: The Working Well Trial, the largest randomized worksite health promotion trial to date, tests the effects of cancer prevention and control interventions on dietary and smoking behaviors of employees and the worksite environment. The trial is a 5-year cooperative agreement conducted in 57 matched pairs of worksites in 16 states by four study centers, a coordinating center, and the National Cancer Institute. The dual aims of this paper are to: (a) present a baseline description of the dietary and smoking habits of 20,801 employees, who are predominantly blue-collar workers; and (b) describe the social and physical environments of their worksites that may facilitate or hinder health behavior changes. METHODS: The self-administered baseline survey of individuals consisted of a core set of questions common across all study centers on diet and smoking. The organizational survey consisted of eight instruments administered via interviews with key informants in each worksite. Continuous variable were analyzed by a mixed linear model and binary data were analyzed by the Generalized Estimating Equation. RESULTS: The population represented is largely male (67.5%) and blue collar (53.5%). Mean levels of fat and fiber intakes were close to the national averages (36.6% of calories as fat and 13.1 g of fiber). Smoking prevalence (25.2%) was slightly lower than the national average. The worksites had a high level of health promotion activities (42% had nutrition programs, 53% had smoking control programs), but lacked environmental support for dietary behavior change and perceived support for smoking cessation. CONCLUSIONS: These findings replicate and extend previous research results to a large sample of diverse, largely blue-collar worksites. In addition the baseline results lay a foundation for the development of new insights into the relationship between individual and organizational level variables that may interact to influence behavioral and cultural norms.

Adult↗

PubMed2002

Psychosocial correlates of physical activity and sedentary leisure habits in young adolescents: the Teens Eating for Energy and Nutrition at School study.

BACKGROUND: Low levels of physical activity (PA) and highly sedentary leisure habits (SLH) in youth may establish behavioral patterns that will predispose youth to increased chronic disease risk in adulthood. The purpose of this paper was to examine associations of demographic and psychosocial factors with self-reported PA and SLH in young adolescents. METHODS: A general linear mixed model predicted self-reported PA and SLH in the spring from demographic and psychosocial variables measured the previous fall in 3798 seventh grade students. RESULTS: PA and SLH differed by race, with Caucasian students reporting among the highest PA and lowest SLH. Perceptions of higher academic rank or expectations predicted higher PA and lower SLH. Depressive symptomatology predicted higher SLH scores but not PA. Higher self-reported value of health, appearance, and achievement predicted higher PA and lower SLH in girls. Girls who reported that their mothers had an authoritative parenting style also reported higher PA and lower SLH. CONCLUSIONS: Determinants of PA and SLH appear to differ from each other, particularly in boys. Development of effective programs to increase PA and/or decrease SLH in young adolescents should be based on a clear understanding of the determinants of these behaviors.

Adolescent↗

PubMed2000

Precision of measurement of tissue concentrations by RLG.

Existing investigations about the precision of radioluminography (RLG) are restricted to descriptive analysis of the tissue samples. The aim of the present experiments was to obtain a general prospective statement about the precision that the RLG method can achieve. Several pharmaceutical companies in Europe participated in the experiments. Albino rats of various strains were dosed with various (14)C-labeled compounds. Whole-body sections were produced, and blood calibration scales were set up with standard radioactivity sources of dog or rat blood. Photostimulated luminescence was detected using Fuji imaging plate BAS-III. For each organ separately, variability was investigated on each of the levels: rat, section of rat, region within section, and residual, with the help of variance components. The producing company was seen as a fixed factor and adjusted for. A mixed linear model was fitted to the log-transformed data. The variance component (SD estimate) for the residual term gave the desired prospective statement about the achievable precision of the RLG method. Exponential back transformation from the logarithmic to the natural scale transformed the SD estimates to multiplication factors. In total, 29 organs were investigated. The RLG method was comparable in precision to the dissection/combustion method.

Animals↗

PubMed2002

Characterization of the main effects, epistatic effects and their environmental interactions of QTLs on the genetic basis of yield traits in rice.

Main effects, epistatic effects and their environmental interactions of QTLs are all important genetic components of quantitative traits. In this study, we analyzed the main effects, epistatic effects of the QTLs, and QTL by environment interactions (QEs) underlying four yield traits, using a population of 240 recombinant inbred lines from a cross between two rice varieties tested in replicated field trials. A genetic linkage map with 220 DNA marker loci was constructed. A mixed linear model approach was used to detect QTLs with main effects, QTLs involved in digenic interactions and QEs. In total, 29 QTLs of main effects, and 35 digenic interactions involving 58 loci were detected for the four traits. Thirteen QTLs with main effects showed QEs; no QE was detected for the QTLs involved in epistatic interactions. The amount of variations explained by the QTLs of main effect were larger than the QTLs involved in epistatic interactions, which in turn were larger than QEs for all four traits. This study illustrates the ability of the analysis to assess the genetic components underlying the quantitative traits, and demonstrates the relative importance of the various components as the genetic basis of yield traits in this population.

Journal Article↗

PubMed2003

The genetic basis of stay-green in rice analyzed in a population of doubled haploid lines derived from an indica by japonica cross.

Delayed leaf-senescence, or stay-green, has been regarded as a desired characteristic for the production of a number of crops including rice. In this study, we analyzed the genetic basis of stay-green using a population of 190 doubled haploid lines from the cross between an indica parent Zhenshan 97 and a stay-green japonica parent Wuyujing 2. The population was tested in replicated field trials in 2 consecutive years, and six traits were defined to evaluate the stay-green characteristics. A genetic linkage map with 179 SSR (simple sequence repeat) marker loci was constructed. The software QTLMapper, based on a mixed linear model approach, was applied to detect QTLs, epistatic effects and their environmental interactions for these traits. A total of 46 main-effect QTLs was detected for the six traits that can be localized to 25 chromosomal regions. The individual effects of all the QTLs were small. Fifty digenic interactions were resolved that involved 66 loci distributed on all 12 chromosomes. Environmental interactions were detected for 18 of the main-effect QTLs and 14 of the epistatic interactions. Collectively, the epistatic effects and QTL by year interactions accounted for large proportions of the phenotypic variations. The results also showed that most of the stay-green traits were negatively correlated with yield and its component traits. The implications of the results in crop improvement were discussed.

Chromosome Mapping↗

PubMed2006

The impact of diabetes mellitus on cognitive decline in the oldest of the old: a prospective population-based study.

AIMS/HYPOTHESIS: Diabetes mellitus is a risk factor for the development of cognitive impairment and dementia in the general population up to 75 years of age. As part of the Leiden 85-plus Study we studied the effects of diabetes on cognition in the oldest old. SUBJECTS AND METHODS: The Leiden 85-plus Study is a prospective population-based study of 599 persons from age 85 onward. Cognitive function was assessed each year from ages 85 to 90 by means of four neuropsychological tests. The presence of diabetes and vascular disease was recorded at baseline, HbA(1c) was assessed by means of a blood sample at ages 85 and 90. The cross-sectional and prospective associations between diabetes and cognitive function were analysed with linear mixed models, adjusted for sex and level of education. RESULTS: At age 85, diabetes was associated with a lower level of cognitive functioning on the Letter Digit Coding test and the Stroop Test. Diabetes was not associated with accelerated cognitive decline during follow-up. Within the group of diabetic patients, macrovascular disease was the most important determinant of cognitive dysfunction. CONCLUSIONS/INTERPRETATION: The association between diabetes and accelerated cognitive decline, which has been documented previously in patients up to 75 years of age, may be less evident after age 85. This suggests that the damage occurs in previous years and that therapies aimed at preventing cognitive decline and dementia should focus on the younger old.

Aged, 80 and over↗

PubMed2026

Delayed maturation of the milk microbiome in women with type 1 diabetes.

AIMS/HYPOTHESIS: The breastmilk microbiome plays a crucial role in gut microbial colonisation and immune development, but little is known about how it is influenced by type 1 diabetes. METHODS: We conducted a longitudinal 16S rRNA gene sequencing study of milk from women with type 1 diabetes (n=69 pregnancies; 174 samples) and women who did not have type 1 diabetes (n=49 pregnancies; 123 samples), collected at seven timepoints from birth to 15 months postpartum. Alpha diversity (richness, inverse Simpson evenness) was analysed by generalised linear mixed models, beta diversity was analysed by Bray-Curtis dissimilarities and PERMANOVA, and differential abundance was analysed by limma. Additionally, we examined associations with maternal genetic risk score (GRS), maternal HLA type, glycaemic management (HbA1c) and breastmilk secretory IgA (sIgA), and performed a parallel analysis for the infant stool microbiome. RESULTS: A significant interaction between type 1 diabetes status and timepoint was observed for alpha diversity, both richness (p=0.01) and inverse Simpson diversity (p=0.003), indicating distinct temporal trajectories between women with and without type 1 diabetes. In those without type 1 diabetes, richness increased significantly between birth and 1 week postpartum, but this early increase was delayed in women with type 1 diabetes to between 1 week and 3 months postpartum (p=0.002). Beta diversity analysis revealed earlier and more extensive compositional shifts in women without type 1 diabetes compared to those with type 1 diabetes. These differences persisted after adjusting for Caesarean delivery, BMI, parity and infant sex, and were not attributable to a delay in initiating breastfeeding. Taxa with delayed enrichment in women with type 1 diabetes included Streptococcus spp. and Rothia mucilaginosa, which metabolise human milk oligosaccharides to short-chain fatty acids to promote development of the infant's gut barrier and immune system. Maternal GRS, HLA, HbA1c or sIgA were not associated with milk microbiota diversity trajectories. In infant stool samples, alpha diversity did not differ between exposure groups, and showed no evidence of delayed maturation. Beta diversity revealed an early compositional shift between birth and 1 week postpartum only in infants born to women without type 1 diabetes. Similarly, significant taxonomic changes between birth and 1 week postpartum were detected only in infants born to women without type 1 diabetes, but with some taxa differing between exposure groups at 1 week. CONCLUSIONS/INTERPRETATION: Maternal type 1 diabetes is associated with delayed early maturation of the breastmilk microbiome. Early compositional differences in microbiota restructuring were also observed in the infant gut, partially mirroring the pattern in the milk microbiome; however, sustained differences in infant gut microbiota diversity were not detected. Further investigation could determine whether these changes affect development of the infant's gut and immune system.

Humans↗

PubMed2006

Irritative effects of fumes and aerosols of bitumen on the airways: results of a cross-shift study.

Possible health hazards of fumes and aerosols of bitumen are in discussion, and data on their adverse effects on human airways under current exposure conditions are limited. To assess the irritative effects of exposure to fumes and aerosols of bitumen on the airways, a cross-sectional cross-shift study was conducted including external and internal exposure measurements, spirometry and especially non-invasive methods like nasal lavage collection and induction of sputum in order to identify and evaluate more precisely inflammatory process in the upper and lower airways. The cross-shift study comprised 74 mastic asphalt workers who were exposed to fumes and aerosols of bitumen and 49 construction workers without this exposure as reference group. Questionnaire, spirometry, ambient monitoring and urinary analysis were performed. Humoral and cellular parameters were measured in nasal lavage fluid (NALF) and induced sputum. For data analysis, a mixed linear model was performed on the different outcomes with exposure group, time of measurement (pre-, post-shift), current smoking, German nationality and age as fixed factors and subjects as random factor. Based on personal exposure measurements during shift, mastic asphalt workers were classified into a low (< or =10 mg/m(3); n = 46) and a high (>10 mg/m(3); n = 28) exposure group. High exposure was accompanied by significant higher urinary post-shift concentrations of 1-hydroxypyrene and the sum of hydroxyphenanthrenes. Acute respiratory symptoms were reported more frequently in the high exposure group after shift. Significant cross-shift declines in lung function parameters (forced expiratory volume in 1 s [FEV(1) (% predicted)] and forced vital capacity [FVC (% predicted)]) were measured in mastic asphalt workers. Pre-shift FEV(1) (% predicted) and FVC (% predicted) were higher in the low exposure group. In pre- and post-shift NALF samples, interleukin (IL)-1beta-, IL-8- and total protein concentrations were lower in the low exposure group compared to the reference and the high exposure group. Pre- and post-shift neutrophil percentages in both nasal and sputum samples were also lower in the low exposure group. Significantly higher pre- and post-shift sputum concentrations of IL-8, IL-6, nitrogen oxide (NO) derivatives and total protein were detected especially in highly exposed workers. Irritative effects of exposure to fumes and aerosols of bitumen on the upper and lower airways were apparent, especially in mastic asphalt workers with exposure above 10 mg/m(3).

Adult↗

PubMed2004

Influence of fluoxetine on positive and negative affect in a clinic-based smoking cessation trial.

RATIONALE: Fluoxetine improves affect in clinical syndromes such as depression and premenstrual dysphoric disorder. Little is known about fluoxetine's influence on mood changes after quitting smoking, which often resemble sub-clinical depression. OBJECTIVES: The present study, a re-analysis of previously published data (Niaura et al. 2002), examined fluoxetine's effect on changes in negative and positive affect following quitting smoking. METHODS: Adult smokers (n=175) without clinically significant depression were randomized on a double-blind basis to receive fluoxetine hydrochloride (30 or 60 mg daily) or placebo for 10 weeks in combination with cognitive-behavioral therapy (CBT) for smoking cessation. We postulated that fluoxetine would beneficially influence post-cessation changes in positive and negative affect. RESULTS: Mood change across treatment was analyzed using mixed linear modeling controlling for initial level of nicotine dependence, plasma fluoxetine metabolites, and change in cotinine (a nicotine metabolite) at each visit. Relative to placebo, those on 60 mg fluoxetine experienced an elevation in positive affect that increased across time [t(526)=2.50, P=0.01], and a reduction in negative affect that returned to baseline across time [t(524)=2.26, P=0.02]. There were no differences between 30 mg and placebo on changes in positive or negative affect. CONCLUSIONS: Results indicate that 60 mg of fluoxetine improves both positive and negative mood states after quitting smoking and that diminished positive affect may be an overlooked affective response to smoking cessation.

Adult↗

PubMed2026

Ossification variants of the distal femoral condyle: longitudinal 3 T MRI evidence of progression to juvenile osteochondritis dissecans in asymptomatic siblings of patients with JOCD.

OBJECTIVE: Ossification variants (OVs) of the femoral condyles are traditionally regarded as benign developmental findings distinct from juvenile osteochondritis dissecans (JOCD). We aimed to characterize the longitudinal MRI behavior of OVs and JOCD lesions in asymptomatic siblings of JOCD patients. MATERIALS AND METHODS: In this HIPAA-compliant longitudinal pilot study, seven asymptomatic siblings of JOCD patients underwent serial 3 T bilateral knee MRI. Two fellowship-trained musculoskeletal radiologists independently assessed 56 studies for bone marrow edema, lesion location, and MRI-defined category (OV or JOCD). RESULTS: OV and MRI-defined JOCD lesions were identified in 21 of 28 condyles (75%, 95% CI: 56.6-87.3%), while 7 condyles (25%, 95% CI: 12.7-43.4%) remained normal throughout follow-up. Six condyles demonstrated MRI-defined JOCD lesions at one or more timepoints. Three OV lesions evolved over time: two progressed to MRI-defined JOCD but remained clinically silent, and one progressed from OV to MRI-defined JOCD and subsequently to clinically manifest JOCD requiring surgery. Using Generalized Linear Mixed model, a statistically significant association was found between bone marrow edema and MRI-defined category (F = 31.73, p < 0.001). OV lesions showed absent or trace edema, whereas JOCD showed definite edema. Inter-reader agreement using Cohen's Kappa was moderate to substantial between the radiologists (κ = 0.479-0.739, 95% CI: 0.314-0.633, 0.644-0.845, p < 0.001). CONCLUSIONS: In siblings of patients with JOCD, OV lesions are common and may represent dynamic MRI phenotypes along a continuum of epiphyseal ossification abnormalities, with occasional progression to MRI-defined JOCD and rare progression to clinically manifest JOCD.

Humans↗

PubMed2005

Quantitative trait mapping in a diallel cross of recombinant inbred lines.

A recombinant inbred intercross (RIX) is created by generating diallel F1 progeny from one or more panels of recombinant inbred (RI) strains. This design was originally introduced to extend the power of small RI panels for the confirmation of quantitative trait loci (QTL) provisionally detected in a parental RI set. For example, the set of 13 C x B (C57BL/6ByJ x BALB/cByJ) RI strains can, in principle, be supplemented with 156 isogenic F1s. We describe and test a method of analysis, based on a linear mixed model, that accounts for the correlation structure of RIX populations. This model suggests a novel permutation algorithm that is needed to obtain appropriate threshold values for genome-wide scans of an RIX population. Despite the combinational multiplication of unique genotypes that can be generated using an RIX design, the effective sample size of the RIX population is limited by the number of progenitor RI genomes that are combined. When using small RI panels such as the C x B there appears to be only modest advantage of the RIX design when compared with the original RI panel for detecting QTLs with additive effects. The RIX, however, does have an inherent ability to detect dominance effects, and, unlike RI strains, the RIX progeny are genetically reproducible but are not fully inbred, providing somewhat more natural genetic context. We suggest a breeding strategy, the balanced partial RIX, that balances the advantage of RI and RIX designs. This involves the use of a partial RIX population derived from a large RI panel in which the available information is maximized by minimizing correlations among RIX progeny.

Animals↗

PubMed2005

Ventilatory changes following head-up tilt and standing in healthy subjects.

Passive tilting increases ventilation in healthy subjects; however, controversy surrounds the proposed mechanism. This study is aimed to evaluate the possible mechanism for changes to ventilation following passive head-up tilt (HUT) and active standing by comparison of a range of ventilatory, metabolic and mechanical parameters. Ventilatory parameters (V (T), V (E), V (E)/VO(2), V (E)/VCO(2), f and PetCO(2)), functional residual capacity (FRC), respiratory mechanics with impulse oscillometry; oxygen consumption (VO(2)) and carbon dioxide production (VCO(2)) were measured in 20 healthy male subjects whilst supine, following HUT to 70 degrees and unsupported standing. Data were analysed using a linear mixed model. HUT to 70 degrees from supine increased minute ventilation (V (E)) (P<0.001), tidal volume (V (T)) (P=0.001), ventilatory equivalent for O(2) (V (E)/VO(2)) (P=0.020) and the ventilatory equivalent for CO(2) (V (E)/VCO(2)) (P<0.001) with no change in f (P=0.488). HUT also increased FRC (P<0.001) and respiratory system reactance (X5Hz) (P<0.001) with reduced respiratory system resistance (R5Hz) (P=0.004) and end-tidal carbon dioxide (PetCO(2)) (P<0.001) compared to supine. Standing increased V (E) (P<0.001), V (T) (P<0.001) and V (E)/VCO(2) (P=0.020) with no change in respiratory rate (f) (P=0.065), V (E)/VO(2) (P=0.543). Similar changes in FRC (P<0.001), R5Hz (P=0.013), X5Hz (P<0.001) and PetCO(2) (P<0.001) compared to HUT were found. In contrast to HUT, standing increased VO(2) (P=0.002) and VCO(2) (P=0.048). The greater increase in V (E) in standing compared to HUT appears to be related to increased VO(2) and VCO(2) associated with increased muscle activity in the unsupported standing position. This has implications for exercise prescription and rehabilitation of critically ill patients who have reduced cardiovascular and respiratory reserve.

Adult↗

PubMed2003

Source partitioning using stable isotopes: coping with too many sources.

Stable isotopes are increasingly being used as tracers in environmental studies. One application is to use isotopic ratios to quantitatively determine the proportional contribution of several sources to a mixture, such as the proportion of various pollution sources in a waste stream. In general, the proportional contributions of n+1 different sources can be uniquely determined by the use of n different isotope system tracers (e.g., delta13C, delta15N, delta18O) with linear mixing models based on mass balance equations. Often, however, the number of potential sources exceeds n+1, which prevents finding a unique solution of source proportions. What can be done in these situations? While no definitive solution exists, we propose a method that is informative in determining bounds for the contributions of each source. In this method, all possible combinations of each source contribution (0-100%) are examined in small increments (e.g., 1%). Combinations that sum to the observed mixture isotopic signatures within a small tolerance (e.g., +/-0.1 per thousand ) are considered to be feasible solutions, from which the frequency and range of potential source contributions can be determined. To avoid misrepresenting the results, users of this procedure should report the distribution of feasible solutions rather than focusing on a single value such as the mean. We applied this method to a variety of environmental studies in which stable isotope tracers were used to quantify the relative magnitude of multiple sources, including (1) plant water use, (2) geochemistry, (3) air pollution, and (4) dietary analysis. This method gives the range of isotopically determined source contributions; additional non-isotopic constraints specific to each study may be used to further restrict this range. The breadth of the isotopically determined ranges depends on the geometry of the mixing space and the similarity of source and mixture isotopic signatures. A sensitivity analysis indicated that the estimated ranges vary only modestly with different choices of source increment and mass balance tolerance parameter values. A computer program (IsoSource) to perform these calculations for user-specified data is available at http://www.epa.gov/wed/pages/models.htm.

Carbon Isotopes↗

PubMed2005

A prospective study of serum ghrelin levels in patients treated with clozapine.

We investigated serum ghrelin levels (SGL) in 12 patients with schizophrenia over a 10-week period after initiation of clozapine treatment. In contrast to increments of body mass indices (BMI, kg/m2) and serum leptin levels (SLL), no significant change in SGL was detected. Inverse correlations between delta SGL and delta SLL did not reach statistical significance. Linear mixed model analysis could not detect effects of age, sex, BMI, SLL and serum clozapine levels on SGL. Our results do not support a causal involvement of ghrelin in clozapine-related weight gain.

Adult↗

PubMed2001

Tactile threshold and pressure pain threshold during treatment of orofacial pain: an explorative study.

The aim of the present study was to evaluate the pressure pain threshold (PPT), tactile threshold (TT) and pain intensity as measured on a Visual Analogue Scale (VAS) in patients with pain in the orofacial region. Twenty-six patients with myogenous pain (7 ss), myogenous and capsular pain (11 ss) or neuropathic pain (8 ss) participated in the study. At baseline, the PPT was evaluated using an algometer and the TT using von Frey hairs. In addition, the pain intensity was rated on a VAS scale and the psychological profile made using the SCL-90 questionnaire. In some of the patients, the measurement procedure was conducted I week later, immediately before active treatment started. As active treatment, patients with myogenous or capsular pain received physical therapy in addition to conscious relaxation of the masticatory system, while patients with neuropathic pain were treated using tricyclic antidepressant medication. After 4 to 6 weeks, the measurements were repeated. Statistical evaluation using a linear mixed model revealed no significant changes in TT. In patients with myogenous and capsular pain, as well as in patients with neuropathic pain, the PPT increased after active treatment, while it decreased in the group with pure myogenous pain. The VAS score decreased in all groups. Regarding psychological profiles, a variety of characteristics were observed and the scale for sleeping problems was especially elevated in a majority of the patients.

Adult↗

PubMed2006

Postal workers' occupational and leisure-time sun safety behaviors (United States).

OBJECTIVES: United States Postal Service letter carriers are exposed to long bouts of UVR and thus are vulnerable to skin cancer. While previous studies have shown that occupational sun protection is often deficient, few studies have examined outdoor workers' behavior during leisure time. METHODS: Subjects (n = 2,660) self-reported widebrim hat and sunscreen use over the past five workdays and past two non-working days using Likert-type scales. Generalized linear mixed models and generalized estimating equations were used to compare hat and sunscreen rates and predictors during occupational and leisure time. RESULTS: On average, carriers spent 3.9 h outside during workdays and 3.3 h during non-working days. Sunscreen and widebrim hat use during the workday is low and rates of use are significantly lower during non-working days. CONCLUSIONS: Sun safety interventions for carriers should encourage sun protection at all times when outdoors.

Adult↗

PubMed2006

Geographic patterns of advanced breast cancer in Los Angeles: associations with biological and sociodemographic factors (United States).

OBJECTIVE: Examination of patterns of advanced breast cancer may provide evidence needed to direct health care resources to those communities or population groups in greatest need. We assessed to what degree biologic, ethnic, and sociodemographic factors could explain such patterns within Los Angeles County. METHODS: The proportion of cases of advanced disease among all breast cancer cases identified during 1992-1996 were analyzed using generalized linear mixed models with random census tract effects. Models included characteristics of the individual and her tumor, census tract of residence, and aggregated health districts. RESULTS: Approximately 6% of cases, ranging from 4% for Asian to 10% for Black women, were diagnosed as advanced, exhibiting striking geographic patterns. Tumor histology and hormone receptor status were most predictive of advanced disease. Sociodemographic variables such as marital status, median income, and distance to nearest mammography unit showed additional association with risk. CONCLUSIONS: These models explain most of the geographical patterns and eliminate differences between White and Hispanic but not Asian or Black women, identify subpopulations at high risk of advanced disease, and suggest cancer control opportunities.

Adult↗

PubMed2026

Incidence of Cirrhosis in Fibrotic Metabolic Dysfunction-Associated Steatohepatitis: A Meta-Analysis of Placebo Arms from Randomized Clinical Trials.

BACKGROUNDS AND AIMS: Metabolic dysfunction-associated steatohepatitis (MASH) with stage F2-F3 fibrosis represents the main target population for emerging pharmacotherapies. However, data on short-term progression to cirrhosis (F4) in this group remain limited. We aimed to evaluate the incidence of cirrhosis in placebo-treated patients with fibrotic MASH in randomized controlled trials (RCTs). METHODS: In this single-arm meta-analysis, we systematically searched PubMed and Cochrane Library from inception to December 13, 2024, for pharmacological Phase ≥ 2 RCTs reporting cirrhosis events (detected in liver biopsy or clinical signs) among patients with fibrotic MASH receiving placebo. Incidence rates were pooled using generalized linear mixed models with Clopper-Pearson confidence intervals (CIs). RESULTS: We identified a total of 11 RCTs, including 586 patients with fibrotic MASH. Total follow-up was 657.23 person-years (PYs), with 83 cirrhosis events reported. The pooled incidence rate was 13.09 per 100 PYs (95% CI 7.81 to 21.12, I2 = 75.6%, τ2 = 0.682). In subgroup analysis, the incidence of cirrhosis was 3.40 per 100 PYs in MASH F2 (95% CI 1.10 to 10.02, I2 = 0%, τ2 = 0) and 17.90 per 100 PYs (95% CI 10.63 to 28.55, I2 = 70.2%, τ2 = 0.561) in MASH F3, with significant differences between stages (p = 0.006). Sensitivity analyses showed consistent estimates. Most RCTs were judged to have a low risk of bias. CONCLUSIONS: This study provides stage-specific data on cirrhosis incidence in fibrotic MASH, highlighting the high short-term risk associated with MASH F3 in trial settings. These data may inform benchmarks to guide event expectations, enrichment strategies, sample size assumptions, and the interpretation of future MASH clinical trials.

Humans↗