Genome-wide Rules of Nucleosome Phasing in Drosophila.

Regular successions of positioned nucleosomes, or phased nucleosome arrays (PNAs), are predominantly known from transcriptional start sites (TSSs). It is unclear whether PNAs occur elsewhere in the genome. To generate a comprehensive inventory of PNAs for Drosophila, we applied spectral analysis to nucleosome maps and identified thousands of PNAs throughout the genome. About half of them are not near TSSs and are strongly enriched for an uncharacterized sequence motif. Through genome-wide reconstitution of physiological chromatin in Drosophila embryo extracts, we uncovered the molecular basis of PNA formation. We identified Phaser, an unstudied zinc finger protein that positions nucleosomes flanking the motif. It also revealed how the global activity of the chromatin remodelers CHRAC/ACF, together with local barrier elements, generates islands of regular phasing throughout the genome. Our work demonstrates the potential of chromatin assembly by embryo extracts as a powerful tool to reconstitute chromatin features on a global scale in vitro.

Integrated sentence-level speech perception evokes strengthened language networks and facilitates early speech development.

Natural poetic speeches (i.e., proverbs, nursery rhymes, and commercial ads) with strong prosodic regularities are easily memorized by children and the harmonious acoustic patterns are suggested to facilitate their integrated sentence processing. Do children have specific neural pathways for perceiving such poetic utterances, and does their speech development benefit from it? We recorded the task-induced hemodynamic changes of 94 children aged 2 to 12 years using functional near-infrared spectroscopy (fNIRS) while they listened to poetic and non-poetic natural sentences. Seventy-three adult as controls were recruited to investigate the developmental specificity of children group. The results indicated that poetic sentences perceiving is a highly integrated process featured by a lower brain workload in both groups. However, an early activated large-scale network was induced only in the child group, coordinated by hubs for connectivity diversity. Additionally, poetic speeches evoked activation in the phonological encoding regions in the children's group rather than adult controls which decreases with children's ages. The neural responses to poetic speeches were positively linked to children's speech communication performance, especially the fluency and semantic aspects. These results reveal children's neural sensitivity to integrated speech perception which facilitate early speech development by strengthening more sophisticated language networks and the perception-production circuit.

Is attention necessary for the representational advantage of good exemplars over bad exemplars?

Real-world (rw-) statistical regularities, or expectations about the visual world learned over a lifetime, have been found to be associated with scene perception efficiency. For example, good (i.e., highly representative) exemplars of basic scene categories, one example of an rw-statistical regularity, are detected more readily than bad exemplars of the category. Similarly, good exemplars achieve higher multivariate pattern analysis (MVPA) classification accuracy than bad exemplars in scene-responsive regions of interest, particularly in the parahippocampal place area (PPA). However, it is unclear whether the good exemplar advantages observed depend on or are even confounded by selective attention. Here, we ask whether the observed neural advantage of the good scene exemplars requires full attention. We used a dual-task paradigm to manipulate attention and exemplar representativeness while recording neural responses with functional magnetic resonance imaging (fMRI). Both univariate analysis and MVPA were adopted to examine the effect of representativeness. In the attend-to-scenes condition, our results replicated an earlier study showing that good exemplars evoke less activity but a clearer category representation than bad exemplars. Importantly, similar advantages of the good exemplars were also observed when participants were distracted by a serial visual search task demanding a high attention load. In addition, cross-decoding between attended and distracted representations revealed that attention resulted in a quantitative (increased activation) rather than qualitative (altered activity patterns) improvement of the category representation, particularly for good exemplars. We, therefore, conclude that the effect of category representativeness on neural representations does not require full attention.

Honey Added to Yogurt with Bifidobacterium animalis subsp. lactis DN-173 010/CNCM I-2494 Supports Probiotic Enrichment but Does Not Reduce Intestinal Transit Time in Healthy Adults: A Randomized, Controlled, Crossover Trial.

BACKGROUND: Honey improves probiotic survival in vitro. However, if this effect translates to humans has not been investigated. OBJECTIVES: We aimed to determine effects of honey plus yogurt containing the probiotic Bifidobacterium animalis subsp. lactis DN-173 010/CNCM I-2494 (B. animalis) on intestinal transit time, probiotic enrichment, digestive health, mood, and cognition in adults. METHODS: Sixty-six healthy adults (34 female; 33.6 ± 9.8 y; 24.6 ± 3.0 kg/m2) in a crossover trial were randomly assigned to 2-wk yogurt conditions in a counterbalanced order with ≥4-wk washout: 1) Honey (HON): yogurt plus honey and 2) Negative Control (NC): heat-treated yogurt plus sugar. Of the participants, n = 62 completed the trial, and n = 37 (17 female; 32.0 ± 8.3 y; 25.0 ± 2.9 kg/m2) elected to enroll in a third condition (a nonrandomized study extension) after ≥4-wk washout with a reference Positive Control (PC): yogurt plus sugar. At baseline and end of each of the 3 conditions, intestinal transit time was measured with dye capsules; probiotic abundance with fecal DNA 16S sequencing; digestive health with symptom/function records, Bristol stool consistency, Gastrointestinal Tolerability, and Gastrointestinal Quality of Life Index; mood with Positive and Negative Affect Schedule-Short Form, Depression Anxiety Stress Scales-42, Patient-Reported Outcomes Measurement Information System questionnaires, and an emotional image task; and cognition with a spatial reconstruction task. Data were analyzed using linear mixed-effects models (LMMs) with significance at P ≤ 0.05. Baseline and end data were included in the LMM, with fixed effects being treatment, time, treatment by time interaction, and baseline covariate, and the random effect being the participant. RESULTS: B. animalis was enriched in HON (d = 3.54; P = 0.0002) compared to controls with linear discriminant analysis effect size. Intestinal transit time, gastrointestinal health, mood, and cognition did not differ between conditions (LMM: Ps > 0.05). CONCLUSIONS: Yogurt + honey enriched B. animalis but did not reduce intestinal transit time or have other functional gastrointestinal, mood, or cognitive effects in adults. This trial was registered at www. CLINICALTRIALS: gov as NCT04187950 and NCT04901390.

A variational approach to frame-indifferent quasistatic viscoelasticity of rate type.

The three-dimensional dynamical model for nonlinear viscoelasticity of strain-rate type is investigated in a quasistatic setting under the assumption of higher-order regularity of the deformation, which in the literature is referred to as the case of non-simple materials. The existence of weak solutions is proven using a time-discretization technique while respecting the condition of dynamical frame indifference. Some observations on frame indifference for strain-rate-type stresses are made, and corrections are proposed for some related work in the literature. Finally, a counterexample is given to show that the assumed higher-order regularity is necessary in order to obtain the required compactness.This article is part of the theme issue 'Non-smooth variational problems with applications in mechanics'.

Cortex2vector: anatomical embedding of cortical folding patterns.

Current brain mapping methods highly depend on the regularity, or commonality, of anatomical structure, by forcing the same atlas to be matched to different brains. As a result, individualized structural information can be overlooked. Recently, we conceptualized a new type of cortical folding pattern called the 3-hinge gyrus (3HG), which is defined as the conjunction of gyri coming from three directions. Many studies have confirmed that 3HGs are not only widely existing on different brains, but also possess both common and individual patterns. In this work, we put further effort, based on the identified 3HGs, to establish the correspondences of individual 3HGs. We developed a learning-based embedding framework to encode individual cortical folding patterns into a group of anatomically meaningful embedding vectors (cortex2vector). Each 3HG can be represented as a combination of these embedding vectors via a set of individual specific combining coefficients. In this way, the regularity of folding pattern is encoded into the embedding vectors, while the individual variations are preserved by the multi-hop combination coefficients. Results show that the learned embeddings can simultaneously encode the commonality and individuality of cortical folding patterns, as well as robustly infer the complicated many-to-many anatomical correspondences among different brains.

Optimizing targeting strategies for lithotripsy through in-vitro and in vivo studies with consideration of respiratory regularity.

BACKGROUND: This work aimed to identify a method to achieve improved stone targeting and safety in shockwave lithotripsy by accounting for respiration. METHODS: We set up an electromotive device simulating renal movement during respiration to place artificial stones within the phantom gel, measuring stone weight changes before and after shockwave exposure and the cavitation damage. We conducted clinical trials using respiratory masks and sensors to monitor and analyze patient respiration during shockwave lithotripsy. RESULTS: The in vitro efficiency of lithotripsy was higher when adjusted for respiration than when respiration was not adjusted for. Slow respiration showed the best efficiency with higher hit rates when not adjusted for respiration. Cavitation damage was also lowest during slow respiration. The clinical study included 52 patients. Respiratory regularity was maintained above 90% in regular respiration. When respiration was regular, the lithotripsy rate was about 65.6%, which stayed at about 40% when respiration was irregular. During the lithotripsy, the participants experienced various events, such as sleep, taking off their masks, talking, movement, coughing, pain, nervousness, and hyperventilation. The generation of shockwaves based on respiratory regularity could reduce pain in patients. CONCLUSION: These results suggest a more accurate lithotripsy should be performed according to respiratory regularity.

Playing hide and seek: Contextual regularity learning develops between 3 and 5 years of age.

The ability to acquire contextual regularities is fundamental in everyday life because it helps us to navigate the environment, directing our attention where relevant events are more likely to occur. Sensitivity to spatial regularities has been largely reported from infancy. Nevertheless, it is currently unclear when children can use this rapidly acquired contextual knowledge to guide their behavior. Evidence of this ability is indeed mixed in school-aged children and, to date, it has never been explored in younger children and toddlers. The current study investigated the development of contextual regularity learning in children aged 3 to 5 years. To this aim, we designed a new contextual learning paradigm in which young children were presented with recurring configurations of bushes and were asked to guess behind which bush a cartoon monkey was hiding. In a series of two experiments, we manipulated the relevance of color and visuospatial cues for the underlying task goal and tested how this affected young children's behavior. Our results bridge the gap between the infant and adult literatures, showing that sensitivity to spatial configurations persists from infancy to childhood, but it is only around the fifth year of life that children naturally start to integrate multiple cues to guide their behavior.

The Agreement between Wearable Sensors and Force Plates for the Analysis of Stride Time Variability.

The variability and regularity of stride time may help identify individuals at a greater risk of injury during military load carriage. Wearable sensors could provide a cost-effective, portable solution for recording these measures, but establishing their validity is necessary. This study aimed to determine the agreement of several measures of stride time variability across five wearable sensors (Opal APDM, Vicon Blue Trident, Axivity, Plantiga, Xsens DOT) and force plates during military load carriage. Nineteen Australian Army trainee soldiers (age: 24.8 ± 5.3 years, height: 1.77 ± 0.09 m, body mass: 79.5 ± 15.2 kg, service: 1.7 ± 1.7 years) completed three 12-min walking trials on an instrumented treadmill at 5.5 km/h, carrying 23 kg of an external load. Simultaneously, 512 stride time intervals were identified from treadmill-embedded force plates and each sensor where linear (standard deviation and coefficient of variation) and non-linear (detrended fluctuation analysis and sample entropy) measures were obtained. Sensor and force plate agreement was evaluated using Pearson's r and intraclass correlation coefficients. All sensors had at least moderate agreement (ICC > 0.5) and a strong positive correlation (r > 0.5). These results suggest wearable devices could be employed to quantify linear and non-linear measures of stride time variability during military load carriage.

Sample Entropy Improves Assessment of Postural Control in Early-Stage Multiple Sclerosis.

Postural impairment in people with multiple sclerosis (pwMS) is an early indicator of disease progression. Common measures of disease assessment are not sensitive to early-stage MS. Sample entropy (SE) may better identify early impairments. We compared the sensitivity and specificity of SE with linear measurements, differentiating pwMS (EDSS 0-4) from healthy controls (HC). 58 pwMS (EDSS ≤ 4) and 23 HC performed quiet standing tasks, combining a hard or foam surface with eyes open or eyes closed as a condition. Sway was recorded at the sternum and lumbar spine. Linear measures, mediolateral acceleration range with eyes open, mediolateral jerk with eyes closed, and SE in the anteroposterior and mediolateral directions were calculated. A multivariate ANOVA and AUC-ROC were used to determine between-groups differences and discriminative ability, respectively. Mild MS (EDSS ≤ 2.0) discriminability was secondarily assessed. Significantly lower SE was observed under most conditions in pwMS compared to HC, except for lumbar and sternum SE when on a hard surface with eyes closed and in the anteroposterior direction, which also offered the strongest discriminability (AUC = 0.747), even for mild MS. Overall, between-groups differences were task-dependent, and SE (anteroposterior, hard surface, eyes closed) was the best pwMS classifier. SE may prove a useful tool to detect subtle MS progression and intervention effectiveness.

A Lifestyle Monitoring System for Older Adults Living Independently Using Low-Resolution Smart Meter Data.

BACKGROUND: Monitoring the lifestyles of older adults helps promote independent living and ensure their well-being. The common technologies for home monitoring include wearables, ambient sensors, and smart household meters. While wearables can be intrusive, ambient sensors require extra installation, and smart meters are becoming integral to smart city infrastructure. Research Gap: The previous studies primarily utilized high-resolution smart meter data by applying Non-Intrusive Appliance Load Monitoring (NIALM) techniques, leading to significant privacy concerns. Meanwhile, some Japanese power companies have successfully employed low-resolution data to monitor lifestyle patterns discreetly. SCOPE AND METHODOLOGY: This study develops a lifestyle monitoring system for older adults using low-resolution smart meter data, mapping electricity consumption to appliance usage. The power consumption data are collected at 15-min intervals, and the background power threshold distinguishes between the active and inactive periods (0/1). The system quantifies activity through an active score and assesses daily routines by comparing these scores against the long-term norms. Key Outcomes/Contributions: The findings reveal that low-resolution data can effectively monitor lifestyle patterns without compromising privacy. The active scores and regularity assessments calculated using correlation coefficients offer a comprehensive view of residents' daily activities and any deviations from the established patterns. This study contributes to the literature by validating the efficacy of low-resolution data in lifestyle monitoring systems and underscores the potential of smart meters in enhancing elderly people's care.

A multimodal cortical network of sensory expectation violation revealed by fMRI.

The brain is subjected to multi-modal sensory information in an environment governed by statistical dependencies. Mismatch responses (MMRs), classically recorded with EEG, have provided valuable insights into the brain's processing of regularities and the generation of corresponding sensory predictions. Only few studies allow for comparisons of MMRs across multiple modalities in a simultaneous sensory stream and their corresponding cross-modal context sensitivity remains unknown. Here, we used a tri-modal version of the roving stimulus paradigm in fMRI to elicit MMRs in the auditory, somatosensory and visual modality. Participants (N = 29) were simultaneously presented with sequences of low and high intensity stimuli in each of the three senses while actively observing the tri-modal input stream and occasionally reporting the intensity of the previous stimulus in a prompted modality. The sequences were based on a probabilistic model, defining transition probabilities such that, for each modality, stimuli were more likely to repeat (p = .825) than change (p = .175) and stimulus intensities were equiprobable (p = .5). Moreover, each transition was conditional on the configuration of the other two modalities comprising global (cross-modal) predictive properties of the sequences. We identified a shared mismatch network of modality general inferior frontal and temporo-parietal areas as well as sensory areas, where the connectivity (psychophysiological interaction) between these regions was modulated during mismatch processing. Further, we found deviant responses within the network to be modulated by local stimulus repetition, which suggests highly comparable processing of expectation violation across modalities. Moreover, hierarchically higher regions of the mismatch network in the temporo-parietal area around the intraparietal sulcus were identified to signal cross-modal expectation violation. With the consistency of MMRs across audition, somatosensation and vision, our study provides insights into a shared cortical network of uni- and multi-modal expectation violation in response to sequence regularities.

Ethnic/racial discrimination and academic grades among adolescents: moderation by sleep regularity.

This study investigates how sleep regularity moderates the association between ethnic/racial discrimination and academic grades among diverse adolescents. The study included a 14-day, daily diary and actigraphy study of ninth-grade adolescents in the United States (N = 265; mean [SD] age 15.26 [0.62] years, 41.51% Asian, 21.13% Black, 37.35% Latinx, 71.32% female) who completed measures of demographic information and ethnic/racial discrimination (Daily Life Experiences Racism and Bother subscale). Sleep data were collected for 14 consecutive days with wrist actigraphy, and sleep regularity was calculated using the Sleep Regularity Index (SRI). Academic grades were provided by the Department of Education. Discrimination frequency was associated with lower academic grades, and the SRI moderated this association. Compared to adolescents who had moderate and regular SRI profiles, adolescents with irregular SRI (i.e., lower sleep regularity) had stronger negative associations between discrimination and grades. On the other hand, for adolescents who had moderate to high sleep regularity, there was no significant association between discrimination and grades. This study underscores the importance of sleep regularity for adolescents' academic achievement.

Greater sleep variability is associated with higher systemic inflammation in type 2 diabetes.

Sleep irregularity and variability have been shown to be detrimental to cardiometabolic health. The present pilot study explored if higher day-to-day sleep irregularity and variability were associated with systemic inflammation, as assessed by high-sensitivity C-reactive protein, in type 2 diabetes. Thirty-five patients with type 2 diabetes (mean age 54.3 years, 54.3% female) who were not shift-workers participated. The presence of diabetic retinopathy was determined. The standard deviation of sleep duration and sleep midpoint across all recorded nights were used to quantify sleep variability and regularity, respectively, assessed by 14-day actigraphy. The presence and severity of sleep apnea were assessed using an overnight home monitor. Low-density lipoprotein, haemoglobin A1C and high-sensitivity C-reactive protein were collected. Multiple regression analysis using natural-log-transformed values was performed to establish an independent association between sleep variability and high-sensitivity C-reactive protein. Twenty-two (62.9%) patients had diabetic retinopathy. The median (interquartile range) of high-sensitivity C-reactive protein was 2.4 (1.4, 4.6) mg L-1 . Higher sleep variability was significantly associated with higher high-sensitivity C-reactive protein (r = 0.342, p = 0.044), as was haemoglobin A1C (r = 0.431, p = 0.010) and low-density lipoprotein (r = 0.379, p = 0.025), but not sleep regularity, sleep apnea severity or diabetic retinopathy. Multiple regression analysis showed that higher sleep variability (B = 0.907, p = 0.038) and higher HbA1c (B = 1.519, p = 0.035), but not low-density lipoprotein, contributed to higher high-sensitivity C-reactive protein. In conclusion, higher sleep variability in patients with type 2 diabetes who were not shift-workers was independently associated with higher systemic inflammation, conferring increased cardiovascular risk. Whether sleep interventions to reduce sleep variability can reduce systemic inflammation and improve cardiometabolic health should be investigated.

Sleep regularity in healthy adolescents: Associations with sleep duration, sleep quality, and mental health.

Current evidence points to the importance of sleep for adolescent physical and mental health. To date, most studies have examined the association between sleep duration/quality and health in adolescence. An emerging line of research suggests that regularity in the timing of sleep may also play an important role in well-being. To address this aspect of sleep, the present study investigated daily variability of sleep, quantified using the sleep regularity index (SRI), in 46 adolescents (M = 12.78 ± 1.07 years) and its association with depressive symptoms/mental health. Sleep was measured during a 6 month period (M = 133.11 ± 36.42 nights) using actigraphs to quantify SRI values calculated for school days, weekends and holidays. Depressive symptoms and general psychopathology were assessed at the beginning (baseline) and end (follow-up) of the actigraphy measurements. Sleep was most regular during school days and associated with a longer total sleep time, shorter sleep onset latency, and higher sleep efficiency. Moreover, a higher SRI on school days was associated with fewer depressive symptoms at follow-up, whereas higher SRI on weekends was associated with less overall psychopathology at follow-up. Furthermore, the change in overall psychopathology, but not depressive symptoms across the two assessments was correlated with sleep regularity index. Our results suggest that regular timing of sleep is associated with sleep that is of longer duration and higher quality and may be protective of adolescent mental health. Therefore, adolescents should be encouraged not only to get enough sleep, but also to retain regular sleeping patterns to promote well-being and mental health.

Elastic integrative analysis of randomised trial and real-world data for treatment heterogeneity estimation.

We propose a test-based elastic integrative analysis of the randomised trial and real-world data to estimate treatment effect heterogeneity with a vector of known effect modifiers. When the real-world data are not subject to bias, our approach combines the trial and real-world data for efficient estimation. Utilising the trial design, we construct a test to decide whether or not to use real-world data. We characterise the asymptotic distribution of the test-based estimator under local alternatives. We provide a data-adaptive procedure to select the test threshold that promises the smallest mean square error and an elastic confidence interval with a good finite-sample coverage property.

Statistical Analysis of Two-Compartment Pharmacokinetic Models with Drug Non-adherence.

Poor drug adherence is considered one of major barriers to achieving the clinical and public health benefits of many pharmacotherapies. In the current paper, we aim to investigate the impact of dose omission on the plasma concentrations of two-compartment pharmacokinetic models with two typical routes of drug administration, namely the intravenous bolus and extravascular first-order absorption. First, we reformulate the classical two-compartment pharmacokinetic models with a new stochastic feature, where a binomial random model of dose intake is integrated. Then, we formalize the explicit expressions of expectation and variance for trough concentrations and limit concentrations, with the latter proved of the existence and uniqueness for steady-state distribution. Moreover, we mathematically demonstrate the strict stationarity and ergodicity of trough concentrations as a Markov chain. In addition, we numerically simulate the impact of drug non-adherence to different extents on the variability and regularity of drug concentration and compare the drug pharmacokinetic preference between one and two compartment pharmacokinetic models. The results of sensitivity analysis also suggest the drug non-adherence as one of the most sensitive model parameters to the expectation of limit concentration. Our modelling and analytical approach can be integrated into the chronic disease models to estimate or quantitatively predict the therapy efficacy with drug pharmacokinetics presumably affected by random dose omissions.

The effect of sodium hyaluronate on tear film stability in patients with dry eye syndrome after cataract surgery.

BACKGROUND: This study aimed to observe the changes in the ocular surface after phacoemulsification in patients with age-related cataracts with respect to the addition of varying concentrations of hyaluronate. METHODS: Patients with dry eye syndrome were treated with 0.3% and 0.1% sodium hyaluronate eye drops to evaluate the clinical improvement in each treatment group. A total of 73 patients (91 eyes) with age-related cataracts suffering from dry eye syndrome after phacoemulsification were divided into treatment group A (30 eyes), undergoing conventional therapy and treatment with 0.3% sodium hyaluronate; treatment group B (31 eyes), undergoing conventional therapy and treatment with 0.1% sodium hyaluronate; and the control group (group C; 30 eyes), undergoing conventional therapy only. Two groups were given different concentrations of sodium hyaluronate eye drops four times a day (should be completed between 8 AM and 8 PM), one drop at a time. RESULTS: Seven days, 2 weeks, 1 month, and 2 months postoperatively, there were significant differences in the Schirmer I test (SIt), first noninvasive tear film break-up time (NIBUTf), average noninvasive tear film break-up time (NIBUTav), tear meniscus height (TMH), and irregularity (when the refractive force of different parts of different meridians on the same meridian is different. The main manifestation is that the two meridians on the anterior surface of the cornea do not show a 90-degree vertical distribution, which cannot be corrected by conventional astigmatism lenses) between the three groups (p < 0.05). When compared with group C, there were significant differences in the SIt, NIBUTf, NIBUTav, TMH, and irregularity of group A and group B (p < 0.05). When compared with group B, there were significant improvements in the SIt, NIBUTf, NIBUTav, and TMH in group A (p < 0.05). CONCLUSIONS: In the early stage after phacoemulsification, the stability of the tear film is reduced. Adding sodium hyaluronate eye drops can restore tear film structure and improve corneal surface regularity, and a 0.3% solution of sodium hyaluronate eye drops is more effective than a 0.1% solution.

Greater temporal regularity of primary care visits was associated with reduced hospitalizations and mortality, even after controlling for continuity of care.

BACKGROUND: Previous studies have shown that more temporally regular primary care visits are associated with improved patient outcomes. OBJECTIVE: To examine the association of temporal regularity (TR) of primary care with hospitalizations and mortality in patients with chronic illnesses. Also, to identify threshold values for TR for predicting outcomes. DESIGN: Retrospective cohort study. PARTICIPANTS: We used data from the electronic health record of a health maintenance organization in Israel to study primary care visits of 70,095 patients age 40 + with one of three chronic conditions (diabetes mellitus, heart failure, chronic obstructive pulmonary disease). MAIN MEASURES: We calculated TR for each patient during a two-year period (2016-2017), and divided patients into quintiles based on TR. Outcomes (hospitalization, death) were observed in 2018-2019. Covariates included the Bice-Boxerman continuity of care score, demographics, and comorbidities. We used multivariable logistic regression to examine TR's association with hospitalization and death, controlling for covariates. KEY RESULTS: Compared to patients receiving the most regular care, patients receiving less regular care had increased odds of hospitalization and mortality, with a dose-response curve observed across quintiles (p for linear trend < 0.001). For example, patients with the least regular care had an adjusted odds ratio of 1.40 for all-cause mortality, compared to patients with the most regular care. Analyses stratified by age, sex, ethnic group, area-level SES, and certain comorbid conditions did not show strong differential associations of TR across groups. CONCLUSIONS: We found an association between more temporally regular care in antecedent years and reduced hospitalization and mortality of patients with chronic illness in subsequent years, after controlling for covariates. There was no clear threshold value for temporal regularity; rather, more regular primary care appeared to be better across the entire range of the variable.

Patient-level predictors of temporal regularity of primary care visits.

BACKGROUND: Patients with chronic diseases should meet with their primary care doctor regularly to facilitate proactive care. Little is known about what factors are associated with more regular follow-up. METHODS: We studied 70,095 patients age 40 + with one of three chronic conditions (diabetes mellitus, heart failure, chronic obstructive pulmonary disease), cared for by Leumit Health Services, an Israeli health maintenance organization. Patients were divided into the quintile with the least temporally regular care (i.e., the most irregular intervals between visits) vs. the other four quintiles. We examined patient-level predictors of being in the least-temporally-regular quintile. We calculated the risk-adjusted regularity of care at 239 LHS clinics with at least 30 patients. For each clinic, compared the number of patients with the least temporally regular care with the number predicted to be in this group based on patient characteristics. RESULTS: Compared to older patients, younger patients (age 40-49), were more likely to be in the least-temporally-regular group. For example, age 70-79 had an adjusted odds ratio (AOR) of 0.82 compared to age 40-49 (p < 0.001 for all findings discussed here). Males were more likely to be in the least-regular group (AOR 1.18). Patients with previous myocardial infarction (AOR 1.07), atrial fibrillation (AOR 1.08), and current smokers (AOR 1.12) were more likely to have an irregular pattern of care. In contrast, patients with diabetes (AOR 0.79) or osteoporosis (AOR 0.86) were less likely to have an irregular pattern of care. Clinic-level number of patients with irregular care, compared with the predicted number, ranged from 0.36 (fewer patients with temporally irregular care) to 1.71 (more patients). CONCLUSIONS: Some patient characteristics are associated with more or less temporally regular patterns of primary care visits. Clinics vary widely on the number of patients with a temporally irregular pattern of care, after adjusting for patient characteristics. Health systems can use the patient-level model to identify patients at high risk for temporally irregular patterns of primary care. The next step is to examine which strategies are employed by clinics that achieve the most temporally regular care, since these strategies may be possible to emulate elsewhere.