A Machine Learning System to Indicate Diagnosis of Idiopathic Pulmonary Fibrosis Non-Invasively in Challenging Cases.

Radiologic usual interstitial pneumonia (UIP) patterns and concordant clinical characteristics define a diagnosis of idiopathic pulmonary fibrosis (IPF). However, limited expert access and high inter-clinician variability challenge early and pre-invasive diagnostic sensitivity and differentiation of IPF from other interstitial lung diseases (ILDs). We investigated a machine learning-driven software system, Fibresolve, to indicate IPF diagnosis in a heterogeneous group of 300 patients with interstitial lung disease work-up in a retrospective analysis of previously and prospectively collected registry data from two US clinical sites. Fibresolve analyzed cases at the initial pre-invasive assessment. An Expert Clinical Panel (ECP) and three panels of clinicians with varying experience analyzed the cases for comparison. Ground Truth was defined by separate multi-disciplinary discussion (MDD) with the benefit of surgical pathology results and follow-up. Fibresolve met both pre-specified co-primary endpoints of sensitivity superior to ECP and significantly greater specificity (p = 0.0007) than the non-inferior boundary of 80.0%. In the key subgroup of cases with thin-slice CT and atypical UIP patterns (n = 124), Fibresolve's diagnostic yield was 53.1% [CI: 41.3-64.9] (versus 0% pre-invasive clinician diagnostic yield in this group), and its specificity was 85.9% [CI: 76.7-92.6%]. Overall, Fibresolve was found to increase the sensitivity and diagnostic yield for IPF among cases of patients undergoing ILD work-up. These results demonstrate that in combination with standard clinical assessment, Fibresolve may serve as an adjunct in the diagnosis of IPF in a pre-invasive setting.

Leveraging electronic health records and knowledge networks for Alzheimer's disease prediction and sex-specific biological insights.

Identification of Alzheimer's disease (AD) onset risk can facilitate interventions before irreversible disease progression. We demonstrate that electronic health records from the University of California, San Francisco, followed by knowledge networks (for example, SPOKE) allow for (1) prediction of AD onset and (2) prioritization of biological hypotheses, and (3) contextualization of sex dimorphism. We trained random forest models and predicted AD onset on a cohort of 749 individuals with AD and 250,545 controls with a mean area under the receiver operating characteristic of 0.72 (7 years prior) to 0.81 (1 day prior). We further harnessed matched cohort models to identify conditions with predictive power before AD onset. Knowledge networks highlight shared genes between multiple top predictors and AD (for example, APOE, ACTB, IL6 and INS). Genetic colocalization analysis supports AD association with hyperlipidemia at the APOE locus, as well as a stronger female AD association with osteoporosis at a locus near MS4A6A. We therefore show how clinical data can be utilized for early AD prediction and identification of personalized biological hypotheses.

How older men live with stress urinary incontinence: Patient experience and navigation to treatment.

OBJECTIVES: To explore the context in which older men navigate treatment for stress urinary incontinence (SUI) following prostate surgery by characterizing lived experience of men with symptomatic SUI. SUBJECTS/PATIENTS AND METHODS: Mixed method study using surveys and semistructured interviews to examine a cohort of men who underwent evaluation for treatment of postprostatectomy SUI. RESULTS: Thirty-six men were interviewed after consultation for SUI and 31 had complete quantitative clinical data. Twenty-six underwent surgery and 10 chose no surgical intervention. In qualitative interviews, respondents experienced substantial decline in quality of life due to incontinence citing concerns associated with use of pads and worrying about incontinence. Most patients reported "workarounds"-efforts to mitigate or manage incontinence including Kegels, physical therapy, and garments. Participants also reported lifestyle changes including less strenuous physical activity, less sexual activity, and/or fewer social gatherings. Patients then described a "breaking point" where incontinence workarounds were no longer sufficient. After seeking evaluation, men described challenges in exploring treatment for SUI, including access to care and provider knowledge of treatment options. CONCLUSION: In a novel study of patients living with SUI a predictable lived experience was observed that culminated in a desire for change or "breaking point." In all men, this led to treatment-seeking behaviors and for many it led to SUI intervention. Despite effective treatments, patients continue to meet barriers gaining access to SUI evaluation and treatment.

Atopic Dermatitis and Cardiovascular Risk in Pediatric Patients: A Systematic Review and Meta-Analysis.

Cardiovascular guidelines recommend early screening and preventative treatment for children with chronic inflammatory diseases. Atopic dermatitis (AD) is associated with cardiovascular risk in adults, but data in children are limited. We systematically searched for studies that examined the association between childhood AD and cardiovascular risk factors and outcomes. Data from 10 publications, including 577,148 individuals, revealed an association between AD and ischemic heart disease (n = 3, OR = 1.68, 95% confidence interval [CI] = 1.29-2.19) and diabetes (n = 4, OR = 1.31, 95% CI = 1.12-1.53), but this did not persist among studies that adjusted for potential confounders (n = 2, OR = 0.98, 95% CI = 0.35-2.75). Similarly, there was an association with lipid disorders but not across the entire population distribution (n = 7, OR = 1.24, 95% CI = 1.13-1.36, 95% prediction interval = 0.95-1.61). AD was not associated with hypertension (n = 5, OR = 1.15, 95% CI = 0.98-1.34, 95% prediction interval = 0.81-1.62) or stroke (n = 2, OR = 1.24, 95% CI = 0.94-1.62). Studies lacked detail on AD severity and important confounders such as body mass index, and the certainty of evidence was very low to low on the basis of GRADE (Grading of Recommendations, Assessment, Development and Evaluation) assessments. Currently, data do not support a clinically meaningful increase in cardiovascular risk for children with AD.

Early-onset Alzheimer's disease explained by polygenic risk of late-onset disease?

Early-onset Alzheimer's disease (AD) is highly heritable, yet only 10% of cases are associated with known pathogenic mutations. For early-onset AD patients without an identified autosomal dominant cause, we hypothesized that their early-onset disease reflects further enrichment of the common risk-conferring single nucleotide polymorphisms associated with late-onset AD. We applied a previously validated polygenic hazard score for late-onset AD to 193 consecutive patients diagnosed at our tertiary dementia referral center with symptomatic early-onset AD. For comparison, we included 179 participants with late-onset AD and 70 healthy controls. Polygenic hazard scores were similar in early- versus late-onset AD. The polygenic hazard score was not associated with age-of-onset or disease biomarkers within early-onset AD. Early-onset AD does not represent an extreme enrichment of the common single nucleotide polymorphisms associated with late-onset AD. Further exploration of novel genetic risk factors of this highly heritable disease is warranted.Highlights: There is a unique genetic architecture of early- versus late-onset Alzheimer's disease (AD).Late-onset AD polygenic risk is not an explanation for early-onset AD.Polygenic risk of late-onset AD does not predict early-onset AD biology.Unique genetic architecture of early- versus late-onset AD parallels AD heterogeneity.

Racial Disparities in Emergency Department Physical Restraint Use: A Systematic Review and Meta-Analysis.

Importance: Recent studies have demonstrated that people of color are more likely to be restrained in emergency department (ED) settings compared with other patients, but many of these studies are based at a single site or health care system, limiting their generalizability. Objective: To synthesize existing literature on risk of physical restraint use in adult EDs, specifically in reference to patients of different racial and ethnic backgrounds. Data Sources: A systematic search of PubMed, Embase, Web of Science, and CINAHL was performed from database inception to February 8, 2022. Study Selection: Included peer-reviewed studies met 3 criteria: (1) published in English, (2) original human participants research performed in an adult ED, and (3) reported an outcome of physical restraint use by patient race or ethnicity. Studies were excluded if they were conducted outside of the US, or if full text was unavailable. Data Extraction and Synthesis: Four independent reviewers (V.E., M.M., D.D., and A.H.) abstracted data from selected articles following Meta-Analysis of Observational Studies in Epidemiology guidelines. A modified Newcastle-Ottawa scale was used to assess quality. A meta-analysis of restraint outcomes among minoritized racial and ethnic groups was performed using a random-effects model in 2022. Main Outcome(s) and Measure(s): Risk of physical restraint use in adult ED patients by racial and ethnic background. Results: The search yielded 1597 articles, of which 10 met inclusion criteria (0.63%). These studies represented 2 557 983 patient encounters and 24 030 events of physical restraint (0.94%). In the meta-analysis, Black patients were more likely to be restrained compared with White patients (RR, 1.31; 95% CI, 1.19-1.43) and to all non-Black patients (RR, 1.27; 95% CI, 1.23-1.31). With respect to ethnicity, Hispanic patients were less likely to be restrained compared with non-Hispanic patients (RR, 0.85; 95% CI, 0.81-0.89). Conclusions and Relevance: Physical restraint was uncommon, occurring in less than 1% of encounters, but adult Black patients experienced a significantly higher risk of physical restraint in ED settings compared with other racial groups. Hispanic patients were less likely to be restrained compared with non-Hispanic patients, though this observation may have occurred if Black patients, with a higher risk of restraint, were included in the non-Hispanic group. Further work, including qualitative studies, to explore and address mechanisms of racism at the interpersonal, institutional, and structural levels are needed.

Impact of Vasodilator Administration on Survival in Patients with Sepsis: A Systematic Review and Meta-Analysis.

Rationale: Sepsis and septic shock are associated with microcirculatory dysfunction, which is believed to contribute to sepsis-induced organ failure. Vasodilators have been proposed to improve tissue perfusion in sepsis, but the overall survival impact of this strategy is unclear. Objectives: To evaluate the impact of systemic vasodilator administration in patients with sepsis and septic shock on mortality. Methods: We conducted a meta-analysis using a random effects model. Published and unpublished randomized trials in adult patients with sepsis and septic shock were included when comparing the use of systemic vasodilators against no vasodilators. The primary outcome was 28-30-day mortality, and secondary outcomes were organ function and resource use measures. Results: We included eight randomized trials (1,076 patients). In patients randomized to vasodilator arms compared with those randomized to treatment without vasodilators, the 28-30-day mortality risk ratio was 0.74 (95% confidence interval, 0.54-1.01). In a chronological cumulative meta-analysis, the association between vasodilators and survival improved over time. In a prespecified subgroup analysis in 104 patients in two randomized trials, prostacyclin analogues were associated with a decreased rate of 28-30-day mortality among patients with sepsis and septic shock (risk ratio, 0.46; 95% confidence interval, 0.25-0.85). Conclusions: In patients with sepsis and septic shock, administration of vasodilators is not associated with decreased 28-30-day mortality, but the confidence interval suggests potential benefit, and the meta-analysis might lack power. Prostacyclin appears the most promising. The results of this meta-analysis should encourage randomized trials evaluating the impact of vasodilators on mortality in sepsis.

Radiation-induced Fistulas in Patients With Prior Pelvic Radiotherapy for Prostate Cancer: A Systematic Review and Meta-analysis.

OBJECTIVE: To systematically aggregate and summarize existing data on fistula prevalence among patients with a history of pelvic radiotherapy for prostate cancer. MATERIALS AND METHODS: We queried PubMed, Embase, and Web of Science on October 7, 2020 for peer-reviewed publications pertaining to radiation-induced fistulas in the pelvis. For meta-analysis, we used the random-effects model. We used the I2 statistic to quantify heterogeneity and the Newcastle-Ottawa Scale to assess risk of bias. RESULTS: Our final meta-analysis included 6 cohort studies with a total of 7665 patients exposed to pelvic radiotherapy between 1967 and 2013. Median follow-up time was 35.5 months (IQR 33.5-57.5). Pooled prevalence of radiation-induced fistula across all 6 cohort studies was 0.2% (95% CI: 0.1-0.4, I2 = 0.000%, P < .608). In subgroup analysis, we did not detect significant heterogeneity in fistula prevalence in patients who were re-irradiated (0.3%, 95% CI: 0.1-0.4; P = .762) or patients on concurrent chemotherapy (0.4%, 95% CI: -0.3 -1.2; P = .664) compared to those receiving their first course of radiotherapy alone. No randomized controlled trials met inclusion criteria due to ambiguous and inconsistent reporting language for fistula occurrence. CONCLUSION: There is limited published literature reporting fistula as an adverse event of prostate cancer radiotherapy, especially in the medium and long-term period. Patients undergoing pelvic radiotherapy for prostate cancer appear at low short-term risk for developing fistulas. Adverse event reporting in randomized controlled trials merits greater granularity where fistulas should be reported with specificity rather than aggregating into broad categories of genitourinary or gastrointestinal adverse events.

Quality of life among colorectal cancer survivors participating in a pilot randomized controlled trial of a web-based dietary intervention with text messages.

PURPOSE: We aimed to estimate the effect of a 12-week web-based dietary intervention with text messages on quality of life (QoL) among colorectal cancer (CRC) survivors. METHODS: Between 2017 and 2018, 50 CRC survivors were randomized (1:1) to receive a 12-week web-based dietary intervention with daily text messages or wait-list control. Health-related QoL was assessed using the European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) and colorectal quality of life module (QLQ-CR29) at baseline, 12, and 24 weeks. Within- and between-group mean changes in health-related QoL with 95% confidence intervals (CI) were calculated for both arms. RESULTS: Compared to the controls, participants receiving the intervention had an improvement in emotional functioning (mean change: 14.3; 95% CI: 3.0, 25.6) at 12 weeks and social functioning (mean change: 13.8; 95% CI: 2.1, 25.5) at 24 weeks. A decrease of fatigue from baseline was also observed in the intervention arm (mean change: - 9.1; 95% CI: - 17.1, - 1.1) at 24 weeks. No other changes in QoL scores were associated with the intervention. CONCLUSION: CRC survivors randomized to receive a web-based dietary intervention with text messages experienced higher emotional and social functioning. Further study with a larger population may be warranted. TRIAL REGISTRATION: clinicaltrials.gov, NCT02965521. Registered 16 November 2016, https://clinicaltrials.gov/ct2/keydates/NCT02965521.

Alzheimer's disease phenotypes show different sleep architecture.

INTRODUCTION: Sleep-wake disturbances are a prominent feature of Alzheimer's disease (AD). Atypical (non-amnestic) AD syndromes have different patterns of cortical vulnerability to AD. We hypothesized that atypical AD also shows differential vulnerability in subcortical nuclei that will manifest as different patterns of sleep dysfunction. METHODS: Overnight electroencephalography monitoring was performed on 48 subjects, including 15 amnestic, 19 atypical AD, and 14 controls. AD was defined based on neuropathological or biomarker confirmation. We compared sleep architecture by visual scoring and spectral power analysis in each group. RESULTS: Overall, AD cases showed increased sleep fragmentation and N1 sleep compared to controls. Compared to atypical AD groups, typical AD showed worse N3 sleep dysfunction and relatively preserved rapid eye movement (REM) sleep. DISCUSSION: Results suggest differing effects of amnestic and atypical AD variants on slow wave versus REM sleep, respectively, corroborating the hypothesis of differential selective vulnerability patterns of the subcortical nuclei within variants. Optimal symptomatic treatment for sleep dysfunction in clinical phenotypes may differ. HIGHLIGHTS: Alzheimer's disease (AD) variants show distinct patterns of sleep impairment. Amnestic/typical AD has worse N3 slow wave sleep (SWS) impairment compared to atypical AD. Atypical AD shows more rapid eye movement deficits than typical AD. Selective vulnerability patterns in subcortical areas may underlie sleep differences. Relatively preserved SWS may explain better memory scores in atypical versus typical AD.

Effect of collaborative dementia care on potentially inappropriate medication use: Outcomes from the Care Ecosystem randomized clinical trial.

INTRODUCTION: Potentially inappropriate medications (PIMs) cause adverse events and death. We evaluate the Care Ecosystem (CE) collaborative dementia care program on medication use among community-dwelling persons living with dementia (PLWD). METHODS: Secondary analysis of a randomized clinical trial (RCT) comparing CE to usual care (UC) on changes in PIMs, over 12 months between March 2015 and May 2020. Secondary outcomes included change in number of medications, clinically relevant PIMs, and anti-dementia medications. RESULTS: Of 804 PLWD, N = 490 had complete medication data. The CE resulted in significantly fewer PIMs compared to UC (-0.35; 95% CI, -0.49 to -0.20; P < 0.0001). Number needed to prevent an increase in 1 PIM was 3. Total medications, PIMs for dementia or cognitive impairment, CNS-active PIMs, anticholinergics, benzodiazepines, and opioids were also fewer. Anti-dementia medication regimens were modified more frequently. CONCLUSION: The CE medication review intervention embedded in collaborative dementia care optimized medication use among PLWD. HIGHLIGHTS: Compared to usual care (UC), the Care Ecosystem (CE) medication review intervention prevented increases in potentially inappropriate medications (PIMs). Use of anticholinergics, benzodiazepines, and opioids were significantly reduced, with a trend for antipsychotics. Anti-dementia medications were adjusted more frequently. The CE medication review intervention embedded in collaborative dementia care optimized medication use.

The impact of in utero transfusions on perinatal outcomes in patients with alpha thalassemia major: the UCSF registry.

Alpha thalassemia major (ATM) is a hemoglobinopathy that usually results in perinatal demise if in utero transfusions (IUTs) are not performed. We established an international registry (NCT04872179) to evaluate the impact of IUTs on survival to discharge (primary outcome) as well as perinatal and neurodevelopmental secondary outcomes. Forty-nine patients were diagnosed prenatally, 11 were diagnosed postnatally, and all 11 spontaneous survivor genotypes had preserved embryonic zeta-globin levels. We compared 3 groups of patients; group 1, prenatally diagnosed and alive at hospital discharge (n = 14), group 2, prenatally diagnosed and deceased perinatally (n = 5), and group 3, postnatally diagnosed and alive at hospital discharge (n = 11). Group 1 had better outcomes than groups 2 and 3 in terms of the resolution of hydrops, delivery closer to term, shorter hospitalizations, and more frequent average or greater neurodevelopmental outcomes. Earlier IUT initiation was correlated with higher neurodevelopmental (Vineland-3) scores (r = -0.72, P = .02). Preterm delivery after IUT was seen in 3/16 (19%) patients who continued their pregnancy. When we combined our data with those from 2 published series, patients who received ≥2 IUTs had better outcomes than those with 0 to 1 IUT, including resolution of hydrops, delivery at ≥34 weeks gestation, and 5-minute appearance, pulse, grimace, activity, and respiration scores ≥7. Neurodevelopmental assessments were normal in 17/18 of the ≥2 IUT vs 5/13 of the 0 to 1 IUT group (OR 2.74; P = .01). Thus, fetal transfusions enable the survival of patients with ATM and normal neurodevelopment, even in those patients presenting with hydrops. Nondirective prenatal counseling for expectant parents should include the option of IUTs.

Efficacy and mortality of rotating sheaths versus laser sheaths for transvenous lead extraction: a meta-analysis.

BACKGROUND: Rotating and laser sheaths are both routinely used in transvenous lead extraction (TLE) which can lead to catastrophic complications including death. The efficacy and risk of each approach are uncertain. To perform a meta-analysis to compare success and mortality rates associated with rotating and laser sheaths. METHODS: We searched electronic academic databases for case series of consecutive patients and randomized controlled trials published 1998-2017 describing the use of rotating and laser sheaths for TLE. Among 48 studies identified, rotating sheaths included 1,094 patients with 1,955 leads in 14 studies, and laser sheaths included 7,775 patients with 12,339 leads in 34 studies. Patients receiving rotating sheaths were older (63 versus 60 years old) and were more often male (74% versus 72%); CRT-P/Ds were more commonly extracted using rotating sheaths (12% versus 7%), whereas ICDs were less common (37% versus 42%), p > 0.05 for all. Infection as an indication for lead extraction was higher in the rotating sheath group (59.8% versus 52.9%, p = 0.002). The mean time from initial lead implantation was 7.2 years for rotating sheaths and 6.3 years for laser sheaths (p > 0.05). RESULTS: Success rates for complete removal of transvenous leads were 95.1% in rotating sheaths and 93.4% in laser sheaths (p < 0.05). There was one death among 1,094 patients (0.09%) in rotating sheaths and 66 deaths among 7,775 patients (0.85%) in laser sheaths, translating to a 9.3-fold higher risk of death with laser sheaths (95% CI 1.3 to 66.9, p = 0.01). CONCLUSIONS: Laser sheaths were associated with lower complete lead removal rate and a 9.3-fold higher risk of death.

A novel approach for the detection of cognitive impairment and delirium risk in older patients undergoing spine surgery.

BACKGROUND: Postoperative delirium is a common postsurgical complication in older patients and is associated with high morbidity and mortality. The objective of this study was to determine whether a digital cognitive assessment and patient characteristics could identify those at-risk. METHODS: Patients 65 years and older undergoing spine surgeries ≥3 h were evaluated as part of a single-center prospective observational cohort study at an academic medical center, from January 1, 2019, to December 31, 2020. Of 220 eligible patients, 161 were enrolled and 152 completed the study. The primary outcome of postoperative delirium was measured by the Confusion Assessment Method for the Intensive Care Unit or the Nursing Delirium Screening Scale, administered by trained nursing staff independent from the study protocol. Baseline cognitive impairment was identified using the tablet-based TabCAT Brain Health Assessment. RESULTS: Of the 152 patients included in this study, 46% were women. The mean [SD] age was 72 [5.4] years. Baseline cognitive impairment was identified in 38% of participants, and 26% had postoperative delirium. In multivariable analysis, impaired Brain Health Assessment Cognitive Score (OR 2.45; 95% CI, 1.05-5.67; p = 0.037), depression (OR 4.54; 95% CI, 1.73-11.89; p = 0.002), and higher surgical complexity Tier 4 (OR 5.88; 95% CI, 1.55-22.26; p = 0.009) were associated with postoperative delirium. The multivariate model was 72% accurate for predicting postoperative delirium, compared to 45% for the electronic medical record-based risk stratification model currently in use. CONCLUSION: In this prospective cohort study of spine surgery patients, age, cognitive impairment, depression, and surgical complexity identified patients at high risk for postoperative delirium. Integration of scalable digital assessments into preoperative workflows could identify high-risk patients, automate decision support for timely interventions that can improve patient outcomes and lower hospital costs, and provide a baseline cognitive assessment to monitor for postoperative cognitive change.

Early-onset Alzheimer's disease shows a distinct neuropsychological profile and more aggressive trajectories of cognitive decline than late-onset.

OBJECTIVES: Early- and late-onset Alzheimer's disease (EOAD and LOAD) share the same neuropathological traits but show distinct cognitive features. We aimed to explore baseline and longitudinal outcomes of global and domain-specific cognitive function in a well characterized cohort of patients with a biomarker-based diagnosis. METHODS: In this retrospective cohort study, 195 participants were included and classified according to their age, clinical status, and CSF AD biomarker profile: 89 EOAD, 37 LOAD, 46 young healthy controls (age ≤ 65 years), and 23 old healthy controls (>65 years). All subjects underwent clinical and neuropsychological assessment, neuroimaging, APOE genotyping and lumbar puncture. RESULTS: We found distinct neuropsychological profiles between EOAD and LOAD at the time of diagnosis. Both groups showed similar performances on memory and language domains, but the EOAD patients displayed worsened deficits in visual perception, praxis, and executive tasks (p < 0.05). Longitudinally, cognitive decline in EOAD was more pronounced than LOAD in the global outcomes at the expense of these non-amnestic domains. We found that years of education significantly influenced the decline in most of the neuropsychological tests. Besides, the APOE ε4 status showed a significant effect on the decline of memory-related tasks within the EOAD cohort (p < 0.05). INTERPRETATION: Age of onset is a main factor shaping the cognitive trajectories in AD patients, with younger age driving to a steeper decline of the non-memory domains. Years of education are related to a transversal decline in all cognitive domains and APOE ε4 status to a specific decline in memory performance in EOAD.

mHealth Interventions to Promote a Healthy Diet and Physical Activity among Cancer Survivors: A Systematic Review of Randomized Controlled Trials.

Background: Technology-based interventions are increasingly used to improve physical activity (PA) and diet. Methods: We conducted a systematic review of randomized controlled trials (RCTs) published up to August 2021 that tested mobile health (mHealth) PA and/or dietary interventions among cancer survivors and reported on the feasibility, satisfaction, behavioral change, and/or quality of life (QOL) outcomes. Results: In total, 61 articles were identified on PubMed, and 23 of those met the inclusion criteria. The most common cancers were breast (n = 1000), prostate (n = 713), and colorectal (n = 650). Participants were predominantly White (median: 84%, interquartile range (IQR): 20%) and college-educated (58%). The interventions varied, but the most common combination of components (six studies) was a website/mobile app with an activity tracker and coaching. In terms of duration, 70% (n = 16) of the interventions lasted 12 weeks. The median total tracker wear was 87% of the study days (IQR: 6%) and the median text-message reply rate was 73% (IQR 4%). Most participants (median: 87%; IQR: 16%) were satisfied with at least one intervention component. Eleven out of 18 studies examining behavioral change reported significant between-group differences and six out of 11 studies examining QoL reported significant improvements. Conclusions: mHealth interventions are a promising approach to improving the PA and diets of cancer survivors. Research in racially/ethnically and socioeconomically diverse populations is needed.

Probabilistic Decision-Making in Children With Dyslexia.

Background: Neurocognitive mechanisms underlying developmental dyslexia (dD) remain poorly characterized apart from phonological and/or visual processing deficits. Assuming such deficits, the process of learning complex tasks like reading requires the learner to make decisions (i.e., word pronunciation) based on uncertain information (e.g., aberrant phonological percepts)-a cognitive process known as probabilistic decision making, which has been linked to the striatum. We investigate (1) the relationship between dD and probabilistic decision-making and (2) the association between the volume of striatal structures and probabilistic decision-making in dD and typical readers. Methods: Twenty four children diagnosed with dD underwent a comprehensive evaluation and MRI scanning (3T). Children with dD were compared to age-matched typical readers (n = 11) on a probabilistic, risk/reward fishing task that utilized a Bayesian cognitive model with game parameters of risk propensity (γ+) and behavioral consistency (ß), as well as an overall adjusted score (average number of casts, excluding forced-fail trials). Volumes of striatal structures (caudate, putamen, and nucleus accumbens) were analyzed between groups and associated with game parameters. Results: dD was associated with greater risk propensity and decreased behavioral consistency estimates compared to typical readers. Cognitive model parameters associated with timed pseudoword reading across groups. Risk propensity related to caudate volumes, particularly in the dD group. Conclusion: Decision-making processes differentiate dD, associate with the caudate, and may impact learning mechanisms. This study suggests the need for further research into domain-general probabilistic decision-making in dD, neurocognitive mechanisms, and targeted interventions in dD.

Deep phenotyping of Alzheimer's disease leveraging electronic medical records identifies sex-specific clinical associations.

Alzheimer's Disease (AD) is a neurodegenerative disorder that is still not fully understood. Sex modifies AD vulnerability, but the reasons for this are largely unknown. We utilize two independent electronic medical record (EMR) systems across 44,288 patients to perform deep clinical phenotyping and network analysis to gain insight into clinical characteristics and sex-specific clinical associations in AD. Embeddings and network representation of patient diagnoses demonstrate greater comorbidity interactions in AD in comparison to matched controls. Enrichment analysis identifies multiple known and new diagnostic, medication, and lab result associations across the whole cohort and in a sex-stratified analysis. With this data-driven method of phenotyping, we can represent AD complexity and generate hypotheses of clinical factors that can be followed-up for further diagnostic and predictive analyses, mechanistic understanding, or drug repurposing and therapeutic approaches.

The severity of neuropsychiatric symptoms is higher in early-onset than late-onset Alzheimer's disease.

BACKGROUND AND PURPOSE: The faster rates of cognitive decline and predominance of atypical forms in early-onset Alzheimer's disease (EOAD) suggest that neuropsychiatric symptoms could be different in EOAD compared to late-onset AD (LOAD); however, prior studies based on non-biomarker-diagnosed cohorts show discordant results. Our goal was to determine the profile of neuropsychiatric symptoms in EOAD and LOAD, in a cohort with biomarker/postmortem-confirmed diagnoses. Additionally, the contribution of co-pathologies was explored. METHODS: In all, 219 participants (135 EOAD, 84 LOAD) meeting National Institute on Aging and Alzheimer's Association criteria for AD (115 amyloid positron emission tomography/cerebrospinal fluid biomarkers, 104 postmortem diagnosis) at the University of California San Francisco were evaluated. The Neuropsychiatric Inventory-Questionnaire (NPI-Q) was assessed at baseline and during follow-up. The NPI-Q mean comparisons and regression models adjusted by cognitive (Mini-Mental State Examination) and functional status (Clinical Dementia Rating Sum of Boxes) were performed to determine the effect of EOAD/LOAD and amnestic/non-amnestic diagnosis on NPI-Q. Regression models assessing the effect of co-pathologies on NPI-Q were performed. RESULTS: At baseline, the NPI-Q scores were higher in EOAD compared to LOAD (p < 0.05). Longitudinally, regression models showed a significant effect of diagnosis, where EOAD had higher NPI-Q total, anxiety, motor disturbances and night-time behavior scores (p < 0.05). No differences between amnestics/non-amnestics were found. Argyrophilic grain disease co-pathology predicted a higher severity of NPI-Q scores in LOAD. CONCLUSIONS: Anxiety, night-time behaviors and motor disturbances are more severe in EOAD than LOAD across the disease course. The differential patterns of neuropsychiatric symptoms observed between EOAD/LOAD could suggest a pattern of selective vulnerability extending to the brain's subcortical structures. Further, co-pathologies such as argyrophilic grain disease in LOAD may also play a role in increasing neuropsychiatric symptoms.