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Atopic dermatitis is known to be common among children, but there are few studies examining the epidemiology across the life course. In particular, there is a paucity of data on atopic dermatitis among older adults. To evaluate participant characteristics, patterns of disease activity and severity, and calendar trends in older adult atopic dermatitis in comparison to other age groups in a large population-based cohort. This was a cohort study of 9,154,936 individuals aged 0-99 years registered in The Health Improvement Network, a database comprised of electronic health records from general practices in the United Kingdom between 1994 and 2013. Atopic dermatitis was defined by a previously validated algorithm using a combination of at least one recorded atopic dermatitis diagnostic code in primary care and two atopic dermatitis therapies recorded on separate days. Cross-sectional analyses of disease prevalence were conducted at each age. Logistic mixed effect regression models were used to identify predictors of prevalent disease over time among children (0-17 years), adults (18-74 years), and older adults (75-99 years). Physician-diagnosed atopic dermatitis was identified in 894,454 individuals with the following proportions in each age group: 18.3% of children, 7.7% of adults, and 11.6% of older adults. Additionally, atopic dermatitis prevalence increased across the 2-decade period (beta from linear regression test for trend in the change in proportion per year = 0.005, p = 0.044). In older adults, atopic dermatitis was 27% less common among females (adjusted OR 0.73, 95% CI 0.70-0.76) and was more likely to be active (59.7%, 95% CI 59.5-59.9%) and of higher severity (mean annual percentage with moderate and severe disease: 31.8% and 3.0%, respectively) than in other age groups. In a large population-based cohort, the prevalence of physician-diagnosed atopic dermatitis has increased throughout adulthood and was most common among males age 75 years and above. Compared to children ages 0-17 and adults ages 18-74, older adult atopic dermatitis was more active and severe. Because the prevalence of atopic dermatitis among older adults has increased over time, additional characterization of disease triggers and mechanisms and targeted treatment recommendations are needed for this population.

Whether functional status before dialysis therapy is maintained after its initiation in elderly patients with end-stage renal disease is unclear. This study assessed functional status in all nursing home residents in the United States who began to undergo dialysis between June 1998 and October 2000. The initiation of dialysis in such residents was associated with a substantial and sustained decline in functional status. The initiation of dialysis in nursing home residents was associated with a substantial and sustained decline in functional status. In the United States, increasing numbers of elderly patients with end-stage renal disease (ESRD) are starting dialysis. 1 In 1999, nursing home residents accounted for 4% of all new patients with ESRD and 11% of new patients with ESRD who were older than 70 years of age. 2 The benefits of dialysis in such patients are uncertain. Mortality in the first year after the initiation of dialysis exceeds 35% among patients older than 70 years of age and exceeds 50% among patients older than 80 years of age. 2 Moreover, the extent to which dialysis extends life and its effect on the quality . . .

Background Evidence links lifestyle factors with Alzheimer’s disease (AD). We report the first randomized, controlled clinical trial to determine if intensive lifestyle changes may beneficially affect the progression of mild cognitive impairment (MCI) or early dementia due to AD. Methods A 1:1 multicenter randomized controlled phase 2 trial, ages 45-90 with MCI or early dementia due to AD and a Montreal Cognitive Assessment (MoCA) score of 18 or higher. The primary outcome measures were changes in cognition and function tests: Clinical Global Impression of Change (CGIC), Alzheimer’s Disease Assessment Scale (ADAS-Cog), Clinical Dementia Rating–Sum of Boxes (CDR-SB), and Clinical Dementia Rating Global (CDR-G) after 20 weeks of an intensive multidomain lifestyle intervention compared to a wait-list usual care control group. ADAS-Cog, CDR-SB, and CDR-Global scales were compared using a Mann-Whitney-Wilcoxon rank-sum test, and CGIC was compared using Fisher’s exact test. Secondary outcomes included plasma Aβ42/40 ratio, other biomarkers, and correlating lifestyle with the degree of change in these measures. Results Fifty-one AD patients enrolled, mean age 73.5. No significant differences in any measures at baseline. Only two patients withdrew. All patients had plasma Aβ42/40 ratios <0.0672 at baseline, strongly supporting AD diagnosis. After 20 weeks, significant between-group differences in the CGIC ( p = 0.001), CDR-SB ( p = 0.032), and CDR Global ( p = 0.037) tests and borderline significance in the ADAS-Cog test ( p = 0.053). CGIC, CDR Global, and ADAS-Cog showed improvement in cognition and function and CDR-SB showed significantly less progression, compared to the control group which worsened in all four measures. Aβ42/40 ratio increased in the intervention group and decreased in the control group ( p = 0.003). There was a significant correlation between lifestyle and both cognitive function and the plasma Aβ42/40 ratio. The microbiome improved only in the intervention group ( p <0.0001). Conclusions Comprehensive lifestyle changes may significantly improve cognition and function after 20 weeks in many patients with MCI or early dementia due to AD. Trial registration Approved by Western Institutional Review Board on 12/31/2017 (#20172897) and by Institutional Review Boards of all sites. This study was registered retrospectively with clinicaltrials.gov on October 8, 2020 (NCT04606420, ID: 20172897).

ObjectiveThis work aims to study (i) the relationship between body mass index (BMI) and knee synovial inflammation using non-contrast-enhanced MRI and (ii) the association of synovial inflammation versus degenerative abnormalities and pain.Materials and methodsSubjects with risk for and mild to moderate radiographic osteoarthritis were selected from the Osteoarthritis Initiative. Subjects were grouped into three BMI categories with 87 subjects per group: normal weight (BMI, 20–24.9 kg/m2), overweight (BMI, 25–29.9 kg/m2), and obese (BMI, ≥ 30 kg/m2), frequency matched for age, sex, race, Kellgren-Lawrence grade, and history of knee surgery and injury. Semi-quantitative synovial inflammation imaging biomarkers were obtained including effusion-synovitis, size and intensity of infrapatellar fat pad signal abnormality, and synovial proliferation score. Cartilage composition was measured using T2 relaxation time and structural abnormalities using the whole-organ magnetic resonance imaging score (WORMS). The Western Ontario and McMasters (WOMAC) Osteoarthritis Index was used for pain assessment. Intra- and inter-reader reproducibility was assessed by kappa values.ResultsOverweight and obese groups had higher prevalence and severity of all synovial inflammatory markers (p ≤ 0.03). Positive associations were found between synovial inflammation imaging biomarkers and average T2 values, WORMS maximum scores and total WOMAC pain scores (p < 0.05). Intra- and inter-reader kappa values for imaging biomarkers were high (0.76–1.00 and 0.60–0.94, respectively).ConclusionBeing overweight or obese was significantly associated with a greater prevalence and severity of synovial inflammation imaging biomarkers. Substantial reproducibility and high correlation with knee structural, cartilage compositional degeneration, and WOMAC pain scores validate the synovial inflammation biomarkers used in this study.

Background The COVID-19 pandemic led to dramatic changes in the lives of children that impact cardiometabolic health. Cities and counties had varying policies with respect to school closure, recreational programs, and efforts to mitigate food insecurity and economic distress. Our objective was to evaluate changes in BMI-z score and prevalence of overweight/obesity prior to and during the pandemic among children in San Francisco, CA, where public schools were closed for 18-months. Methods This was an electronic medical record-based retrospective cohort study. We included 15,401 children, 4–17 years of age at study onset. Our exposure was time into each of three time periods: (1) March 2018-February 2019; (2) March 2019-February 2020; (3) March 2020-August 2021 (the pandemic period of school closure). Generalized estimating equations (GEE) were used to assess changes in BMI-z score and overweight/obesity across the three time periods. We assessed for effect modification by age-category, insurance status, and race/ethnicity. Results Mean BMI-z score increased by 0.06 per year in time period 2, the year prior to the pandemic ( p  < 0.001, 95% CI: 0.04, 0.09), and by 0.12 per year during time period 3, the first 18 months of the pandemic ( p  < 0.001, 95% CI 0.10, 0.13). The proportion of children with overweight/obesity increased by 1.4% points per year during time period 2 ( p  = 0.012, 95% CI: 0.03, 2.46) and by 4.9% points per year during the first 18 months of the pandemic ( p  < 0.001, 95% CI: 4.11, 5.67). The effect modification analysis demonstrated that the youngest age group, publicly insured children (versus privately insured), and Black, Latino, and Asian children (versus White children) experienced greater increases in BMI-z score during the pandemic ( p  < 0.01 for all comparisons). The youngest age group ( p  = 0.022) and publicly insured children (versus privately insured children) ( p  < 0.001) also experienced greater increases in the proportion of children with overweight/obesity during the pandemic. Conclusions Among children in San Francisco, increases in BMI-z score and overweight/obesity were greater during the pandemic compared to prior changes, with the most pronounced increases among younger and publicly insured children. These findings support the need for more targeted and effective policies for addressing childhood overweight/obesity, especially among these high-risk populations.

An analysis of NIH funding in 1996 found that the strongest predictor of funding, disability-adjusted life-years (DALYs), explained only 39% of the variance in funding. In 1998, Congress requested that the Institute of Medicine (IOM) evaluate priority-setting criteria for NIH funding; the IOM recommended greater consideration of disease burden. We examined whether the association between current burden and funding has changed since that time. We analyzed public data on 2006 NIH funding for 29 common conditions. Measures of US disease burden in 2004 were obtained from the World Health Organization's Global Burden of Disease study and national databases. We assessed the relationship between disease burden and NIH funding dollars in univariate and multivariable log-linear models that evaluated all measures of disease burden. Sensitivity analyses examined associations with future US burden, current and future measures of world disease burden, and a newly standardized NIH accounting method. In univariate and multivariable analyses, disease-specific NIH funding levels increased with burden of disease measured in DALYs (p = 0.001), which accounted for 33% of funding level variation. No other factor predicted funding in multivariable models. Conditions receiving the most funding greater than expected based on disease burden were AIDS ($2474 M), diabetes mellitus ($390 M), and perinatal conditions ($297 M). Depression ($719 M), injuries ($691 M), and chronic obstructive pulmonary disease ($613 M) were the most underfunded. Results were similar using estimates of future US burden, current and future world disease burden, and alternate NIH accounting methods. Current levels of NIH disease-specific research funding correlate modestly with US disease burden, and correlation has not improved in the last decade.

To determine whether acute renal failure (ARF) increases the long-term risk of progressive chronic kidney disease (CKD), we studied the outcome of patients whose initial kidney function was normal or near normal but who had an episode of dialysis-requiring ARF and did not develop end-stage renal disease within 30 days following hospital discharge. The study encompassed 556,090 adult members of Kaiser Permanente of Northern California hospitalized over an 8 year period, who had pre-admission estimated glomerular filtration rates (eGFR) equivalent to or greater than 45ml/min/1.73m2 and who survived hospitalization. After controlling for potential confounders such as baseline level of eGFR and diabetes status, dialysis-requiring ARF was independently associated with a 28-fold increase in the risk of developing stage 4 or 5 CKD and more than a twofold increased risk of death. Our study shows that in a large, community-based cohort of patients with pre-existing normal or near normal kidney function, an episode of dialysis-requiring ARF was a strong independent risk factor for a long-term risk of progressive CKD and mortality.

End-stage renal disease increases the risks of death and of cardiovascular disease and the use of specialized health care, but the effects of less severe kidney dysfunction on these outcomes are not well defined. In this study of adults with known creatinine levels, the adjusted risks of death, cardiovascular events, and hospitalization were inversely proportional to the estimated glomerular filtration rate. In this study of 1.1 million adults, the risks of death, cardiovascular events, and hospitalization were inversely proportional to the estimated glomerular filtration rate. More than 400,000 Americans have end-stage renal disease, and over 300,000 of these patients require maintenance dialysis. 1 Mortality rates remain above 20 percent per year with the use of dialysis, with more than half of the deaths related to cardiovascular disease. The annual direct medical costs for end-stage renal disease are nearly $23 billion. 1 Although an estimated 8 million adults in the United States have chronic kidney disease of at least stage 3 (as defined by an estimated glomerular filtration rate [GFR] of less than 60 ml per minute per 1.73 m 2 of body-surface area), 2 less is known about the . . .

Abstract BACKGROUND: The supplementary grading system for brain arteriovenous malformations (AVMs) was introduced in 2010 as a tool for improving preoperative risk prediction and selecting surgical patients. OBJECTIVE: To demonstrate in this multicenter validation study that supplemented Spetzler-Martin (SM-Supp) grades have greater predictive accuracy than Spetzler-Martin (SM) grades alone. METHODS: Data collected from 1009 AVM patients who underwent AVM resection were used to compare the predictive powers of SM and SM-Supp grades. Patients included the original 300 University of California, San Francisco patients plus those treated thereafter (n = 117) and an additional 592 patients from 3 other centers. RESULTS: In the combined cohort, the SM-Supp system performed better than SM system alone: area under the receiver-operating characteristics curve (AUROC) = 0.75 (95% confidence interval, 0.71–0.78) for SM-Supp and AUROC = 0.69 (95% confidence interval, 0.65-0.73) for SM (P < .001). Stratified analysis fitting models within 3 different follow-up groupings (<6 months, 6 months-2 years, and >2 years) demonstrated that the SM-Supp system performed better than SM system for both medium (AUROC = 0.71 vs 0.62; P = .003) and long (AUROC = 0.69 vs 0.58; P = .001) follow-up. Patients with SM-Supp grades ⩽6 had acceptably low surgical risks (0%-24%), with a significant increase in risk for grades >6 (39%-63%). CONCLUSION: This study validates the predictive accuracy of the SM-Supp system in a multicenter cohort. An SM-Supp grade of 6 is a cutoff or boundary for AVM operability. Supplemented grading is currently the best method of estimating neurological outcomes after AVM surgery, and we recommend it as a starting point in the evaluation of AVM operability.

The degree of thigh intramuscular fat in individuals without OA is fundamental for distinguishing natural variations in intramuscular fat from pathological changes. The goals of this study were to estimate the degree of thigh intramuscular fat in individuals without radiographic OA or frequent pain and assess the associations of age, sex, and BMI with the degree of intramuscular fat. Individuals without knee or hip radiographic OA, without total knee/hip arthroplasty, and without frequent knee/hip pain were selected from the OAI database (n = 710). Goutallier Grades (GGs) of the quadriceps and hamstring muscles were assessed based on 3 T MR images on a scale from 0 (normal muscle) to 4 (more fat than muscle). The associations between demographic variables and GG outcomes were evaluated using mixed effects models. The most prevalent GGs among the muscles were Grades 1 and 2; Grade 4 was infrequent (< 1%). Greater BMI (p < 0.001) and age (p < 0.001) were each associated with greater GG. Women had greater GG than men (greatest difference in the vastus medialis: coeff. = 0.214, p < 0.001). At lower BMI, women had greater intramuscular fat than men; at higher BMI, men had greater intramuscular fat than women (p = 0.029 for BMI-sex interaction). While individuals without radiographic OA or frequent pain generally had low thigh intramuscular fat, higher BMI and age were associated with greater intramuscular fat, and GGs were greater in women than men. The relationship between BMI and intramuscular fat was sex-dependent. Thus, demographic variables must be considered when evaluating intramuscular fat.