Development and Validation of eRADAR: A Tool Using EHR Data to Detect Unrecognized Dementia.

ObjectivesEarly recognition of dementia would allow patients and their families to receive care earlier in the disease process, potentially improving care management and patient outcomes, yet nearly half of patients with dementia are undiagnosed. Our aim was to develop and validate an electronic health record (EHR)-based tool to help detect patients with unrecognized dementia (EHR Risk of Alzheimer's and Dementia Assessment Rule [eRADAR]).DesignRetrospective cohort study.SettingKaiser Permanente Washington (KPWA), an integrated healthcare delivery system.ParticipantsA total of 16 665 visits among 4330 participants in the Adult Changes in Thought (ACT) study, who undergo a comprehensive process to detect and diagnose dementia every 2 years and have linked KPWA EHR data, divided into development (70%) and validation (30%) samples.MeasurementsEHR predictors included demographics, medical diagnoses, vital signs, healthcare utilization, and medications within the previous 2 years. Unrecognized dementia was defined as detection in ACT before documentation in the KPWA EHR (ie, lack of dementia or memory loss diagnosis codes or dementia medication fills).ResultsOverall, 1015 ACT visits resulted in a diagnosis of incident dementia, of which 498 (49%) were unrecognized in the KPWA EHR. The final 31-predictor model included markers of dementia-related symptoms (eg, psychosis diagnoses, antidepressant fills), healthcare utilization pattern (eg, emergency department visits), and dementia risk factors (eg, cerebrovascular disease, diabetes). Discrimination was good in the development (C statistic = .78; 95% confidence interval [CI] = .76-.81) and validation (C statistic = .81; 95% CI = .78-.84) samples, and calibration was good based on plots of predicted vs observed risk. If patients with scores in the top 5% were flagged for additional evaluation, we estimate that 1 in 6 would have dementia.ConclusionThe eRADAR tool uses existing EHR data to detect patients with good accuracy who may have unrecognized dementia. J Am Geriatr Soc 68:103-111, 2019

Developmental changes in the expression of creatine synthesizing enzymes and creatine transporter in a precocial rodent, the spiny mouse

Background : Creatine synthesis takes place predominately in the kidney and liver via a two-step process involving AGAT (L-arginine:glycine amidinotransferase) and GAMT (guanidinoacetate methyltransferase). Creatine is taken into cells via the creatine transporter (CrT), where it plays an essential role in energy homeostasis, particularly for tissues with high and fluctuating energy demands. Very little is known of the fetal requirement for creatine and how this may change with advancing pregnancy and into the early neonatal period. Using the spiny mouse as a model of human perinatal development, the purpose of the present study was to comprehensively examine the development of the creatine synthesis and transport systems.Results : The estimated amount of total creatine in the placenta and brain significantly increased in the second half of pregnancy, coinciding with a significant increase in expression of CrT mRNA. In the fetal brain, mRNA expression of AGAT increased steadily across the second half of pregnancy, although GAMT mRNA expression was relatively low until 34 days gestation (term is 38&ndash;39 days). In the fetal kidney and liver, AGAT and GAMT mRNA and protein expression were also relatively low until 34&ndash;37 days gestation. Between mid-gestation and term, neither AGAT or GAMT mRNA or protein could be detected in the placenta.Conclusion : Our results suggest that in the spiny mouse, a species where, like the human, considerable organogenesis occurs before birth, there appears to be a limited capacity for endogenous creatine synthesis until approximately 0.9 of pregnancy. This implies that a maternal source of creatine, transferred across the placenta, may be essential until the creatine synthesis and transport system matures in preparation for birth. If these results also apply to the human, premature birth may increase the risk of creatine deficiency.<br /

Key dating features for timber-framed dwellings in Surrey

This article is made available through the Brunel Open Access Publishing Fund. Copyright @ The Vernacular Architecture Group 2013. MORE OpenChoice articles are open access and distributed under the terms of the Creative Commons Attribution License 3.0.The main component of the Surrey Dendrochronology Project is the accurate dating of 177 ‘dwellings’, nearly all by tree-ring analysis. The dates are used to establish date ranges for 52 ‘key features’, which cover many aspects of timber-framing from building type to details of carpentry. It is shown that changes of method and fashion were in many cases surprisingly rapid, almost abrupt in historical terms. Previous dating criteria for timber-framed dwellings in the county have been refined and new criteria introduced. Clusters of change from the 1440s and the 1540s are shown and some possible historical links suggested.The Heritage Lottery Fund, the Domestic Buildings Research Group (Surrey), the Surrey Archaeological Society and the historical societies of Charlwood, Farnham and Nutfield

A Prospective Assessment of Racial/Ethnic Differences in Future Mammography Behavior among Women Who had Early Mammography

29% of women aged 30-39 report having had a mammogram though sensitivity and specificity are low. We investigate racial/ethnic differences in future mammography behavior among women who had a baseline screening mammogram prior to age 40

Analysis of Successful Immune Responses in Persons Infected with Hepatitis C Virus

Although hepatitis C virus (HCV) infection is very common, identification of patients during acute infection is rare. Consequently, little is known about the immune response during this critical stage of the disease. We analyzed the T lymphocyte response during and after acute resolving HCV infection in three persons, using interferon (IFN)-γ enzyme-linked immunospot (ELISPOT) and human histocompatibility leukocyte antigen (HLA) peptide tetramer assays. Acute infection was associated with a broadly directed T helper and cytotoxic T lymphocyte (CTL) response, which persisted after resolution of clinical hepatitis and clearance of viremia. At the earliest time point studied, highly activated CTL populations were observed that temporarily failed to secrete IFN-γ, a “stunned” phenotype, from which they recovered as viremia declined. In long-term HCV-seropositive persons, CTL responses were more common in persons who had cleared viremia compared with those with persistent viremia, although the frequencies of HCV-specific CTLs were lower than those found in persons during and after resolution of acute HCV infection. These studies demonstrate a strong and persistent CTL response in resolving acute HCV infection, and provide rationale to explore immune augmentation as a therapeutic intervention in chronic HCV infection

Are there racial/ethnic disparities among women younger than 40 undergoing mammography?

While the probability of a woman developing invasive breast cancer at age <40 is low (<1%), mammography use reported among younger women (age <40) is substantial, and varies by race/ethnicity. Little detail is known about mammography use among women aged <40, particularly by race/ethnicity. We describe racial/ethnic differences in: (1) mammography indication after considering underlying risk factors (breast symptoms and family history); (2) follow-up recommendations, and (3) mammography outcomes for first mammograms in women aged <40. These 1996–2005 Breast Cancer Surveillance Consortium data are prospectively pooled from seven U.S. mammography registries. Our community-based sample included 99,615 women aged 18–39 who self-reported race/ethnicity and presented for a first mammogram (screening or diagnostic) with no history of breast cancer. Multivariable analyses controlled for registry site, age, family history of breast cancer, symptoms, and exam year. Overall, 73.6% of the women in our sample were seen for a screening mammogram. Following screening mammography, African American (AA) women were more likely than white women to be recommended for additional workup [relative risk (RR): 1.15 (95% CI: 1.07–1.23)]. Following diagnostic mammography, AA [RR: 1.30 (95% CI: 1.17–1.44)] and Asian [RR: 1.44 (95% CI: 1.26–1.64)] women were more likely to be recommended for biopsy, fine-needle aspiration, or surgical consultation. Depending on race/ethnicity, and considering the rate of true positive to total first screening mammograms of younger women, a women has a likelihood of a true positive of 1 in 363–1,122; she has a likelihood of a false positive of 1 in 7–10. This study of community-based practice found racial/ethnic variability in mammography indication, recommendations, and outcomes among women undergoing first mammography before 40. These findings highlight important areas for future research to understand the motivating factors for these practice patterns and the implications of early mammography use

Multicentre service evaluation of presentation of newly diagnosed cancers and type 1 diabetes in children in the UK during the COVID-19 pandemic

Background: The COVID-19 pandemic led to changes in patterns of presentation to emergency departments. Child health professionals were concerned that this could contribute to the delayed diagnosis of life-threatening conditions, including childhood cancer (CC) and type 1 diabetes (T1DM). Our multicentre, UK-based service evaluation assessed diagnostic intervals and disease severity for these conditions.Methods: We collected presentation route, timing and disease severity for children with newly diagnosed CC in three principal treatment centres and T1DM in four centres between 1 January and 31 July 2020 and the corresponding period in 2019. Total diagnostic interval (TDI), patient interval (PI), system interval (SI) and disease severity across different time periods were compared.Results: For CCs and T1DM, the route to diagnosis and severity of illness at presentation were unchanged across all time periods. Diagnostic intervals for CCs during lockdown were comparable to that in 2019 (TDI 4.6, PI 1.1 and SI 2.1 weeks), except for an increased PI in January–March 2020 (median 2.7 weeks). Diagnostic intervals for T1DM during lockdown were similar to that in 2019 (TDI 16 vs 15 and PI 14 vs 14 days), except for an increased PI in January–March 2020 (median 21 days).Conclusions: There is no evidence of diagnostic delay or increased illness severity for CC or T1DM, during the first phase of the pandemic across the participating centres. This provides reassuring data for children and families with these life-changing conditions

γγ\gamma\gamma Event Generators

The report from the working group on '\gamma\gamma Event Generators' of the LEP 2 workshopComment: 42 pages, tared, gzipped, uuencoded. To be published in the proceedings of the LEP 2 Worksho

Complex modeling with detailed temporal predictors does not improve health records-based suicide risk prediction

Suicide risk prediction models can identify individuals for targeted intervention. Discussions of transparency, explainability, and transportability in machine learning presume complex prediction models with many variables outperform simpler models. We compared random forest, artificial neural network, and ensemble models with 1500 temporally defined predictors to logistic regression models. Data from 25,800,888 mental health visits made by 3,081,420 individuals in 7 health systems were used to train and evaluate suicidal behavior prediction models. Model performance was compared across several measures. All models performed well (area under the receiver operating curve [AUC]: 0.794-0.858). Ensemble models performed best, but improvements over a regression model with 100 predictors were minimal (AUC improvements: 0.006-0.020). Results are consistent across performance metrics and subgroups defined by race, ethnicity, and sex. Our results suggest simpler parametric models, which are easier to implement as part of routine clinical practice, perform comparably to more complex machine learning methods