TARP as immunotherapeutic target in AML expressed in the LSC compartment

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Hip fractures in elderly people:Surgery or no surgery? A systematic review and meta-analysis

Iintroduction:  Increasing numbers of patients with hip fractures also have advanced comorbidities. A majority are treated surgically. However, a significantly increasing percentage of medically unfit patients with unacceptably high risk of perioperative death are treated nonoperatively. Important questions about patients' prefracture quality of life (QOL) and future perspectives should be asked before considering different treatment options to assess what kind of treatment is advisable in frail elderly high-risk patients with a hip fracture. Objective:  The aim of this review was to provide an overview of differences in mortality, health-related QOL [(HR)QOL], functional outcome, and costs between nonoperative management (NOM) and operative management (OM) of hip fractures in patients above 65 years. Methods:  A systematic literature search was performed in EMBASE, OvidSP, PubMed, Cochrane Central, and Web of Science for observational studies and trials. Observational studies and randomized controlled trials comparing NOM with OM in hip fracture patients were selected. The methodological quality of the selected studies was assessed according to the Methodological Index for Nonrandomized Studies (MINORS) or Furlan checklist. Results:  Seven observational studies were included with a total of 1189 patients, of whom 242 (20.3%) were treated conservatively. The methodological quality of the studies was moderate (mean: 14.7, standard deviation [SD]: 1.5). The 30-day and 1-year mortalities were higher in the nonoperative group (odds ratio [OR]: 3.95, 95% confidence interval [CI]: 1.43-10.96; OR: 3.84, 95% CI: 1.57-9.41). None of the included studies compared QOL, functional outcome, or health-care costs between the 2 groups. Conclusion:  This systematic review and meta-analysis demonstrated that only a few studies with small number of patients comparing NOM with OM were published. A significantly higher 30-day and 1-year mortality was revealed in nonoperatively treated hip fracture patients. No data were found examining (HR)QOL and costs. Further work is needed to enable shared decision-making and to initiate NOM in frail elderly patients with advanced comorbidity and limited life expectancy

Health care and productivity costs of non-fatal traffic injuries: A comparison of road user types

This study aimed to provide a detailed overview of the health care and productivity costs of non-fatal road traffic injuries by road user type. In a cohort study in the Netherlands, adult injury patients admitted to a hospital as a result of a traffic accident completed questionnaires 1 week and 1, 3, 6, 12 and 24 months after injury, including the iMTA Medical Consumption and Productivity Cost Questionnaire. In-hospital, post-hospital medical costs and productivity costs were calculated up to two years after traffic injury. In total, 1024 patients were included in this study. The mean health care costs per patient were € 8200. The mean productivity costs were € 5900. Being female, older age, with higher injury severity and having multiple comorbidities were associated with higher health care costs. Higher injury severity and being male were associated with higher productivity costs. Pedestrians aged ≥ 65 years had the highest mean health care costs (€ 18,800) and motorcyclists the highest mean productivity costs (€ 9000). Bicycle injuries occurred most often in our sample (n = 554, 54.1%) and accounted for the highest total health care and productivity costs. Considering the high proportion of total costs incurred by bicycle injuries, this is an important area for the prevention of traffic injuries

Whole Grain, Bran, and Germ Intake and Risk of Type 2 Diabetes: A Prospective Cohort Study and Systematic Review

Background: Control of body weight by balancing energy intake and energy expenditure is of major importance for the prevention of type 2 diabetes, but the role of specific dietary factors in the etiology of type 2 diabetes is less well established. We evaluated intakes of whole grain, bran, and germ in relation to risk of type 2 diabetes in prospective cohort studies. Methods and Findings: We followed 161,737 US women of the Nurses' Health Studies (NHSs) I and II, without history of diabetes, cardiovascular disease, or cancer at baseline. The age at baseline was 37–65 y for NHSI and 26–46 y for NHSII. Dietary intakes and potential confounders were assessed with regularly administered questionnaires. We documented 6,486 cases of type 2 diabetes during 12–18 y of follow-up. Other prospective cohort studies on whole grain intake and risk of type 2 diabetes were identified in searches of MEDLINE and EMBASE up to January 2007, and data were independently extracted by two reviewers. The median whole grain intake in the lowest and highest quintile of intake was, respectively, 3.7 and 31.2 g/d for NHSI and 6.2 and 39.9 g/d for NHSII. After adjustment for potential confounders, the relative risks (RRs) for the highest as compared with the lowest quintile of whole grain intake was 0.63 (95% confidence interval [CI] 0.57–0.69) for NHSI and 0.68 (95% CI 0.57–0.81) for NHSII (both: p-value, test for trend <0.001). After further adjustment for body mass index (BMI), these RRs were 0.75 (95% CI 0.68–0.83; p-value, test for trend <0.001) and 0.86 (95% CI 0.72–1.02; p-value, test for trend 0.03) respectively. Associations for bran intake were similar to those for total whole grain intake, whereas no significant association was observed for germ intake after adjustment for bran. Based on pooled data for six cohort studies including 286,125 participants and 10,944 cases of type 2 diabetes, a two-serving-per-day increment in whole grain consumption was associated with a 21% (95% CI 13%–28%) decrease in risk of type 2 diabetes after adjustment for potential confounders and BMI. Conclusions: Whole grain intake is inversely associated with risk of type 2 diabetes, and this association is stronger for bran than for germ. Findings from prospective cohort studies consistently support increasing whole grain consumption for the prevention of type 2 diabetes

Trends in Antihypertensive Medication Discontinuation and Low Adherence Among Medicare Beneficiaries Initiating Treatment From 2007 to 2012

Low antihypertensive medication adherence is common. During recent years, the impact of low medication adherence on increased morbidity and healthcare costs has become more recognized, leading to interventions aimed at improving adherence. We analyzed a 5% sample of Medicare beneficiaries initiating antihypertensive medication between 2007 and 2012 to assess whether reductions occurred in discontinuation and low adherence. Discontinuation was defined as having no days of antihypertensive medication supply for the final 90 days of the 365 days after initiation. Low adherence was defined as having a proportion of days covered <80% during the 365 days after initiation among beneficiaries who did not discontinue treatment. Between 2007 and 2012, 41 135 Medicare beneficiaries in the 5% sample initiated antihypertensive medication. Discontinuation was stable during the study period (21.0% in 2007 and 21.3% in 2012; P-trend=0.451). Low adherence decreased from 37.4% in 2007 to 31.7% in 2012 (P-trend<0.001). After multivariable adjustment, the relative risk of low adherence for beneficiaries initiating treatment in 2012 versus in 2007 was 0.88 (95% confidence interval, 0.83-0.92). Low adherence was more common among racial/ethnic minorities, beneficiaries with Medicaid buy-in (an indicator of low income), and those with polypharmacy, and was less common among females, beneficiaries initiating antihypertensive medication with multiple classes or a 90-day prescription fill, with dementia, a history of stroke, and those who reached the Medicare Part D coverage gap in the previous year. In conclusion, low adherence to antihypertensive medication has decreased among Medicare beneficiaries; however, rates of discontinuation and low adherence remain high

Racial Differences in Abnormal Ambulatory Blood Pressure Monitoring Measures: Results From the Coronary Artery Risk Development in Young Adults (CARDIA) Study

Background: Several ambulatory blood pressure monitoring (ABPM) measures have been associated with increased cardiovascular disease risk independent of clinic blood pressure (BP). African Americans have higher clinic BP compared with Whites but few data are available on racial differences in ABPM measures. Methods: We compared ABPM measures between African American (n = 178) and White (n = 103) participants at the Year 5 Coronary Artery Risk Development in Young Adults study visit. BP was measured during a study visit and the second and third measurements were averaged. ABPM was conducted over the following 24 hours. Results: Mean ± SD age of participants was 29.8±3.8 years and 30.8±3.5 years for African Americans and Whites, respectively. Mean daytime systolic BP (SBP) was 3.90 (SD 1.18) mm Hg higher among African Americans compared with Whites (P < 0.001) after age–gender adjustment and 1.71 (SD 1.03) mm Hg higher after multivariable adjustment including mean clinic SBP (P = 0.10). After multivariable adjustment including mean clinic SBP, nighttime SBP was 4.83 (SD 1.11) mm Hg higher among African Americans compared with Whites (P < 0.001). After multivariable adjustment, the African Americans were more likely than Whites to have nocturnal hypertension (prevalence ratio: 2.44, 95% CI: 0.99–6.05) and nondipping (prevalence ratio: 2.50, 95% CI: 1.39–4.48). The prevalence of masked hypertension among African Americans and Whites was 4.4% and 2.1%, respectively, (P = 0.49) and white coat hypertension was 3.3% and 3.9%, respectively (P = 0.99). Twenty-four hour BP variability on ABPM was higher among African Americans compared with Whites. Conclusions: These data suggest racial differences in several ABPM measures exist

Prediction of Cognitive Recovery after Stroke:The Value of Diffusion-Weighted Imaging–Based Measures of Brain Connectivity

Background and Purpose: Prediction of long-term recovery of a poststroke cognitive disorder (PSCD) is currently inaccurate. We assessed whether diffusion-weighted imaging (DWI)–based measures of brain connectivity predict cognitive recovery 1 year after stroke in patients with PSCD in addition to conventional clinical, neuropsychological, and imaging variables. Methods: This prospective monocenter cohort study included 217 consecutive patients with a clinical diagnosis of ischemic stroke, aged ≥50 years, and Montreal Cognitive Assessment score below 26 during hospitalization. Five weeks after stroke, patients underwent DWI magnetic resonance imaging. Neuropsychological assessment was performed 5 weeks and 1 year after stroke and was used to classify PSCD as absent, modest, or marked. Cognitive recovery was operationalized as a shift to a better PSCD category over time. We evaluated 4 DWI-based measures of brain connectivity: global network efficiency and mean connectivity strength, both weighted for mean diffusivity and fractional anisotropy. Conventional predictors were age, sex, level of education, clinical stroke characteristics, neuropsychological variables, and magnetic resonance imaging findings (eg, infarct size). DWI-based measures of brain connectivity were added to a multivariable model to assess additive predictive value. Results: Of 135 patients (mean age, 71 years; 95 men [70%]) with PSCD 5 weeks after ischemic stroke, 41 (30%) showed cognitive recovery. Three of 4 brain connectivity measures met the predefined threshold of P<0.1 in univariable regression analysis. There was no added value of these measures to a multivariable model that included level of education and infarct size as significant predictors of cognitive recovery. Conclusions: Current DWI-based measures of brain connectivity appear to predict recovery of PSCD but at present have no added value over conventional predictors

Role of amyloid-β glycine 33 in oligomerization, toxicity, and neuronal plasticity

The aggregation of the amyloid-{beta} (Abeta) peptide plays a pivotal role in the pathogenesis of Alzheimer's disease, as soluble oligomers are intimately linked to neuronal toxicity and inhibition of hippocampal long-term potentiation (LTP). In the C-terminal region of Abeta there are three consecutive GxxxG dimerization motifs, which we could previously demonstrate to play a critical role in the generation of Abeta. Here, we show that glycine 33 (G33) of the central GxxxG interaction motif within the hydrophobic Abeta sequence is important for the aggregation dynamics of the peptide. Abeta peptides with alanine or isoleucine substitutions of G33 displayed an increased propensity to form higher oligomers, which we could attribute to conformational changes. Importantly, the oligomers of G33 variants were much less toxic than Abeta(42) wild type (WT), in vitro and in vivo. Also, whereas Abeta(42) WT is known to inhibit LTP, Abeta(42) G33 variants had lost the potential to inhibit LTP. Our findings reveal that conformational changes induced by G33 substitutions unlink toxicity and oligomerization of Abeta on the molecular level and suggest that G33 is the key amino acid in the toxic activity of Abeta. Thus, a specific toxic conformation of Abeta exists, which represents a promising target for therapeutic interventions

Physical Activity and Incident Hypertension in African Americans: The Jackson Heart Study

There is limited empirical evidence to support the protective effects of physical activity in the prevention of hypertension among African Americans. The purpose of this study was to examine the association of physical activity with incident hypertension among African Americans. We studied 1311 participants without hypertension at baseline enrolled in the Jackson Heart Study, a community-based study of African Americans residing in Jackson, Mississippi. Overall physical activity, moderate–vigorous physical activity, and domain-specific physical activity (work, active living, household, and sport/exercise) were assessed by self-report during the baseline examination (2000–2004). Incident hypertension, assessed at examination 2 (2005–2008) and examination 3 (2009–2013), was defined as the first visit with systolic/diastolic blood pressure ≥140/90 mm Hg or self-reported antihypertensive medication use. Over a median follow-up of 8.0 years, there were 650 (49.6%) incident hypertension cases. The multivariable-adjusted hazard ratios (95% confidence interval) for incident hypertension comparing participants with intermediate and ideal versus poor levels of moderate–vigorous physical activity were 0.84 (0.67–1.05) and 0.76 (0.58–0.99), respectively (P trend=0.038). A graded, dose–response association was also present for sport/exercise-related physical activity (Quartiles 2, 3, and 4 versus Quartile 1: 0.92 [0.68–1.25], 0.87 [0.67–1.13], 0.75 [0.58–0.97], respectively; P trend=0.032). There were no statistically significant associations observed for overall physical activity, or work, active living, and household-related physical activities. In conclusion, the results of the current study suggest that regular moderate–vigorous physical activity or sport/exercise-related physical activity may reduce the risk of developing hypertension in African Americans