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

Reflection of neutrons from an optical grating

Specular and off-specular neutron intensities were measured at grazing incidence from an optical grating. Thee periodicity of the grating was determined from the locations of the intensity peaks in the off-specular data. An analysis of the widths of the off-specular intensity peaks showed that the effect of the coherence length of the neutron beam on the determination of a surface length scale {approximately}30 {mu}m was negligible compared to that of the instrument resolution. Although the structure of an optical grating used in this paper is simple, it has served to illustrate the simple relationship between the off-specular data structure and the real-space properties. For more general rough systems, a practical theoretical model will be needed to relate the off-specular data to the real-space roughness structure so that the diffusive data can be analyzed. Owing to the intrinsic complexity of diffuse scattering, the development of such a theoretical model will be a significant technical challenge, and its solution will constitute a major breakthrough in the development of the diffuse reflectivity technique for rough surface/interface characterization

Effect of smoke-free legislation on the incidence of sudden circulatory arrest in the Netherlands

Objective To investigate whether smoke-free legislation in the Netherlands led to a decreased incidence of out-of-hospital sudden circulatory arrest (SCA). Smoke-free legislation was implemented in two phases: a workplace ban in 2004 and an extension of this ban to the hospitality sector on 1 July 2008. Design Weekly incidence data on SCA were obtained from the ambulance registry of South Limburg, the Netherlands. Three time periods were distinguished: the pre-ban period (1 January 2002-1 January 2004), the first post-ban period (1 January 2004-1 July 2008) and the second post-ban period (1 July 2008-1 May 2010). Trends in absolute SCA incidence were analysed using Poisson regression, adjusted for population size, ambient temperature, air pollution and influenza rates. Results A total of 2305 SCA cases were observed (mean weekly incidence 5.3 +/- 2.3 SD). The adjusted Poisson regression model showed a small but significant increase in SCA incidence during the pre-ban period (+0.20% cases per week, p = 0.044). This trend changed significantly after implementation of the first ban (with -0.24% cases per week, p = 0.043), translating into a 6.8% (22 cases) reduction in the number of SCA cases after 1 year of smoke-free legislation. No further decrease was seen after the second smoking ban. Conclusions After introduction of a nationwide workplace smoking ban in 2004, a significant decrease in the incidence of out-of-hospital SCA was seen in South Limburg. Poor enforcement of the 2008 hospitality sector ban may account for the fact that no further decrease in the incidence of SCA was seen at this time

Neuro-Cells therapy improves motor outcomes and suppresses inflammation during experimental syndrome of amyotrophic lateral sclerosis in mice

Aims: Mutations in DNA/RNA-binding factor (fused-in-sarcoma) FUS and superoxide dismutase-1 (SOD-1) cause amyotrophic lateral sclerosis (ALS). They were reproduced in SOD-1-G93A (SOD-1) and new FUS[1-359]-transgenic (FUS-tg) mice, where inflammation contributes to disease progression. The effects of standard disease therapy and anti-inflammatory treatments were investigated using these mutants. Methods: FUS-tg mice or controls received either vehicle, or standard ALS treatment riluzole (8 mg/kg/day), or anti-inflammatory drug a selective blocker of cyclooxygenase-2 celecoxib (30 mg/kg/day) for six weeks, or a single intracerebroventricular (i.c.v.) infusion of Neuro-Cells (a preparation of 1.39 × 106 mesenchymal and hemopoietic human stem cells, containing 5 × 105 of CD34+ cells), which showed anti-inflammatory properties. SOD-1 mice received i.c.v.-administration of Neuro-Cells or vehicle. Results: All FUS-tg-treated animals displayed less marked reductions in weight gain, food/water intake, and motor deficits than FUS-tg-vehicle-treated mice. Neuro-Cell-treated mutants had reduced muscle atrophy and lumbar motor neuron degeneration. This group but not celecoxib-FUS-tg-treated mice had ameliorated motor performance and lumbar expression of microglial activation marker, ionized calcium-binding adapter molecule-1 (Iba-1), and glycogen-synthase-kinase-3ß (GSK-3ß). The Neuro-Cells-treated-SOD-1 mice showed better motor functions than vehicle-treated-SOD-1 group. Conclusion: The neuropathology in FUS-tg mice is sensitive to standard ALS treatments and Neuro-Cells infusion. The latter improves motor outcomes in two ALS models possibly by suppressing microglial activation. © 2019 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons LtdWe thank ?5-100? Russian Excellence Program, Prof. Daniel C. Anthony, Diana Babayevskaya, and Arina Kosakova for their highly valuable contribution. ?Neuro-Cells? preparation was provided by Neuroplast BV, Maastricht, Netherlands

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

The Ki-67 and Repoman mitotic phosphatases assemble via an identical, yet novel mechanism

Ki-67 and RepoMan have key roles during mitotic exit. Previously (Booth et al, eLife, 2014), we showed that Ki-67 organizes the mitotic chromosome periphery and recruits protein phosphatase 1 (PP1) to chromatin at anaphase onset, in a similar manner as RepoMan. Here we show how Ki-67 and RepoMan form mitotic exit phosphatases by recruiting PP1, how they distinguish between distinct PP1 isoforms and how the assembly of these two holoenzymes are dynamically regulated by Aurora B kinase during mitosis. Unexpectedly, our data also reveal that Ki-67 and RepoMan bind PP1 using an identical, yet entirely novel mechanism, interacting with a PP1 pocket that is engaged only by these two PP1 regulators. These findings not only show how two distinct mitotic exit phosphatases are recruited to their substrates, but also provides immediate opportunities for the design of novel cancer therapeutics that selectively target the Ki-67:PP1 and RepoMan:PP1 holoenzymes

Effect of frailty on quality of life in elderly patients after hip fracture:A longitudinal study

Objectives The aims of this study were to examine the pattern of changes over time in health status (HS) and quality of life (QoL) in the first year after hip fracture and to quantify the association between frailty at the onset of hip fracture and the change in HS and QoL 1 year later. The major hypothesis was that frailty, a clinical state of increased vulnerability, is a good predictor of QoL in patients recovering from hip fracture. Design Prospective, observational, follow-up cohort study. Setting Secondary care. Ten participating centres in Brabant, the Netherlands. Participants 1091 patients entered the study and 696 patients completed the study. Patients with a hip fracture aged 65 years and older or proxy respondents for patients with cognitive impairment were included in this study. Main outcome measures The primary outcomes were HS (EuroQol-5 Dimensions questionnaire) and capability well-being (ICEpop CAPability measure for Older people). Prefracture frailty was defined with the Groningen Frailty Indicator (GFI), with GFI >= 4 indicating frailty. Participants were followed up at 1 month, 3 months, 6 months and 1 year after hospital admission. Results In total, 371 patients (53.3%) were considered frail. Frailty was negatively associated with HS (beta -0.333; 95% CI -0.366 to -0.299), self-rated health (beta -21.9; 95% CI -24.2 to -19.6) and capability well-being (beta -0.296; 95% CI -0.322 to -0.270) in elderly patients 1 year after hip fracture. After adjusting for confounders, including death, prefracture HS, age, prefracture residential status, prefracture mobility, American Society of Anesthesiologists grading and dementia, associations were weakened but remained significant. Conclusions We revealed that frailty is negatively associated with QoL 1 year after hip fracture, even after adjusting for confounders. This finding suggests that early identification of prefracture frailty in patients with a hip fracture is important for prognostic counselling, care planning and the tailoring of treatment

Johnston Press and the Crisis in Ireland's Local Newspaper Industry, 2005-2014

Reflecting international trends, Ireland’s local newspaper industry has suffered steep circulation and advertising revenue falls since the late-2000s, and has struggled to reshape traditional business models for the digital era. In harsh trading conditions, local titles are operating on reduced editorial resources and are weakened in their capacity to fulfil their traditional watchdog and informed-citizenry functions. Perhaps no company better encapsulates the industry’s recent difficulties than UK media group Johnston Press. In 2005, it paid more than €200m to acquire fourteen local titles in Ireland, but nine years later sold them for just €8.5m. The article draws on this case-study to consider wider issues related to the corporatisation of local news provision, the sustainability of local news industries in small media markets such as Ireland’s, and the increasing disconnect between local journalism’s commodity value and its public good value

Inverse planned stereotactic intensity modulated radiotherapy (IMRT) in the treatment of incompletely and completely resected adenoid cystic carcinomas of the head and neck: initial clinical results and toxicity of treatment

BACKGROUND: Presenting the initial clinical results in the treatment of complex shaped adenoid cystic carcinomas (ACC) of the head and neck region by inverse planned stereotactic IMRT. MATERIALS: 25 patients with huge ACC in different areas of the head and neck were treated. At the time of radiotherapy two patients already suffered from distant metastases. A complete resection of the tumor was possible in only 4 patients. The remaining patients were incompletely resected (R2: 20; R1: 1). 21 patients received an integrated boost IMRT (IBRT), which allow the use of different single doses for different target volumes in one fraction. All patients were treated after inverse treatment planning and stereotactic target point localization. RESULTS: The mean folllow-up was 22.8 months (91 – 1490 days). According to Kaplan Meier the three year overall survival rate was 72%. 4 patients died caused by a systemic progression of the disease. The three-year recurrence free survival was according to Kaplan Meier in this group of patients 38%. 3 patients developed an in-field recurrence and 3 patient showed a metastasis in an adjacent lymph node of the head and neck region. One patient with an in-field recurrence and a patient with the lymph node recurrence could be re-treated by radiotherapy. Both patients are now controlled. Acute side effects >Grade II did only appear so far in a small number of patients. CONCLUSION: The inverse planned stereotactic IMRT is feasible in the treatment of ACC. By using IMRT, high control rates and low side effects could by achieved. Further evaluation concerning the long term follow-up is needed. Due to the technical advantage of IMRT this treatment modality should be used if a particle therapy is not available