Eighty years on, we are seeing a resurgence of the antiregulatory and antigovernment forces that lost the battle of the New Deal. President Trump's administration has proclaimed the "deconstruction ...of the administrative state" to be one of its main objectives. Early Trump executive actions quickly delivered on this pledge, with a wide array of antiregulatory actions and a budget proposing to slash many agencies' funding. Invoking the long-dormant Congressional Review Act, the Republican-controlled Congress has eagerly repealed numerous regulations promulgated late in the Obama Administration. Other major legislative and regulatory repeals are pending, and bills that would impose the most significant restrictions on administrative governance since the Administrative Procedure Act was adopted in 1946 -- like the proposed Regulatory Accountability Act -- now stand a chance of enactment. This resistance to administrative government reflects antigovernment themes that have been a consistent presence in national politics since President Reagan's election in 1980.
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BFBNIB, DOBA, IZUM, KILJ, NMLJ, NUK, PILJ, PNG, PRFLJ, SAZU, UILJ, UKNU, UL, UM, UPUK
Multimorbidity and the associated use of multiple medicines (polypharmacy), is common in the older population. Despite this, there is no consensus definition for polypharmacy. A systematic review was ...conducted to identify and summarise polypharmacy definitions in existing literature.
The reporting of this systematic review conforms to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) checklist. MEDLINE (Ovid), EMBASE and Cochrane were systematically searched, as well as grey literature, to identify articles which defined the term polypharmacy (without any limits on the types of definitions) and were in English, published between 1st January 2000 and 30th May 2016. Definitions were categorised as i. numerical only (using the number of medications to define polypharmacy), ii. numerical with an associated duration of therapy or healthcare setting (such as during hospital stay) or iii. Descriptive (using a brief description to define polypharmacy).
A total of 1156 articles were identified and 110 articles met the inclusion criteria. Articles not only defined polypharmacy but associated terms such as minor and major polypharmacy. As a result, a total of 138 definitions of polypharmacy and associated terms were obtained. There were 111 numerical only definitions (80.4% of all definitions), 15 numerical definitions which incorporated a duration of therapy or healthcare setting (10.9%) and 12 descriptive definitions (8.7%). The most commonly reported definition of polypharmacy was the numerical definition of five or more medications daily (n = 51, 46.4% of articles), with definitions ranging from two or more to 11 or more medicines. Only 6.4% of articles classified the distinction between appropriate and inappropriate polypharmacy, using descriptive definitions to make this distinction.
Polypharmacy definitions were variable. Numerical definitions of polypharmacy did not account for specific comorbidities present and make it difficult to assess safety and appropriateness of therapy in the clinical setting.
Seven P2X ion channel nucleotide receptor subtypes have been cloned and characterised. P2X7 receptors (P2X7R) are unusual in that there are extra amino acids in the intracellular C terminus. Low ...concentrations of ATP open cation channels sometimes leading to cell proliferation, whereas high concentrations of ATP open large pores that release inflammatory cytokines and can lead to apoptotic cell death. Since many diseases involve inflammation and immune responses, and the P2X7R regulates inflammation, there has been recent interest in the pathophysiological roles of P2X7R and the potential of P2X7R antagonists to treat a variety of diseases. These include neurodegenerative diseases, psychiatric disorders, epilepsy and a number of diseases of peripheral organs, including the cardiovascular, airways, kidney, liver, bladder, skin and musculoskeletal. The potential of P2X7R drugs to treat tumour progression is discussed.
The IRS targets Tea Party organizations' applications for nonprofit tax-exempt status for special scrutiny. Newly opened online federal health exchanges fail to function. Officials at some Veterans ...Administration hospitals engage in widespread falsification of wait times. A key theme linking these examples is that they all involve managerial and supervisory failure. This should come as no surprise. Supervision and other systemic features of government administration have long been fundamental in shaping how an agency operates, and their importance is only more acute today. New approaches to program implementation and regulation mean that a broader array of actors is wielding broader discretionary governmental authority. The centrality of systemic administration in practice contrasts starkly with its virtual exclusion from contemporary U. S. constitutional law. This exclusion of administration takes a variety of doctrinal guises, but it surfaces repeatedly in both structural and individual rights contexts. This Article argues that the exclusion of systemic administration from constitutional law is a mistake. This exclusion creates a deeply troubling disconnect between the realities of government and the constitutional requirements imposed on exercises of governmental power. Just as importantly, the current doctrinal exclusion of administration stands at odds with the Constitution's text and structure, which repeatedly emphasize one particular systemic administrative feature: supervision. This emphasis on supervision is most prominently manifest in Article II's Take Care Clause, but it also surfaces more broadly as a constitutional prerequisite of delegation of governmental power. Whether it is rooted in Article II, general separation of powers principles, or due process, a duty to supervise represents a basic precept of our federal constitutional structure. Moreover, concerns about judicial role do not justify the Court's refusal to engage with systemic administration, and judicial recognition of a constitutional duty to supervise is critical even if the duty is entirely politically enforced. Indeed, recognizing a constitutional duty to supervise is as central to the overall project of constitutional interpretation as it is to the aim of better keying constitutional law to the realities of contemporary governance. Recognizing this duty underscores the need for greater attention to how courts can support constitutional enforcement by the other branches and highlights the porous and critical relationship between constitutional and subconstitutional law.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, IZUM, KILJ, NMLJ, NUK, PILJ, PNG, PRFLJ, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Appropriations lie at the core of the administrative state and are becoming increasingly important as deep partisan divides have stymied substantive legislation. Both Congress and the President ...exploit appropriations to control government and advance their policy agendas, with the border wall battle being just one of several recent high-profile examples. Yet in public law doctrine, appropriations are ignored, pulled out for special legal treatment, or subjected to legal frameworks ill-suited for appropriations realities. This Article documents how appropriations are marginalized in a variety of public law contexts and assesses the reasons for this unjustified treatment. Appropriations’ doctrinal marginalization does not affect the political branches equally, but instead enhances executive branch and presidential power over appropriations at the expense of Congress. Yet legal doctrines governing appropriations should have the opposite effect because constitutional text, structure, and history make clear the central importance of Congress’s appropriations power. Appropriations’ doctrinal marginalization undermines the separation of powers even further by undercutting political accountability through Congress and creating de facto presidential spending authority, with the executive branch able to violate governing statutes on appropriations with minimal legal consequences. This Article then turns to the question of what taking appropriations seriously might mean for public law doctrine. It concludes that appropriations exceptionalism is not problematic if it reflects the realities of the appropriations process and does not downplay appropriations’ significance. Doctrines should attend to the separation of powers dynamics raised by appropriations and reinforce Congress’s power of the purse. Among other consequences, this leads to jurisdictional doctrines that put primacy on congressional enforcement of appropriations limits in court.
Background: the efficacy of warfarin for prevention of stroke in patients with atrial fibrillation (AF) is well established, but many people with AF who would benefit from warfarin are not receiving ...it. This systematic review aims to determine physicians' attitudes to the prescription of warfarin for AF, and identify reasons for its underuse.
Methods: an electronic search of MEDLINE (1950-present), EMBASE (1980-present), CINAHL (1994-present), PsycINFO (1987-present) and Web of Knowledge (1970-present) was performed in November 2010 to identify all studies which addressed, via survey, physicians' attitudes regarding anticoagulation for patients with AF.
Results: a total of 1,375 citations were identified. Of these citations, 44 full text studies were obtained for scrutinisation; 14 of these studies were rejected leaving 30 studies which were included in the review. All included studies were cross-sectional surveys and addressed physicians' opinions of anticoagulation in AF as a primary or secondary aim. Increasing age, increased bleeding risk, previous bleeds, falls risk, co-morbidities and ability to comply with treatment influenced whether physicians would prescribe anticoagulation for AF.
Conclusion: physicians are reticent to recommend warfarin for elderly patients in AF, despite evidence of increased benefit in these patients compared with younger patients. Risk of falls and previous bleeding were also shown to be disproportionate barriers to warfarin prescription. Further studies are required to determine how best to overcome these perceived barriers to appropriate anticoagulation.
Background
Improving upper limb function is a core element of stroke rehabilitation needed to maximise patient outcomes and reduce disability. Evidence about effects of individual treatment ...techniques and modalities is synthesised within many reviews. For selection of effective rehabilitation treatment, the relative effectiveness of interventions must be known. However, a comprehensive overview of systematic reviews in this area is currently lacking.
Objectives
To carry out a Cochrane overview by synthesising systematic reviews of interventions provided to improve upper limb function after stroke.
Methods
Search methods: We comprehensively searched the Cochrane Database of Systematic Reviews; the Database of Reviews of Effects; and PROSPERO (an international prospective register of systematic reviews) (June 2013). We also contacted review authors in an effort to identify further relevant reviews.
Selection criteria: We included Cochrane and non‐Cochrane reviews of randomised controlled trials (RCTs) of patients with stroke comparing upper limb interventions with no treatment, usual care or alternative treatments. Our primary outcome of interest was upper limb function; secondary outcomes included motor impairment and performance of activities of daily living. When we identified overlapping reviews, we systematically identified the most up‐to‐date and comprehensive review and excluded reviews that overlapped with this.
Data collection and analysis: Two overview authors independently applied the selection criteria, excluding reviews that were superseded by more up‐to‐date reviews including the same (or similar) studies. Two overview authors independently assessed the methodological quality of reviews (using a modified version of the AMSTAR tool) and extracted data. Quality of evidence within each comparison in each review was determined using objective criteria (based on numbers of participants, risk of bias, heterogeneity and review quality) to apply GRADE (Grades of Recommendation, Assessment, Development and Evaluation) levels of evidence. We resolved disagreements through discussion. We systematically tabulated the effects of interventions and used quality of evidence to determine implications for clinical practice and to make recommendations for future research.
Main results
Our searches identified 1840 records, from which we included 40 completed reviews (19 Cochrane; 21 non‐Cochrane), covering 18 individual interventions and dose and setting of interventions. The 40 reviews contain 503 studies (18,078 participants). We extracted pooled data from 31 reviews related to 127 comparisons. We judged the quality of evidence to be high for 1/127 comparisons (transcranial direct current stimulation (tDCS) demonstrating no benefit for outcomes of activities of daily living (ADLs)); moderate for 49/127 comparisons (covering seven individual interventions) and low or very low for 77/127 comparisons.
Moderate‐quality evidence showed a beneficial effect of constraint‐induced movement therapy (CIMT), mental practice, mirror therapy, interventions for sensory impairment, virtual reality and a relatively high dose of repetitive task practice, suggesting that these may be effective interventions; moderate‐quality evidence also indicated that unilateral arm training may be more effective than bilateral arm training. Information was insufficient to reveal the relative effectiveness of different interventions.
Moderate‐quality evidence from subgroup analyses comparing greater and lesser doses of mental practice, repetitive task training and virtual reality demonstrates a beneficial effect for the group given the greater dose, although not for the group given the smaller dose; however tests for subgroup differences do not suggest a statistically significant difference between these groups. Future research related to dose is essential.
Specific recommendations for future research are derived from current evidence. These recommendations include but are not limited to adequately powered, high‐quality RCTs to confirm the benefit of CIMT, mental practice, mirror therapy, virtual reality and a relatively high dose of repetitive task practice; high‐quality RCTs to explore the effects of repetitive transcranial magnetic stimulation (rTMS), tDCS, hands‐on therapy, music therapy, pharmacological interventions and interventions for sensory impairment; and up‐to‐date reviews related to biofeedback, Bobath therapy, electrical stimulation, reach‐to‐grasp exercise, repetitive task training, strength training and stretching and positioning.
Authors' conclusions
Large numbers of overlapping reviews related to interventions to improve upper limb function following stroke have been identified, and this overview serves to signpost clinicians and policy makers toward relevant systematic reviews to support clinical decisions, providing one accessible, comprehensive document, which should support clinicians and policy makers in clinical decision making for stroke rehabilitation.
Currently, no high‐quality evidence can be found for any interventions that are currently used as part of routine practice, and evidence is insufficient to enable comparison of the relative effectiveness of interventions. Effective collaboration is urgently needed to support large, robust RCTs of interventions currently used routinely within clinical practice. Evidence related to dose of interventions is particularly needed, as this information has widespread clinical and research implications.
Type III interferons (IFN-lambdas(λ)) are important cytokines that inhibit viruses and modulate immune responses by acting through a unique IFN-λR1/IL-10RB heterodimeric receptor. Until now, the ...primary antiviral function of IFN-λs has been proposed to be at anatomical barrier sites. Here, we examine the regulation of IFN-λR1 expression and measure the downstream effects of IFN-λ3 stimulation in primary human blood immune cells, compared with lung or liver epithelial cells. IFN-λ3 directly bound and upregulated IFN-stimulated gene (ISG) expression in freshly purified human B cells and CD8+ T cells, but not monocytes, neutrophils, natural killer cells, and CD4+ T cells. Despite similar IFNLR1 transcript levels in B cells and lung epithelial cells, lung epithelial cells bound more IFN-λ3, which resulted in a 50-fold greater ISG induction when compared to B cells. The reduced response of B cells could be explained by higher expression of the soluble variant of IFN-λR1 (sIFN-λR1), which significantly reduced ISG induction when added with IFN-λ3 to peripheral blood mononuclear cells or liver epithelial cells. T-cell receptor stimulation potently, and specifically, upregulated membrane-bound IFNLR1 expression in CD4+ T cells, leading to greater antiviral gene induction, and inhibition of human immunodeficiency virus type 1 infection. Collectively, our data demonstrate IFN-λ3 directly interacts with the human adaptive immune system, unlike what has been previously shown in published mouse models, and that type III IFNs could be potentially utilized to suppress both mucosal and blood-borne viral infections.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary The most common neuropsychiatric outcomes of stroke are depression, anxiety, fatigue, and apathy, which each occur in at least 30% of patients and have substantial overlap of prevalence and ...symptoms. Emotional lability, personality changes, psychosis, and mania are less common but equally distressing symptoms that are also challenging to manage. The cause of these syndromes is not known, and there is no clear relation to location of brain lesion. There are important gaps in knowledge about how to manage these disorders, even for depression, which is the most studied syndrome. Further research is needed to identify causes and interventions to prevent and treat these disorders.
Psychiatric disorders are equally common during pregnancy as among non-pregnant women, and many of these conditions are treated with psychotropic medicines. Relatively little is known about patterns ...of use of many these agents during pregnancy, and specifically of how rates may have shifted during the last decade. We aimed to quantify the rate of pregnancy related exposures to categories of psychotropic medicines stratified according to the primary indication for use (antidepressants, antipsychotics, anxiolytics, and psychostimulants), trimester of pregnancy, trends over time and region, and indication for use.
We conducted a retrospective cohort study of pregnancies among women in the Truven Health MarketScan database (source population 70 million Americans), which captures person-specific clinical use and includes detailed information on filled prescriptions, hospitalizations and outpatient visits for all privately insured employees and their dependents. We classified psychotropic medicines of interest using ATC level 3 accordingly: antipsychotics (N05A); anxiolytics (N05B); antidepressants (N06A); psychostimulants, agents used for ADHD and cognitive enhancement (N06B). We also examined temporal and regional trends in use.
We included 343,299 women who had a live birth between Jan 1, 2006 and Dec 31, 2011, of whom 10.3% were dispensed one or more psychotropic medicines during pregnancy. This rate varied from 6% to 15% between states. The rate of use of psychotropic medicines was relatively stable between 2006 and 2011. The most commonly used psychotropic medicines were selective serotonin reuptake inhibitors (5.1%) and benzodiazepine or benzodiazepine-like medicines (3.9%). Among psychotropic users, the most commonly associated psychiatric diagnosis was depression (25.0%), followed by anxiety disorders (24.4%). Approximately 1.6% of women used more than one category of psychotropic medicine in pregnancy, most commonly an antidepressant and an anxiolytic medicine (1.2%).
Given this relatively high rate of use, the lack of evidence that the most frequently used medications improve birth outcomes and the safety concerns associated with both early and late pregnancy use for many frequently-used medications, there is a need for further study of factors driving psychotropic medication use during pregnancy.
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