Suboptimal Use of Oral Anticoagulants in Atrial Fibrillation: Has the Introduction of Direct Oral Anticoagulants Improved Prescribing Practices?

Background and Objectives

Atrial fibrillation (AF) and the associated risk of stroke are emerging epidemics throughout the world. Suboptimal use of oral anticoagulants for stroke prevention has been widely reported from observational studies. In recent years, direct oral anticoagulants (DOACs) have been introduced for thromboprophylaxis. We conducted a systematic literature review to evaluate current practices of anticoagulation in AF, pharmacologic features and adoption patterns of DOACs, their impacts on proportion of eligible patients with AF who receive oral anticoagulants, persisting challenges and future prospects for optimal anticoagulation.

Literature Source and Selection Criteria

In conducting this review, we considered the results of relevant prospective and retrospective observational studies from real-world practice settings. PubMed (MEDLINE), Scopus (RIS), Google Scholar, EMBASE and Web of Science were used to source relevant literature. There were no date limitations, while language was limited to English. Selection was limited to articles from peer reviewed journals and related to our topic.

Results

Most studies identified in this review indicated suboptimal use of anticoagulants is a persisting challenge despite the availability of DOACs. Underuse of oral anticoagulants is apparent particularly in patients with a high risk of stroke. DOAC adoption trends are quite variable, with slow integration into clinical practice reported in most countries; there has been limited impact to date on prescribing practice.

Conclusion

Available data from clinical practice suggest that suboptimal oral anticoagulant use in patients with AF and poor compliance with guidelines still remain commonplace despite transition to a new era of anticoagulation featuring DOACs.

     

Community pharmacists’ knowledge and perspectives of reporting adverse drug reactions in Australia: a cross-sectional survey

International Journal of Clinical Pharmacy - Background Under-reporting of adverse drug reactions (ADRs) by healthcare professionals is prevalent worldwide. Community pharmacists are the most...     

心脏主动脉双叶瓣流固耦合模型定常流场数值的分析

目的:人工心脏瓣膜置换术后的并发症均与心瓣膜置换后引起的血流特性紊乱有关,因此分析心脏主动脉位置双叶人工机械心瓣/血液耦合系统的血流动力学特性和瓣叶机械应力分布情况,为机械心瓣的设计、优化和临床研究提供一定理论依据。方法:采用大型有限元分析软件ANSYS中的CFD(计算流体动力学)模块并运用顺序耦合分析方法分别建立物理环境和结构环境对双叶人工机械心脏瓣膜与其周围血液进行单向流固耦合分析。结果:获得了瓣膜在稳态流动情况下合理的血流速度场、压力场和流体切应力的分布情况及瓣阀的机械应力分布图。在减速时相下,人工机械瓣的速度场出现明显的湍流区、回流区及漩涡区;跨瓣压差较小,压力场有低压力分布;最大雷诺切应力出现在瓣叶窄流道附近,下游壁面附近有低切应力(雷诺切应力)分布,且峰值切应力远离壁面;人工机械瓣叶上无应力集中现象产生。结论:采用大型有限元分析软件ANSYS,建立了主动脉机械双叶瓣-血液耦合运动的两维数值模型,初步采用CFD中的顺序耦合分析方法对血液通过主动脉位置的人工机械瓣进行了单向流固耦合分析的方法是可行的。     

Time course of detection of viral and serologic markers preceding human immunodeficiency virus type 1 seroconversion: implications for screening of blood and tissue donors

BACKGROUND: Almost all human immunodeficiency virus (HIV) transmission via blood or tissues that has occurred since anti-HIV screening was implemented in 1985 is traceable to blood given after infection but before antibody seroconversion, a time that is referred to as the window period. In this study, the performance of newer assays designed to detect viral and serologic markers soon after infection is assessed, and the reduction in the window period achieved by these assays is estimated. STUDY DESIGN AND METHODS: Three cohort studies of persons at high risk for acquiring HIV infection were identified. These studies included well-controlled HIV type 1 (HIV-1) polymerase chain reaction (PCR) analyses of serial preseroconversion specimens from HIV-1- seroconverting homosexual men or intravenous drug users. Of 81 enrollees with anti-HIV-1 seroconversion documented by a viral lysate anti-HIV-1 enzyme immunosorbent assay (EIA) available in 1989, 13 (16%) had PCR-positive preseroconversion specimens. In the present study, sera from these 13 PCR-positive samples were further tested for anti- HIV by 10 contemporary EIAs and 6 supplemental assays, as well as being tested for plasma p24 antigen and HIV-1 RNA. Preseroconversion sera from 38 HIV-1 DNA PCR-negative cohort participants were also tested by selected anti-HIV EIAs and tested for p24 antigen and HIV-1 RNA. On the basis of these laboratory data and the intervals between blood drawing in all 81 men, the reduction in the preseroconversion window period achieved by these new assays was estimated with a mathematical model developed to analyze seroconversion data. RESULTS: Nine (69%) of the 13 preseroconversion PCR-positive samples had anti-HIV that was detectable by one or more contemporary anti-HIV-1 or anti-HIV type 2 EIA. Supplemental antibody assays were negative on all four EIA-nonreactive preseroconversion samples and negative or indeterminate on a high proportion of the nine EIA-reactive PCR-positive samples. Eight (61%) of the 13 samples were p24 antigen-positive, and 11 (85%) were HIV-1 RNA-positive. The estimated reductions in the window period (relative to the index viral lysate-based anti-HIV EIA) were as follows: contemporary anti-HIV-1/2 EIAs, 20.3 days (95% Cl, 8.0–32.5); p24 antigen and DNA PCR, 26.4 days (95% Cl, 12.6–38.7); and RNA PCR, 31.0 days (95% Cl, 16.7–45.3). CONCLUSION: Recent improvement in the sensitivity of anti-HIV assays has resulted in significant shortening of the preseroconversion window period. Consequently, the incremental reduction in the window period that could be achieved by implementing direct virus-detection assays has diminished significantly.     

Perceived feasibility of a community pharmacy-based asthma intervention: a qualitative follow-up study

What is known and Objective: Asthma is a National Health Priority Area in Australia; however, recent evidence suggests that its management remains suboptimal. Community pharmacists are in a unique position to help patients manage asthma, and a number of community pharmacy‐based asthma interventions have demonstrated effectiveness with improved patient outcomes. This study aimed to explore the views of general practitioners (GPs), community pharmacists and patients towards a pharmacy‐based intervention that saw patients with poorly managed asthma supplied with educational material and referred to their GP for an asthma management review. Methods: A qualitative follow‐up study of participants who had been involved in the intervention was conducted. A sample of six GPs, 10 community pharmacists and 10 patients participated in semi‐structured face‐to‐face interviews. Data were analysed using interpretive phenomenology. Results and Discussion: General practitioners accepted the intervention process if they had positive relationships with pharmacists. There was also some hesitance of GPs towards the intervention, related to a perceived encroachment on their area of responsibility and a perceived conflict of interest of pharmacists in providing health care. GPs indicated the need to be more involved with the intervention process, and expressed that patients were rarely forthcoming about problems with their asthma. Community pharmacists felt that patients can be apathetic about asthma and often fail to seek medical advice. The intervention was implemented very easily, with minimal disruptions to the pharmacists’ workflow, and pharmacists suggested that it would be better if GPs were more involved with the intervention process. Patients’ general satisfaction with pharmacy services was high, but their expectations were quite low. Although there was an appreciation by patients of community pharmacists’ interest in their health, this did not necessarily translate into appointments with GPs for an asthma management review. The reason for this related primarily to patients’ under‐estimation of their asthma severity. What is new and Conclusion: A wider rollout of the asthma intervention, with an improved process for involving GPs, would be feasible and well accepted. Further research should determine the best approach in influencing patients’ perceptions of asthma control and whether these perceptions are amenable to a more intensive educational intervention. This could result in more efficient asthma interventions, translating to improved patient outcomes.     

Hematopoietic Stem Cell and Gene Therapy Corrects Primary Neuropathology and Behavior in Mucopolysaccharidosis IIIA Mice

Mucopolysaccharidosis IIIA (MPS IIIA or Sanfilippo disease) is a neurodegenerative disorder caused by a deficiency in the lysosomal enzyme sulfamidase (SGSH), catabolizing heparan sulfate (HS). Affected children present with severe behavioral abnormalities, sleep disturbances, and progressive neurodegeneration, leading to death in their second decade. MPS I, a similar neurodegenerative disease accumulating HS, is treated successfully with hematopoietic stem cell transplantation (HSCT) but this treatment is ineffectual for MPS IIIA. We compared HSCT in MPS IIIA mice using wild-type donor cells transduced ex vivo with lentiviral vector-expressing SGSH (LV-WT-HSCT) versus wild-type donor cell transplant (WT-HSCT) or lentiviral-SGSH transduced MPS IIIA cells (LV-IIIA-HSCT). LV-WT-HSCT results in 10% of normal brain enzyme activity, near normalization of brain HS and GM2 gangliosides, significant improvements in neuroinflammation and behavioral correction. Both WT-HSCT and LV-IIIA-HSCT mediated improvements in GM2 gangliosides and neuroinflammation but were less effective at reducing HS or in ameliorating abnormal HS sulfation and had no significant effect on behavior. This suggests that HS may have a more significant role in neuropathology than neuroinflammation or GM2 gangliosides. These data provide compelling evidence for the efficacy of gene therapy in conjunction with WT-HSCT for neurological correction of MPS IIIA where conventional transplant is ineffectual.     

Warfarin management after discharge from hospital: a qualitative analysis

What is Known and Objective: Warfarin is recognized as a high‐risk medication for adverse events, and the risks are particularly heightened in the period immediately following a patient’s discharge from hospital. This qualitative study aimed to explore the experiences of Australian patients and healthcare professionals of warfarin management in the post‐discharge period and identify the benefits and deficiencies of existing systems, to inform the development of a model for a new collaborative post‐discharge warfarin management service. Methods: Healthcare professionals, professional organization representatives and patients recently discharged from hospital taking warfarin (consumers) were recruited via purposive, criterion‐based sampling within two Australian states. Semi‐structured telephone interviews were conducted between August and October 2008 using standard discussion guides. Data were manually analyzed to identify emergent themes using a phenomenological approach. Results: Forty‐seven participants were involved in the telephone interviews. Three major themes emerged: (i) appropriate warfarin education is integral to effective warfarin management, (ii) problems occur in communication along the continuum of care and (iii) home‐delivered services are valuable to both patients and healthcare professionals. Discussion: Although high‐quality warfarin education and effective communication at the hospital–community interface were identified as important in post‐discharge warfarin management, deficiencies were perceived within current systems. The role of home‐delivered services in ensuring timely follow‐up and promoting continuity of care was recognized. Previous studies exploring anticoagulation management in other settings have identified similar themes. Post‐discharge management should therefore focus on providing patients with a solid foundation to minimize future problems. What is New and Conclusion: Addressing the three identified facets of care within a new, collaborative post‐discharge warfarin management service may address the perceived deficiencies in existing systems. Improvements may result in the short‐ and longer‐term health outcomes of patients discharged from hospital taking warfarin, including a reduction in their risk of adverse events.     

Impending cardiac herniation: the snow cone sign

Two cases of cardiac herniation and volvulus that occurred after right pneumonectomy are presented. Both asymptomatic patients demonstrated an unusual bulging contour to the right side of the heart on radiographs obtained in the recovery room, before complete herniation and volvulus occurred. In an autopsy preparation, a similar right contour was produced after partial cardiac herniation through a pericardial defect. The hemispheric contour from partial cardiac herniation resembles the shape of a snow cone. Clinical awareness of this sign of impending herniation is important, so risk factors known to produce herniation may be modified.     

Dopamine Transporter Regulation during Four Nights of REM Sleep Deprivation Followed by Recovery – An in vivo Molecular Imaging Study in Humans

Objectives:

To assess the influence of total or selective REM sleep deprivation on the dopamine transporter (DAT) densities and sleep patterns of healthy volunteers.

Design:

Prospective study.

Setting:

Evaluation of polysomnography recordings and DAT density after 4 nights of selective REM sleep deprivation followed by 3 nights of sleep recovery compared to a control group and a group that was subjected to 2 nights of total sleep deprivation. Single positron emission computed tomography and [^99mTc]TRODAT-1 were used to assess the cerebral DAT density in the striatum at baseline, after REM sleep deprivation and total sleep deprivation as well as after sleep recovery. Blood was collected daily to examine prolactin and estradiol levels, which were correlated with dopaminergic activity.

Patients or Participants:

Thirty healthy male volunteers ranging from 19 to 29 years of age were randomly assigned to one of three experimental groups after giving written informed consent (10 non-sleep deprived, 10 total sleep deprived, and 10 REM sleep deprived).

Measurements and Results:

Four nights of REM sleep deprivation and 2 nights of total sleep deprivation induced distinct and heterogeneous patterns of sleep recovery. No significant modulation of DAT availability was observed within groups. In the recovery nights, changes in cortisol, prolactin and estradiol concentrations were significantly correlated with specific sleep stages in the total and REM sleep deprived groups. In addition, DAT density was positively correlated with estradiol concentration and inversely associated with SWS latency only after total sleep deprivation.

Conclusion:

Our study demonstrates that although sleep deprivation did not promote significant alterations in DAT density within the striatum, there were significant correlations among transporter availability, hormonal concentrations and sleep parameters.

Citation:

Martins, RCS; Andersen ML; Garbuio SA; Bittencourt LR: Guindalini C; Shih MC; Hoexter MQ; Bressan RA; Castiglioni MLV; Tufik S. Dopamine transporter regulation during four nights of REM sleep deprivation followed by recovery – an in vivo molecular imaging study in humans. SLEEP 2010;33(2):243-251.