Patients' perspectives on taking warfarin: qualitative study in family practice

BACKGROUND: Despite the well-documented benefits of using warfarin to prevent stroke, physicians remain reluctant to initiate therapy, and especially so with the elderly owing to the higher risk of hemorrhage. Prior research suggests that patients are more accepting of the risk of bleeding than are physicians, although there have been few qualitative studies. The aim of this study was to employ qualitative methods to investigate the experience and perspective of individuals taking warfarin. METHODS: We conducted face-to-face interviews with 21 older patients (12 male, 9 female) who had been taking warfarin for a minimum of six months. Participants were patients at a family practice clinic situated in a large, tertiary care teaching hospital. We used a semistructured interview guide with four main thematic areas: decision-making, knowledge/education, impact, and satisfaction. Data were analysed according to the principles of content analysis. RESULTS AND DISCUSSION: Participants tended to have minimal input into the decision to initiate warfarin therapy, instead relying in great part on physicians' expertise. There appeared to be low retention of information received regarding the therapy; half the patients in our sample possessed only a superficial level of understanding of the risks and benefits. This notwithstanding, participants reported a high level of satisfaction with the care provided and a low level of impact on their day-to-day lives. CONCLUSIONS: Minimal patient involvement in the initial decision and modest knowledge did not appear to diminish satisfaction with warfarin management. At the same time, care providers exert a tremendous influence on the initiation of warfarin therapy and should strive to incorporate patient preferences and expectations into the decision-making process

A randomized trial to assess the impact of an antithrombotic decision aid in patients with nonvalvular atrial fibrillation: the DAAFI trial protocol [ISRCTN14429643]

BACKGROUND: Decision aids are often advocated as a means to assist patient and health care provider decision making when faced with complicated treatment or screening decisions. Despite an exponential growth in the availability of decision aids in recent years, their impact on long-term treatment decisions and patient adherence is uncertain due to a paucity of rigorous studies. The choice of antithrombotic therapy for nonvalvular atrial fibrillation (NVAF) is one condition for which a trade-off exists between the potential risks and benefits of competing therapies, and the need to involve patients in decision making has been clearly identified. This study will evaluate whether an evidence-based patient decision aid for patients with NVAF can improve the appropriateness of antithrombotic therapy use by patients and their family physicians. DESIGN: A multi-center, two-armed cluster randomized trial based in community family practices in which patients with NVAF will be randomized to decision aid or usual care. Patients will receive one of four decision aids depending on their baseline stroke risk. The primary outcome is the provision of "appropriate antithrombotic therapy" at 3 months to study participants (appropriateness defined as per the 2001 American College of Chest Physicians recommendations for NVAF). In addition, the impact of this decision aid on patient knowledge, decisional conflict, well-being, and adherence will be assessed after 3 months, 6 months, and 12 months

Evaluation of an electronic warfarin nomogram for anticoagulation of hemodialysis patients

<p>Abstract</p> <p>Background</p> <p>Warfarin nomograms to guide dosing have been shown to improve control of the international normalized ratio (INR) in the general outpatient setting. However, the effectiveness of these nomograms in hemodialysis patients is unknown. We evaluated the effectiveness of anticoagulation using an electronic warfarin nomogram administered by nurses in outpatient hemodialysis patients, compared to physician directed therapy.</p> <p>Methods</p> <p>Hemodialysis patients at any of the six outpatient clinics in Calgary, Alberta, treated with warfarin anticoagulation were included. Two five-month time periods were compared: prior to and post implementation of the nomogram. The primary endpoint was adequacy of anticoagulation (proportion of INR measurements within range ± 0.5 units).</p> <p>Results</p> <p>Overall, 67 patients were included in the pre- and 55 in the post-period (with 40 patients in both periods). Using generalized linear mixed models, the adequacy of INR control was similar in both periods for all range INR levels: in detail, range INR 1.5 to 2.5 (pre 93.6% (95% CI: 88.6% - 96.5%); post 95.6% (95% CI: 89.4% - 98.3%); p = 0.95); INR 2.0 to 3.0 (pre 82.2% (95% CI: 77.9% - 85.8%); post 77.4% (95% CI: 72.0% - 82.0%); p = 0.20); and, INR 2.5 to 3.5 (pre 84.3% (95% CI: 59.4% - 95.1%); post 66.8% (95% CI: 39.9% - 86.0%); p = 0.29). The mean number of INR measurements per patient decreased significantly between the pre- (30.5, 95% CI: 27.0 - 34.0) and post- (22.3, 95% CI: 18.4 - 26.1) (p = 0.003) period. There were 3 bleeding events in each of the periods.</p> <p>Conclusions</p> <p>An electronic warfarin anticoagulation nomogram administered by nurses achieved INR control similar to that of physician directed therapy among hemodialysis patients in an outpatient setting, with a significant reduction in frequency of testing. Future controlled trials are required to confirm the efficacy of this nomogram.</p

The Two Different Isoforms of the RSC Chromatin Remodeling Complex Play Distinct Roles in DNA Damage Responses

The RSC chromatin remodeling complex has been implicated in contributing to DNA double-strand break (DSB) repair in a number of studies. Both survival and levels of H2A phosphorylation in response to damage are reduced in the absence of RSC. Importantly, there is evidence for two isoforms of this complex, defined by the presence of either Rsc1 or Rsc2. Here, we investigated whether the two isoforms of RSC provide distinct contributions to DNA damage responses. First, we established that the two isoforms of RSC differ in the presence of Rsc1 or Rsc2 but otherwise have the same subunit composition. We found that both rsc1 and rsc2 mutant strains have intact DNA damage-induced checkpoint activity and transcriptional induction. In addition, both strains show reduced non-homologous end joining activity and have a similar spectrum of DSB repair junctions, suggesting perhaps that the two complexes provide the same functions. However, the hypersensitivity of a rsc1 strain cannot be complemented with an extra copy of RSC2, and likewise, the hypersensitivity of the rsc2 strain remains unchanged when an additional copy of RSC1 is present, indicating that the two proteins are unable to functionally compensate for one another in DNA damage responses. Rsc1, but not Rsc2, is required for nucleosome sliding flanking a DNA DSB. Interestingly, while swapping the domains from Rsc1 into the Rsc2 protein does not compromise hypersensitivity to DNA damage suggesting they are functionally interchangeable, the BAH domain from Rsc1 confers upon Rsc2 the ability to remodel chromatin at a DNA break. These data demonstrate that, despite the similarity between Rsc1 and Rsc2, the two different isoforms of RSC provide distinct functions in DNA damage responses, and that at least part of the functional specificity is dictated by the BAH domains

Changes in heart failure medications in patients hospitalised and discharged

BACKGROUND: To date, evidence-based recommendations help doctors to manage patients with heart failure (HF). However, the implementation of these recommendations in primary care is still problematic as beneficial drugs are infrequently prescribed. The aim of the study was to determine whether admission to hospital increases usage of beneficial HF medication and if this usage is maintained directly after discharge. METHODS: The study was conducted from November 2002 until January 2004. In 77 patients hospitalised with heart failure (HF), the medication prescribed by the referring general practitioner (GP) and drug treatment directed by the hospital physicians was documented. Information regarding the post-discharge (14 d) therapy by the GP was evaluated via a telephone interview. Ejection fraction values, comorbidity and specifics regarding diagnostic or therapeutic intervention were collected by chart review. RESULTS: When compared to the referring GPs, hospital physicians prescribed more ACE-inhibitors (58.4% vs. 76.6%; p = 0.001) and beta-blockers of proven efficacy in HF (metoprolol, bisoprolol, carvedilol; 58.4% vs. 81.8%). Aldosterone antagonists were also administered more frequently in the hospital setting compared to general practice (14.3% vs. 37.7%). The New York Heart Association classification for heart failure did not influence whether aldosterone antagonists were administered either in primary or secondary care. Fourteen days after discharge, there was no significant discontinuity in discharge medication. CONCLUSION: Patients suffering from HF were more likely to receive beneficial medication in hospital than prior to admission. The treatment regime then remained stable two weeks after discharge. We suggest that findings on drug continuation in different cardiovascular patients might be considered validated for patients with HF

Effectiveness and safety of opicapone in Parkinson's disease patients with motor fluctuations: The OPTIPARK open-label study

BACKGROUND: The efficacy and safety of opicapone, a once-daily catechol-O-methyltransferase inhibitor, have been established in two large randomized, placebo-controlled, multinational pivotal trials. Still, clinical evidence from routine practice is needed to complement the data from the pivotal trials. METHODS: OPTIPARK (NCT02847442) was a prospective, open-label, single-arm trial conducted in Germany and the UK under clinical practice conditions. Patients with Parkinson’s disease and motor fluctuations were treated with opicapone 50 mg for 3 (Germany) or 6 (UK) months in addition to their current levodopa and other antiparkinsonian treatments. The primary endpoint was the Clinician’s Global Impression of Change (CGI-C) after 3 months. Secondary assessments included Patient Global Impressions of Change (PGI-C), the Unified Parkinson’s Disease Rating Scale (UPDRS), Parkinson’s Disease Questionnaire (PDQ-8), and the Non-Motor Symptoms Scale (NMSS). Safety assessments included evaluation of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). RESULTS: Of the 506 patients enrolled, 495 (97.8%) took at least one dose of opicapone. Of these, 393 (79.4%) patients completed 3 months of treatment. Overall, 71.3 and 76.9% of patients experienced any improvement on CGI-C and PGI-C after 3 months, respectively (full analysis set). At 6 months, for UK subgroup only (n = 95), 85.3% of patients were judged by investigators as improved since commencing treatment. UPDRS scores at 3 months showed statistically significant improvements in activities of daily living during OFF (mean ± SD change from baseline: − 3.0 ± 4.6, p < 0.0001) and motor scores during ON (− 4.6 ± 8.1, p < 0.0001). The mean ± SD improvements of − 3.4 ± 12.8 points for PDQ-8 and -6.8 ± 19.7 points for NMSS were statistically significant versus baseline (both p < 0.0001). Most of TEAEs (94.8% of events) were of mild or moderate intensity. TEAEs considered to be at least possibly related to opicapone were reported for 45.1% of patients, with dyskinesia (11.5%) and dry mouth (6.5%) being the most frequently reported. Serious TEAEs considered at least possibly related to opicapone were reported for 1.4% of patients. CONCLUSIONS: Opicapone 50 mg was effective and generally well-tolerated in PD patients with motor fluctuations treated in clinical practice. TRIAL REGISTRATION: Registered in July 2016 at clinicaltrials.gov (NCT02847442)

A role for pharmacists in community-based post-discharge warfarin management: protocol for the 'the role of community pharmacy in post hospital management of patients initiated on warfarin' study

<p>Abstract</p> <p>Background</p> <p>Shorter periods of hospitalisation and increasing warfarin use have placed stress on community-based healthcare services to care for patients taking warfarin after hospital discharge, a high-risk period for these patients. A previous randomised controlled trial demonstrated that a post-discharge service of 4 home visits and point-of-care (POC) International Normalised Ratio (INR) testing by a trained pharmacist improved patients' outcomes. The current study aims to modify this previously trialled service model to implement and then evaluate a sustainable program to enable the smooth transition of patients taking warfarin from the hospital to community setting.</p> <p>Methods/Design</p> <p>The service will be trialled in 8 sites across 3 Australian states using a prospective, controlled cohort study design. Patients discharged from hospital taking warfarin will receive 2 or 3 home visits by a trained 'home medicines review (HMR)-accredited' pharmacist in their 8 to 10 days after hospital discharge. Visits will involve a HMR, comprehensive warfarin education, and POC INR monitoring in collaboration with patients' general practitioners (GPs) and community pharmacists. Patient outcomes will be compared to those in a control, or 'usual care', group. The primary outcome measure will be the proportion of patients experiencing a major bleeding event in the 90 days after discharge. Secondary outcome measures will include combined major bleeding and thromboembolic events, death, cessation of warfarin therapy, INR control at 8 days post-discharge and unplanned hospital readmissions from any cause. Stakeholder satisfaction will be assessed using structured postal questionnaire mailed to patients, GPs, community pharmacists and accredited pharmacists at the completion of their study involvement.</p> <p>Discussion</p> <p>This study design incorporates several aspects of prior interventions that have been demonstrated to improve warfarin management, including POC INR testing, warfarin education and home visits by trained pharmacists. It faces several potential challenges, including the tight timeframe for patient follow-up in the post-discharge period. Its strengths lie in a strong multidisciplinary team and the utilisation of existing healthcare frameworks. It is hoped that this study will provide the evidence to support the national roll-out of the program as a new Australian professional community pharmacy service.</p> <p>Trial Registration</p> <p>Australian New Zealand Clinical Trials Registry Number <a href="http://www.anzctr.org.au/trial_view.aspx?ID=82959">12608000334303</a>.</p

Rate accelerations in nuclear 18S rDNA of mycoheterotrophic and parasitic angiosperms

Rate variation in genes from all three genomes has been observed frequently in plant lineages with a parasitic and mycoheterotrophic mode of life. While the loss of photosynthetic ability leads to a relaxation of evolutionary constraints in genes involved in the photosynthetic apparatus, it remains to be determined how prevalent increased substitution rates are in nuclear DNA of non-photosynthetic angiosperms. In this study we infer rates of molecular evolution of 18S rDNA of all parasitic and mycoheterotorphic plant families (except Lauraceae and Polygalaceae) using relative rate tests. In several holoparasitic and mycoheterotrophic plant lineages extremely high substitution rates are observed compared to other photosynthetic angiosperms. The position and frequency of these substitutions have been identified to understand the mutation dynamics of 18S rRNA in achlorophyllous plants. Despite the presence of significantly elevated substitution rates, very few mutations occur in major functional and structural regions of the small ribosomal molecule, providing evidence that the efficiency of the translational apparatus in non-photosynthetic plants has not been affected

Operons

Operons (clusters of co-regulated genes with related functions) are common features of bacterial genomes. More recently, functional gene clustering has been reported in eukaryotes, from yeasts to filamentous fungi, plants, and animals. Gene clusters can consist of paralogous genes that have most likely arisen by gene duplication. However, there are now many examples of eukaryotic gene clusters that contain functionally related but non-homologous genes and that represent functional gene organizations with operon-like features (physical clustering and co-regulation). These include gene clusters for use of different carbon and nitrogen sources in yeasts, for production of antibiotics, toxins, and virulence determinants in filamentous fungi, for production of defense compounds in plants, and for innate and adaptive immunity in animals (the major histocompatibility locus). The aim of this article is to review features of functional gene clusters in prokaryotes and eukaryotes and the significance of clustering for effective function