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Table 26 summarises the characteristics of these participants generic 5mg emsam amex anxiety box. TABLE 24 Baseline demographic and clinical characteristics for questionnaire respondents Variable Proportion % Gender Group All Female 736/1403 52 buy emsam visa anxiety symptoms not anxious. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed cheap emsam 5mg amex anxiety symptoms in head, the full report) may be included in professional journals 51 provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising discount 5mg emsam otc anxiety symptoms women. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. CLINICAL EFFECTIVENESS TABLE 24 Baseline demographic and clinical characteristics for questionnaire respondents (continued) Variable Proportion % PRISM risk group 4 Female 68/140 48. S i g ni fi cantcov ari ates and factors ( p unless oth erw i se stated) are: a g e atstudy day 1 p W h ealth component and PR I S M score. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journals 55 provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. CLINICAL EFFECTIVENESS TABLE 26 Baseline demographic and clinical characteristics for the technical performance subsample (continued) Mean SD n Study PRISM score Group All 6. Analysis The data are summarised, first, as a ROC curve (Figure 5) and, second, again consistent with interpreting a PRISM score, as a probability of an emergency hospital admission in 12 months, by comparing observed and expected numbers of emergency hospital admissions between 1 August 2012 and 31 July 2013, for both the overall subsample and the PRISM risk group (Table 27). Table 27 shows that overall PRISM performed well, with some variation – fewer than expected admissions at risk level 1, but more admissions than expected at risk levels 2–4. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journals 57 provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. Processing of the ISAs was estimated to take 20 minutes from discussion with the research team. The different downloading and activation scenarios are shown with associated costs. These were based on support requirements in the actual trial general practices. TABLE 28 Cost components of PRISM activation in general practices Cost (£) Cost component/resources required Staff involved Unit Overall Pre-activation phase General practice staff opportunity costs: GP; PM 109. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journals 59 provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. HEALTH ECONOMICS RESULTS TABLE 28 Cost components of PRISM activation in general practices (continued) Cost (£) Cost component/resources required Staff involved Unit Overall Scenario 3 Site visit required by NWIS IT technician to IT technician; band 4 £10. This cost of setting up PRISM represents the costs incurred during the trial period. Resource use and cost of GP trainers are shown in Table 29. The costs include GP trainer training, GP trainer time during training, as well as GP opportunity cost. Predictive risk stratification model running and maintenance costs The tasks required and costs of PRISM on a regular basis are summarised in Table 30. The annual running costs were calculated using the unit cost of each component of operating and maintaining the PRISM software system and deriving an annual cost from the unit cost. Running monthly data uploads were calculated at £79 per month, which equates to £952 per year for all practices. It was estimated that maintenance of the PRISM software would be required every 2 years and calculated to cost £2048, which equates to £1024 per year. The staff cost (opportunity cost) of participating general practices was calculated as part of the implementation costs for the PRISM scoring tool. Two general practices (numbers 13 and 30) were excluded from this analysis. Practice 13 was the GP champion practice working alongside the trial research team and hence logged into the PRISM software far more frequently than would be expected from routine use (29 times). Practice 30 was also initially a GP champion practice, but dropped out after approximately 1 month. The high frequency of logins by GPs during this early phase was also considered non-routine use. Trial team members travelled to the GPs to deliver training Training session in general practice on how to use Trainer GP × 1-hour 62. However, the login statistics from NWIS did not provide information on how much time was spent using the PRISM software. Average length of time spent using PRISM software/data was therefore derived from the interviews held with general practice staff and the corresponding online questionnaire. However, there are several limitations associated with the following data. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journals 61 provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. HEALTH ECONOMICS RESULTS TABLE 30 Cost components of PRISM maintenance (provider costs) Cost (£) Cost component/resource used Staff involved Unit Overall Running monthly data uploads and providing e-mail support IT technician; band 10. Loading of demographic data received from GP surgeries 2. Refresh PRISM database with GP data and secondary care data (inpatients/outpatients) 4. Confirming updates to general practices via the PRISM website (10-minute activity) 6. E-mail support for PRISM enquiries (during the trial NWIS have received fewer than five e-mail enquiries per month) NWIS estimate that these tasks take approximately 1 day of IT staff time per month for all 32 practices Maintenance/updates of PRISM software: NWIS estimate Band 7 IT technician 18. Table 31 shows the available data on frequency and duration of PRISM use by different users within the participating practices. The overall staff cost in the first 9 months post implementation for all 30 trial practices included in the analysis was £9182. Costs associated with general practice staff using the PRISM software were calculated by extrapolating the 9-month cost of £9182 to 12 months resulting in a yearly staff opportunity cost of £12,242, which equates to £408 per practice. The total annual cost of operating and maintaining the PRISM software tool across the general practices of the trial area are therefore estimated to be £14,218. This means that use of the PRISM software might be estimated to cost £25,350. These figures are based on trial figures, include staff opportunity cost but exclude any server or other hardware requirements. The 32 practices included in the study had 230,099 patients registered at the beginning of the study, of which 220,683 were included in the intervention phase analysis, equating to a PRISM implementation cost of £0. Cost analysis of primary and secondary health care The mean annualised costs of primary and secondary care per patient, as observed in the control and intervention phases, are summarised in Table 32.

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Proc Natl Acad Sci tivity in the prefrontal cortex of subjects with schizophrenia: re- USA 1995;92:11175–11179 purchase emsam 5 mg without a prescription anxiety and high blood pressure. Long-lasting potentiation of synaptic trans- nous substrates in the induction of long-term potentiation cheap 5mg emsam with amex anxiety 6 things you can touch with your hands. J Biol mission in the dentate area of the anaesthetized rabbit following Chem 1995;270:6119–6124 5mg emsam with visa anxiety tattoos. Long-lasting potentiation of syn- term potentiation Science 1997;276:2042–2045 cheap emsam anxiety symptoms abdominal pain. Autophosphoryla- following stimulation of the perforant path. J Physiol (Lond) tion at Thr286 of the alpha calcium-calmodulin kinase II in LTP 1973;232:357–374. Learning from LTP: a comment on recent at- Science 1998;280:1940–1942. A critical period for long-term poten- strength and Ca2 /calmodulin-dependent kinase II autophos- tiation at thalamocortical synapses. Development and plasticity of cortical processing ar- NMDA receptor-dependent long-term potentiation. The current excitement in with astrocyte transporter currents during LTP. Long-term potentiation: evidence against term potentiation in the hippocampus. Nature 1993;361:31– an increase in transmitter release probability in the CA1 region 39. Use-dependent AMPA receptor 156 Neuropsychopharmacology: The Fifth Generation of Progress block in mice lacking GluR2 suggests postsynaptic site for LTP 64. Homosynaptic long-term depression in tal size by synaptic activity in the hippocampus. Science 1996; area CA1 of hippocampus and effects of N-methyl-D-aspartate 271:1294–1297. Neuron 1994;12:127– requirements for long-term depression in the hippocampus. Postsynaptic factors control the duration of synap- pre- and post-synaptic mechanisms maintain long-term potentia- tic enhancement in area CA1 of the hippocampus. A mechanism for the Hebb and the anti-Hebb pro- propionate-type glutamate receptor. J Biol Chem 1997;272: cesses underlying learning and memory. An essential role for of the alpha-amino-3-hydroxy-5-methylisoxazole4-propionic protein phosphatases in hippocampal long-term depression. Sci- acid receptor GluR1 subunit by calcium/calmodulin-dependent ence 1993;261:1051–1055. Ca2 /calmodulin-kinase cineurin/inhibitor-1 phosphatase cascade in hippocampal long- II enhances channel conductance of alpha-amino-3-hydroxy-5- term depression. Rapid, activation-in- Acad Sci USA 1999;96:3269–3274. Modulation of AMPA receptor tured hippocampal neurons. The site of expression of NMDA in hippocampal cultures. Evidence for silent synapses: imparting both stability and flexibility to synaptic function. Activation of postsynaptically based motility in dendritic spines. Proc Natl Acad Sci USA 1999; silent synapses during pairing-induced LTP in CA1 region of 96:10433–10437. Dendritic spine changes associated with Neurobiol 1998;8:364–369. Long-term synaptic depression in the mammalian Neurosci 2000;3:545–550. Synaptic tagging: implications for late main- of multiple spine synapses between a single axon terminal and a tenance of hippocampal long-term potentiation. Anatomy and electrophysiology of fast central syn- 90. Science 1999; apses lead to a structural model for long-term potentiation. Plasticity in the central nervous system: Sci 1999;354:2027–2052. OLSEN GABA IS THE MAJOR INHIBITORY doxal phosphate and the subcellular localization (7). GABA NEUROTRANSMITTER IN THE NERVOUS was shown to be released from electrically stimulated inhibi- SYSTEM tory nerve cells (8), and a mechanism of rapid removal from the synaptic release site was demonstrated by identification Several amino acids are found in high concentrations in of high-affinity transporter proteins (9,10). The application brain, and some have been established as neurotransmitters. Glycine is a secondary rapid inhibitory neurotransmitter, especially in the spinal cord (1,2). Because of the widespread presence and utiliza- PHYSIOLOGY AND PHARMACOLOGY OF tion of glutamate and GABA as transmitters, one could say GABAA,GABA ,B AND GABAC RECEPTORS that they are involved in all functions of the central nervous system (CNS), as well as in all diseases. At any point in the GABA-mediated synaptic inhibition involves rapid, less CNS, one is either at a cell that uses or responds to gluta- than 100-millisecond, inhibitory postsynaptic potentials mate and GABA or no more than one cell removed. Many and slower, more than 100-millisecond, inhibitory post- clinical conditions including psychiatric disorders appear synaptic potentials. The former were shown by voltage to involve an imbalance in excitation and inhibition, and clamp to involve increased chloride ion permeability and therapeutics thus involve attempts to restore the balance. The rapid chloride cur- ics, general anesthetics, and anticonvulsants (3). See the rent defined a physiologic receptor mechanism termed the chapters on GABA in previous editions of this book (1,4). GABAA receptor, also pharmacologically defined by the an- Since its discovery in the CNS in the early 1950s (5,6), tagonist bicuculline, as well as picrotoxin, and the agonist GABA was shown to fulfill the criteria for establishment as muscimol (Fig. Thus, the GABAA receptor is a chlo- a neurotransmitter (Fig. It is synthesized by a specific ride channel regulated by GABA binding, and it is now enzyme, l-glutamic acid decarboxylase (GAD), in one step grouped in the superfamily of ligand-gated ion channel re- from l-glutamate. Thus, in addition to its role in protein ceptors, which includes the well-characterized nicotinic ace- synthesis, in cofactors such as folic acid and in hormones tylcholine receptor, present at the skeletal neuromuscular such as thyrotropin-releasing hormone, and its action as a junction (13,14). Much of the ron by virtue of stabilizing the membrane potential near glutamate and GABA used as neurotransmitter is derived the resting level.

This percentage is irrespective of the distribution channels (book wholesaler cheap emsam 5mg line anxiety meds for dogs, sponsors) buy emsam with a mastercard anxiety symptoms grinding teeth. Profit: depending on circulation 5 mg emsam amex anxiety 40 weeks pregnant, profit is somewhere between 27 (100% - 45% - 28%) and more than 40% (100% - 45% - 13 best purchase for emsam anxiety test questionnaire. The future reader (R) goes into a bookshop (B) and pays the retail price (yellow arrow). The bookseller or wholesaler pays the publishing house (X) after deducting a sales margin of 30 to 45%. The publisher has previously transferred payment for the printing costs to the print shop (P) and pays the authors off over several months or years. The thickness of the yellow arrows reflects the volume of money which flows. The publishers are out of the game and the authors market the books directly through the most important specialised medical bookshops. The future reader (R) goes into the bookstore (B), pays the retail price, and the bookseller remits 70% of this to the authors (A). The authors have previously transferred payment of the printing costs to the print shop (P). The thickness of the yellow arrows reflects the volume of money which flows. In this diagram, we have replaced the bookstore with a sponsor, such as a foundation (S). The sponsor pays the authors for the discounted books, and the authors in turn pay the printer (P). The reader (R) generally receives the books free of charge and is grateful (blue arrow). One or more sponsors have taken on a circulation of 1000 books and give the books away to doctors who are interested. The thickness of the yellow arrows reflects the volume of money which flows. Blue arrow: gratitude In chapters 2 and 4 we go on to develop the thoroughly fascinating subject of financing and we will see that it is by no means ruinous to manufacture and market books. We also investigate the sales figures needed to make book production financially interesting. The most important subjects can be covered in 100 textbooks. We need 100 clever, dedicated and far- sighted doctors. Whoever starts running now might be first past the post, and whoever gets established first will have a head start which will make it hard for competitors to catch up. If you keep your copyright, you are your own master and can enjoy previously undreamed of liberties. This freedom makes things possible which would have been considered utopian just a few years ago. Copyright removal is one of the magic words you have come across in connection with HIVMedicine. Just say the word, and your texts will emerge in half a dozen different languages. That depends on whether you are an editor, an author, a doctor, a student or an interested bystander. Editor/Publisher ƒ Today, a text should be published simultaneously in a book and on free internet sites. If you write for a book only, you reach considerably fewer readers than someone who publishes both in a book and on the internet at the same time. In a direct comparison of book only and book + internet, “books only” have little chance of survival. Author ƒ If an editor asks you to write a chapter for a medical textbook, ask him if the text will be accessible free of charge on the internet. If not, find out if there are any better projects to be had. Flying Publisher – and the chapters you write – do not deserve to be locked up in a book only. Doctor ƒ If you have the choice between two equally good and comparably substantial books, buy the book which is available free of charge on the internet. Student ƒ Ask your professors if they have ever worked on a Flying Publisher textbook. Bystander ƒ Would you have believed that doctors have the knowledge and skills needed to produce their own textbooks? You intend to take on one of the 100 important medical topics and contribute to the task of making medical information available without restriction and free of charge. As you know, if your book project is well-organised, it can be completed in 9 months, 12 at the most. Before you begin to structure your topic and put together the group of authors, here are a few brief comments concerning your own personal qualifications. Personal qualifications Firstly: in order to write a medical book, you need expertise (Table 2. You should therefore know enough experienced colleagues who can take on a chapter of your project and deal with it competently. This assumes that you know your way around the national scene. This requirement can usually only be fulfilled if you come from a university institute or one of the big teaching hospitals. A rule of thumb is: most texts are produced between 9 p. This means that at least a minimum level of enthusiasm is necessary. Sometimes, the thought that the sacrifice is only temporary and the subsequent editions will require considerably less work can help. You push the project through and then say “never again! Some things you only do once, but once they are done, they are done. But first, here are two thoughts which will help you to avoid wasting time: ƒ Your should only write if your book can become the No. There are as many mediocre books out there as there are rats in the sewers of Paris.

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Jessurun ER buy 5mg emsam mastercard anxiety treatment for children, van Hemel NM generic 5mg emsam amex anxiety pill names, Defauw JJ generic 5mg emsam visa anxiety blood pressure, et Randomized comparison between al discount emsam master card anxiety symptoms confusion. A randomized study of combining maze pulmonary vein antral isolation versus surgery for atrial fibrillation with mitral complex fractionated electrogram ablation valve surgery. Ablation of superior pulmonary of catheter ablation and surgical CryoMaze veins compared to ablation of all four procedure in patients with long-lasting pulmonary veins. J Cardiovasc persistent atrial fibrillation and rheumatic Electrophysiol. Comparison of effectiveness of circumferential pulmonary vein isolation carvedilol versus bisoprolol for maintenance preferable to stepwise segmental pulmonary of sinus rhythm after cardioversion of vein isolation for patients with paroxysmal persistent atrial fibrillation. J isolation for atrial fibrillation: a randomized Cardiovasc Electrophysiol. Kochiadakis GE, Igoumenidis NE, Hamilos Noninducibility of atrial fibrillation as an MI, et al. Long-term maintenance of normal end point of left atrial circumferential sinus rhythm in patients with current ablation for paroxysmal atrial fibrillation: a symptomatic atrial fibrillation: amiodarone randomized study. Kochiadakis GE, Igoumenidis NE, Comparison of surgical cut and sew versus Marketou ME, et al. Low dose amiodarone radiofrequency pulmonary veins isolation and sotalol in the treatment of recurrent, for chronic permanent atrial fibrillation: a symptomatic atrial fibrillation: a randomized study. Amiodarone, sotalol, Maintenance of sinus rhythm after electrical or propafenone in atrial fibrillation: which is cardioversion of persistent atrial fibrillation; preferred to maintain normal sinus rhythm? Surgical treatment of permanent atrial Bhuripanyo K, et al. A randomized clinical fibrillation using microwave energy trial of the efficacy of radiofrequency ablation: a prospective randomized clinical catheter ablation and amiodarone in the trial. Does Pulmonary vein isolation and linear lesions additional linear ablation after in atrial fibrillation ablation. J Interv Card circumferential pulmonary vein isolation Electrophysiol. PMID: improve clinical outcome in patients with 17318445. Randomized study comparing combined pulmonary vein-left atrial junction 279. Radiofrequency ablation vs antiarrhythmic drugs as first-line treatment 280. Epicardial microwave ablation of permanent atrial fibrillation during a coronary bypass 281. Pulmonary randomized assessment of the incremental vein isolation combined with superior vena role of ablation of complex fractionated cava isolation for atrial fibrillation ablation: atrial electrograms after antral pulmonary a prospective randomized study. Am ablation after left atrial ablation of complex Heart J. PMID: fractionated atrial electrograms for long- 17383295. Thyroid function abnormalities during PMID: 19808388. Systematic electrocardioversion for atrial An evaluation of the strategy of maintenance fibrillation and role of antiarrhythmic drugs: of sinus rhythm by antiarrhythmic drug a substudy of the SAFE-T trial. Heart therapy after ablation and pacing therapy in Rhythm. Quality of life variables in the selection of rate versus rhythm control 296. Quality of life improves with treatment in the Canadian Trial of Atrial Fibrillation. PMID: Rhythm or rate control in atrial fibrillation— 12075253. Pharmacological Intervention in Atrial Fibrillation (PIAF): a randomised trial. PMID: Amiodarone reduces procedures and costs 11117910. Rate control vs rhythm control in patients with nonvalvular persistent atrial fibrillation: 291. Pappone C, Vicedomini G, Giuseppe A, et randomised, controlled study of rate versus al. Radiofrequency Catheter Ablation and rhythm control in patients with chronic atrial Antiarrhythmic Drug Therapy: A fibrillation and heart failure: (CAFE-II Prospective, Randomized 4-Year Follow-Up Study). Maintenance of sinus rhythm and survival in Improvements in symptoms and quality of patients with heart failure and atrial life in patients with paroxysmal atrial fibrillation. Comparison of rate and rhythm control in hypertension patients with atrial fibrillation. Pulmonary-vein isolation for atrial Discerning the incidence of symptomatic fibrillation in patients with heart failure. PMID: fibrillation before and after catheter ablation 18946063. MacDonald MR, Connelly DT, Hawkins 2013;173(2):149-56. Radiofrequency ablation for persistent atrial fibrillation in patients with 308. Food and Drug Administration HR hazard ratio HRS Heart Rhythm Society ICD implantable cardioverter defibrillator; ICTRP International Clinical Trials Registry Platform IOM Institute of Medicine IQR interquartile range J Joules KQ(s) Key Question(s) LVEF left ventricular ejection fraction LVH left ventricular hypertrophy MI myocardial infarction NR not reported NS not statistically significant NYHA New York Heart Association PICOTS Populations, Interventions, Comparators, Outcomes, Timings, and Settings of interest PRISMA Preferred Reporting Items for Systematic Reviews and Meta-Analyses PV pulmonary vein PVI pulmonary vein isolation RACE(-II) Rate Control Efficacy in Permanent Atrial Fibrillation(-II) RCT(s) randomized controlled trial(s) 151 RFA radiofrequency ablation RV right ventricular SD standard deviation SF-36 Medical Outcomes Study 36-Item Short Form Health Survey TEP Technical Expert Panel VVIR ventricular demand rate-responsive WHO World Health Organization 152 Appendix A. Exact Search Strings ® PubMed Search Strategy (Final Search Date August 1, 2012) KQ 1—What are the comparative safety and effectiveness of pharmacological agents used for ventricular rate control in patients with atrial fibrillation? Do the comparative safety and effectiveness of these therapies differ among specific patient subgroups of interest? Set # Terms #1 “Atrial Fibrillation”[Mesh] OR “atrial fibrillation”[tiab] OR (atrial[tiab] AND fibrillation[tiab]) OR afib[tiab] OR “atrial flutter”[MeSH Terms] OR “atrial flutter”[tiab] #2 ”Anti-Arrhythmia Agents”[Mesh] OR “Anti-Arrhythmia Agents”[Pharmacological Action] OR ((antiarrhythmic[tiab] OR antiarrhythmia[tiab]) AND (agent[tiab] OR agents[tiab] OR drug[tiab] OR drugs[tiab])) OR “metoprolol”[MeSH Terms] OR “metoprolol”[tiab] OR “atenolol”[MeSH Terms] OR “atenolol”[tiab] OR “carvedilol”[Supplementary Concept] OR “carvedilol”[tiab] OR “bisoprolol”[MeSH Terms] OR “bisoprolol”[tiab] OR “timolol”[MeSH Terms] OR “timolol”[tiab] OR “esmolol”[Supplementary Concept] OR “esmolol”[tiab] OR “nebivolol”[Supplementary Concept] OR “nebivolol”[tiab] OR verapamil[tiab] OR “verapamil”[MeSH Terms] OR “diltiazem”[MeSH Terms] OR “diltiazem”[tiab] OR “digoxin”[MeSH Terms] OR “digoxin”[tiab] OR “Adrenergic beta-Antagonists”[Mesh] OR “Adrenergic beta- Antagonists”[Pharmacological Action] OR beta-blocker[tiab] OR beta-blockers[tiab] OR “Calcium Channel Blockers”[Mesh] OR “Calcium Channel Blockers” [Pharmacological Action] OR “Acebutolol”[Mesh] OR acebutolol[tiab] OR “Nadolol”[Mesh] OR Nadolol[tiab] OR “Amiodarone”[Mesh] OR Amiodarone[tiab] OR “dronedarone” [Supplementary Concept] OR dronedarone[tiab] #3 “evaluation studies”[Publication Type] OR “evaluation studies as topic”[MeSH Terms] OR “evaluation study”[tw] OR evaluation studies[tw] OR “intervention studies”[MeSH Terms] OR “intervention study”[tw] OR “intervention studies”[tw] OR “case-control studies”[MeSH Terms] OR “case-control”[tw] OR “cohort studies”[MeSH Terms] OR cohort[tw] OR “longitudinal studies”[MeSH Terms] OR “longitudinal”[tw] OR longitudinally[tw] OR “prospective”[tw] OR prospectively[tw] OR “retrospective studies”[MeSH Terms] OR “retrospective”[tw] OR “follow up”[tw] OR “comparative study”[Publication Type] OR “comparative study”[tw] OR systematic[sb] OR “meta-analysis”[Publication Type] OR “meta-analysis as topic”[MeSH Terms] OR “meta-analysis”[tw] OR “meta-analyses”[tw] OR randomized controlled trial[pt] OR controlled clinical trial[pt] OR randomized[tiab] OR randomised[tiab] OR randomization[tiab] OR randomisation[tiab] OR placebo[tiab] OR “drug therapy”[Subheading] OR randomly[tiab] OR trial[tiab] OR groups[tiab] OR Clinical trial[pt] OR “clinical trial”[tw] OR “clinical trials”[tw] NOT (Editorial[ptyp] OR Letter[ptyp] OR Case Reports[ptyp] OR Comment[ptyp]) #4 #1 AND #2 AND #3 #5 #4 NOT (animals[mh] NOT humans[mh]) #6 #5 limits: English, Publication Date from 2000-present KQ 2—What are the comparative safety and effectiveness of a strict rate-control strategy versus a more lenient rate-control strategy in patients with atrial fibrillation? Do the comparative safety and effectiveness of these therapies differ among specific patient subgroups of interest? Set # Terms #1 “Atrial Fibrillation”[Mesh] OR “atrial fibrillation”[tiab] OR (atrial[tiab] AND fibrillation[tiab]) OR afib[tiab] OR “atrial flutter”[MeSH Terms] OR “atrial flutter”[tiab] #2 ((rate[tiab] OR “heart rate”[MeSH Terms]) AND control[tiab]) AND (strategy[tiab] OR lenient[tiab] OR strict[tiab]) #3 “evaluation studies”[Publication Type] OR “evaluation studies as topic”[MeSH Terms] OR “evaluation study”[tw] OR evaluation studies[tw] OR “intervention studies”[MeSH Terms] OR “intervention study”[tw] OR “intervention studies”[tw] OR “case-control studies”[MeSH Terms] OR “case-control”[tw] OR “cohort studies”[MeSH Terms] OR cohort[tw] OR “longitudinal studies”[MeSH Terms] OR “longitudinal”[tw] OR longitudinally[tw] OR “prospective”[tw] OR prospectively[tw] OR “retrospective studies”[MeSH Terms] OR “retrospective”[tw] OR “follow up”[tw] OR “comparative study”[Publication Type] OR “comparative study”[tw] OR systematic[sb] OR “meta-analysis”[Publication Type] OR “meta-analysis as topic”[MeSH Terms] OR A-1 Set # Terms “meta-analysis”[tw] OR “meta-analyses”[tw] OR randomized controlled trial[pt] OR controlled clinical trial[pt] OR randomized[tiab] OR randomised[tiab] OR randomization[tiab] OR randomisation[tiab] OR placebo[tiab] OR “drug therapy”[Subheading] OR randomly[tiab] OR trial[tiab] OR groups[tiab] OR Clinical trial[pt] OR “clinical trial”[tw] OR “clinical trials”[tw] NOT (Editorial[ptyp] OR Letter[ptyp] OR Case Reports[ptyp] OR Comment[ptyp]) #4 #1 AND #2 AND #3 #5 #4 NOT (animals[mh] NOT humans[mh]) #6 #5 limits: English, Publication Date from 2000-present KQ 3—What are the comparative safety and effectiveness of newer procedural and other nonpharmacological rate-control therapies compared with pharmacological agents in patients with atrial fibrillation who have failed initial pharmacotherapy? Do the comparative safety and effectiveness of these therapies differ among specific patient subgroups of interest? Set # Terms #1 “Atrial Fibrillation”[Mesh] OR “atrial fibrillation”[tiab] OR (atrial[tiab] AND fibrillation[tiab]) OR afib[tiab] OR “atrial flutter”[MeSH Terms] OR “atrial flutter”[tiab] #2 nonpharmacological[tiab] OR non-pharmacological[tiab] OR “Pacemaker, Artificial”[Mesh] OR pacemaker[tiab] OR (cardiac[tiab] AND (pace[tiab] OR pacing[tiab]) AND artificial[tiab]) OR “Cardiac Pacing, Artificial”[Mesh] OR “Atrioventricular Node”[Mesh] OR AVN[tiab] OR ((atrioventricular[tiab] OR atrio- ventricular[tiab]) AND (nodal[tiab] OR node[tiab])) OR “catheter ablation”[MeSH Terms] OR “catheter ablation”[tiab] #3 rate[tiab] OR heart rate[Mesh] #4 “evaluation studies”[Publication Type] OR “evaluation studies as topic”[MeSH Terms] OR “evaluation study”[tw] OR evaluation studies[tw] OR “intervention studies”[MeSH Terms] OR “intervention study”[tw] OR “intervention studies”[tw] OR “case-control studies”[MeSH Terms] OR “case-control”[tw] OR “cohort studies”[MeSH Terms] OR cohort[tw] OR “longitudinal studies”[MeSH Terms] OR “longitudinal”[tw] OR longitudinally[tw] OR “prospective”[tw] OR prospectively[tw] OR “retrospective studies”[MeSH Terms] OR “retrospective”[tw] OR “follow up”[tw] OR “comparative study”[Publication Type] OR “comparative study”[tw] OR systematic[subset] OR “meta-analysis”[Publication Type] OR “meta-analysis as topic”[MeSH Terms] OR “meta-analysis”[tw] OR “meta-analyses”[tw] OR randomized controlled trial[pt] OR controlled clinical trial[pt] OR randomized[tiab] OR randomised[tiab] OR randomization[tiab] OR randomisation[tiab] OR placebo[tiab] OR “drug therapy”[Subheading] OR randomly[tiab] OR trial[tiab] OR groups[tiab] OR Clinical trial[pt] OR “clinical trial”[tw] OR “clinical trials”[tw] NOT (Editorial[ptyp] OR Letter[ptyp] OR Case Reports[ptyp] OR Comment[ptyp]) #5 #1 AND #2 AND #3 AND #4 #6 #5 NOT (animals[mh] NOT humans[mh]) #7 #6 limits: English, Publication Date from 2000-present KQ 4—What are the comparative safety and effectiveness of available antiarrhythmic agents and electrical cardioversion for conversion of atrial fibrillation to sinus rhythm? Do the comparative safety and effectiveness of these therapies differ among specific patient subgroups of interest? Set # Terms #1 “Atrial Fibrillation”[Mesh] OR “atrial fibrillation”[tiab] OR (atrial[tiab] AND fibrillation[tiab]) OR afib[tiab] OR “atrial flutter”[MeSH Terms] OR “atrial flutter”[tiab] A-2 Set # Terms #2 “Anti-Arrhythmia Agents”[Mesh] OR “Anti-Arrhythmia Agents”[Pharmacological Action] OR ((antiarrhythmic[tiab] OR antiarrhythmia[tiab]) AND (agent[tiab] OR agents[tiab] OR drug[tiab] OR drugs[tiab])) OR “flecainide”[MeSH Terms] OR “flecainide”[tiab] OR “propafenone”[MeSH Terms] OR “propafenone”[tiab] OR “amiodarone”[MeSH Terms] OR “amiodarone”[tiab] OR “sotalol”[MeSH Terms] OR “sotalol”[tiab] OR “ibutilide”[Supplementary Concept] OR “ibutilide”[tiab] OR “dofetilide”[Supplementary Concept] OR “dofetilide”[tiab] OR “dronedarone”[Supplementary Concept] OR “dronedarone”[tiab] OR “Disopyramide”[Mesh] OR Disopyramide[tiab] #3 “electric countershock”[MeSH Terms] OR electrical[tiab] OR cardioversion[tiab] #4 “evaluation studies”[Publication Type] OR “evaluation studies as topic”[MeSH Terms] OR “evaluation study”[tw] OR evaluation studies[tw] OR “intervention studies”[MeSH Terms] OR “intervention study”[tw] OR “intervention studies”[tw] OR “case-control studies”[MeSH Terms] OR “case-control”[tw] OR “cohort studies”[MeSH Terms] OR cohort[tw] OR “longitudinal studies”[MeSH Terms] OR “longitudinal”[tw] OR longitudinally[tw] OR “prospective”[tw] OR prospectively[tw] OR “retrospective studies”[MeSH Terms] OR “retrospective”[tw] OR “follow up”[tw] OR “comparative study”[Publication Type] OR “comparative study”[tw] OR systematic[subset] OR “meta-analysis”[Publication Type] OR “meta-analysis as topic”[MeSH Terms] OR “meta-analysis”[tw] OR “meta-analyses”[tw] OR randomized controlled trial[pt] OR controlled clinical trial[pt] OR randomized[tiab] OR randomised[tiab] OR randomization[tiab] OR randomisation[tiab] OR placebo[tiab] OR “drug therapy”[Subheading] OR randomly[tiab] OR trial[tiab] OR groups[tiab] OR Clinical trial[pt] OR “clinical trial”[tw] OR “clinical trials”[tw] NOT (Editorial[ptyp] OR Letter[ptyp] OR Case Reports[ptyp] OR Comment[ptyp]) #5 #1 AND (#2 OR #3) AND #4 #6 #5 NOT (animals[mh] NOT humans[mh]) #7 #6 limits: English, Publication Date from 2000-present KQ 5—What are the comparative safety and effectiveness of newer procedural rhythm- control therapies, other nonpharmacological rhythm-control therapies, and pharmacological agents for maintenance of sinus rhythm in atrial fibrillation patients?

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