AF Information for Clinicians
Medical Journals and Reports
The North-South NHS Divide: How where you are not what you need dictates your care
CCG variation ‘The North-South NHS Divide: how where you are not what you need dictates your care’ has now been released – please see the report online here. The report highlights regional disparities in commissioning and waiting times in the areas most relevant to medical technology. The report looked at NHS 18 Week RTT results and the Atlas of Variation to get an overview of how each CCG was performing- this highlighted a north-south divide in favour of the north.
Screening strategies for atrial fibrillation: a systematic review and cost-effectiveness analysis- June 2017
A national screening programme for atrial fibrillation is likely to represent a cost-effective use of resources, with systematic opportunistic screening more likely to be cost-effective than systematic population screening. Nurse pulse palpation or modified blood pressure monitors would be appropriate screening tests, with confirmation by diagnostic 12-lead electrocardiography interpreted by a trained GP, with referral to a specialist in the case of an unclear diagnosis. Implementation strategies to operationalise uptake of systematic opportunistic screening in primary care should accompany any screening recommendations.
Cardiac tachyarrhythmias and patient values and preferences for their management: the European Heart Rhythm Association (EHRA) consensus document endorsed by the Heart Rhythm Society (HRS), Asia Pacific Heart Rhythm Society (APHRS), and Sociedad Latinoamericana de Estimulación Cardíaca y Electrofisiología (SOLEACE)- June 2017
Cardiac tachyarrhythmias are recurrent or chronic and in some cases life-threatening conditions. Heart rhythm disturbances are often highly symptomatic and the psychological impact of the disease can be significant. Patients' beliefs and knowledge about their health (and illness), medications, and healthcare they receive are important determinants of whether or not they accept recommended treatments; influence their coping responses to their illness and treatment; adherence to recommended therapy; and ultimately affects health outcomes. Incorporation of patients' values and preferences for therapy should now be considered as an integral part of the decision-making process and treatment strategy. It is important to acknowledge and understand the impact of cardiac tachyarrhythmias on the patient. To address this issue, a Task Force was convened by the European Heart Rhythm Association (EHRA), and endorsed by the Heart Rhythm Society (HRS), Asia-Pacific Heart Rhythm Society (APHRS), and Sociedad Latinoamericana de Estimulación Cardíaca y Electrofisiología (SOLEACE), with the remit to comprehensively review the published evidence available, to publish a joint consensus document on patient values and preferences for the management of cardiac tachyarrhythmias, and to provide up-to-date consensus recommendations for use in clinical practice.
National tariff payment system 2017/18 and 2018/19
A set of prices and rules to help providers of NHS care and commissioners provide best value to their patients.
This guide is not for direct distribution to patients and is intended to support healthcare professional and patient discussion on atrial fibrillation (AF).
It will take about ten minutes and will help you make the most of the consultation time.
Frontline pharmacists: Making a difference for people with long term conditions
November 2016 - Royal Pharmaceutical Society
The Royal Pharmaceutical Society (RPS) believes that pharmacists have a crucial role to play in the support of people with long term conditions.
The management of long term conditions represents a significant strain on an already overstretched primary care system and an unnecessary burden on secondary care resources through avoidable hospital admissions.
The RPS believes that the expertise and clinical knowledge of pharmacists must be fully utilised to support people with long term conditions and help them to achieve the desired outcomes from their medicines, thereby making more efficient use of National Health Service (NHS) resources.
Managing reversal of direct oral anticoagulants in emergency situations
Anticoagulation is the cornerstone of prevention and treatment of venous thromboembolism (VTE) and stroke prevention in patients with atrial fibrillation (AF). However, the mechanisms by which anticoagulants confer therapeutic benefit also increase the risk of bleeding. As such, reversal strategies are critical. Until recently, the direct oral anticoagulants (DOACs) dabigatran, rivaroxaban, apixaban, and edoxaban lacked a specific reversal agent. This report is based on findings from the Anticoagulation Education Task Force, which brought together patient groups and professionals representing different medical specialties with an interest in patient safety and expertise in AF, VTE, stroke, anticoagulation, and reversal agents, to discuss the current status of anticoagulation reversal and fundamental changes in management of bleeding associated with DOACs occasioned by the approval of idarucizumab, a specific reversal agent for dabigatran, as
well as recent clinical data on specific reversal agents for factor Xa inhibitors.
British Cardiovascular Society Working Group Report:
Out-Of-Hours Cardiovascular Care: Management of Cardiac Emergencies and Hospital In-Patients
Delivery of ‘out-of-hours’ cardiovascular care is of particular concern. Patients who require emergency treatment for heart disease should have immediate access to appropriate and timely investigation and treatment at any time of day or night. For many inpatients, however, the treatment pathway pauses overnight or at weekends as tests and senior medical staff may not be readily available. This variation in care can influence service quality and can delay discharge of patients from hospital with a knock-on effect for service delivery at other times during the week.
The British Cardiovascular Society commissioned a working group to gain some insight into the provision of ‘out-of-hours’ cardiovascular care across the United Kingdom. The working group report sets standards for the delivery of ‘out-of-hours’ cardiovascular services and makes recommendations to ensure equitable access to prompt, safe, effective and high quality care at all times.
ESC - August 2016
Despite good progress in the management of patients with atrial fibrillation (AF), this arrhythmia remains one of the major causes of stroke, heart failure, sudden death, and cardiovascular morbidity in the world. Furthermore, the number of patients with AF is predicted to rise steeply in the coming years. To meet the growing demand for effective care of patients with AF, new information is continually generated and published, and the last few years have seen substantial progress. Therefore, it seems timely to publish this 2nd edition of the ESC guidelines on AF.
The Lancet - August 2016
When did you or your primary care physician last palpate your wrist to check for a regular heart rate? This simple action, followed by an electrocardiogram if the heart rate is irregular, might be crucial in preventing death and disability from ischaemic stroke, heart failure, or myocardial infarction.
The Lancet - August 2016
Atrial fibrillation is found in a third of all ischaemic strokes, even more after post-stroke atrial fibrillation monitoring. Data from stroke registries show that both unknown and untreated or under treated atrial fibrillation is responsible for most of these strokes, which are often fatal or debilitating.
National Audit of Cardiac Rhythm Management Devices
Foreword from Trudie Lobban, CEO of the Arrhythmia Alliance
Firstly, I would like to thank all the contributors to the audit from the designated cardiac implantation centres across the UK, and to the audit team and authors for producing the 10th UK Cardiac Rhythm Management Audit report. The robust data within the report must now be used as a catalyst and stimulus for action as it clearly demonstrates significant variation in implantation rates across the UK, and an overall unacceptable level of performance when compared to our European counterparts.
Although this audit was not structured to measure patient outcomes related to the levels of implantation rates recorded, we can only assume that many patients and their families have suffered unnecessary negative outcomes through lack of cardiac implantation to manage their symptoms – and we must find ways to measure the direct impact of low implantation rates on patients, and how many patients this affects in the UK.
Arrhythmia Alliance, the UK’s leading heart rhythm charity, believes in working together to improve the diagnosis, treatment and quality of life for all those affected by arrhythmias – and as stated in the recommendations of this report all patients with symptomatic bradycardia, without AV block, or with an arrhythmia and/or heart failure, where device implantation is the most appropriate treatment, MUST be able to have this treatment on the NHS. This is our mandate for action!
The audit report raises a number of fundamental questions that need to be explored and addressed if we are to see any significant improvement in implantation rates at a local and national level, we believe this can only be done by driving through best practice that is resonant and applicable at the local level. Guidance on its own is not enough to ensure positive change.
Where is the breakdown? Is it a lack of understanding and/or referral at primary care level, is there a need for better co‐ordination and provision of cardiac implantation services to manage local populations? Are there identifiable resource challenges? We can only hypothesise on the reasons until we get down to grass roots level to identify the problems and explore solutions.
During 2015 Arrhythmia Alliance ran a series of educational Cardiac Update meetings related to the management of arrhythmias and ran a number of pilot projects in areas where implantation rates needed to improve in partnership with local clinical physiologists, commissioners, primary care and industry. In 2016 we intend to extend the pilot program to at least 10 areas in the UK where implantation rates need to improve and local, multidisciplinary teams want to work together to create local action plans to improve the overall management and treatment of patients with arrhythmias.
Trudie Lobban MBE FRCP (Edin)
Founder & CEO Arrhythmia Alliance
Healthcare Pioneers Reports
Thank you to all of those who submitted a case study. The submissions were all of excellent quality, however our AF expert judging panel have chosen the one’s that identify best practice in delivering care for AF patients from identification, diagnosis through to treatment – perfecting the patient care pathway.
The Healthcare Pioneers report is developed by the AF Association and endorsed by the All-Party Parliamentary Group on Atrial Fibrillation (APGAF) and identifies best practice in the diagnosis, treatment and care of patients with atrial fibrillation (AF) and is used as a benchmark across CCG's to improve on how they deliver their services.
Find out more about submitting a case study by clicking here
You can read or download all Healthcare Pioneers Reports by clicking the images below.
|EU Healthcare Pioneers- 2017||EU Healthcare Pioneers - 2016|
Click here to read the full article.
Celine Gallagher, Jeroen M. L. Hendriks, Rajiv Mahajan, Melissa E. Middeldorp, Adrian D. Elliott, Rajeev K. Pathak, Prashanthan Sanders &
Dennis H. Lau - 3 May 2016
Identification of patients with atrial fibrillation in UK community pharmacy: an evaluation of a new service
M. J. Twigg, T. Thornley, N. Scobie - April 2016
Many patients with atrial fibrillation (AF) are asymptomatic and diagnosed via opportunistic screening. Community pharmacy has been advocated as a potential resource for opportunistic screening and lifestyle interventions. Objective The objective of this evaluation is to describe the outcomes from an AF service, in terms of referrals and interventions provided to patients identified as not at risk. Methods Eligibility was assessed from pharmacy records and the completion of a short questionnaire. Once consented, patients were screened for AF and their blood pressure was measured. Results Of 594 patients screened, nine were identified as at risk of having AF and were referred to their GP. The service also identified 109 patients with undiagnosed hypertension, 176 patients with a Body Mass Index [30, 131 with an Audit-C score [5 and 59 smokers. Pharmacists provided 413 interventions in 326 patients aimed at weight reduction (239), alcohol consumption (123) and smoking cessation (51). Conclusion This evaluation characterises the interventions provided to, not only those identified with the target condition—in this case AF—but also those without it. The true outcome of these additional interventions, along with appropriate follow-up, should be the focus of future studies.
In Pursuit of Excellence in the Prevention of AF-Related Stroke
In January 2016, AF Association release the In Pursuit of Excellence in the Prevention of AF-Related Stroke Report. The report captures insights and discussion from a multi-stakeholder group, generated as part of a roundtable meeting and through follow-up with experts, to assess the current situation for the management of AF patients in England, including challenges to optimal care, best practice examples and practical solutions.
To view and download the report click here.
Association of Smoking, Alcohol, and Obesity with Cardiovascular Death and Ischemic Stroke in Atrial Fibrillation: The Atherosclerosis Risk in Communities (ARIC) Study and Cardiovascular Health Study (CHS)
12 January 2016
In 2014 The National Institute for Health and Care Excellence (NICE) issued a clinical guideline on the management of atrial fibrillation (AF), which included recommendations on the use of optimal anticoagulation for prevention of AF-related stroke.
This report looks at data one year on to consider what has changed.
This report sets out the current situation in the prevention of AF-related stroke and identifies how stakeholders across the NHS can embrace innovation in stroke prevention, utilising the availability of these new therapies to evaluate and optimise existing anticoagulation services, improving outcomes and easing the emotional and financial burden of this condition in England.
The Future of Anticoagulation Management in Atrial Fibrillation in Europe
An assessment of today's challenges with recommendations for the future.
Effect of Active Smoking on Comparative Efficacy of Antithrombotic Therapy in Patients With Atrial Fibrillation: The Loire Valley Atrial Fibrillation Project
National Audit of Cardiac Ablation 2013-14
The National Cardiac Rhythm Management Ablation Audit is managed by the National Institute for Cardiovascular Outcomes Research (NICOR), which is part of the National Centre for Cardiovascular Prevention and Outcomes, based at University College London. Specialist clinical knowledge and leadership is provided by the British Cardiovascular Society and British Heart Rhythm Society. The strategic direction and development of the audit is determined by the Audit Steering Group. This includes major stakeholders in the audit, including cardiologists, the professional societies, physiologists, commissioners and patient group representatives.
European Atlas on the Prevention of AF-Related Stroke
Thursday 27 November 2014
New European atlas on the prevention of AF-related stroke launched: The Route Map and European Atlas on the prevention of AF-related stroke is a new report that shows the state of play in different countries across Europe on the prevention of AF-related stroke. This comprehensive report presents key data documenting the burden posed by AF-related strokes across Europe, highlights key issues and challenges in implementing best practice and provides examples of successful initiatives that have made a difference to patients in different countries.
Trudie Lobban MBE FCRP (Edin), AF Association Founder & CEO, Professor John Camm, St Georges University of London and Arrhythmia Alliance President, and Eve Knight, from AntiCoagulation Europe, formed the steering committee which oversaw the development of the report.
Over twenty different clinical experts and patient organisations contributed to the report. It is a powerful reminder that efforts are still needed to improve understanding of the increased risk of stroke in people with AF and to ensure that AF patients in all countries have equal access to appropriate treatment and care to help reduce their risk of stroke.
Incidence, mortality, and sex differences of non-valvular atrial fibrillation: A population-based study.
American Heart Association, 3 November 2014
It is unclear whether the incidence of non-valvular atrial fibrillation (NVAF) has been increasing over time. We (American Heart Association) aimed to provide contemporary estimates of the incidence and case-fatality of NVAF in a well-defined population, using the computerised databases of the Régie de l’assurance maladie du Québec.
AF Association, 2 September 2014
The Grasp the Initiative Action Plan has been developed in line with current guidelines for the management and treatment of AF. Far too many AF patients are still at high risk of stroke and remain on aspirin or are taking no anticoagulation. This plan sets out recommendations for treatment of patients presenting with AF in a range of circumstances.
Anticoagulation services and patient access to INR self-monitoring in the NHS in England
July 2014 - AntiCoagulation self-Monitoring Alliance
Fewer than two percent of the people in the UK on warfarin therapy self-monitor their INR level, despite evidence that self-monitoring can cut the risk of death by nearly
two-fifths and more than halve the risk of strokes.
Responses to Freedom of Information requests for details on the current anticoagulation services offered by CCGs highlight substantial room for improvement in the role of CCGs, in enabling suitable people on long-term warfarin to have access to self-monitoring opportunities.
NICE Implementation Collaborative: Consensus
Learn about changes to the role of anticoagulation in the management of AF-related stroke, as outlined in the new NICE clinical guideline on the management of AF.
2014: A Year in AF
Written by Dr Shouvik Haldar from Imperial College London, this report outlines findings from studies into treatments and medications for AF over the past 12 months, and it looks at developments in the field at a national level.
ABPI SAFI Report
1 April 2014
The Association of British Pharmaceutical Industry's 'Stroke in AF Initiative' (SAFI) has launched a one-stop resource for those interested in AF-related stroke, how it is managed by the NHS, the role of the NOACs, barriers to their use, and examples of good practice in their adoption by the NHS to improve patient outcomes within available resources
For more information about ABPI, please click here
MyDiagnostick AF screening tool
Patients with asymptomatic and undiagnosed atrial fibrillation are at increased risk of heart failure and ischaemic stroke. A study validates a new diagnostic device, the MyDiagnostick, for detection of AF by general practitioners and patients.
MyDiagnostick records and stores a Lead I electrocardiogram (ECG) which is automatically analysed for the presence of AF.
The high AF detection performance of the MyDiagnostick, combined with the ease of use of the device, facilitates large screening programmes for detection of undiagnosed AF and can complement GP consultations discreetly.
The impact of smoking on thromboembolism and mortality in patients with incident atrial fibrillation: insights from the Danish Diet, Cancer, and Health study
1 March 2014
Atrial fibrillation and anticoagulation -
challenges and considerations
AF Association, September 2013
This publication explains AF, why anticoagulation is so important, and what treatments are available.
Rising to the challenge: Delivering QIPP by preventing AF-related stroke
UKCPA, July 2013
This report breaks the challenges to delivering the ideal pathway
down into where they occur during the patient pathway
(screening; risk assessment; anticoagulation; and audit). It also makes recommendations of how to prevent AF-related stroke.
Don't Fail on Heart Failure
ABHI, June 2013
This report illustrates how ICDs and CRT-Ds help heart failure patients and the NHS.
It was launched in Parliament in association with ABHI, Pumping Marvellous, Cardiomyopathy Association and the AF Association.
AF Association and Boehringer Ingelheim, June 2013
AF Association, in partnership with Boehringer Ingelheim, launched the AF Infographic in Parliament. The launch was attended by Public Health Minister, Anna Soubry MP.
The interactive report gives a regional breakdown of AF and stroke.
Assessing kidney function in oral anticoagulant prescribing: an aid for safer drug and dose choices
BJC, June 2013
AF Association Trustee, Dr Matthew Fay co-wrote this feature on the incidence of stroke attributable to AF.
Taking the nation's pulse to reduce risk of stroke
The Times, 9 May 2013
AF Association featured in The Times Raconteur health pull-out to raise awareness of stroke risk.
Support for Commissioning: Anticoagulation Therapy
The AF Association welcomes NICE's commissioning guidelines for anticoagulation therapy published 14 May 2013. This resource supports commissioners, clinicians and managers to commission high quality evidence-based care for adults across England, and updates and replaces the NICE guide for commissioners on anticoagulation therapy services published in 2007.
Whole Hearted: Working together to save lives
Our sister charity, Arrhythmia Alliance, has launched the Whole Hearted campaign aimed at improving the lives of those affected by sudden cardiac arrest (SCA). The UK is lagging behind in ICD implant rates compared to its European neighbours. Whole Hearted hopes to address this shortfall by:
- campaigning for the Government to increase ICD implantation in the UK
- raising public awaress of SCA
- promoting the need for specialist nursing care for heart rhythm patients
- calling for a review on UK implant centres in line with Heart Rhythm UK guidelines
- working to develp a NICE Quality Standard on SCA
- lobbying for the Government to increase the number of public-access automated external defibrillators (AEDs)
Cardiovascular Disease Outcomes Strategy
AF Association welcomes the government’s first step to improve management of AF; prevent strokes; save lives. The Department of Health published the Cardiovascular Disease (CVD) Outcomes Strategy. The implications for AF patients are considerable. Listed within the Strategy, mandate is now clear for successful implementation of guidelines to ensure improved early diagnosis, assessment of risks and effective management of symptoms and risk factors.
- Improve prevention and risk management
- Improve case finding through screening of high risk groups at every opportunity
- Identify and support early management
- Evaluate and disseminate approaches to assessment to improve care for patients
- Improve and utilise audits and registries to inform commissioning and improve outcomes
- Recognise and tackle inequalities in access to therapy and patient care
Take Action Now (2012)
Two of the most challenging issues facing the effective care of AF patients at risk of stroke the world over are:
- Poor local adoption of international treatment guidelines that recommend anticoagulation for all but low risk patients
- Low patient and physician awareness of AF, its treatment and its consequences
To assist patient advocacy organisations all over the world to tackle these problems, the AF Association launched the Take Action Now – Action Plan. The plan was developed in partnership with the Arrhythmia Alliance (A-A), AntiCoagulation Europe (ACE) and the Stroke Alliance for Europe (SAFE) to provide practical guidance on how to campaign effectively for the improved management of AF so that stroke risk is properly managed in all those patients for whom anticoagulation therapy is required.
Living with warfarin...the reality of life on anticoagulation therapy
AF Association and ACE. 2012
This report is aimed at giving an insight into what it is like for people who are taking warfarin. It is not just a treatment but a lifestyle change.
Herbal and non-herbal supplement use in warfarin-treated patients and the impact on warfarin safety and efficacy
The Journal of Innovations in Cardiac Rhythm Management, January 2012
This article explores th use of supplements by people who take warfarin, the interactions and the data obtained from studies in this area.
For healthcare professionals, covering all aspects of AF; including the cost of AF to individuals and society, diagnosis and treatment, preventing AF-related stroke, guidelines and challenges.
Taking the pulse of NHS services
This report brings together data and evidence on variations that exist in the diagnosis, treatment and quality of life for patients living with atrial fibrillation and AF-related stroke.
Commissioning effective anticoagulation services for the future
This resource pack for commissioners has been developed by AntiCoagulation Europe (ACE). It focuses on services for patients on long term anticoagulation therapy across various groups, including people with AF, who have suffered stroke or a heart attack and people with artificial heart valves.
Grasp the Initiative
This report found 8,000 strokes could be prevented in England every year if GP's use a free detection tool that identifies the risk of AF-related stroke; GRASP-AF. This would also trim annual NHS spending by £96m.
AntiArrhythmic Drugs for AF
This booklet provides a summarry of antiarrhythmic drugs for atrial fibrillation, as of 2012. These are broken down by rhythm control and rate control.
Stroke Prevention in AF, Avoiding a Stroke Crisis
Action for Stroke Prevention, an alliance of cardiologists, neurologists, family doctors and patient groups, have urged EU policymakers to improve stroke risk assessment and diagnosis of atrial fibrillation before the increasing frequency of strokes becomes "a major public health crisis.’’
NHS Stroke Improvement Programme: Atrial Fibrillation – Detection and Optimal Therapy in Primary Care
Paper reviewing opportunistic screening of pulse palpitation in patients over 65 years of age.
Heart and Stroke Improvement
Commissioning for Stroke, Prevention in Primary Care -
The Role of Atrial Fibrillation
This booklet showcases ten case studies of local practices that have successfully implemented measures to improve AF diagnosis and treatments. They have contributed to significant health benefits to patients and savings to the NHS.
Atrial fibrillation and anticoagulation - challenges and considerations
This booklet outlines why anticoagulation is so important in atrial fibrillation. It details the various forms of anticoagulation therapy available, along with the respective considerations.
Pulse: Why the UK must address the personal, clinical and economic impact of atrial fibrillation
This report looks into the outcomes failing to diagnose and effectively treat atrial fibrillation, the most common arrhythmia in the UK. It explores the personal impact to patients and their families, the strain on healthcare services and financial burden.
This report looks into the outcomes failing to diagnose and effectively treat atrial fibrillation, the most common arrhythmia in the UK. It explores the personal impact to patients and their families, the strain on healthcare services and financial burden specifically in Wales.
Primary Care Cardiovascular Journal
The only UK journal written specifically for GPs (primary care physicians) managing patients with cardiovascular disease, diabetes and related diseases.
As part of a Media partnership with Touch Briefings, AFA members receive free eBook access to Touch Briefings ‘European Cardiology’ Volume 7 Issue 3
European Cardiology is a quarterly peer-reviewed journal that includes review articles, case reports, practice guidelines and original research. Guided by an Editorial Board of world-renowned physicians, European Cardiology comprises articles from recognised thought leaders to deliver comprehensive update on the most important clinical issues facing everyday cardiovascular care. In this latest issue – Volume 7 Issue 3 – Patrick T Murray et al contribute an insightful article entitled ‘Neutrophil Gelatinase-associated Lipocalin as a Cardiovascular Biomarker’. The review explores the novel roles of NGAL in the cardiovascular system, and highlights some of the key research findings in this rapidly evolving field. Elsewhere, Rajarshi Banerjee and Paul Leeson examine risk reduction in childhood obesity. The article provides timely update on recent studies into potential interventions in childhood that may ameliorate the future burden of weight-related disease.
To access the current edition in full and free eBook format, please click here.
Touch Briefings ‘US Cardiology’ Volume 8 Issue 2
US Cardiology is a bi-annual peer-reviewed journal that includes review articles, case reports, practice guidelines and original research. Guided by an Editorial Board of world-renowned physicians, US Cardiology comprises articles from recognised thought leaders to deliver comprehensive update on the most important clinical issues facing everyday cardiovascular care. In this latest issue – Volume 8 Issue 2 – Barry L Carter contributes an article entitled ‘Blood Pressure Control—Implementing a Team Approach’ in which he reports that team-based care models have achieved far higher rates of BP control than other strategies. Dr Carter suggests that because healthcare teams can substantially improve outcomes, implementing pay-for-performance and other means may make such approaches much more attractive to providers and health systems. Elsewhere, Peter A McCullough and colleagues review the array of treatments used in combination for stable coronary disease and ACS and provide insightful critical guidance concerning benefits, risks, and dose adjustments required for patients with baseline CKD.
To access the current edition in full and free eBook format, please click here.
For more information, please visit our Touch Cardiology website.
'Treatment Strategies - Cardiology', free to view e-Book
Treatment Strategies - Cardiology is a print and on-line eBook publication that provides its readership with a collection of comprehensive and thought provoking articles from the most respected key opinion leaders, leading doctors and authorities in the cardiology field. The series informs and educates clinicians on the latest therapeutic and technological advances.