ResearchPad - current-opinion Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[EAPCI Position Statement on Invasive Management of Acute Coronary Syndromes during the COVID-19 pandemic]]> The coronavirus disease 2019 (COVID-19) pandemic poses an unprecedented challenge to healthcare worldwide. The infection can be life threatening and require intensive care treatment. The transmission of the disease poses a risk to both patients and healthcare workers. The number of patients requiring hospital admission and intensive care may overwhelm health systems and negatively affect standard care for patients presenting with conditions needing emergency interventions. This position statements aims to assist cardiologists in the invasive management of acute coronary syndrome (ACS) patients in the context of the COVID-19 pandemic. To that end, we assembled a panel of interventional cardiologists and acute cardiac care specialists appointed by the European Association of Percutaneous Cardiovascular Interventions (EAPCI) and from the Acute Cardiovascular Care Association (ACVC) and included the experience from the first and worst affected areas in Europe. Modified diagnostic and treatment algorithms are proposed to adapt evidence-based protocols for this unprecedented challenge. Various clinical scenarios, as well as management algorithms for patients with a diagnosed or suspected COVID-19 infection, presenting with ST- and non-ST-segment elevation ACS are described. In addition, we address the need for re-organization of ACS networks, with redistribution of hub and spoke hospitals, as well as for in-hospital reorganization of emergency rooms and cardiac units, with examples coming from multiple European countries. Furthermore, we provide a guidance to reorganization of catheterization laboratories and, importantly, measures for protection of healthcare providers involved with invasive procedures.

<![CDATA[Resuming elective surgical services in times of COVID-19 infection]]> The consequences of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus have been devastating to the healthcare system.

As the positive effects of social distancing, mandatory masking, and societal lockdown on the spread of the disease and its incidence in the community were documented, societal and financial pressures mounted worldwide, prompting efforts to “re-open” countries, states, communities, businesses, and schools. The same happened with hospital, which had to start developing strategies to resume elective surgery activities. This manuscript describes the pre-requisites as well as the strategies for resuming surgical activity, be it in the outpatient or inpatient setting.

<![CDATA[Biosimilar Pegfilgrastim: Improving Access and Optimising Practice to Supportive Care that Enables Cure]]> Febrile neutropenia (FN) is a serious complication of chemotherapy, which can cause significant morbidity and mortality, result in dose delays and reductions and, ultimately, reduce cancer survival. Over the past decade, the availability of biosimilar filgrastim (short-acting granulocyte colony-stimulating factor [G-CSF]) has transformed patient access, with clear evidence of clinical benefit at preventing FN at reduced costs. In 2019, seven biosimilar pegfilgrastims (long-acting G-CSFs) were licensed, creating optimal market conditions and choice for prescribers. FN affects up to 117 per 1000 cancer patients, with mortality rates in the range of 2–21%. By reducing FN incidence and improving chemotherapy relative dose intensity (RDI), G-CSF has been associated with a 3.2% absolute survival benefit. Guidelines recommend primary prophylaxis and that filgrastim be administered for 10–14 days, while pegfilgrastim is administered once per cycle. When taken according to the guidelines, pegfilgrastim and filgrastim are equally effective. However, in routine clinical practice, filgrastim is often under-dosed (< 7 days) and has been shown to be inferior to pegfilgrastim at reducing FN incidence, hospitalisations and maintaining RDI. Once-per-cycle administration with pegfilgrastim might also aid patient adherence. The introduction of biosimilar pegfilgrastim should instigate a rethink of neutropenia management. Biosimilar pegfilgrastim offers countries using biosimilar filgrastim opportunities to improve adherence and thus cancer survival, whilst offering economic benefits for countries using reference pegfilgrastim. These benefits can be realised in full if biosimilar pegfilgrastim becomes part of routine clinical practice supported by drug and therapeutic committees implementing guidelines with multidisciplinary support in the hospital.

Electronic supplementary materialThe online version of this article (10.1007/s40259-020-00411-4) contains supplementary material, which is available to authorized users. ]]>
<![CDATA[The Cava]]> <![CDATA[eClinic: increasing use of telehealth as a risk reduction strategy during the covid-19 pandemic]]> Prior to the covid-19 pandemic, telehealth was already being rapidly adopted nationally by healthcare systems. During the covid-19 pandemic, increased use of telehealth may be considered as a risk reduction strategy. Benefits of this strategy may be conferred to both patients and health providers.

<![CDATA[Trends in the Development and Approval of Monoclonal Antibodies for Viral Infections]]>

Monoclonal antibodies (mAbs) developed for either the prevention or treatment of viral diseases represent a small, but valuable, class of products. Since 1985, commercial firms have initiated clinical studies involving a total of 28 mAbs. To date, one product (palivizumab) has been approved and eight candidates are currently in clinical study.

Most commercial mAbs studied as antiviral agents in the clinic have either directly or indirectly targeted human immunodeficiency virus, respiratory syncytial virus, or hepatitis C virus infections. However, the ability of mAbs to bind to specific targets and utilize various anti-infective modes of action would seem to make them well suited for the prevention and/or treatment of a wider variety of viral diseases. A number of factors, including the continuing need for innovative medicines for viral infections, the global spread of viral infections, and increased government funding for the study of pathogen countermeasures, have prompted companies to reconsider mAbs as antiviral agents. Public sector research into the use of mAbs against emerging pathogens, such as severe acute respiratory syndrome coronavirus, may have already provided candidates for further development.

<![CDATA[The Future of Antisense Oligonucleotides in the Treatment of Respiratory Diseases]]>

Antisense oligonucleotides (ASO) are short synthetic DNA molecules designed to inhibit translation of a targeted gene to protein via interaction with messenger RNA. More recently, small interfering (si)RNA have been developed as potent tools to specifically inhibit gene expression. ASO directed against signaling molecules, cytokine receptors, and transcription factors involved in allergic immune and inflammatory responses, have been applied in experimental models of asthma and demonstrate potential as therapeutics. Several ASO-based drugs directed against oncogenes have been developed for therapy of lung cancer, and some have recently reached clinical trials. ASO and siRNA to respiratory syncytial virus infection have demonstrated good potential to treat this condition, particularly in combination with an antiviral drug. Although ASO-based therapeutics are promising for lung diseases, issues of specificity, identification of correct molecular targets, delivery and carrier systems, as well as potential adverse effects must be carefully evaluated before clinical application.

<![CDATA[Antimicrobial Agents are Societal Drugs]]>

This paper is concerned with how those who prescribe antimicrobials should consider the wider repercussions of their actions. It is accepted that in an ecological system, pressure will cause evolution; this is also the case with antimicrobials, the result being the development of resistance and the therapeutic failure of drugs. To an extent, this can be ameliorated through advances by the pharmaceutical industry, but that should not stop us from critically appraising our use and modifying our behavior to slow this process down.

Up to 50% of prescribing in human medicine and 80% in veterinary medicine and farming has been considered questionable. The Alliance for the Prudent Use of Antimicrobials (APUA) was approached by the WHO to review the situation. Their recommendations include decreasing the prescribing of antibacterials for nonbacterial infections. In the UK, there has been an initiative called ‘the path of least resistance’. This encourages general practitioners to avoid prescribing or reduce the duration of prescriptions for conditions such as upper respiratory tract infections and uncomplicated urinary tract infections; this approach has been successful. Another recommendation is to reduce the prescribing of broad-spectrum antibacterials. In UK hospitals, the problems identified with the inappropriate use of antibacterials are insufficient training in infectious disease, difficulty in selecting empirical antibacterial therapy, poor use of available microbiological information, the fear of litigation and the fact that the majority of antibacterials are prescribed by the least experienced doctors. With close liaison between the laboratories and clinicians, and the development of local protocols, this can be addressed. Another recommendation is to tighten the use of antibacterial prophylaxis and to improve patient compliance. Through a combination of improved education for doctors and patients, and improved communication skills, these problems can be addressed. A further recommendation is to encourage teaching methods that modify prescribing habits. It has been shown that workshops have led to a significant reduction in the prescribing of broad-spectrum antibacterials in the community. Auditing the prescribing of antibacterials has also been recommended.

Surveillance systems around the world monitor trends in resistance: the European Antimicrobial Resistance Surveillance Progamme (EARSS) monitors antibacterial resistance; the WHO and the International Union Against Tuberculosis and Lung Disease collaborate to monitor tuberculosis; the WHO and the International AIDS Society monitor HIV.

In the third world, a bigger problem than resistance is whether drugs are even effective, as they are often spoiled by climactic conditions, and poor quality generics and counterfeit drugs are common. Also, patients may not be able to complete a course for financial reasons.

Facts about Antimicrobial resistance in Animals (and agriculture) and Impact on Resistance (FAAIR) was commissioned by APUA. They conclude that the nonhuman use of antibacterials can lead to the development of antibacterial resistance in human pathogens. The European commission banned the use of antibacterials as growth promoters in 1999.

In the Western world, we should improve our diagnosis of sepsis, access local guidelines and consider withholding treatment pending investigations, decide if treatment can be stopped earlier and treat the patient not the result. Many developing countries need improved access to more antimicrobials, preferably in the controlled environment of appropriate medical advice.

<![CDATA[Role of Antimicrobial Agents in the Management of Exacerbations of COPD]]>

Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are a common occurrence and characterize the natural history of the disease. Over the past decade, new knowledge has substantially enhanced our understanding of the pathogenesis, outcome and natural history of AECOPD. The exacerbations not only greatly reduce the quality of life of these patients, but also result in hospitalization, respiratory failure, and death. The exacerbations are the major cost drivers in consumption of healthcare resources by COPD patients. Although bacterial infections are the most common etiologic agents, the role of viruses in COPD exacerbations is being increasingly recognized. The efficacy of antimicrobial therapy in acute exacerbations has established a causative role for bacterial infections. Recent molecular typing of sputum isolates further supports the role of bacteria in AECOPD. Isolation of a new strain of Haemophilus influenzae, Moraxella catarrhalis, or Streptococcus pneumoniae was associated with a considerable risk of an exacerbation. Lower airway bacterial colonization in stable patients with COPD instigates airway inflammation, which leads to a protracted self-perpetuating vicious circle of progressive lung damage and disease progression. A significant proportion of patients treated for COPD exacerbation demonstrate incomplete recovery, and frequent exacerbations contribute to decline in lung function. The predictors of poor outcome include advanced age, significant impairment of lung function, poor performance status, comorbid conditions and history of previous frequent exacerbations requiring antibacterials or systemic corticosteroids. These high-risk patients, who are likely to harbor organisms resistant to commonly used antimicrobials, should be identified and treated with antimicrobials with a low potential for failure. An aggressive management approach in complicated exacerbations may reduce costs by reducing healthcare utilization and hospitalization.

<![CDATA[Smoothness: an Unexplored Window into Coordinated Running Proficiency]]>

Over the expanse of evolutionary history, humans, and predecessor Homo species, ran to survive. This legacy is reflected in many deeply and irrevocably embedded neurological and biological design features, features which shape how we run, yet were themselves shaped by running.

Smoothness is a widely recognised feature of healthy, proficient movement. Nevertheless, although the term ‘smoothness’ is commonly used to describe skilled athletic movement within practical sporting contexts, it is rarely specifically defined, is rarely quantified and remains barely explored experimentally. Elsewhere, however, within various health-related and neuro-physiological domains, many manifestations of movement smoothness have been extensively investigated. Within this literature, smoothness is considered a reflection of a healthy central nervous system (CNS) and is implicitly associated with practiced coordinated proficiency; ‘non-smooth’ movement, in contrast, is considered a consequence of pathological, un-practiced or otherwise inhibited motor control.

Despite the ubiquity of running across human cultures, however, and the apparent importance of smoothness as a fundamental feature of healthy movement control, to date, no theoretical framework linking the phenomenon of movement smoothness to running proficiency has been proposed. Such a framework could, however, provide a novel lens through which to contextualise the deep underlying nature of coordinated running control. Here, we consider the relevant evidence and suggest how running smoothness may integrate with other related concepts such as complexity, entropy and variability. Finally, we suggest that these insights may provide new means of coherently conceptualising running coordination, may guide future research directions, and may productively inform practical coaching philosophies.

<![CDATA[Do Non-Responders to Exercise Exist—and If So, What Should We Do About Them?]]>

It is well established that exercise is an important component in the maintenance of good health, and yet recent studies have demonstrated that a sub-section of individuals experience no significant improvements following an exercise training intervention. Such individuals are commonly termed “non-responders”. However, recently a number of researchers have taken a skeptical view as to whether exercise non-response either exists, or is clinically relevant. Here, we explore the research underpinning exercise response, to determine whether non-response to exercise actually exists. We discuss the impact of measurement error and assessment type on the identification of “non-responders”, and whether such non-response is global- or modality-specific. Additionally, we discuss whether, if non-response to an exercise intervention is meaningful and relevant, certain additional interventions—in the form of increasing exercise intensity, volume, or duration—could be made in order to enhance training adaptations. Consequently, based on our interpretations of the available evidence, we suggest that it is unlikely that global non-responders to exercise exist. Furthermore, we suggest this realization effectively counters the perception that some individuals will not positively respond to exercise, and that in turn, this insight serves to encourage health professionals to create more nuanced, efficacious, and individually-focused exercise prescriptions designed to circumvent and overcome apparent non-responsiveness. Adopting a more individually-adaptive approach to exercise prescription could, subsequently, prove a powerful tool in promoting population health.

<![CDATA[The Current State of Subjective Training Load Monitoring—a Practical Perspective and Call to Action]]>

This commentary delivers a practical perspective on the current state of subjective training load (TL) monitoring, and in particular sessional ratings of perceived exertion, for performance enhancement and injury prevention. Subjective measures may be able to reflect mental fatigue, effort, stress, and motivation. These factors appear to be important moderators of the relationship TL has with performance and injury, and they also seem to differ between open and closed skill sports. As such, mental factors may affect the interaction between TL, performance, and injury in different sports. Further, modeling these interactions may be limited due to the assumption that an independent signal can adequately account for the performance or injury outcomes. An independent signal model does not accurately reflect training environments where multiple stressors (e.g., mechanical, emotional, nutritional) impact adaptations. Common issues with using subjective TL monitoring, including a lack of differentiation between biomechanical, physiological, and cognitive load, may be overcome by considering psychometric measurement best practices, finer graded scales, and differential ratings of perceived exertion. Methods of calculating TL, including different acute and chronic time periods, may also need to be individualized to different sports and potentially different individuals within the same sport. As TL monitoring is predominately a “chronic” decision-making tool, “acute” decision-making tools, e.g., subjective wellness and autonomic nervous system measures, should be combined in a bespoke multivariate model to aid sports coaches. A call to action is presented for future research on key issues associated with TL monitoring that will have relevance for practitioners in an applied setting.

<![CDATA[Optimizing the trauma resuscitation bay during the covid-19 pandemic]]> The covid-19 global pandemic due to the SARS-CoV2 (CoV2) virus has created the need to adapt hospital workspaces and staffing models, and trauma is no exception. While the optimal configuration of a trauma resuscitation area is debatable, the space needs to be large enough to accommodate the trauma team and ancillary staff. It also needs to have ready access to supplies and equipment to quickly and easily control hemorrhage, secure an airway and initiate fluid resuscitation. Lastly, stores of personal protective equipment in the form of fluid resistant gowns, head covering, face shield, and gloves (both sterile and non-sterile) should be readily available but under strict access. As CoV2 carriers increased in our population in New Jersey, we treated each incoming trauma patient as a potentially CoV2-positive case and sought to reconfigure out trauma resuscitation area to minimize exposure of our supplies to aerosolized virus. ]]> <![CDATA[Research into the Health Benefits of Sprint Interval Training Should Focus on Protocols with Fewer and Shorter Sprints]]>

Over the past decade, it has been convincingly shown that regularly performing repeated brief supramaximal cycle sprints (sprint interval training [SIT]) is associated with aerobic adaptations and health benefits similar to or greater than with moderate-intensity continuous training (MICT). SIT is often promoted as a time-efficient exercise strategy, but the most commonly studied SIT protocol (4–6 repeated 30-s Wingate sprints with 4 min recovery, here referred to as ‘classic’ SIT) takes up to approximately 30 min per session. Combined with high associated perceived exertion, this makes classic SIT unsuitable as an alternative/adjunct to current exercise recommendations involving MICT. However, there are no indications that the design of the classic SIT protocol has been based on considerations regarding the lowest number or shortest duration of sprints to optimise time efficiency while retaining the associated health benefits. In recent years, studies have shown that novel SIT protocols with both fewer and shorter sprints are efficacious at improving important risk factors of noncommunicable diseases in sedentary individuals, and provide health benefits that are no worse than those associated with classic SIT. These shorter/easier protocols have the potential to remove many of the common barriers to exercise in the general population. Thus, based on the evidence summarised in this current opinion paper, we propose that there is a need for a fundamental change in focus in SIT research in order to move away from further characterising the classic SIT protocol and towards establishing acceptable and effective protocols that involve minimal sprint durations and repetitions.

<![CDATA[Assumption versus evidence: the case of digoxin in atrial fibrillation and heart failure]]> ]]> <![CDATA[Tyrosine Kinase Inhibitors and Proton Pump Inhibitors: An Evaluation of Treatment Options]]>

Tyrosine kinase inhibitors (TKIs) have rapidly become an established factor in oncology, and have been shown to be effective in a wide variety of solid and hematologic malignancies. Use of the oral administration route of TKIs offers flexibility and is convenient for the patient; however, despite these advantages, the oral route of administration also causes a highly relevant new problem. Acid-inhibitory drugs, such as proton pump inhibitors (PPIs), increase the intragastric pH, which may subsequently decrease TKI solubility, bioavailability, and treatment efficacy. Clear and practical advice on how to manage PPI use during TKI therapy is currently not available in the literature. Since PPIs are extensively used during TKI therapy, prescribers are presented with a big dilemma as to whether or not to continue the combined treatment, resulting in patients possibly being deprived of optimal therapy. When all pharmacological characteristics and data of either TKIs and PPIs are considered, practical and safe advice on how to manage this drug combination can be given.

<![CDATA[The Patient’s Voice in Pharmacovigilance: Pragmatic Approaches to Building a Patient-Centric Drug Safety Organization]]>

Patient-centeredness has become an acknowledged hallmark of not only high-quality health care but also high-quality drug development. Biopharmaceutical companies are actively seeking to be more patient-centric in drug research and development by involving patients in identifying target disease conditions, participating in the design of, and recruitment for, clinical trials, and disseminating study results. Drug safety departments within the biopharmaceutical industry are at a similar inflection point. Rising rates of per capita prescription drug use underscore the importance of having robust pharmacovigilance systems in place to detect and assess adverse drug reactions (ADRs). At the same time, the practice of pharmacovigilance is being transformed by a host of recent regulatory guidances and related initiatives which emphasize the importance of the patient’s perspective in drug safety. Collectively, these initiatives impact the full range of activities that fall within the remit of pharmacovigilance, including ADR reporting, signal detection and evaluation, risk management, medication error assessment, benefit–risk assessment and risk communication. Examples include the fact that manufacturing authorization holders are now expected to monitor all digital sources under their control for potential reports of ADRs, and the emergence of new methods for collecting, analysing and reporting patient-generated ADR reports for signal detection and evaluation purposes. A drug safety department’s ability to transition successfully into a more patient-centric organization will depend on three defining attributes: (1) a patient-centered culture; (2) deployment of a framework to guide patient engagement activities; and (3) demonstrated proficiency in patient-centered competencies, including patient engagement, risk communication and patient preference assessment. Whether, and to what extent, drug safety departments embrace the new patient-centric imperative, and the methods and processes they implement to achieve this end effectively and efficiently, promise to become distinguishing factors in the highly competitive biopharmaceutical industry landscape.

<![CDATA[Making Patient Engagement a Reality]]>

Patients are increasingly recognised as the true customers of healthcare. By providing insights and perspectives, patients can help the wider healthcare community better understand their needs and ultimately enhance the value of healthcare solutions being developed. In the development of new medicines, for example, meaningful patient engagement can enable the pharmaceutical industry, healthcare providers and other stakeholders to achieve more meaningful health outcomes. While both the pharmaceutical industry and regulators have achieved some progress in incorporating patient perspectives into their activities, the lack of standardised best practices and metrics has made it challenging to achieve consistency and measure success in patient engagement. Practical guidance for patient engagement can facilitate better interactions between patients or patient groups and other collaborators, e.g. industry, regulators and other healthcare stakeholders. Accordingly, UCB has developed an internal model for Patient Group Engagement incorporating four key principles, based on shared ambition, transparency, accountability and respect, essential for effective collaborations.

<![CDATA[Proceedings from the 2nd European Clinical Consensus Conference for device-based therapies for hypertension: state of the art and considerations for the future]]>