Neuraminidase inhibitors for preventing and treating influenza in healthy adults and children

BACKGROUND: Neuraminidase inhibitors (NIs) are stockpiled and recommended by public health agencies for treating and preventing seasonal and pandemic influenza. They are used clinically worldwide. OBJECTIVES: To describe the potential benefits and harms of NIs for influenza in all age groups by reviewing all clinical study reports of published and unpublished randomised, placebo-controlled trials and regulatory comments. SEARCH METHODS: We searched trial registries, electronic databases (to 22 July 2013) and regulatory archives, and corresponded with manufacturers to identify all trials. We also requested clinical study reports. We focused on the primary data sources of manufacturers but we checked that there were no published randomised controlled trials (RCTs) from non-manufacturer sources by running electronic searches in the following databases: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE (Ovid), EMBASE, Embase.com, PubMed (not MEDLINE), the Database of Reviews of Effects, the NHS Economic Evaluation Database and the Health Economic Evaluations Database. SELECTION CRITERIA: Randomised, placebo-controlled trials on adults and children with confirmed or suspected exposure to naturally occurring influenza. DATA COLLECTION AND ANALYSIS: We extracted clinical study reports and assessed risk of bias using purpose-built instruments. We analysed the effects of zanamivir and oseltamivir on time to first alleviation of symptoms, influenza outcomes, complications, hospitalisations and adverse events in the intention-to-treat (ITT) population. All trials were sponsored by the manufacturers. MAIN RESULTS: We obtained 107 clinical study reports from the European Medicines Agency (EMA), GlaxoSmithKline and Roche. We accessed comments by the US Food and Drug Administration (FDA), EMA and Japanese regulator. We included 53 trials in Stage 1 (a judgement of appropriate study design) and 46 in Stage 2 (formal analysis), including 20 oseltamivir (9623 participants) and 26 zanamivir trials (14,628 participants). Inadequate reporting put most of the zanamivir studies and half of the oseltamivir studies at a high risk of selection bias. There were inadequate measures in place to protect 11 studies of oseltamivir from performance bias due to non-identical presentation of placebo. Attrition bias was high across the oseltamivir studies and there was also evidence of selective reporting for both the zanamivir and oseltamivir studies. The placebo interventions in both sets of trials may have contained active substances. Time to first symptom alleviation. For the treatment of adults, oseltamivir reduced the time to first alleviation of symptoms by 16.8 hours (95% confidence interval (CI) 8.4 to 25.1 hours, P 1000) and nausea whilst on treatment (RD 4.15%, 95% CI 0.86 to 9.51); NNTH = 25 (95% CI 11 to 116). AUTHORS' CONCLUSIONS: Oseltamivir and zanamivir have small, non-specific effects on reducing the time to alleviation of influenza symptoms in adults, but not in asthmatic children. Using either drug as prophylaxis reduces the risk of developing symptomatic influenza. Treatment trials with oseltamivir or zanamivir do not settle the question of whether the complications of influenza (such as pneumonia) are reduced, because of a lack of diagnostic definitions. The use of oseltamivir increases the risk of adverse effects, such as nausea, vomiting, psychiatric effects and renal events in adults and vomiting in children. The lower bioavailability may explain the lower toxicity of zanamivir compared to oseltamivir. The balance between benefits and harms should be considered when making decisions about use of both NIs for either the prophylaxis or treatment of influenza. The influenza virus-specific mechanism of action proposed by the producers does not fit the clinical evidence

Meditation-based interventions for family caregivers of people with dementia: a review of the empirical literature

Objectives: Providing care for a family member with dementia is associated with increased risk of adverse mental health sequelae. Recently, interventions utilising meditation-based techniques have been developed with the aim of reducing psychological distress among dementia caregivers. The present review aimed to critically evaluate the extant empirical literature in order to determine: (1) whether meditation-based interventions can reduce depression among dementia caregivers and (2) whether meditation-based interventions can reduce subjective burden among dementia caregivers. Method: After adhering to inclusion and exclusion criteria, a total of eight studies were included in the present review. Methodological quality was assessed using one of two scales dependent on study design. Results: The results provide tentative evidence that meditation-based interventions do indeed improve levels of depression and burden in family dementia caregivers. Conclusions: The review highlighted the strengths and weakness of the studies’ methodological designs. Whilst this novel review offers evidence in support of meditation-based interventions to improve the psychological distress of family dementia caregivers, future research should direct efforts to conduct larger scale, more rigorous studies. Clinical implications of the findings are also discussed

Mechanisms and Difference-Making

I argue that difference-making should be a crucial element for evaluating the quality of evidence for mechanisms, especially with respect to the robustness of mechanisms, and that it should take central stage when it comes to the general role played by mechanisms in establishing causal claims in medicine. The difference- making of mechanisms should provide additional compelling reasons to accept the gist of Russo-Williamson thesis and include mechanisms in the protocols for Evidence- Based Medicine (EBM), as the EBM+ research group has been advocatin

The friendly relationship between therapeutic empathy and person-centred care

‘Person-centred care’ and ‘empathy’ are receiving an increasing amount of attention in the healthcare literature. These two concepts are related; however, their relationship has hitherto not been rigorously explored. In this paper we review the differences and commonalities between common definitions of the two concepts. We found that therapeutic empathy requires both interpersonal understanding (achieved via one of several potential means) as well as caring action. We also found that person-centred care could be defined as follows: Person-centred care is therapeutic empathy (interpersonal understanding and caring action) together with continuity, coordination, teamwork, access and empowerment. Conceived this way, therapeutic empathy is included within person-centred care, but not vice-versa. There are three important consequences of our analysis. First, empathy training can provide one of the means by which (part of) person-centred care can be achieved. Second, researchers and practitioners can use our analysis of empathy and person-centred care to collaborate in approaches to both research and training. Third, philosophers, who sometimes take empathy to be a foundational concept in interpersonal understanding, can use our findings to inform their work. Finally, we hope to have provided more clarity not just on the relationship between empathy and person-centred care, but also on the nature of those two individual concepts

Managing Projects in an Uncertain and Volatile World: Engaging Stakeholders, and Building a Systemic View of Risk

As evidenced through both a historical and contemporary number of over-runs managing projects can be a risky business. Managers are faced with effectively working with a multitude of parties, dealing with a wealth of interlocking uncertainties and frequently undertaking these activities within a compressed timeframe. This paper describes a risk management process developed to assist managers facing such situations. The process explicitly engages a range of stakeholders using a group support system and causal mapping process and provides not only a comprehensive appreciation of the risks identified but also a greater understanding of their subtleties. Using a real case the paper will describe the process and outcomes along with its implications, before reflecting on the insights, limitations and future research

Learning from mixed OR method practice: The NINES case study

Despite continued interest in the use of mixed OR/MS methods, limited attention has been paid in the literature to generic lessons that could be gained from mixing methods . in practice. Many organisational problems demand the use of a mixed method approach and thus recognising and sharing lessons could prove beneficial to both practitioners and researchers. This paper reports on an in-depth evaluation of a case study involving risk identification and quantification of the Northern Isles New Energy Solutions (NINES) project which sought to trial and plan a new energy system. The intervention involved a mixed method approach and client feedback on the efficacy of the approach was sought. The evaluation reported in this paper is carried out using a set of themes taken from the literature and seeks to highlight transferable lessons. The set of lessons that emerge are presented along with their implications for both general OR modelling practice and the specific situation of mixing OR/MS methods. The paper concludes by discussing the implications of the work and directions for future work which will be of interest to both practitioners and researchers interested in mixed method OR/MS work

Effects of placebos without deception compared with no treatment: a systematic review and meta-analysis

Aim Our aim was to address the clinical efficacy of open-label placebos compared with no treatment by systematic review, and meta-analysis where possible. Methods We searched the Cochrane Injuries Group's Specialised Register, The Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE(R) In-Process & Other NonIndexed Citations (OvidSP), EMBASE (OvidSP), and clinical trials registers and screened reference lists. We ran the most recent search on April 27 2015. All randomised controlled trials of any medical condition, which had both open-label placebo and no-treatment or treatment as usual groups were included. Two authors independently applied the selection criteria and extracted data. The risk of bias of included studies was assessed using the Cochrane criteria. We used random-effects model for meta-analysis. Results After removing duplicates we screened 348 publications, assessed 24 articles for eligibility and identified 5 trials (260 participants) that met our inclusion criteria. The clinical conditions were: irritable bowel syndrome (IBS), depression, allergic rhinitis, back pain and attention deficit hyperactivity disorder (ADHD). The overall risk of bias was moderate. All 5 trials were eligible for meta-analysis. We found a positive effect for non-deceptive placebos (standardized mean difference (SMD) 0.88, 95% CI 0.62 to 1.14, P<0.00001, I2= 1%). Conclusions Open-label placebos appear to have favorable clinical outcomes, compared to no treatment or no additional treatment. Caution is warranted when interpreting the results due to the limitations including the small number of trials and lack of blinding. Larger definitive trials are now warranted to explore the potential patient benefit of open-label placebos

Understanding patients' satisfaction with physician assistant/associate encounters through communication experiences: a qualitative study in acute hospitals in England.

BACKGROUND: Physician assistants/associates (PAs) are a recent innovation in acute hospital teams in England and many other countries worldwide. Although existing evidence indicates generally high levels of patient satisfaction with their PA hospital encounters, little is known about the factors associated with this outcome. There is a lack of evidence on the process of PA-patient communication in hospital encounters and how this might influence satisfaction. This study therefore aimed to understand patients' satisfaction with PA acute hospital encounters through PA-patient communication experiences. METHODS: A qualitative study was conducted among patients and representatives of patients seen by or receiving care from one of the PAs working in acute hospital services in England. Semi-structured interviews were undertaken face-to-face with study participants in the hospital setting and shortly after their PA encounter. Data were coded and analysed using thematic analysis. The study was framed within a theoretical model of core functions of medical encounter communication. RESULTS: Fifteen patients and patient representatives who had experienced a PA encounter participated in interviews, across five hospitals in England. Four interrelated communication experiences were important to participants who were satisfied with the encounter in general: feeling trust and confidence in the relationship, sharing relevant and meaningful information, experiencing emotional care and support, and sharing discussion on illness management and treatment. However, many participants misconceived PAs to be doctors, raising a potential risk of reduced trust in the PA relationship and negative implications for satisfaction with their PA encounter. Participants considered it beneficial that patients be informed about the PA role to prevent confusion. CONCLUSIONS: PA encounters offer a constructive example of successful clinician-patient communication experiences in acute hospital encounters from the patient's perspective. Study participants were generally naïve to the PA role. Hospital services and organisations introducing these mid-level or advanced care practitioner roles should consider giving attention to informing patients about the roles

Effect of placental transfusion on neonatal resuscitation attempts

Objective: Overall, neonatal mortality has been shown to be reduced by: placental transfusion (the transfer of blood from the placenta to the neonatal circulation after birth); delayed cord clamping (DCM) (waiting for the umbilical cord to stop pulsating before clamping and cutting the cord); and umbilical cord milking (UCM) (clamping and cutting the cord immediately before milking the cord towards the neonate to expel remaining volume). This systematic review aimed to determine whether placental transfusion negatively impacts resuscitation by delaying it or has any effect on infant mortality, and to identify any barriers to performing it. Methods: CINAHL, MEDLINE, AMED and the British Nursing Index were searched using key terms to identify relevant English language publications between 2017 and 2019. Results: Five papers were selected for critical analysis—three randomised control trials and two cohort studies. Conclusion: Placental transfusion was not found to have a negative impact on neonatal resuscitation but, equally, had no significant effect on Apgar at 5 minutes; however, Apgar is a crude measure of infant mortality. The question remains around the proven multifaceted benefit of placental transfusion in the prehospital environment, which requires further research. There is evidence to suggest prehospital clinicians should be looking to change practice. Further research, considerations and consultations are required to ascertain the best way to implement the procedure with a balanced and proportionate approach considering neonatal thermoregulation and maternal management. The main reported barrier to placental transfusion was a lack of appropriate equipment