Persistent Pain: Physiotherapy Student Experiences of Person-Centred Care in Musculoskeletal Outpatient Departments

Person-centred care is championed throughout healthcare and emphasised in the management of persistent pain. Research reports that physiotherapists and physiotherapy students have struggled to integrate person-centred care into their practice and clinical work with people experiencing persistent pain. The aim of the study was to explore physiotherapy students’ experiences of person-centred care with people with persistent pain in a musculoskeletal outpatients’ placement setting, and to understand what affects physiotherapy students’ ability to implement person-centred practice. An interpretive qualitative method was used with data being collected by semi-structured focus groups of a purposive sample of undergraduate final-year physiotherapy students. A thematic approach to data analysis was completed using a cyclical immersive process. Three themes emerged: understanding of person-centred care, learning, and influences on clinical practice. The students showed an understanding of person-centred care in line with current literature. Person-centred care was generally deemed ‘well taught’ at university however this did not translate into their practice in a placement setting. Several factors influenced their ability to implement person-centred care, and this impacted upon their learning and their management of people presenting with persistent pain. In conclusion, physiotherapy students struggled to integrate learning of person-centred care from university into their practice on a musculoskeletal outpatient’s placement. It is recommended that physiotherapy course teams consider their curricula so that university and placement teaching facilitate person-centred learning and improve the management of persistent pain

Persistent pain: physiotherapy student experiences of person-centred care in musculoskeletal outpatient departments

Person-centred care is championed throughout healthcare and emphasised in the management of persistent pain. Research reports that physiotherapists and physiotherapy students have struggled to integrate person-centred care into their practice and clinical work with people experiencing persistent pain. The aim of the study was to explore physiotherapy students’ experiences of person-centred care with people with persistent pain in a musculoskeletal outpatients’ placement setting, and to understand what affects physiotherapy students’ ability to implement person-centred practice. An interpretive qualitative method was used with data being collected by semi-structured focus groups of a purposive sample of undergraduate final-year physiotherapy students. A thematic approach to data analysis was completed using a cyclical immersive process. Three themes emerged: understanding of person-centred care, learning, and influences on clinical practice. The students showed an understanding of person-centred care in line with current literature. Person-centred care was generally deemed ‘well taught’ at university however this did not translate into their practice in a placement setting. Several factors influenced their ability to implement person-centred care, and this impacted upon their learning and their management of people presenting with persistent pain. In conclusion, physiotherapy students struggled to integrate learning of person-centred care from university into their practice on a musculoskeletal outpatient’s placement. It is recommended that physiotherapy course teams consider their curricula so that university and placement teaching facilitate person-centred learning and improve the management of persistent pain

Structural and mechanistic mapping of a unique fumarate reductase

The 1.8 Å resolution crystal structure of the tetraheme flavocytochrome c3, Fcc3, provides the first mechanistic insight into respiratory fumarate reductases or succinate dehydrogenases. The multi-redox center, three-domain protein shows a 40 Å long ‘molecular wire’ allowing rapid conduction of electrons through a new type of cytochrome domain onto the active site flavin, driving the reduction of fumarate to succinate. In this structure a malate-like molecule is trapped in the enzyme active site. The interactions between this molecule and the enzyme suggest a clear mechanism for fumarate reduction in which the substrate is polarized and twisted, facilitating hydride transfer from the reduced flavin and subsequent proton transfer. The enzyme active site in the oxidized form is completely buried at the interface between the flavin-binding and the clamp domains. Movement of the cytochrome and clamp domains is postulated to allow release of the product

Lamotrigine versus levetiracetam or zonisamide for focal epilepsy and valproate versus levetiracetam for generalised and unclassified epilepsy: two SANAD II non-inferiority RCTs

BackgroundLevetiracetam (Keppra®, UCB Pharma Ltd, Slough, UK) and zonisamide (Zonegran®, Eisai Co. Ltd, Tokyo, Japan) are licensed as monotherapy for focal epilepsy, and levetiracetam is increasingly used as a first-line treatment for generalised epilepsy, particularly for women of childbearing age. However, there is uncertainty as to whether or not they should be recommended as first-line treatments owing to a lack of evidence of clinical effectiveness and cost-effectiveness.ObjectivesTo compare the clinical effectiveness and cost-effectiveness of lamotrigine (Lamictal®, GlaxoSmithKline plc, Brentford, UK) (standard treatment) with levetiracetam and zonisamide (new treatments) for focal epilepsy, and to compare valproate (Epilim®, Sanofi SA, Paris, France) (standard treatment) with levetiracetam (new treatment) for generalised and unclassified epilepsy.DesignTwo pragmatic randomised unblinded non-inferiority trials run in parallel.SettingOutpatient services in NHS hospitals throughout the UK.ParticipantsThose aged ≥ 5 years with two or more spontaneous seizures that require anti-seizure medication.InterventionsParticipants with focal epilepsy were randomised to receive lamotrigine, levetiracetam or zonisamide. Participants with generalised or unclassifiable epilepsy were randomised to receive valproate or levetiracetam. The randomisation method was minimisation using a web-based program.Main outcome measuresThe primary outcome was time to 12-month remission from seizures. For this outcome, and all other time-to-event outcomes, we report hazard ratios for the standard treatment compared with the new treatment. For the focal epilepsy trial, the non-inferiority limit (lamotrigine vs. new treatments) was 1.329. For the generalised and unclassified epilepsy trial, the non-inferiority limit (valproate vs. new treatments) was 1.314. Secondary outcomes included time to treatment failure, time to first seizure, time to 24-month remission, adverse reactions, quality of life and cost-effectiveness.ResultsFocal epilepsy. A total of 990 participants were recruited, of whom 330 were randomised to receive lamotrigine, 332 were randomised to receive levetiracetam and 328 were randomised to receive zonisamide. Levetiracetam did not meet the criteria for non-inferiority (hazard ratio 1.329) in the primary intention-to-treat analysis of time to 12-month remission (hazard ratio vs. lamotrigine 1.18, 97.5% confidence interval 0.95 to 1.47), but zonisamide did meet the criteria (hazard ratio vs. lamotrigine 1.03, 97.5% confidence interval 0.83 to 1.28). In the per-protocol analysis, lamotrigine was superior to both levetiracetam (hazard ratio 1.32, 95% confidence interval 1.05 to 1.66) and zonisamide (hazard ratio 1.37, 95% confidence interval 1.08 to 1.73). For time to treatment failure, lamotrigine was superior to levetiracetam (hazard ratio 0.60, 95% confidence interval 0.46 to 0.77) and zonisamide (hazard ratio 0.46, 95% confidence interval 0.36 to 0.60). Adverse reactions were reported by 33% of participants starting lamotrigine, 44% starting levetiracetam and 45% starting zonisamide. In the economic analysis, both levetiracetam and zonisamide were more costly and less effective than lamotrigine and were therefore dominated. Generalised and unclassifiable epilepsy. Of 520 patients recruited, 260 were randomised to receive valproate and 260 were randomised to receive to levetiracetam. A total of 397 patients had generalised epilepsy and 123 had unclassified epilepsy. Levetiracetam did not meet the criteria for non-inferiority in the primary intention-to-treat analysis of time to 12-month remission (hazard ratio 1.19, 95% confidence interval 0.96 to 1.47; non-inferiority margin 1.314). In the per-protocol analysis of time to 12-month remission, valproate was superior to levetiracetam (hazard ratio 1.68, 95% confidence interval 1.30 to 2.15). Valproate was superior to levetiracetam for time to treatment failure (hazard ratio 0.65, 95% confidence interval 0.50 to 0.83). Adverse reactions were reported by 37.4% of participants receiving valproate and 41.5% of those receiving levetiracetam. Levetiracetam was both more costly (incremental cost of £104, 95% central range -£587 to £1234) and less effective (incremental quality-adjusted life-year of -0.035, 95% central range -0.137 to 0.032) than valproate, and was therefore dominated. At a cost-effectiveness threshold of £20,000 per quality-adjusted life-year, levetiracetam was associated with a probability of 0.17 of being cost-effective.LimitationsThe SANAD II trial was unblinded, which could have biased results by influencing decisions about dosing, treatment failure and the attribution of adverse reactions.Future workSANAD II data could now be included in an individual participant meta-analysis of similar trials, and future similar trials are required to assess the clinical effectiveness and cost-effectiveness of other new treatments, including lacosamide and perampanel.ConclusionsFocal epilepsy - The SANAD II findings do not support the use of levetiracetam or zonisamide as first-line treatments in focal epilepsy. Generalised and unclassifiable epilepsy - The SANAD II findings do not support the use of levetiracetam as a first-line treatment for newly diagnosed generalised epilepsy. For women of childbearing potential, these results inform discussions about the benefit (lower teratogenicity) and harm (worse seizure outcomes and higher treatment failure rate) of levetiracetam compared with valproate.Trial registrationCurrent Controlled Trials ISRCTN30294119 and EudraCT 2012-001884-64.FundingThis project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 75. See the NIHR Journals Library website for further project information

Study protocol for a pragmatic randomised controlled trial comparing the effectiveness and cost-effectiveness of levetiracetam and zonisamide versus standard treatments for epilepsy: a comparison of standard and new antiepileptic drugs (SANAD-II)

Introduction: Antiepileptic drugs (AEDs) are the mainstay of epilepsy treatment. Over the past 20 years, a number of new drugs have been approved for National Health Service (NHS) use on the basis of information from short-term trials that demonstrate efficacy. These trials do not provide information about the longer term outcomes, which inform treatment policy. This trial will assess the long-term clinical and cost-effectiveness of the newer treatment levetiracetam and zonisamide. Methods and analysis: This is a phase IV, multicentre, open-label, randomised, controlled clinical trial comparing new and standard treatments for patients with newly diagnosed epilepsy. Arm A of the trial randomised 990 patients with focal epilepsy to standard AED lamotrigine or new AED levetiracetam or zonisamide. Arm B randomised 520 patients with generalised epilepsy to standard AED sodium valproate or new AED levetiracetam. Patients are recruited from UK NHS outpatient epilepsy, general neurology and paediatric clinics. Included patients are aged 5 years or older with two or more spontaneous seizures requiring AED monotherapy, who are not previously treated with AEDs. Patients are followed up for a minimum of 2 years. The primary outcome is time to 12-month remission from seizures. Secondary outcomes include time to treatment failure (including due to inadequate seizure control or unacceptable adverse reactions); time to first seizure; time to 24-month remission; adverse reactions and quality of life. All primary analyses will be on an intention to treat basis. Separate analyses will be undertaken for each arm. Health economic analysis will be conducted from the perspective of the NHS to assess the cost-effectiveness of each AED. Ethics and dissemination: This trial has been approved by the North West-Liverpool East REC (Ref. 12/NW/0361). The trial team will disseminate the results through scientific meetings, peer-reviewed publications and patient and public involvement. Trial registration numbers: EudraCT 2012-001884-64; ISRCTN30294119

Data quality influences the predicted distribution and habitat of four southern-hemisphere albatross species

Few studies have assessed the influence of data quality on the predicted probability of occurrence and preferred habitat of marine predators. We compared results from four species distribution models (SDMs) for four southern-hemisphere albatross species, Buller’s (Thalassarche bulleri), Campbell (T. impavida), grey-headed (T. chrysostoma), and white-capped (T. steadi), based on datasets of differing quality, ranging from no location data to twice-daily locations of individual birds collected by geolocation devices. Two relative environmental suitability (RES) models were fit using minimum and maximum preferred and absolute values for each environmental variable based on (1) monthly 50% kernel density contours and background environmental data, and (2) primary literature or expert opinion. Additionally, two boosted regression tree (BRT) models were fit using (1) opportunistic sightings data, and (2) geolocation data from bird-borne electronic tags. Using model-specific threshold values, habitat was quantified for each species and model. Model variables included distance from land, bathymetry, sea surface temperature, and chlorophyll-a concentration. Results from both RES models and the BRT model fit with opportunistic sightings were compared to those from the BRT model fit using geolocation data to assess the influence of data quality on predicted occupancy and habitat. For all species, BRT models outperformed RES models. BRT models offer a predictive advantage over RES models by being able to identify relevant variables, incorporate environmental interactions, and provide spatially explicit estimates of model uncertainty. RES models resulted in larger, less refined areas of predicted habitat for all species. Our study highlights the importance of data quality in predicting the distribution and habitat of albatrosses and emphasises the need to consider the pros and cons associated with different levels of data quality when using SDMs to inform management decisions. Furthermore, we examine the overlap in preferred habitat predicted by each SDM with fishing effort. We discuss the influence of data quality on predicting the wide-scale distributions of pelagic seabirds and how these impacts could result in different protection measures