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Segmentation of running data into gait cycles and stance/swing phases is crucial for evaluating running biomechanics. The benefit of magneto-inertial sensors is their ability to capture data in outdoor conditions. However, state-of-the-art inertial-based methods for estimating running temporal parameters are limited to a restricted range of running speeds and, thus, not able to analyze running at variable speeds. This limitation prevents their use for real-world analysis for a wide range of runners and for sports disciplines where athletes vary their running speed. This study evaluated the speed-dependance of eight relevant foot-mounted inertial-based methods from previous research and proposed a novel method that could be robust to speed changes. The proposed method applied, for the first time, a template-matching algorithm based on dynamic time warping to running analysis and compared it to existing methods. All the implemented methods were tested on 30 runners at different speeds ranging from jogging to sprinting (8 km/h, 10 km/h, 14 km/h, 19-30 km/h) on both treadmill and overground. The most speed-robust performance was achieved by the proposed template-based method, providing estimation errors below 0.1% in stride, between 7%-19% in stance, and between 3%-6% in swing across running speeds. Conversely, all the tested methods from the literature were significantly speed-dependent. Thus, this study suggested that template-based approach is a valid solution for the inertial-based estimation of temporal parameters during running from slow jogging to fast sprinting. MATLAB codes and templates have been made available online.

IntroductionCross-education is an established yet not fully understood phenomenon involving interhemispheric processes within the corpus callosum (CC) that result in strength gains in the untraining limb following training of the contralateral homologous muscles. There is a substantial lack of cross-education studies employing lesional models. This study employed the model of multiple sclerosis, a condition typically featuring demyelinating callosal lesions, to pinpoint CC subregions that mediate cross-education, potentially fostering the mechanistic understanding of the interlimb transfer.MethodsNine individuals with relapsing-remitting multiple sclerosis (median Expanded Disability Status Scale: 3.5) and focal CC lesions underwent a 6-week, high-intensity isokinetic training program (≥80% maximal effort at 10°/s) targeting their stronger ankle dorsiflexors. Sagittal FLAIR MRI scans were segmented into five CC subregions (CC1–CC5), with lesion volumes quantified for each subregion. Strength (peak concentric torque at 10°/s) was measured bilaterally before (PRE) and after (POST) training to determine cross-education, defined as the percentage increase in torque of the untrained, weaker limb. Correlations between lesion volumes in CC subregions and cross-education were analyzed.ResultsBoth the trained (+21.5 ± 15.8%, p = 0.002) and untrained (+35.2 ± 24.9%, p = 0.003) limbs demonstrated post-training strength gains, reducing but not eliminating inter-limb asymmetry. Lesions specifically in the rostral body (CC2) correlated with reduced cross-education magnitude (rs = −0.670, p = 0.048) and smaller improvements in strength asymmetry (rs = 0.809, p = 0.008). No associations were detected in other CC subregions.ConclusionThese findings highlight the pivotal role of specific CC subregions, particularly the rostral body, in mediating cross-education of strength. These findings advance our understanding of CC role in the interhemispheric dynamics underpinning cross-education. Routine MRI can identify patients without CC2 lesions who may benefit from cross-education, providing a practical approach to improving muscle strength when weaker muscles cannot be directly trained.Clinical Trial RegistrationClinicaTrials.Gov, identifier NCT02010398

Abstract Introduction The delivery of COVID-19 vaccines was successful in reducing hospitalizations and mortality. However, emergence of the Omicron variant resulted in increased virus transmissibility. Consequently, booster vaccination programs were initiated to decrease the risk of severe disease and death among vulnerable members of the population. This study aimed to estimate the effects of the booster program and alternative vaccination strategies on morbidity and mortality due to COVID-19 in the UK. Method A Susceptible-Exposed-Infectious-Recovered (SEIR) model was used to assess the impact of several vaccination strategies on severe outcomes associated with COVID-19, including hospitalizations, mortality, National Health Service (NHS) capacity quantified by hospital general ward and intensive care unit (ICU) bed days, and patient productivity. The model accounted for age-, risk- and immunity-based stratification of the UK population. Outcomes were evaluated over a 48-week time horizon from September 2022 to August 2023 considering the actual UK autumn 2022/spring 2023 booster campaigns and six counterfactual strategies. Results The model estimated that the autumn 2022/spring 2023 booster campaign resulted in a reduction of 18,921 hospitalizations and 1463 deaths, compared with a no booster scenario. Utilization of hospital bed days due to COVID-19 decreased after the autumn 2022/spring 2023 booster campaign. Expanding the booster eligibility criteria and improving uptake improved all outcomes, including averting twice as many ICU admissions, preventing more than 20% additional deaths, and a sevenfold reduction in long COVID, compared with the autumn 2022/spring 2023 booster campaign. The number of productive days lost was reduced by fivefold indicating that vaccinating a wider population has a beneficial impact on the morbidities associated with COVID-19. Conclusion Our modelling demonstrates that the autumn 2022/spring 2023 booster campaign reduced COVID-19-associated morbidity and mortality. Booster campaigns with alternative eligibility criteria warrant consideration in the UK, given their potential to further reduce morbidity and mortality as future variants emerge.

Background Arising in blood and lymph-forming tissues, haematological malignancies (leukaemias, lymphomas and myelomas) are the fifth most common group of cancers. Around 60% are currently incurable and follow a chronic, remitting–relapsing pathway often initially managed by ‘watch & wait’. This involves hospital-based monitoring, followed by treatment if the cancer progresses (which not all do) and then further observation, in a process that may continually repeat. New treatments are constantly emerging, survival is improving and prevalence is rising, but population-based data documenting entire care pathway are sparse. Hence, empirically-based incidence and prevalence estimates about various treatment states (watch and wait, first-line treatment, observation, second-line treatment, etc.) and patterns of healthcare activity are lacking. Likewise, despite complex trajectories, anxiety-provoking watch and wait, and therapies that impede quality of life and incur marked healthcare costs, evidence about patient preferences for information sharing and treatment decisions is scant. Objectives Primary – to generate high-quality, evidence-based information about the care pathways of the general population of patients with chronic haematological malignancies. Secondary – to produce information resources suitable for testing in routine National Health Service practice. Design Population-based cohort of ≈ 8000 patients with chronic haematological malignancies, incorporating five nested work packages, each with its own individual design: (1) exploration of patient experiences: information and treatment decisions; (2) population-based analyses; (3) health economics; (4) development of information resources to support decision-making; and (5) patient well-being and decision-making survey. Setting This programme is predicated on the infrastructure of the United Kingdom’s Haematological Malignancy Research Network (www.hmrn.org); which provides ‘real-world’, robust, generalisable data to inform research and clinical practice, nationally and internationally. Set in Yorkshire and Humberside, the Haematological Malignancy Research Network’s catchment population of ≈ 4 million has a comparable sex, age, urban/rural, and area-based deprivation (Index of Multiple Deprivation, income domain) distribution to the United Kingdom as a whole; and in terms of ethnic diversity the region is centrally ranked, with around 80% of residents identifying as White British, 9% as Asian and 2% as black. Within the Haematological Malignancy Research Network, clinical practice adheres to national guidelines, and all patients with blood cancers are centrally diagnosed (≈ 2500 each year), tracked through their treatment pathways and linked to national databases (deaths, cancer registrations and Hospital Episode Statistics). Linked to the same national databases, the Haematological Malignancy Research Network also contains an age- and sex-matched general-population cohort. Participants Patients aged ≥ 18 years, resident in the study region, and diagnosed with chronic lymphocytic leukaemia, follicular lymphoma or myeloma. Methods Core Haematological Malignancy Research Network data were used to compare the hospital activity of patients with chronic lymphocytic leukaemia, follicular lymphoma and myeloma with that of the general population. Following additional linkages to genetic and clinical data, follicular lymphoma prognostic factors were examined. Two self-administered questionnaires addressing (1) quality of life and well-being and (2) decision-making were iteratively developed, piloted and deployed. Linkage to quality of life, clinical information and Hospital Episode Statistics enabled economic (myeloma) model development. In-depth interviews were conducted with 35 patients (10 alongside relatives). Results Trajectories of ≈ 8000 patients were mapped, and patient-pathway visualisations summarising individual and aggregate information were developed. As expected, patients with chronic blood cancers experienced higher levels of hospital activity than their general population counterparts, the largest effects being for myeloma. Following survey deployment, 3153 patients were recruited across 14 hospitals, 1282 with chronic lymphocytic leukaemia, follicular lymphoma or myeloma. Over half of the questionnaires were completed by patients on watch and wait; the remainder were completed during treatment or post-chemotherapy monitoring. Information gathered, coupled with in-depth interviews, demonstrated patients’ marked anxiety and fluctuating preferences for information sharing and decision-making, contingent on complex, inter-related factors. In turn, prognostic and microsimulation economic models were used to predict individual-level trajectories across multiple treatment lines, examining associated overall survival, costs and quality-adjusted life-years. Limitations Survey mapping to individual care pathways could not be completed because the COVID-19 pandemic delayed clinical data collection. Patients who attended clinics and participated in the survey were more likely than non-attenders to have had first-line chemotherapy, be slightly younger and live in more affluent areas. Conclusions This programme collated high-quality, population-based evidence. Previously lacking, this, coupled with new findings on preferences for information sharing and treatment decisions, provides the foundation for future research. Future work The translation of information accrued into resources suitable for testing in routine NHS practice is key. In this regard, COVID-19 has changed the communication landscape. The visualisations developed by this programme require further refinement/testing using participatory co-design with stakeholder groups. Underpinned by a suitable protocol applied within a single multidisciplinary team setting, prior to further evaluation within/outside the region, such outputs require testing in a cluster-randomised trial. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Programme Grants for Applied Research programme (NIHR award ref: RP-PG-0613-20002) and is published in full in Programme Grants for Applied Research; Vol. 12, No. 5. See the NIHR Funding and Awards website for further award information. Plain language summary Around half of all blood cancers (leukaemias, lymphomas and myeloma) are chronic and incurable. Management often involves ‘watch and wait’, which begins with hospital-based monitoring and is followed by treatment if the cancer progresses. This typically leads to further observation and treatment in an ongoing process over time. Patients often experience anxiety and distress about not being treated at diagnosis and also because of uncertainty about ‘if’ and ‘when’ chemotherapy might be needed. Information is critical if patients are to (1) understand what may happen to them in the future and (2) be involved treatment decisions. However, evidence about the care pathways most patients follow is lacking. This programme was designed to fill this gap, tracking all patients with chronic blood cancers through their care pathways. We collected information about diagnosis, treatment and outcome on approximately 8000 patients. These data were used to develop models that could be used to examine outcomes and costs. When compared with the general population, patients with blood cancer were confirmed to have more healthcare activity (e.g. hospital appointments and admissions). Computer programs were developed to electronically generate visual care-pathway ‘maps’ that revealed key similarities and differences between patient groups. Two questionnaires exploring quality of life and involvement in treatment decisions were developed and completed by 3153 patients in 14 hospitals. Thirty-five patients were interviewed about their preferences for information sharing and decision-making; needs were found to differ between patients and over time, and treatment recommendations from clinical staff were generally preferred. Emotional difficulties associated with uncertain trajectories were also clearly described. Yielding new information about the pathways of patients with chronic haematological malignancies, findings from this programme can be built on to improve future care. Final information resources could not be developed or tested in practice due to COVID-19, which continues to impact how health care is delivered. Scientific summary Background Population-based data are required to inform aetiological hypotheses, plan healthcare services and monitor the impact of therapeutic change in the general patient population. This need for data is particularly pertinent in fast-moving areas such as haemato-oncology, where treatments change rapidly and ‘gold-standard’ randomised controlled trials are absent or restricted to specific subgroups (often younger patients with fewer comorbidities), to specific time points (commonly first-line treatment) or by factors such as socioeconomic status, gender or ethnicity. Arising in blood and lymph-forming tissues, haematological malignancies (leukaemias, lymphomas and myelomas) are, collectively, the fifth most common cancer. With diverse aetiologies, treatments and outcomes, more than 100 subtypes are currently recognised by the World Health Organization. Although the incidence of these cancers is stable in high-income countries such as the UK, prevalence is increasing due to population ageing and the development of new multifaceted regimens (e.g. chemotherapies, radiotherapy, stem cell transplants, novel targeted agents). However, around 60% of blood cancers remain incurable, with management often beginning with regular hospital-based monitoring, known as ‘watch & wait’ (W&W). While some patients may never need treatment, others often experience a remitting–relapsing care pathway, requiring treatment at progression interspersed with further monitoring. As with many chronic conditions, there are often uncertainties regarding how individual trajectories will progress, and variations are evident in the need for (and response to) treatment; the most effective regimen; the time when treatment is required (if ever); and the impact of treatment (and non-treatment) on quality of life. Despite such complex trajectories, many of which are associated with anxiety-provoking W&W, and therapies that impede quality of life and incur marked healthcare costs, empirically-based incidence and prevalence estimates relating to treatment states (W&W, first-line treatment, second-line treatment, etc.) are lacking, and granular population-based evidence to guide treatment decisions is sparse. Importantly, new data-gathering measures to redress this deficit have been introduced in the UK but are presently insufficiently mature to guide decisions, and the rapidly evolving nature of haemato-oncology means that generic sources may never be adequate for assessing particular therapies and their impact on individuals. Furthermore, most health economic models have been developed to reflect specific (often static) decision problems, despite effective clinical management being dynamic, involving treatment, monitoring and therapy switching, and depending on treatment response and disease evolution. To summarise, there is a dearth of accessible, reliable information to guide clinicians and patients about treatment and associated healthcare activities, physical health (e.g. disruption to daily life), psychosocial well-being, quality of life and life expectancy. This situation, which is particularly difficult for patients who face uncertain pathways and unresolved anxiety about the future, is compounded by the fact that little is known about preferences for information sharing and the desire to engage in treatment decisions. Objectives This programme sought to address the deficits described above, the premise being that the provision of personalised evidence-based information at key decision points would facilitate treatment decisions, support clinical practice and improve patient experiences. The objectives were as follows: primary – to generate high-quality, longitudinal, real-world information about the care pathways of the general population of patients with chronic haematological malignancies, incorporating data on healthcare costs, and patient preferences for information sharing and engagement in treatment decisions secondary – to produce accessible information resources suitable for testing in routine NHS practice. Design This was a population-based cohort of ≈ 8000 patients with chronic haematological malignancies, incorporating 5 distinct, but inter-related, nested work packages with individual designs, including longitudinal studies, cross-sectional surveys, data linkage and qualitative investigation of patient experiences, as follows: in-depth exploration of patient experiences: information and decision-making population-based analyses health economics development of information resources to support decision-making patient well-being and decision-making survey. Setting This programme is predicated on the established expertise and infrastructure of the UK’s Haematological Malignancy Research Network (HMRN; www.hmrn.org), which was initiated in 2004 to provide robust, generalisable data to inform research and clinical practice. Set in Yorkshire and Humberside, HMRN’s population of ≈ 4 million people has a comparable sex, age, urban/rural and area-based deprivation (Index of Multiple Deprivation, income domain) distribution to that of the UK. Within HMRN, clinical practice adheres to national guidelines, and all patients are centrally diagnosed (≈ 2500 each year), tracked through their care pathways and linked to nationwide health administrative databases (deaths, cancer registrations and Hospital Episode Statistics). HMRN also contains a general-population cohort linked to the same nationwide administrative databases as the patient cohort. HMRN has ethics approval (Leeds West Research Ethics Committee 04/Q1205/69) and Section 251 support [NHS Act 2006: Patient Information and Advisory Group 1-05(h)2007], which provides the legal basis for data collection/linkage. Research building on HMRN’s infrastructure requires supplementary approvals, granted for this programme by the London, City and East Committee (Research Ethics Committee 16/LO/0740). Participants Participants were patients aged ≥ 18 years resident in the study area and diagnosed with one of the three commonest chronic haematological malignancies: chronic lymphocytic leukaemia, follicular lymphoma or myeloma. Patient public involvement and engagement Patient and public involvement and engagement is integral to HMRN, and lay individuals are routinely involved in all research activities via the Patient Partnership, which was established in 2009 and is overseen by a Partnership Committee comprising patients, relatives/carers and researchers. The Partnership includes several hundred people who have agreed to further contact for research purposes, including directing HMRN’s activities and participating in surveys and individual/group discussions. HMRN also benefits from a group that act as a ‘sounding board’, ensuring that all our research is patient-centred and relevant. Patients and relatives were involved in the current programme as applicants and participants. Discussions preceding our application identified issues for investigation, based on patient experiences. Information was considered an area requiring improvement because of widespread concern about W&W and the anxiety and distress that this was said to instil due to uncertainty about ‘if’ and ‘when’ treatment may be required, and its likely impact. Such stories underpinned this programme, alongside our ability (via HMRN) to provide information, mapped to pathways. Changes to programme Following piloting, the survey instrument was split and the content expanded. Questionnaire 1 focused on quality of life and was to be completed pre appointment, and questionnaire 2 targeted treatment decisions and was to be completed post appointment. The number of in-depth interviews was finalised at 35 as the purposeful sampling strategy identified ‘information-rich’ sources and high-quality data. Finally, the secondary objective was curtailed by the COVID-19 pandemic (see Conclusions). Results Patient characteristics and treatment pathways With a median diagnostic age of 71 years, chronic lymphocytic leukaemia and myeloma occur more frequently in men than in women. By contrast, with a younger median age of 65.5 years, follicular lymphoma has a slight preponderance among female patients. First-line management varied markedly by subtype; 84.7% of chronic lymphocytic leukaemia patients were monitored via W&W, compared with 40.9% with follicular lymphoma and 20.2% with myeloma. Furthermore, with a 5-year relative survival of 47.7%, patients with myeloma fared less well than those with chronic lymphocytic leukaemia (5-year relative survival 84.1%) or follicular lymphoma (5-year relative survival 88.1%). To quantify/visualise the data, two software applications were developed. First, a tree-based approach aggregated patients into pathway subgroups, beginning with the initial management or event (chemotherapy, observation or death) and ending with the last. Diversity by cancer subtype was clearly evident: among those diagnosed between 2004 and 2010 who were initially managed by W&W, 40.6% (419/1031) with chronic lymphocytic leukaemia, 38.4% (93/242) with follicular lymphoma and 26.5% (90/339) with myeloma were still on W&W at the end of follow-up (5–11 years later). Second, a patient pathway generator was developed in-house from a Data-Driven Documents (D3) JavaScript library (https://d3js.org/), followed by an iterative graphical restructuring algorithm that displayed visualisations of entire pathways that included all diagnoses, investigations, treatments/responses and hospital activity in real time (generation < 1 second). Population-based analysis and prognostic model Facilitating the identification of patients requiring alternative treatment strategies and separating those at high-risk of disease progression and/or transformation from those who are not is important for clinicians and patients. With a view to incorporating genetic data into conventional prognostic models and the future development of novel targeted treatments, we examined the mutational data of patients newly diagnosed with follicular lymphoma. The molecular investigations undertaken determined that aberrant somatic hypermutations played a leading role in the genetic substructure of follicular lymphoma, with a small number of key genetic mutations, including STAT6, having a marked impact on prognosis. These clusters have implications both for understanding pathogenesis and for potential future treatment strategies. However, separation of follicular lymphoma according to mutational status despite being linked to apparent underlying mechanistic differences provides only limited prognostic information in conventionally treated patients. Hospital activity patterns Patients often question the difference their disease, or treatment, is likely to have on their survival, future healthcare needs and quality of life. As expected, inpatient and outpatient Hospital Episode Statistics activity post diagnosis was considerably higher among patients with chronic haematological malignancies than in the general population, the largest differences being for myeloma. For all three diagnoses, hospital activity peaks around the time of diagnosis, outpatient activity remaining high but levelling around 12 months after diagnosis, and inpatient activity around 8 months post diagnosis for chronic lymphocytic leukaemia and 36 months for follicular lymphoma. Health economics A microsimulation model was developed for myeloma to reflect multiple lines of treatment, post-treatment surveillance and overall survival. The model was used to predict long-term costs, and quality-adjusted life-years to enable future assessment of the expected impact of new treatments and policies. Input parameters were estimated by analysing individual-level time-to-event data (to represent patients’ trajectories), the EuroQol-5 Dimensions, five-level version (to derive quality-adjusted life-years), and HMRN treatment data (to model treatment sequences). Healthcare costs were estimated from Hospital Episode Statistics, based on national tariffs. The model is flexible enough to incorporate evidence from other sources, including clinical trials. Results were based on 2687 patients with myeloma, diagnosed 2004–15 and followed up until December 2017. Patient survey Two questionnaires for use in haemato-oncology outpatient clinics were developed in-house and piloted: questionnaire 1 (health-related quality of life) was to be completed before the clinic appointment, and questionnaire 2 (treatment decisions) was to be completed after. The survey was successfully implemented in all 14 HMRN hospitals, 2016–8, with 3153 patients participating, 1282 with chronic lymphocytic leukaemia, follicular lymphoma or myeloma. Providing information across the pathway, over half of patients completed questionnaires while on W&W; the remainder either received chemotherapy or were monitored post treatment. Survey distribution and data collection were found to be simple and effective, and patients said that they appreciated the opportunity to ‘give back’ via taking part in research. Patient preferences for information sharing and engagement in treatment decisions Interviews were conducted with 35 patients who had experienced varying treatment pathways, and 10 relatives. A large, rich data set generated multifaceted findings. The unpredictable nature of chronic haematological malignancies was confirmed, as were the challenges of coping with uncertain pathways. This caused prolonged anxiety, which could be more distressing than any physical symptoms and difficult to resolve because of infrequent clinic visits and an absence of definitive information. Preferences for information (timing, content, depth and format) varied markedly, both between patients and across individual pathways over time. Regarding treatment decisions, most interviewees said that they preferred a discussion about options, but did not wish, or felt ill-equipped, to make choices themselves. Finally, individual access to a support network (e.g. family, friends or clinical staff) was found to impact positively on experiences and preferences. Conclusions Enhancing understanding about the pathways of the general population of patients with chronic haematological malignancies, this programme has accrued an abundance of new evidence. Data collection instruments have been developed, pathway visualisation programmes have been written, and detailed quantitative and qualitative information, to an extent not previously captured, are now available. We have demonstrated that it is possible to distribute questionnaires and collect longitudinal data in hospital settings, and assemble, summarise and visualise longitudinal pathways, including data on diagnostics, prognostics, treatments, transformations/progressions, hospital episodes, outcomes and costs. Regarding health economics, we have shown the utility of using longitudinal data to estimate how many patients are on each treatment line, post treatment after each line, receiving palliative care, and so on, thereby facilitating cost calculations and resource planning. Such models could potentially be used by commissioners and healthcare managers to simulate the impact of novel policies, treatments and pathway changes prior to their introduction. The marked, ongoing anxiety experienced by some patients due to uncertain pathways suggests that benefits could be accrued from increased awareness about the extent and impact of this, alongside interventions to counteract such difficulties. Addressing varied preferences for information (content, depth, format and timing) would require a broad range and depth of material (from a basic overview to detailed options), complexity (from simple terminology to more complicated graphs) and methods for sharing (verbal, written or electronic), thereby enabling patients to access what they want to know, when they want to know it. As most (but not all) people reported a preference for clinicians to make treatment recommendations, this should also be considered. Changing preferences means that strategies for patient engagement with information-sharing and treatment decisions may need to be tailored to individual needs over time, assessed by routine clinician monitoring. Clinicians might also explore the social infrastructure and support network available to patients, so that they are aware of gaps that could be addressed. Based on several thousand patients, and exceeding any evidence previously generated, this programme collated, assessed and successfully mapped high-quality evidence-based information about the pathways of the general population of patients with chronic haematological malignancies. Previously lacking, these data, coupled with new evidence on preferences for information-sharing and treatment decisions garnered directly from patients, provide the foundation to improve clinical practice. Unfortunately, the final part of the programme could not be completed due to the COVID-19 pandemic; hence, the key future priority is the translation of the data accrued into accessible information resources suitable for testing in routine NHS practice. These would need to be responsive to both the rapidly changing haemato-oncology landscape and the varying needs of clinicians and patients at different points on the pathway. Building on the foundations of the present programme, future research, in collaboration with clinicians and patients, could include: co-refinement of electronic visualisations for use in multidisciplinary team settings co-design of resources for use in clinician–patient consultations development of cluster randomised trial protocols to test resources developed in (1) and (2) across a single multidisciplinary team area using the data collection instruments developed, prior to further evaluation within/outside the region. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Programme Grants for Applied Research programme (NIHR award ref: RP-PG-0613-20002) and is published in full in Programme Grants for Applied Research; Vol. 12, No. 5. See the NIHR Funding and Awards website for further award information.

Introduction Despite the high number of operations and surgical advancement, rehabilitation after rotator cuff repair has not progressed for over 20 years. The traditional cautious approach might be contributing to suboptimal outcomes. Our aim is to assess whether individualised (early) patient-directed rehabilitation results in less shoulder pain and disability at 12 weeks after surgical repair of full-thickness tears of the rotator cuff compared with current standard (delayed) rehabilitation.Methods and analysis The rehabilitation after rotator cuff repair (RaCeR 2) study is a pragmatic multicentre, open-label, randomised controlled trial with internal pilot phase. It has a parallel group design with 1:1 allocation ratio, full health economic evaluation and quintet recruitment intervention. Adults awaiting arthroscopic surgical repair of a full-thickness tear are eligible to participate. On completion of surgery, 638 participants will be randomised. The intervention (individualised early patient-directed rehabilitation) includes advice to the patient to remove their sling as soon as they feel able, gradually begin using their arm as they feel able and a specific exercise programme. Sling removal and movement is progressed by the patient over time according to agreed goals and within their own pain and tolerance. The comparator (standard rehabilitation) includes advice to the patient to wear the sling for at least 4 weeks and only to remove while eating, washing, dressing or performing specific exercises. Progression is according to specific timeframes rather than as the patient feels able. The primary outcome measure is the Shoulder Pain and Disability Index total score at 12-week postrandomisation. The trial timeline is 56 months in total, from September 2022.Trial registration number ISRCTN11499185.

Abstract Background Estimates of future survival can be a key evidence source when deciding if a medical treatment should be funded. Current practice is to use standard parametric models for generating extrapolations. Several emerging, more flexible, survival models are available which can provide improved within-sample fit. This study aimed to assess if these emerging practice models also provided improved extrapolations. Methods Both a simulation study and a case-study were used to assess the goodness of fit of five classes of survival model. These were: current practice models, Royston Parmar models (RPMs), Fractional polynomials (FPs), Generalised additive models (GAMs), and Dynamic survival models (DSMs). The simulation study used a mixture-Weibull model as the data-generating mechanism with varying lengths of follow-up and sample sizes. The case-study was long-term follow-up of a prostate cancer trial. For both studies, models were fit to an early data-cut of the data, and extrapolations compared to the known long-term follow-up. Results The emerging practice models provided better within-sample fit than current practice models. For data-rich simulation scenarios (large sample sizes or long follow-up), the GAMs and DSMs provided improved extrapolations compared with current practice. Extrapolations from FPs were always very poor whilst those from RPMs were similar to current practice. With short follow-up all the models struggled to provide useful extrapolations. In the case-study all the models provided very similar estimates, but extrapolations were all poor as no model was able to capture a turning-point during the extrapolated period. Conclusions Good within-sample fit does not guarantee good extrapolation performance. Both GAMs and DSMs may be considered as candidate extrapolation models in addition to current practice. Further research into when these flexible models are most useful, and the role of external evidence to improve extrapolations is required.

Abstract Purpose To compare rates of persistent postoperative pain (PPP) after lumbar spine surgery—commonly known as Failed Back Surgery Syndrome—and healthcare costs for instrumented lumbar spinal fusion versus decompression/discectomy. Methods The UK population-based healthcare data from the Hospital Episode Statistics (HES) database from NHS Digital and the Clinical Practice Research Datalink (CPRD) were queried to identify patients with PPP following lumbar spinal surgery. Rates of PPP were calculated by type of surgery (instrumented and non-instrumented). Total healthcare costs associated with the surgery and covering the 24-month period after index hospital discharge were estimated using standard methods for classifying health care encounters into major categories of health care resource utilization (i.e., inpatient hospital stays, outpatient clinic visits, accident and emergency attendances, primary care encounters, and medications prescribed in primary care) and applying the appropriate unit costs (expressed in 2013 GBP). Results Increasing the complexity of surgery with instrumentation was not associated with an increased rate of PPP. However, 2-year healthcare costs following discharge after surgery are significantly higher among patients who underwent instrumented surgery compared with decompression/discectomy. Conclusions Although there is a not insubstantial risk of ongoing pain following spine surgery, with 1-in-5 patients experiencing PPP within 2 years of surgery, the underlying indications for surgical modality and related choice of surgical procedure do not, by itself, appear to be a driving factor.

Hypoxia can impair cognitive performance, whereas exercise can enhance it. The effects of hypoxia on cognitive performance during exercise appear to be moderated by exercise duration and intensity and by severity and duration of hypoxia and cognitive task. In normal individuals, exercise under hypoxia can evoke adverse post-exercise mood states, such as tension and fatigue. However, little is known about the effects of hypoxia during exercise in trained athletes. The purpose of this study was to investigate how hypoxia affected executive functions and mood states, assessed, respectively, during and post-exercise and to explore the role of motivation moderators, such as inhibition and activation systems (BIS-BAS). Two different sessions of exercise in normoxia and hypoxia (FiO2 13%), each lasting 18 min, were randomly assigned in a counterbalanced order and administered to seventeen male athletes. During exercise bouts, participants performed a mental task (BST) aimed to produce cognitive interference and suppression. Reaction times and accuracy of responses were recorded. After 5 min, all participants completed two questionnaires assessing mood states (ITAMS) and incidence of symptoms potentially related to hypoxia (AMS-C). The results show that hypoxia impairs cognitive performance in terms of slower reaction times, but a high BAS attenuates this effect. Participants with high BAS show an equivalent cognitive performance under hypoxia and normoxia conditions. No effects were found on mood states. Further research is required to investigate the role of BAS, cognitive abilities, and mood states in prolonged hypoxic conditions.

Objectives To describe the design, development and pilot of a multicomponent intervention aimed at supporting withdrawal of opioids for people with chronic non-malignant pain for future evaluation in the Improving the Wellbeing of people with Opioid Treated CHronic pain (I-WOTCH) randomised controlled trial.Design The I-WOTCH intervention draws on previous literature and collaboration with stakeholders (patient and public involvement). Intervention mapping and development activities of Behaviour Change Taxonomy are described.Setting The intervention development was conducted by a multidisciplinary team with clinical, academic and service user perspectives. The team had expertise in the development and testing of complex health behaviour interventions, opioid tapering and pain management in primary and secondary care, I.T programming, and software development—to develop an opioid tapering App.Participants The I-WOTCH trial participants are adults (18 years and over) with chronic non-malignant pain using strong opioids for at least 3 months and on most days in the preceding month.Outcomes A multicomponent self-management support package to help people using opioids for chronic non-malignant pain reduce opioid use.Interventions and results Receiving information on the impact of long-term opioid use, and potential adverse effects were highlighted as important facilitators in making the decision to reduce opioids. Case studies of those who have successfully stopped taking opioids were also favoured as a facilitator to reduce opioid use. Barriers included the need for a ‘trade-off to fill the deficit of the effect of the drug’. The final I-WOTCH intervention consists of an 8–10 week programme incorporating: education; problem-solving; motivation; group and one to one tailored planning; reflection and monitoring. A detailed facilitator manual was developed to promote consistent delivery of the intervention across the UK.Conclusions We describe the development of an opioid reduction intervention package suitable for testing in the I-WOTCH randomised controlled trial.Trial registration number ISRCTN49470934.

Introduction Over the last two decades, the use of opioids for the treatment of chronic pain in England has steadily increased despite lack of evidence of both long-term effectiveness in pain relief and significant, well-documented physical and mental adverse events. Guidelines recommend tapering when harms outweigh benefits, but the addictive nature of opioids hinders simple dose-reduction strategies. Improving the Well-being of people with Opioid Treated CHronic pain (I-WOTCH) trial tests a multicomponent self-management intervention aimed to help patients with chronic non-malignant pain taper opioid doses. This paper outlines the methods to be used for the economic analysis of the I-WOTCH intervention compared with the best usual care.Methods and analysis Economic evaluation alongside the I-WOTCH study, prospectively designed to identify, measure and value key healthcare resource use and outcomes arising from the treatment strategies being compared. A within-trial cost-consequences analysis and a model-based long-term cost-effectiveness analysis will be conducted from the National Health Service and Personal Social Service perspective in England. The former will quantify key parameters to populate a Markov model designed to estimate the long-term cost and quality-adjusted life years of the I-WOTCH intervention against best usual care. Regression equations will be used to estimate parameters such as transition probabilities, utilities, and costs associated with the model’s states and events. Probabilistic sensitivity analysis will be used to assess the impact of parameter uncertainty onto the predicted costs and health outcomes, and the resulting value for money assessment of the I-WOTCH intervention.Ethics and dissemination Full ethics approval was granted by Yorkshire & The Humber—South Yorkshire Research Ethics Committee on 13 September 2016 (16/YH/0325). Current protocol: V.1.7, date 31 July 2019. Findings will be disseminated in peer-reviewed journals, scientific conferences, newsletters and websites.Trial registration number International Standard Randomised Controlled Trial Number (49 470 934); Pre-result.

Historical, educational, and technical barriers have been reported to limit the use of surface electromyography (sEMG) in clinical neurorehabilitation settings. In an attempt to identify, review, rank, and interpret potential factors that may play a role in this scenario, we gathered information on (1) current use of sEMG and its clinical potential; (2) professional figures primarily dealing with sEMG; (3) educational aspects, and (4) possible barriers and reasons for its apparently limited use in neurorehabilitation. To this aim, an online 30-question survey was sent to 52 experts on sEMG from diverse standpoints, backgrounds, and countries. Participants were asked to respond to each question on a 5-point Likert scale or by ranking items. A cut-off of 75% agreement was chosen as the consensus threshold. Thirty-five invitees (67%) completed the electronic survey. Consensus was reached for 77% of the proposed questions encompassing current trends in sEMG use in neurorehabilitation, educational, technical, and methodological features as well as its translational utility for clinicians and patients. Data evidenced the clinical utility of sEMG for patient assessment, to define the intervention plan, and to complement/optimize other methods used to quantify muscle and physical function. The aggregate opinion of the interviewed experts confirmed that sEMG is more frequently employed in technical/methodological than clinical research. Moreover, the slow dissemination of research findings and the lack of education on sEMG seem to prevent prompt transfer into practice. The findings of the present survey may contribute to the ongoing debate on the appropriateness and value of sEMG for neurorehabilitation professionals and its potential translation into clinical settings.

Background: Scopus is a leading bibliometric database. It contains a large part of the articles cited in peer-reviewed publications. The journals included in Scopus are periodically re-evaluated to ensure they meet indexing criteria and some journals might be discontinued for 'publication concerns'. Previously published articles may remain indexed and can be cited. Their metrics have yet to be studied. This study aimed to evaluate the main features and metrics of journals discontinued from Scopus for publication concerns, before and after their discontinuation, and to determine the extent of predatory journals among the discontinued journals. Methods: We surveyed the list of discontinued journals from Scopus (July 2019). Data regarding metrics, citations and indexing were extracted from Scopus or other scientific databases, for the journals discontinued for publication concerns. Results: A total of 317 journals were evaluated. Ninety-three percent of the journals (294/317) declared they published using an Open Access model. The subject areas with the greatest number of discontinued journals were Medicine (52/317; 16%), Agriculture and Biological Science (34/317; 11%), and Pharmacology, Toxicology and Pharmaceutics (31/317; 10%). The mean number of citations per year after discontinuation was significantly higher than before (median of difference 16.89 citations, p

Background: Cost-effectiveness analysis using quality-adjusted life-years as the measure of health benefit is commonly used to aid decision-makers. Clinical studies often do not include preference-based measures that allow the calculation of quality-adjusted life-years, or the data are insufficient. ‘Mapping’ can bridge this evidence gap; it entails estimating the relationship between outcomes measured in clinical studies and the required preference-based measures using a different data set. However, many methods for mapping yield biased results, distorting cost-effectiveness estimates. Objectives: Develop existing and new methods for mapping; test their performance in case studies spanning different preference-based measures; and develop methods for mapping between preference-based measures. Data sources: Fifteen data sets for mapping from non-preference-based measures to preference-based measures for patients with head injury, breast cancer, asthma, heart disease, knee surgery and varicose veins were used. Four preference-based measures were covered: the EuroQoL-5 Dimensions, three-level version (n = 11), EuroQoL-5 Dimensions, five-level version (n = 2), Short Form questionnaire-6 Dimensions (n = 1) and Health Utility Index Mark 3 (n = 1). Sample sizes ranged from 852 to 136,327. For mapping between generic preference-based measures, data from FORWARD, the National Databank for Rheumatic Diseases (which includes the EuroQoL-5 Dimensions, three-level version, and EuroQoL-5 Dimensions, five-level version, in its 2011 wave), were used. Main methods developed: Mixture-model-based approaches for direct mapping, in which the dependent variable is the health utility value, including adaptations of methods developed to model the EuroQoL-5 Dimensions, three-level version, and beta regression mixtures, were developed, as were indirect methods, in which responses to the descriptive systems are modelled, for consistent multidirectional mapping between preference-based measures. A highly flexible approach was designed, using copulas to specify the bivariate distribution of each pair of EuroQoL-5 Dimensions, three-level version, and EuroQoL-5 Dimensions, five-level version, responses. Results: A range of criteria for assessing model performance is proposed. Theoretically, linear regression is inappropriate for mapping. Case studies confirm this. Flexible, direct mapping methods, based on different variants of mixture models with appropriate underlying distributions, perform very well for all preference-based measures. The precise form is important. Case studies show that a minimum of three components are required. Covariates representing disease severity are required as predictors of component membership. Beta-based mixtures perform similarly to the bespoke mixture approaches but necessitate detailed consideration of the number and location of probability masses. The flexible, bi-directional indirect approach performs well for testing differences between preference-based measures. Limitations: Case studies drew heavily on EuroQoL-5 Dimensions. Indirect methods could not be undertaken for several case studies because of a lack of coverage. These methods will often be unfeasible for preference-based measures with complex descriptive systems. Conclusions: Mapping requires appropriate methods to yield reliable results. Evidence shows that widely used methods such as linear regression are inappropriate. More flexible methods developed specifically for mapping show that close-fitting results can be achieved. Approaches based on mixture models are appropriate for all preference-based measures. Some features are universally required (such as the minimum number of components) but others must be assessed on a case-by-case basis (such as the location and number of probability mass points). Future research priorities: Further research is recommended on (1) the use of the monotonicity concept, (2) the mismatch of trial and mapping distributions and measurement error and (3) the development of indirect methods drawing on methods developed for mapping between preference-based measures. Funding: This 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. 24, No. 34. See the NIHR Journals Library website for further project information. This project was also funded by a Medical Research Council grant (MR/L022575/1).

Predatory journals (PJ) exploit the open-access model promising high acceptance rate and fast track publishing without proper peer review. At minimum, PJ are eroding the credibility of the scientific literature in the health sciences as they actually boost the propagation of errors. In this article, we identify issues with PJ and provide several responses, from international and interdisciplinary perspectives in health sciences. Authors, particularly researchers with limited previous experience with international publications, need to be careful when considering potential journals for submission, due to the current existence of large numbers of PJ. Universities around the world, particularly in developing countries, might develop strategies to discourage their researchers from submitting manuscripts to PJ or serving as members of their editorial committees.

Mediastinal lymphadenopathy is a condition in which one or more mediastinal lymph nodes are enlarged for malignant or benign causes, generally more than 10 mm. For a long time, the only way to approach the mediastinum was surgery, while in last decades endoscopic techniques gained their role in neoplastic diseases. At the present time, EBUS is the technique of choice for studying the mediastinum in the suspicion of cancer, while there are not strong indications in guidelines for the study of benign mediastinal lymphadenopathy. We reviewed the literature, looking for evidence of the role of EBUS in the diagnostics of non-neoplastic mediastinal lymphadenopathy, with special regard for granulomatous disease, both infectious and non-infectious. EBUS is a reliable alternative to surgery in non-neoplastic mediastinal lymphadenopathy, even if more evidence is needed for granulomatous diseases other than tuberculosis and sarcoidosis.

Some patients benefit from a treatment while others may do so less or do not benefit at all. We have previously developed a two-stage network meta-regression prediction model that synthesized randomized trials and evaluates how treatment effects vary across patient characteristics. In this article, we extended this model to combine different sources of types in different formats: aggregate data (AD) and individual participant data (IPD) from randomized and non-randomized evidence. In the first stage, a prognostic model is developed to predict the baseline risk of the outcome using a large cohort study. In the second stage, we recalibrated this prognostic model to improve our predictions for patients enrolled in randomized trials. In the third stage, we used the baseline risk as effect modifier in a network meta-regression model combining AD, IPD randomized clinical trial to estimate heterogeneous treatment effects. We illustrated the approach in the re-analysis of a network of studies comparing three drugs for relapsing--remitting multiple sclerosis. Several patient characteristics influence the baseline risk of relapse, which in turn modifies the effect of the drugs. The proposed model makes personalized predictions for health outcomes under several treatment options and encompasses all relevant randomized and non-randomized evidence.

Over the past three decades, the incidence of oropharyngeal squamous cell carcinoma has increased, primarily related to the spread of human papillomavirus. Treatment has always been preferentially unimodal (surgery or radiotherapy) for early stage disease and multimodal (surgery with adjuvant therapy or concomitant chemoradiotherapy) for advanced stages. Recently, the surgical approach has gained renewed interest due to the morbidity of non-surgical treatments and also to technical innovations. We have coined the term 3Des (3D exoscope surgery) to describe the use of the 3D Vitom Exoscope System for transoral surgery of oropharyngeal cancers. During the period from June 2017 to May 2018, 10 patients with oropharyngeal cancer were treated by oropharyngeal surgery with the 3Des approach at FPO IRCCS Institute of Candiolo. The aim of the present prospective study was to evaluate the utility of 3Des for the treatment of early-stage oropharyngeal cancer. 3Des could represent a viable alternative to the operating microscope and robotic surgery thanks to its excellent ability to provide 3D visual information, depth of field, magnification, image contrast, color imaging, and low running costs. It promises great utility in the learning process, with the possibility of recording in high definition.

Introduction The Improving the Wellbeing of people with Opioid Treated CHronic Pain (I-WOTCH) randomised controlled trial uses a multicomponent self-management intervention to help people taper their opioid use. This approach is not widely used and its efficacy is unknown. A process evaluation alongside the trial will help to assess how the intervention was delivered, looking at the dose of intervention received and the fidelity of the delivery. We will explore how the intervention may have brought about change through the experiences of the participants receiving and the staff delivering the intervention and whether there were contextual factors involved.Methods and analysis A mixed methods process evaluation will assess how the processes of the I-WOTCH intervention fared and whether these affected the outcomes. We will collect quantitative data, for example, group attendance analysed with statistical methods. Qualitative data, for example, from interviews and feedback forms will be analysed using framework analysis. We will use a ‘following a thread’ and a mixed methods matrix for the final integrated analysis.Ethics and dissemination The I-WOTCH trial and process evaluation were granted full ethics approval by Yorkshire and The Humber—South Yorkshire Research Ethics Committee on 13 September 2016 (16/YH/0325). All data were collected in accordance with data protection guidelines. Participants provided written informed consent for the main trial, and all interviewees provided additional written informed consent. The results of the process evaluation will be published and presented at conferences.Trial registration number ISRCTN49470934; Pre-results.

Introduction Chronic non-malignant pain has a major impact on the well-being, mood and productivity of those affected. Opioids are increasingly prescribed to manage this type of pain, but with a risk of other disabling symptoms, when their effectiveness has been questioned. This trial is designed to implement and evaluate a patient-centred intervention targeting withdrawal of strong opioids in people with chronic pain.Methods and analysis A pragmatic, multicentre, randomised controlled trial will assess the clinical and cost-effectiveness of a group-based multicomponent intervention combined with individualised clinical facilitator led support for the management of chronic non-malignant pain against the control intervention (self-help booklet and relaxation compact disc). An embedded process evaluation will examine fidelity of delivery and investigate experiences of the intervention. The two primary outcomes are activities of daily living (measured by Patient-Reported Outcomes Measurement Information System Pain Interference Short Form (8A)) and opioid use. The secondary outcomes are pain severity, quality of life, sleep quality, self-efficacy, adverse events and National Health Service (NHS) healthcare resource use. Participants are followed up at 4, 8 and 12 months, with a primary endpoint of 12 months. Between-group differences will indicate effectiveness; we are looking for a difference of 3.5 points on our pain interference outcome (scale 40 to 77). We will undertake an NHS perspective cost-effectiveness analysis using quality adjusted life years.Ethics and dissemination Full approval was given by Yorkshire & The Humber - South Yorkshire Research Ethics Committee on 13 September, 2016 (16/YH/0325). Appropriate local approvals were sought for each area in which recruitment was undertaken. The current protocol version is 1.6 date 19 December 2018. Publication of results in peer- reviewed journals will inform the scientific and clinical community. We will disseminate results to patient participants and study facilitators in a study newsletter as well as a lay summary of results on the study website.Trial registration number ISRCTN49470934; Pre-results.

Abstract Background Network meta-analysis methods, which are an extension of the standard pair-wise synthesis framework, allow for the simultaneous comparison of multiple interventions and consideration of the entire body of evidence in a single statistical model. There are well-established advantages to using individual patient data to perform network meta-analysis and methods for network meta-analysis of individual patient data have already been developed for dichotomous and time-to-event data. This paper describes appropriate methods for the network meta-analysis of individual patient data on continuous outcomes. Methods This paper introduces and describes network meta-analysis of individual patient data models for continuous outcomes using the analysis of covariance framework. Comparisons are made between this approach and change score and final score only approaches, which are frequently used and have been proposed in the methodological literature. A motivating example on the effectiveness of acupuncture for chronic pain is used to demonstrate the methods. Individual patient data on 28 randomised controlled trials were synthesised. Consistency of endpoints across the evidence base was obtained through standardisation and mapping exercises. Results Individual patient data availability avoided the use of non-baseline-adjusted models, allowing instead for analysis of covariance models to be applied and thus improving the precision of treatment effect estimates while adjusting for baseline imbalance. Conclusions The network meta-analysis of individual patient data using the analysis of covariance approach is advocated to be the most appropriate modelling approach for network meta-analysis of continuous outcomes, particularly in the presence of baseline imbalance. Further methods developments are required to address the challenge of analysing aggregate level data in the presence of baseline imbalance.

Patients with atopic dermatitis (AD) who do not adequately respond to topical therapy and phototherapy often need systemic immunomodulatory treatment to control their symptoms. Conventional systemic agents, such as ciclosporin, azathioprine, and methotrexate, have been used for decades, but there are concerns about their safety profile. There are now many novel systemic agents emerging through clinical trials, which may have great potential in the treatment of AD. Despite this, there are very few data comparing the performance of these drugs against each other. The purpose of this article is to review the current systemic therapies in AD and present an indirect comparison of systemic AD treatments using effectiveness and safety data from published randomised controlled trials, highlighting important remaining gaps in knowledge. Although the latest developments in systemic AD treatments are exciting and dearly needed, further work is required before the promise of a therapeutic revolution becomes reality.

Objectives: To investigate brainstem function in idiopathic REM sleep Behavior Disorder (iRBD), a condition occurring as a result of a derangement of connections within brainstem structures, with a battery of Vestibular Evoked Myogenic Potentials (VEMPs), neurophysiological tools suited for the functional investigation of the brainstem. Neurophysiological data were correlated with clinical characteristics of patients.Methods: Twenty patients with iRBD and 22 healthy controls underwent cervical (cVEMP), masseter (mVEMP) and ocular (oVEMP) VEMP recording. Patients were assessed clinically according to presence of motor as well as non-motor symptoms such as constipation, depression, and hyposmia. Also, they were screened for postural instability through the Berg Balance Scale (BBS). VEMPs were categorized as for increasing degrees of abnormalities, namely latency delay, amplitude reduction and absence; a VEMP score was built accordingly.Results: Compared with controls, iRBD had higher rates of abnormalities both in the VEMP battery (iRBD 75%, Controls 23%; p < 0.01) as well as in each single VEMP (cVEMP: 45 vs. 5%; mVEMP: 65 vs. 13.6%; oVEMP: 50 vs. 5%; p < 0.01), which exhibited significantly lower amplitudes (cVEMP and oVEMP: p < 0.0001; mVEMP: p = 0.001) in iRBD. Within altered reflexes, absence was predominant in oVEMP (81%), amplitude reduction in mVEMP (50%) and cVEMP (70%). Severity of VEMP alterations was significantly higher in iRBD compared with controls (p < 0.05 for all VEMPs), as indicated by the larger VEMP scores in the former. The oVEMP score correlated inversely with poor performances on the BBS.Conclusion: VEMPs unveil consistent and extensive brainstem abnormalities in iRBD patients. Further studies are warranted for testing the potential of VEMPs in the monitoring of the evolution of iRBD over time.

Illnesses and interventions can affect the health status of family carers in addition to patients. However economic evaluation studies rarely incorporate data on health status of carers.We investigated whether changes in carer health status could be 'predicted' from the health data of those they provide care to (patients), as a means of incorporating carer outcomes in economic evaluation.We used a case study of the family impact of meningitis, with 497 carer-patient dyads surveyed at two points. We used regression models to analyse changes in carers' health status, to derive predictive algorithms based on variables relating to the patient. We evaluated the predictive accuracy of different models using standard model fit criteria.It was feasible to estimate models to predict changes in carers' health status. However, the predictions generated in an external testing sample were poorly correlated with the observed changes in individual carers' health status. When aggregated, predictions provided some indication of the observed health changes for groups of carers.At present, a 'one-size-fits-all' predictive model of carer outcomes does not appear possible and further research aimed to identify predictors of carer's health status from (readily available) patient data is recommended. In the meanwhile, it may be better to encourage the targeted collection of carer data in primary research to enable carer outcomes to be better reflected in economic evaluation.

BACKGROUND:There is limited information on the costs and benefits of alternative adjunct non-pharmacological treatments for knee osteoarthritis and little guidance on which should be prioritised for commissioning within the NHS. This study estimates the costs and benefits of acupuncture, braces, heat treatment, insoles, interferential therapy, laser/light therapy, manual therapy, neuromuscular electrical stimulation, pulsed electrical stimulation, pulsed electromagnetic fields, static magnets and transcutaneous electrical nerve Stimulation (TENS), based on all relevant data, to facilitate a more complete assessment of value. METHODS:Data from 88 randomised controlled trials including 7,507 patients were obtained from a systematic review. The studies reported a wide range of outcomes. These were converted into EQ-5D index values using prediction models, and synthesised using network meta-analysis. Analyses were conducted including firstly all trials and secondly only trials with low risk of selection bias. Resource use was estimated from trials, expert opinion and the literature. A decision analytic model synthesised all evidence to assess interventions over a typical treatment period (constant benefit over eight weeks or linear increase in effect over weeks zero to eight and dissipation over weeks eight to 16). RESULTS:When all trials are considered, TENS is cost-effective at thresholds of £20-30,000 per QALY with an incremental cost-effectiveness ratio of £2,690 per QALY vs. usual care. When trials with a low risk of selection bias are considered, acupuncture is cost-effective with an incremental cost-effectiveness ratio of £13,502 per QALY vs. TENS. The results of the analysis were sensitive to varying the intensity, with which interventions were delivered, and the magnitude and duration of intervention effects on EQ-5D. CONCLUSIONS:Using the £20,000 per QALY NICE threshold results in TENS being cost-effective if all trials are considered. If only higher quality trials are considered, acupuncture is cost-effective at this threshold, and thresholds down to £14,000 per QALY.

Background: There has been an increase in the utilisation of acupuncture in recent years, yet the evidence base is insufficiently well established to be certain about its clinical effectiveness and cost-effectiveness. Addressing the questions related to the evidence base will reduce uncertainty and help policy- and decision-makers with regard to whether or not wider access is appropriate and provides value for money. Aim: Our aim was to establish the most reliable evidence on the clinical effectiveness and cost-effectiveness of acupuncture for chronic pain by drawing on relevant evidence, including recent high-quality trials, and to develop fresh evidence on acupuncture for depression. To extend the evidence base we synthesised the results of published trials using robust systematic review methodology and conducted a randomised controlled trial (RCT) of acupuncture for depression. Methods and results: We synthesised the evidence from high-quality trials of acupuncture for chronic pain, consisting of musculoskeletal pain related to the neck and low back, osteoarthritis of the knee, and headache and migraine, involving nearly 18,000 patients. In an individual patient data (IPD) pairwise meta-analysis, acupuncture was significantly better than both sham acupuncture (p

Background: Scopus is a leading bibliometric database. It contains the largest number of articles cited in peer-reviewed publications . The journals included in Scopus are periodically re-evaluated to ensure they meet indexing criteria and some journals might be discontinued for publication concerns. These journals remain indexed and can be cited. Their metrics have yet to be studied. This study aimed to evaluate the main features and metrics of journals discontinued from Scopus for publication concerns, before and after their discontinuation, and to determine the extent of predatory journals among the discontinued journals. Methods: We surveyed the list of discontinued journals from Scopus (July 2019). Data regarding metrics, citations and indexing were extracted from Scopus or other scientific databases, for the journals discontinued for publication concerns. Results: A total of 317 journals were evaluated. Ninety-three percent of the journals (294/318) declared they published using an Open Access model. The subject areas with the greatest number of discontinued journals were Medicine (52/317; 16%), Agriculture and Biological Science (34/317; 11%), and Pharmacology, Toxicology and Pharmaceutics (31/317; 10%). The mean number of citations per year after discontinuation was significantly higher than before (median of difference 64 citations, p Conclusions: The citation count of journals discontinued for publication concerns increases despite discontinuation and predatory behaviors seemed common. This paradoxical trend can inflate scholars’ metrics prompting artificial career advancements, bonus systems and promotion. Countermeasures should be taken urgently to ensure the reliability of Scopus metrics both at the journal- and author-level for the purpose of scientific assessment of scholarly publishing.