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Janet Ford,1 Russell M Nichols,1 Wenyu Ye,1 Antje Tockhorn-Heidenreich,1 Sarah Cotton,2 James Jackson2 1Eli Lilly and Company, Indianapolis, IN, USA; 2Adelphi Real World, Bollington, UKCorrespondence: Janet FordEli Lilly and Company, Indianapolis, IN, 46285, USATel +1 317-903-8199Email ford_janet@lilly.comPurpose: To evaluate patient-reported outcomes (PROs) among patients with migraine, including those who were preventive-naïve and preventive-treated.Methods: This was a point-in-time, real-world study of patients with migraine in the US and EU5 (France, Germany, Spain, Italy, and UK) and their physicians using data from the Adelphi Migraine Disease Specific Programme (DSP™). Physicians completed patient record forms (PRFs) for the next nine consulting patients with migraine plus a tenth patient, who did not need to be consecutive, for whom prior preventive migraine treatments had failed at least once, in order to achieve oversampling of such patients. Patients were given self-completion (PSC) forms that included the Migraine-Specific Quality of Life Questionnaire v2.1 (MSQ), Migraine Disability Assessment Scale (MIDAS), and Work Productivity and Activity Impairment (WPAI) questionnaire. Populations of interest included preventive-naïve and preventive-treated patients defined by the number of treatment lines (1– 2 or 3+ preventive regimens). Continuous variables were compared using t-test or ANOVA if normally distributed and Mann–Whitney if not. Chi-squared was used for categorical variables.Results: During August–December 2017, 615 physicians (359 PCPs, 256 neurologists) completed PRFs for 5785 patients (71% female; mean age 40 (± 14) years; 65% in full- or part-time employment). Of these, 2798 completed a PSC (preventive-naïve/1– 2/3+ preventive lines, n=1707/1034/57). Preventive-treated patients had a greater patient-reported burden across multiple measures versus preventive-naïve patients. Preventive-treated patients had lower MSQ scores indicating greater functional impairment, higher MIDAS scores indicating greater migraine-associated disability, and higher WPAI scores indicating greater overall work and activity impairment than preventive-naïve patients. The magnitude of difference was greatest for the 3+ preventive-treatments cohort. Patterns were similar in the US and EU5.Conclusion: Among patients with migraine who are preventive-treated, including those with multiple lines of therapy, there remain considerable unmet needs in terms of restoring patient function.Keywords: migraine, preventive, patient-reported outcomes, real-world

Background Since the emergence of SARS-CoV-2, evolutionary pressure has driven large increases in the transmissibility of the virus. However, with increasing levels of immunity through vaccination and natural infection the evolutionary pressure will switch towards immune escape. Genomic surveillance in regions of high immunity is crucial in detecting emerging variants that can more successfully navigate the immune landscape. Methods We present phylogenetic relationships and lineage dynamics within England (a country with high levels of immunity), as inferred from a random community sample of individuals who provided a self-administered throat and nose swab for rt-PCR testing as part of the REal-time Assessment of Community Transmission-1 (REACT-1) study. During round 14 (9 September–27 September 2021) and 15 (19 October–5 November 2021) lineages were determined for 1322 positive individuals, with 27.1% of those which reported their symptom status reporting no symptoms in the previous month. Results We identified 44 unique lineages, all of which were Delta or Delta sub-lineages, and found a reduction in their mutation rate over the study period. The proportion of the Delta sub-lineage AY.4.2 was increasing, with a reproduction number 15% (95% CI 8–23%) greater than the most prevalent lineage, AY.4. Further, AY.4.2 was less associated with the most predictive COVID-19 symptoms (p = 0.029) and had a reduced mutation rate (p = 0.050). Both AY.4.2 and AY.4 were found to be geographically clustered in September but this was no longer the case by late October/early November, with only the lineage AY.6 exhibiting clustering towards the South of England. Conclusions As SARS-CoV-2 moves towards endemicity and new variants emerge, genomic data obtained from random community samples can augment routine surveillance data without the potential biases introduced due to higher sampling rates of symptomatic individuals.

The evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus leads to new variants that warrant timely epidemiological characterization. Here we use the dense genomic surveillance data generated by the COVID-19 Genomics UK Consortium to reconstruct the dynamics of 71 different lineages in each of 315 English local authorities between September 2020 and June 2021. This analysis reveals a series of subepidemics that peaked in early autumn 2020, followed by a jump in transmissibility of the B.1.1.7/Alpha lineage. The Alpha variant grew when other lineages declined during the second national lockdown and regionally tiered restrictions between November and December 2020. A third more stringent national lockdown suppressed the Alpha variant and eliminated nearly all other lineages in early 2021. Yet a series of variants (most of which contained the spike E484K mutation) defied these trends and persisted at moderately increasing proportions. However, by accounting for sustained introductions, we found that the transmissibility of these variants is unlikely to have exceeded the transmissibility of the Alpha variant. Finally, B.1.617.2/Delta was repeatedly introduced in England and grew rapidly in early summer 2021, constituting approximately 98% of sampled SARS-CoV-2 genomes on 26 June 2021.

Sara Bruce Wirta,1 Bogdan Balas,2 Catia C Proenca,3 Hollie Bailey,4 Zoe Phillips,4 James Jackson,4 Sarah Cotton4 1Real World Evidence, Cardio-Metabolic Franchise, Novartis Sweden, Stockholm, Sweden; 2Real World Evidence, Cardio-Metabolic Franchise, Novartis Pharma, Basel, Switzerland; 3Wellmera AG, Basel, Switzerland; 4Real World Research, Adelphi Real World, Bollington, UK Purpose: Explore the extent to which heart failure (HF) symptoms and side effects of HF treatment experienced by patients are recognized by cardiologists, and concordance between patient–cardiologist perceptions of HF severity and patients’ contributions to treatment decision-making. Methods: A multinational, cross-sectional survey of cardiologists and patients with HF was conducted. Patient-record forms (PRFs) were completed by cardiologists for consecutive consulting patients with HF, who completed a patient self-completion questionnaire (PSC). Responses from PRFs with an associated PSC were analyzed to compare patient- and cardiologist-reported occurrences of HF symptoms and treatment side effects, patient-perceived severity of HF and cardiologists’ perceived risk of death within 12 months, and patient input into treatment decisions. Concordance was calculated as the number of response agreements between PSCs and PRFs for total number of matched pairs. Over- or underreporting of symptoms and side effects by cardiologists relative to patient-reported occurrences were calculated. Results: Overall, 2,454 patient–cardiologist pairs were identified. High levels of concordance between matched pairs were observed for the occurrence of reported HF symptoms (93%), side effects (77%–98%) and degree of patient input into treatment decisions (74%); for perceived HF severity, concordance was 54%. Most symptoms (except dyspnea when active and fatigue/weakness, experienced by >50% of patients) were underreported by cardiologists. Of patients reporting to have been informed by their cardiologist that their HF was mild, 28% were perceived by their cardiologist to have a moderate–high/very high risk of death within 12 months. Treatment choice was not discussed with almost a third of patients. When discussed, 94% of patients (n=1,540) reported the cardiologist made the final decision. Cardiologists more often under- than overreported the occurrence of side effects reported by patients. Conclusion: Improved patient–cardiologist dialogue and shared decision-making is required for optimizing patient care and outcomes in HF. Keywords: patient influence, disease awareness, treatment decision-making, patient-reported outcomes, disease-specific program, real world

As wireless connectivity becomes increasingly ubiquitous, a greater emphasis will be placed upon the seamless integration of dissimilar networking technologies. One such example of this will occur in urban environments, where wearable devices and vehicular networks will operate in close proximity to one another. Clearly, a natural extension to both types of network is their interconnectivity through vehicle-to-pedestrian (V2P) or equivalently pedestrian-to-vehicle (P2V) communications as part of a much greater vehicle-to-X (V2X)-based intelligent transportation system. To this end, we empirically investigate the P2V communications channel at 5.8 GHz for the case of a moving vehicle when a person positioned by the edge of a road was either stationary or walking parallel to the side of the highway. The measurements considered a chest-mounted transmitter and four receiver locations on the vehicle covering the front wing mirrors and two positions on the roof, which simultaneously recorded the received signal power. To characterize the propagation mechanisms which are responsible for shaping the received signal in the P2V channel, we decomposed it into its path loss (PL), large-scale, and small-scale fading components. We first show that although there was evidence of interference caused by multiple rays interacting with one another, the popular two-ray ground-reflection PL model was unable to adequately describe the compounded effects of the vehicle and pedestrian’s body on the signal attenuation in the majority of the considered scenarios. Instead, we found that the overall PL was well characterized using a dual-slope log-distance model, with lognormal large-scale fading. Due to the often severe small-scale fading that was observed in the P2V channel, we have been able to utilize the κ-μ extreme distribution with considerable success

The Nigerian Field, 30 (2), 82-84

The ability of a population to adapt to changing environments depends critically on the amount and kind of genetic variability it possesses. Mutations are an important source of new genetic variability and may lead to new adaptations especially if the population size is large. Mutation rates are extremely variable between and within species and males usually have higher mutation rates as a result of elevated rates of male germ cell division. This male bias affects the overall mutation rate. We examined the factors that influence male mutation bias and focused on the effects of classical life history parameters such as the average age at reproduction and elevated rates of sperm production in response to sexual selection and sperm competition. We argue that human induced changes in age at reproduction or in sexual selection will affect male mutation biases and hence overall mutation rates. Depending on the effective population size these changes are likely to influence the long term persistence of a population.

Soil or growing media salinity is an increasing problem in agriculture throughout the world. Therefore, there is a real interest in a better understanding of the mechanisms set by the plants to respond to this stress. The present study concerns tomato, which is one of the most important cultivated vegetables. Tomato seeds (Lycopersicon esculentum var. ‘Moneymaker’) were disinfected and a salt stress (NaCl 100 mM) was applied 8 days after the onset of germination. Samples were collected after 4 days of stress. In this study, attention was focused on the antioxidant system and the lipoxygenase pathway because salt stress is often associated with an increased production of reactive oxygen species and polyunsaturated fatty acids are one of the most susceptible targets to oxidative attacks. The perception of the stress by the plantlets was confirmed by the overexpression of an aquaporin-coding gene (aqua2). Concerning the antioxidant system, the activities of ascorbate peroxydase and catalase enzymes were studied but no significant variation was observed between stressed seedlings and controls. Similar results were obtained for ascorbate measurements. Complementarily, the lipoxygenase pathway was studied at three levels in the plantlets. The expression of two genes (lipoxygenase-A and oxo-phytodienoic acid reductase) was first followed at the mRNA level by RT-PCR. The oxylipin content was determined by HPLC and the lipoxygenase activity as well as the hydroperoxide degradation activity were measured spectrophotometrically. The obtained results indicate that no clear accumulation of oxylipin occurs in our stress conditions. However, an increase in lipoxygenase and hydroperoxide degradation activities was observed and seems to indicate that several enzymes of the lipoxygenase pathway are involved in the plant response to salt stress.

It is becoming increasingly recognized that fishing (and other forms of nonrandom harvesting) can have profound evolutionary consequences for life history traits. A recent and welcome publication provided the first description of how sexual selection might influence the outcome of fisheries-induced evolution (FIE). One of the main conclusions was that if sexual selection generates a positive relationship between body size and reproductive success, increased fishing pressure on large individuals causes stronger selection for smaller body size. Here, we re-evaluate the sexual selection interpretation of the relationship between body size and reproductive success, and suggest it may in fact be representative of a more general case of pure natural selection. The consequences of sexual selection on FIE are likely to be complicated and dynamic, and we provide additional perspectives to these new and exciting results. Selection differentials and trait variance are considered, with density-dependent and genetic effects on the strength and the direction of sexual selection given particular attention. We hope that our additional views on the role of sexual selection in FIE will encourage more theoretical and empirical work into this important application of evolutionary biology.

Background The treatment of patients with varicose veins constitutes a considerable workload and financial burden to the National Health Service. This study aimed to assess the cost-effectiveness of ultrasound-guided foam sclerotherapy (UGFS) and endovenous laser ablation (EVLA) compared with conventional surgery as treatment for primary varicose veins. Methods Participant cost and utility data were collected alongside the UK CLASS multicentre randomized clinical trial, which compared EVLA, surgery and UGFS. Regression methods were used to estimate the effects of the alternative treatments on costs to the health service and quality-adjusted life-years (QALYs) at 6 months. A Markov model, incorporating available evidence on clinical recurrence rates, was developed to extrapolate the trial data over a 5-year time horizon. Results Compared with surgery at 6 months, UGFS and EVLA reduced mean costs to the health service by £655 and £160 respectively. When additional overhead costs associated with theatre use were included, these cost savings increased to £902 and £392 respectively. UGFS produced 0·005 fewer QALYs, whereas EVLA produced 0·011 additional QALYs. Extrapolating to 5 years, EVLA was associated with increased costs and QALYs compared with UGFS (costing £3640 per QALY gained), and generated a cost saving (£206–439) and QALY gain (0·078) compared with surgery. Applying a ceiling willingness-to-pay ratio of £20 000 per QALY gained, EVLA had the highest probability (78·7 per cent) of being cost-effective. Conclusion The results suggest, for patients considered eligible for all three treatment options, that EVLA has the highest probability of being cost-effective at accepted thresholds of willingness to pay per QALY.

OBJECTIVES: Clinical staging is widespread in medicine - it informs prognosis, clinical course, and treatment, and assists individualized care. Staging places an individual on a probabilistic continuum of increasing potential disease severity, ranging from clinically at-risk or latency stage through first threshold episode of illness or recurrence, and, finally, to late or end-stage disease. The aim of the present paper was to examine and update the evidence regarding staging in bipolar disorder, and how this might inform targeted and individualized intervention approaches. METHODS: We provide a narrative review of the relevant information. RESULTS: In bipolar disorder, the validity of staging is informed by a range of findings that accompany illness progression, including neuroimaging data suggesting incremental volume loss, cognitive changes, and a declining likelihood of response to pharmacological and psychosocial treatments. Staging informs the adoption of a number of approaches, including the active promotion of both indicated prevention for at-risk individuals and early intervention strategies for newly diagnosed individuals, and the tailored implementation of treatments according to the stage of illness. CONCLUSIONS: The nature of bipolar disorder implies the presence of an active process of neuroprogression that is considered to be at least partly mediated by inflammation, oxidative stress, apoptosis, and changes in neurogenesis. It further supports the concept of neuroprotection, in that a diversity of agents have putative effects against these molecular targets. Clinically, staging suggests that the at-risk state or first episode is a period that requires particularly active and broad-based treatment, consistent with the hope that the temporal trajectory of the illness can be altered. Prompt treatment may be potentially neuroprotective and attenuate the neurostructural and neurocognitive changes that emerge with chronicity. Staging highlights the need for interventions at a service delivery level and implementing treatments at the earliest stage of illness possible.

BACKGROUND:There is a need for an instrument to measure the psychosocial burden of receiving an abnormal cervical cytology result which can be used regardless of the clinical management women receive.METHODS:3331 women completed the POSM as part of baseline psychosocial assessment in a trial of management of low grade cervical cytological abnormalities. Factor analysis and reliability assessment of the POSM were conducted.RESULTS:Two factors were extracted from the POSM: Factor 1, containing items related to worry; and Factor 2 containing items relating to satisfaction with information and support received and change in the way women felt about themselves. Factor 1 had good reliability (Cronbach's alpha 0.769), however reliability of the Factor 2 was poorer (0.482). Data collected at four subsequent time points demonstrated that the factor structure was stable over time.CONCLUSION:This study demonstrates the presence and reliability of a scale measuring worries within the POSM. This analysis will inform its future use in this population and in other related contexts.

In a community-wide screening program conducted in Jacksonville, Florida, 564 participants received free screening for prostate cancer. Frequency of positive results of prostate-specific antigen measurement and digital rectal examination was comparable to that found in similar programs in other communities. The estimated cost for each participant was $231, and the cost to discover each cancer was $7,240. If one also includes initial therapy in cost estimates, then the cost per participant was $520, and the cost to find and treat each patient was $16,300. The value of screening for prostate cancer must be judged by treatment outcome and underlying costs.

A critical aspect of blood transfusion is the timely provision of high quality blood products. This task remains a significant challenge for many blood services and blood systems reflecting the difficulty of balancing the recruitment of sufficient donors, the optimal utilization of the donor's gift, the increasing safety related restrictions on blood donation, a growing menu of specialized blood products and an ever-growing imperative to increase the efficiency of blood product provision from a cost perspective. As our industry now faces questions about our standard practices including whether or not the age of blood has a negative impact on recipients, it is timely to take a look at our collective inventory management practices. This International Forum represents an effort to get a snap shot of inventory management practices around the world, and to understand the range of different products provided for patients. In addition to sharing current inventory management practices, this Forum is intended to foster an exchange of ideas around where we see our field moving with respect to various issues including specialty products, new technologies, and reducing recipient risk from blood transfusion products.

The ability of a population to adapt to changing environments depends critically on the amount and kind of genetic variability it possesses. Mutations are an important source of new genetic variability and may lead to new adaptations, especially if the population size is large. Mutation rates are extremely variable between and within species, and males usually have higher mutation rates as a result of elevated rates of male germ cell division. This male bias affects the overall mutation rate. We examined the factors that influence male mutation bias, and focused on the effects of classical life-history parameters, such as the average age at reproduction and elevated rates of sperm production in response to sexual selection and sperm competition. We argue that human-induced changes in age at reproduction or in sexual selection will affect male mutation biases and hence overall mutation rates. Depending on the effective population size, these changes are likely to influence the long-term persistence of a population.

Poster-Abstract

In the last few years there have been considerable changes in the National Health Service Arguably the most significant of these has been the introduction of competition into health care, that is the split of the health service into purchasers and providers of care. Central to this development has been the introduction of General Practice Fundholding, whereby practices are able to purchase health care for their patients directly from competing suppliers Those practices which have become fundholders have faced considerable challenges in developing their purchasing function given the complexities of contracting within the context of the NHS Internal Market Although one of the original aims of GP Fundholding was to facilitate locally responsive purchasing, such have been the complexities of contracting that many fundholding practices have attempted to reduce the managerial demands of purchasing through membership of purchasing consortia. Based on an in-depth study of GP Fundholders across Scotland, this paper explores the development of consortia based purchasing. Specifically this paper seeks to address three issues central to the evolution of inter-organisational purchasing networks Firstly the patterns of organisational structure and evolving operational dynamics of such consortia Secondly the impact of such networks on the process and pattern of organisational purchasing Thirdly the managerial implications of purchasing through such inter-organisational networks for the participating organisations These issues will be addressed within the context of evolving perspectives on inter-organisational networks and the dynamics of purchasing centres This examination should serve to throw further light on both the dynamics of health care purchasing and contribute to the understanding of the evolution of inter-organisational purchasing networks In particular it will address whether such patterns of purchaser development has impacted on the evolution of locally responsive purchasing.

In the last few years there have been considerable changes in the National Health Service. Perhaps the most significant of these has been the introduction of competition into health care, that is the split of the health service into purchasers and providers of care. Central to this development has been the introduction of General Practice Fundholding, whereby practices are able to purchase health care for their own practices directly from competing suppliers. Those practices which have become fundholders have faced considerable challenges in developing their purchasing function. At the same time, provider units in areas where fundholding has become established face an increasingly fragmented purchasing base.

After a review of the current status of turbulence and diffusion modeling in the planetary boundary layer (PBL) and engineering fluid mechanics, the Working Group on Large Eddy Simulation (LES) concluded that inherent uncertainty is a major complication to atmospheric experiments and modeling and that data bases for future models of PBL are unlikely to be derived from field experiments. The roles of LES in quantifying inherent uncertainty and in providing appropriate data bases for analysis are discussed. Long range guidelines for PBL research using LES are presented (I) for the technical components of a program--turbulence theory, computational problems and requirements, physical and numerical experiments and transfer of technology to less complex models--and (II) for the management program to simulate research in environmental fluid mechanics.

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To be effective, the next generation of conservation practitioners and managers need to be critical thinkers with a deep understanding of how to make evidence-based decisions and of the value of evidence synthesis. If, as educators, we do not make these priorities a core part of what we teach, we are failing to prepare our students to make an effective contribution to conservation practice. To help overcome this problem we have created open access online teaching materials in multiple languages that are stored in Applied Ecological Resources. So far, 117 educators from 23 countries have acknowledged the importance of this and are already teaching or about to teach skills in appraising or using evidence in conservation decision-making. This includes 145 undergraduate, postgraduate or professional development courses. We call for wider teaching of the tools and skills that facilitate evidence-based conservation and also suggest that providing online teaching materials in multiple languages could be beneficial for improving global understanding of other subject areas.

Critical Review of the Literature Many trans* people experience high levels of mental health difficulties. Different gender-affirmative interventions exist which aim to alleviate gender dysphoria, with the hope that this in turn will improve the mental health and quality of life of trans* people. This systematic review aims to examine the effectiveness of affirmative dysphoria-focused interventions in improving mental health outcomes. Only studies with pre- and post-intervention measurements were included. Database searches were conducted from Medline, PsycInfo, Web of Science, Scopus and Embase with additional hand-searching (database inception to May 2022). Quality assessment of studies used the EPHPP Quality Assessment Tool. Twenty-six studies were identified that quantitatively assessed, via prospective pre- and post-test design, mental health outcomes (including depression, anxiety and self-esteem) following hormone, surgical and/or psychotherapeutic interventions. The majority of studies of hormone treatments found that mental health significantly improved following intervention and at follow-up. There was no significant change following surgical interventions at post-test to 6-month follow-up, although improvements were reported at longer follow-up time points. The majority of psychological interventions reported improvements in various mental health outcomes. The quality of the majority of included studies was assessed as being ‘medium’ or ‘weak’. There were no found qualitative pre- and post-intervention research or research examining voice and communication therapy or hair removal/electrolysis. This review indicates that interventions for gender dysphoria, especially hormone and psychological treatments, may have mental health benefits for trans* people. Further research is required to examine the relationship between mental health post-intervention and minority stressors, visual congruity with one’s gender and intersectional factors. Service Improvement Project Adolescents with eating disorders experience higher levels of psychological distress compared to the general population. Distress is particularly pronounced during the first stage of the Family Based Treatment due to the focus on refeeding and weight restoration. It is feasible that equipping adolescents to manage distress early on in treatment may positively impact on later engagement and recovery. This service improvement project describes the feasibility and implementation of a brief distress-tolerance intervention delivered alongside the first phase of FBT in a community Child and Adolescent Eating Disorder Service. This study was approved by the service NHS Research and Development team (ID: 286525). 15 adolescents (aged 11-18) in the first phase of FBT received two fortnightly 1-1 sessions with an Assistant Psychologist. Intervention content was based on distress tolerance dialectical-behavioural strategies. The Distress Tolerance Inventory (DTI) was administered at pre-test and two-week follow-up. Participants were interviewed about their experience and usefulness of the intervention sessions. Paired sample t-tests indicated tentative effectiveness of the intervention. Thematic analysis identified key superordinate themes: ‘Empowerment and Skilling Up’, ‘Delivery and Relevance’ and ‘Connection and Psychological Support’. The intervention was seen as highly acceptable and empowering for participants starting FBT. More sessions may be needed to ensure consolidation of newly learnt skills. Next steps regarding wider service implementation and empirically evaluating impact (e.g. on crisis referrals) are discussed. Theoretically Driven Research Project Individuals suffering from OCD experience a heightened sense of responsibility compared to community sample and anxious controls. This responsibility may vary depending on the subject of potential harm (e.g. I am responsible for my own safety vs I am responsible for other people’s safety). 5 causal factors or ‘pathways’ to the development of heightened responsibility have been proposed. This study aims to examine the relationship between the pathways to heightened responsibility towards oneself vs towards others. 60 participants with OCD and 60 community controls completed an online questionnaire measuring childhood and early adulthood experiences and responsibility dimensions. Regression analyses established the predictive value of each pathway. ‘Responsibility for oneself’, ‘responsibility for others’ and four of the five pathway subscales were significantly higher for the OCD group. The extent that participants had acted to influence misfortune was a significant predictor of heightened responsibility for oneself. Increased responsibility as a child and experience of overprotective parenting significantly predicted responsibility for others. This study indicates that heightened responsibility for oneself vs others may develop via separate pathways. Prospective studies are needed to understand how responsibility and other OCD-related beliefs develop in adolescence and early adulthood.