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Purpose Upper respiratory tract infections (URTI) and related symptoms are widespread and a common reason for visiting primary care with cough and sore throat being most prevalent. Despite their impact on daily activities, no studies have explored the impact on health-related quality of life (HRQOL) in representative general populations. We aimed to understand the short-term impact of the two most prevalent URTI symptoms on HRQOL. Methods Online 2020 surveys including acute (≤ 4 weeks) respiratory symptoms (sore throat and cough) and SF-36® health survey (all with 4-week recall) were analysed using analysis of covariance (ANCOVA) in comparison with adult US population norms. Linear T-score transformation of SF-6D utility (ranging from 0 to 1) enabled direct comparisons with SF-36. Results In total, 7563 US adults responded (average age: 52 years; range: 18–100 years). Sore throat and cough lasting at least several days were experienced by 14% and 22% participants, respectively. Chronic respiratory conditions were reported by 22% of the sample. A clear and consistent pattern of group HRQOL means declining significantly (p Conclusion Declines in HRQOL with acute cough and sore throat symptoms consistently exceeded MID standards and should not be ignored as self-limiting without intervention. Future studies on early self-care for symptom relief and its implications on HRQOL and health economics would be valuable to understand the benefits on healthcare burden and need for updating treatment guidelines.

PurposeThis qualitative study aimed to construct an observer-reported outcome measure (ObsRO) that evaluates fever distress in young children.MethodsA literature review was conducted to identify fever-related concepts. Clinical experts were interviewed for feedback on these concepts. Parents of young children were interviewed to identify behaviours the child exhibited during a recent fever episode. Fever sign and behaviour concepts endorsed by ≥20% parents were used to create items for the draft ObsRO. Parents of young children who recently had fever completed the ObsRO and gave feedback during two successive rounds of cognitive interviews.ResultsTwenty-five parents participated in the concept elicitation. Mean child age was 2.7 years (range: 0.6‑5.8). Fever sign and behaviour concepts endorsed by ≥20% participants were high temperature (80%), skin hot to touch (32%), skin redness/flushing (32%), reduced appetite/drink (48‑96%), needy/clingy/irritable (48‑92%), less active/interactive (68‑84%) and lethargic (64‑88%). Eighteen items, four in the Fever Signs Module and 14 in the Fever Behaviours Module, were developed for the draft ObsRO. Chosen recall period was 24 hours. Thirty participants (Round 1: n=17; Round 2: n=13), participated in cognitive interviews. Mean child age was 2.4 years (range: 0.3‑5.8). Round 1 feedback resulted in two Fever Signs items being combined. Three Fever Behaviour items were deleted, six revised and four unchanged. No changes were made following Round 2 feedback. Most participants understood all aspects of the ObsRO and found it user-friendly.ConclusionThe ObsRO will undergo further development in validation studies testing measurement properties of each item.

This work was funded by Grant No. N00014-20-1-2748 from the United States Office of Naval Research (ONR) awarded to M.W. Tag development was supported by ONR Grant Nos. N00014-16-1-2852, N00014-18-1-2062, and N00014-20-1-2709. M.J. was supported by the Aarhus University Research Foundation and the EU H2020 research and innovation program under Marie Skłodowska-Curie Grant No. 754513. Empirical measurements of odontocete hearing are limited to captive individuals, constituting a fraction of species across the suborder. Data from more species could be available if such measurements were collected from unrestrained animals in the wild. This study investigated whether electrophysiological hearing data could be recorded from a trained harbor porpoise (Phocoena phocoena) using a non-invasive, animal-attached tag. The results demonstrate that auditory brainstem responses to external and self-generated stimuli can be measured from a stationary odontocete using an animal-attached recorder. With additional development, tag-based electrophysiological platforms may facilitate the collection of hearing data from freely swimming odontocetes in the wild. Publisher PDF

Adam B Smith,1 Andria Hanbury,1 Igor Beitia Ortiz de Zarate,2 Florence Hammes,2 Gerard de Pouvourville,3 Katharina Buesch4 1York Health Economics Consortium, University of York, York, UK; 2PTC Therapeutics France, Paris, France; 3Department of Economics, ESSEC, Paris, France; 4PTC Therapeutics GmbH, Zug, SwitzerlandCorrespondence: Adam B SmithYork Health Economics Consortium, University of York, Enterprise House, Innovation Way, YO10 5NQ, UKTel +44 1904 323620Fax +44 1904 323628Email adam.smith@york.ac.ukPurpose: Health-related quality of life (HRQoL) is difficult to measure in rare diseases, especially in paediatric populations, yet capturing HRQoL is critical to evaluating treatment, including the cost-effectiveness of treatments. Given the ultra-rare nature of AADC deficiency indirect elicitation of HRQoL data through proxy caregiver/parent ratings is not feasible. In these circumstances, HRQoL data may be derived through vignette studies using the general population. The aim of the study was to generate health utility values specific for France for AADC deficiency using vignettes.Methods: The study was completed online by panel participants from a French representative sample. Five health state vignettes, reflecting key milestones in the eladocagene exuparvovec clinical trials and economic model, were presented to the participants: “bedridden”, “head control”, “sitting unsupported”, “standing with assistance” and “walking with assistance”. The vignettes had been previously developed with input from parents of patients with AADC deficiency, patients and expert opinion. Participants also completed the Health Utilities Index-3 for the “bedridden” health state.Results: A total of 1001 participants (51% females; mean age 46 years) completed the vignettes. Utilities increased linearly as the health state improved for both the time trade-off (TTO): 0.47 (standard deviation, SD 0.36) to 0.54 (SD 0.36) and standard gamble (SG): 0.61 (SD 0.29) to 0.67 (SD 0.27). A significant minority had incongruent responses (high utilities for the bedridden compared to walking health states) for the vignette (27%). When these were removed, the TTO health utilities (N=729) ranged from 0.39 (SD 0.36) to 0.56 (SD 0.38) and 0.61 (SD 0.30) to 0.69 (SD 0.27) for the SG.Conclusion: Health utilities were derived for AADC deficiency which will be used for a cost-effectiveness model of an AADC deficiency treatment.Keywords: AADC deficiency, vignettes, time trade-off, standard gamble

Determining the distribution and environmental preferences of rare species threatened by global change has long been a focus of conservation. Typical minimum suggested number of occurrences ranges from ∼5 to 30, but many species are represented by even fewer occurrences. However, several newer methods may be able to accommodate such low samples sizes. These include Bayesian joint species distribution models (JSDMs) which allow rare species to statistically “borrow strength” from more common species with similar niches, and ensembles of small models (ESMs), which reduce the number of parameters by averaging smaller models. Here we explore how niche breadth and niche position relative to other species influence model performance at low sample sizes (N=2, 4, 8, 16, 32, 64) using virtual species within a community of real species. ESMs were better at discrimination tasks for most species, and yielded better-than-random accuracy even for N=2. In contrast, “traditional” single species or JSDMs were better able to estimate the underlying response curves of variables that influenced the niche, but at low sample sizes also were more likely to incorrectly identify unimportant factors as influential. Species with niches that were narrow and peripheral to the available environmental space yielded models with better discrimination capacity than species with broad niches or niches that were similar to those of other species, regardless of whether the modeling algorithm allowed for borrowing of strength. Our study suggests that some rare species may be able to be modeled reliably at very low sample sizes, although the best algorithm depends on number of occurrences and whether the niche or distribution is the focus.

Purpose The aim of this study was to evaluate the impact of work-related musculoskeletal (MSK) lower body pain on health-related quality of life (HRQoL) in a large sample of workers in the United Kingdom, as well as evaluating the potential economic impact of MSK pain.MethodsParticipants with self-reported work-related MSK pain completed the Brief Pain Inventory (BPI), the Work Productivity and Activity Impairment (WPAI) scale and the AQoL-4D online. Sociodemographic details, work patterns and healthcare resource utilisation were also collected. UK industry-specific weekly wages were used to evaluate the economic cost.ResultsA total of 1035 completed the survey (57.4% female; mean age 43.4 years). Participants reported spending all (25.2%) or most (53%) of their time at work on their feet. Mean BPI severity score was 4.63 (standard deviation: 2.07); mean BPI interference score was 4.37 (2.49). There was a linear relationship between length of shift, time on feet and pain. Mean AQoL-4D scores were 0.609 (0.254). A mean of 4.12 hours was lost per week due to work-related pain. Mean levels of absenteeism over the last 7 days were 9.5% (20.7%), and presenteeism 33.3% (24.9%). On average there were 1.55 visits to family practitioners (total cost: £19,866) and 1 hospital visit had been made over the year (£37,320) due to work-related MSK pain. ConclusionLower-body work-related MSK pain has a high prevalence. Given this, these results indicate that work-related lower body pain has a significant impact in terms of individual HRQoL and as an economic societal burden.

Purpose To generate UK health-related quality-of-life (HRQoL) data for adult patients with moderate-to-severe limbal stem cell deficiency (LSCD), unilateral or bilateral, due to physical or chemical ocular burns to help inform economic evaluations of treatments. Patients and Methods EQ-5D-3L with vision bolt-on scores was prospectively measured for one of five clinical scenarios of LSCD described in vignettes in a demographically representative population of 520 UK adults. These were converted to health state utilities using three different UK value sets. A standard gamble (SG) was then undertaken using 12 SG scenarios to examine the component drivers of health utility for the treatment of LSCD. Results For the EQ-5D-3L scenarios, the mean disutility for LSCD with poor visual acuity, pain and disfigurement in both eyes compared to one eye was -0.084 (range=-0.156 to -0.045 across the value sets). The mean disutility of bilateral LSCD with pain, disfigurement, and poor visual acuity compared to unilateral LSCD with only poor visual acuity in one eye was -0.104 (range=-0.151 to -0.078). Similarly, where one eye was affected, pain and disfigurement in combination were associated with a greater mean disutility than improvements in visual acuity alone: -0.011 (range=-0.04 to 0.005). Mean SG utilities were within a narrow range (0.682-0.765). Where one eye was affected, the main driver was disfigurement: mean utility was 0.731 (0.709-0.753) compared to 0.682 (0.659-0.704) when disfigurement was removed compared to vision restored to normal. For bilateral LSCD, mean utilities were 0.693 (0.672-0.715) for normal vision and 0.75 (0.73-0.771) when disfigurement and pain were removed. Conclusion Improvements in pain and disfigurement appeared to be the main factors driving differences in health utilities associated with symptom profiles in LSCD, with improvements in visual acuity having lesser impact.

Background Gastroesophageal reflux disease (GORD) is a common condition affecting 30% of infants aged 0-23 months. The Infant Gastroesophageal Questionnaire Revised version (I-GERQ-R) is an observer-reported outcome measures (ObsRO) developed to evaluate the impact of GORD on young infants. However, evidence regarding the clinically important difference (CID) for the I-GERQ-R is limited. The aim of this study was to determine a CID for the I-GERQ-R. Methods A literature review was undertaken (PsycInfo, Embase, MedLine and EconLit databases) for longitudinal studies involving the I-GERQ-R. Articles were not limited by language or publication date. A random effects model was applied to calculate an overall CID, along with I2 and Q statistics. Publication bias was also assessed. Results The search identified 42 articles; 11 were selected for full-text review and 7 articles were identified for full data extraction. The studies included a total of 661 infants (range: 30 to 313); 424 infants had been diagnosed with GORD (64%). The age range of the infants across the studies was from birth to 7 months. The overall CID was -6.54 (95% confidence interval: -4.35 to -8.74), Q = 17.96, p=0.08 and I2=22.04. Conclusion This study derived a CID for the I-GERQ-R and indicated a threshold around 6 could signify a clinically important difference for this instrument. The lower limit of the 95% confidence interval suggested a threshold of 3 to 4 could represent a minimally important difference. These results may help inform clinical decisions in evaluating meaningful change in symptom severity in children affected by GORD.

Background Antibiotics are inappropriately prescribed to many people with sore throat. As most cases of sore throat are viral and/or self-limiting, guidelines recommend symptomatic management as first-line treatment. This paper reviews the available clinical evidence for the efficacy and safety of low-dose (8.75 mg) flurbiprofen, locally delivered to the throat for the symptomatic management of pharyngitis/sore throat. Method A literature search was performed on 27 February 2019 using PubMed. Studies that met the following criteria were included in a narrative review: (1) studies evaluating the effectiveness of flurbiprofen for pharyngitis/sore throat; (2) randomized controlled studies; (3) locally administered formulation of study drug/comparator; and (4) flurbiprofen administered at 8.75 mg dose (single- or multiple-dose administration). Results A total of 17 papers were included in the review: 15 publications reporting data from nine unique clinical studies of flurbiprofen for acute pharyngitis, and two reporting studies of flurbiprofen for the prevention of postoperative sore throat (POST). Studies in acute pharyngitis demonstrated that single- and multiple-dose flurbiprofen 8.75 mg, locally administered in lozenge, spray or microgranule form, was well tolerated and provided early onset and long-lasting symptomatic relief from throat pain and soreness, sensation of swollen throat, difficulty swallowing, and other associated symptoms. This included patients with more severe symptoms, patients with confirmed Streptococcus A/C sore throat, and patients taking concomitant antibiotics. In addition, a single preoperative dose of flurbiprofen lozenge was shown to be effective for relieving early POST in patients undergoing general anesthesia. Conclusion Locally administered, low-dose flurbiprofen offers a useful first-line treatment option for symptomatic relief in patients with "uncomplicated" acute pharyngitis/sore throat associated with upper respiratory tract infection, thus potentially helping to reduce unnecessary antibiotic prescribing. It also offers an effective preoperative treatment option for the reduction of early POST severity and incidence.

Neil Fawkes, Evi Tselenti, Neil Shah, Victoria Lappin, Neil Smith, Arjun Narasimhan, Adam B Smith Reckitt Benckiser Health Care Ltd., Hull, HU8 7DS, UKCorrespondence: Neil FawkesReckitt Benckiser Health Care Ltd., Dansom Lane, Hull, HU8 7DS, UKEmail neil.fawkes@rb.comBackground: Skin sensitivity characteristics and triggers have been identified in populations in previous studies. However, few have compared these characteristics among self-reported sensitive skin.Objective: The aim of the study was to evaluate and compare specific intrinsic and extrinsic triggers of skin sensitivity between individuals with self-reported sensitive skin and non-sensitive skin.Methods: A systematic literature review was undertaken to identify intrinsic and extrinsic factors associated with sensitive skin. A 167-item survey was developed on the basis of the literature review. The survey was completed online by a sample of adult participants drawn from the general United Kingdom population. Participants also completed sociodemographic and self-reported health questions.Results: A total of 3050 surveys were completed: 1526 participants with self-reported skin sensitivity and 1524 participants not reporting skin sensitivity. There was a decrease in self-reported skin sensitivity with increasing age (p< 0.05), and proportionally more women reported sensitive skin. Smoking also led to a higher frequency of sensitive skin. All signs and symptoms of sensitive skin, such as itch, dryness/flakiness, roughness and flushing/blushing were more commonly reported by those with self-reported sensitive skin. These were frequently reported in association with external factors (cold/windy weather, clothes and fabrics), as well as internal factors such as pre-existing skin conditions and atopy.Conclusion: The study evaluated self-reported sensitive skin against a non-sensitive skin in order to identify common inherent and external triggers to distinguish between these groups in a large general population study in the United Kingdom. The key symptoms and signs of this syndrome identified in the literature were confirmed to be reported significantly more when compared with those without sensitive skin. However, no correlation or pattern of symptomology could be identified, reinforcing the complexity of this condition. Given the strong differentiation from the non-sensitive group, the results of this research could be utilised for the development of a clinically meaningful screening tool.Keywords: sensitive skin, smoking, age, asthma, atopy

AimMuseum and herbarium specimen records are frequently used to assess species’ conservation status and responses to climate change. Typically, occurrences with imprecise geolocality information are discarded because they cannot be matched confidently to environmental conditions, and are thus expected to increase uncertainty in downstream analyses. However, using only precisely georeferenced records risks undersampling of species’ environmental and geographic distributions. We present two related methods to allow the use of imprecisely georeferenced occurrences in biogeographic analysis.InnovationOur two procedures assign imprecise records to the 1) locations or 2) climates that are closest to the geographic or environmental centroid of the precise records of a species. For virtual species, including imprecise records alongside precise records improved the accuracy of ecological niche models projected to the present and the future, especially for species with~20 or fewer precise occurrences. Using only precise records underestimates loss in suitable habitat and overestimates the amount of suitable habitat in both the present and future. Including imprecise records also improves estimates of niche breadth and extent of occurrence. An analysis of 44 species of North AmericanAsclepias(Apocynaceae) yielded similar results.Main conclusionsExisting studies examining the effects of spatial imprecision compare outcomes based on precise records to the same records with spatial error added to them. However, in real-world cases, analysts possess a mix of precise and imprecise records and must decide whether to retain or discard the latter. Discarding imprecise records can undersample species’ geographic and environmental distributions and lead to mis-estimation of responses to past and future climate change. Our method, for which we provide a software implementation in the enmSdmX package for R, is simple to employ and can help leverage the large number of specimen records that are typically deemed “unusable” because of spatial imprecision in their geolocation.

Accounting for within-species variability in the relationship between occurrence and climate is essential to forecasting species’ responses to climate change. Few climate-vulnerability assessments explicitly consider intraspecific variation, and those that do typically assume that variability is best explained by genetic affinity. Here, we evaluate how well heterogeneity in responses to climate by a cold-adapted mammal, the American pika (Ochotona princeps), aligns with subdivisions of the geographic range by phylogenetic lineage, physiography, elevation or ecoregion. We find that variability in climate responses is most consistently explained by an ecoregional subdivision paired with background sites selected from a broad spatial extent indicative of long-term (millennial-scale) responses to climate. Our work challenges the common assumption that intraspecific variation in climate responses aligns with genetic affinity. Accounting for the appropriate context and scale of heterogeneity in species’ responses to climate will be critical for informing climate-adaptation management strategies at the local (spatial) extents at which such actions are typically implemented. Intraspecies response to climate change is expected to align with genetic affinity. Using the American pika as a case study suggests that divisions of species distributions best explain intraspecific heterogeneity in climate relationships.

A primary focus of historical biogeography is to understand changes in species ranges, abundance and genetic connectivity, and changes in community composition. Traditionally, biogeographic inference has relied on distinct lines of evidence, including DNA sequences, fossils and hindcasted ecological niche models. In this review we propose that the development of integrative modeling approaches that leverage multiple distinct data types from diverse disciplines has the potential to revolutionize the field of biogeography. Although each data type contains information on a distinct aspect of species’ biogeographic histories, few studies formally integrate multiple types in analysis. For example, post hoc congruence among analyses based on different data types (e.g. fossils and genetics) is commonly assumed to indicate likely biogeographic histories. Unfortunately, analyses of different data often reach discordant conclusions. Thus, fundamental and unresolved debates continue regarding speed and timing of postglacial migration, location and size of glacial refugia, and degree of long distance dispersal. Formal statistical integration can help address these issues. More specifically, formal integration can leverage all available evidence, account for inherent biases associated with different data types, and quantify data and process uncertainty. Novel, quantitative integration of data and models across fields is now possible due to recent advances in cyberinfrastructure, spatial modeling, online and aggregated ecological databases, data processing and quantitative methods. Our purpose is to make the case for and give examples of rigorous integration of genetic, fossil and environmental/occurrence data for inferring biogeographic history. In particular, we 1) review the need for such a framework; 2) explain common data types and approaches used to infer biogeographic history (and the challenges with each); 3) review state‐of‐the‐art examples of data integration in biogeography; 4) lay out a series of novel, suggested improvements on current methods; and 5) provide an outlook on technical feasibility and future opportunities.

Objectives: Differences in testosterone replacement therapy (TRT) gel products may affect patient satisfaction, quality-of-life, and treatment response and adherence. This study investigated preferences for TRT gel in terms of formulation and administration. Methods: 525 male adults aged 45 years and over completed a discrete choice experiment. Respondents made repeated choices between two hypothetical testosterone gel treatments described according to four attributes: form, ease of use, impact of use on showering/swimming, and location/dosage of the application. Choice data were analyzed using a latent class model. Results: Three preference classes were identified. Respondents across all classes displayed a preference for the gel being dispensed in smaller units with accurate dosing, waiting shorter times after the gel application before swimming/showering, and using 2.5 gm of gel to be applied to the inner thigh/abdomen as opposed 5 gm to shoulder/abdomen. The importance of these characteristics differed across classes, with preference class membership predicted by age and education level. For instance, younger men (aged 45-64 years) were more likely to belong to a class that prioritized reduced waiting time before being able to undertake activities. Formulation was not an important driver of choice. Conclusions: Preferences demonstrate a predilection for TRT gel dispensed in small units allowing precise dosing, shorter waiting time after application, and application to the inner thigh/abdomen. However, the strength of importance of these characteristics differs between men. This study highlights the attributes of TRT gel considered important to patient subgroups, and which may ultimately affect treatment response, medication adherence, and patient quality-of-life.

Background Obesity is the most common chronic disease in the United States today. Additional therapies are needed to improve obesity treatment. Objective A swallowable, gas-filled intragastric balloon system was approved for the treatment of obesity by Food and Drug Administration in September 2016 and commercialization started January 2017. A registry was made available to physicians to capture evidence of safety and effectiveness with use. Setting United States private clinics, surgery centers, and hospitals. Methods This study is a retrospective analysis of a prospective registry of patients with body mass index (BMI) ≥25 kg/m2 that initiated therapy in the first year. Data on demographics, procedural timing, weight loss, adverse events, and device deficiencies were captured. Results The final analysis comprised 1343 patients across 108 treating physicians (mean age 45.7 ± 10.8 yr, 78.6% female, baseline BMI of 35.4 ± 5.4 kg/m2). Nonserious and serious adverse events were reported in 14.2% and .15% of patients, respectively. There were 7 balloon deflations, none caused obstruction. Weight loss in the indicated use (BMI 30–40 kg/m2) was 9.7 ± 6.1 kg and 10.0 ± 6.1% total body weight loss (TBWL). Weight loss in other BMI categories was 8.2 ± 5.6 kg or 10.3 ± 7.0% total body weight loss for BMI 25 to 29.9 kg/m2 and 11.6 ± 7.8 kg or percent total body weight loss 9.3 ± 6.0 for BMI >40 kg/m2. Conclusions This swallowable gas-filled intragastric balloon system is safe and effective at inducing weight loss and offers physicians another tool for patients whose obesity has been resistant to noninvasive treatments.

Many prior studies have uncovered evidence for local adaptation using reciprocal transplant experiments. However, these studies are rarely conducted for a long enough time to observe succession and competitive dynamics in a community context, limiting inferences for long-lived species. Furthermore, the genetic basis of local adaptation and genetic associations with climate has rarely been identified. Here, we report on a long-term (6-year) experiment conducted under natural conditions focused on Andropogon gerardii, the dominant grass of the North American Great Plains tallgrass ecosystem. We focus on this foundation grass that comprises 80% of tallgrass prairie biomass and is widely used in 20,000 km2 of restoration. Specifically, we asked the following questions: (a) Whether ecotypes are locally adapted to regional climate in realistic ecological communities. (b) Does adaptive genetic variation underpin divergent phenotypes across the climate gradient? (c) Is there evidence of local adaptation if the plants are exposed to competition among ecotypes in mixed ecotype plots? Finally, (d) are local adaptation and genetic divergence related to climate? Reciprocal gardens were planted with 3 regional ecotypes (originating from dry, mesic, wet climate sources) of Andropogon gerardii across a precipitation gradient (500-1,200 mm/year) in the US Great Plains. We demonstrate local adaptation and differentiation of ecotypes in wet and dry environments. Surprisingly, the apparent generalist mesic ecotype performed comparably under all rainfall conditions. Ecotype performance was underpinned by differences in neutral diversity and candidate genes corroborating strong differences among ecotypes. Ecotype differentiation was related to climate, primarily rainfall. Without long-term studies, wrong conclusions would have been reached based on the first two years. Further, restoring prairies with climate-matched ecotypes is critical to future ecology, conservation, and sustainability under climate change.

The Weight-specific Adolescent Instrument for Economic evaluation (WAItE) is a 7-item condition-specific tool assessing the impact of weight status on seven dimensions of quality of life. The content of the WAItE was developed with both treatment-seeking and non-treatment-seeking adolescents aged 11-18 years. The aim of this study was to assess the psychometric properties of the WAItE in adolescent and adult populations.Treatment-seeking adolescents with obesity (females n = 155; males n = 123; mean age = 13.3; 13.1 years, respectively) completed the WAItE twice. An adult general population sample completed the WAItE via an online survey (females n = 236; males n = 231; mean age = 41.2; 44.3 years, respectively). The Partial Credit Model was applied to the data and item fit evaluated against published criteria.The WAItE had a unidimensional structure both for adolescents and adults. There was no item misfit observed for either participant samples and no differential item functioning (DIF) was present by age or gender for the adolescents. Some DIF was observed across age groups for the adult sample. For the adolescent sample, stable item locations were observed over time.The aim of the WAItE is to assess the impact of weight status on the lives of adolescents in cost-effectiveness evaluation of weight management programmes. The results of this study demonstrated that the WAItE has reliable psychometric properties. The instrument may therefore be used to aid informed decision around the identification of cost-effective weight management programmes in both adolescent and adult populations.

Patient-reported outcomes are increasingly used by clinical teams as indicators of quality when assessing treatment after a diagnosis of head and neck cancer. About a third of patients report reduced sexual interest or enjoyment after such treatment but, despite that, there is no questionnaire about intimacy that has been developed specifically for them. The aim of this study was to develop such a questionnaire, to gain an indication of the relative incidence of individual items, and to compare characteristics such as age, stage, treatment, time since treatment for an established head and neck cancer, and a health-related quality of life (QoL) measure (European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-C30 with the Head and Neck 35 module). The development of the new instrument was based on an exploratory observational study that included quantitative and qualitative methods. The qualitative element was achieved by the generation of items - from published studies, the comments of patients and carers, and a cross-sectional survey of patients with head and neck cancer who were alive and free of disease. The quantitative element comprised analysis of exploratory and confirmatory factors, internal reliability assessment (Cronbach's alpha), and a correlation analysis. Forty-two patients were included in the focus groups, and 101 patients participated in the cross-sectional survey (both male and female, in a relationship and single, age range 30-70 years for the focus group, and 62-117 in the cross-sectional survey). All treatments were included. We found that the ability to enjoy a sex life had been adversely affected in about half the sample and that this had significantly changed from before their cancer in a third. The qualitative part of the study resulted in 22 items that covered a range of domains from dry mouth and thick saliva to loss of sensation (lips, fingertips), restricted head/neck movement, fatigue, and pain. The exploratory analysis covered four domains (physical, sensation, movement, and communication) from 12 of 22 items. Cronbach's alphas ranged from 0.62 to 0.84, and the correlation analysis indicated "good fit" statistics for these domains. In terms of the EORTC QoL Questionnnaire - Head and Neck 35, the four MHK domains showed good levels of association with anticipated domains. Head and neck cancer and its associated treatments significantly adversely affect intimacy and sexuality in half the population sampled. The MHK tool may be used to identify specific issues related to intimacy in patients with a history of diagnosis and treatment of head and neck cancer. Further work is essential to identify its precise role and to help develop specific interventions.

Adam B Smith,1 Andria Hanbury,1 Jennifer A Whitty,2 Katharina Buesch3 1York Health Economics Consortium, University of York, York, UK; 2Norwich Medical School, University of East Anglia, Norwich, UK; 3PTC Therapeutics, Zug, 6300, SwitzerlandCorrespondence: Adam B SmithYork Health Economics Consortium, Enterprise House, Innovation Way, University of York, York, YO10 5NQ, UKTel +44 1904 323620Fax +44 1904 323628Email adam.smith@york.ac.ukPurpose: Deriving health utilities for rare medical conditions such as aromatic L-amino acid decarboxylase (AADC) deficiency poses challenges. The rarity of AADC deficiency and the fact that this genetic condition often presents in very young children means that robust utility values cannot be derived from the child or their parent/caregiver. Alternative approaches, eg, discrete choice experiments (DCE), are required in order to provide health utilities. The aim of the study was to generate health utilities for AADC deficiency using a DCE.Methods: The DCE was completed online by panel participants from a UK representative sample. The DCE comprised 6 AADC deficiency attributes (2– 6 levels): mobility, muscle weakness, oculogyric crises, feeding ability, cognitive impairment and screaming. These were identified from published literature, clinician input, parent interviews and expert opinion. Participants were presented with 10 choice sets specified using an orthogonal design, including a repeat task to evaluate choice consistency. Participants were presented with 5 health state vignettes prior to the DCE. These were used to elicit time trade-off (TTO) utilities. Multinomial logit models were estimated for the DCE data. The TTO utilities for the worst/best health states were used as anchors to convert indirect DCE part-worth utilities to health utilities.Results: A total of 1596 participants completed the DCE. The majority (70.7%) gave consistent responses to the repeated choice task; only 1.7% (27) always chose the same alternative for every choice set. Five models were evaluated. There was one preference reversal (“sitting unaided”/“standing with assistance”) occurring in all models; these two mobility level coefficients were set to be equal in the final model. Rescaled utilities ranged from 0.494 to 0.7279, corresponding to the worst (633233) and best (111111) health states.Conclusion: Health utilities were derived for AADC deficiency through a DCE. These will be used for a cost-effectiveness model of an AADC deficiency treatment.Keywords: AADC deficiency, discrete choice experiment, health state utilities, health utilities

The digitization of museum collections as well as an explosion in citizen science initiatives has resulted in a wealth of data that can be useful for understanding the global distribution of biodiversity, provided that the well-documented biases inherent in unstructured opportunistic data are accounted for. While traditionally used to model imperfect detection using structured data from systematic surveys of wildlife, occupancy-detection models provide a framework for modelling the imperfect collection process that results in digital specimen data. In this study, we explore methods for adapting occupancy-detection models for use with biased opportunistic occurrence data from museum specimens and citizen science platforms using 7 species of Anacardiaceae in Florida as a case study. We explored two methods of incorporating information about collection effort to inform our uncertainty around species presence: (1) filtering the data to exclude collectors unlikely to collect the focal species and (2) incorporating collection covariates (collection type and history of previous detections) into a model of collection probability. We found that the best models incorporated both the background data filtration step as well as the incorporation of collector covariates associated with the probability of collection. We found that month, method of collection and whether a collector had previously collected the focal species were important predictors of collection probability. Efforts to standardize meta-data associated with data collection will improve efforts for modeling the spatial distribution of a variety of species.

Andria Hanbury,1 Adam B Smith,1 Katharina Buesch2 1York Health Economics Consortium, University of York, York YO10 5NQ, UK; 2PTC Therapeutics, Zug 6300, SwitzerlandCorrespondence: Adam B SmithYork Health Economics Consortium, Enterprise House, Innovation Way, University of York, York YO10 5NQ, UKTel +44 (0)1904 323620Fax +44 (0)1904 323628Email adam.smith@york.ac.ukPurpose: Aromatic l-amino acid decarboxylase (AADC) deficiency is a rare genetic condition, characterised by movement disorder, and speech and cognitive functioning impairment. To enable economic evaluation of treatments, health-related quality of life or utilities need to be derived. These are currently lacking in the literature. This is challenging, where patient numbers are small, particularly in paediatric populations. This study outlines the 5-stage development of vignettes describing AADC, for use in a subsequent health-state utility elicitation study, with an emphasis on caregiver and clinician engagement.Methods: To align with the economic model, 5 vignettes describing 5 AADC deficiency motor milestones were developed, ranging from “bedridden” to “walking with assistance”. Stage 1 comprised identification of symptoms/impairments from the literature and AADC deficiency charity websites. Stage 2 comprised group discussion with 3 caregivers. A symptoms matrix was developed, followed by draft vignettes (Stage 3). Eight clinicians reviewed these, alongside the same 3 caregivers via a survey (Stage 4). The vignettes were revised at stage 5.Results: There was high consensus regarding symptoms at Stages 1 and 2, although the literature highlighted behavioural and autonomic symptoms, which caregivers did not. The symptoms were grouped into neuromuscular, autonomic, cognitive, behavioural and functional impairments. Clinician and caregiver vignette feedback highlighted the idiopathic nature of AADC. Despite this, clinicians suggested only 2 additional symptoms. Similarly, caregivers suggested 4 symptoms and a change to the wording used for the cognitive symptoms. Not all changes were included.Conclusion: The differing focus of caregivers, clinicians and the literature reinforces the importance of patient/caregiver engagement. The vignettes need to comprehensively capture what it is like to live with AADC deficiency, in order for the subsequent utilities to be robust. A focus on evidence triangulation, especially for idiopathic conditions, and how engagement is sought from caregivers are important future avenues of research.Keywords: aromatic l-amino acid decarboxylase deficiency, AADC deficiency, vignettes, caregivers, clinicians

Identifying biophysical factors that define species’ niches and influence geographical ranges is a fundamental pursuit of ecology. Frequently, models of species’ distributions or niches are used to infer the importance of range- and niche-defining variables. However, very few—if any—studies examine how reliably distribution and niche models can be used for inference. Here we use a simulation approach to understand the conditions under which species distribution models reliably measure variable importance. Using a set of scenarios of increasing complexity, we explore how well models can be used to 1) discriminate between variables that vary in importance and 2) calibrate the effect of variables relative to an “omniscient” model used to simulate the species. Variable importance was assessed using a sensitivity test in which each predictor was permuted in turn. Importance was inferred by comparing model performance between permuted and unpermuted predictions and by calculating the correlation between permuted and unpermuted predictions. Of five metrics of importance (correlation statistic and AUC each calculated with presences/absences or presences/background sites, plus the Continuous Boyce Index), only the Continuous Boyce Index was capable of indicating absolute (versus relative) variable importance. In simple scenarios with one influential environmental variable with a linear spatial gradient and one uninfluential randomly-distributed variable, models were unable to discriminate reliably between variables under conditions that are typically challenging (low sample size, high prevalence, small spatial extent, coarse spatial data resolution with low spatial autocorrelation, and high collinearity between variables). In more complex scenarios with two influential environmental variables, models successfully discriminated between variables when they acted unequally, but overestimated the importance of the stronger variable and underestimated the importance of the weaker variable. When variables had equal influence, models underestimated importance when niche breadth was narrow. Generalized additive models and Maxent had better discrimination accuracy than boosted regression trees. Our work demonstrates that permutation tests can reliably discriminate between variables with different levels of influence but cannot accurately measure the magnitude of influence. The frequency with which distribution and niche models are used to identify influential variables begs further research into methods for assessing variable importance.

Background The impact of different disease stages and treatment for human epidermal growth factor 2 positive (HER2-positive) breast cancer (BC) on work productivity and health-related quality of life (HRQoL) is poorly understood. Methods This was a UK cross-sectional study of 299 adult patients with HER2-positive early or metastatic BC (NCT03099200). Productivity was assessed using the work productivity and activity impairment scale; HRQoL was measured using EuroQol-5 Dimensions-5 levels (EQ-5D-5L), and Functional Assessment of Cancer Therapy Breast (FACT-G and -B) instruments. Three balanced patient groups were recruited: (1) early BC on treatment post-surgery, (2) early BC after completion of adjuvant treatment, (3) during metastatic BC treatment. Between-group comparisons were performed using an analysis of variance. Results Group 1 comprised 89 patients, Group 2, 108 and Group 3, 102. Age, ethnicity and comorbidities were similar across groups. Patients in Group 3 reported more often being unable to work (significant Bonferroni adjusted p p = 0.002). Group 2 also had significantly lower levels of work absenteeism and overall work impairment compared with Group 1 (p p ≤ 0.002), moderate or worse problems in the EQ-5D-5L self-care and usual activity domains (p ≤ 0.001), and lower HRQoL as assessed by FACT summary scores (p p Conclusions Metastatic disease and treatment of HER2-positive BC adversely impacted on work productivity and HRQoL. The results of this study support the idea that being able to delay or prevent the metastatic recurrence of BC, for example by extending the time patients are in remission or at early stage of BC, has wider benefits in terms of patient productivity and HRQoL.

Background: Vaginal dryness is a highly prevalent condition. Much of previous research has focused on postmenopausal women. The aim of this study was to evaluate the impact of vaginal dryness on a ...

Premise A disjunct distribution, where a species' geographic range is discontinuous, can occur through vicariance or long-distance dispersal. Approximately 75 North American plant species exhibit a ~650 km disjunction between the Ozark and Appalachian regions. This disjunction is attributed to biogeographic forces including: (1) Eocene-Oligocene vicariance by the formation of the Mississippi embayment; (2) Pleistocene vicariance from interglacial flooding; (3) post-Pleistocene northward colonization from separate glacial refugia; (4) Hypsithermal vicariance due to climate fluctuations; and (5) recent long-distance dispersal. We investigated which of these pathways most likely gave rise to the Appalachian-Ozark disjunction in Delphinium exaltatum. Methods We genotyped populations of D. exaltatum from five Ozark and seven Appalachian localities, analyzed genetic structure, tested the order and timing of divergences using DIYABC, and conducted niche reconstructions up to 21,000 years before present (YBP). Results Populations fell into five main genetic clusters, i.e., a group in the central Appalachians, and four "lowland" groups. DIYABC analyses showed the central Appalachian and lowland lineages diverging 11,300 to17,000 YBP, and the lowland groups diverging 6800 to 10,900 YBP. Niche reconstructions showed that suitable climate for the central Appalachian lineage experienced large spatial discontinuity starting 14,000 YBP, such that divergence and persistence before this period is less plausible than divergence thereafter. Conclusions Our results did not fully support any of the original hypotheses. Rather, the oldest divergence likely occurred after 13,500 YBP through expansion into newly opened habitat in the Appalachians. The Appalachian-Ozark disjunction likely resulted from northward dispersal of the lowland lineage as climate warmed during the Holocene.

In 2002, Florida enacted the first statewide building code based on wind engineering principles. After a tragic tornado in 2013, which killed 24, including seven school children, Moore, Okl...

Aim: The Qualities of Sore Throat Index (QuaSTI) assesses the status of patient-reported pharyngeal pain. One study used QuaSTI in isolation; a separate study used QuaSTI plus the Sore Throat Scale (STS). Both studies also used a Sore Throat Pain Intensity Scale (STPIS). This study evaluates STS and STPIS as instruments to refine the QuaSTI. Materials & methods: Correlational analysis determined the degree of association between STPIS and STS. Confirmatory factor analyses evaluated the proposed factor structure of QuaSTI. Results: A strong correlation between STS and STPIS (r = 0.91; p

Purpose\ud Allergic rhinitis and asthma symptoms are detrimental to health-related quality of life (HRQoL). Health technology appraisal agencies often require cost–utility analysis when assessing new interventions. Appropriate utility estimates, which quantify the value of different conditions in cost–utility analyses, are scarce for allergic rhinitis and asthma health states. This study aimed to generate utilities for allergic rhinitis and asthma health states from a European general population sample of adults and children.\ud \ud Methods\ud Health state descriptions incorporating symptoms, impact of symptoms on daily life and symptom treatment were developed using clinical guidelines. Descriptions were amended with clinician and patient input, and incorporated into a survey in which each health state was followed by a standard gamble (adults) or visual analogue scale (children) item. The survey was distributed to samples of adults and children aged 8 to 11 from four European countries that were stratified to represent the general population within that country.\ud \ud Results\ud 1454 adults and 1082 children completed the survey. Mean health utilities ranged from 0.635 to 0.880 and those elicited in children were lower (0.635 to 0.705) than those elicited in adults (0.812 to 0.880). Disutilities assessing the impact of increased allergic rhinitis severity and comorbidities were also greater in children than in adults.\ud \ud Conclusions\ud Symptoms of allergic rhinitis and asthma were valued as having a clinically meaningful impact on HRQoL. Children valued health states as poorer than adults, and further research should investigate whether this reflects true preferential differences or results from methodological and/or comprehension differences between the two groups.

Extreme weather and climate-related events affect human health by causing death, injury, and illness, as well as having large socioeconomic impacts. Climate change has caused changes in extreme event frequency, intensity, and geographic distribution, and will continue to be a driver for change in the future. Some of these events include heat waves, droughts, wildfires, dust storms, flooding rains, coastal flooding, storm surges, and hurricanes. The pathways connecting extreme events to health outcomes and economic losses can be diverse and complex. The difficulty in predicting these relationships comes from the local societal and environmental factors that affect disease burden. More information is needed about the impacts of climate change on public health and economies to effectively plan for and adapt to climate change. This paper describes some of the ways extreme events are changing and provides examples of the potential impacts on human health and infrastructure. It also identifies key research gaps to be addressed to improve the resilience of public health to extreme events in the future. IMPLICATIONS: Extreme weather and climate events affect human health by causing death, injury, and illness, as well as having large socioeconomic impacts. Climate change has caused changes in extreme event frequency, intensity, and geographic distribution, and will continue to be a driver for change in the future. Some of these events include heat waves, droughts, wildfires, flooding rains, coastal flooding, surges, and hurricanes. The pathways connecting extreme events to health outcomes and economic losses can be diverse and complex. The difficulty in predicting these relationships comes from the local societal and environmental factors that affect disease burden.

OBJECTIVES: Health-related quality of life (HRQoL) and ability to work in patients treated for HER2+ early breast cancer (EBC) are poorly understood. This study compared HRQoL and ability to work in 3 HER2+ patient cohorts: EBC during adjuvant treatment, EBC after treatment, and metastatic disease (MBC). METHODS: A cross-sectional observational cohort study of 299 female consenting patients with HER2+BC, from 14 UK secondary care centres. Group1 (n=89): receiving targeted HER2 therapy±chemotherapy for EBC; Group2 (n=108): in follow up post-targeted treatment for eBC; Group3 (n=102): MBC on treatment. Data collected between Dec 2016-Mar 2017: HRQoL, demographic and employment status data collected via patient-reported questionnaires (including EQ-5D-5L and Functional Assessment of Cancer Therapy [FACT-B]); clinical data collected from medical records. Inter-group differences were assessed using univariate Analysis of variance (ANOVA) and chi-square tests as appropriate. [NCT03099200]. RESULTS: Table1 shows patient demographics, disease characteristics, employment status, and EQ-5D-5L scores. Group1 and Group2 patients did not differ in overall health utility or visual analogue scale (VAS) scores. However, Group3 patients reported significantly poorer health utility than Group1 (p CONCLUSIONS: HRQoL in patients with EBC was similar whether on or off treatment, and better than those with MBC. HRQoL scores reported on the generic EQ-5D will be compared with those from the disease-specific FACT-B. A smaller proportion of patients with MBC were employed compared to the EBC groups, reflecting the impact of advanced disease. Fewer patients with EBC reported being unable to work than we expected, suggesting these patients maintain function. Table1 Group1 (n=89)Group2 (n=108)Group3 (n=102)Age (years)↑55 (11)58 (11)55 (11)Hormone receptor status¥Positive64 (72%)84 (78%)74 (73%)Negative25 (28%)24 (22%)26 (26%)Unknown0 (0%)0 (0%)2 (2%)Time since diagnosis (months)+EBC9 (6)45 (32) (n=103)80 (82) (n=71*)MBC--39 (36) (n=101)Employment status¥Employed45 (51%)55 (51%)28 (28%)§Not employed41 (46%)52 (48%)69 (68%)Retired22 (25%)39 (36%)33 (32%)Unable to work7 (8%)5 (5%)§27 (27%)§Other12 (14%)8 (7%)9 (9%)Unknown3 (3%)1 (1%)5 (5%)EQ-5D summary scoresVisual analogue scale72.7 (18.4)†77.0 (17.5)†65.8 (22.9)† (n=99)Utility value0.809 (0.170)† (n=86)0.818 (0.181)†0.695 (0.262)† (n=97)↑mean (standard deviation); ¥n (%); +median (interquartile range); *excludes 27/102 patients (27%) with de novo MBC. Bold text: observed differences between three groups at significance thresholds of ‡p Citation Format: Verrill M, Wardley A, Retzler J, Smith AB, McNicol D, Dando S, Tran I, Leslie I, Schmid P. Quality of life and ability to work in patients at different disease stages of HER2+ breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-12-14.