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Ralph HB Benedict,1 Pamela Vo,2 Nicholas Adlard,2 Olwyn Grennan,3 Ashley Enstone,4 Daisy Bridge,4 Robin Wyn,4 Stanley L Cohan5 1Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, Buffalo, NY, USA; 2Novartis Pharma AG, Basel, Switzerland; 3Novartis Ireland, Dublin, Ireland; 4Adelphi Values PROVE, Bollington, UK; 5Providence Brain and Spine Institute, Providence St. Joseph Health, Portland, OR, USACorrespondence: Pamela Vo, Email pamela.vo@novartis.comIntroduction: Cognitive impairment, especially relating to cognitive processing speed, is a major cause of disability in people with multiple sclerosis (MS). Utility values are quantitative estimates of the quality of life experienced in specific health states and are a key component of cost-effectiveness modelling. However, existing health state utility values in MS typically focus on physical ability and are generally derived using generic (not disease-specific) measures of quality of life. The objective of the current study was to generate health state utility values for levels of cognitive impairment. We used a direct utility elicitation approach called the time trade-off (TTO) methodology.Materials and Methods: Health state descriptions were created following interviews with healthcare professionals, patients, and caregivers in the United States (n=35), and with healthcare professionals in the UK (n=5). Three health states (mild, moderate, and severe impairment) were defined based upon a well-established and validated test for cognitive dysfunction called the Symbol Digit Modalities Test (SDMT) and described using qualitative interview findings. Next, interviews with members of the general public in the UK were conducted to estimate utility values for each health state using the TTO methodology. The procedure was based on the established Measurement and Valuation of Health (MVH) protocol, which generates values on a scale from 0.0 to 1.0.Results: Mean health state utility values were 0.77 ± 0.24 in “mild impairment” (SDMT 43-40), 0.57 ± 0.26 in “moderate impairment” (SDMT 39-32), and 0.34 ± 0.28 in “severe impairment” (SDMT ≤ 31).Discussion: Results indicate that the public perceives that health states of cognitive slowing (as observed in MS) are associated with a substantial reduction in affected individuals’ health-related quality of life, quantified using the TTO methodology. Future economic modeling should consider how utility impacts of both cognitive and physical disability can be appropriately incorporated.Keywords: cognitive impairment, processing speed, health state utility, health-related quality of life, multiple sclerosis, time trade-off

Paul O’Brien,1 Ashley Enstone,2 Daisy Bridge,2 Robin Wyn,2 Judit Banhazi3 1Novartis Ireland, Dublin, Ireland; 2Adelphi Values PROVE, Bollington, UK; 3Novartis Pharma AG, Basel, SwitzerlandCorrespondence: Paul O’Brien, Email paul-2.obrien@novartis.comIntroduction: Retinitis pigmentosa (RP) is an inherited retinal pathology associated with “night blindness” and progressive loss of peripheral vision, in some cases leading to complete blindness. Health state utility values are required for activities such as modelling disease burden or the cost-effectiveness of new interventions. The current study aimed to generate utility values for health states of varying levels of functional vision in RP, with members of the general public in the UK.Methods: Five health states were defined according to standard clinical measures of visual ability. Health state descriptions were developed following interviews with patients with RP in the UK (n=5). Further interviews were conducted for confirmation with healthcare professionals with specific experience of managing patients with RP in the UK (n=2). Interviews with members of the general public in the UK were conducted to value health states. A time trade-off (TTO) process based on the established Measurement and Valuation of Health (MVH) protocol was used. Due to the ongoing COVID-19 pandemic, all interviews were web-enabled and conducted 1:1 by a trained moderator.Results: In total, n=110 TTO interviews were conducted with members of the UK general public. Mean TTO utility values followed the logical and expected order, with increasing visual impairment leading to decreased utility. Mean values varied between 0.78 ± 0.20 (“moderate impairment”), and 0.33 ± 0.26 (“hand motion” to “no light perception”). Supplementary visual analogue scale (VAS) scores also followed the logical and expected order: mean VAS values varied between 47.95 ± 15.38 (“moderate impairment”) and 17.22 ± 12.49 in (“hand motion” to “no light perception”).Discussion: These data suggest that individuals living with RP have substantially impaired quality of life. Utility values for RP have been elicited here using a method and sample that is suitable for economic modelling and health technology assessment purposes.Keywords: retinitis pigmentosa, inherited retinal disease, health state utility, health-related quality of life, time trade-off, vignette study

BACKGROUND: It has long been known that nasal inoculation with influenza A virus produces asymptomatic to febrile infections. Uncertainty persists about whether these infections are sufficiently similar to natural infections for studying human-to-human transmission. METHODS: We compared influenza A viral aerosol shedding from volunteers nasally inoculated with A/Wisconsin/2005 (H3N2) and college community adults naturally infected with influenza A/H3N2 (2012-2013), selected for influenza-like illness with objectively measured fever or a positive Quidel QuickVue A&B test. Propensity scores were used to control for differences in symptom presentation observed between experimentally and naturally infected groups. RESULTS: Eleven (28%) experimental and 71 (86%) natural cases shed into fine particle aerosols (P

Uncertainty about the importance of influenza transmission by airborne droplet nuclei generates controversy for infection control. Human challenge-transmission studies have been supported as the most promising approach to fill this knowledge gap. Healthy, seronegative volunteer 'Donors' (n = 52) were randomly selected for intranasal challenge with influenza A/Wisconsin/67/2005 (H3N2). 'Recipients' randomized to Intervention (IR, n = 40) or Control (CR, n = 35) groups were exposed to Donors for four days. IRs wore face shields and hand sanitized frequently to limit large droplet and contact transmission. One transmitted infection was confirmed by serology in a CR, yielding a secondary attack rate of 2.9% among CR, 0% in IR (p = 0.47 for group difference), and 1.3% overall, significantly less than 16% (p

Little is known about the amount and infectiousness of influenza virus shed into exhaled breath. This contributes to uncertainty about the importance of airborne influenza transmission. We screened 355 symptomatic volunteers with acute respiratory illness and report 142 cases with confirmed influenza infection who provided 218 paired nasopharyngeal (NP) and 30-minute breath samples (coarse >5-µm and fine ≤5-µm fractions) on days 1-3 after symptom onset. We assessed viral RNA copy number for all samples and cultured NP swabs and fine aerosols. We recovered infectious virus from 52 (39%) of the fine aerosols and 150 (89%) of the NP swabs with valid cultures. The geometric mean RNA copy numbers were 3.8 × 104/30-minutes fine-, 1.2 × 104/30-minutes coarse-aerosol sample, and 8.2 × 108 per NP swab. Fine- and coarse-aerosol viral RNA were positively associated with body mass index and number of coughs and negatively associated with increasing days since symptom onset in adjusted models. Fine-aerosol viral RNA was also positively associated with having influenza vaccination for both the current and prior season. NP swab viral RNA was positively associated with upper respiratory symptoms and negatively associated with age but was not significantly associated with fine- or coarse-aerosol viral RNA or their predictors. Sneezing was rare, and sneezing and coughing were not necessary for infectious aerosol generation. Our observations suggest that influenza infection in the upper and lower airways are compartmentalized and independent.

Simple Summary: This research examined UK cat owners' preferences for treatments for feline osteoarthritis, including preferences for quality of life improvements, safety considerations, and costs associated with hypothetical new pain therapies. Aspects of quality of life from previous research were extracted and included in exploratory interviews with cat owners (n = 3) to identify the key domains that contribute to the quality of life of cats. Descriptions of the quality of life of cats with osteoarthritis and hypothetical product characteristics were developed and validated through interviews with veterinarians (n = 3). An online survey was subsequently shared with 255 pet owners in the UK. Pet owners were presented with quality of life descriptions and hypothetical product characteristics to gather their preferences for quality of life improvements and their willingness to pay for (unbranded) pain therapies at various levels of price. Pet owners were motivated to improve their cats' quality of life, which translated into a willingness to pay for therapies; specifically, pet owners valued quality of life improvements in mobility, pain expression, and well-being. When presented with a product profile of the hypothetical new injection treatment and its cost, 50% of cat owners were willing to pay more for the new injection treatment, which is expected to have improved efficacy and safety when compared to a hypothetical standard treatment. Significantly more pet owners also preferred the new injection treatment to the standard treatment when the price was not presented (p < 0.01), with product efficacy and safety driving pet owners' decision-making. The majority of pet owners did not agree that taking their cats to the veterinarian once a month for treatment would be burdensome. Cat owners in the UK are motivated to improve their cats' quality of life, which translates into a willingness to pay for effective treatment of pain associated with osteoarthritis. Veterinarians should offer cat owners the pain treatment they feel is best suited for improving the cats' quality of life and ensuring the relationship between cat and owner is preserved. This research aimed to explore UK cat owners' preferences for treatments for feline osteoarthritis (OA) by exploring preferences around quality of life (QoL) improvements, safety considerations, and costs associated with hypothetical innovative pain therapies. Aspects identified in an existing conceptual framework were extracted for inclusion in exploratory interviews with cat owners (n = 3) to identify key domains that contribute to the QoL of cats. QoL descriptions for cats with OA and hypothetical product attributes were developed and validated through interviews with veterinarians (n = 3). An online survey was subsequently shared with 255 pet owners in the UK. Pet owners were presented with QoL descriptions and hypothetical product attributes to gather their preferences for QoL improvements and their willingness to pay (WTP) for (unbranded) pain therapies at various price points. Pet owners were motivated to improve their cats' QoL, which translated into WTP for therapies; specifically, pet owners valued QoL improvements in mobility, pain expression, and well-being. When presented with a product profile of the hypothetical novel monoclonal antibody (mAb) and cost, 50% of cat owners were willing to pay more for a mAb that is expected to have improved efficacy and safety when compared to a hypothetical standard of care (SoC). Significantly more pet owners preferred the mAb than the SoC when price was not presented (p < 0.01), with product efficacy and safety driving pet owners' decision-making. The majority of pet owners did not agree that taking their cats to the veterinarian once a month for their treatment would be burdensome. Cat owners in the UK are motivated to improve their cats' QoL, which translates into WTP for the efficacious treatment of pain associated with osteoarthritis. Veterinarians should offer cat owners the pain treatment they feel is best suited for improving the cat's QoL and to ensure subsequent owner-pet bond is preserved. [ABSTRACT FROM AUTHOR]

Simple Summary: Oclacitinib is a tablet-based therapy given for itching that is caused by allergic or atopic dermatitis in dogs. The objective of this study was to understand pet owners' perceptions of the conventional film-coated form of oclacitinib and the chewable form of oclacitinib in terms of convenience and value. Firstly, an interview phase with pet owners and veterinarians was used to develop detailed written profiles of these treatment options. Then, pet owners were invited to participate in a survey about their experiences and preferences. Overall, 1590 pet owners provided survey responses. Most respondents (62%) reported having experienced challenges giving tablet-based therapies to their dog(s), and half of the respondents (52%) had experience giving flavoured or chewable tablets to their dog. Comparing oclacitinib and chewable oclacitinib (with or without associated costs), the majority of the respondents preferred the chewable formulation in all countries for both short-term and long-term itch (≥58%; all p < 0.05). Chewable and/or palatable treatment options may be welcomed by pet owners and may have potential positive impacts on convenience, compliance, outcomes, quality of life, and the human–animal bond. Oclacitinib is an oral therapy indicated for pruritus associated with allergic or atopic dermatitis in dogs. This study sought to assess pet owners' perceptions of the relative convenience and value of the conventional film-coated formulation and the chewable formulation. A quantitative discrete-choice experimental methodology was applied, comparing (conventional, film-coated) oclacitinib versus chewable oclacitinib using unbranded treatment profiles. Initially, a qualitative interview phase with pet owners and veterinarians was conducted to develop detailed treatment profiles. Subsequently, pet owners participated in a quantitative survey. Overall, 1590 pet owners provided survey responses. Most respondents (62%) reported having experienced challenges administering tablet-based therapies to their dog(s). Half of all respondents (52%) had experience administering flavoured or chewable tablets to their dog. Comparing oclacitinib and chewable oclacitinib (with or without associated costs), the majority of the respondents preferred the chewable formulation in all regions across short-term and long-term scenarios (≥58%; all p < 0.05). The current research is one of few survey-driven studies for treatment preferences in companion animal medicine. Veterinarians may offer chewable or palatable treatment options where available, with potential positive impacts on convenience, compliance, outcomes, quality of life, and the human–animal bond. [ABSTRACT FROM AUTHOR]

Abstract Background International and national travelling has made the rapid spread of infectious diseases possible. Little information is available on the role of major traffic hubs, such as airports, in the transmission of respiratory infections, including seasonal influenza and a pandemic threat. We investigated the presence of respiratory viruses in the passenger environment of a major airport in order to identify risk points and guide measures to minimize transmission. Methods Surface and air samples were collected weekly at three different time points during the peak period of seasonal influenza in 2015–16 in Finland. Swabs from surface samples, and air samples were tested by real-time PCR for influenza A and B viruses, respiratory syncytial virus, adenovirus, rhinovirus and coronaviruses (229E, HKU1, NL63 and OC43). Results Nucleic acid of at least one respiratory virus was detected in 9 out of 90 (10%) surface samples, including: a plastic toy dog in the children’s playground (2/3 swabs, 67%); hand-carried luggage trays at the security check area (4/8, 50%); the buttons of the payment terminal at the pharmacy (1/2, 50%); the handrails of stairs (1/7, 14%); and the passenger side desk and divider glass at a passport control point (1/3, 33%). Among the 10 respiratory virus findings at various sites, the viruses identified were: rhinovirus (4/10, 40%, from surfaces); coronavirus (3/10, 30%, from surfaces); adenovirus (2/10, 20%, 1 air sample, 1 surface sample); influenza A (1/10, 10%, surface sample). Conclusions Detection of pathogen viral nucleic acids indicates respiratory viral surface contamination at multiple sites associated with high touch rates, and suggests a potential risk in the identified airport sites. Of the surfaces tested, plastic security screening trays appeared to pose the highest potential risk, and handling these is almost inevitable for all embarking passengers.

Introduction: Setting and monitoring progress towards targets for HIV controlis criticalin ensuring responsive programmes. Here, we explore how to apply targets for reduction in HIV incidence to localsettings and which indicators give the strongest signal of a change in incidence in the population and are therefore most important to monitor. Methods: We use location-specific HIV transmission models, tailored to the epidemics in the counties and major cities in Kenya, to project a wide range of plausible future epidemic trajectories through varying behaviours, treatment coverage and prevention interventions. We look at the change in incidence across modelled scenarios in each location between 2015 and 2030 to inform local target setting. We also simulate the measurement of a library of potential indicators and assess which are most strongly associated with a change in incidence. Results: Considerable variation was observed in the trajectory of the local epidemics under the plausible scenarios defined (only 10 of 48 locations saw a median reduction in incidence of greater than or equalto an 80% target by 2030). Indicators that provide strong signals in certain epidemic types may not perform consistently well in settings with different epidemiological features. Predicting changes in incidence is more challenging in advanced generalized epidemics compared to concentrated epidemics where changes in high-risk sub-populations track more closely to the population as a whole. Many indicators demonstrate only limited association with incidence (such as 'condom use' or 'pre-exposure prophylaxis coverage'). This is because many other factors (low effectiveness, impact of other interventions, countervailing changes in risk behaviours, etc.) can confound the relationship between interventions and their ultimate long-term impact, especially for an intervention with low expected coverage. The population prevalence of viral suppression shows the most consistent associations with long-term changes in incidence even in the largest generalized epidemics. Conclusions: Target setting should be appropriate for the local epidemic and what can feasibly be achieved. There is no one universally reliable indicator to predict future HIV incidence across settings. Thus, the signature of epidemic controlmust contain indications of success across a wide range of interventions and outcomes. Keywords: programme evaluation; population surveillance; models; theoretical; HIV Infections; epidemiology; forecasting, Additional Supporting Information may be found online in the Supporting information tab for this article. 1 INTRODUCTION From early in the HIV pandemic, efforts have been made to measure and [...]

Summary: In a multi-center, prospective, observational study over two influenza seasons, we sought to quantify and correlate the amount of virus recovered from the nares of infected subjects with that recovered from their immediate environment in community and hospital settings. We recorded the symptoms of adults and children with A(H1N1)pdm09 infection, took nasal swabs, and sampled touched surfaces and room air. Forty-two infected subjects were followed up. The mean duration of virus shedding was 6.2 days by PCR (Polymerase Chain Reaction) and 4.2 days by culture. Surface swabs were collected from 39 settings; 16 (41%) subject locations were contaminated with virus. Overall, 33 of the 671 (4.9%) surface swabs were PCR positive for influenza, of which two (0.3%) yielded viable virus. On illness Day 3, subjects yielding positive surface samples had significantly higher nasal viral loads (geometric mean ratio 25.7; 95% CI 1.75, 376.0, p = 0.021) and a positive correlation (r = 0.47, p = 0.006) was observed between subject nasal viral loads and viral loads recovered from the surfaces around them. Room air was sampled in the vicinity of 12 subjects, and PCR positive samples were obtained for five (42%) samples. Influenza virus shed by infected subjects did not detectably contaminate the vast majority of surfaces sampled. We question the relative importance of the indirect contact transmission of influenza via surfaces, though our data support the existence of super-spreaders via this route. The air sampling results add to the accumulating evidence that supports the potential for droplet nuclei (aerosol) transmission of influenza. Keywords: Influenza, Environmental, Deposition, Infection, Control