Orexin 2 receptor-selective agonist danavorexton improves narcolepsy phenotype in a mouse model and in human patients.

Narcolepsy type 1 (NT1) is a sleep disorder caused by a loss of orexinergic neurons. Narcolepsy type 2 (NT2) is heterogeneous; affected individuals typically have normal orexin levels. Following evaluation in mice, the effects of the orexin 2 receptor (OX2R)-selective agonist danavorexton were evaluated in single- and multiple-rising-dose studies in healthy adults, and in individuals with NT1 and NT2. In orexin/ataxin-3 narcolepsy mice, danavorexton reduced sleep/wakefulness fragmentation and cataplexy-like episodes during the active phase. In humans, danavorexton administered intravenously was well tolerated and was associated with marked improvements in sleep latency in both NT1 and NT2. In individuals with NT1, danavorexton dose-dependently increased sleep latency in the Maintenance of Wakefulness Test, up to the ceiling effect of 40 min, in both the single- and multiple-rising-dose studies. These findings indicate that OX2Rs remain functional despite long-term orexin loss in NT1. OX2R-selective agonists are a promising treatment for both NT1 and NT2.

A Mimicker of Differentiated Vulvar Intraepithelial Neoplasia: Reactive Atypia From Noncompliance With Lichen Sclerosus Therapy.

ABSTRACT: Differentiated vulvar intraepithelial neoplasia (d-VIN) is an HPV-independent precursor to vulvar squamous cell carcinoma. The histology of d-VIN lesions is difficult to differentiate from that of non-neoplastic epithelial disorders, especially lichen sclerosus (LS). The authors present a case of LS, where relying on histopathology alone could have led to misdiagnosis. The patient was a 17-year-old female patient with clinical features of vulvar dermatitis and LS for 2 years. She was counseled to apply clobetasol 0.05% to the affected area daily but reported no improvement after 6 months. A biopsy of the right labia majora revealed histologic findings typical of d-VIN and near-contiguous p53 expression. These features are characteristic of d-VIN. However, d-VIN is exceedingly rare in young patients. The case was reviewed by 6 dermatopathologists and gynecologic pathologists, who observed that the degree of inflammation would be unusual postclobetasol therapy and could be due to noncompliance. A review of the patient's chart revealed that she "does not always remember to apply" clobetasol. The patient's clinician confirmed that there were compliance issues, and the follow-up biopsy was negative for d-VIN. The case was signed out as LS, with a note describing the above, and to rebiopsy if concern persisted. The authors conjecture that inflammatory infiltrates in the biopsied area caused reactive atypia due to lack of adherence to treatment. Although the patient's age helped rule out d-VIN, similar cases in elderly patients may be occurring. Pathologists must be aware that reactive forms of untreated LS can mimic d-VIN, to avoid misdiagnosis.

Food and non-alcoholic beverage marketing via Fortnite streamers on Twitch: A content analysis.

Food and non-alcoholic beverage (hereafter: food) marketing is prevalent in digital media and predominantly for foods high in fats, salt and/or sugar (HFSS). However, little is known about food marketing in videogame livestreaming platforms - a hybridisation of social and gaming media where individuals can watch influencers (i.e., streamers) play videogames. No studies have explored food cues within the streamed content or content likely to be viewed by adolescents. The current study analysed the food cues in Twitch (the leading videogame livestreaming platform) videos (n = 52, 52h) uploaded to the platform during October 2020-September 2021 by influencers likely to be popular with adolescents. Food cues (n = 133, 2.56 per hour) were coded for exposure (e.g., display type, healthfulness) and power (e.g., presentation) using a World Health Organization (WHO) protocol and the UK Nutrient Profile Model. The majority (70.7%) of cues were HFSS, with energy drinks being the most featured food category (62.4%). Most cues were branded (80.5%) and featured as either product placement (44.4%) or a looping image (40.6%). Influencers were more likely to consume healthy (88.5%) than HFSS items (33.4%). The mean duration of each food cue was 20 min and 25 s per hour. Only 2.3% of cues had an advertising disclosure. This study provides the first empirical assessment of food cues on Twitch in livestreamed content likely to be popular with adolescents and has implications for digital food marketing policy development.

A biallelic SNIP1 Amish founder variant causes a recognizable neurodevelopmental disorder.

SNIP1 (Smad nuclear interacting protein 1) is a widely expressed transcriptional suppressor of the TGF-ß signal-transduction pathway which plays a key role in human spliceosome function. Here, we describe extensive genetic studies and clinical findings of a complex inherited neurodevelopmental disorder in 35 individuals associated with a SNIP1 NM_024700.4:c.1097A>G, p.(Glu366Gly) variant, present at high frequency in the Amish community. The cardinal clinical features of the condition include hypotonia, global developmental delay, intellectual disability, seizures, and a characteristic craniofacial appearance. Our gene transcript studies in affected individuals define altered gene expression profiles of a number of molecules with well-defined neurodevelopmental and neuropathological roles, potentially explaining clinical outcomes. Together these data confirm this SNIP1 gene variant as a cause of an autosomal recessive complex neurodevelopmental disorder and provide important insight into the molecular roles of SNIP1, which likely explain the cardinal clinical outcomes in affected individuals, defining potential therapeutic avenues for future research.

Store-and-forward (asynchronous) doctor-to-dermatologist non-skin cancer specific teledermatology services in Australia: A scoping review.

Store-and-forward teledermatology (SAFT) has become increasingly popular as a means to increase access to specialist care and address healthcare disparities such as those experienced by rural communities. A contemporary systematic overview of the Australian SAFT services and outcomes for all dermatological conditions is missing. This scoping review provides an overview of Australian SAFT models. Twelve studies were identified through web databases, grey literature sites and reference lists of eligible articles. Eligibility criteria included studies evaluating doctor-to-dermatologist Australian SAFT services provided to Australians for all skin conditions but excluded the studies that solely focused on skin cancers. Data on study design, setting, population, SAFT model, referral characteristics, patient, and general practitioner perspectives, diagnostic concordance, and measured outcomes such as follow up, investigation and waiting time were extracted. Quality of the included studies was assessed using CASP tools. Synthesis reveals that SAFT can be used for patients with any dermatological condition, provides more accurate diagnostics compared to cases without dermatologist input, may reduce waiting times for dermatological expertise, and users generally had positive experiences with SAFT. Although results are positive, this review reveals the heterogenous nature of the literature on SAFT in Australia and a need to establish a uniform approach to assessing the outcomes and impacts of such services.

Australian dental school academics' perceptions of gerodontology education in the undergraduate curriculum.

INTRODUCTION: Australia's rapidly growing population of dentate, frail, care-dependent older people require graduates skilled in managing the health needs of this patient group. The perceptions of academics teaching gerodontology may inform future dental curricula recommendations. This study explored the perceptions of gerodontology education amongst Australian dental school academics. MATERIALS AND METHODS: All nine Australian dental schools providing entry-to-practice dentistry programs were invited to participate in semi-structured interviews. Academics from six dentistry programs took part, and the data were analysed using a thematic approach. RESULTS: The three main themes identified from interviews included 'clinical exposure', 'organisational levers', and 'sociological barriers'. The attitudes of students, as well as society and health professionals, were seen as strongly influential in preparing the workforce for managing the oral health of older people. The themes inter-linked with a knock-on effect where societal attitudes and organisational levers impact on the ability to successfully support students' preparation for gerodontology practice. Limited resources were barriers to achieving ideal learning and teaching and continued upon graduation as oral health care for older people was perceived as undervalued and under-resourced. CONCLUSION: There has been a continued cycle of failure in healthcare schemes and advocacy for the improvement of oral health for older people which has contributed to the inadequate preparation of dental graduates for managing frail and care-dependent older people. Organisational, societal, and political change is needed to support the education of dental students in this area to ensure graduate dentists are competent to manage the oral care needs of this growing population.

Rural generalist medicine: a developing approach to health care in rural and island Japan.

INTRODUCTION: Despite universal health coverage and high life expectancy, Japan faces challenges in health care that include providing care for the world's oldest population, increasing healthcare costs, physician maldistribution and an entrenched medical workforce and training system. Primary health care has typically been practised by specialists in other fields, and general medicine has only been certified as an accredited specialty since 2018. There are continued challenges to develop an awareness and acceptance of the primary health medical workforce in Japan. The impact of these challenges is highest in rural and island areas of Japan, with nearly 50% of rural and remote populations considered 'elderly'. Concurrently, these areas are experiencing physician shortages as medical graduates gravitate to urban areas and choose medical specialties more commonly practised in cities. This study aimed to understand the views on the role of rural generalist medicine (RGM) in contributing to solutions for rural and island health care in Japan. METHODS: This was a descriptive qualitative study. Data were collected via semi-structured interviews with 16 participants, including Rural Generalist Program Japan (RGPJ) registrars and supervisors, the RGPJ director, government officials, rural health experts and academics. Interviews were of 35-50 minutes duration and conducted between May and July 2019. Some interviews were conducted in person at the WONCA Asia-Pacific Conference in Kyoto, some onsite in hospital settings and some were videoconferenced. Interviews were recorded and transcribed. All transcripts were analysed through an inductive thematic process based on the grouping of codes. RESULTS: From the interview analysis, six main themes were identified: (1) key issues facing rural and island health in Japan; (2) participant background; (3) local demography and population; (4) identity, perception and role of RGM; (5) RGPJ experience; and (6) suggested reforms and recommendations. DISCUSSION: The RGPJ was generally considered to be a positive step toward reshaping the medical workforce to address the geographic inequities in Japan. While improvements to the program were suggested by participants, it was also generally agreed that a more systematic, national approach to RGM was needed in Japan. Key findings from this study are relevant to this goal. This includes considering the drivers to participating in the RGPJ for future recruitment strategies and the need for an idiosyncratic Japanese model of RGM, with agreed advanced skills and supervision models. Also important are the issues raised by participants on the need to improve community acceptance and branding of rural generalist doctors to support primary care in rural and island areas. CONCLUSION: The RGPJ represents an effort to bolster the national rural medical workforce in Japan. Discussions from participants in this study indicate strong support to continue research, exploration and expansion of a national RGM model that is contextualised for Japanese conditions and that is branded and promoted to build community support for the role of the rural generalist.

Direct Synthesis of 1-Butanol with High Faradaic Efficiency from CO2 Utilizing Cascade Catalysis at a Ni-Enhanced (Cr2O3)3Ga2O3 Electrocatalyst.

Electrochemical transformation of CO2 into energy-dense liquid fuels provides a viable solution to challenges regarding climate change and nonrenewable resource dependence. Here, we report on the modification of a Cr-Ga oxide electrocatalyst through the introduction of nickel to generate a catalyst that generates 1-butanol at unprecedented faradaic efficiencies (ξ = 42%). This faradaic efficiency occurs at -1.48 V vs Ag/AgCl, with 1-butanol production commencing at an overpotential of 320 mV. At this potential, minor products include formate, methanol, acetic acid, acetone, and 3-hydroxybutanal. At -1.0 and -1.4 V, 3-hydroxybutanal becomes the primary product. This is in contrast to the nickel-free (Cr2O3)3(Ga2O3) system, where neither 3-hydroxybutanal nor 1-butanol was detected. Mechanistic studies show that formate is the initial CO2 reduction product and identify acetaldehyde as the key intermediate. Nickel is found responsible for the coupling and reduction of acetaldehyde to generate the higher molecular weight carbon products observed. To the best of our knowledge, this is the first electrocatalyst to generate 1-butanol with high faradaic efficiency.

Using Light and Electrons to Bend Carbon Dioxide: Developing and Understanding Catalysts for CO2 Conversion to Fuels and Feedstocks.

Our global society generates an unwieldy amount of CO2 per unit time. Therefore, the capture of this greenhouse gas must involve a diverse set of strategies. One solution to this problem is the conversion of CO2 into a more useful chemical species. Again, a multiplicity of syntheses and products will be necessary. No matter how elegant the chemistry is, commercial markets often have little use for a small set of compounds made in tremendous yield. Following this reasoning, the Bocarsly Research Group seeks to develop new electrochemical and photochemical processes that may be of utility in the conversion of CO2 to organic compounds. We focus on investigating proton-coupled charge transfer mechanisms that produce both C1 and carbon-carbon bonded products (C2+).In early work, we considered the reduction of CO2 to formate at electrocatalytic indium and tin electrodes. These studies demonstrated the key role of surface oxides in catalyzing the reduction of CO2. This work generated efficient systems for the formation of formate and paved the way to studies using non-copper, intermetallic electrocatalysts for the generation of C2+ species. Most notable is the efficient formation of oxalate at an oxidized Cr3Ga electrode. Oxalate has recently been suggested as a potential nonfossil, alternate organic feedstock.Separately, we have focused on the electrocatalytic effects of pyridine on the reduction of CO2 in aqueous electrolyte. These studies demonstrated that electrodes that normally yield a low hydrogen overpotential (Pd and Pt) show suppressed H2 evolution and strongly enhanced activity for CO2 reduction in the presence of pyridinium. Methanol was observed to form in high Faradaic yield at low overpotential using this system. The 6-electron, 6-proton reduction of CO2 in the presence of pyridinium was intriguing, and significant effort was placed on understanding the mechanism of this reaction both on metal electrodes and on semiconducting photocathodes. P-GaP electrodes were found to provide exceptional behavior for the formation of methanol using only light as the energy source.The pyridinium studies highlighted the role of protons in the overall reduction of CO2, stimulating our interest in the chemistry of MnBr(bpy)(CO)3 and related compounds. This complex was reported to electrochemically reduce CO2 to CO. We saw these reports as an opportunity to study the detailed nature of the proton-coupled electron transfer (PCET) mechanism associated with CO2 reduction. Our investigation of this system revealed the role of hydrogen-bonding in CO2 reduction and pointed the way for the construction of a photochemical process for CO generation using a [(bpy)(CO)3Mn(CN)Mn(bpy)(CO)3]+ photocatalyst.Based on our studies to date, it appears likely that heterogeneous systems can be assembled to convert CO2 into products that are "beyond C2 products." This may open up new practical chemistry in the area of fossil-based replacements for both synthesis and fuels. Systems with pragmatic efficiencies are close to reality. Electrochemical reactors using heterogeneous electrocatalysts show the stability and product selectivity needed to generate industrial opportunities. Continued growth of mechanistic understanding is expected to facilitate the chemical design of cogent systems for the taming of CO2.

Orexin 2 receptor-selective agonist danavorexton (TAK-925) promotes wakefulness in non-human primates and healthy individuals.

The orexin 2 receptor-selective agonist danavorexton (TAK-925) has been shown to produce wake-promoting effects in wild-type mice, narcolepsy-model mice, and individuals with narcolepsy type 1 and type 2. Here, we report wake-promoting effects of danavorexton in non-human primates and healthy men during their sleep phase. Electroencephalogram analyses revealed that subcutaneous administration of danavorexton significantly increased wakefulness in common marmosets (p < 0.05 at 0.1 mg kg-1 , and p < 0.001 at 1 mg kg-1 and 10 mg kg-1 ) and cynomolgus monkeys (p ≤ 0.05 at 1 mg kg-1 and 3 mg kg-1 ). In a phase 1b crossover, randomized, double-blind, placebo-controlled and active-controlled study in sleep-deprived healthy participants (ClinicalTrials.gov identifier: NCT03522506), modafinil 300 mg (used to demonstrate assay sensitivity) and continuous infusion of danavorexton 44 mg and danavorexton 112 mg showed statistically superior wake-promoting effects to placebo (n = 18). Measured using the Maintenance of Wakefulness Test, mean (standard deviation) sleep latencies during infusion of danavorexton 44 mg, danavorexton 112 mg and placebo were 21.4 (8.9), 31.8 (3.2) and 9.2 (6.4) min, respectively. Least-squares mean difference from placebo in average sleep latency was 16.8 min with danavorexton 44 mg and 30.2 min with danavorexton 112 mg (both p < 0.001). Karolinska Sleepiness Scale scores were statistically significantly lower (indicating decreased sleepiness) for participants receiving danavorexton than for those receiving placebo during infusion (danavorexton 44 mg, p = 0.010; danavorexton 112 mg, p < 0.001). Together, these results indicate that an orexin 2 receptor agonist increases wakefulness in non-human primates and healthy individuals during their sleep phase.

User engagement with a popular food brand before, during and after a multi-day interactive marketing campaign on a popular live streaming platform.

OBJECTIVE: To assess viewer engagement of a food advertising campaign on the live streaming platform Twitch.tv, a social media platform that allows creators to live stream content and communicate with their audience in real time. DESIGN: Observational analysis of chat comments across the Twitch platform containing the word 'Wendy's' or 'Wendys' during a 5-day ad campaign compared with two 5-day non-campaign time periods. Comments were categorised as positive, negative or neutral in how their sentiment pertained to the brand Wendy's. SETTING: Twitch chatrooms. PARTICIPANTS: None. RESULTS: There were significantly more chatroom messages related to the Wendy's brand during the campaign period. When considering all messages, the proportion of messages was statistically different (x2 = 1417·41, P < 0·001) across time periods, with a higher proportion of neutral and positive messages and a lower proportion of negative messages during the campaign compared with the comparison periods. Additionally, the proportion of negative messages following the campaign was lower than before the campaign. When considering only positive and negative messages, the proportion of messages was statistically different (x2 = 366·38, P < 0·001) across each time period with a higher proportion of positive messages and a lower proportion of negative messages during the campaign when compared with the other time periods. Additionally, there was a higher proportion of positive messages and a lower portion of negative messages following the campaign when compared with before the campaign. CONCLUSIONS: This study demonstrates the impact and sustained impact of a fast-food brand ad campaign on brand engagement on the live streaming platform Twitch.

Patient and carer experiences of lung cancer referral pathway in a regional health service: a qualitative study.

BACKGROUND: Lung cancer referral pathways aim to reduce delays and improve referral patterns of people with suspected lung cancer. AIM: As part of implementing a lung cancer referral pathway at a regional Australian hospital, this study aimed to explore the experiences and perceptions of people with lung cancer and their carers. METHODS: In-depth interviews were used to elicit data for thematic analysis in this cross-sectional descriptive qualitative study. Patients with newly diagnosed lung cancer and their carers at a regional academic cancer centre were invited to participate in interviews. Five interviews were conducted face-to-face, and 14 interviews were conducted by telephone (as per interviewee preference). Interviews were audiorecorded, transcribed and qualitatively analysed. Descriptive phrases were used to generate initial inductive codes and themes. RESULTS: Nineteen participants approached agreed to take part in the study. Factors that positively impacted the care experience were good communication, timeliness and patient advocacy and support. Improper communication, long waiting times for investigations and appointments, uncertainty about the process and inconsistent advice from providers negatively impacted the care experience. Participants preferred face-to-face or video-linked consultations over telephone consultations. CONCLUSIONS: Understanding the experiences of rural and regional patients and carers with the lung cancer referral pathway is important to improve quality of care. Implementing changes to the referral pathway to improve patient and carer experiences needs to be an ongoing quality improvement exercise.

Recall of food marketing on videogame livestreaming platforms: Associations with adolescent diet-related behaviours and health.

Digital media has become an integral part of adolescents' lives. Mirroring this trend, food and non-alcoholic beverage (hereafter: food) brands increasingly promote products in digital media to maximise reach with young consumers. Videogame livestreaming platforms, where individuals can broadcast or watch streamed videogame footage, are a growing form of digital media. The top three platforms (market share by hours watched) are Twitch (72%), YouTube Gaming (13%), and Facebook Gaming Live (9%), with a combined 34.6 billion hours watched in 2021. These platforms represent a hybridisation of two popular digital trends amongst teenagers: viewing online video content and playing videogames. On these platforms, gaming influencers promote food brands and products, with energy drinks and fast-food restaurants representing the most frequently promoted categories. Evidence suggests that food marketing via Twitch is associated with food craving, purchasing and consumption in adults. Yet, despite the evident teenage appeal and prevalence of food marketing on these platforms, research is yet to explore its associations with adolescent eating behaviour. Adolescents (n = 490, Mage = 16.81, 30.2% female) completed an online cross-sectional questionnaire exploring their recall of food marketing on the top three videogame livestreaming platforms, and relevant behavioural (purchase, consumption) and health (Body Mass Index) outcomes. Structural equation modelling was used to explore hierarchical relationships between the key variables. Results showed that recall of unhealthy food marketing on these platforms was significantly associated with purchase and consumption of marketed food categories. Attitudes towards unhealthy foods mediated this relationship. Findings are the first to demonstrate the relationships between unhealthy food marketing via videogame livestreaming platforms and adolescent eating behaviours, which has implications for the design of policies to restrict digital food marketing to young people.

Assessing cultural safety in general practice consultations for Indigenous patients: protocol for a mixed methods sequential embedded design study.

BACKGROUND: Assessment of cultural safety in general practice consultations for Indigenous patients is a complex notion. Design and development of any assessment tool needs to be cognizant that cultural safety is determined by Indigenous peoples and incorporates defined components of cultural safety and current educational theory. Consideration of how social, historical, and political determinants of health and well-being impact upon the cultural safety of a consultation is also important. Given this complexity, we assume that no single method of assessment will be adequate to determine if general practice (GP) registrars are demonstrating or delivering culturally safe care. As such, we propose that development and assessment of cultural safety can be conceptualised using a model that considers these variables. From this, we aim to develop a tool to assess whether GP registrars are conducting a culturally safe consultation, where cultural safety is determined by Aboriginal and Torres Strait Islander peoples. METHODS: This protocol will be situated in a pragmatic philosophical position to explore cultural safety primarily from the Australian Aboriginal and Torres Strait Islander patients' perspective with triangulation and validation of findings with the GP and GP registrar perspective, the Aboriginal and Torres Strait Islander community, and the medical education community. The study will integrate both quantitative and qualitative data through three sequential phases. Data collection will be through survey, semi-structured interviews, an adapted nominal group technique, and a Delphi questionnaire. We aim to recruit approximately 40 patient and 20 GP participants for interviews, conduct one to five nominal groups (seven to 35 participants) and recruit fifteen participants for the Delphi process. Data will be analysed through a content analysis approach to identify components of an assessment of cultural safety for GP registrars. DISCUSSION: This study will be one of the first to explore how cultural safety, as determined by Indigenous peoples, can be assessed in general practice consultations. This protocol is shared to stimulate awareness and discussion around this significant issue and prompt other studies in this area.

Perceptions of Australians with diabetes-related foot disease on requirements for effective secondary prevention.

INTRODUCTION: Secondary prevention is essential in reducing recurrence of diabetes-related foot disease (DFD) but is frequently poorly implemented in clinical practice. OBJECTIVE: To explore the perceptions of people with diabetes-related foot disease (DFD) on their self-perceived knowledge in managing DFD, facilitators and barriers influencing their DFD care, and ideas and preferences for a secondary prevention program. DESIGN: Sixteen people with a history of DFD from Queensland and Victoria, Australia, underwent semi-structured interviews. Interviews were audio-recorded over telephone and transcribed and analysed following a thematic framework. Participants were asked about their experiences and perceptions relating to DFD and factors influencing the care they receive for DFD relevant to the development of a secondary prevention program for DFD. FINDINGS AND DISCUSSION: Participants had high self-perceived knowledge in managing DFD, especially in implementing healthy lifestyle changes and conducting daily foot checks and foot care, though most received support from family members acting as carers. However, issues with access and adherence to offloading footwear, and a lack of clear education received on footwear and other aspects of DFD care were perceived as major barriers. Improved patient education, provided in a consistent manner by proactive clinicians was perceived as an essential part of secondary prevention. Telehealth was perceived positively through facilitating faster care and considered a good adjunct to standard care. Health and technological literacy were considered potentially major barriers to the effectiveness of remote care. CONCLUSION: People with DFD require improved access to offloading footwear and education about secondary prevention, which could be provided by telehealth with adequate support.

The effect of duration of therapy for treatment of Staphylococcus aureus blood stream infection: an application of cloning to deal with immortal-time bias in an analysis of data from a cohort study (BSI-FOO).

OBJECTIVE: To estimate the effect of treatment duration on in-hospital mortality in patients with Staphylococcus aureus blood stream infection and demonstrate the biases that can arise when immortal-time bias is ignored. EXPOSURE: We compared three treatment strategies: short therapy (<10 days), intermediate (10-18 days) and long (>18 days). MAIN OUTCOME MEASURES: Twenty-eight-day all-cause in-hospital mortality. METHODS: Using data from the BSI-FOO study, we implemented an approach proposed by Hernán to overcome confounding and immortal-time biases. The first stage is to clone all participants, so that each participant is assigned to each treatment strategy. Second, observations are censored when their data becomes inconsistent with their assigned strategy. Finally, inverse-probability weights are applied to adjust for potential selection. We compared our results to a naïve approach where immortal-time bias is ignored. RESULTS: Of the 1903 participants in BSI-FOO, 587 were eligible and included in the analysis. After cloning, the weighted estimates of hazard ratio of mortality for short versus long therapy was 1.74 (95% CI 1.36, 2.24) and for intermediate versus long therapy was 1.09 (0.98, 1.22). In the naïve approach, the hazard ratios with reference to the long therapy group are 37.4 (95% CI 18.9 to 74.4) in the short therapy group and 4.1 (95% CI 1.9 to 8.9) in the intermediate therapy group. CONCLUSIONS: Our findings suggest that duration of therapy >18 days is beneficial with respect to 28-day in-hospital mortality, however, there remains uncertainty around the efficacy of reducing duration of treatment to 10-18 days.

A scoping review of outdoor food marketing: exposure, power and impacts on eating behaviour and health.

BACKGROUND: There is convincing evidence that unhealthy food marketing is extensive on television and in digital media, uses powerful persuasive techniques, and impacts dietary choices and consumption, particularly in children. It is less clear whether this is also the case for outdoor food marketing. This review (i) identifies common criteria used to define outdoor food marketing, (ii) summarises research methodologies used, (iii) identifies available evidence on the exposure, power (i.e. persuasive creative strategies within marketing) and impact of outdoor food marketing on behaviour and health and (iv) identifies knowledge gaps and directions for future research. METHODS: A systematic search was conducted of Medline (Ovid), Scopus, Science Direct, Proquest, PsycINFO, CINAHL, PubMed, the Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials and a number of grey literature sources. Titles and abstracts were screened by one researcher. Relevant full texts were independently checked by two researchers against eligibility criteria. RESULTS: Fifty-three studies were conducted across twenty-one countries. The majority of studies (n = 39) were conducted in high-income countries. All measured the extent of exposure to outdoor food marketing, twelve also assessed power and three measured impact on behavioural or health outcomes. Criteria used to define outdoor food marketing and methodologies adopted were highly variable across studies. Almost a quarter of advertisements across all studies were for food (mean of 22.1%) and the majority of advertised foods were unhealthy (mean of 63%). The evidence on differences in exposure by SES is heterogenous, which makes it difficult to draw conclusions, however the research suggests that ethnic minority groups have a higher likelihood of exposure to food marketing outdoors. The most frequent persuasive creative strategies were premium offers and use of characters. There was limited evidence on the relationship between exposure to outdoor food marketing and eating behaviour or health outcomes. CONCLUSIONS: This review highlights the extent of unhealthy outdoor food marketing globally and the powerful methods used within this marketing. There is a need for consistency in defining and measuring outdoor food marketing to enable comparison across time and place. Future research should attempt to measure direct impacts on behaviour and health.

Interest in and uptake of genetic counseling for preconception carrier screening when offered to predominantly white reproductive-age persons seeking gynecologic care at a single U.S. academic medical center.

The objective of this study was to assess the level of interest in preconception carrier screening among reproductive-aged persons presenting for gynecologic care and to identify demographic factors predictive of pursuing screening. Patients aged 18-40 who were presenting for gynecologic care at a single U.S. academic medical center were provided with information about current options for preconception carrier screening and were offered genetic counseling referral with the possibility to undergo screening. Outcomes of interest were desire for genetic counseling referral and attendance at genetic counseling visit. Statistical analyses were performed as appropriate using R version 3.6.1 with variables significant at 0.1 included in a multivariable logistic regression. Of 193 participants, 79 (41%) desired genetic counseling referral. Participants aged 25-34 (OR 3.39, 95% CI 1.47-8.10) and nulliparas (OR 2.69, 95% CI 1.23-6.03) were more likely to desire referral. Thirty-five participants (44.3% of those who desired referral) attended a visit with genetic counseling. Having an advanced degree (OR 3.27, 95% CI 1.06-10.4) was associated with visit attendance. Thirteen participants underwent screening, and five were found to be a carrier of at least one X-linked or autosomal recessive condition. Surprisingly, presenting for a gynecologic visit directly related to planning a pregnancy was not associated with increased interest in preconception carrier screening. Nulliparas and those aged 25-34 likely expressed greater interest in referral due to high potential for future childbearing in these groups. The increased level of visit attendance in participants with advanced degrees is likely confounded by the high level of health literacy and financial resources in this group.

Epidemiology of Surgical Procedures, Anesthesia, and Imaging Studies by Gestational Age during the First Year of Life in Medicaid-Insured Infants.

OBJECTIVES: To evaluate the rate of surgical procedures, anesthetic use, and imaging studies by prematurity status for the first year of life we analyzed data for Texas Medicaid-insured newborns. STUDY DESIGN: We developed a retrospective population-based live birth cohort of newborn infants insured by Texas Medicaid in 2010-2014 with 4 subcohorts: extremely premature, very premature, moderate/late premature, and term. RESULTS: In 1 102 958 infants, surgical procedures per 100 infants were 135.9 for extremely premature, 35.4 for very premature, 15.5 for moderate/late premature, and 6.5 for term. Anesthetic use was 62.0 for extremely premature, 20.8 for very premature, 11.1 for moderate/late premature, and 5.6 for the term subcohort. The most common procedures in the extremely premature were neurosurgery, intubations, and procedures that facilitated caloric intake (gastrostomy tubes and fundoplications). The annual rates for the first year of life for chest radiograph ranged from 15.0 per year for the extremely premature cohort to 0.6 for term infants and for magnetic resonance imaging (MRI) from 0.3 to 0.01. MRI was the most common imaging study with anesthesia support in all maturity levels. MRIs were done in extremely premature without anesthesia in over 90% and in term infants in 57.2%. CONCLUSIONS: Surgical procedures, anesthetic use, and imaging studies in infants are common and more frequent with higher a degree of prematurity while the use of anesthesia is lower in more premature newborns. These findings can provide direction for outcome studies of surgery and anesthesia exposure.

Analytical challenges in estimating the effect of exposures that are bounded by follow-up time: experiences from the Blood Stream Infection-Focus on Outcomes study.

OBJECTIVE: To illustrate the challenges of estimating the effect of an exposure that is bounded by duration of follow-up on all-cause 28-day mortality, whilst simultaneously addressing missing data and time-varying covariates. STUDY DESIGN AND METHODS: BSI-FOO is a multicentre cohort study with the primary aim of quantifying the effect of modifiable risk factors, including time to initiation of therapy, on all-cause 28-day mortality in patients with bloodstream infection. The primary analysis involved two Cox proportional hazard models, first one for non-modifiable risk factors and second one for modifiable risk factors, with a risk score calculated from the first model included as a covariate in the second model. Modifiable risk factors considered in this study were recorded daily for a maximum of 28 days after infection. Follow-up was split at daily intervals from day 0 to 28 with values of daily collected data updated at each interval (i.e., one row per patient per day). ANALYTICAL CHALLENGES: Estimating the effect of time to initiation of treatment on survival is analytically challenging since only those who survive to time t can wait until time t to start treatment, introducing immortal time bias. Time-varying covariates representing cumulative counts were used for variables bounded by survival time e.g. the cumulative count of days before first receipt of treatment. Multiple imputation using chained equations was used to impute missing data, using conditional imputation to avoid imputing non-applicable data e.g. ward data after discharge. CONCLUSION: Using time-varying covariates represented by cumulative counts within a one row per day per patient framework can reduce the risk of bias in effect estimates. The approach followed uses established methodology and is easily implemented in standard statistical packages.