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Purpose: Individuals with diabetes have an elevated risk of depression. The occurrence of the COVID-19 pandemic may have further impacted the mental health of patients living with diabetes. This study aims to examine: 1) factors associated with the development of depression during the COVID-19 pandemic among individuals with diabetes without a history of depression; and 2) factors associated with the persistence or recurrence of depression during the pandemic among those with diabetes, and a pre-pandemic history of depression. Methods: Secondary analysis of four waves of the Canadian Longitudinal Study on Aging surveys. Canadian residents between the ages of 45–85 were recruited in 2012–2015 and subsequently completed three follow-up surveys. A total of 2,730 individuals with diabetes were included in this study. Results: Among those without a prior history of depression, the incidence of new depression was 12.9 % (95 % CI 11.3–14.4 %) during the pandemic. Among those with a history of depression, approximately half (48.5 %; 95 % CI 45.4–51.7 %) were depressed during the pandemic. Factors associated with increased risk of incident and recurrent depression during the pandemic among older adults with diabetes include being female, greater educational attainment, higher income/savings, functional limitations, loneliness/social isolation, chronic pain, family conflict, and difficulties accessing health care. Conclusion: Among Canadians living with diabetes, both the incidence and recurrence of depression increased during the pandemic. Continued efforts to support the psychological well-being of older adults with diabetes are needed.

Abstract Ocular delivery of lipid nanoparticle (LNPs) packaged mRNA can enable efficient gene delivery and editing. We generated LNP variants through the inclusion of positively charged-amine-modified polyethylene glycol (PEG)-lipids (LNPa), negatively charged-carboxyl-(LNPz) and carboxy-ester (LNPx) modified PEG-lipids, and neutral unmodified PEG-lipids (LNP). Subretinal injections of LNPa containing Cre mRNA in the mouse show tdTomato signal in the retinal pigmented epithelium (RPE) like conventional LNPs. Unexpectedly, LNPx and LNPz show 27% and 16% photoreceptor transfection, respectively, with striking localization extending from the photoreceptor synaptic pedicle to the outer segments, displaying pan-retinal distribution in the photoreceptors and RPE. LNPx containing Cas9 mRNA and sgAi9 leads to the formation of an oval elongated structure with a neutral charge resulting in 16.4% editing restricted to RPE. Surface modifications of LNPs with PEG variants can alter cellular tropism of mRNA. LNPs enable genome editing in the retina and in the future can be used to correct genetic mutations that lead to blindness.

Abstract Background Small airways disease plays a key role in the pathogenesis of chronic obstructive pulmonary disease (COPD) and is a major cause of obstruction; therefore, it is a critical pharmacotherapy target. This study evaluated lung deposition of two inhaled corticosteroid (ICS)/long-acting β2-agonist/long-acting muscarinic antagonist single-inhaler triple therapies using in silico functional respiratory imaging (FRI). Deposition was assessed using real-world inhalation profiles simulating everyday use where optimal inhalation may be compromised. Methods Three-dimensional airway models were produced from 20 patients with moderate-to-very severe COPD. Total, central, and regional small airways deposition as a percentage of delivered dose of budesonide/glycopyrronium/formoterol fumarate dihydrate (BGF) 160/7.2/5 µg per actuation and fluticasone furoate/umeclidinium/vilanterol (FF/UM/VI) 100/62.5/25 µg were evaluated using in silico FRI based on in vitro aerodynamic particle size distributions of each device. Simulations were performed using multiple inhalation profiles of varying durations and flow rates representing patterns suited for a pressurized metered-dose inhaler or dry-powder inhaler (four for BGF, two for FF/UM/VI, with one common profile). For the common profile, deposition for BGF versus FF/UM/VI was compared post-hoc using paired t-tests. Results Across inhalation profiles, mean total lung deposition was consistently higher with BGF (47.0–54.1%) versus FF/UM/VI (20.8–22.7%) and for each treatment component, with greater deposition for BGF also seen in the central large airways. Mean regional small airways deposition was also greater across inhalation profiles with BGF (16.9–23.6%) versus FF/UM/VI (6.8–8.7%) and for each treatment component. For the common profile, total, central, and regional small airways deposition were significantly greater for BGF versus FF/UM/VI (nominal p

Abstract Background Universal immunisation is the cornerstone of preventive medicine for children, The World Health Organisation (WHO) recommends diphtheria-tetanus-pertussis (DTP) vaccine administered at 6, 10 and 14 weeks of age as part of routine immunisation. However, globally, more than 17 unique DTP-containing vaccine schedules are in use. New vaccines for other diseases continue to be introduced into the infant immunisation schedule, resulting in an increasingly crowded schedule. The OptImms trial will assess whether antibody titres against pertussis and other antigens in childhood can be maintained whilst adjusting the current Expanded Programme on Immunisation (EPI) schedule to provide space for the introduction of new vaccines. Methods The OptImms studies are two randomised, five-arm, non-inferiority clinical trials in Nepal and Uganda. Infants aged 6 weeks will be randomised to one of five primary vaccination schedules based on age at first DTwP-vaccination (6 versus 8 weeks of age), number of doses in the DTwP priming series (two versus three), and spacing of priming series vaccinations (4 versus 8 weeks). Additionally, participants will be randomised to receive their DTwP booster at 9 or 12 months of age. A further sub-study will compare the co-administration of typhoid vaccine with other routine vaccines at one year of age. The primary outcome is anti-pertussis toxin IgG antibodies measured at the time of the booster dose. Secondary outcomes include antibodies against other vaccine antigens in the primary schedule and their safety. Discussion These data will provide key data to inform policy decisions on streamlining vaccination schedules in childhood. Trial registrations ISRCTN12240140 (Nepa1, 7th January 2021) and ISRCTN6036654 (Uganda, 17th February 2021).

ABSTRACT Lactiplantibacillus plantarum ATCC 202195 has probiotic properties that may be beneficial in early infancy. Since the effects of probiotics are often strain and dose specific, tools are needed to identify and enumerate L. plantarum ATCC 202195 with high sensitivity and specificity. Herein, a probe-based real-time quantitative PCR (qPCR) assay was developed to detect and enumerate L. plantarum ATCC 202195. The probe sequence contained a single nucleotide polymorphism within gene FEE41_08190 that was unique to L. plantarum ATCC 202195 at the time of the assay’s design. The linear dynamic range of the assay spanned five orders of magnitude with an R 2 that did not deviate from linearity and an amplification efficiency that ranged from 97% to 110% across six independent plates. At 95% confidence, the limit of detection in the assay was estimated at roughly 15 cells. No amplification was observed for reactions containing gDNA from seven other Lactobacillus species. This is the first report of a qPCR assay that detects and quantifies L. plantarum ATCC 202195. The assay is intended to be used as a resource for future clinical trials and commercial manufacturing settings. IMPORTANCE When administered for seven consecutive days shortly after birth, the probiotic bacterium Lactiplantibacillus plantarum ATCC 202195 plus fructooligosaccharide (FOS) was reported to reduce sepsis and lower respiratory tract infection events during early infancy in a randomized trial in India. Since probiotic effects are often strain specific, strain-level detection and quantification by routine molecular methods enables the monitoring of safety outcomes, such as probiotic-associated bacteremia, and allows for the quality of probiotic interventions to be assessed and monitored (i.e., verify strain identity and enumerate). Despite the potential clinical applications of L. plantarum ATCC 202195, an assay to detect and quantify this strain has not previously been described. Herein, we report the design of primer and probe sequences to detect L. plantarum ATCC 202195 and the development and optimization of a real-time PCR assay to detect and quantify the strain with high specificity and high sensitivity.

Background and purpose: Pancreatic ductal adenocarcinoma (PDAC) remains one of the leading causes of cancer-related deaths in the world. For patients with PDAC who are not eligible for surgery, radiation therapy improves local disease control, yet safely delivering therapeutic doses of radiation remains challenging due to off-target toxicities in surrounding normal tissues. NBTXR3, a novel radioenhancer composed of functionalized hafnium oxide crystalline nanoparticles, has recently shown clinical activity in soft tissue sarcoma, hepatocellular carcinoma, head and neck squamous cell carcinoma, and advanced solid malignancies with lung or liver metastases. Here we report the first patient with pancreatic cancer treated with NBTXR3. Materials and methods: A 66-year-old male with unresectable locally advanced PDAC was enrolled on our clinical trial to receive NBTXR3 activated by radiation therapy. Local endoscopic delivery of NBTXR3 was followed by intensity modulated radiation therapy (IMRT). Follow-up assessment consisted of physical examination, laboratory studies including CA19-9, and CT of the chest, abdomen, and pelvis. Results: The patient received NBTXR3 by local endoscopic delivery without any acute adverse events. Radiation treatment consisted of 45 Gy in 15 daily fractions using IMRT. The patient began radiation twelve days after NBTXR3 injection. Daily CT-on-rails imaging demonstrated retention of NBTXR3 within the tumor for the duration of treatment. At initial follow-up evaluation, the lesion remained radiographically stable and the patient did not demonstrate treatment-related toxicity. Conclusion: This report demonstrates initial feasibility of local endoscopic delivery of NBTXR3 activated by radiation therapy for patients with pancreatic cancer who are not eligible for surgery.

Introduction Inactivated, viral vector and mRNA vaccines have been used in the Nepali COVID-19 vaccination programme but there is little evidence on the effectiveness of these vaccines in this setting. The aim of this study is to describe COVID-19 vaccine effectiveness in Nepal and provide information on infections with SARS-CoV-2 variants.Methods and analysis This is a hospital-based, prospective test-negative case–control study conducted at Patan Hospital, Kathmandu. All patients >18 years of age presenting to Patan Hospital with COVID-19-like symptoms who have received a COVID-19 antigen/PCR test are eligible for inclusion. The primary outcome is vaccine effectiveness of licensed COVID-19 vaccines against laboratory-confirmed COVID-19 disease.After enrolment, information will be collected on vaccine status, date of vaccination, type of vaccine, demographics and other medical comorbidities. The primary outcome of interest is laboratory-confirmed SARS-CoV-2 infection. Cases (positive for SARS-CoV-2) and controls (negative for SARS-CoV-2) will be enrolled in a 1:4 ratio. Vaccine effectiveness against COVID-19 disease will be analysed by comparing vaccination status with SARS-CoV-2 test results.Positive SARS-CoV-2 samples will be sequenced to identify circulating variants and estimate vaccine effectiveness against common variants.Measuring vaccine effectiveness and identifying SARS-CoV-2 variants in Nepal will help to inform public health efforts. Describing disease severity in relation to specific SARS-CoV-2 variants and vaccine status will also inform future prevention and care efforts.Ethics and dissemination Ethical approval was obtained from the University of Oxford Tropical Ethics Committee (OxTREC) (ref: 561-21) and the Patan Academy of Health Sciences Institutional Review Board (ref: drs2111121578). The protocol and supporting study documents were approved for use by the Nepal Health Research Council (NHRC 550-2021). Results will be disseminated in peer-reviewed journals and to the public health authorities in Nepal.

Introduction: Fibroblasts are mesenchymal cells that predominantly produce and maintain the extracellular matrix (ECM) and are critical mediators of injury response. In the heart, valve interstitial cells (VICs) are a population of fibroblasts responsible for maintaining the structure and function of heart valves. These cells are regionally distinct from myocardial fibroblasts, including left ventricular cardiac fibroblasts (LVCFBs), which are located in the myocardium in close vicinity to cardiomyocytes. Here, we hypothesize these subpopulations of fibroblasts are transcriptionally and functionally distinct.Methods: To compare these fibroblast subtypes, we collected patient-matched samples of human primary VICs and LVCFBs and performed bulk RNA sequencing, extracellular matrix profiling, and functional contraction and calcification assays.Results: Here, we identified combined expression of SUSD2 on a protein-level, and MEOX2, EBF2 and RHOU at a transcript-level to be differentially expressed in VICs compared to LVCFBs and demonstrated that expression of these genes can be used to distinguish between the two subpopulations. We found both VICs and LVCFBs expressed similar activation and contraction potential in vitro, but VICs showed an increase in ALP activity when activated and higher expression in matricellular proteins, including cartilage oligomeric protein and alpha 2-Heremans-Schmid glycoprotein, both of which are reported to be linked to calcification, compared to LVCFBs.Conclusion: These comparative transcriptomic, proteomic, and functional studies shed novel insight into the similarities and differences between valve interstitial cells and left ventricular cardiac fibroblasts and will aid in understanding region-specific cardiac pathologies, distinguishing between primary subpopulations of fibroblasts, and generating region-specific stem-cell derived cardiac fibroblasts.

The COVID-19 pandemic and associated public health measures have exacerbated many known risk factors for depression that may be particularly concerning for individuals with chronic health conditions, such as peptic ulcer disease (PUD). In a large longitudinal sample of older adults with PUD, the current study examined the incidence of depression during the pandemic among those without a pre-pandemic history of depression (n = 689) and the recurrence of depression among those with a history of depression (n = 451). Data came from four waves of the Canadian Longitudinal Study on Aging (CLSA). Multivariate logistic regression analyses were conducted to identify factors associated with incident and recurrent depression. Among older adults with PUD and without a history of depression, approximately 1 in 8 (13.0%) developed depression for the first time during the COVID-19 pandemic. Among those with a history of depression, approximately 1 in 2 (46.6%) experienced depression during the pandemic. The risk of incident depression and recurrent depression was higher among those who were lonely, those with functional limitations, and those who experienced an increase in family conflict during the pandemic. The risk of incident depression only was higher among women, individuals whose income did not satisfy their basic needs, those who were themselves ill and/or those whose loved ones were ill or died during the pandemic, and those who had disruptions to healthcare access during the pandemic. The risk of recurrent depression only was higher among those with chronic pain and those who had difficulty accessing medication during the pandemic. Implications for interventions are discussed.

Previous research in human-robot interaction has explored using robots to increase objective and hedonic aspects of well-being and quality of life, but there is no literature on how robots might be used to support eudaimonic aspects of well-being (such as meaning in life). A sense of meaning has been shown to positively affect health and longevity. We frame our study around the Japanese concept of ikigai, which is widely used with Japanese older adults to enhance their everyday lives, and is closely related to the concept of eudaimonic well-being (EWB) known in Western countries. Using a mixed-methods and exploratory approach, including interviews with 17 older adults and the collection of 100 survey responses, we explored how older adults in the US experience a sense of meaning, and if and how a social robot could be used to help foster this sense. We find that meaning for older adults is often obtained by helping others, through family connections, and/or through activities of daily life, and that sources of meaning often differ based on the older adults’ living situation. Assessing how meaning compares to happiness and social connection, we highlight general similarities and differences, and also find that living situation influences older adults’ sources of happiness, desire for social connection, and barriers to well-being, in addition to companionship and happiness having a weaker correlation with meaning for those who live alone than for those who live with others. Additionally, we evaluated initial perceptions of a social robot (QT) meant to enhance ikigai and overall well-being, finding mostly positive perceptions, though those who live alone also reported being less willing to adopt a social robot into their homes. Using both data collected on older adults’ meaning and the potential use of QT to support meaning, we make several design recommendations with regards to using robots to enhance ikigai, such as by prompting daily reflecting, enhancing family bonds, and suggesting new experiences and volunteer opportunities.

Summary: Background: There are known differences in vaccine reactogenicity and immunogenicity by sex. Females have been shown to report greater reactogenicity and generate higher humoral and cellular immune responses than males following vaccination with several different vaccines. Whether this is also the case for COVID-19 vaccines is currently unknown, as COVID-19 vaccine study data disaggregated by sex are not routinely reported. Therefore, we have assessed the influence of sex on reactogenicity, immunogenicity and efficacy of COVID-19 vaccine ChAdOx1 nCoV-19. Methods: Vaccine efficacy was assessed in 15169 volunteers enrolled into single-blind randomised controlled trials of ChAdOx1 nCoV-19 in Brazil and the UK, with the primary endpoint defined as nucleic acid amplification test (NAAT)-positive symptomatic SARS-CoV-2 infection. All participants were electronically randomised to receive two standard doses of vaccine or the control product. Logistic regression models were fitted to explore the effect of age and sex on reactogenicity, and linear models fitted to log-transformed values for immunogenicity data. Reactogenicity data were taken from self-reported diaries of 788 trial participants. Pseudovirus neutralisation assay data were available from 748 participants and anti-SARS-CoV-2 spike IgG assay data from 1543 participants. Findings: 7619 participants received ChAdOx1 nCoV-19 and 7550 received the control. Vaccine efficacy in participants after two doses of ChAdOx1 nCoV-19 (4243 females and 3376 males) was 66.1% (95% CI 55.9-73.9%) in males and 59.9% (95% CI 49.8-67.9%) in females; with no evidence of a difference in efficacy between the sexes (vaccine by sex interaction term P=0.3359). A small, statistically significant difference in anti-spike IgG was observed (adjusted GMR 1.14; 95% CI 1.04-1.26), with higher titres in females than males, but there were no statistically significant differences in other immunological endpoints. Whilst the majority of individuals reported at least one systemic reaction following a first dose of ChAdOx1 nCoV-19, females were twice as likely as males to report any systemic reaction after a first dose (OR 1.95; 95% CI 1.37-2.77). Measured fever of 38°C or above was reported in 5% of females and 1% of males following first doses. Headache and fatigue were the most commonly reported reactions in both sexes. Interpretation: Our results show that there is no evidence of difference in efficacy of the COVID-19 vaccine ChAdOx1 nCoV-19 in males and females. Greater reactogenicity in females was not associated with any difference in vaccine efficacy. Funding: Studies were registered with ISRCTN 90906759 (COV002) and ISRCTN 89951424 (COV003) and follow-up is ongoing. Funding was received from the UK Research and Innovation, Engineering and Physical Sciences Research Council, National Institute for Health Research, Coalition for Epidemic Preparedness Innovations, National Institute for Health Research Oxford Biomedical Research Centre, Chinese Academy of Medical Sciences Innovation Fund for Medical Science, Thames Valley and South Midlands NIHR Clinical Research Network, the Lemann Foundation, Rede D'Or, the Brava and Telles Foundation, the Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior, Brazil, and AstraZeneca.

Stereotactic radiosurgery (SRS) has replaced whole brain radiotherapy (WBRT) as standard therapy for most patients with four or fewer brain metastases due to improved cognitive outcomes and more favorable health related quality of life (QoL). Whether SRS or WBRT is the optimal radiation modality for patients with five to fifteen brain metastases remains an open question. Efforts are underway to develop prospective evidence to answer this question. One of the planned trials is a Canadian Cancer Trials Group (CCTG)-lead North American intergroup trial. In general cancer treatments must have two basic aims: prolonging and improving QoL. In this vein, the selection of overall survival and QoL metrics as outcomes appear obvious. Potential secondary outcomes are numerous: patient/disease related, treatment related, economic, translational, imaging, and dosimetric. In designing a trial, one must also ponder what is standard WBRT—specifically, whether it should be associated with memantine. With the rapid accrual of an intergroup trial of hippocampal-sparing WBRT, we may find that the standard WBRT regimen changes in the course of planned trials. As up-front radiosurgery is increasingly used for more than 4 brain metastases without high level evidence, we have a window of opportunity to develop high quality evidence which will help guide our future clinical and policy decisions.

Background Studies demonstrate that large pictorial warnings (PHWs) on both sides of the pack have greater impact than text-only warnings. For over a decade, Brazil has had 100% pictorial warnings but only on the back of pack. In 2009, Brazil introduced dramatic fear-arousing images. In 2016, Brazil finally added a front warning although text-only and 30%. This study evaluated the 2009 and 2016 changes on key perceptual and behavioural indicators of warning impact. Methods Data were analyzed from Waves 1-3 (2009-2016) of the International Tobacco Control (ITC) Brazil Survey, a longitudinal cohort survey of representative samples of adult smokers in Rio de Janeiro, São Paulo, and Porto Alegre (N=1,719). Key outcomes were 6 validated indicators of warning impact. The 2009 warning revision was implemented 2 months after Wave 1 (2009) and 3 years before Wave 2 (2012-13). The 2016 warning revision (introducing front 30% text warnings) was implemented 3 years after Wave 2 (2012-13) and 8 months before Wave 3 (2016-17). Thus, pre-post evaluations of the two revisions were conducted by testing differences in the impact indicators across the three waves. Results Three indicators of warning effectiveness increased significantly between W1 and W2 (showing greater effectiveness of introducing dramatic fear-arousing images of the 2009 revision) and declined at W3 (showing lack of effectiveness of introducing the front text-only warning): noticing (W1=45%; W2=51%; W3=49%), reading (W1=34%; W2=41%; W3=36%), avoiding labels (W1=43%; W2=45%; W3=34%). The remaining 3 indicators (forgoing smoking, thinking about risks, and thinking about quitting) declined at W2 and W3. Conclusions Introducing dramatic fear-arousing images (2009) increased warning effectiveness, but introducing 30% text-only front warnings (2016) did not. There was also evidence of “wearout” of warning impact. These findings demonstrate the importance of frequent warning revision, and the need for pictorial warnings on the FRONT of the pack, consistent with FCTC Article 11 Guidelines.

Background Little is known about the harmfulness perceptions of e-cigarettes (ECs) outside of high-income countries. This study examined reasons for EC use and harmfulness perceptions of ECs compared to regular cigarettes among smokers in Brazil, where 18.3% of smokers and 2.2% of non-smokers have tried ECs. Methods Data were from Waves 2 (2012-13) and 3 (2016-17) of the International Tobacco Control (ITC) Brazil Survey, a cohort survey of 1200 adult smokers and 600 non-smokers in Rio de Janeiro, São Paulo, and Porto Alegre. At Wave 3, EC users (those who used ECs daily, weekly, monthly, and less than monthly; total n=48) were asked why they started and reasons for using ECs. At Waves 2 and 3, smokers who had ever heard of ECs (N=392 at Wave 2; N=859 at Wave 3) were asked whether they thought ECs are more, less, or equally harmful as regular cigarettes. Results Among the 43 smokers who reported using ECs, the most common reasons for using e-cigarettes were: “using ECs is less harmful than smoking to other people” (69.3%), “out of curiosity” (59.4%), “they may not be as bad for your health” (59.0%), and “as a way to help you quit” (57.5%). Between 2012-13 and 2016-17, the percentage of smokers who “don't know” about the relative harmfulness of ECs decreased (41.6% to 28.0%; p< .001) and the percentage who believed that ECs are equally or more harmful than cigarettes increased (22.7% to 35.2%; p< .001). Conclusions Smokers using ECs most commonly use ECs to reduce harm to others, reduce harm to their own health, and to help them to quit smoking. More smokers now have an opinion about the relative harmfulness of ECs, and a greater percentage of smokers now incorrectly believe that ECs are equally or more harmful than cigarettes.

Background Research in high-income countries shows that exposure to point-of-sale (POS) product displays encourages youth smoking, promotes impulse purchasing, and undermines quitting, and that there is strong public support for POS advertising bans. Brazil banned tobacco advertising, promotion, and sponsorship (TAPS) in most channels in 2000 and POS advertising in 2014. However, public awareness of tobacco promotion remains high in Brazil compared to other countries, and POS product displays are still permitted.This study evaluated the impact of the 2014 Brazil POS advertising ban, and assessed public support for complete bans on in-store advertising and POS displays. Methods Data were from Waves 1-3 of the ITC Brazil Survey, a cohort survey of approximately 1200 adult smokers and 600 non-smokers residing in Rio de Janeiro, São Paulo, and Porto Alegre. Waves 1 and 2 were conducted before the 2014 POS advertising ban (2009 and 2012-13), and Wave 3 was conducted after the ban (2016-17). Data were analyzed using GEE logistic regression models. Results From 2009 (pre-ban) to 2016-17 (post-ban), noticing things that promote smoking decreased among smokers (42.3% to 34.4%, p< .01) and non-smokers (34.0% to 25.8%, p< .05). Following the 2014 POS advertising ban, 19.9% of smokers and 20.0% of non-smokers noticed signs/items with cigarette logos in stores; 61.3% of smokers and 58.5% of non-smokers noticed cigarette displays in stores. There was strong support for complete bans on in-store advertising (74.2% smokers, 87.8% non-smokers) and POS cigarette displays (71.9% smokers, 85.5% non-smokers); and generally no differences in support between cities. Conclusions TAPS bans in Brazil have reduced exposure to tobacco marketing, but POS advertising continues to be visible. These findings demonstrate that Brazil should implement a complete ban on in-store tobacco advertising, including POS displays, and that such a ban would be supported by the majority of smokers and non-smokers.

Background In 2000, Brazil implemented a comprehensive ban on tobacco advertising (except point-of-sale), promotion, and sponsorship, including sponsorship by tobacco brands of national sporting and arts events, then in 2005 adding international sport events. However, a loophole in the law permits company names for sponsorship. This study examines whether this loophole has been exploited by the industry via Brazilians' awareness of tobacco company sponsorship of sporting and arts events between 2009 and 2016-17. Methods Data were from Waves 1 to 3 (2009, 2012-13, 2016-17) of the International Tobacco Control (ITC) Brazil Survey - a cohort survey of approximately 1200 adult smokers and 600 non-smokers in Rio de Janeiro, São Paulo, and Porto Alegre. At all three waves, respondents were asked whether they had seen or heard about (1) sport or sporting events and/or (2) music, theatre, art or fashion events sponsored by or connected with cigarette companies. At Waves 2 and 3, tobacco company name recognition was tested by asking respondents whether the following are tobacco companies: Souza Cruz, Nestle, and Pirelle. Data were analyzed using GEE logistic regression models. Results Awareness of a sport or sporting event sponsored by a cigarette company decreased between 2009 and 2016-17 among both smokers (from 8.7% to 4.7%; p=0.004) and non-smokers (from 11.8% to 5.7%; p=0.008). Awareness of an arts event sponsored by a tobacco company decreased among smokers (from 6.3% to 1.4%; p< .001), but not significantly among non-smokers (from 6.1% to 3.8%; p=0.235). Over 93% of smokers and non-smokers correctly stated that Souza Cruz is a tobacco company and over 98% correctly stated that Nestle and Pirelle are not. Conclusions Although Brazil has not specifically banned tobacco company sponsorship, public awareness of tobacco company sponsorship has decreased over 7 years, possibly suggesting that the industry has not (yet) taken advantage of the loophole.

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Background: This study aims to evaluate the inter-rater reliability and perceived usability of a newly developed drug-related problem (DRP) classification system for use by pharmacists in the intermediate and long-term care (ILTC) setting in Singapore. Methods: This was a cross-sectional survey study involving the use of a self-administered questionnaire. All 55 pharmacists affiliated to the Pharmaceutical Society of Singapore (PSS) ILTC Pharmacists Workgroup who were above 21 years old and not authors of the classification system were invited to participate. The inter-rater reliability of participants’ classification of 46 mock DRP cases using the new DRP classification system was determined using Fleiss’s kappa (κ). Participants’ perceived usability of the classification system was evaluated using six items with five-point Likert scales (1—“strongly disagree”, 5—“strongly agree”). Results: Thirty-three pharmacists responded to the survey. Overall inter-rater reliability was found to be substantial (κ = 0.614; 95% CI: 0.611–0.617). All usability items received positive ratings (“strongly agree” or “agree”) from at least 69% of participants. Conclusion: The new DRP classification system has substantial external validity and appears to be suitable for use by pharmacists to document and report DRPs in the ILTC setting in Singapore and facilitate evaluation of the impact of pharmaceutical care in the ILTC setting.