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The Mexico City Prospective Study is a prospective cohort of more than 150,000 adults recruited two decades ago from the urban districts of Coyoacán and Iztapalapa in Mexico City1. Here we generated genotype and exome-sequencing data for all individuals and whole-genome sequencing data for 9,950 selected individuals. We describe high levels of relatedness and substantial heterogeneity in ancestry composition across individuals. Most sequenced individuals had admixed Indigenous American, European and African ancestry, with extensive admixture from Indigenous populations in central, southern and southeastern Mexico. Indigenous Mexican segments of the genome had lower levels of coding variation but an excess of homozygous loss-of-function variants compared with segments of African and European origin. We estimated ancestry-specific allele frequencies at 142 million genomic variants, with an effective sample size of 91,856 for Indigenous Mexican ancestry at exome variants, all available through a public browser. Using whole-genome sequencing, we developed an imputation reference panel that outperforms existing panels at common variants in individuals with high proportions of central, southern and southeastern Indigenous Mexican ancestry. Our work illustrates the value of genetic studies in diverse populations and provides foundational imputation and allele frequency resources for future genetic studies in Mexico and in the United States, where the Hispanic/Latino population is predominantly of Mexican descent.

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INTRODUCTION: Tobacco industry documents reveal companies' knowledge of a similar young adult market across countries in terms of attitudes and lifestyle aspirations. Some tobacco companies, therefore, use similar marketing approaches across different jurisdictions. We examined young adults' perceptions of flavored cigarette packs, including those containing flavor capsules, in Mexico and the Philippines. METHODS: We conducted a secondary analysis of five focus groups held in Mexico and four in the Philippines with young adults who smoke (aged 18-24 years), separated by gender, in which participants interacted with cigarette packs purchased locally. Transcribed and translated data were thematically analyzed and compared between countries. RESULTS: Three major themes were identified: 1) Flavor capsules cigarettes are recognizable via pack design through imagery on the pack that is understood to signify capsules; 2) Colors signal flavor and make the pack attractive; and 3) Young adults who smoke identify the target audience for these products as young people and those who are beginning to smoke. CONCLUSIONS: Young adults who smoke in Mexico and the Philippines interpreted flavored cigarette pack design similarly and thought that young people are the main audience for these products. This suggests a successful marketing approach creating shared perceptions of flavored cigarette packs in different world regions. It is likely that similar tactics are used in other countries around the world. Therefore, jurisdictions might use evidence from other jurisdictions to support the implementation of evidence-based tobacco control policies. These findings also support the implementation of plain and standardized packaging and flavor bans that would also limit product innovation such as capsules.

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OBJECTIVE: To assess the hypothesis that plexiform neurofibroma (PN) growth rates increase during puberty. STUDY DESIGN: PN growth rates before and during puberty were compared in a retrospective cohort of children with neurofibromatosis type 1 with puberty defined by Tanner staging. Of 33 potentially eligible patients, 25 had adequate quality magnetic resonance imaging for volumetric analysis and were included in ≥1 anchor cohort. Volumetric analysis was performed for all available imaging studies within the 4 years before and after puberty, and before and after 9- and 11-year-old anchor scans. Linear regression was performed to estimate the slope of change (PN growth rate); growth rates were compared with paired t test or Wilcoxon matched-pairs signed rank test. RESULTS: There were no significant difference in rates of PN growth in milliliters per month or milliliters per kilogram per month in the prepubertal vs pubertal periods (mean, 1.33 ± 1.67 vs 1.15 ± 1.38 [P = .139] and -0.003 ± 0.015 vs -0.002 ± 0.02 [P = .568]). Percent increases of PN volumes from baseline per month were significantly higher prepubertally (1.8% vs 0.84%; P = .041) and seemed to be related inversely to advancing age. CONCLUSIONS: Puberty and its associated hormonal changes do not seem to influence PN growth rate. These findings support those previously reported, but from a typical population of children with neurofibromatosis type 1 with puberty confirmed by Tanner staging.

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Despite increased attention and efforts to improve HIV care among female sex workers (FSWs), they continue to have suboptimal HIV outcomes. Exploring the socio-structural dynamics related to the quality of HIV care received by FSWs is critical to further strengthen interventions to improve their HIV care continuum outcomes. In this study, we conducted two rounds of qualitative in-depth interviews with 20 FSWs living with HIV in the Dominican Republic to explore how healthcare experiences contributed to their quality of HIV care. Data was analyzed using a thematic analytic approach exploring diverse structural and relational aspects of the quality of HIV care affecting FSWs as they navigate the clinic environment. Results indicated that quality of HIV care was influenced by both structural and relational factors within clinics. At the structural level, insufficient stock of antiretroviral therapy and the financial burden created by HIV care related costs hindered FSWs' satisfaction with their current HIV care and presented a barrier in FSWs' ability to access HIV care services. Quality of care was also closely linked to relational aspects of the HIV care environment, including FSWs' relationship and communication with their clinical providers, as FSWs often expressed their satisfaction with HIV care experiences based on these interpersonal factors. Lastly, personal agency emerged as an important factor contributing to the quality of HIV care, specifically as FSWs' treatment literacy resulted in greater advocacy and demands for quality care. Programmatic efforts should be directed to improving the quality of HIV care experiences of FSWs in the clinic environment. These include addressing resource shortages, promoting positive and effective patient-provider relationships, and facilitating HIV treatment education opportunities for FSWs.

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Exposure to tobacco marketing is positively associated with smoking initiation and behaviours. There is limited literature examining disparities among reported exposure in low- and middle-income countries. This study sought to fill this gap with a survey among 1427 adolescents and 889 adult smokers in Mexico City in 2020. Data were analysed using chi-square and hierarchical regression models. Two-thirds of adolescents noticed cigarette pack displays in stores. Participants from low- and mid-socioeconomic status (SES) neighbourhoods were more exposed to tobacco marketing than their counterparts through several channels. After addressing the shared variance among participants from the same household nested in neighbourhood SES level and controlling for gender, adolescent non-smokers and adult smokers who noticed pack displays were more likely to be susceptible to smoking (OR = 1.8, 95% CI 1.4-2.4) and to smoke more (OR = 1.7, 95% CI 1.21-2.47); adult smokers who noticed tobacco marketing at more places were less likely to be certain about smoking risks (OR = 0.9, 95% CI 0.8-0.9). The results suggest that the tobacco industry targets youth and individuals from low-SES neighbourhoods through several channels. Greater exposure to tobacco marketing was associated with increased susceptibility to smoking and decreased risk perception. These findings support a comprehensive ban on tobacco marketing in Mexico.

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BACKGROUND: Flavoured cigarettes are popular in Mexico. We examined how cigarette packaging design features used to communicate flavour influence perceptions of appeal, harm, perceived interest and pack preference among Mexico City residents. METHODS: We conducted an experimental survey. Participants aged 13-34 years were randomly assigned to one of three conditions, viewed packs with systematically manipulated design features (colour, capsule image and flavour name) and answered questions on appeal, perceived harm, perceived interest and pack preference. Data were analysed using mixed effects and conditional logistic regression. RESULTS: 1500 adolescents and 950 adults participated. Regardless of flavour, cigarette packs with a background colour and capsule image were more appealing to adolescents (OR=13.19, 95% CI 11.53 to 15.10; OR=1.68, 95% CI 1.45 to 1.88) and adults (OR=4.18, 95% CI 3.73 to 4.69; OR=1.66, 95% CI 1.49 to 1.85) than packs without. Among adolescents, 'Tropical Burst' named packs were more appealing (OR=1.43, 95% CI 1.20 to 1.72) than packs without a flavour name and among adults, 'Arctic Air' named packs were more appealing (OR=1.20, 95% CI 1.02 to 1.14). Adolescents and adults reported a preference for trying packs that displayed a flavour name, background colour or capsule image (b=0.104, b=0.702, b=1.316, p<0.001 and b=0.126, b=0.619, b=0.775, p<0.001). CONCLUSIONS: Colours and flavour capsule images appeal to adolescents and adults in Mexico. Mexico should consider adopting plain packaging to reduce appeal and interest.

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BACKGROUND: Straw cigarettes are hand-rolled tobacco in a corn straw, common in Brazil and believed to be less harmful by consumers. Traditionally consumed in rural areas and by men, a recent increase in use among young people in urban areas was observed. This study assessed marketing appeals of straw cigarette packaging in Brazil. METHODS: Following a systematic protocol, unique straw cigarette packs were purchased in 2013, 2016 and 2019 from three cities: Manaus, Salvador and São Paulo. Packs were double-coded for the absence/presence of marketing appeals (ie, luxury/quality, masculinity, classic/timeless, flavours and less harm). RESULTS: The number of unique straw cigarette packs purchased as part of the overall sample increased in the most recent collection: 2.3% (n=3), 1.3% (n=2) and 15.5% (n=27) in 2013, 2016 and 2019, respectively. Across the years, all packs presented luxury/quality elements (eg, images of crests); 93.8% (n=30) included the word 'artisanal'. Masculine appeal (eg, images of men) was present on 56.3% (n=18) of packs. Almost half had classic/timeless elements, including the words 'tradition'/'original'. In 2019, 59.3% (n=16) of the packs were flavoured compared with none in previous years. Over a quarter of all packs presented a less harm appeal (eg, 'smooth'). CONCLUSION: We identified an increase in availability of unique straw cigarette packs, strong branding and use of misleading descriptors on the packs. The adoption of plain packaging and the implementation of Brazil's additive ban could help to reduce the appeal of straw cigarettes and curb the current increase in use among youth.

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BACKGROUND: Despite evidence on peer navigation's association with positive HIV outcomes, such as engagement in HIV care and antiretroviral therapy (ART) initiation, the mechanisms through which peer navigation may influence these outcomes have been less explored. The purpose of this study is to describe the role of peer navigation and support on enhancing the quality of HIV treatment and care services experienced by female sex workers (FSWs). METHODS: Survey data was derived from a quantitative cohort (n = 211) of FSWs living with HIV in the Dominican Republic and complemented with data from two rounds of in-depth interviews (IDIs) from a qualitative subsample (n = 20 per round). Descriptive statistics and multivariable logistic regressions were used to explore the association between peer navigation and relational aspects of care and overall satisfaction of the quality of HIV treatment and care. Thematic analysis was employed to code and synthesize textual data from IDIs. RESULTS: 41.2% of the participants reported having had contact with a peer navigator in the last 6 months. Qualitative data revealed that peer navigation and support was instrumental in assisting FSWs linkage to HIV care after diagnosis, elevating FSWs' ability to access more comprehensive clinical care facilities, and promoting agency by improving FSWs' skills to more strategically and effectively engage with the clinic environment and health care providers. Peer navigation was positively associated with experiencing more respectful treatment by clinic staff (AOR: 6.65, 95% CI: 2.32-19.02), and greater satisfaction with overall HIV care services (AOR: 2.57, 95% CI: 1.77-3.74). CONCLUSION: Promoting the full integration of peer navigation into healthcare structures is a strategic approach to enhance the quality of HIV care experienced by FSWs and improve their HIV-related outcomes.

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BACKGROUND: NVX-CoV2373 is an adjuvanted, recombinant spike protein nanoparticle vaccine that was shown to have clinical efficacy for the prevention of coronavirus disease 2019 (Covid-19) in phase 2b-3 trials in the United Kingdom and South Africa, but its efficacy had not yet been tested in North America. METHODS: We conducted a phase 3, randomized, observer-blinded, placebo-controlled trial in the United States and Mexico during the first half of 2021 to evaluate the efficacy and safety of NVX-CoV2373 in adults (≥18 years of age) who had not had severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Participants were randomly assigned in a 2:1 ratio to receive two doses of NVX-CoV2373 or placebo 21 days apart. The primary objective was to determine vaccine efficacy against reverse-transcriptase-polymerase-chain-reaction-confirmed Covid-19 occurring at least 7 days after the second dose. Vaccine efficacy against moderate-to-severe disease and against different variants was also assessed. RESULTS: Of the 29,949 participants who underwent randomization between December 27, 2020, and February 18, 2021, a total of 29,582 (median age, 47 years; 12.6% ≥65 years of age) received at least one dose: 19,714 received vaccine and 9868 placebo. Over a period of 3 months, 77 cases of Covid-19 were noted - 14 among vaccine recipients and 63 among placebo recipients (vaccine efficacy, 90.4%; 95% confidence interval [CI], 82.9 to 94.6; P<0.001). Ten moderate and 4 severe cases occurred, all in placebo recipients, yielding vaccine efficacy against moderate-to-severe disease of 100% (95% CI, 87.0 to 100). Most sequenced viral genomes (48 of 61, 79%) were variants of concern or interest - largely B.1.1.7 (alpha) (31 of the 35 genomes for variants of concern, 89%). Vaccine efficacy against any variant of concern or interest was 92.6% (95% CI, 83.6 to 96.7). Reactogenicity was mostly mild to moderate and transient but was more frequent among NVX-CoV2373 recipients than among placebo recipients and was more frequent after the second dose than after the first dose. CONCLUSIONS: NVX-CoV2373 was safe and effective for the prevention of Covid-19. Most breakthrough cases were caused by contemporary variant strains. (Funded by Novavax and others; PREVENT-19 ClinicalTrials.gov number, NCT04611802.).

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Objectives: Cigarette packs are relevant to branding strategies, designed to appeal to specific groups. There is little research on how pack features increase product appeal among key constituents such as youth in low- and middle-income countries. Methods: We conducted 10 focus group discussions (FGDs) with adolescents and 5 FGDs with young adult smokers in Mexico City, separated by age, gender, smoking, and socioeconomic status. Participants separated 23 cigarette packs into "appealing" and "unappealing" groups, and were asked to explain their decisions, describing the features that supported their views. FGDs were video-recorded, transcribed in Spanish, translated into English, and subjected to thematic analysis. Results: Pack groupings did not differ greatly across FGDs; bold, contrasting colors and elements communicating flavor and promotion increased cigarette pack appeal and desire to try. Participants perceived packs with these features to be used by and designed for youth, like themselves. Conclusion: Our findings reinforce the importance of packaging design in attracting new consumers and maintaining current ones. Mexico should consider stronger tobacco advertising policies that include packaging color and depiction of flavor to reduce product appeal.

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OBJECTIVES: We developed a tool, Serial Neurologic Assessment in Pediatrics, to screen for neurologic changes in patients, including those who are intubated, are sedated, and/or have developmental disabilities. Our aims were to: 1) determine protocol adherence when performing Serial Neurologic Assessment in Pediatrics, 2) determine the interrater reliability between nurses, and 3) assess the feasibility and acceptability of using Serial Neurologic Assessment in Pediatrics compared with the Glasgow Coma Scale. DESIGN: Mixed-methods, observational cohort. SETTING: Pediatric and neonatal ICUs. SUBJECTS: Critical care nurses and patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Serial Neurologic Assessment in Pediatrics assesses Mental Status, Cranial Nerves, Communication, and Motor Function, with scales for children less than 6 months, greater than or equal to 6 months to less than 2 years, and greater than or equal to 2 years old. We assessed protocol adherence with standardized observations. We assessed the interrater reliability of independent Serial Neurologic Assessment in Pediatrics assessments between pairs of trained nurses by percent- and bias- adjusted kappa and percent agreement. Semistructured interviews with nurses evaluated acceptability and feasibility after nurses used Serial Neurologic Assessment in Pediatrics concurrently with Glasgow Coma Scale during routine care. Ninety-eight percent of nurses (43/44) had 100% protocol adherence on the standardized checklist. Forty-three nurses performed 387 paired Serial Neurologic Assessment in Pediatrics assessments (149 < 6 mo; 91 ≥ 6 mo to < 2 yr, and 147 ≥ 2 yr) on 299 patients. Interrater reliability was substantial to near-perfect across all components for each age-based Serial Neurologic Assessment in Pediatrics scale. Percent agreement was independent of developmental disabilities for all Serial Neurologic Assessment in Pediatrics components except Mental Status and lower extremity Motor Function for patients deemed "Able to Participate" with the assessment. Nurses reported that they felt Serial Neurologic Assessment in Pediatrics, compared with Glasgow Coma Scale, was easier to use and clearer in describing the neurologic status of patients who were intubated, were sedated, and/or had developmental disabilities. About 92% of nurses preferred to use Serial Neurologic Assessment in Pediatrics over Glasgow Coma Scale. CONCLUSIONS: When used by critical care nurses, Serial Neurologic Assessment in Pediatrics has excellent protocol adherence, substantial to near-perfect interrater reliability, and is feasible to implement. Further work will determine the sensitivity and specificity for detecting clinically meaningful neurologic decline.

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BACKGROUND: Resuscitation with crystalloid fluid is a cornerstone of pediatric septic shock treatment. However, the optimal type of crystalloid fluid is unknown. We aimed to determine the feasibility of conducting a pragmatic randomized trial to compare balanced (lactated Ringer's [LR]) with 0.9% normal saline (NS) fluid resuscitation in children with suspected septic shock. METHODS: Open-label pragmatic randomized controlled trial at a single academic children's hospital from January to August 2018. Eligible patients were >6 months to <18 years old who were treated in the emergency department for suspected septic shock, operationalized as blood culture, parenteral antibiotics, and fluid resuscitation for abnormal perfusion. Screening, enrollment, and randomization were carried out by the clinical team as part of routine care. Patients were randomized to receive either LR or NS for up to 48 hours following randomization. Other than fluid type, all treatment decisions were at the clinical team's discretion. Feasibility outcomes included proportion of eligible patients enrolled, acceptability of enrollment via the U.S. federal exception from informed consent (EFIC) regulations, and adherence to randomized study fluid administration. RESULTS: Of 59 eligible patients, 50 (85%) were enrolled and randomized. Twenty-four were randomized to LR and 26 to NS. Only one (2%) of 44 patients enrolled using EFIC withdrew before study completion. Total median (interquartile range [IQR]) crystalloid fluid volume received during the intervention window was 107 (60 to 155) mL/kg and 98 (63 to 128) mL/kg in the LR and NS arms, respectively (p = 0.50). Patients randomized to LR received a median (IQR) of only 20% (13 to 32) of all study fluid as NS compared to 99% (64% to 100%) of study fluid as NS in the NS arm (absolute difference = 79%, 95% CI = 48% to 85%). CONCLUSIONS: A pragmatic study design proved feasible to study comparative effectiveness of LR versus NS fluid resuscitation for pediatric septic shock.

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OBJECTIVES: Estimate the inter-rater reliability of critical care nurses performing a pediatric modification of the Glasgow Coma Scale in a contemporary PICU. DESIGN: Prospective observation study. SETTING: Large academic PICU. PATIENTS/SUBJECTS: All 274 nurses with permanent assignments in the PICU were eligible to participate. A subset of 18 nurses were selected as study registered nurses. All PICU patients were eligible to participate. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: PICU nurses were educated and demonstrated proficiency on a pediatric modification of the Glasgow Coma Scale we created to make it more applicable to a diverse PICU population that included patients who are sedated, mechanically ventilated, and/or have developmental disabilities. Each study registered nurse observed a sample of nurses perform the Glasgow Coma Scale, and they independently scored the Glasgow Coma Scale. Patients were categorized as having developmental disabilities if their preillness Pediatric Cerebral Performance Category score was greater than or equal to 3. Fleiss' Kappa (κ), intraclass correlation coefficient, and percent agreement assessed inter-rater reliability for each Glasgow Coma Scale component (eye, verbal, motor) and age-specific scale (≥ 2 and < 2-yr-old). The overall percent agreement between study registered nurses and nurses was 89% for the eye, 91% for the verbal, and 79% for the motor responses. Inter-rater reliability ranged from good (intraclass correlation coefficient = 0.75) to excellent (intraclass correlation coefficient = 0.96) for testable patients. Agreement on the motor response was significantly lower for children with developmental disabilities (< 2 yr: 59% vs 95%; p = 0.0012 and ≥ 2 yr: 55% vs 91%; p = 0.0012). Agreement was significantly worse for intermediate range Glasgow Coma Scale motor responses compared with responses at the extremes (e.g., motor responses 2, 3, 4 vs 1, 5, 6; p < 0.05). CONCLUSIONS: A pediatric modification of the Glasgow Coma Scale performed by trained PICU nurses has excellent inter-rater reliability, although reliability was reduced in patients with developmental disabilities and for intermediate range Glasgow Coma Scale responses. Further research is needed to determine the effectiveness of this Glasgow Coma Scale modification to detect clinical deterioration.

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OBJECTIVES: Low- and middle-income countries (LMICs) are vital to the global tobacco market. The pack is key to cigarette branding, and review of cigarette packs revealed English as a common feature. The prevalence of English and its potential branding utility is explored. METHODS: Every available unique cigarette pack was purchased from diverse retailers in six LMICs where English is not the official language (Bangladesh, Brazil, China, Egypt, Ukraine, Vietnam). Packs' front panels were coded for English on pack fronts. English penetration was quantified by country and a comparison of English use between multinational and national brands was undertaken. A qualitative analysis of symbolic and utilitarian usage of English was conducted. RESULTS: Of 1303 unique cigarette packs analyzed, 67% (n = 876) included some English. English text conveyed product information and usage instruction. English was more prevalent for multinational brands. Qualitatively, English use frequently connected cigarettes with concepts of quality, style, luxury, and aspirational lifestyle. CONCLUSIONS: Restricting English use should be incorporated into plain packaging policy to protect populations from deceptive branding practices, specifically presenting cigarettes as an aspirational product.

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BACKGROUND/AIMS: To estimate and compare price differences between legal and illicit cigarettes in 14 low- and middle-income countries (LMIC). DESIGN: A cross-sectional census of all packs available on the market was purchased. SETTING: Cigarette packs were purchased in formal retail settings in three major cities in each of 14 LMIC: Bangladesh, Brazil, China, Egypt, India, Indonesia, Mexico, Pakistan, the Philippines, Russia, Thailand, Turkey, Ukraine and Vietnam. PARTICIPANTS: A total of 3240 packs were purchased (range = 58 packs in Egypt to 505 in Russia). Packs were categorized as 'legal' or 'illicit' based on the presence of a health warning label from the country of purchase and existence of a tax stamp; 2468 legal and 772 illicit packs were in the analysis. MEASUREMENTS: Descriptive statistics stratified by country, city and neighborhood socio-economic status were used to explore the association between price and legal status of cigarettes. FINDINGS: The number of illicit cigarettes in the sample setting was small (n < 5) in five countries (Brazil, Egypt, Indonesia, Mexico, Russia) and excluded from analysis. In the remaining nine countries, the median purchase price of legal cigarettes ranged from US$0.32 in Pakistan (n = 72) to US$3.24 in Turkey (n = 242); median purchase price of illicit cigarettes ranged from US$0.80 in Ukraine (n = 14) to US$3.08 in India (n = 41). The difference in median price between legal and illicit packs as a percentage of the price of legal packs ranged from 32% in Philippines to 455% in Bangladesh. Median purchase price of illicit cigarette packs was higher than that of legal cigarette packs in six countries (Bangladesh, India, Pakistan, Philippines, Thailand, Vietnam). Median purchase price of illicit packs was lower than that of legal packs in Turkey, Ukraine and China. CONCLUSIONS: The median purchase price of illicit cigarettes is higher than that of legal cigarette packs in Bangladesh, India, Pakistan, Philippines, Thailand, and Vietnam, Brazil, Egypt, Indonesia, Mexico, Russia appear to have few or no illicit cigarettes for purchase from formal, urban retailers.

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BACKGROUND: Trauma is a leading cause of death and represents a major problem in developing countries where access to good quality emergency care is limited. Médecins Sans Frontières delivered a standard package of care in two trauma emergency departments (EDs) in different violence settings: Kunduz, Afghanistan, and Tabarre, Haiti. This study aims to assess whether this standard package resulted in similar performance in these very different contexts. METHODS: A cross-sectional study using routine programme data, comparing patient characteristics and outcomes in two EDs over the course of 2014. RESULTS: 31 158 patients presented to the EDs: 22 076 in Kunduz and 9082 in Tabarre. Patient characteristics, such as delay in presentation (29.6% over 24 h in Kunduz, compared to 8.4% in Tabarre), triage score, and morbidity pattern differed significantly between settings. Nevertheless, both EDs showed an excellent performance, demonstrating low proportions of mortality (0.1% for both settings) and left without being seen (1.3% for both settings), and acceptable triage performance. Physicians' maximum working capacity was exceeded in both centres, and mainly during rush hours. CONCLUSIONS: This study supports for the first time the plausibility of using the same ED package in different settings. Mapping of patient attendance is essential for planning of human resources needs.

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