Suchergebnisse

Background: The greatest risk factor for cardiovascular disease is hypertension, which can be alleviated via diet, exercise, and adherence to medication. Yet, blood pressure control in Nepal is inadequate, which is partly hindered by a lack of evidence-based, low-cost, scalable, and cost-effective cardiovascular disease prevention programmes. The the community-based management of hypertension in Nepal (COBIN) study was a 12-month community-based hypertension management programme of blood pressure monitoring and lifestyle counselling intervention undertaken by female community health volunteers (FCHVs) in Nepal, against usual care, which showed success in reducing blood pressure. Here we aimed to retrospectively quantify the budget impact and cost-effectiveness of the scale-up of the programme. Methods: In this retrospective analysis, we collected participant-level data from the COBIN study; programme delivery cost data from programme administrators from the COBIN study group; and popualtion and other data from WHO, the World Bank, and the Nepalese Government. We estimated costs per participant and total costs of a national scale-up of the COBIN programme focusing on two scenarios: scenario A, delivery of the intervention to only people aged 25–65 years with hypertension; and scenario B, delivery of the intervention to all adults aged 25–65 years regardless of hypertension status. Effectiveness was based on in-trial blood pressure reductions converted to cardiovascular disease disability-adjusted life-years (DALYs) averted. The primary cost-effectiveness measure was incremental cost per averted cardiovascular disease DALY (calculated using the incremental cost-effectiveness ratio [ICER]) from a health system perspective, including programme delivery and incremental medication costs. We did univariate sensitivity analyses of scenario B to assess the effect of uncertainty in key parameter values in our calculations. Findings: From a health system perspective, the first-year budget impact was US$7·1 million in scenario A and $10·8 million in scenario B. With each subsequent year, the costs decreased by approximately 50%. In the base-case cost-effectiveness analysis, from the health system perspective, scenario A resulted in an ICER of $582 per DALY averted and scenario B resulted in an ICER of $411 per DALY averted. The ICER was most sensitive to uncertainty in the number of total avertable cardiovascular disease DALYs in the eligible population. Interpretation: The programme is projected to be highly cost-effective in both scenarios compared with the WHO thresholds for cost-effectiveness for Nepal. For policy makers intending to meet the UN Sustainable Development Goal of reducing premature mortality from non-communicible diseases, this intervention should be considered. Funding: Duke-NUS Medical School, Singapore.

PharmD ; Leukaemia accounts for the highest age-standardised mortality rate among haematological malignancies in Europe. Evidence of efficacy for antineoplastic agents may be valued differently by regulatory and health technology assessment (HTA) bodies in the European Union (EU), impacting decision-making and access to novel medicines. The aims of the study were to analyse the evolvement of efficacy parameters studied in leukaemia clinical trials (CTs), to explore scientific expert opinions on evidence generated and clinical assessments for antineoplastic therapies and to determine core efficacy outcomes prioritised by EU decision-makers for leukaemia CTs. Part I data collection on trends in efficacy parameters involved the following: (1) Phase II to Phase IV leukaemia CTs were identified from the EU Clinical Trials Register database throughout an 11-year period (2007-2017), (2) CTs were screened against inclusion criteria, (3) efficacy endpoints were extracted and grouped according to type of measurement, (4) data mining of trends was performed using descriptive and inferential statistics. Part II data collection exploring scientific expert opinions consisted of these steps: (1) the Response Evaluation in Leukaemia (ReVALeu) surveying tool was developed and tested for validity and reliability, (2) the tool was disseminated in an e-Delphi process with two independent panels composed of regulatory and HTA oncology experts, (3) core efficacy outcomes reaching consensus were determined. Thirty-six unique efficacy endpoints were identified from the final dataset of CTs (N=431) and grouped into clusters of survival (n=5), time-to-event (n=6), response rates and biomarkers (n=16) and other (n=9). Complete response rate was the most studied primary endpoint (CTs: 19%, n=81), with progression-free survival (PFS) and minimal residual disease (MRD) registering the highest frequency change pre- and post-2012 (PFS: 8%, p=0.01; MRD: 8%, p=0.003). Thirty-six panellists were recruited in the eDelphi; 24 regulatory representatives from the European Medicines Agency (EMA) and 12 experts from HTA bodies in 9 EU countries. Opinions on the quality of pre- and post-authorisation evidence generated for antineoplastic agents were statistically different (pre-authorisation: p=0.01, post-authorisation: p=0.04). Six efficacy endpoints achieving consensus were common to both regulatory and HTA groups of decisionmakers and identified as the core outcomes. Biomarker-based endpoints are emerging as primary efficacy measures in leukaemia CTs. Decision-makers perceive the quality of evidence generated for antineoplastic therapy differently. The identification of core efficacy outcomes may potentially optimise CT data packages for regulatory and reimbursement approvals. ; N/A

Solvency II (European Parliament Directive 2009/138/EC) establishes the criteria and the quantitative and qualitative standards that insurance companies operating in the European Union must undertake to ensure their solvency and financial stability. Solvency II is structured in three pillars and covers, through a modular scheme, the various risks to which an insurer is exposed. This paper focuses on some of the life business modules and studies the Solvency Capital Requirement (SCR) for three types of insurances: endowment policy, whole life insurance and immediate renters insurance. In particular, the work analyzes, within the standard model, the calculus of the capital requirement for the mortality and longevity sub-modules and presents a very simple tool that, given the life table, simplifies SCR operations for any single policy of these sub-modules. The analysis shows how the SCR for a portfolio may be predicted through a linear function by grouping policies by age and/or timing. Contrary to what would be expected from the law of large numbers, relative capital requirements do not decrease with the size of the portfolio. ; Solvencia II (Directiva parlamentaria europea 2009/138/EC) establece los criterios y normas de carácter cuantitativo y cualitativo que las entidades aseguradoras que operan en la Unión Europea deben acometer para garantizar su solvencia y estabilidad financiera. Solvencia II está estructurada en tres pilares y abarca, a través de un esquema modular, los distintos riesgos a los que está expuesta una entidad aseguradora. Este trabajo se centra en algunos de los submódulos del negocio de vida y estudia el Solvency Capital Requirement (SCR) para tres tipos de seguros: seguro de capital diferido, seguro de vida entera y seguro de renta inmediata. En concreto, analiza dentro del modelo estándar el cálculo del requerimiento de capital en los submódulos del riesgo de mortalidad y de longevidad y presenta una herramienta de cálculo muy sencilla para, prefijada la tabla de mortalidad, simplificar al máximo el cálculo del SCR de cualquier cartera de asegurados de estos submódulos. Se muestra cómo agrupando el total de pólizas de una cartera por edad del asegurado y/o temporalidad puede predecirse el capital requerido de solvencia para una cartera y un riesgo determinado a través de una función lineal. Al contrario de lo que cabría esperar por la ley de los grandes números, los requerimientos relativos de capital no decrecen con el tamaño de la cartera.

Background: Government policies can strongly influence migrants' health. Using a Health in All Policies approach, we systematically reviewed evidence on the impact of public policies outside of the health-care system on migrant health. Methods: We searched the PubMed, Embase, and Web of Science databases from Jan 1, 2000, to Sept 1, 2017, for quantitative studies comparing the health effects of non-health-targeted public policies on migrants with those on a relevant comparison population. We searched for articles written in English, Swedish, Danish, Norwegian, Finnish, French, Spanish, or Portuguese. Qualitative studies and grey literature were excluded. We evaluated policy effects by migration stage (entry, integration, and exit) and by health outcome using narrative synthesis (all included studies) and random-effects meta-analysis (all studies whose results were amenable to statistical pooling). We summarised meta-analysis outcomes as standardised mean difference (SMD, 95% CI) or odds ratio (OR, 95% CI). To assess certainty, we created tables containing a summary of the findings according to the Grading of Recommendations Assessment, Development, and Evaluation. Our study was registered with PROSPERO, number CRD42017076104. Findings: We identified 43 243 potentially eligible records. 46 articles were narratively synthesised and 19 contributed to the meta-analysis. All studies were published in high-income countries and examined policies of entry (nine articles) and integration (37 articles). Restrictive entry policies (eg, temporary visa status, detention) were associated with poor mental health (SMD 0·44, 95% CI 0·13–0·75; I2=92·1%). In the integration phase, restrictive policies in general, and specifically regarding welfare eligibility and documentation requirements, were found to increase odds of poor self-rated health (OR 1·67, 95% CI 1·35–1·98; I2=82·0%) and mortality (1·38, 1·10–1·65; I2=98·9%). Restricted eligibility for welfare support decreased the odds of general health-care service use (0·92, 0·85–0·98; I2=0·0%), but did not reduce public health insurance coverage (0·89, 0·71–1·07; I2=99·4%), nor markedly affect proportions of people without health insurance (1·06, 0·90–1·21; I2=54·9%). Interpretation: Restrictive entry and integration policies are linked to poor migrant health outcomes in high-income countries. Efforts to improve the health of migrants would benefit from adopting a Health in All Policies perspective.

Objectives
Prevalence, and associated morbidity and mortality of chronic sleep disorders have been limited to small cohort studies, however, administrative data may be used to provide representation of larger population estimates of disease. With no guidelines to inform the identification of cases of sleep disorders in administrative data, the objective of this study was to develop and validate a set of ICD-codes used to define sleep disorders including narcolepsy, insomnia, and obstructive sleep apnea (OSA) in administrative data.
Methods
A cohort of adult patients, with medical records reviewed by two independent board-certified sleep physicians from a sleep clinic in Calgary, Alberta between January 1, 2009 and December 31, 2011, was used as the reference standard. We developed a general ICD-coded case definition for sleep disorders which included conditions of narcolepsy, insomnia, and OSA using: 1) physician claims data, 2) inpatient visit data, 3) emergency department (ED) and ambulatory care data. We linked the reference standard data and administrative data to examine the validity of different case definitions, calculating estimates of sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV).
Results
From a total of 1186 patients from the sleep clinic, 1045 (88.1%) were classified as sleep disorder positive, with 606 (51.1%) diagnosed with OSA, 407 (34.4%) with insomnia, and 59 (5.0%) with narcolepsy. The most frequently used ICD-9 codes were general codes of 307.4 (Nonorganic sleep disorder, unspecified), 780.5 (unspecified sleep disturbance) and ICD-10 codes of G47.8 (other sleep disorders), G47.9 (sleep disorder, unspecified). The best definition for identifying a sleep disorder was an ICD code (from physician claims) 2 years prior and 1 year post sleep clinic visit: sensitivity 79.2%, specificity 28.4%, PPV 89.1%, and NPV 15.6%. ICD codes from ED/ambulatory care data provided similar diagnostic performance when at least 2 codes appeared in a time period of 2 years prior and 1 year post sleep clinic visit: sensitivity 71.9%, specificity 54.6%, PPV 92.1%, and NPV 20.8%. The inpatient data yielded poor results in all tested ICD code combinations.
Conclusion
Sleep disorders in administrative data can be identified mainly through physician claims data and with some being determined through outpatient/ambulatory care data ICD codes, however these are poorly coded within inpatient data sources. This may be a function of how sleep disorders are diagnosed and/or reported by physicians in inpatient and outpatient settings within medical records. Future work to optimize administrative data case definitions through data linkage are needed.

Background: We aimed to estimate socioeconomic disparities in the incidence of hospitalisation for first-ever stroke, quality of care, and post-stroke survival for the adult population of England. Methods In this cohort study, we obtained data collected by a nationwide register on patients aged 18 years or older hospitalised for first-ever acute ischaemic stroke or primary intracerebral haemorrhage in England from July 1, 2013, to March 31, 2016. We classified socioeconomic status at the level of Lower Super Output Areas using the Index of Multiple Deprivation, a neighbourhood measure of deprivation. Multivariable models were fitted to estimate the incidence of hospitalisation for first stroke (negative binomial), quality of care using 12 quality metrics (multilevel logistic), and all-cause 1 year case fatality (Cox proportional hazards). Findings Of the 43·8 million adults in England, 145 324 were admitted to hospital with their first-ever stroke: 126 640 (87%) with ischaemic stroke, 17 233 (12%) with intracerebral haemorrhage, and 1451 (1%) with undetermined stroke type. We observed a socioeconomic gradient in the incidence of hospitalisation for ischaemic stroke (adjusted incidence rate ratio 2·0, 95% CI 1·7–2·3 for the most vs least deprived deciles) and intracerebral haemorrhage (1·6, 1·3–1·9). Patients from the lowest socioeconomic groups had first stroke a median of 7 years earlier than those from the highest (p<0·0001), and had a higher prevalence of pre-stroke disability and diabetes. Patients from lower socioeconomic groups were less likely to receive five of 12 care processes but were more likely to receive early supported discharge (adjusted odds ratio 1·14, 95% CI 1·07–1·22). Low socioeconomic status was associated with a 26% higher adjusted risk of 1-year mortality (adjusted hazard ratio 1·26, 95% CI 1·20–1·33, for highest vs lowest deprivation decile), but this gradient was largely attenuated after adjustment for the presence of pre-stroke diabetes, hypertension, and atrial fibrillation (1·11, 1·05–1·17). Interpretation Wide socioeconomic disparities exist in the burden of ischaemic stroke and intracerebral haemorrhage in England, most notably in stroke hospitalisation risk and case fatality and, to a lesser extent, in the quality of health care. Reducing these disparities requires interventions to improve the quality of acute stroke care and address disparities in cardiovascular risk factors present before stroke. Funding NHS England and the Welsh Government.

International audience ; Lao People Democratic Republic (PDR; Laos), a landlocked country in Southeast Asia, has made important progress in reducing malaria morbidity and mortality in the past 5-6 years, and the northern provinces have very low reported incidence. To support national progress towards elimination, it is critical to verify and understand these changes in disease burden. Methods: A two-stage cluster cross-sectional survey was conducted in four districts within four northern provinces (Khua, Phongsaly Province; Paktha, Bokeo Province; Nambak, Luang Prabang, and Muang Et, Huaphanh Province). During September and October 2016, demographics and malaria risk factors were collected from a total of 1492 households. A total of 5085 persons consented to collection of blood samples for testing, by rapid diagnostic test (RDT) and polymerase chain reaction (PCR)-based testing. Risk factors for infection were examined using logistic regression; and a randomized subset of males was tested for glucose-6-phosphate dehydrogenase (G6PD) deficiencies using a combined PCR and sequencing approach.Results: There were zero positives by RDT, and PCR detected Plasmodium infections in 39 (0.77%; 95% CI 0.40-1.47%) of 5082 analysable samples. The species distribution was Plasmodium vivax (28 total); Plasmodium falciparum/P. vivax (5); P. falciparum (3), Plasmodium malariae (2), and P. vivax/P. malariae (1). In multivariable analysis, the main risk factors included having any other cases within the household [aOR 12.83 (95% CI 4.40 to 37.38), p < 0.001]; and lack of bed net ownership within the household [aOR 10.91 (95% 5.42-21.94), p < 0.001]; age, sex and forest-travel were not associated with parasitaemia. A total of 910 males were tested for the six most common G6PDd in SE Asia; and 30 (3.3%; 95% CI 2.1-5.1%) had a G6PD variant allele associated with G6PD deficiency, with the majority being the Union (14) and Viangchan (11) polymorphisms, with smaller numbers of Canton and Mahidol.Conclusion: This is the first rigorous PCR-based population survey for malaria infection in Northern Lao PDR, and found a very low prevalence of asymptomatic Plasmodium infections by standard PCR methods, with P. vivax predominating in the surveyed districts. Clustering of cases within households, and lack of a bed nets suggest reactive case detection, and scale-up of coverage should be prioritized. The predominance of infections with P. vivax, combined with moderate levels of serious G6PD deficiencies highlight the need for careful rollout of primaquine towards elimination goals.

The Nigerian economy remains dependent on the small oil sector (under 10 percent of GDP) for the bulk of its fiscal revenues and foreign exchange earnings. This makes Nigeria's balance of payments and government budgets vulnerable to volatilities in oil prices. Indeed, growth and investment in Nigeria have been negatively impacted by repeated oil-price driven boom-bust cycles. The oil price shock of late 2014 and its aftermath pushed the economy into recession and precipitated a major budgetary crisis at the national and state levels which brought to light the longer-term trend of weak domestic revenue mobilization. Nigeria's weak revenue mobilization has major implications for growth and development, including for improving its dire social service delivery outcomes. Thus, the country needs to take concrete steps to break its oil dependency to improve its economic and social outcomes. Oil revenues are recovering with increasing oil prices, but distributions to the tiers of government are constrained by the unbudgeted fuel subsidy and other deductions. The fuel subsidy, no longer an explicit first line deduction from oil revenues, mostly benefits the affluent and it is also widely-known that a portion of Nigeria's imported petrol is smuggled out to neighboring countries where petrol is more expensive. The constrained net oil revenues, combined with non-oil revenues that are constrained by limited tax policy reforms and are thus stagnated (relative to GDP), limit overall revenue realization, thus constraining budget execution and the build-up of fiscal buffers. The growth in the public debt stock between the first half of 2017 and the first half of 2018 was mainly attributable to the increased Eurobond issuances, some of which were used to liquidate costlier domestic short-term debt. The Nigeria Economic Recovery and Growth Plan (ERGP) 2017-2020 aims to achieve macroeconomic stability and economic diversification and there is thus the need to accelerate its implementation progress. The special focus topic for this report is on human capital development in Nigeria. Studies show that between 10 and 30 percent of the differences in per capita income between countries can be attributed to human capital. The economic burden of malaria alone in Nigeria, accounting for direct and indirect costs excluding mortality, is estimated at 13.5 percent of GDP. However, in the quest for sustainable growth, Nigeria, like many other countries, has underinvested in human capital. While physical capital remains critical, it does not fully account for improvements in growth.

The gut microbiome metabolizes choline and carnitine to release trimethylamine (TMA), which subsequently undergoes hepatic conversion to trimethylamine N-oxide (TMAO). Elevated TMAO levels are associated with cardiovascular disease and all-cause mortality risk. Dietary flavanols modulate the composition and function of the gut microbiome. Therefore, the possibility exists that these compounds could reduce intestinal TMA production and lower circulating TMAO. However, this hypothesis has never been tested in humans. A secondary analysis was performed on blood samples from a clinical study in which obese subjects at risk for insulin resistance consumed tea or cocoa flavanols in a randomized crossover design while consuming a controlled diet. These subjects generally had elevated TMAO levels (approximate to 5 M) compared to levels previously measured in healthy subjects (approximate to 1 M). None of the interventions significantly altered TMAO levels. Individual variability for choline and carnitine was relatively low. However, TMAO exhibited somewhat greater inter-individual variability. No differences in mean TMAO concentrations observed across interventions were seen based on separating subjects by glycemic status, body mass index (BMI), race, age, or gender. However, subject minimum and maximum values observed across the interventions appeared to be more strongly associated with glycemic status and age than mean values across interventions, suggesting that average TMAO values over time may be less useful than maximum or minimum values as markers of disease risk. Traditional physiological characteristics do not appear to predict TMAO responsiveness to flavanol interventions. However, African-American subjects appeared less responsive compared to non-Hispanic white subjects for both green tea and high cocoa treatments, and female subjects appeared less responsive than males for the high cocoa treatment. The present results suggest that a short-term flavanol intervention does not generally reduce fasting TMAO levels in subjects with elevated circulating TMAO. ; Virginia Agricultural Experiment Station; Hatch Program of the National Institute of Food and Agriculture, U.S. Department of Agriculture; U.S. Department of AgricultureUnited States Department of Agriculture (USDA); Virginia Tech Translational Obesity Research Interdisciplinary Graduate Education program (TOR IGEP) ; Funding for the present work was provided, in part, by the Virginia Agricultural Experiment Station and the Hatch Program of the National Institute of Food and Agriculture, U.S. Department of Agriculture (APN, KPD). Funding for the original study was provided by the U.S. Department of Agriculture (DJB, JAN). Funding for LEG was provided by the Virginia Tech Translational Obesity Research Interdisciplinary Graduate Education program (TOR IGEP). ; Public domain authored by a U.S. government employee

The severity of the acute form of CSF is responsible for the high mortality rate and has been the subject of many studies. Nevertheless, some animals are likely to develop a mild, chronic, or unapparent form of the disease. Paradoxically, this clinical form of the disease has not been well studied, especially regarding its pathogenesis. In this study, we investigated the infection in domestic pigs that is caused by the CSFV Cat01 strain, which is responsible for the 2001-2002 CSFV outbreak in Catalonia, Spain, and which caused mild and nonspecific clinical signs compared to the infection that is caused by another CSFV strain that is responsible for inducing severe clinical symptoms of disease. We assessed the impact of the CSFV infection in the immune system of domestic pigs, mainly on the kinetics of different cytokines, such as IFN-α (innate immunity) and IFN-γ (adaptive immune response), during the first weeks after infection. In addition, we evaluated the impact on the induction of the humoral response and its relation to the course of infection and the RNA CSFV viral load. The IFN-α levels in the serum samples from the pigs that developed a milder form of the CSF disease (infected with Cat01 strain) were lower than those that were detected in the pig with severe clinical CSF signs (Margarita strain). After infection with Cat01 strain, the IFN-γ levels in response to CSFV were detected in addition to the humoral response. Interestingly, in the serum samples of these animals, we detected the lowest load of CSFV RNA. Similarly, the lowest viral load levels were detected in the tonsils of these pigs. Both the T cells and the humoral response that were generated in most of the pigs that were infected with strain Cat01 may be related to the protection in the symptom progression of CSF against this viral strain. These results explain the antiviral role of IFN-γ in the absence of an antibody response. Likewise, these results corroborate the relevance and relationship that exists between the intensity of the T cell response and the protection against CSFV replication. Additionally, these results also explain how the failure to induce optimal levels of humoral and cellular responses after CSFV infection promotes the spread and persistence of the virus. ; We thank Iván Cordón and David Solanes for their help in theanimal facilities. This research was supported by grant AGL2012-38343 from the Spanish Government.

Antimicrobial resistance (AMR) is emerging and is a threat for human and animal health. This increasing resistance results into treatment failures and increased mortality in humans and animals. If there is no action to reduce antimicrobial use (AMU), it is forecasted that the number of people dying due to AMR will increase considerably in the near future. AMU in animals poses a potential risk for public health as it contributes to the selection and spread of AMR which can disseminate to humans. Therefore, at global level WHO, FAO and OIE combined efforts in a such called One Health approach to minimize the public health impact of AMR associated with AMU in farm animals. The Global Action Plan on antimicrobial resistance (GAP) has been adopted by the World Health Assembly in 2015. This plan contains five strategic objectives. WHO urged all member states to develop a National Action Plan in line with the five objectives of the GAP, and with a One Health approach. Indonesia has submitted the National Action Plan on Antimicrobial Resistance 2017-2019 in the Library of National Action Plans of WHO.Although it is not clear to what level AMU in animal production contributes to the AMR problem humans, there is a worldwide urge to reduce AMU in animal production to a minimum to protect human health. The basis of this so-called 'antimicrobial stewardship' is focusing on (preventive) measures which enable animals to remain healthy and thus take away the need for antimicrobial treatment. Another pillar of stewardship is limiting and strictly regulating the use of so-called ''critically important antimicrobials for human medicine'', like fluoroquinolones. It can be difficult to change AMU practices which have become habits for farmers and veterinarians; therefore specific triggers are required. In the Netherlands the total therapeutic AMU (in mass sold) in farm animals doubled between 1990 and 2007; parallel to the EU-ban of antimicrobial growth promotors which were completely phased out by 2006. From 2005 onwards, several events triggered a series of measures and initiatives to reduce AMU in livestock with almost 70%. This reduction was followed by reduced AMR levels in livestock. Some key success factors were: clear reduction targets defined by the government, having full transparency on antimicrobial prescription and usage, the existence of a surveillance system for AMR, and a close collaboration of all stakeholders and a shared goal. Although specific contexts differ between countries and production systems, tailored approaches taking into account specific contexts and stakeholders can be effective in responsible use of antimicrobials.

Note: This article was submitted to Gastrointestinal Cancers, a section of the journal Frontiers in Oncology. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. ; Gastrointestinal cancers, including oesophageal, gastric and colorectal cancers (CRC) have high rates of disease recurrence despite curative resection. There are a number of recent studies that have investigated the use of circulating tumor DNA (ctDNA) for prognostic value in these cancers. We reviewed studies that had been published prior to March 2018 that assessed the prognostic values of ctDNA in patients with oesophageal and gastric cancers, gastrointestinal stromal tumors (GIST) and CRC. We identified 63 eligible clinical studies that focussed on recurrence and survival. Studies assessed investigated various ctDNA biomarkers in patients with different stages of cancer undergoing surgical resection, chemotherapy and no treatment. For oesophageal squamous cell carcinoma and oesophageal adenocarcinoma, methylation of certain genes such as APC and DAPK have been highlighted as promising biomarkers for prognostication, but these studies are limited and more comprehensive research is needed. Studies focusing on gastric cancer patients showed that methylation of ctDNA in SOX17 and APC were independently associated with poor survival. Two studies demonstrated an association between ctDNA and recurrence and survival in GIST patients, but more studies are needed for this type of gastrointestinal cancer. A large proportion of the literature was on CRC which identified both somatic mutations and DNA methylation biomarkers to determine prognosis. ctDNA biomarkers that identified somatic mutations were more effective if they were personalized based on mutations found in the primary tumor tissue, but ctDNA methylation studies identified various biomarkers that predicted increased risk of recurrence, poor disease free survival and overall survival. While the use of non-invasive ctDNA biomarkers for prognosis is promising, larger studies are needed to validate the clinical utility for optimizing treatment and surveillance strategies to reduce mortality from gastrointestinal cancers. ; CK and GY are recipients of grant funding from Cancer Council SA's Beat Cancer Project on behalf of its donors and the State Government of South Australia through the Department of Health, and Flinders Foundation through the generous support of its donors.

Background: Necrotizing soft tissue infections (NSTI) are severe skin infections and form a me-dico-surgical emergency. Methods: A monocentric retrospective description was made in a French military hospital in Toulon from January 2014 to march 2017. Patients were included based on the 10th International Classification of Diseases code for necrotizing fasciitis and other skin infections associated with a surgical act. Demographic, clinical, biological, micro-biological, treatment and morbimortality characteristics were described. Results: 51 cases were included (31 men) with a mean age of 64 years. 20% of patients were immunodeficient. Erythema (100%), edema (98%) and intense pain (64%) were the most common clinical find-ings. 51% of patients had skin necrosis at the first emergency encounter. 79% of cases were located on a limb. Biological inflammatory findings were common in more than 60% of cases. Pseudomonas aeruginosa was the most common found bacteria. The median time before the first surgical debridement was 11 hours, 8% of cases underwent an amputation and overall mortality rate was 20%. Conclusions: This study describes NSTI's characteristics treated in a French military hospital and shows a high prevalence of skin necrosis and Pseudomonas aeru-ginosa as a causative bacteria. ; Introduction : les dermohypodermites bactériennes nécrosantes avec ou sans fasciite nécro-sante (DHBN-FN) sont des infections graves menaçant le pronostic vital et constituent des urgences médicochirurgicales. Matériels et méthodes : il s'agit d'une étude rétrospective descriptive monocentrique réalisée entre janvier 2014 et mars 2017 à l'Hôpital d'Instructions des Armées Sainte Anne - Toulon en France (HIASA). Les patients répondant au code de la 10ème classification internationale des maladies pour la fasciite nécrosante et d'autres infections cutanées associées à un acte chirurgical ont été inclus. Les variables décrites étaient démographiques, clinique, paraclinique et microbiologique, de prise en charge et de morbi-mortalités. Résultats : 51 cas ont été inclus (31 hommes). L'âge moyen est de 64 ans. 20% des patients étaient immunodéficients. Les signes les plus fréquents étaient l'érythème (100%), l'œdème (98%), la douleur intense (64%) et la nécrose cutanée d'emblée (51%). Les membres étaient majoritairement atteints dans 79% des cas. Un syndrome inflammatoire biologique était présent dans plus de 60% des cas. Le Pseudomonas aeruginosa était la bactérie la plus souvent rencontrée (29%). Le délai médian de première chirurgie était de 11 heures avec 8% d'amputations et 20% de décès.Conclusions : cette étude permet de décrire les caractéristiques de DHBN-FN pris en charge à l'HIASA et montre des hautes prévalences de nécroses cutanées d'emblée et d'infection à Pseudomonas aeruginosa.

Ankit Parikh,1 Krishna Kathawala,1 Jintao Li,1,2 Chi Chen,1,3 Zhengnan Shan,1 Xia Cao,3 Yan-Jiang Wang,4 Sanjay Garg,1 Xin-Fu Zhou1 1School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, Australia; 2Neuroscience Institute, Kunming Medical University, Kunming, Yunnan, China; 3Central Laboratory, Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China; 4Department of Neurology, Daping Hospital, Third Military Medical University, Chongqing, Sichuan, China Background: Alzheimer's disease (AD) is a devastating neurodegenerative disorder that lacks any disease-modifying drug for the prevention and treatment. Edaravone (EDR), an approved free radical scavenger, has proven to have potential against AD by targeting multiple key pathologies including amyloid-beta (Aβ), tau phosphorylation, oxidative stress, and neuroinflammation. To enable its oral use, novel edaravone formulation (NEF) was previously developed. The aim of the present investigation was to evaluate safety and efficacy of NEF by using in vitro/in vivo disease model. Materials and methods: In vitro therapeutic potential of NEF over EDR was studied against the cytotoxicity induced by copper metal ion, H2O2 and Aβ42 oligomer, and cellular uptake on SH-SY5Y695 amyloid-β precursor protein (APP) human neuroblastoma cell line. For in vivo safety and efficacy assessment, totally seven groups of APP/PS1 (five treatment groups, one each as a basal and sham control) and one group of C57BL/6 mice as a positive control for behavior tests were used. Three groups were orally treated for 3 months with NEF at an equivalent dose of EDR 46, 138, and 414 μmol/kg, whereas one group was supplied with each Donepezil (5.27 μM/kg) and Soluplus (amount present in NEF of 414 μmol/kg dose of EDR). Behavior tests were conducted to assess motor function (open-field), anxiety-related behavior (open-field), and cognitive function (novel objective recognition test, Y-maze, and Morris water maze). For the safety assessment, general behavior, adverse effects, and mortality were recorded during the treatment period. Moreover, biochemical, hematological, and morphological parameters were determined. Results: Compared to EDR, NEF showed superior cellular uptake and neuroprotective effect in SH-SY5Y695 APP cell line. Furthermore, it showed nontoxicity of NEF up to 414 μM/kg dose of EDR and its potential to reverse AD-like behavior deficits of APP/PS1 mice in a dose-dependent manner. Conclusion: Our results indicate that oral delivery of NEF holds a promise as a safe and effective therapeutic agent for AD. Keywords: edaravone, Soluplus, dose–response relationship, APPSwe/PS1deE9 mice, learning and memory, safety assessment

Aliya Naheed,1,* Victoria Haldane,2,* Tazeen H Jafar,3,4 Nantu Chakma,1 Helena Legido-Quigley2 On behalf of the COBRA-BPS Study Group 1Initiative for Noncommunicable Diseases, International Centre for Diarrhoeal Disease Research (icddr), Dhaka, Bangladesh; 2Saw Swee Hock School of Public Health, National University of Singapore, Singapore; 3Program for Health Services and Systems Research, Duke NUS Medical School, Singapore; 4Duke Global Health Institute, Duke University, Durham, NC, USA *These authors contributed equally to this work Purpose: Hypertension is an increasing threat to global public health, a leading cause of premature death, and an important modifiable risk factor for cardiovascular and cerebrovascular disease. Despite evidence on the efficacy of antihypertensive medication for blood-pressure control and mortality prevention, a large proportion of individuals are undiagnosed and untreated, especially in resource-constrained settings. This qualitative study explored patient pathways to care, as well as knowledge of and adherence to hypertension care. Methods: We conducted in-depth interviews with 20 hypertensive patients in two rural districts in Bangladesh. Interviews were conducted and transcribed in Bangla and translated to English. QSR NVivo 10 software was used for analyses. We mapped patient pathways and report here on patient experiences accessing care from local pharmacies, the government, and private clinics. Results: Overall, most patients reported hypertension awareness prior to diagnosis and were conscious about consequences of hypertension. However, patients had little knowledge about prevention and treatment strategies. Most patients considered hypertension an important disease, albeit reporting taking medication only when symptomatic. Patients were aware of dietary advice; however, they were largely sedentary. Qualified doctors in both private and government settings diagnosed hypertension in the majority of the patients, and some were diagnosed by an informal provider and a few reported self-care at home. Patients followed three pathways: specialized hospitals for acute care, private hospitals/local pharmacy for nonacute symptoms, and incidental hypertension identification while being treated for another condition. Conclusion: We identify barriers to access to hypertension prevention and care that prevented patients from seeking and receiving treatment from government facilities. Challenges included a lack of support to enable community screening by government health workers, long waiting times, and inadequate supplies for hypertension treatment. Expanding community-health workers' scope in the dissemination of chronic-disease information may improve patient pathways to hypertension care in rural communities in Bangladesh. Keywords: Bangladesh, hypertension, diagnosis, awareness, medication, barrier, qualitative