Neuroendocrine Tumor of the Ampulla of Vater: A Case Report

Neuroendocrine tumors (NETs) of the ampulla of Vater are extremely rare. Here, we discuss the clinical presentation, diagnostic challenges, and treatment options of a recently experienced case of NET of the ampulla of Vater in light of the literature. A 56-year-old woman presented with recurrent upper abdominal pain. Ultrasonography (USG) of the whole abdomen showed multiple gallstones along with a dilated common bile duct (CBD). For evaluating the dilated CBD, a magnetic resonance cholangiopancreatography was performed, which revealed the double-duct sign. Subsequently, an upper gastrointestinal endoscopy showed a bulged-out ampulla of the Vater. Biopsy and histopathological examination of the growth yielded the diagnosis of adenocarcinoma. A Whipple procedure was performed. Macroscopically, a 2 cm growth was noted involving the ampulla of Vater, and microscopic findings were consistent with a well-differentiated NET, grade 1 (low grade). The diagnosis was further confirmed by immunohistochemical staining (pan-cytokeratin positive, synaptophysin positive, and focally chromogranin positive). Her postoperative course was uneventful except for delayed gastric emptying. A detailed evaluation and a high index of suspicion are required for the diagnosis of this rare tumor. Treatment is relatively easier after a proper diagnosis

A Cognitive Approach To Designing Effective Implementation Of Industrial Policies : C-Solutions for Vehicle Maintenance Regulations (VMR) Implementation in Sarawak

Policy implementation science has moved from its traditional top-down ‘’how-to’’ approach that focuses primarily on the policy implementers while neglecting those affected by the implementation, to the hybrid ‘’what-and-how-to’’ approach, where the policy implementation mechanics incorporate the understanding of the ‘’meaning’’ and ‘’benefits’’ of the policy from the perspective of all the stakeholders - those who will be doing the enforcement, and those who will be impacted upon by the policy. Theories from the science of the mind, or cognitive science, such as the theories of social cognition and distributed cognition, have gained popularity in policy implementation science in the developed countries since a decade ago. This new approach however, is still at inception stage in many developing countries. This research explored the utility of cognitive science approach in designing the implementation of industrial policies, in the case of implementing the Vehicle Maintenance Regulations (VMR) regulations, a set of mandatory regulations passed to regulate safe and healthy vehicle maintenance industry in Malaysia. The benefits of the cognitive approach, over the ‘’implementer-oriented’’ rational choice theory approach conventionally adopted in policy implementation were explored. The cognitive science approach is expected to increase the effectiveness of the VMR policy implementation by integrating the ‘sense-making’ and ‘meaning-making’ of all stakeholders whose cooperation and cooperativeness are highly essential in ensuring successful implementation. This research yielded both, an industrial working model, and an academic model. The C-Solutions Model suggests a win-win implementation plan that could garner support from all VMR stakeholders – the car workshop operators, the car owners, and the government implementer agents. The ‘’Cognitive Model of VMR Implementation’ was produced to describe how understanding the cognitive functions of the stakeholders could be utilised to collect their best support for the VMR regulations implementation

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Phosphoinositide-3 Kinase-Akt Pathway Controls Cellular Entry of Ebola Virus

The phosphoinositide-3 kinase (PI3K) pathway regulates diverse cellular activities related to cell growth, migration, survival, and vesicular trafficking. It is known that Ebola virus requires endocytosis to establish an infection. However, the cellular signals that mediate this uptake were unknown for Ebola virus as well as many other viruses. Here, the involvement of PI3K in Ebola virus entry was studied. A novel and critical role of the PI3K signaling pathway was demonstrated in cell entry of Zaire Ebola virus (ZEBOV). Inhibitors of PI3K and Akt significantly reduced infection by ZEBOV at an early step during the replication cycle. Furthermore, phosphorylation of Akt-1 was induced shortly after exposure of cells to radiation-inactivated ZEBOV, indicating that the virus actively induces the PI3K pathway and that replication was not required for this induction. Subsequent use of pseudotyped Ebola virus and/or Ebola virus-like particles, in a novel virus entry assay, provided evidence that activity of PI3K/Akt is required at the virus entry step. Class 1A PI3Ks appear to play a predominant role in regulating ZEBOV entry, and Rac1 is a key downstream effector in this regulatory cascade. Confocal imaging of fluorescently labeled ZEBOV indicated that inhibition of PI3K, Akt, or Rac1 disrupted normal uptake of virus particles into cells and resulted in aberrant accumulation of virus into a cytosolic compartment that was non-permissive for membrane fusion. We conclude that PI3K-mediated signaling plays an important role in regulating vesicular trafficking of ZEBOV necessary for cell entry. Disruption of this signaling leads to inappropriate trafficking within the cell and a block in steps leading to membrane fusion. These findings extend our current understanding of Ebola virus entry mechanism and may help in devising useful new strategies for treatment of Ebola virus infection

Global, regional, and national burden of epilepsy, 1990 - 2016 : a systematic analysis for the Global Burden of Disease Study 2016

Background: Seizures and their consequences contribute to the burden of epilepsy because they can cause health loss (premature mortality and residual disability). Data on the burden of epilepsy are needed for health-care planning and resource allocation. The aim of this study was to quantify health loss due to epilepsy by age, sex, year, and location using data from the Global Burden of Diseases, Injuries, and Risk Factors Study. Methods: We assessed the burden of epilepsy in 195 countries and territories from 1990 to 2016. Burden was measured as deaths, prevalence, and disability-adjusted life-years (DALYs; a summary measure of health loss defined by the sum of years of life lost [YLLs] for premature mortality and years lived with disability), by age, sex, year, location, and Socio-demographic Index (SDI; a compound measure of income per capita, education, and fertility). Vital registrations and verbal autopsies provided information about deaths, and data on the prevalence and severity of epilepsy largely came from population representative surveys. All estimates were calculated with 95% uncertainty intervals (UIs). Interpretation: Despite the decrease in the disease burden from 1990 to 2016, epilepsy is still an important cause of disability and mortality. Standardised collection of data on epilepsy in population representative surveys will strengthen the estimates, particularly in countries for which we currently have no or sparse data and if additional data is collected on severity, causes, and treatment. Sizeable gains in reducing the burden of epilepsy might be expected from improved access to existing treatments in low-income countries and from the development of new effective drugs worldwide

Epidemiology of injuries from fire, heat and hot substances : global, regional and national morbidity and mortality estimates from the Global Burden of Disease 2017 study

Background Past research has shown how fires, heat and hot substances are important causes of health loss globally. Detailed estimates of the morbidity and mortality from these injuries could help drive preventative measures and improved access to care. Methods We used the Global Burden of Disease 2017 framework to produce three main results. First, we produced results on incidence, prevalence, years lived with disability, deaths, years of life lost and disability-adjusted life years from 1990 to 2017 for 195 countries and territories. Second, we analysed these results to measure mortality-to-incidence ratios by location. Third, we reported the measures above in terms of the cause of fire, heat and hot substances and the types of bodily injuries that result. Results Globally, there were 8 991 468 (7 481 218 to 10 740 897) new fire, heat and hot substance injuries in 2017 with 120 632 (101 630 to 129 383) deaths. At the global level, the age-standardised mortality caused by fire, heat and hot substances significantly declined from 1990 to 2017, but regionally there was variability in age-standardised incidence with some regions experiencing an increase (eg, Southern Latin America) and others experiencing a significant decrease (eg, High-income North America). Conclusions The incidence and mortality of injuries that result from fire, heat and hot substances affect every region of the world but are most concentrated in middle and lower income areas. More resources should be invested in measuring these injuries as well as in improving infrastructure, advancing safety measures and ensuring access to care.Peer reviewe

Global economic burden of unmet surgical need for appendicitis

Background: There is a substantial gap in provision of adequate surgical care in many low-and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods: Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results: Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion: For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially

Transport injuries and deaths in the Eastern Mediterranean Region : findings from the Global Burden of Disease 2015 Study

Transport injuries (TI) are ranked as one of the leading causes of death, disability, and property loss worldwide. This paper provides an overview of the burden of TI in the Eastern Mediterranean Region (EMR) by age and sex from 1990 to 2015. Transport injuries mortality in the EMR was estimated using the Global Burden of Disease mortality database, with corrections for ill-defined causes of death, using the cause of death ensemble modeling tool. Morbidity estimation was based on inpatient and outpatient datasets, 26 cause-of-injury and 47 nature-of-injury categories. In 2015, 152,855 (95% uncertainty interval: 137,900-168,100) people died from TI in the EMR countries. Between 1990 and 2015, the years of life lost (YLL) rate per 100,000 due to TI decreased by 15.5%, while the years lived with disability (YLD) rate decreased by 10%, and the age-standardized disability-adjusted life years (DALYs) rate decreased by 16%. Although the burden of TI mortality and morbidity decreased over the last two decades, there is still a considerable burden that needs to be addressed by increasing awareness, enforcing laws, and improving road conditions.Peer reviewe

Maternal mortality and morbidity burden in the Eastern Mediterranean region : findings from the Global Burden of Disease 2015 study

Assessing the burden of maternal mortality is important for tracking progress and identifying public health gaps. This paper provides an overview of the burden of maternal mortality in the Eastern Mediterranean Region (EMR) by underlying cause and age from 1990 to 2015. We used the results of the Global Burden of Disease 2015 study to explore maternal mortality in the EMR countries. The maternal mortality ratio in the EMR decreased 16.3% from 283 (241-328) maternal deaths per 100,000 live births in 1990 to 237 (188-293) in 2015. Maternal mortality ratio was strongly correlated with socio-demographic status, where the lowest-income countries contributed the most to the burden of maternal mortality in the region. Progress in reducing maternal mortality in the EMR has accelerated in the past 15 years, but the burden remains high. Coordinated and rigorous efforts are needed to make sure that adequate and timely services and interventions are available for women at each stage of reproductive life

Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-Adjusted life-years for 29 cancer groups, 1990 to 2017 : A systematic analysis for the global burden of disease study

Importance: Cancer and other noncommunicable diseases (NCDs) are now widely recognized as a threat to global development. The latest United Nations high-level meeting on NCDs reaffirmed this observation and also highlighted the slow progress in meeting the 2011 Political Declaration on the Prevention and Control of Noncommunicable Diseases and the third Sustainable Development Goal. Lack of situational analyses, priority setting, and budgeting have been identified as major obstacles in achieving these goals. All of these have in common that they require information on the local cancer epidemiology. The Global Burden of Disease (GBD) study is uniquely poised to provide these crucial data. Objective: To describe cancer burden for 29 cancer groups in 195 countries from 1990 through 2017 to provide data needed for cancer control planning. Evidence Review: We used the GBD study estimation methods to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-Adjusted life-years (DALYs). Results are presented at the national level as well as by Socio-demographic Index (SDI), a composite indicator of income, educational attainment, and total fertility rate. We also analyzed the influence of the epidemiological vs the demographic transition on cancer incidence. Findings: In 2017, there were 24.5 million incident cancer cases worldwide (16.8 million without nonmelanoma skin cancer [NMSC]) and 9.6 million cancer deaths. The majority of cancer DALYs came from years of life lost (97%), and only 3% came from years lived with disability. The odds of developing cancer were the lowest in the low SDI quintile (1 in 7) and the highest in the high SDI quintile (1 in 2) for both sexes. In 2017, the most common incident cancers in men were NMSC (4.3 million incident cases); tracheal, bronchus, and lung (TBL) cancer (1.5 million incident cases); and prostate cancer (1.3 million incident cases). The most common causes of cancer deaths and DALYs for men were TBL cancer (1.3 million deaths and 28.4 million DALYs), liver cancer (572000 deaths and 15.2 million DALYs), and stomach cancer (542000 deaths and 12.2 million DALYs). For women in 2017, the most common incident cancers were NMSC (3.3 million incident cases), breast cancer (1.9 million incident cases), and colorectal cancer (819000 incident cases). The leading causes of cancer deaths and DALYs for women were breast cancer (601000 deaths and 17.4 million DALYs), TBL cancer (596000 deaths and 12.6 million DALYs), and colorectal cancer (414000 deaths and 8.3 million DALYs). Conclusions and Relevance: The national epidemiological profiles of cancer burden in the GBD study show large heterogeneities, which are a reflection of different exposures to risk factors, economic settings, lifestyles, and access to care and screening. The GBD study can be used by policy makers and other stakeholders to develop and improve national and local cancer control in order to achieve the global targets and improve equity in cancer care. © 2019 American Medical Association. All rights reserved.Peer reviewe