Epstein-barr virus in gastro-esophageal adenocarcinomas - single center experiences in the context of current literature.

Epstein-Barr virus (EBV)-associated gastric carcinomas (GC) represent a distinct and well-recognized subtype of gastric cancer with a prevalence of around 10% of all GC. In contrast, EBV has not been reported to play a major role in esophageal adenocarcinomas (EAC) and adenocarcinomas of the gastro-esophageal junction (GEJ). We report our experiences on EBV in collections of gastro-esophageal adenocarcinomas from two surgical centers and discuss the current state of research in this field. Tumor samples from 465 primary resected gastro-esophageal adenocarcinomas (118 EAC, 73 GEJ, and 274 GC) were investigated. Presence of EBV was determined by EBV-encoded small RNAs (EBER) in situ hybridization. Results were correlated with pathologic parameters (UICC pTNM category, Her2 status, tumor grading) and survival. EBER positivity was observed in 14 cases. None of the EAC were positive for EBER. In contrast, we observed EBER positivity in 2/73 adenocarcinomas of the GEJ (2.7%) and 12/274 GC (4.4%). These were of intestinal type (seven cases) or unclassifiable (six cases), while only one case was of diffuse type according to the Lauren classification. No association between EBV and pT, pN, or tumor grading was found, neither was there a correlation with clinical outcome. None of the EBER positive cases were Her2 positive. In conclusion, EBV does not seem to play a role in the carcinogenesis of EAC. Moreover, adenocarcinomas of the GEJ show lower rates of EBV positivity compared to GC. Our data only partially correlate with previous reports from the literature. This highlights the need for further research on this distinct entity. Recent reports, however, have identified specific epigenetic and genetic alterations in EBV-associated GC, which might lead to a distinct treatment approach for this specific subtype of GC in the future.

TREAT-AND-EXTEND REGIMENS WITH ANTI-VEGF AGENTS IN RETINAL DISEASES: A Literature Review and Consensus Recommendations

PURPOSE A review of treat-and-extend regimens (TERs) with intravitreal anti-vascular endothelial growth factor agents in retinal diseases. METHODS There is a lack of consensus on the definition and optimal application of TER in clinical practice. This article describes the supporting evidence and subsequent development of a generic algorithm for TER dosing with anti-vascular endothelial growth factor agents, considering factors such as criteria for extension. RESULTS A TER algorithm was developed; TER is defined as an individualized proactive dosing regimen usually initiated by monthly injections until a maximal clinical response is observed (frequently determined by optical coherence tomography), followed by increasing intervals between injections (and evaluations) depending on disease activity. The TER regimen has emerged as an effective approach to tailoring the dosing regimen and for reducing treatment burden (visits and injections) compared with fixed monthly dosing or monthly visits with optical coherence tomography-guided regimens (as-needed or pro re nata). It is also considered a suitable approach in many retinal diseases managed with intravitreal anti-vascular endothelial growth factor therapy, given that all eyes differ in the need for repeat injections. CONCLUSION It is hoped that this practical review and TER algorithm will be of benefit to health care professionals interested in the management of retinal diseases.

Time relevance, citation of reporting guidelines, and breadth of literature search in systematic reviews in orthodontics

INTRODUCTION As the importance of systematic review (SR) conclusions relies upon the scientific rigor of methods and the currency of evidence, we aimed to investigate the currency of orthodontic SRs using as proxy the time from the initial search to publication. Additionally, SR information regarding reporting guidelines, registration, and literature searches were recorded when available. MATERIALS AND METHODS A systematic PubMed search was carried out using the Clinical Queries page to identify orthodontic SRs cited between 1 January 2008 and 7 November 2013. Data related to reporting guidelines, review registration, dates of review processing, literature search, and abstract reporting were retrieved and classified by journal type. Survival analysis was used to assess the time to reach predefined manuscript stages for orthodontic and non-orthodontic journals. RESULTS One hundred twenty seven of the originally identified 585 SRs were considered eligible. The median interval from search until publication was 13.2 months (interquartile range: IQR = 9.7 months) irrespective of the journal type. There was evidence (P = 0.05) that SRs published by non-orthodontic journals appeared in PubMed faster than in orthodontic journals (non-orthodontic: median = 6.5 months; IQR = 5.7 months; orthodontic: median = 10.2 months; IQR = 5.6 months) from submission to publication and from acceptance to publication (non-orthodontic: median = 1.5 months; IQR = 2.4 months; orthodontic: median = 6.0 months; IQR = 6.2 months; P < 0.001). More than half of these SRs did not cite adherence to any reporting guidelines, whereas all but five studies were not prospectively registered. Search of unpublished research was undertaken in approximately 21 per cent and 29 per cent of the SRs published in non-orthodontic and orthodontic periodicals, respectively. CONCLUSIONS This study indicates that SR users should be aware that median time for orthodontic SRs from search to publication is 13.2 months. SRs published in non-orthodontic journals are likely to be more current in terms of submission until time to publication and acceptance until time to publication compared with those published in orthodontic journals.

New Clinical Indications for (18)F/(11)C-choline, New Tracers for Positron Emission Tomography and a Promising Hybrid Device for Prostate Cancer Staging: A Systematic Review of the Literature

CONTEXT Radiolabelled choline positron emission tomography has changed the management of prostate cancer patients. However, new emerging radiopharmaceutical agents, like radiolabelled prostate specific membrane antigen, and new promising hybrid imaging will begin new challenges in the diagnostic field. OBJECTIVE The continuous evolution in nuclear medicine has led to the improvement in the detection of recurrent prostate cancer (PCa), particularly distant metastases. New horizons have been opened for radiolabelled choline positron emission tomography (PET)/computed tomography (CT) as a guide for salvage therapy or for the assessment of systemic therapies. In addition, new tracers and imaging tools have been recently tested, providing important information for the management of PCa patients. Herein we discuss: (1) the available evidence in literature on radiolabelled choline PET and their recent indications, (2) the role of alternative radiopharmaceutical agents, and (3) the advantages of a recent hybrid imaging device (PET/magnetic resonance imaging) in PCa. EVIDENCE ACQUISITION Data from recently published (2010-2015), original articles concerning the role of choline PET/CT, new emerging radiotracers, and a new imaging device are analysed. This review is reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. EVIDENCE SYNTHESIS In the restaging phase, the detection rate of choline PET varies between 4% and 97%, mainly depending on the site of recurrence and prostate-specific antigen levels. Both 68gallium (68Ga)-prostate specific membrane antigen and 18F-fluciclovine are shown to be more accurate in the detection of recurrent disease as compared with radiolabelled choline PET/CT. Particularly, Ga68-PSMA has a detection rate of 50% and 68%, respectively for prostate-specific antigen levels < 0.5ng/ml and 0.5-2ng/ml. Moreover, 68Ga- PSMA PET/magnetic resonance imaging demonstrated a particularly higher accuracy in detecting PCa than PET/CT. New tracers, such as radiolabelled bombesin or urokinase-type plasminogen activator receptor, are promising, but few data in clinical practice are available today. CONCLUSIONS Some limitations emerge from the published papers, both for radiolabelled choline PET/CT and also for new radiopharmaceutical agents. Efforts are still needed to enhance the impact of published data in the world of oncology, in particular when new radiopharmaceuticals are introduced into the clinical arena. PATIENT SUMMARY In the present review, the authors summarise the last evidences in clinical practice for the assessment of prostate cancer, by using nuclear medicine modalities, like positron emission tomography/computed tomography and positron emission tomography/magnetic resonance imaging.

Do multiple true-false items beat the commonly used one-best-answers questions regarding to the Ottawa Criteria for Good Assessment? Results of a literature review

Background: Multiple True-False-Items (MTF-Items) might offer some advantages compared to one-best-answer-questions (TypeA) as they allow more than one correct answer and may better represent clinical decisions. However, in medical education assessment MTF-Items are seldom used. Summary of Work: With this literature review existing findings on MTF-items and on TypeA were compared along the Ottawa Criteria for Good Assessment, i.e. (1) reproducibility, (2) feasibility, (3) validity, (4) acceptance, (5) educational effect, (6) catalytic effects, and (7) equivalence. We conducted a literature research on ERIC and Google Scholar including papers from the years 1935 to 2014. We used the search terms “multiple true-false”, “true-false”, “true/false”, and “Kprim” combined with “exam”, “test”, and “assessment”. Summary of Results: We included 29 out of 33 studies. Four of them were carried out in the medical field Compared to TypeA, MTF-Items are associated with (1) higher reproducibility (2) lower feasibility (3) similar validity (4) higher acceptance (5) higher educational effect (6) no studies on catalytic effects or (7) equivalence. Discussion and Conclusions: While studies show overall good characteristics of MTF items according to the Ottawa criteria, this type of question seems to be rather seldom used. One reason might be the reported lower feasibility. Overall the literature base is still weak. Furthermore, only 14 % of literature is from the medical domain. Further studies to better understand the characteristics of MTF-Items in the medical domain are warranted. Take-home messages: Overall the literature base is weak and therefore further studies are needed. Existing studies show that: MTF-Items show higher reliability, acceptance and educational effect; MTF-Items are more difficult to produce

Evaluation of association between childhood obesity and depression: A systematic literature review

Obesity has become a major public health concern throughout the world. Both developing as well as developed countries have been facing the consequences of obesity. [1, 2] According to World Health Organization, worldwide prevalence of overweight among adults was 1.6 billion and that of obesity was 400 million by the end of year 2005. At the same time, around 20 million children of less than 5 years of age were overweight worldwide. [3] ^ From amongst the obese children, around 15% of children manifest symptoms of depression before 18 years of age as compared to non-obese children of the same age group. Approximately 3-5% of these obese individuals develop major depressive disorders (MDD). [4, 5] The incidence of depression increases markedly as the child reaches puberty. The risk of persistent depression in childhood as well as in adulthood is two to four times higher if the child is obese as compared to those depressed adult individuals who are not obese in their childhood. [6, 7] ^ This paper will review the scientific literature concerning the association between childhood obesity and depression. ^

The influence of socioeconomic status on the relationship between diabetes and amputations: A systematic review of the literature

This paper synthesizes the current knowledge available regarding the impact of socioeconomic status on diabetes and amputations. In September 2009, searches in the OVID Medline and PubMed databases were performed using keywords associated with race/ethnicity, educational level, insurance status, veteran status, low income, diabetes, and lower extremity amputation. Articles published between 1996 and the search date were used. The pertinent articles were analyzed, summarized, and synthesized. ^ The majority of the articles agreed that African American, American Indian, and Latino minorities experience significantly higher rates of diabetes-related lower extremity amputation (LEA) when compared to whites. Few articles suggested that the disparity experienced by minorities and others of low SES was due to biology; most articles link it to a combination of lower income, lower educational attainment, uninsured or underinsured status, and a greater prevalence of detrimental health behaviors such as smoking. These, in turn, are linked to decreased knowledge of self-care, delayed health care seeking, delayed diagnoses and treatment, discrimination, and low quality health care. Interventions focused on patient education, established regimens of treatment, foot care, and control of diabetes have been shown to be effective, although none have lowered the rate of diabetes-related LEA to rates found in the general population.^

A literature review of the use of DDT to fight malaria

Background. First synthesized in 1874, dichlorodiphenyltrichloroethane (DDT) was not used until the second half of World War II after its insecticidal properties were discovered in 1939. For decades DDT has been used globally with the intent of eradicating malaria. This began in 1955 when the eighth World Health Assembly launched a global campaign selecting DDT as the chemical of choice for the eradication of malaria. The United States banned DDT use in 1972 partially due to the publication of “Silent Spring” by Rachel Carson in 1962 which suggested that DDT was harmful to the environment, wildlife and is a carcinogen. ^ Objectives. To critically review the literature on DDT, and evaluate its importance in malaria prevention and control. Methods: The design of this systematic literature review is a narrative summary and evaluation of the papers reviewed. The data came from searches using PubMed and MEDLINE which are free and publicly available databases. Inclusive criteria that were considered during the search are English language peer reviewed journal articles published in the last 20 years. The keywords were: “insecticidal and agricultural use of DDT”, “human impact of malaria”, “economic impact of malaria”, “benefits of DDT”, “effects of DDT”, “importance of malaria control”, and alternatives to DDT for malaria control. ^ Results. Malaria continues to be one of the most common infectious diseases and creates a tremendous global public health problem. WHO recommends DDT for malaria vector control because compared to other pesticides, it is the most persistent in indoor spraying. ^ Conclusion. Indoor spraying of DDT in malaria endemic areas may cause increased exposure of the chemical to humans; however I conclude that the overall benefits outweigh the risks because more lives are saved due to fewer infections with malaria.^

Literature review of elasmobranch bycatch and retention rate

To address growing concern over the effects of fisheries non-target catch on elasmobranchs worldwide, the accurate reporting of elasmobranch catch is essential. This requires data on a combination of measures, including reported landings, retained and discarded non-target catch, and post-discard survival. Identification of the factors influencing discard vs. retention is needed to improve catch estimates and to determine wasteful fishing practices. To do this we compared retention rates of elasmobranch non-target catch in a broad subset of fisheries throughout the world by taxon, fishing country, and gear. A regression tree and random forest analysis indicated that taxon was the most important determinant of retention in this dataset, but all three factors together explained 59% of the variance. Estimates of total elasmobranch removals were calculated by dividing the FAO global elasmobranch landings by average retention rates and suggest that total elasmobranch removals may exceed FAO reported landings by as much as 400%. This analysis is the first effort to directly characterize global drivers of discards for elasmobranch non-target catch. Our results highlight the importance of accurate quantification of retention and discard rates to improve assessments of the potential impacts of fisheries on these species.

CDAPubMed: a browser extension to retrieve EHR-based biomedical literature

Over the last few decades, the ever-increasing output of scientific publications has led to new challenges to keep up to date with the literature. In the biomedical area, this growth has introduced new requirements for professionals, e.g., physicians, who have to locate the exact papers that they need for their clinical and research work amongst a huge number of publications. Against this backdrop, novel information retrieval methods are even more necessary. While web search engines are widespread in many areas, facilitating access to all kinds of information, additional tools are required to automatically link information retrieved from these engines to specific biomedical applications. In the case of clinical environments, this also means considering aspects such as patient data security and confidentiality or structured contents, e.g., electronic health records (EHRs). In this scenario, we have developed a new tool to facilitate query building to retrieve scientific literature related to EHRs. Results: We have developed CDAPubMed, an open-source web browser extension to integrate EHR features in biomedical literature retrieval approaches. Clinical users can use CDAPubMed to: (i) load patient clinical documents, i.e., EHRs based on the Health Level 7-Clinical Document Architecture Standard (HL7-CDA), (ii) identify relevant terms for scientific literature search in these documents, i.e., Medical Subject Headings (MeSH), automatically driven by the CDAPubMed configuration, which advanced users can optimize to adapt to each specific situation, and (iii) generate and launch literature search queries to a major search engine, i.e., PubMed, to retrieve citations related to the EHR under examination. Conclusions: CDAPubMed is a platform-independent tool designed to facilitate literature searching using keywords contained in specific EHRs. CDAPubMed is visually integrated, as an extension of a widespread web browser, within the standard PubMed interface. It has been tested on a public dataset of HL7-CDA documents, returning significantly fewer citations since queries are focused on characteristics identified within the EHR. For instance, compared with more than 200,000 citations retrieved by breast neoplasm, fewer than ten citations were retrieved when ten patient features were added using CDAPubMed. This is an open source tool that can be freely used for non-profit purposes and integrated with other existing systems.

Treatment approach in patients with hyperbilirubinemia secondary to liver metastases in gastrointestinal malignancies: a case series and review of literature

BACKGROUND: Treatment of patients with severe liver dysfunction including hyperbilirubinemia secondary to liver metastases of gastrointestinal (GI) cancer is challenging. Regimen of oxaliplatin and fluoropyrimidine (FP)/folinic acid (FA) ± a monoclonal antibody (moAb), represents a feasible option considering the pharmacokinetics. Clinical data on the respective dosage and tolerability are limited and no recommendations are available. METHODS: Consecutive patients with severe hyperbilirubinemia [>2 × upper limit of the normal range (ULN) and >2.4 mg/dl] due to liver metastases of GI cancer without options for drainage receiving oxaliplatin, FP/FA ± moAb were analyzed. To collect further data a review of the literature was performed. RESULTS: A total of 12 patients were identified between 2011 and 2015. At treatment start, median bilirubin level was 6.1 mg/dl (>5 × ULN, range 2.7-13.6). The majority of patients (n = 11) received dose-reduced regimen with oxaliplatin (60-76%) and FP/FA (0-77%), rapidly escalating to full dose regimen. During treatment, bilirubin levels dropped more than 50% within 8 weeks or normalized within 12 weeks in 6 patients (responders). Median overall survival was 5.75 months (range 1.0-16.0 months) but was significantly prolonged in responders compared to nonresponders [9.7 and 3.0 months, p = 0.026 (two-sided test); 95% confidence interval (CI): 1.10-10.22]. In addition, case reports or series comprising a further 26 patients could be identified. Based on the obtained data a treatment algorithm was developed. CONCLUSION: Treatment with oxaliplatin, FP/FA ± moAb is feasible and may derive relevant benefits in patients with severe liver dysfunction caused by GI cancer liver metastases without further options of drainage.

The mythology and rites of the British druids, ascertained by national documents; and compared with the general traditions and customs of heathenism, as illustrated by the most eminent antiquaries of our age. With an appendix, containing ancient poems and extracts, with some remarks on ancient British coins ...

Index to the author's Celtic researches: 6 p. at end.

Sindhi-Jersey and Sindhi-Holstein crosses : their external form and internal anatomy compared with those of purebred Jerseys and Holsteins /

Caption title.

Cost-effectiveness of combination peginterferon alpha-2a and ribavirin compared with interferon alpha-2b and ribavirin in patients with chronic hepatitis C

BACKGROUND: Sustained virological response (SVR) is the primary objective in the treatment of chronic hepatitis C (CHC). Results from a recent clinical trial of patients with previously untreated CHC demonstrate that the combination of peginterferon alpha-2a and ribavirin produces a greater SVR than interferon alpha-2b and ribavirin combination therapy. However, the cost-effectiveness of peginterferon alpha-2a plus ribavirin in the U.S. setting has not been investigated. METHODS: A Markov model was developed to investigate cost-effectiveness in patients with CHC using genotype to guide treatment duration. SVR and disease progression parameters were derived from the clinical trials and epidemiologic studies. The impact of treatment on life expectancy and costs were projected for a lifetime. Patients who had an SVR were assumed to remain virus-free for the rest of their lives. In genotype 1 patients, the SVRs were 46% for peginterferon alpha-2a plus ribavirin and 36% for interferon alpha-2b plus ribavirin. In genotype 2/3 patients, the SVRs were 76% for peginterferon alpha-2a plus ribavirin and 61% for interferon alpha-2b plus ribavirin. Quality of life and costs were based on estimates from the literature. All costs were based on published U.S. medical care costs and were adjusted to 2003 U.S. dollars. Costs and benefits beyond the first year were discounted at 3%. RESULTS: In genotype 1, peginterferon alpha-2a plus ribavirin increases quality-adjusted life expectancy (QALY) by 0.70 yr compared to interferon alpha-2b plus ribavirin, producing a cost-effectiveness ratio of $2,600 per QALY gained. In genotype 2/3 patients, peginterferon alpha-2a plus ribavirin increases QALY by 1.05 yr in comparison to interferon alpha-2b plus ribavirin. Peginterferon alpha-2a combination therapy in patients with HCV genotype 2 or 3 is dominant (more effective and cost saving) compared to interferon alpha-2b plus ribavirin. Results weighted by genotype prevalence (75% genotype 1; 25% genotype 2 or 3) also show that peginterferon alpha-2a plus ribavirin is dominant. Peginterferon alpha-2a and ribavirin remained cost-effective (below $16,500 per QALY gained) under sensitivity analyses on key clinical and cost parameters. CONCLUSION: Peginterferon alpha-2a in combination with ribavirin with duration of therapy based on genotype, is cost-effective compared with conventional interferon alpha-2b in combination with ribavirin when given to treatment-naive adults with CHC.

Comparative efficacy and safety of biosimilar infliximab and other biological treatments in ankylosing spondylitis: systematic literature review and meta-analysis.

OBJECTIVES: To compare the efficacy and safety of infliximab-biosimilar with other biological drugs for the treatment of active ankylosing spondylitis (AS). METHODS: Systematic literature review for randomized controlled trials (RCTs) with adalimumab, etanercept, golimumab, infliximab and infliximab-biosimilar in AS was performed and indirect meta-analysis (Bayesian mixed treatment comparison) was carried out. The proportion of patients reaching 20 % improvement by the assessment of Spondyloarthritis International Society response criteria (ASAS20) at weeks 12 and 24 was used as efficacy endpoints, and the occurrence of serious adverse events at week 24 was applied to compare the safety of the biologicals. RESULTS: Altogether, 13 RCTs, identified by the systematic literature search, were included in the analysis. Results on the ASAS20 efficacy endpoint were reported for week 12 in 12 RCTs involving 2,395 patients, and for week 24 in 5 RCTs comprising 1,337 patients. All the five biological agents proved to be significantly superior to placebo. Infliximab showed the highest odds ratio (OR) of 7.2 (95 % CI 3.68-13.19) compared to placebo, followed by infliximab-biosimilar with OR 6.25 (95 % CI 2.55-13.14), both assessed at week 24. No significant difference was found between infliximab-biosimilar and other biological treatments regarding their efficacy and safety. CONCLUSIONS: This is the first study which includes a biosimilar drug in the meta-analysis of biological treatments in AS. The results have proven the similar efficacy and safety profile of infliximab-biosimilar treatment compared to other biologicals.