High Incidence Countries Research Articles

Real-life data on the impact of successful downstaging in patients with hepatocellular carcinoma: A Dutch Multicenter Study

Patients with Barcelona Clinic Liver Cancer intermediate stage hepatocellular carcinoma (HCC) theoretically are an excellent group to consider downstaging using locoregional therapy (LRT) since they do not have extrahepatic spread or vascular invasion. Once successful, this can change the treatment strategy from palliative to curative intention. Although downstaging therapy is suggested in guidelines, it is still not widely accepted. Moreover, studies on downstaging are mainly performed in high-incidence HCC countries. Therefore, our aim was to gain insight in therapeutic strategies in patients with intermediate stage HCC and their impact on intention-to-treat survival in a real-life setting in a low-incidence HCC country.We retrospectively analyzed data from the national Dutch HCC registry. From this database, consisting of 1409 patients with a diagnosis of HCC between 2005-2013 in 5 Dutch tertiary referral centers, we identified 165 patients with intermediate stage HCC. Out of these patients, 63 (38%) were not offered LRT, whereas 102 (62%) did receive LRT. Subsequently, 50 (49%) of the 102 patients who received LRT were successfully downstaged. Eleven patients (22% of successfully downstaged patients) eventually underwent liver transplantation. Cox regression analysis showed that a lower MELD score, an AFP value <100 ng/ml, successful downstaging and liver transplantation (all ≤p = 0.01) were positively associated to overall survival.In conclusion, our results demonstrate that LRT is not routinely offered to intermediate stage HCC patients in the Netherlands. Nevertheless, we showed that patients with intermediate stage HCC who are successfully downstaged have a survival benefit compared to those who were not.

Salmonella Paratyphi A infection: implications for public health management of extra-intestinal presentations – case study of a neck abscess

This study explores the implications of unusual presentations of Salmonella enterica subsp. enterica ser. Paratyphi (S. Paratyphi) infection for public health management, through a literature review and case study. In 2016, a 36-year-old male presented with a five-day history of right sided painful neck swelling, coryza and a two-day history of fevers after arriving in Australia from India nine weeks earlier. S. Paratyphi A was isolated from a fine needle aspirate sample. A descriptive epidemiological review was performed of confirmed cases of S. Paratyphi notified in New South Wales between 2008 and 2017. S. Paratyphi was isolated in blood and/or faecal samples in 247 cases (98.4%). Only four specimens (1.6%) were from a focal site. A literature review of extraintestinal infections of S. Paratyphi A or B was performed. Of the 41 such cases reported, 16 (39%) had a clear history of a prior gastroenteritis and/or febrile illness, or information suggested this was highly likely. No preceding gastroenteritis or febrile illness occurred in 15 (37%) of the cases. Information was reviewed and presented with a public health lens, valuable for ‘evidence-informed’ public health risk assessment of contacts and exposures related to these types of S. Paratyphi infection. S. Paratyphi infection usually presents as an enteric fever illness. Our case illustrates the variable nature of infectious diseases and the importance of laboratory testing in obtaining a diagnosis. S. Paratyphi can have unusual presentations, which may require adjustment in the public health management of the case. Public health staff should keep an open mind when investigating possible sources and assessing risk. In Western Sydney, this disease is largely associated with residents travelling to high-incidence countries to visit family and friends, and receiving family visits from these countries. The increasing number of cases of S. Paratyphi (prior to COVID-19) in Western Sydney and the importance of awareness of the risk of enteric fever to travellers to endemic regions is highlighted.

Delayed diagnosis of active pulmonary tuberculosis - potential risk factors for patient and healthcare delays in Portugal

BackgroundEarly diagnosis and treatment of pulmonary tuberculosis (PTB) is essential for an effective control of the tuberculosis (TB) epidemic. Delayed diagnosis and treatment of TB increases the chance of complications and mortality for the patients, and enhances TB transmission in the population. Therefore, the aim of this study was to characterize patient, healthcare and total delay in diagnosing PTB and assess the effect of clinical and sociodemographic factors on the time until first contact with healthcare or reaching a PTB diagnosis.MethodsRetrospective cohort study that included active PTB patients notified in the National Tuberculosis Surveillance System (SVIG-TB), between 2008 and 2017. Descriptive statistics, Kaplan-Meier estimates, logrank test and Cox proportional hazards model were used to characterize patient, healthcare and total delay and estimate the effect of clinical and sociodemographic variables on these delays. Significance level was set at 0.05.ResultsMedian patient, healthcare and total delays was 37 days (Interquartile range (IQR): 19–71), 8 days (IQR: 1–32) and 62 days (IQR: 38–102), respectively.The median patient delay showed a constant increase, from 33 days in 2008 to 44 days in 2017. The median total delay presented a similar trend, increasing from 59 days in 2008 to 70 days in 2017. Healthcare delay remained constant during the study period. More than half of the PTB cases (82.9%) had a delay > 1 month between symptom onset and diagnosis.In the final Cox model, alcohol abuse, unemployment and being from a high TB incidence country were factors significantly associated with longer patient delay, while being female, having more than 45 years, oncologic and respiratory diseases were associated with longer healthcare delay. Being female, having more than 45 years and being from a high TB incidence country were associated with longer total delay.ConclusionsPatient delay and total delay have increased in recent years. Older patients, patients with alcohol problems, other comorbidities, unemployed or from countries with high TB incidence would benefit from the development of specific public health strategies that could help reduce the delay in TB diagnosis observed in our study.This study emphasizes the need to promote awareness of TB in the general population and among the healthcare community, especially at ambulatory care level, in order to reduce the gap between beginning of symptoms and TB diagnosis.

Targeting screening and treatment for latent tuberculosis infection towards asylum seekers from high-incidence countries \u2013 a model-based cost-effectiveness analysis

BackgroundEnhancing tuberculosis (TB) prevention and care in a post-COVID-19-pandemic phase will be essential to ensure progress towards global TB elimination. In low-burden countries, asylum seekers constitute an important high-risk group. TB frequently arises post-immigration due to the reactivation of latent TB infection (LTBI). Upon-entry screening for LTBI and TB preventive treatment (TPT) are considered worthwhile if targeted to asylum seekers from high-incidence countries who usually present with higher rates of LTBI. However, there is insufficient knowledge about optimal incidence thresholds above which introduction could be cost-effective. We aimed to estimate, among asylum seekers in Germany, the health impact and costs of upon-entry LTBI screening/TPT introduced at different thresholds of country-of-origin TB incidence.MethodsWe sampled hypothetical cohorts of 30–45 thousand asylum seekers aged 15 to 34 years expected to arrive in Germany in 2022 from cohorts of first-time applicants observed in 2017–2019. We modelled LTBI prevalence as a function of country-of-origin TB incidence fitted to data from observational studies. We then used a probabilistic decision-analytic model to estimate health-system costs and quality-adjusted life years (QALYs) under interferon gamma release assay (IGRA)-based screening for LTBI and rifampicin-based TPT (daily, 4 months). Incremental cost-effectiveness ratios (ICERs) were calculated for scenarios of introducing LTBI screening/TPT at different incidence thresholds.ResultsWe estimated that among 15- to 34-year-old asylum seekers arriving in Germany in 2022, 17.5% (95% uncertainty interval: 14.2–21.6%) will be latently infected. Introducing LTBI screening/TPT above 250 per 100,000 country-of-origin TB incidence would gain 7.3 (2.7–14.8) QALYs at a cost of €51,000 (€18,000–€114,100) per QALY. Lowering the threshold to ≥200 would cost an incremental €53,300 (€19,100–€122,500) per additional QALY gained relative to the ≥250 threshold scenario; ICERs for the ≥150 and ≥ 100 thresholds were €55,900 (€20,200–€128,200) and €62,000 (€23,200–€142,000), respectively, using the next higher threshold as a reference, and considerably higher at thresholds below 100.ConclusionsLTBI screening and TPT among 15- to 34-year-old asylum seekers arriving in Germany could produce health benefits at reasonable additional cost (with respect to international benchmarks) if introduced at incidence thresholds ≥100. Empirical trials are needed to investigate the feasibility and effectiveness of this approach.

Estimating the population at high risk for tuberculosis through household exposure in high-incidence countries: a model-based analysis.

BackgroundHousehold contacts of people with pulmonary tuberculosis (TB) have greater risk of developing TB. Recent guidelines conditionally recommended TB preventive treatment (TPT) for household contacts of any age living in TB high-incidence countries, expanding earlier guidance to provide TPT to household contacts under five. The all-age population of household contacts has not been estimated.MethodsOur model-based estimation included 20 countries with >80% of incident TB globally in 2019. We developed country-specific distributions of household composition by age and sex using bootstrap resampling from health surveys and census data. We incorporated age-, sex-, year-, and location-specific estimates of pulmonary TB incidence from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019 to estimate the population in each country sharing a household with someone with incident pulmonary TB, and quantified uncertainty using a Monte Carlo approach.FindingsWe estimate that 38 million [95% uncertainty interval (UI) 33- 43 million] individuals lived in a household with someone with incident pulmonary TB in 2019 in these 20 countries. Children under five made up 12% of the population with household exposure, while adults were 65%. Zimbabwe, Mozambique, Zambia, and Pakistan had the highest proportion of the population with household exposure, while India had the highest number of contacts (11·4 million, 95% UI 9·7-13·4 million).InterpretationExpanding TPT evaluation to household contacts of all ages in high-incidence countries could include a population more than 7-times larger than the under-5 contacts previously prioritized. This would substantially increase the impact of household contact investigation on reducing TB morbidity and mortality.FundingJMR is supported by the National Institute of Allergy and Infectious Diseases (K01 AI138620). This research was funded in part by a 2020 developmental grant from the University of Washington / Fred Hutch Center for AIDS Research, an NIH funded program under award number AI027757 which is supported by the following NIH Institutes and Centers: NIAID, NCI, NIMH, NIDA, NICHD, NHLBI, NIA, NIGMS, NIDDK. This work was funded in part by the National Science Foundation (DMS-1839116).

Patient and healthcare delays in critical and non-critical pulmonary tuberculosis incidence areas in Portugal: are there differences?

ObjectivesTo characterize patient, healthcare, and total delay in diagnosing pulmonary tuberculosis (PTB) in critical (higher PTB incidence) and non-critical (lower PTB incidence) areas and their determinants considering clinical and sociodemographic factors. Study designRetrospective cohort study. MethodsData was retrieved from the Portuguese National Tuberculosis Surveillance System (SVIG-TB). Were included in the study all active PTB patients (n = 11,762) notified between 2008 and 2017. Spatial analysis was used to define critical and non-critical areas. Kaplan–Meier estimator, logrank test, and Cox regression were conducted, stratified by area. ResultsPTB cases in critical areas (n = 6594, 56.1%) presented longer patient median delay (41 vs 31days), shorter healthcare median delay (7 vs 10 days), and longer total median delay (63 vs 61days) t.han non-critical areas. Patient and total delay increased in both areas over time, while healthcare delay only increased in non-critical areas. Icn both areas, being from a high TB incidence country and alcohol abuse were associated with longer patient delays. Being female, older age, and oncologic diseases were associated with longer healthcare delays. Respiratory diseases were only associated with a longer healthcare delay in non-critical areas. Being female, older, and from a high TB incidence country were associated with a longer total delay in both areas. ConclusionsPatient delay was significantly longer in critical areas, and healthcare delay was significantly longer in non-critical areas. Several factors associated with longer delays have been identified, most of which are shared by critical and non-critical areas. Differences in patient and healthcare delay, for example, by sex, age, or country of birth, highlight the need for targeted public health interventions to help reduce these differences.

Screening for active and latent TB among migrants in France.

SETTING: Migrants to Europe face a disproportionate burden of infections, including TB, yet little is known about the approach taken by primary and secondary care providers to screening and treatment. We therefore explored policy and practice relating to screening of active TB and latent TB infection (LTBI) in France.METHODS: We conducted an online national survey of French primary and secondary care physicians regarding their practices in relation to TB/LTBI screening among migrants.RESULTS: 367 physicians responded to the questionnaire among which 195 (53.1%) were primary care physicians, 126 (34.3%) were TB specialists in secondary care, and 46 (12.5%) other physicians; 303 (85.5%) were involved daily in the care of migrants. Most respondents recommended systematic TB screening with chest X-ray for migrants from medium and high-incidence countries (71.9%). Primary care physicians were less likely to offer screening than physicians in other settings (aOR 0.21, 95% CI 0.09-0.48). 220 (61.8%) offered LTBI screening for children (<15 years) and 34.0% for all migrants from high incidence countries.CONCLUSION: Improving awareness on TB screening is a critical next step to improve health outcomes in migrant groups and meet regional targets for tackling TB.

Factors Associated with Acid Fast Bacilli and Sputum Culture Conversion in Patients with Multidrug-Resistant Tuberculosis in Surabaya

Introduction: Indonesia is a high incidence country of multidrug-resistant tuberculosis. There are approximately 11,000 MDR TB cases, 2.8% of them are new cases and 16% of them are relapse cases. Although guidelines for MDR-TB are frequently designed, medication freely provided, and centers for treatment duly expanded, studies on time to sputum culture conversion have been very limited in Indonesia. Therefore the aim of the study is to identify risk factors that effect on sputum and culture conversion.Methods: Data on short-term regimen for MDR TB in Dr. Soetomo General Hospital from January 1st – December 31st, 2018 were collected with a total sampling approach, and fulfill the inclusion and exclusion. Data were analyzed by computer software IBM SPSS Statistic 24 for windows. Results: Male is more likely to have delayed sputum conversion and culture conversion but no statistical difference is observed (p&gt;0.05). Smoking history is more likely to have delayed sputum and culture conversion but only in sputum smear test shows a significant difference (p≤ 0.05). Alcohol consumption has delay effect on sputum and culture conversion but there is statistically difference in only culture conversion (p&lt;0.05). The high baseline smear test also affects delay the sputum and culture conversion but only in sputum smear reveals a significant effect (p&lt;0.05).Conclusion: In this present study, we identified sex, smoking history, high bacillary loads as significant factors on sputum conversion. In addition, we revealed that alcohol-consumption history is a significant factor affecting on culture conversion.

S1455 Heightened Risk for Gastric Cancer Among Immigrant Populations in New York State From High-Incidence Countries

S1455 Heightened Risk for Gastric Cancer Among Immigrant Populations in New York State From High-Incidence Countries

Simultaneous Recognition of Atrophic Gastritis and Intestinal Metaplasia on White Light Endoscopic Images Based on Convolutional Neural Networks: A Multicenter Study.

INTRODUCTION:Patients with atrophic gastritis (AG) or gastric intestinal metaplasia (GIM) have elevated risk of gastric adenocarcinoma. Endoscopic screening and surveillance have been implemented in high incidence countries. The study aimed to evaluate the accuracy of a deep convolutional neural network (CNN) for simultaneous recognition of AG and GIM.METHODS:Archived endoscopic white light images with corresponding gastric biopsies were collected from 14 hospitals located in different regions of China. Corresponding images by anatomic sites containing AG, GIM, and chronic non-AG were categorized using pathology reports. The participants were randomly assigned (8:1:1) to the training cohort for developing the CNN model (TResNet), the validation cohort for fine-tuning, and the test cohort for evaluating the diagnostic accuracy. The area under the curve (AUC), sensitivity, specificity, and accuracy with 95% confidence interval (CI) were calculated.RESULTS:A total of 7,037 endoscopic images from 2,741 participants were used to develop the CNN for recognition of AG and/or GIM. The AUC for recognizing AG was 0.98 (95% CI 0.97–0.99) with sensitivity, specificity, and accuracy of 96.2% (95% CI 94.2%–97.6%), 96.4% (95% CI 94.8%–97.9%), and 96.4% (95% CI 94.4%–97.8%), respectively. The AUC for recognizing GIM was 0.99 (95% CI 0.98–1.00) with sensitivity, specificity, and accuracy of 97.9% (95% CI 96.2%–98.9%), 97.5% (95% CI 95.8%–98.6%), and 97.6% (95% CI 95.8%–98.6%), respectively.DISCUSSION:CNN using endoscopic white light images achieved high diagnostic accuracy in recognizing AG and GIM.

Real World Data of Penile Cancer Treatment at a High-Volume Center in South America: Insights and Survival Trends

To report survival trends and oncological outcomes of penile cancer surgically treated patients, at a high-volume center, treating more than 25 patients each year, in a high incidence country. Clinical charts of all patients that underwent surgical management for penile cancer were reviewed. The primary end points were cancer specific survival (CSS), progression-free survival, and local recurrence free survival. Kaplan-Meier plots were used for survival analyses. Multivariate analysis was performed using cox proportional hazard age-adjusted models to determine the effect of pN, pT, lymphovascular invasion for CSS. A total of 209 patients were identified, with a median follow up of 96 months (IQR 49-133). Organ-sparing surgerywas performed in 72.7%, 56.9% underwent dynamic sentinel lymph node biopsy, 110 patients underwent inguinal lymph node dissection, and 45 (21.5%) pelvic lymph node dissection. A total of 75 (35.8%) of patients relapsed, median time to relapse of 12 months (IQR 6-25). Overall estimates of CSS showed an 8-year CSS of 68.9%. Eight-year CSS was 90.5% for N0, and 32.8% in pN3 (P <.001). The Cox proportional hazard model showed that pN1-3, pT2-4, lymphovascular invasion and positive dynamic sentinel lymph node biopsy were the variables associated with worse 8-year CSS. To the best of our knowledge, we report one of the largest cohorts on the survival outcomes of penile cancer surgical treatment, in a single institution, over a long period of time, were most patients are referred with high-risk, locally advanced or nodal disease.

Invited Commentary: The Role of Tuberculosis Screening Among Migrants to Low-Incidence Settings in (Not) Achieving Elimination.

The cost-effectiveness of migrant tuberculosis prevention programs is highly relevant to many countries with low tuberculosis incidence as they attempt to eliminate the disease. Dale et al. (Am J Epidemiol. 2022;191(2):255-270) evaluated strategies for tuberculosis infection screening and treatment among new migrants to Australia. Screening for infection before migration, and then administering preventive treatment after arrival, was more cost-effective than performing both screening and treatment after arrival. From the Australian health payer perspective, the improved cost-effectiveness of premigration screening partly reflected the shift of screening costs to migrants, which may raise ethical concerns. Key sensitivity analyses highlighted the influence of health disutility associated with tuberculosis preventive treatment, and of posttreatment sequelae of tuberculosis disease. Both considerations warrant greater attention in future research. For all strategies, the impact on tuberculosis incidence among migrants was modest (<15%), suggesting enhanced migrant screening will not achieve tuberculosis elimination in low-incidence settings. This emphasizes the need to increase investment and effort in global tuberculosis prevention and care, which will ultimately reduce the prevalence of tuberculosis infection and therefore the risk of tuberculosis disease among migrants. Such efforts will benefit high and low tuberculosis incidence countries alike, and advance all countries further toward tuberculosis elimination.

Cross-sectional study of prevalence and risk factors, and a cost-effectiveness evaluation of screening and preventive treatment strategies for latent tuberculosis among migrants in Singapore

ObjectivesWHO recommends that low burden countries consider systematic screening and treatment of latent tuberculosis infection (LTBI) in migrants from high incidence countries. We aimed to determine LTBI prevalence and risk...

Prevalence of Latent TB and Effectiveness of BCG Vaccination Against Latent Tuberculosis: An Observational Study

This study aimed to determine the prevalence of latent tuberculosis infection (LTBI) in immigrant children and adolescents (aged 0-17 years) living or recently arriving in Sweden. It also aimed to estimate the effectiveness of Bacillus Calmette-Guérin (BCG) against LTBI in immigrant children coming to Sweden from high-incidence countries, most of them being asylum seekers. LTBI was defined as a positive Quantiferon or a tuberculin skin test (TST) of ≥ 10 mm in small children from whom it was difficult to obtain 3 mL of blood. A typical BCG scar was used as a substitute for written documentation of BCG vaccination. The study comprised 1,404 immigrants aged 0-17 years. The arms and legs of all of them were inspected for a BCG scar, and Quantiferon or TST was performed. The study was a retrospective, observational, comparative cohort study. LTBI was found in 123 of 1,011 (12%) children with a BCG scar and in 116 of 393 (29.5%) without a BCG scar, giving an estimated vaccine effectiveness of 59%. LTBI was common among the immigrant children (17%). LTBI can progress to active TB and then spread in the immigrant population and to the general population if all immigrant arrivals are not tested and given prophylactic treatment if they have LTBI. The BCG vaccine was found to have a significant effect on LTBI (59%).

Equity in clinical trials for HIV-associated cryptococcal meningitis: A systematic review of global representation and inclusion of patients and researchers.

BackgroundIt is essential that clinical trial participants are representative of the population under investigation. Using HIV-associated cryptococcal meningitis (CM) as a case study, we conducted a systematic review of clinical trials to determine how inclusive and representative they were both in terms of the affected population and the involvement of local investigators.MethodsWe searched Medline, EMBASE, Cochrane, Africa-Wide, CINAHL Plus, and Web of Science. Data were extracted for 5 domains: study location and design, screening, participants, researchers, and funders. Data were summarised and compared over 3 time periods: pre-antiretroviral therapy (ART) (pre-2000), early ART (2000 to 2009), and established ART (post-2010) using chi-squared and chi-squared for trend. Comparisons were made with global disease burden estimates and a composite reference derived from observational studies.ResultsThirty-nine trials published between 1990 and 2019 were included. Earlier studies were predominantly conducted in high-income countries (HICs) and recent studies in low- and middle-income countries (LMICs). Most recent studies occurred in high CM incidence countries, but some highly affected countries have not hosted trials. The sex and ART status of participants matched those of the general CM population. Patients with reduced consciousness and those suffering a CM relapse were underrepresented. Authorship had poor representation of women (29% of all authors), particularly as first and final authors. Compared to trials conducted in HICs, trials conducted in LMICs were more likely to include female authors (32% versus 20% p = 0.014) but less likely to have authors resident in (75% versus 100%, p < 0.001) or nationals (61% versus 93%, p < 0.001) of the trial location.ConclusionsThere has been a marked shift in CM trials over the course of the HIV epidemic. Trials are primarily performed in locations and populations that reflect the burden of disease, but severe and relapse cases are underrepresented. Most CM trials now take place in LMICs, but the research is primarily funded and led by individuals and institutions from HICs.

Citizen science initiative points at childhood BCG vaccination as a risk factor for COVID-19.

Current results do not provide conclusive evidence on the effect of BCG vaccination on COVID‐19 alone or in combination with other factors. To address this limitation, in this study we used a citizen science initiative on the COVID‐19 pandemic to collect data worldwide during 2 October 2020–30 October 2020 (1,233 individuals) in a structured way for analysing factors and characteristics of affected individuals in relation to BCG vaccination. For the first time, the results of our study suggested that vaccination with BCG may increase the risk for COVID‐19 at certain age, particularly in individuals vaccinated at childhood. Childhood BCG vaccination increased the likelihood of being diagnosed with COVID‐19 fivefold in COVID‐19 low‐incidence countries and threefold in high‐incidence countries. A reasonable explanation for this effect is the activation of certain innate immunity mechanisms associated with inflammatory reactions. These factors should be considered when analysing the risks associated with this global pandemic.

Genome-Wide DNA Methylation Profiling of Esophageal Squamous Cell Carcinoma from Global High-Incidence Regions Identifies Crucial Genes and Potential Cancer Markers.

Epigenetic mechanisms such as aberrant DNA methylation (DNAme) are known to drive esophageal squamous cell carcinoma (ESCC), yet they remain poorly understood. Here, we studied tumor-specific DNAme in ESCC cases from nine high-incidence countries of Africa, Asia, and South America. Infinium MethylationEPIC array was performed on 108 tumors and 51 normal tissues adjacent to the tumors (NAT) in the discovery phase, and targeted pyrosequencing was performed on 132 tumors and 36 NAT in the replication phase. Top genes for replication were prioritized by weighting methylation results using RNA-sequencing data from The Cancer Genome Atlas and GTEx and validated by qPCR. Methylome analysis comparing tumor and NAT identified 6,796 differentially methylated positions (DMP) and 866 differential methylated regions (DMR), with a 30% methylation (Δβ) difference. The majority of identified DMPs and DMRs were hypermethylated in tumors, particularly in promoters and gene-body regions of genes involved in transcription activation. The top three prioritized genes for replication, PAX9, SIM2, and THSD4, had similar methylation differences in the discovery and replication sets. These genes were exclusively expressed in normal esophageal tissues in GTEx and downregulated in tumors. The specificity and sensitivity of these DNAme events in discriminating tumors from NAT were assessed. Our study identified novel, robust, and crucial tumor-specific DNAme events in ESCC tumors across several high-incidence populations of the world. Methylome changes identified in this study may serve as potential targets for biomarker discovery and warrant further functional characterization. SIGNIFICANCE: This largest genome-wide DNA methylation study on ESCC from high-incidence populations of the world identifies functionally relevant and robust DNAme events that could serve as potential tumor-specific markers. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/81/10/2612/F1.large.jpg.

Incidence of childhood type 1 diabetes mellitus in Ireland remains high but no longer rising.

The global incidence of type 1 diabetes mellitus (T1DM) varies considerably geographically. Ireland has a high incidence of T1DM. Incidence accelerated between 1997 and 2008, although more recent data (2008-2013) suggested stabilisation in the incidence rate (IR). This study sought to determine IRs for 2014 to 2018. Incident cases were prospectively recorded through the established Irish Childhood Diabetes National Register (ICDNR). Cases were verified, and IRs were calculated. Capture-recapture methodology was identical to previous studies. Age and seasonality data were compared. A total of 1429 cases were reported (age range 0.45-14.98years), with significantly more males (772, 54%) and male-to-female ratio of 1.17 (95% CI 1.05, 1.29). Standardised IRs for T1DM in the period were 28.0; 29.6; 30.9; 27.0; and 27.1/100,000/year, respectively. There was a slight reduction in standardised IR, more marked in females than males (9.9% v 1.6%). The highest IR remains in the 10- to 14-year-old age group (44% of total cases). Seasonality of diagnosis is persistently higher in autumn and winter. Ireland remains a high incidence country, despite a minor reduction in incidence rates. Ongoing incidence monitoring through national registers is vital to inform healthcare services, research relating to aetiology and paediatric diabetes management.

Molecular targeted treatment and drug delivery system for gastric cancer.

Gastric cancer is still a major cancer worldwide. The early diagnosis rate of gastric cancer in most high incidence countries is low. At present, the overall treatment effect of gastric cancer is poor, and the median overall survival remains low. Most of the patients with gastric cancer are in an advanced stage when diagnosed, and drug treatment has become the main means. Thus, new targeted drugs and therapeutic strategies are the hope of improving the therapeutic effect of gastric cancer. In this review, we summarize the new methods and advances of targeted therapy for gastric cancer, including novel molecular targeted therapeutic agents and drug delivery systems, with a major focus on the development of drug delivery systems (drug carriers and targeting peptides). Elaborating these new methods and advances will contribute to the management of gastric cancer.

Risk of latent and active tuberculosis infection in travellers: a systematic review and meta-analysis.

Achieving tuberculosis (TB) elimination in low TB incidence countries requires identification and treatment of individuals at risk for latent TB infection (LTBI). Persons travelling to high TB incidence countries are potentially at risk for TB exposure. This systematic review and meta-analysis estimates incident LTBI and active TB among individuals travelling from low to higher TB incidence countries. Five electronic databases were searched from inception to 18 February 2020. We identified incident LTBI and active TB among individuals travelling from low (<10 cases/100 000 population) to intermediate (10-100/100 000) or high (>100/100 000) TB incidence countries. We conducted a meta-analysis and meta-regression using a random effects model of log-transformed proportions (cumulative incidence). Subgroup analyses investigated the impact of travel duration, travel purpose and TB incidence in the destination country. Our search identified 799 studies, 120 underwent full-text review, and 10 studies were included. These studies included 1 154 673 travellers observed between 1994 and 2013, comprising 443 health care workers (HCW), 1 068 636 military personnel and 85 594 general travellers/volunteers. We did not identify any studies that estimated incidence of LTBI or active TB among people travelling to visit friends and relatives (VFRs). The overall cumulative incidence of LTBI was 2.3%, with considerable heterogeneity. Among individuals travelling for a mean/median of up to 6months, HCWs had the highest cumulative incidence of LTBI (4.3%), whereas the risk was lower for military (2.5%) and general travellers/volunteers (1.6%). Meta-regression did not identify a difference in incident LTBI based on travel duration and TB incidence in the destination country. Five studies reported cases of active TB, with an overall pooled estimate of 120.7 cases per 100 000 travellers. We found that travelling HCWs were at highest risk of developing LTBI. Individual risk activities and travel purpose were most associated with risk of TB infection acquired during travel.