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Guidelines suggest screening of individuals who are at increased risk of esophageal adenocarcinoma (EAC). Tools for identifying patients at risk of Barrett's esophagus have been validated. Here, we aimed to compare and validate the tools for the primary outcomes of interest: EAC and esophagogastric junction adenocarcinoma (EGJAC). Retrospective longitudinal analysis of the Kaiser Permanente Northern California Multiphasic Health Checkup Cohort, a community-based cohort including 206,974 patients enrolled between 1964 and 1973 followed through 2016. Baseline questionnaires and anthropometrics classified predictor variables for each tool and were linked to cancer registry outcomes. Analyses used logistic regression, Cox proportional hazards regression, and Kaplan-Meier survival curves. We identified 168 incident EAC cases and 151 EGJAC cases at a mean of 32 years after enrollment (mean follow-up among controls 26 years). Gastroesophageal reflux disease (GERD) symptoms predicted incident EAC (hazard ratio 2.66; 95% confidence interval 1.01, 7.00), but not EGJAC. The Nord-Trøndelag Health Study tool, Kunzmann tool, and Michigan Barrett's Esophagus pREdiction Tool were more accurate than GERD for predicting EAC, with individuals in the fourth quartile of Kunzmann having 17-fold the risk of those in the 1st quartile (hazard ratio = 16.7, 95% confidence interval = 4.72, 58.8). Each tool also predicted incident EGJAC with smaller magnitudes of effect. The study independently validated 4 tools for predicting incident EAC and EGJAC in a large community-based population. The Kunzmann tool appears best calibrated; all appear preferable to using GERD alone for risk stratification. Future studies should determine how best to implement such tools into clinical practice.

INTRODUCTION:Guidelines suggest screening of individuals who are at increased risk of esophageal adenocarcinoma (EAC). Tools for identifying patients at risk of Barrett's esophagus have been validated. Here, we aimed to compare and validate the tools for the primary outcomes of interest: EAC and esophagogastric junction adenocarcinoma (EGJAC).METHODS:Retrospective longitudinal analysis of the Kaiser Permanente Northern California Multiphasic Health Checkup Cohort, a community-based cohort including 206,974 patients enrolled between 1964 and 1973 followed through 2016. Baseline questionnaires and anthropometrics classified predictor variables for each tool and were linked to cancer registry outcomes. Analyses used logistic regression, Cox proportional hazards regression, and Kaplan-Meier survival curves.RESULTS:We identified 168 incident EAC cases and 151 EGJAC cases at a mean of 32 years after enrollment (mean follow-up among controls 26 years). Gastroesophageal reflux disease (GERD) symptoms predicted incident EAC (hazard ratio 2.66; 95% confidence interval 1.01, 7.00), but not EGJAC. The Nord-Trøndelag Health Study tool, Kunzmann tool, and Michigan Barrett's Esophagus pREdiction Tool were more accurate than GERD for predicting EAC, with individuals in the fourth quartile of Kunzmann having 17-fold the risk of those in the 1st quartile (hazard ratio = 16.7, 95% confidence interval = 4.72, 58.8). Each tool also predicted incident EGJAC with smaller magnitudes of effect.DISCUSSION:The study independently validated 4 tools for predicting incident EAC and EGJAC in a large community-based population. The Kunzmann tool appears best calibrated; all appear preferable to using GERD alone for risk stratification. Future studies should determine how best to implement such tools into clinical practice.

Introduction: Quantitative fecal hemoglobin immunochemical tests (FITs) are the most commonly used screening tests for colorectal cancer worldwide. We quantified the change in colorectal cancer and advanced adenoma detection and number of positive tests at different positivity thresholds for quantitative FIT and differences in FIT performance by sex and age. Methods: We updated a 2014 systematic review by searching MEDLINE and EMBASE between January 2012 and May 2018. We included studies that evaluated the sensitivity and specificity of quantitative FIT for colorectal cancer and advanced adenoma detection in asymptomatic, average-risk adults using colonoscopy as the reference standard. We summarized studies that stratified by sex and age and performed stratified analyses by positivity threshold. The number of cancers, advanced adenomas, and positive tests from a theoretical screening cohort of 100,000 participants was calculated at positivity thresholds ≤10, 10 to ≤15, 15 to ≤20, 20 to ≤30, and >30 µg hemoglobin/g feces. Results: We included 40 eligible articles describing 50 studies, including 38 studies with colonoscopy follow-up of all participants. Of the five studies that investigated sex-specific diagnostic performance, four studies showed higher sensitivity and lower specificity in men than women; and of the four studies that investigated age-specific diagnostic performance, 3 studies showed decreasing sensitivity and specificity with increasing age. Stratified analyses of studies with colonoscopy follow-up showed that sensitivity for colorectal cancer increased from 66% (95%CI 57-73) for studies with a threshold of >30 µg/g to 81% (95%CI 77-84) for studies with a threshold ≤10 µg/g, while specificity decreased from 96% (95%CI 95-97) to 91% (95%CI 89-93). Sensitivity for advanced adenomas increased from 20% (95%CI 16-25) to 30% (95%CI 27-34). A threshold of ≤10 µg/g would detect 70 more cancers and 540 more advanced adenomas than a threshold of >30 µg/g per 100,000 participants, with 5,047 additional positive tests (Figure). Conclusion: FIT sensitivity for colorectal cancer appears to be higher and specificity lower in men than women, while trends in sensitivity and specificity with increasing age are less clear. Decreasing the positivity threshold from >30 µg/g to ≤10 µg/g results in the detection of 23% more cancers and 50% more advanced adenomas, and generates 118% more positive tests requiring colonoscopy.

Talaromyces marneffei is a dimorphic fungus that causes substantial disease in Asia, especially among persons infected with the human immunodeficiency virus. In this randomized, controlled trial, initial therapy with amphotericin B was found to be superior to itraconazole. The dimorphic fungus Talaromyces (previously Penicillium ) marneffei causes a life-threatening mycosis in immunocompromised persons living in or traveling to Southeast Asia, China, and India. 1 Talaromycosis (previously penicilliosis) is a major cause of human immunodeficiency virus (HIV)–related death; its prevalence is surpassed only by the prevalence of tuberculosis and cryptococcosis, 2 and it leads to 4 to 15% of HIV-related hospital admissions in regions in which the disease is endemic. 3 – 7 Talaromycosis is increasingly diagnosed among patients who are not infected with HIV but who have other immunodeficiency conditions 8 and is reported to be the second most common cause of all . . .

In ophthalmology, the designation of trachoma, onchocerciasis and leprosy as neglected tropical diseases (NTDs) has sustained efforts to combat these blinding conditions worldwide. Over the past 50 years, NTD designations have enabled the joining of political, social and economic forces to promote research and interventions for diseases that overwhelmingly affect the 3 billion people who subsist on less than 2 United States dollars (US$) a day. The global public health landscape is still dominated by focus on human immunodeficiency virus (HIV), tuberculosis and malaria. However, NTDs are now increasingly recognized as important causes of morbidity and mortality in low-income settings, perpetuating stigma and social isolation, with many NTDs leading to disfiguring complications. In international public health diplomacy, formal disease recognition is essential. The pursuit of this recognition drives proposals from World Health Organization’s (WHO’s) Member States to include additional diseases in the list of NTDs. The intention is to strengthen the development of partnerships, epidemiological frameworks and commitment of resources to achieve the aims set by the sustainable development goals