Time to establish an international vaccine candidate pool for potential highly infectious respiratory disease: a community's view.

In counteracting highly infectious and disruptive respiratory diseases such as COVID-19, vaccination remains the primary and safest way to prevent disease, reduce the severity of illness, and save lives. Unfortunately, vaccination is often not the first intervention deployed for a new pandemic, as it takes time to develop and test vaccines, and confirmation of safety requires a period of observation after vaccination to detect potential late-onset vaccine-associated adverse events. In the meantime, nonpharmacologic public health interventions such as mask-wearing and social distancing can provide some degree of protection. As climate change, with its environmental impacts on pathogen evolution and international mobility continue to rise, highly infectious respiratory diseases will likely emerge more frequently and their impact is expected to be substantial. How quickly a safe and efficacious vaccine can be deployed against rising infectious respiratory diseases may be the most important challenge that humanity will face in the near future. While some organizations are engaged in addressing the World Health Organization's "blueprint for priority diseases", the lack of worldwide preparedness, and the uncertainty around universal vaccine availability, remain major concerns. We therefore propose the establishment of an international candidate vaccine pool repository for potential respiratory diseases, supported by multiple stakeholders and countries that contribute facilities, technologies, and other medical and financial resources. The types and categories of candidate vaccines can be determined based on information from previous pandemics and epidemics. Each participant country or region can focus on developing one or a few vaccine types or categories, together covering most if not all possible potential infectious diseases. The safety of these vaccines can be tested using animal models. Information for effective candidates that can be potentially applied to humans will then be shared across all participants. When a new pandemic arises, these pre-selected and tested vaccines can be quickly tested in RCTs for human populations

Cost of detecting malignant lesions by endoscopy in 2741 primary care dyspeptic patients without alarm symptoms.

BACKGROUND & AIMS: Current guidelines recommend empirical, noninvasive approaches to manage dyspeptic patients without alarm symptoms, but concerns about missed lesions persist; the cost savings afforded by noninvasive approaches must be weighed against treatment delays. We investigated the prevalence of malignancies and other serious abnormalities in patients with dyspepsia and the cost of detecting these by endoscopy. METHODS: We studied 2741 primary-care outpatients, 18-70 years in age, who met Rome II criteria for dyspepsia. Patients with alarm features (dysphagia, bleeding, weight loss, etc) were excluded. All patients underwent endoscopy. The cost and diagnostic yield of an early endoscopy strategy in all patients were compared with those of endoscopy limited to age-defined cohorts. Costs were calculated for a low, intermediate, and high cost environment. RESULTS: Endoscopies detected abnormalities in 635 patients (23%). The most common findings were reflux esophagitis with erosions (15%), gastric ulcers (2.7%), and duodenal ulcers (2.3%). The prevalence of upper gastrointestinal malignancy was 0.22%. If all dyspeptic patients 50 years or older underwent endoscopy, 1 esophageal cancer and no gastric cancers would have been missed. If the age threshold for endoscopy were set at 50 years, at a cost of $500/endoscopy, it would cost$82,900 (95% CI, $35,714-$250,000) to detect each case of cancer. CONCLUSIONS: Primary care dyspeptic patients without alarm symptoms rarely have serious underlying conditions at endoscopy. The costs associated with diagnosing an occult malignancy are large, but an age cut-off of 50 years for early endoscopy provides the best assurance that an occult malignancy will not be missed

Rationale, design, implementation, and baseline characteristics of patients in the DIG trial: A large, simple, long-term trial to evaluate the effect of digitalis on mortality in heart failure

This article provides a detailed overview of the rationale for key aspects of the protocol of the Digitalis Investigation Group (DIG) trial. It also highlights unusual aspects of the study implementation and the baseline characteristics. The DIG trial is a large, simple, international placebo-controlled trial whose primary objective is to determine the effect of digoxin on all cause mortality in patients with clinical heart failure who are in sinus rhythm and whose ejection fraction is less than or equal to 0.45. An ancillary study examines the effect in those with an ejection fraction > 0.45. Key aspects of the trial include the simplicity of the design, broad eligibility criteria, essential data collection, and inclusion of various types of centers. A total of 302 centers in the United States and Canada enrolled 7788 patients between February 1991 and September 1993. Follow-up continued until December 1995 with the results available in Spring 1996