Recruitment strategies and consent rates in a national prospective colorectal cancer screening cohort: results from year 1 of the Voyage Study.

OBJECTIVE: To identify the optimal incentive protocol for maximising participation while managing study costs during the Voyage trial. DESIGN: Prospective cohort (Voyage trial) of colorectal cancer (CRC) incidence and mortality outcomes in individuals screened with multitarget stool DNA (mt-sDNA) served as the population. A subset was randomised to receive postage stamps as a pre-consent incentive, or as a post-consent incentive after completion of the consent and questionnaire. Descriptive statistics from year 1 are reported. RESULTS: During year 1 of the Voyage trial, a total of 600 258 individuals with mt-sDNA orders received at Exact Sciences Laboratories were randomly selected and invited to participate. Of those, 26 429 (4.4%) opted in, 14 365 of whom (54.3%) consented. The opt-in and consent samples were similar to the target population with respect to sex but differed by geographic residence and age (p<0.001). For the embedded incentive experiment, 2333 were randomised to the pre-incentive arm, while 2342 were randomised to the post-incentive arm. Overall consent rate in the incentive trial was 56.4% (60.9% for the pre-consent incentive arm (1421/2333) vs 52.0% for the post-consent incentive arm (1217/2342), p<0.001). Cost reduction was observed for the pre-consent incentive group, and higher response rates were seen among older versus younger individuals. CONCLUSIONS: Pre-consent incentive option was associated with a higher participation rate and lower costs and was used for the remainder of study recruitment. CRC incidence and mortality vary with age; thus, adjusting for differential participation by age and region will be important in analyses of Voyage data. TRIAL REGISTRATION NUMBER: NCT04124406.

Colorectal cancer outcomes after screening with the multi-target stool DNA assay: protocol for a large-scale, prospective cohort study (the Voyage study).

Introduction: Population-level screening has been shown to reduce the incidence and mortality of colorectal cancer (CRC). Unfortunately, adherence to screening recommendations among eligible US adults remains below national goals. A relatively new non-invasive screening modality, the Food and Drug Administration-approved multi-target stool DNA (mt-sDNA) assay (commercialised as Cologuard), which combines the detection of haemoglobin and DNA abnormalities, has been completed by more than 3 million individuals. Given mt-sDNA's recent availability, the effectiveness of mt-sDNA screening with respect to CRC incidence and mortality reduction has not yet been established. Methods and analysis: Through an academic-industry collaboration, a prospective cohort study (Voyage) was designed with an initial enrolment target of 150 000 individuals with mt-sDNA ordered by their healthcare provider for CRC screening. Consented participants will be asked to complete a baseline questionnaire to collect sociodemographic and health information. Additional questionnaires will be provided after 1 year, and every 3 years thereafter, to collect data regarding CRC screening follow-up in order to estimate rates of CRC incidence and other health outcomes. Linkage to the National Death Index will be used to estimate mortality rates. Ethics and dissemination: The Voyage study will be conducted in accordance with international guidelines and local regulatory requirements and laws. Data will be stored and retained at Mayo Clinic. Only limited data elements required for research purposes will be transmitted between Mayo Clinic and Exact Sciences Laboratories. Results of the Voyage study will be disseminated through scientific presentations and publications. Trial registration number: NCT04124406.

Evaluation of an enzyme immunoassay for antibodies to a recombinant Blastomyces adhesin-1 repeat antigen as an aid in the diagnosis of blastomycosis in dogs.

OBJECTIVE: To evaluate the sensitivity and specificity of an enzyme immunoassay (EIA) for antibodies to a recombinant Blastomyces adhesin-1 repeat antigen (rBAD-1) to aid in the diagnosis of blastomycosis in dogs and compare the findings with results from other tests used for this purpose. DESIGN: Prospective analytic study. SAMPLE: Serum and urine from 70 dogs with and without blastomycosis. PROCEDURES: Serum and urine samples were collected from dogs with blastomycosis (n = 21), histoplasmosis (8), or nonfungal pulmonary disease (21) and from healthy control dogs living in a blastomycosis-endemic area (20). Serum was tested for antibodies against Blastomyces dermatitidis with the rBAD-1 antibody EIA and an A-antigen antibody agar gel immunodiffusion (AGID) assay. Serum and urine were tested for B dermatitidis antigen with a quantitative EIA. RESULTS: Sensitivity of the quantitative antigen EIA was 100% in serum and urine samples from dogs with blastomycosis, with specificity of 95% in urine samples from dogs with nonfungal pulmonary disease and 100% in urine samples from healthy dogs. Sensitivity of the rBAD-1 antibody EIA (95%) was significantly greater than that of the A-antigen antibody AGID assay (65%). Specificity of the antibody EIA was 88% in dogs with histoplasmosis, 95% in healthy dogs, and 100% in dogs with nonfungal pulmonary disease. CONCLUSIONS AND CLINICAL RELEVANCE: The rBAD-1 antibody EIA had greater sensitivity than the A-antigen antibody AGID assay in dogs with blastomycosis. This antibody EIA may assist in distinguishing histoplasmosis from blastomycosis. Further evaluation in a larger prospective study is needed to verify these results.

Histoplasmosis among hospitalized febrile patients in northern Tanzania.

Histoplasmosis may be common in East Africa but the diagnosis is rarely confirmed. We report 9 (0.9%) cases of probable histoplasmosis retrospectively identified among 970 febrile inpatients studied in northern Tanzania. Median (range) age was 31 (6, 44) years, 6 (67%) were female, 6 (67%) HIV-infected; 7 (78%) were clinically diagnosed with tuberculosis or bacterial pneumonia. Histoplasmosis is an important cause of febrile illness in Tanzania but is rarely considered in the differential diagnosis. Increased clinician awareness and availability of reliable diagnostic tests may improve patient outcomes.

Evaluation of Coccidioides antigen detection in dogs with coccidioidomycosis.

Antigen detection has been reported to be a promising method for rapid diagnosis of coccidioidomycosis in humans. Coccidioides antigen detection has not been previously reported in dogs with coccidioidomycosis and was evaluated in 60 cases diagnosed based on detection of anti-Coccidioides antibodies at titers of 1:16 or more in serum. Controls included dogs with presumed histoplasmosis or blastomycosis, other fungal infections, or nonfungal diseases and healthy dogs. Urine and serum specimens were tested using an enzyme immunoassay for Coccidioides galactomannan antigen. Antibody testing was performed at commercial veterinary reference laboratories. Antigen was detected in urine or serum of 12 of 60 (20.0%), urine only in 2 of 57 (3.5%), and serum only in 11 of 58 (19.0%) dogs with coccidioidomycosis. Antigen was detected in the urine of 3 of 43 (7.0%) and serum of 1 of 37 (2.7%) dogs with histoplasmosis or blastomycosis but not in 13 dogs with other fungal infections (serum, 9; urine, 13), 41 dogs with nonfungal diseases (urine, 41; serum, 18), or healthy dogs (serum, 21; urine, 21). Detection of antigen was an insensitive method for diagnosis of coccidioidomycosis in dogs in which the diagnosis was based primarily upon detection of antibodies at titers of 1:16 or higher, and the highest sensitivity was in serum.

Histoplasma antigen clearance during treatment of histoplasmosis in patients with AIDS determined by a quantitative antigen enzyme immunoassay.

Clearance of Histoplasma antigen has been used as a marker for response to treatment of progressive disseminated histoplasmosis (PDH) in patients with AIDS. Advancements in Histoplasma antigen detection permit accurate quantification of antigen concentration. We compared the clearance of antigenemia and antigenuria during effective treatment of PDH. Urine and serum specimens were serially collected from patients with AIDS who were successfully treated for PDH as part of two prospective clinical trials. Samples were stored frozen until they were tested in the quantitative Histoplasma antigen enzyme immunoassay. The kinetics of antigen clearance during the first 12 weeks of therapy were assessed in urine and serum during treatment with liposomal or deoxycholate amphotericin B followed by itraconazole and, in a separate analysis, in patients receiving only itraconazole. Latent class growth analysis was performed to define patterns of antigen clearance over time. In patients receiving amphotericin B, antigen levels declined the most during the first 2 weeks of treatment and antigenemia decreased more rapidly than antigenuria (5.90 ng/ml per week versus 4.21 ng/ml per week, respectively; P = 0.09). Mean reductions of antigen levels from baseline at weeks 2 and 12 were greater in sera than in urine: 11.26 ng/ml versus 7.65 ng/ml (P = 0.0948) and 18.52 ng/ml versus 14.64 ng/ml (P = 0.0440), respectively. In patients who received itraconazole alone, most of the decline in antigenuria occurred later during treatment and was overall slower than that seen with amphotericin B (P < 0.0001). Results of latent class growth modeling showed two distinct trajectories for each parameter. With effective therapy, Histoplasma antigenemia decreases more rapidly than antigenuria, providing a more sensitive early laboratory marker for response to treatment. Antigenuria declines earlier with amphotericin B than with itraconazole.