Daiga Santare

Improving uptake of screening for colorectal cancer: a study on invitation strategies and different test kit use.

ObjectiveThe aim of this study was to compare the uptake of mail-delivered tests for colorectal cancer screening. We assessed the effect of an advance notification letter and a reminder letter, and analysed the proportion of inappropriately handled tests. Materials and methodsFifteen thousand randomly selected residents of Latvia aged 50–74 years were allocated to receive one of three different test systems: either a guaiac faecal occult blood test (gFOBT) or one of two laboratory-based immunochemical tests (FIT) – FOB Gold or OC-Sensor. Half of the target population received an advance notification letter; all nonresponders were sent a reminder letter. ResultsThe uptake of screening was 31.2% for the gFOBT, 44.7% for FOB Gold and 47.4% for the OC-Sensor (odds ratio 0.55; 95% confidence interval 0.51–0.60 for gFOBT vs. FOB Gold; odds ratio 0.90; 95% confidence interval 0.83–0.98 for FOB Gold vs. OC-Sensor). The uptake in the gFOBT group was improved by the advance notification letter (7.7%, P<0.0001). 30.9% returned tests were received after the reminder letter. The proportion of tests that could not be analysed because of inadequate handling was 0.9% for gFOBT, 4.4% for FOB Gold and 0.2% for the OC-Sensor (P=0.002 for gFOBT vs. OC-Sensor; P<0.001 for all comparisons vs. FOB Gold). ConclusionThe use of FIT resulted in higher uptake. Receipt of a reminder letter was critical to participation, but the use of an advance notification letter was important mainly for gFOBT. The proportion of inappropriately handled tests was markedly higher for FOB Gold.

Helicobacter pylori and allergy: Update of research

Recently a lot of literature has been published about the possible preventive action of Helicobacter pylori (H. pylori) against allergy. The present review summarizes research data about the association between H. pylori and allergic diseases, as well as discusses possible hypotheses about the preventive action of H. pylori against atopy. There is evidence from observational studies to support a weak inverse association between prevalence of H. pylori infection and allergy. However, confounders like some unidentified socioeconomic factors, antibiotic use and others could bias the association. Although data from cohort studies point to a possible association of H. pylori with some of the allergic diseases, no definite proof for causal relationship has been clearly demonstrated yet. A biological mechanism proposed to explain the preventive action of H. pylori to allergy is reduced exposure to a major stimulus for the generation of Treg cells in individuals without H. pylori infection. In addition, H. pylori could be an indicator for changes in gut microbiome, reflecting the complex interaction between microbes and immune system.

Multicentric randomised study of Helicobacter pylori eradication and pepsinogen testing for prevention of gastric cancer mortality: the GISTAR study

Introduction Population-based eradication of Helicobacter pylori has been suggested to be cost-effective and is recommended by international guidelines. However, the potential adverse effects of widespread antibiotic use that this would entail have not been sufficiently studied. An alternative way to decrease gastric cancer mortality is by non-invasive search for precancerous lesions, in particular gastric atrophy; pepsinogen tests are the best currently available alternative. The primary objective of GISTAR is to determine whether H pylori eradication combined with pepsinogen testing reduces mortality from gastric cancer among 40–64-year-old individuals. The secondary objectives include evaluation of H pylori eradication effectiveness in gastric cancer prevention in patients with precancerous lesions and evaluation of the potential adverse events, including effects on microbiome. Methods and analysis Individuals are recruited from general population (50% men) in areas with high gastric cancer risk in Europe and undergo detailed lifestyle and medical history questionnaire before being randomly allocated to intervention or control groups. The intervention group undergoes H pylori testing and is offered eradication therapy if positive; in addition, pepsinogen levels are detected in plasma and those with decreased levels are referred for upper endoscopy. All participants are offered faecal occult blood testing as an incentive for study participation. Effectiveness of eradication and the spectrum of adverse events are evaluated in study subpopulations. A 35% difference in gastric cancer mortality between the groups is expected to be detectable at 90% power after 15 years if 30 000 individuals are recruited. Biological materials are biobanked for the main and ancillary studies. The study procedure and assumptions will be tested during the pilot phase. Ethics and dissemination The study was approved by the respective ethics committees. An independent Data Safety and Monitoring Board has been established. The findings will be published in peer-reviewed journals and presented at scientific meetings. Trial registration number NCT02047994

Comparison of the yield from two faecal immunochemical tests at identical cutoff concentrations - a randomized trial in Latvia.

Objective We have compared the performance of two faecal immunochemical tests (FIT) in an average-risk population. Materials and methods Altogether, 10 000 individuals aged 50–74 were selected randomly from the population of Latvia in 2011 and assigned randomly either to OC-Sensor or to FOB Gold single-time testing. Positivity of the test, frequency of colonic lesions, number needed to screen (NNscreen) and scope for the detection of an advanced neoplasm (cancer and advanced adenoma) were compared between the tests using the same cutoff concentrations in µg/g faeces. Confidence intervals (CIs) at 95% were calculated. Results Positivity with the cutoff set at 10 µg/g faeces was 12.8% (95% CI: 11.4–14.2) for FOB Gold and 8.3% (95% CI: 7.2–9.4) for OC-Sensor (P<0.001). Positivity was higher in men and the older age groups. Colonoscopy compliance was 55.5%. There was no significant difference between the two tests at comparable cutoff concentrations in µg/g, colonoscopy attendance rate or colonoscopy results. For advanced neoplasm detection, there was no significant difference in number needed to scope and NNscreen at a cutoff of 10 µg/g faeces; however, lower NNscreen was required to detect advanced neoplasms with the FOB Gold test at increased cutoff concentrations. Conclusion Different quantitative FIT systems may report different positivity rate at identical cutoff concentrations, which has to be considered when implementing the use of FIT in national screening programmes.

Generation of a novel next-generation sequencing-based method for the isolation of new human papillomavirus types

With the advent of new molecular tools, the discovery of new papillomaviruses (PVs) has accelerated during the past decade, enabling the expansion of knowledge about the viral populations that inhabit the human body. Human PVs (HPVs) are etiologically linked to benign or malignant lesions of the skin and mucosa. The detection of HPV types can vary widely, depending mainly on the methodology and the quality of the biological sample. Next-generation sequencing is one of the most powerful tools, enabling the discovery of novel viruses in a wide range of biological material. Here, we report a novel protocol for the detection of known and unknown HPV types in human skin and oral gargle samples using improved PCR protocols combined with next-generation sequencing. We identified 105 putative new PV types in addition to 296 known types, thus providing important information about the viral distribution in the oral cavity and skin.

Accuracy of two plasma antibody tests and faecal antigen test for non-invasive detection of H. pylori in middle-aged Caucasian general population sample

Abstract Objective: The aim of the study was to assess the accuracy of two plasma Helicobacter pylori (H. pylori) antibody test-systems and a stool antigen test (SAT) system in a general population sample in Latvia. Materials and methods: Blood and faecal samples were analysed in healthy individuals (40–64 years), referred for upper gastrointestinal endoscopy according to pilot study protocol within a population-based study investigating gastric cancer prevention strategies (GISTAR pilot study). Antibodies to H. pylori were assessed in plasma by latex-agglutination test and enzyme-linked immunosorbent assay (ELISA). H. pylori antigen in faecal samples was detected by a monoclonal enzyme immunoassay-based SAT. Histological assessment of H. pylori based on a modified Giemsa staining method was used as the gold standard. Individuals having received H. pylori eradication within one year prior to enrolment were excluded. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and overall accuracy were calculated. Receiver-operating characteristic curves were designed to estimate the optimal diagnostic cut-off value of tests. Results: The analysis included 779 participants for latex-agglutination test, 1002 for ELISA and 672 individual samples for SAT. The sensitivity, specificity, PPV, NPV and overall accuracy were as follows: latex-agglutination test (86;81;87;80;84%), ELISA (97;72;83;94;86%) and SAT (87;81;87;81;85%), respectively. The optimal diagnostic cut-off value for ELISA test was ≥50.26 g/L. Conclusions: Although the performance of the three tests was comparable to each other, the three test systems showed suboptimal accuracy, with important implications for public health programs based on ‘test-and-treat’ strategy.